1. health and fitness
2. disease

136th Annual Meeting of the
American Neurological Association
September 25–27, 2011
Manchester Grand Hyatt, San Diego, CA
Poster Listings
Derek Denny-Brown New Member
Symposium Abstracts
Poster Session Abstracts
Works in Progress Abstracts
Career Development Abstracts
Author Index
Subject Index
1–3
4–18
19–21
22
112–123
124–126
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Poster Listings
Sunday, September 25, 2011
Posters
Poster Listing Pages
Topic
101–144
3–5; 19
23–32; 99–100
Movement Disorders
201–240
5–7; 19
32–41; 100–101
Sleep Disorders and Circadian Rhythm
301–303
7
42
Education
401–408
7–8
42–44
Career Development
515–531
22
111
Poster Listing Pages
Abstract Pages
Posters
Behavioral Neurology
601–622
8–9; 19
44–49; 102
Epilepsy
701–732
9–10; 19–20
49–55; 102–104
Neuromuscular Disease
801–841
10–11; 20
55–63; 104–105
Neurogenetics
1001–1013
11–12; 20
63–65; 105–106
Trauma/Injury
1101–1107
12
65–66
Neurology Critical Care
1201–1206
12; 20
66–67; 106
Pediatric Neurology
1301–1304
12–13
67–68
Rehabilitation and Regeneration
1401–1403
13
68–69
Poster Listing Pages
Abstract Pages
Tuesday, September 27, 2011
Topic
I
Posters
Dementia and Aging
1501–1542
13–15; 20
69–79; 107–108
Headache and Pain
1601–1623
15–16; 21
79–84; 108
Neuroimmunology and Demyelinating Disease
1701–1747
16–28; 21
84–94; 108–110
Neurooncology
1801–1809
18
94–96
Neurovirology
1901–1908
18
96–98
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Poster Listings
Cerebrovascular Disease
Monday, September 26, 2011
Topic
ID: senthilk
Abstract Pages
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136th Annual Meeting Tuesday,
September 27, 2011 Derek
Denny-Brown New Member
Symposium Abstracts
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new work using olfactory intracranial EEG techniques in
patients with medically refractory epilepsy. By recording
directly from olfactory limbic brain regions, we have begun to
gain direct insights into the electrophysiological organization of
the human olfactory system. Preliminary results suggest that
the emotional content of a smell modulates piriform activity
in the gamma-band range, and that cortical stimulation at piriform cortex elicits short-latency (<15 ms) orbitofrontal
responses. Findings from this work will be instrumental in
confirming (or refuting) long-accepted basic notions about the
neurobiology of human olfaction and may help inform clinical
translational models of neurodegenerative disorders, such as
Alzheimer’s and Parkinson’s diseases, in which olfactory impairments often arise prior to the onset of overt symptoms.
Derek Denny-Brown Neurological Scholar Award: Can
We Detect Alzheimer’s Disease a Decade Before
Dementia, and Why Would We Want To?
Reisa Sperling, M.D. Center for Alzheimer Research and
Treatment, Brigham and Women’s Hospital, Massachusetts
General Hospital, Harvard Medical School
Poster Session Abstracts
The pathophysiological process of Alzheimer’s disease (AD)
is thought to begin years, if not decades, prior to the onset
of clinical dementia. Converging data from PET amyloid
imaging, cerebrospinal fluid studies, and large autopsy series
suggest that approximately one-third of clinically normal
older individuals harbor a substantial burden of cerebral
amyloid-b deposition. Recent multi-modality imaging studies, using PET amyloid imaging and functional MRI, have
demonstrated that amyloid-b deposition in normal elderly is
associated with aberrant fMRI activity in the default network, in a pattern strongly resembling that seen in AD dementia. AD-like patterns of atrophy have also been detected
in amyloid-positive normal older individuals, and recent evidence suggests that specific patterns of cortical thinning are
predictive of who will develop dementia a decade later. A
small number of studies have reported an association
between higher amyloid burden and lower memory performance even among the range of clinically normal older
individuals, particularly those studies employing more challenging neuropsychological measures. These findings provide
support for the hypothesis that amyloid-b accumulation is
linked to synaptic dysfunction in the networks supporting
memory processes, and that brain dysfunction is detectable
prior to the emergence of significant cognitive impairment.
It is likely, however, that many additional factors modulate
the likelihood of subsequent clinical decline. Longitudinal
studies are ongoing to determine if these amyloid-positive
older individuals are indeed in the preclinical stages of AD,
and to elucidate the endophenotype that best predicts those
who will progress to AD dementia. In parallel with these
natural history studies, we must begin secondary prevention
trials to determine if altering amyloid burden can delay the
emergence of clinical symptoms. It is likely that, similar to
cancer, diabetes, cardiovascular and most other chronic diseases, many therapies for AD will be most efficacious in the
early stages of the pathophysiological process.
M701. Controlled Cortical Impact in Adult Rats and
Posttraumatic Seizures and Epilepsy
Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller,
Bo Lu and Zakaria Mtchedlishvili; Pittsburgh, PA and
Philadelphia, PA
The CCI model of TBI has been used in mice and immature rats to model posttraumatic epilepsy. We used young
adult rats and long-term video and video-EEG with cortical
and hippocampal electrodes to investigate posttraumatic epileptogenesis and associated neuropathological changes. A
total of 28,956 hours of monitoring was obtained from 128
CCI-injured and 15 sham-operated animals. Class 3–5 provoked seizures occurred in 7/72 (9.7%) animals video-monitored for 1 week immediately after CCI. Epileptic seizures
occurred in 26/118 (22%) animals monitored beyond 1
week post-CCI. Class 3–5 seizures occurred in 19 animals;
ictal discharges appeared generalized at onset or from the
contralateral frontal cortex. Nonconvulsive seizures occurred
in 7 animals characterized by motor arrest or no behavioral
change associated with continuous 1–2 Hz high amplitude
spikes or spike-waves averaging 26.262.8 seconds. No control animal had seizures. CCI resulted in severe cortical and
subcortical injury and alterations in NeuN and GFAP staining. Timm staining showed mossy fiber sprouting in the
inner molecular layer of the dentate gyrus of epileptic and
nonepileptic animals. These results indicate that the CCI
model can be used in adult animals to investigate mechanisms underlying posttraumatic epileptogenesis.
Study supported by: Pennsylvania Department of Health
Research Formula Fund RFA 01-07-26 and Epilepsy Foundation Research Grant (ZM)
M704. Gray Matter Heterotopia in an Epileptic Brain
Malformation Are Functionally Connected to Overlying
Cortex
Joanna A. Christodoulou, Linsey M. Walker, Stephanie N. Del
Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E.
Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA
and Haifa, Israel
Derek Denny-Brown Neurological Scholar Award: The
Human Sense of Smell at Millisecond Speed
Jay A. Gottfried, MD, PhD, Northwestern University,
Chicago, IL
Objective: Periventricular nodular heterotopia (PNH) are
associated with epilepsy and dyslexia. Evidence suggests that
heterotopia have a functional role and connectivity defects
may be important in this disorder. We investigated the restingstate functional connectivity of heterotopic nodules in PNH.
Methods: Eleven subjects were studied using functional
connectivity MRI with bold oxygenation level-dependent
(BOLD) imaging acquired during rest. The functional correlation between heterotopic nodules and other brain voxels
was systematically identified and relationships to clinical
measures analyzed.
Very little is known about the basic anatomy, connectivity,
and physiology of the human olfactory system. What we do
know is largely inferential, derived from non-human animal
studies that may hold scant relevance for the human sense
of smell. Although functional imaging studies have
expanded our general understanding of human olfactory
neurobiology, these techniques have poor temporal resolution and provide only correlative information. Thus even
the most basic assumptions about human olfaction have not
been systematically tested. In this presentation I will discuss
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Results: Forty-three of 45 heterotopia (96%) showed
functional correlation with discrete regions of overlying cortex (mean peak coefficient 0.61). Nodules also demonstrated
correlation with contralateral cortex (62%), other nodules
(51%), ipsilateral nonoverlying cortex (42%), and basal ganglia/cerebellum (13%). The peak degree of connectivity
between heterotopia and other gray matter regions was significantly related to epilepsy duration.
Interpretation: Nearly all heterotopia in PNH are functionally connected to overlying cortex, and the strength of
aberrant connectivity increases with duration of epilepsy.
Along with prior evidence that cortico-cortical tract defects
underlie dyslexia in this disorder, these results suggest that
altered connections are a critical substrate for neurological
dysfunction in brain malformations.
Study supported by: NIH/NINDS, Epilepsy Foundation,
William F. Milton Fund
Amyloid-beta clearance rate is decreased by 30% in AD
compared to controls. Changes in clinical, cognitive, MRI,
PET, CSF, and blood biomarkers in autosomal dominant
AD indicate the pathophysiologic cascade begins up to 20
years before the expected age of onset.
The pathophysiologic changes of AD can be specifically
measured and targeted for clinical trials. Autosomal dominant AD prevention trials offer a unique opportunity to
lead the way to effective treatments for all AD.
Study supported by: NIH K-23-AG03094601, NIH R-01NS065667, NIH 3P-01-AG02627603S1 (FACS), NIH 1U01-AG03243801 (DIAN), ADRC (P50 AG05681-22),
HASD (P01 AG03991-22), WU CTSA award (UL1
RR024992), Mass Spectrometry Resource (NIH RR000954),
Eli Lilly research collaboration
R.J.B. is a co-founder of a company (C2N Diagnostics)
that has licensed a Washington University patent on some
of the technology described in this abstract.
M810. Evaluating Mechanoreceptors in Glabrous Skin
in Diabetic Neuropathy
Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier;
Nashville, TN
T1505. Components of Blood Pressure and Progression
of Cerebral Leukoaraiosis: The ARIC Study
Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker,
Josef Coresh, Clifford R. Jack, Jr., David S. Knopman,
Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and
Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC;
Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle,
WA and Jackson, MS
Meissner corpuscles (MCs) and their myelinated afferents
are found only in glabrous skin. We hypothesized that alterations in MCs occur in diabetic neuropathy and correlate
with other measures of axonal loss. Immunohistochemistry
was performed on 2 and 3 mm skin punches from the index
finger and distal leg, respectively. Four diabetic patients
(ages 45–75), with neuropathy confirmed by exam and
nerve conduction studies and four control patients (aged
35–50), were studied. Average Meissner corpuscle density
(MCD) in control patients was 15.3 6 7.1 MCs/ mm2 with
significant reductions observed in two patients (3.3, 6.2 MCs/
mm2) with near normal or higher density in two other
patients (11.1, 28.1 MCs/mm2), suggestive of proliferation.
MCs in diabetics often displayed abnormal morphology.
Density of intrapapillary myelinated endings (IME) correlated with MCD in all patients (r ¼ 0.97). Diabetic
patients’ intraepidermal nerve fiber density (IENFD) in the
distal leg was 4.2 6 5.9 fibers/mm, compared to 13.7 6
1.3 in controls. IME density did not correlate with IENFD,
suggesting that these populations of fibers are independently
affected by hyperglycemia. Glabrous skin biopsies afford
evaluation of mechanoreceptors which are important in
studying pathophysiology of diabetic neuropathy.
Study supported by: Supported by NINDS K23
NS056009 (A.C. P.), NINDS R01NS066927-01(J.L.), Vanderbilt CTSA grant 1 UL1 RR024975.
Background The contribution of blood pressure (BP) components to the burden and progression of cerebral white
matter hyperintensity (WMH) is poorly understood. We
evaluated these associations in the population-based Atherosclerosis Risk in Communities (ARIC) cohort.
Methods 983 participants each underwent 2 brain MRIs
10 years apart. Systolic (SBP) and diastolic BP (DBP) were
measured at 4 study visits. Four BP components were examined as predictors of WMH progression: 1) mean arterial
pressure (MAP); 2) pulse pressure (PP); 3) orthostatic hypotension (OH); and 4) 10-year change in BP.
Results Baseline (preceding MRI #1) MAP value predicted WMH progression (OR 1.39 (1.20–1.62), per 10
mm Hg increase), but PP did not. Presence of OH did not
predict WMH progression, but OH severity did (OR 1.21
(1.02–1.42) per 10 mm Hg SBP decrease). Change in DBP
over 10 years had a U-shaped relationship with WMH progression: extreme increases and decreases, independent of
antihypertensive use, were both associated with greater
WMH progression (p¼0.007).
Discussion WMH progression is significantly predicted
by MAP and extent of orthostatic SBP reduction. Significant
changes over time in DBP, whether positive or negative, predict WMH progression, cautioning against simplified interpretations of blood pressure associations.
Study supported by: The Atherosclerosis Risk in Communities
Study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute contracts (HHSN26820
1100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN26820
11000010C, HHSN2682011000011C, HHSN2682011000012C).
T1501. Amyloid-Beta Dynamics and Prevention Trials
in Dominantly Inherited Alzheimer’s Disease
Randall J. Bateman and on behalf of the Dominantly
Inherited Alzheimer Network; St. Louis, MO
Amyloid-beta is a key pathologic protein in Alzheimer’s disease(AD) and extensive research has started an era of clinical
trials targeting amyloid-beta. Understanding the dynamics
of amyloid-beta formation and clearance in the human
CNS and the processes that lead to clinical disease are essential to design better clinical trials. Developing efforts to prevent AD in autosomal dominant mutation carriers may test
the amyloid hypothesis, determine the timing of treatment,
and lead the way to AD prevention.
Amyloid-beta production and clearance rates were measured with stable isotope labeling kinetics. The Dominantly
Inherited Alzheimer’s Network interim findings of clinical,
cognitive, MRI, PET, CSF, and blood biomarkers were analyzed with respect to the expected age of onset.
Works in Progress Abstracts
M839. Virtual Demyelination in pmp22 Deficiency
Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman,
Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li;
Nashville; San Diego; Cleveland; Zurich, Swaziland and
Nashville, TN
Safety factor for action potential propagation in pmp22þ/
nerves appears impaired (Bai et al, J Neurosci 2010). The
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present study investigates mechanisms responsible for the
impairment. Fluorescent dyes with different molecular sizes
were injected into sciatic nerves. After 4-hour incubation,
sciatic nerves were teased into individual nerve fibers, and
examined under fluorescence microscopy. Fluorescence was
of strong intensity in about a half of paranodal tomacula of
pmp22þ/ nerves (15 mice), but absent or minimal in the
paranodes of wild-type nerves (11 mice). This finding suggests
that myelin is abnormaly leaky, and may result in excessive outward current. Application of potassium channel blocker, 4AP, to
reduce outward current improved the amplitude of motor
response during nerve stimulation. Western blot and immunohistochemistry revealed alterations of tight junction protein assembly,
a potential molecular mechanism for the myelin leakage.
Conclusions: Our results show excessive leakage in
pmp22þ/ myelin in the absence of demyelination. This
leakage is functionally similar to demyelination. These findings not only reveal novel mechanism for conduction block
but also establish new therapeutic approach for this disease.
Study supported by: NIH
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43 Canadian families with 4 or more individuals with MS.
Genetic linkage analysis and genotyping of candidate genes
in these families has not fully explained familial disease
clustering although alleles of GWAS genes are
overrepresented.
Methods: Whole exome sequencing was performed to
further understand heightened prevalence of MS in these
families.
Findings: Forty-three individuals with MS (one/family)
were sequenced. On average over 58000 variants were identified in each individual. Searching for rare variants in
known or candidate MS susceptibility genes led to identification of a rare loss-of- function variant in the CYP27B1
gene. This variant in 2716 parent-affected child trios
showed significant association to MS P¼6105. Further
genotyping of other variants in over 11,000 individuals
showed that rare CYP27B1 variants conferred significant
risk of MS, Peto odds ratio ¼ 4.1 (95% confidence interval
1.5–11.1).
Interpretation: Causative role for CYP27B1 in MS risk
is supported. CYP27B1 encodes the vitamin D activating 1alpha hydroxylase enzyme. A role for vitamin D in MS
pathogenesis is strongly implicated. We show the utility of
using extreme multicase families to identify rare variants.
Study supported by: This study was supported by grant
funding from the MS Society of the United Kingdom and
the Scientific Foundation of the Canadian MS Society.
M1012. Exome Sequencing Identifies a Rare Variant in
the CYP27B1 Gene Associated with Multiple Sclerosis
George C. Ebers and Sreeram V. Ramagopalan; Oxford,
Oxfordshire, United Kingdom
Background: Multiple sclerosis (MS) is a complex neurological disease. We previously described the ascertainment of
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136th Annual Meeting Sunday,
September 25, 2011
Poster Session
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S109 Incidence of Nocturnal Blood Pressure Dipping
during Hospital Admission and Discharge among
African American Stroke Patients
Lien Diep, John Kwagyan, Joseph Kurantsin-Mills, Janaki
Kalyanam, Amy Wong, Kermit Crowder, Bonnie Davis, Leia
Harbour, Jean Edson and Annapurni Jayam-Trouth;
Washington, DC and Baltimore, MD
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
S110 Preoperative Factors Associated with In-Hospital
Mortality Following Minimally Invasive Hematoma
Aspiration and Thrombolysis for Intracerebral
Hemorrhage
Feng Xu, Zhouping Tang, Huicong Kang, Dengji Pan,
Suiqiang Zhu and Wei Wang; Wuhan, China
Cerebrovascular Disease
S111 Does Incidental Micro-Hemorrhage, Detected by
Gradient Echo Sequence MRI, Predict Hemorrhagic
Transformation of an Ischemic Stroke?
Konark Malhotra and Yousef M. Mohammad; Chicago, IL
S101 Duration of Diabetes and Ischemic Stroke Risk:
The Northern Manhattan Study
Julio R. Vieira*, Chirantan Banerjee, Yeseon P. Moon,
Myunghee C. Paik, Tatjana Rundek, Ralph L. Sacco and
Mitchell S.V. Elkind; New York, NY and Miami, FL
S112 Younger Patients Have Lower Quality of Life after
Intracranial Aneurysm Diagnosis
Nerissa Ko, Richard Hornung, Charles Moomaw, Laura
Sauerbeck and Joseph Broderick; San Francisco, CA and
Cincinnati, OH
S102 Functional Outcomes in CREST among Patients
with Periprocedural Stroke and Myocardial Infarction
Bart M. Demaerschalk, Robert J. Hye, O.W. Brown, Donald
V. Heck, Irfan Altafullah, Jenifer H. Voeks, George Howard,
James F. Meschia and Thomas G. Brott; Phoenix, AZ; San
Diego, CA; Royal Oak, MI; Winston Salem, NC; Robbinsdale,
MN; Birmingham, AL and Jacksonville, FL
S113 Aggressive Medical Management of Primary
Intracerebral Hemorrhage: Cost/Benefit Analysis
Luis Cava, Diane C. Andress-Rothrock and John F. Rothrock;
Birmingham, AL
S103 Inhibition and Scavenging of Complement as
Therapeutic Targets in the Mouse Model of Acute
Ischemic Stroke
Xinzhi Chen, Mark P. Mattson and Milan Basta; Baltimore,
MD and Potomac, MD
S114 Withdrawn.
S115 Genetic Analysis of Strain-Specific Stroke
Sesceptibility in Mice: How To Classify C57BL/6?
Amy K. Guzik, Sean S. Li, Ira M. Hall, Charles R. Farber,
Brian H. Annex and Bradford B. Worrall; Charlottesville, VA
S104 Does ACE (rs4646994) and a ADDUCIN (rs4961)
Gene Polymorphisms Predicts the Recurrence of
Hypertensive Intracerebral Hemorrhage
Usha K. Misra, Jayantee Kalita, Bindu I. Somarajan,
Bishwanath Kumar, Moromi Das and Balraj Mittal;
Lucknow, Uttar Pradesh, India
S116 Risk Factor Control in a Phase 3 Carotid
Revascularization Trial
James F. Meschia, Pierre P. Leimgruber, Vito A. Mantese,
Carlos H. Timaran, David Chiu, Bart M. Demaerschalk,
Mary E. Longbottom, Jenifer H. Voeks, George Howard and
Thomas G. Brott; Jacksonville, FL; Spokane, WA; St. Louis,
MO; Dallas, TX; Houston, TX; Phoenix, AZ and
Birmingham, AL
S105 Risk of Intracerebral Hemorrhage in t-PA Treated
Patients with Elevated INR
William P. Neil, Rema Raman, Ernstrom Karin and Thomas
M. Hemmen; San Diego, CA
S106 Toward a Further Clinical Physiological
Elucidation: Immediate Regression of Leukoaraiosis after
Carotid Artery Revascularization
and Yu-Ming Chuang; New Taipei City, Taiwan
S117 Radiologic Analysis of Thrombolysis-Induced
Intracerebral Hemorrhage and the Role of Early Blood
Pressure Management
Maxim Mokin, Tareq Kass-Hout, Omar Kass-Hout, Robert
Zivadinov and Bijal Mehta; Buffalo, NY
S107 Ischemic Stroke Exome Pilot Study
John W. Cole, Xinyeu Liu, Luke J. Tallon, Lisa K. Sadzewicz,
Oscar C. Stine, Nicole Dueker, Yuching Cheng, Marcella A.
Wozniak, Barney J. Stern, James F. Mitchell, Braxton D.
Mitchell, Steven J. Kittner and Jeffrey R. O’Connell;
Baltimore, MD and Jacksonville, FL
S118 Anterior Circulation Stroke Causing Dizziness or
Vertigo: A Systematic Review
Yun Zhou, Seung-hun Lee, Ali S. Saber Tehrani, Karen A.
Robinson and David E. Newman-Toker; Baltimore, MD and
Gwangju, Korea
S108 Phosphodiesterase Inhibitors Modulate Human
Brain Microvascular Endothelial Cell Barrier Properties
and Response to Injury
Shuo Liu, Fan Yang, Chuanhui Yu, Annlia Paganini-Hill and
Mark Fisher; Irvine, CA
S119 The Presence of Intracranial Vascular Calcification
May Protect Against Vasospasm Following Subarachnoid
Hemorrhage
Joya Paul, Mohamed Zghouzi, Yousef Mohammad, Shyam
Prabhakaran, Sudeep Bhabad and Bichun Ouyang; Chicago, IL
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S120 Stroke Knowledge: A Nation-Wide, Internet-Based
Survey of 11,121 Inhabitants in Japan
Hisanao Akiyama, Kanako Shimizu, Yoshiaki Tokuyama and
Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan
S132 Size Matters: Predictors of Intracranial
Hemorrhage in Stroke Patients on Anticoagulation
Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and
Rebecca F. Gottesman; Baltimore, MD
S121 Is Anti Epileptic Drug Necessary in Cortical
Venous Thrombosis?
Velmurugendran Cannigaiper Uthamaroyan, Kaushik Sundar,
Meenakshisundaram Umaiorubahan and Shankar
Venkatasubramaniam; Chennai, Tamilnadu, India
S133 A Rare Presentation of Anterior and Posterior
Spinal Arteries Ischemia during Dilaysis
Noor Yono, Adrian Marchidann and Rabih Kashouty;
Manhasset, NY and New York, NY
S122 Race and Insurance Disparities in Cardiovascular
Risk Factors Control in Patients with Acute Stroke
Anna M. Cervantes, Jose R. Romero, Helena Lau, Feliks
Koyfman, Aleksandra Pikula, Thanh N. Nguyen, Carlos S.
Kase and Viken L. Babikian; Boston, MA
S134 Neurosarcoidosis: A Case Presentation
Amtul Farheen, Nancy Gadallah, Rony Dekermenjian,
Michael Rosenberg and Sushanth Bhat; Edison, NJ
S135 Stroke Outcomes Based on MERCI/PENUMBRA
Intervention and Hemodynamics
Jay-Ming Wang**, Zahid I. Choudary, Shazia Z. Choudhary,
Michael Sloan, Harry R. Van Loveren, Karen R. Wilson and
David A. Decker; Tampa, FL
S123 A Population-Based Verbal Autopsy Study of 1250
Stroke Deaths in Bangladesh
Farrah J. Mateen, Nurul Alam, Marco Carone and Robert E.
Black; Baltimore, MD; Dhaka, Bangladesh and Berkeley, CA
S136 Migraine-Related ICH – A Case Study and
Review
Shivani Ghoshal**, Sankalp Gokhale and Louis Caplan;
Boston, MA
S124 Heparin-Induced Thrombocytopenia Associated
with Cerebral Venous Sinus Thrombosis Following
Postoperative Enoxaparin Administration in a 64 YearOld Female
Robert A. Fishman and Ashis Tayal; Pittsburgh, PA
S137 Stroke as a Complication of Tuberculous
Meningitis
Amtul Farheen, Sumaiya Salim, Zoha Fasih, Rony
Dekermenjian and Sushanth Bhat; Edison, NJ
S125 Renal Failure Increases Risk for Intracranial
Hemorrhage Following Stroke
Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and
Rebecca F. Gottesman; Baltimore, MD
S138 Patterns and Mechanisms of Head-Shaking
Nystagmus in Anterior Inferior Cerebellar Artery
Infarction
Young Eun Huh and Ji Soo Kim; Seongnam-si,
Gyeonggi-do, Korea
S126 Dominant Vertebral Artery Occlusion during
Ipsilateral Head Tilt
In Soo Moon, Jae-Hwan Choi and Kwang-Dong Choi; Busan,
Korea
S139 Co-Complaints Influence Odds of Stroke
Diagnosis in ED Dizziness
Ali S. Saber Tehrani, Yu-Hsiang Hsieh, Jonathan A. Edlow,
Carlos A. Camargo and David E. Newman-Toker; Baltimore,
MD and Boston, MA
S127 A Novel Presentation of Mesodiencephalic
Ischemic Stroke: Case Report and Literature Review
Khalid S. Alqadi, Tariq Alfahad and Kathleen Burger;
Washington, DC
S128 Fatal Postpartum Cerebral Vasoconstriction
Syndrome
Jennifer E. Fugate, Eelco F.M. Wijdicks, Kelly D. Flemming
and Alejandro A. Rabinstein; Rochester, MN
S140 Eclamptic Versus Non-Eclamptic PRES (Posterior
Reversible Encephalopathy Syndrome): Comparison of
Clinical Features and Response to Treatment
Pavan Bhargava, Fazeel Siddiqui, Vivek Patel, Rodger J. Elble
and Srikanth Vallurupalli; Springfield, IL
S129 Racial Disparities in Secondary Stroke Prevention
Practices
Pratik Bhattacharya, Seemant Chaturvedi, Flicia Mada, Leeza
Salowich-Palm, Sabrina Hinton, Scott Millis, Sam Watson
and Kumar Rajamani; Detroit, MI and Lansing, MI
Movement Disorders
S201 Allele Specific RNAi Against Triplet Repeat
Disease-Causing Alleles in Huntington Disease
Hirokazu Furuya, Masaki Takahashi, Shoko Watanabe,
Miho Murata, Ichiro Kanazawa, Keiji Wada and Hirohiko
Hohjoh; Omuta, Fukuoka, Japan and Kodaira, Tokyo,
Japan
S130 Predicting Ischemic Stroke Outcomes Based on
Volume of Lesion
Shazia Z. Choudhary, Jay-Ming Wang, Zahid Choudary,
Michael Sloan, Harry R. Van Loveren, Karen R. Wilson,
Morgan Wang and David A. Decker; Tampa, FL and
Orlando, FL
S202 Antigen-Sensitized Dendritic Cell Vaccine Against
Human a-Synuclein: A Potential Cell-Based Therapy
Against Parkinson’s Disease
Chuanhai Cao, Xiaoyang Lin, Wang Li, Cai Jianfeng, Li
Kunyu, Song Shijie and Juan Sanchez-Ramos; Tampa
S131 Treatment Outside the NINDS Stroke Study
Exclusion Criteria: A Case Report
Nhu T. Bruce and Brett C. Meyer; San Diego, CA
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S203 Depressive Symptoms and Neurodegeneration in
the Locus Coeruleus: The Honolulu-Asia Aging Study
Ross Webster, Robert D. Abbott, Helen Petrovitch, Kamal H.
Masaki, Caroline M. Tanner, Jane H. Uyehara-Lock and Lon
R. White; Honolulu, HI; Hiroshima, Japan and Sunnyvale,
CA
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S212 Loss of Cortical Gray Matter in Parkinson’s
Disease
Suman Sen, Paul J. Eslinger, Daymond Wagner, Guangwei
Du, Mechelle M. Lewis, Michel L. Shaffer and Xuemei
Huang; Hershey, PA
S213 Association of PSP with Chemical Occupational
Exposure Factors
Irene Litvan, Christopher R. Cunningham, Peter Lees, Leila
Jackson, Jorge Juncos, David Riley, Yvette Bordelon, David
Standaert, Stephen Reich, Alex C. Cambon, Joseph Jankovic,
Deborah A. Hall, Richard Dubinsky, Cassandra Shepherd,
Claire Henchcliffe, Ryan Uitti, Benzi Kluger, David Shprecher,
Connie Marras, Eliza Gallin, James Leverenz and Shesh N.
Rai; Louisville, KY; Baltimore, MD; Cleveland, OH; Atlanta,
GA; Los Angeles, CA; Birmingham, AL; Houston, TX; Chicago,
IL; Kansas City, KS; New York, NY; Jacksonville, Fl; Boulder,
CO; Salt Lake City, UT; Toronto, Canada and Seattle, WA
S204 MRI in HDLS Shows a Unique Mechanism of
Neuroaxonal Degeneration
C. Sundal*, C. Wider, J.A. Van Gerpen, J. Lash, J.Y.
Garbern, K.J. Schweitzer, J. Aasly, B. Goodman, B.K.
Woodruff, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S.
DeArmond, R. Rademakers, D.W. Dickson, D.F. Broderick, O.
Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville,
FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; San
Francisco, CA; Rochester, MN and Munchen, Germany
S205 Appropriate Outcome Measures for Cognitive
Trials in Huntington’s Disease
Jody Corey-Bloom, Jody Goldstein, Shea Gluhm, Charles Van
Liew, Stephanie Lessig, Jagan Pillai and Steven D. Edland; La
Jolla, CA
S214 Psychiatric Co-Morbidities and Mortality among
Hospitalized Parkinson Disease Patients
Nicte Mejia and Zeina Chemali; Boston, MA
S215 Comparison of Subthalamic (STN) and Pallidal
(GPi) Deep Brain Stimulation (DBS) on Gait and
Balance in Patients with Parkinson’s Disease (PD)
Jyhgong Gabriel Hou, Minn Thant, Aliya Sarwar, Linda
Fincher, Monthaporn S. Bryant, Farrah Atassi and Eugene C.
Lai; Houston, TX and Galveston, TX
S206 Distinctive Neurocognitive Profiles Associated with
Right and Left Motor Symptom Onset in Parkinson’s
Disease
Paul J. Eslinger, Daymond Wagner, Suman Sen, Mechelle M.
Lewis, Guangwei Du, Michele L. Shaffer and Xuemei Huang;
Hershey, PA
S216 Reliability of Self-Reported Parkinson’s Disease
(PD) Features
Caroline M. Tanner, Cheryl Meng, Ira Shoulson, Anthony E.
Lang, David Oakes, Roger Kurlan, Alberto Ascherio, Flint Beal,
Emily Flagg, Jennifer Harman, Michael Schwarzchild, James
Beck, Bernard Ravina, Kenneth Marek, Shirley Eberly, Karen
Marder and Robin Elliott; Sunnyvale, CA; Washington, DC;
Toronto, ON, Canada; Rochester, NJ; Summit, NJ; Boston,
MA; New York, NY; Cambridge, MA and New Haven, CT
S207 The Clinical and Pathological Features of Familial
Parkinsonism with EIF4G1Gene Mutation
Shinsuke Fujioka, Owen A. Ross, Rosa Rademakers, Matthew
J. Farrer, Dennis W. Dickson and Zbigniew K. Wszolek;
Jacksonville, FL and Vancouver, BC, Canada
S208 Alcohol Consumption and Risk of Parkinson
Disease
Rui Liu, Yikyung Park, Xuemei Huang, Xuguang Guo, Albert
Hollenbeck, Aaron Blair and Honglei Chen; Research Triangle
Park, NC; Rockville, MD; Hershey, PA and Washington, DC
S217 First Neurological Examination Can Predict
Course of Parkinson’s Disease (PD)
Ali H. Rajput, Michele L. Rajput and Alex H. Rajput;
Saskatoon, SK, Canada
S209 Hereditary Diffuse Leukoencephalopathy with
Spheroids: An Under-Diagnosed Disease
C. Sundal, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern,
E.A. Shuster, K.J. Schweitzer, J. Aasly, B. Goodman, B.K.
Woodruff, W. Kupsky, A. Tselis, C.W. Christine, M. Baker,
J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W.
Dickson, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden;
Jacksonville, FL; Rochester, NY; Trondheim, Norway;
Scottsdale, AZ; Detroit, MI; San Francisco, CA; Rochester,
MN and Munchen, Germany
S218 Difficulty with Balance Occurs Early in PD: It
Isn’t Appreciated Because It’s Not Asked about Nor
Tested For
Abraham N. Lieberman, Samea Husain, Naomi Salins and
Anthony Santiago; Phoenix, AZ
S219 Poor Dementia Screening with Mattis Dementia
Rating Scale Cutoffs in Highly Educated Parkinson’s
Disease Patients
Travis H. Turner and Vanessa Hinson; Charleston, SC
S210 Co-Existing HTT and ATXN8OS Repeat
Expansions and a ‘Face of the Giant Panda’ Sign on
MRI in a Patient with a Complex Movement Disorder
Shin C. Beh, Cherian A. Karunapuzha and Shilpa Chitnis;
Dallas, TX
S220 Impaired Social Problem-Solving in Huntington’s
Disease
Charles Van Liew, Jody Goldstein, Shea Gluhm, Jagan Pillai
and Jody Corey-Bloom; San Diego, CA
S221 Association of Psychological Symptoms with
Impulse-Control Behaviors after Dopamine Agonist
Therapy for Parkinson’s Disease: A Longitudinal Study
S211 Clinical Differences among PD-MCI Subtypes
Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard and
Christopher G. Goetz; Chicago, IL
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S233 Gender Differences in the Interleukin-6 G-174C
Polymorphism and the Risk of Parkinson’s Disease
Marta San Luciano, Laurie J. Ozelius, Richard B.. Lipton,
Deborah Raymond, Kaili M. Stanley, Susan B. Bressman and
Rachel Saunders-Pullman; New York, NY and Bronx, NY
Jennifer S. Hui, Steven Cen, Megan Gomez and Lauice Yang;
Los Angeles, CA and Pasadena, CA
S222 Balance Difficulty in PD Correlates with Step
Length and Velocity
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
S234 Serum Cholesterol Is Linked with Nigrostriatal
Iron Deposition in Parkinson’s Disease
Guangwei Du, Mechelle M. Lewis, Michele L. Shaffer,
Honglei Chen, Richard B. Mailman and Xuemei Huang;
Hershey, PA and Research Triangle Park, NC
S223 Motor Asymmetry in SCAs
Mitra Assadi, Bhavpreet Dham, Gazelle Zerafati, Jon Veloski
and Paola Leone; Camden, NJ and Philadelphia, PA
S235 Balance Difficulty Differs from Gait Difficulty in PD
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
S224 Neurotoxin Injection for Treatment of Cervical
Dystonia
Chandler E. Gill, Anna L. Molinari, Neil D. Manus, Michael
W. Pelster, Jason A. Cook, Wallace Title and David Charles;
Maywood, IL; Nashville, TN; Minneapolis, MN and New
Orleans, LA
S236 Adult Onset Dopamine Responsive Dystonia
(DRD): Is There a New Gene?
Hossein Ansari, Ludwig Gutmann and Laurie Gutmann;
Morgantown, WV
S237 Dystonia Induced Mechanical Stress as a Cause of
DBS Extension Fracture and Expulsion
Massimo Mondani, Elisa Petacchi, Roberto Eleopra, Silvia
Molteni, Sabrina Gualdi, Miran Skrap and Andrea
Martinuzzi; Udine, UD, Italy; Conegliano, TV, Italy and
Sesto San Giovanni, MI, Italy
S225 The Association between Mediterranean-Type Diet
Adherence and Parkinson’s Disease
Roy N. Alcalay, Yian Gu, Helen Mehia-Santana, Lucien Cote,
Karen S. Marder and Nicholas Scarmeas; New York, NY
S226 Autonomic Dysfunction in Early Parkinson’s
Disease
Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song
and P. David Charles; Nashville, TN
Sleep Disorders and Circadian Rhythm
S301 Endogenous GABAA Receptor Enhancement
Modulates Vigilance in the Primary Hypersomnias
David B. Rye, Kathy Parker, Lynn Marie Trotti, Paul S.
Garcia, James C. Ritchie, Michael J. Owens, Leslie Morrow,
Donald L. Bliwise and Andrew Jenkins; Atlanta, GA;
Rochester, NY and Chapel Hill, NC
S227 Balance Difficulty in PD Correlates with the BNI
Balance Scale
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
S228 STEADY-PD. Safety and Tolerability of Isradipine
CR in Early Parkinson’s Disease. Interim Tolerability
Data Analysis
Tanya Simuni, Kevin Biglan, David Oakes, Cheryl Deeley,
Irenita Gardiner, Parkinson Study Group and STEADY PD
Investigators; Chicago, IL and Rochester, NY
S302 Frequency of Parsaomnias in Patients with NonEpileptic Seizures
Mitchell G. Miglis, Michael Boffa, Sujata Thawani, Alcibiades
Rodriguez and Anuradha Singh; New York, NY
S303 Endothelial Function in Patients with Obstructive
Sleep Apnea
Kanika Bagai, James Muldowney, Yanna Song, Lily Wang,
Douglas E. Vaughan and Beth A. Malow; Nashville, TN and
Chicago, IL
S229 Nigella sativa Oil Controls Astrogliosis and
Reduces Haloperidol-Induced Deficit in Rats
Tafheem Malik**, Darakhshan Jabeen Haleem, Shema Husan,
Shahid Pervez and Tasneem Fatima; Karachi, Sind, Pakistan
and Karachi, Pakistan
Education
S230 Cost-Benefit Assessment of Two Forms of
Botulinum Toxin Type-A in Different Pathologies
Humberto Juarez, Santamaria Salvador, Leticia Hernandez
and Enrique Molina; Mexico City, Mexico, Mexico
S401 The Effectiveness of Education Intervention on
Health Knowledge among Neurological Patients
Mercedes Jacobson and Polina Pomerants; Philadelphia, PA
S231 Weight and Height Distribution in Children with
Tourette Syndrome
Katie Kompoliti, Glenn T. Stebbins and Christopher G. Goetz;
Chicago, IL
S402 Teleneurology in Leading U.S. Medical Institutions
Benjamin P. George**, Nicholas J. Scoglio, Jason I. Reminick,
Kevin M. Biglan and E. Ray Dorsey; Rochester, NY and
Baltimore, MD
S232 Motor Deterioration after Medication Withdrawal
in Early Parkinson’s Disease
Chandler E. Gill**, Anna L. Molinari, Thomas L. Davis,
Mark Bliton, Stuart G. Finder, Michael G. Tramontana, Peter
E. Konrad and David Charles; Maywood, IL; Nashville, TN
and Los Angeles, CA
S403 Standardized Sign-Out Improves Communication
Skills
Brian D. Moseley, Jonathan H. Smith, Gloria E. DiazMedina, Mateo Paz Soldan, Meredith Wicklund, Radhika
Dhamija, Haatem Reda, Michael F. Presti and Jeffrey W.
Britton; Rochester, MN
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S404 Improved Scores on the AAN Resident Inservice
Training Examination (RITE) after Lecture Curriculum
Intervention
L. John Greenfield, Vicki Ramsey-Williams, Theresa Marshall
and Boyd Koffmann; Toledo, OH and Little Rock, AR
Stage:
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M605 Areas of Ischemia Associated with ‘‘Frontal Lobe’’
Task Failure
Yessenia Gomez and Argye E. Hillis; Baltimore, MD
M606 Thalamic Atrophy in Gastric Bypass Patients with
Cognitive Complaints
Jonathan Graff-Radford, Jennifer Whitwell, Max R. Trenerry,
J.E. Ahlskog, Michael D. Jensen, Clifford R. Jack, Jr. and
Keith A. Josephs; Rochester, MN
nd
S405 Evidence Based Medicine(EBM) in the 2 Year
Neurosciences Curriculum
Michael J. Schneck and Edward Neafsey; Maywood, IL
S406 Adapting a Teaching Hospital Inpatient Neurology
Service to New Duty Hour Requirements: The
Washington University Adult Neurology Experience
Robert Bucelli and Barbara J. Snider; Saint Louis, MO
M607 Parietal Lobe Lesions Affect the Generation of
Antisaccades
James A. Sharpe, Ping Cheng and Moshe Eizenamn; Toronto,
ON, Canada
S407 Translational Research in Neuro-AIDS and Mental
Health
Amanda Brown, Valerie Wojna, Bruce Shiramizu, Avindra
Nath and Justin C. McArthur; Baltimore, MD; San Juan, PR
and Honolulu, HI
M608 Cognitive Ability Correlates of Psychiatric and
Social Behaviors in Williams Syndrome
Rowena Ng, Anna Ja¨rvinen-Pasley and Ursula Bellugi;
San Diego, CA
M609 Human Brain Mapping at the Single Cellular
Level: Neuronal and Area Specific Differences in Health
and Diseases
Ryan P. Moore, Irisa Mahaparn, Eliezer Masliah and
Pavel V. Belichenko; La Jolla, CA
S408 Relationship between Medical Student Feedback
and Grading
and James M. Stankiewicz; Boston, MA
136th Annual Meeting Monday,
September 26, 2011
Poster Session
M610 Cognitive and Behavioral Differences between
ADHD Populations (Inattentive Type Versus ADHD
Plus) Using Neuropsychological Testing and
Self-Reported Symptoms in Diagnosed Population
from Years 1991–2008
Barbara C. Fisher, Danielle M. Garges and Stephany Fulda;
Shelby Township, MI and Munich, Germany
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
M611 The Use of Quetiapine in Agitated Patients
with Acquired Brain Injury: A Case Control
Study
Sara Piccoli, Gabriella Paparella, Alec Vestri and Andrea
Martinuzzi; Pieve di Soligo, TV, Italy
Behavioral Neurology
M601 Behaviorally-Driven Anatomical Mapping of
Hemispatial Neglect
Alex R. Carter, Mark P. Mcavoy, Serguei V. Astafiev, Jennifer
Rengachary, Daniel L.W. Pope, Abraham Z. Snyder, Kristi
Zinn, Nick Metcalf, Gordon L. Shulman and Maurizio
Corbetta; Saint Louis, MO
M612 On-Line Lexical-Semantics in the Semantic
Variant of Primary Progressive Aphasia
David S. Race and Argye E. Hillis; Baltimore, MD
M613 Differences in Time Interval Distributions
Reveal Controlled and Automatic Contributions to
Cued Word Retrieval
Kyongje Sung, Erin J. Pickett, Kerry Ledoux, Tracy D.
Vannorsdall, Mohammad Elsayed, Nia M. Billings,
Jessica Silva, David J. Schretlen and Barry Gordon;
Baltimore, MD
M602 Markers of Celiac Disease and Gluten Sensitivity
in Patients with Cerebellar Ataxia
Caroline Tan, Peter H. Green, Khalaf O. Bushara, Donald D.
Kasarda, Ejaz Shamim, Norman Latov, Mark Hallett and
Armin Alaedini; New York, NY; Minneapolis, MN; Albany,
CA and Bethesda, MD
M614 Gender Differences across the Lifespan in
Neuropsychological Testing Performance in ADHD
Population from the Years 1991–2008
Barbara C. Fisher, Danielle M. Garges and Stephany Fulda;
Shelby Township, MI and Munich, Germany
M603 Early Signs of Cognitive Impairment among
Multiple Sclerosis Patients with Clinically Isolated
Syndrome
Theodora Panou, Vasileios Mastorodemos, Efrosyni Papadaki,
Panagiotis G. Simos and Andreas Plaitakis; Heraklion, Greece
and Rethymnon, Greece
M615 Hazard Perception in Cognitively Impaired Older
Drivers
Nazan Aksan, Monica Lees, John D. Lee, Shaun Vecera and
Matthew Rizzo; Mountain View, CA; Madison, WI and Iowa
City, IA
M604 Motor Chunking Is Correlated with Sensorimotor
Cortex and Striatum Activation
Nicholas Wymbs and Scott T. Grafton; Santa Barbara, CA
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M616 Differentiation of Alzheimer’s Disease and
Depression with Standard Cognitive Measures
Meredith C. Frederick**, Stefan Sillau, David B. Arciniegas,
C. Alan Anderson, Katherine L. Howard and Christopher M.
Filley; Aurora, CO and Denver, CO
M705 JAK/STAT Inhibition Slows the Progression of
Temporal Lobe Epilepsy in an Animal Model
Heidi L. Grabenstatter, Yasmin Cruz Del Angel, Marco I.
Gonzalez, Yogendra H. Raol, Shelley J. Russek and Amy R.
Brooks-Kayal; Aurora, CO and Boston, MA
M617 Attention Deficit Hyperactivity Disorder in
Depressed Adults
Ildefonso Rodrı´guez Leyva, Rube´n Haro SIlva and Ana A.
Renterı´a Palomo; San Luis Potosi, San Luis Potosi, Mexico
M706 Long-Term Changes in mGluR-Mediated LongTerm Depression Following a Single Episode of Early
Life Seizures in Rats
Paul B. Bernard, Anna Castano and Tim A. Benke; Aurora,
CO
M618 Cognition and EEG Abnormalities in NonEpileptic AD(H)D/LD Patients with and without AntiEpileptic Drug/Stimulant Therapy
Brittany M. DiVito, Heather A. Koch, Spencer A. Leblang,
Erik C. Bakken and Drake D. Duane; Scottsdale, AZ and
Tempe, AZ
M707 Heterozygous Loss of the Epilepsy-Associated
GABAA Receptor a1 Subunit Causes Spontaneous EEG
Spike Discharges in Two Mouse Strains
Fazal M. Arain and Martin J. Gallagher; Nashville, TN
M708 Regional Network Disruption in Temporal Lobe
Epilepsy
Luigi Maccotta* and Edward Hogan; St. Louis, MO
M619 Evolution of EEG Abnormalities in Non-Epileptic
AD(H)D/LD Patients with and without Anti-Epileptic
Drug/Stimulant Therapy
Heather A. Koch, Brittany M. DiVito, Spencer A. Leblang,
Erik C Bakken and Drake D. Duane; Scottsdale, AZ and
Tempe, AZ
M709 Mice Deficient in SNAREs/SNARE Regulators
Predict Kindling Phenotype
John T. Slevin, Elena E. Matveeva, Sidney W. Whiteheart,
Greg A. Gerhardt and Thomas C. Vanaman; Lexington, KY
M620 Transection of CA3 Does Not Affect Memory in
Rats
Mohamad Z. Koubeissi, Saifur Rashid, Gemma Casadesus,
Joseph LaManna, Kui Xu, Hans Luders and Dominique
Durand; Cleveland, OH
M710 Pharmacokinetic Equivalence between ImmediateRelease and Extended-Release Topiramate
Lawrence J. Lambrecht, Wesley M. Todd and Mark B.
Halvorsen; Maple Grove, MN
M711 Cingulate Epilepsy, Reporting 3 Clinical and
Electrophysiologic Subtypes with Surgical Outcomes
Mhd Rafeed Alkawadri, Norman K. So, Paul C. Van Ness
and Andreas V. Alexopoulos; Cleveland, OH and Dallas, TX
M621 Cruetzfeldt-Jakob Disease Presenting as a Rapidly
Progressing Dementia with Non-Convulsive Status
Epilepticus
Natasha Tilluckdharry, Megan McGarry and Dipak P.
Pandya; Paterson, NJ
M712 GABAB Receptor Antagonists Reduce ProEpileptic Activity in Hippocampal Slices of Ts65Dn
Mice, a Genetic Model of Down Syndrome
Alexander M. Kleschevnikov, Brett Rasmuss, Pavel V.
Belichenko and William Mobley; La Jolla, CA
Epilepsy
M701 Controlled Cortical Impact in Adult Rats and
Posttraumatic Seizures and Epilepsy
Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller, Bo Lu
and Zakaria Mtchedlishvili; Pittsburgh, PA and
Philadelphia, PA
M713 Lacosamide: Long-Term Safety and Efficacy in
Partial-Onset Seizures
William Rosenfeld, Nathan B. Fountain, Gintaras Kaubrys,
Elinor Ben-Menachem, Cindy McShea, Jouko Isojarvi and
Pamela Doty; St. Louis; Charlottesville; Vilnius, Lithuania;
Go¨teborg, Sweden and Raleigh
M702 Serotonin 1A Receptors and Memory in Temporal
Lobe Epilepsy
William H. Theodore, Edythe Wiggs, Ashley Martinez, Irene
Dustin, Omar Khan, Shmuel Appel, Patricia Reeves-Tyer and
Susumu Sato; Bethesda
M714 Lacosamide: Long-Term Safety in Partial-Onset
Seizures
Robert F. LeRoy, Gregory Krauss, Nathan B.. Fountain,
Deanne Dilley, O’Neill D’Cruz and Pamela Doty; Dallas, TX;
Baltimore, MD; Charlottesville, VA and Raleigh, NC
M703 Ictal Hypoxemia Is Associated with Cardiac
Repolarization Abnormalities
Lisa M. Bateman, Franchette Pascual, Michael Lee, ChinShang Li and Masud Seyal; Sacramento, CA and Los Angeles,
CA
M715 Withdrawn.
M716 Computational Models of Ligand-Gated Receptor
Function Characterize Anticonvulsant Drug Actions at
GABAergic and Glutamatergic Synapses
and David E. Naylor; Torrance, CA
M704 Gray Matter Heterotopia in an Epileptic Brain
Malformation Are Functionally Connected to Overlying
Cortex
Joanna A. Christodoulou, Linsey M. Walker, Stephanie N. Del
Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E.
Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA
and Haifa, Israel
M717 Status Epilepticus: An Independent Predictor of
Poor Survival after Anoxic Brain Injury
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M806 Reevaluating Disease Progression in
Facioscapulohumeral Dystrophy
Jeffrey M. Statland*, William B. Martens, Kathryn R. Wagner,
John Kissel, Shree Pandya, Michael P. McDermott and Rabi
Tawil; Rochester, NY; Baltimore, MD and Columbus, OH
Jennie Luna, Nelly Awkar, Megan McGarry, Deepthi
Karanam and Dipak P. Pandya; Paterson, NJ
M718 Periodic Lateralized Epileptiform Discharges
(PLEDs)-Rhythmic Discharges (RDs) in Anoxic
Encephalopathy
Sushanth Bhat, Sombabu Maganti, Eli S. Neiman, Divya
Gupta and Sudhansu Chokroverty; Edison, NJ
M807 Dysferlin (DYSF) Is Absent from the Muscle-Fiber
Sarcolemma in Various Neuromuscular Diseases, and in
Sporadic Inclusion-Body Myositis (s-IBM) It Forms
Cytoplasmic Inclusions Colocalizing with Amyloid-b42
(Ab42)
Mafalda Cacciottolo, Anna Nogalska, Carla D’Agostino, W
King Engel and Valerie Askanas; Los Angeles, CA
M719 Periodic Lateralizing Epileptiform Discharges
(PLEDs) Causing Persistent Magnetic Resonance
Imaging (MRI) Changes in Ipsilateral Thalamus
Umang Shah, Umer Akber and Chunyang Wang; Camden, NJ
M808 Novel Demonstration of ConformationallyModified Tau in Sporadic Inclusion-Body Myositis
(s-IBM) Muscle Fibers. Possible Importance to s-IBM
Pathogenesis
Anna Nogalska, Carla D’Agostino, King W. Engel and Valerie
Askanas; Los Angeles, CA
M720 Ammoniacal Encephalopathy Presenting as
Complex Partial Seizure-Like Episodes: A Case Series
Darine Kassar and Stanley Iyadurai; Saint Louis, MO
M721 Status Epilepticus as an Initial Manifestation of
Sneddon’s Syndrome
Anish Shah, Saurav Sen, Jennie Luna and Dipak P. Pandya;
Paterson, NJ
M809 Anti-Ganglioside Antibodies Mimic CNS
Inhibitors of Axon Regeneration
Kazim Sheikh and Gang Zhang; Houston, TX
M722 Status Epilepticus Secondary to Milk Alkali
Syndrome Induced by Hypercalcemia (Oral Antacids)
Rabih Kashouty, Noor Yono and Mershed Al Samara;
Manhattan, NY; Manhasset, NY and Southfield, MI
M810 Evaluating Mechanoreceptors in Glabrous Skin in
Diabetic Neuropathy
Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier;
Nashville, TN
M723 A Case of Magnesium-Responsive Paraneoplastic
Non-Convulsive Status Epilepticus
Robert K. Shin, Anna V. Rosenbaum and Nicholas Frost;
Baltimore, MD
M811 Amiodarone Associated Myopathy. A Report of 4
Cases
Eoin P. Flanagan, Charles M. Harper, Erik K. St. Louis,
Michael H. Silber, Ronald C. Petersen and Keith A. Josephs;
Rochester, MN
M724 Withdrawn.
Neuromuscular Disease
M812 Cervical Cord 1H-Magnetic Resonance Spectroscopy
(1H-MRS) in Amyotrophic Lateral Sclerosis (ALS):
Relationship to Clinoco- Electrophysiological Dysfunction
Ken Ikeda, Yasuhiro Yoshii, Kiyoko Murata, Riya Nagata,
Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan
M801 Nicotinamide Mononucleotide (NMN) Treatment
of Diabetic Neuropathy
Ankit Sura, Mitch Onken, Krish Chandrasekaran, Helen Chen
and James W. Russell; Baltimore, MD
M813 Localization of FIG4 in the Nervous System
Jiasong Guo, Qing Yan and Jun Li; Nashville, TN
M802 Defining Outcome Measures in Sporadic IBM for
a Follistatin Gene Transfer Clinical Trial
Linda P. Lowes, Lindsay N. Alfano, Laurence ViolletCallendret, Xiomara Q. Rosales, Brian Kaspar, K. Reed Clark,
Zarife Sahenk, Kevin M. Flanigan and Jerry R. Mendell;
Columbus, OH
M814 High Frequency Chest Wall Oscillation
(HFCWO) in Amyotrophic Lateral Sclerosis (ALS)
Patients Decreases Respiratory Infections Requiring
Antibiotics and/or Hospitalization: A Pre-Post
Observational Study
Benjamin R. Brooks, Velma L. Langford, Amber L. Ward,
Nicole M. Williams, Mindy S. Nichols, Elena Bravver and
Scott C. Lindblom; Charlotte, NC
M803 Tomaculous Formation in HNPP
Jun Li, Zahara M. Jaffer, Xuebao Zhang, Qing Yan, Michael
E. Shy, Ueli Suter, Jonathan Chernoff and Jiasong Guo;
Nashville, TN; Philadelphia; Nashville; Detroit and Zurich,
Swaziland
M815 Dominant Cardiomyopathy and Very Distal
Myopathy with Rod, Myofibrillar and AVSF
Myopathology
Stanley J. Iyadurai, Chris Weihl, Bob Baloh and Alan
Pestronk; St. Louis, MO
M804 Zebrafish Models of Amyotrophic Lateral
Sclerosis
Stacey A. Sakowski, J. Simon Lunn, Angela S. Busta, Carey
Backus, Sang Su Oh, James J. Dowling and Eva L. Feldman;
Ann Arbor, MI
M816 Adult-Onset Rod Myopathy Syndrome (AORMS):
Sustained Benefit from IVIG Plus Rituximab
Shalini Mahajan, King W. Engel, Valerie Askanas,
Indermohan Luthra and Varun Gupta; Los Angeles, CA and
Rancho Mirage, CA
M805 ALS-Like Spinal Cord Pathology in Transgenic Mice
with a Mutation in the Valosin-Containing Protein Gene
Hong Z. Yin, Tahseen Mozaffar, Virginia E. Kimonis and
John H. Weiss; Irvine, CA
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M817 Geographic Trends of ALS in Minnesota
Eric J. Sorenson and Lisa Kronk; Rochester, MN and
Minneapolis, MN
Stage:
Page: 11
M827 Subacute Paraneoplastic Motor Neuronopathy
with Ri Immunoeactivity and Breast Cancer: A
Clinicopathologically Studied Patient
and David S. Younger; New York, NY
M818 Clinical Features Associated with Fine Specificity
of IgG Anti-GQ1b Antibodies
Susumu Kusunoki, Seiko Suzuki, Masami Ueda and Motoi
Kuwahara; Osaka-Sayama, Osaka, Japan
M828 Magnetic Resonance Neurography Versus
Electromyography for the Diagnosis of
Radigulopathy
Youssef A. Dakka, Andrew Biondo, John Corrigan,
Shehanaz Ellik and Ximena Arcilla-Londono;
Detroit, MI
M819 Amyotrophic Lateral Sclerosis [ALS] Dashboard:
Cognitive, Behavioral, Bulbar, Respiratory, Arm, Leg
Domain-Specific Disease Staging – Statistically
Significant Larger Proportion of Stage 3 Behavioral,
Bulbar, Arm and Leg, but Not Cognitive or Re
Benjamin R. Brooks, Mohammed S. Sanjak, Elena Bravver,
William L. Bockenek, Urvi G. Desai, Scott C. Lindblom,
Thomas J. Paccico, Nicole M. Williams, Mindy S. Nichols,
Amber L. Ward, Kathryn A. Wright, Mifflin O’Neill, Velma
L. Langford, Kristy Walgren, Priscilla Russo, Anne Blythe and
Heather Oplinger; Charlotte, NC
M829 Denervation Causes Lower Expression of Heat
Shock Protein 27 in Regenerating Skeletal Muscle
Takahiro Jimi, Yoshihiro Wakayama and Hajime Hara;
Yokohama, Japan
M830 Rapid Magnetic Stimulation Versus Conventional
Physiotherapy in Bell’s Palsy
Devathasan Gobinathan and Lea Dosado; Singapore,
Singapore
M820 A New Phenotype in Neurodegeneration:
Trigeminal Sensory Deficits Preceding Rostro-Caudal
Progressive Motor and Sensory Neuronopathy, Chorea
and Dementia
Camilo Toro, Justin Y. Kwan, Tanya J. Lehky, Bryan J.
Traynor, Catherine A. Groden, Rena A. Godfrey, Michele E.
Nehrebecky, Wiggs A. Edythe and Gahl William; Bethesda, MD
M831 Establishing a Rare Disease Center in China: The
Periodic Paralysis Program
Qing Ke, Benyan Luo, Ming Ming, Michael Hanna, Jacob
Levitt, Barbara Herr and Robert C. Griggs; Hang Zhou, Zhe
Jiang, China; Rochester, NY; London, United Kingdom and
New York, NY
M821 Update on a Phase 1 Study of ISIS 333611 in
Familial ALS Due to SOD1 Mutations
Timothy M. Miller, Richard Smith, Swati Aggarwal, Alan
Pestronk, William David, Jeffrey Rothstein, Ericka Simpson,
Benjamin Brooks, Isaac Bakst, Patricia Andres, Peggy Allred,
Katie Alexander, Kathie Bishop, C.F. Bennett and Merit
Cudkowicz; St. Louis, MO; La Jolla, CA; Boston, MA;
Baltimore, MD; Houston, TX; Charlotte, NC and
Carlsbad, CA
M832 Effect of Fatigue on Pulmonary Function Studies
in ALS Patients
Kathleen S. Alfuth, Ericka P. Simpson and Aparajitha K.
Verma; Houston, TX
M833 Monomelic Amyotrophy – A Rare Case
Presentation
Amtul Farheen, Manpreet Multani, Aiesha Ahmed, Raji
Grewal and Raji Grewal; Edison, NJ
M822 Retrospective Analysis of a Cohort of Non
Systemic Vasculitic Neuropathy
Raghav Govindarajan, Jagadish B. Agadi, Anita Mahadevan
and S.K. Shankar; Weston, FL and Bangalore, India
M834 Botulism: A Case Report
Peter Struck, Amtul Farheen and Sushanth Bhat; New
Brunswick and Edison, NJ
M835 A Novel Pentameric Thiophene Derivative
(p-FTAA) Strongly Highlights Clusters of Paired Helical
Filaments Containing Phosphorylated Tau in Sporadic
Inclusion-Body Myositis (s-IBM) Muscle Fibers
There´se Klingstedt, Anna Nogalska, Cristiane Blechschmidt,
Stefan Prokop, Frank L. Heppner, King W. Engel, Valerie
Askanas and Peter K.R. Nilsson; Linko¨ping, Sweden; Los
Angeles and Berlin, Germany
M823 Optimizing a Hospital Discharge Database for
Passive Surveillance of Guillain-Barre Syndrome (GBS)
Christopher D. Lee and Timothy F. Jones; Nashville, TN
M824 Gene Expression Analysis in Patients with
Amyotrophic Lateral Sclerosis and Multifocal Motor
Neuropathy
Alexander Shtilbans, Soon Gang Choi, Mary E. Fowkes, Greg
Khitrov, Mona Shahbazi, Jess Ting, Stuart C. Sealfon and
Dale J. Lange; New York, NY
Neurogenetics
M1001 Withdrawn.
M825 Small-Fiber Polyneuropathy (SFPN) Can Cause
Chronic Pain and Somatic Complaints in Youth
and Anne Louise Oaklander; Boston, MA
M1002 Clinico-Genetic Characterization of a
Large Italian Cohort with Primary Spastic
Paraplegia
Andrea Martinuzzi, Mariateresa Bassi, Grazia D’Angelo,
Sara Bonato, Gabriella Paparella, Olimpia Musumeci,
Mariagiovanna Rossetto, Marianna Fantin, Francesca Peruch,
Alessia Arnoldi, Claudia Crimella, Erika Tenderini, Paolo
M826 Median Nerve Ultrasound in Diabetic PN with
and without Carpal Tunnel Syndrome
Anhar Hassan, Andrea Leep Hunderford, James Watson,
Andrea Boon and Eric Sorenson; Rochester, MN
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M1102 Computed Tomography Characteristics of
Pediatric Traumatic Brain Injury
Korak Sarkar and Kia Shahlaie; Sacramento
Bonanni, Vanessa Casanova, Giovanni Meola, Giacomo Comi,
Antonio Toscano and Nereo Bresolin; Conegliano, TV,
Italy; Bosisio Parini, LC, Italy; Messina, Italy and
Milano, Italy
M1103 Neurological Outcome Scale for Traumatic Brain
Injury: Predictive Validity and Sensitivity to Change
Paolo Moretti, Stephen R. McCauley, Elisabeth A. Wilde,
James N. Scott and Guy L. Clifton; Houston, TX and Calgary,
AB, Canada
M1003 A Study of ACE and ADD1 Gene Polymorphism
in Extra and Intracranial Atherosclerosis in Patients with
Ischemic Stroke
Jayantee Kalita, Usha K. Misra, Sunil Kumar, Bishwanath
Kumar, Bindu I. Somarajan and Balraj Mittal; Lucknow,
Uttar Pradesh, India
M1104 Determination of Awareness in Patients with
Severe Brain Injury Using EEG Spectral Analysis
Andrew M. Goldfine, Jonathan D. Victor, Mary M. Conte,
Jonathan C. Bardin and Nicholas C. Schiff; New York, NY
and White Plains, NY
M1004 Generation and Characterization of MeCP2_270
Mutant Mice
Chiranjeevi Bodda, Karolina Can, Liakath Ali Kifayathulla,
Hope Yao Agbemenyah and Ashraf U. Mannan; Goettingen,
Germany
M1105 Orthopedic Injuries in Multiple Sclerosis
Patients: Analysis of the Incidence of Injury in This
Vulnerable Population
Daniel Mandell** and William Tosches; Worcester, MA
M1005 Identification of Epigenomic Modifications as
Biomarkers for Amyotrophic Lateral Sclerosis
Claudia Figueroa-Romero, Junguk Hur, Yu Hong, John S.
Lunn, Crystal Pacut, Colin E. Delaney, Raymond Yung,
Brian Callaghan and Eva L. Feldman;
Ann Arbor, MI
M1106 Raising the Dead: Barriers to Therapeutic
Hypothermia Post Cardiac Arrest
and Mark Andrews; Palo Alto, CA
M1006 A Drosophila Model of Williams Syndrome
Ralph J. Greenspan and Jenee Wagner; La Jolla, CA
M1107 Abnormal Oculomotor Function among BlastInjured Combat Veterans
Bruce P. Capehart, Adam Mehlenbacher, Carol SmithHammond, Dale Bass and James Burke; Durham, NC
M1007 Clinical and Pathological Features of Progressive
Supranuclear Palsy with Family History
Shinsuke Fujioka, Avi Algom, Audrey Strongosky, Dennis W.
Dickson and Zbigniew K. Wszolek; Jacksonville, FL
Neurology Critical Care
M1201 Withdrawn.
M1008 Aberrant Methylation by Mutations of DNA
Methyltransferase 1 Cause Peripheral and Central
Axonal Degeneration
Christopher J. Klein, Maria V. Botuyan, Yanhong Wu,
Christopher J. Ward, Garth A. Nicholson, Simon Hammans,
Hiromitch Yamanishi, Adam R. Karpf, Douglas C. Wallace,
Mariella Simon, Cecilie Lander, Julie M. Cunningham,
Glenn E. Smith, William J. Litchy, Benjamin Boes,
Elizabeth J. Atkinson, Sumit Middha, P. James Dyck,
Joseph E. Parisi, Georges Mer, David I. Smith and Peter J.
Dyck; Rochester, MN; Sydney, Australia; Southampton,
United Kingdom; Hyogo, Japan; Buffalo, NY; Irvine, CA;
Herston, Australia and Indianapolis, IN
M1202 Predictors of Outcome in Prolonged Refractory
Status Epilepticus
Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M.
Wijdicks and Alejandro A. Rabinstein; Rochester, MN
M1203 Refractory Status Epilepticus and Heart Damage
– A Warning for Neurologists
Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M.
Wijdicks and Alejandro A. Rabinstein; Rochester, MN
M1204 Safety and Feasibility of Intrathecal Nicardipine
for Vasospasm after Subarachnoid Hemorrhage
William D. Freeman, Sothear Luke, Christina Campbell, Dan
Jackson and James F. Meschia; Jacksonville, FL
M1009 Common and Distinct Associations of
HLA-DRB1 and -DPB1 Alleles with Neuromyelitis
Optica and Multiple Sclerosis in Japanese
Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita,
Tomomi Yonekawa, Katsuhisa Masaki and Jun-ichi Kira;
Fukuoka, Japan
M1205 Acute Bacterial Meningitis as a Possible Cause of
Severe Dysautonomia Leading to Death
Yadira Velazquez-Rodriguez, Umer Akbar and Evren
Burakgazi-Dalkili; Camden, NJ
M1010 Computer Simulations of Striatal Atrophy and
Age at Onset of Huntington’s Disease
Steven D. Edland and Jagan Pillai; La Jolla, CA
Pediatric Neurology
M1301 Diffusion Tensor MRI Tractography Reveals
Altered Brainstem Fiber Connections Accompanying
Agenesis of the Corpus Callosum
Juebin Huang, Jian Chen, Haipeng Cai, Robert P. Friedland,
Mohamad Z. Koubeissi, David H. Laidlaw and Alexander P.
Auchus; Jackson, MS; Hattiesburg, MS; Louisville, KY;
Cleveland, OH and Providence, RI
Trauma/Injury
M1101 A Human Natural IgM Drives Axon Outgrowth
Xiaohua Xu, Arthur Warrington, Brent Wright, Allan Bieber,
Virginia Van Keulen, Larry Pease and Moses Rodriguez;
Rochester, MN
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M1302 Neurofibromatosis 1 (NF1) Vasculopathy in
Children – An Emerging Entity
Partha S. Ghosh, A.D. Rothner and Manikum Moodley;
Cleveland, OH
Stage:
Page: 13
Mariet Allen, Minerva M. Carrasquillo, Christopher N.
Rowley, Otto Pedraza, Morad Ansari, Caroline Hayward,
Igor Rudan, Harry Campbell, Ozren Polasek, Nicholas D.
Hastie, Asha A. Nair, Sumit Middha, Sooraj Maharjan,
Thuy Nguyen, Li Ma, Kimberly G. Malphrus, Ryan Palusak,
Sarah Lincoln, Gina Bisceglio, Constantin Georgescu,
Christopher P. Kolbert, Jin Jen, Zbigniew Wszolek, Maria
Barcikowska, Sigrid B. Sando, Jan Aasly, Kevin Morgan,
Clifford Jack, Ronald C. Petersen, Neill R. Graff-Radford,
Alan Wright, Dennis W. Dickson and Steven G. Younkin;
Jacksonville, FL; Rochester, MN; Edinburgh, United
Kingdom; Split, Croatia; Zagreb, Croatia; Warsaw,
Poland; Trondheim, Norway and Nottingham,
United Kingdom
M1303 Macro CK-1 a Cause of Spuriously
Elevated CK Associated with Leukoencephalopathy
in an Infant
and John B. Bodensteiner; Phoenix, AZ
M1304 Pharmaceuticals in the Environment: A
Focus on Neurological Medications
and Ilene Ruhoy; Seattle, WA
Rehabilitation and Regeneration
T1504 Insulin-Like Growth Factor 1 (IGF-1) and Risk
of Alzheimer’s Disease: The Framingham Study
Andrew J. Westwood*, Alexa S. Baiser, Ramachandran S.
Vasan, Tamara B. Harris, Ronenn Roubenoff, Aleksandra
Pikula, Rhoda Au, Charles DeCarli, Philip A. Wolf and
Sudha Seshadri; Boston, MA; Framingham, MA; Bethesda,
MD and Sacremento, CA
M1401 Human Induced Pluripotent Stem
Cell-Derived Neural Progenitor Grafting into
Rat Hippomcapus
Alison L. Althaus, Yu Liu, Duriel Hardy and Jack M. Parent;
Ann Arbor, MI
M1402 Local Molecular Manipulation and Peripheral
Nerve Regeneration
Douglas W. Zochodne, Kimberly J. Christie, Christine A.
Webber, Chu Cheng and Jose A. Martinez; Calgary, AB,
Canada and Edmonton, AB, Canada
T1505 Components of Blood Pressure and Progression
of Cerebral Leukoaraiosis: The ARIC Study
Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker,
Josef Coresh, Clifford R. Jack, Jr., David S. Knopman,
Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and
Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC;
Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle,
WA and Jackson, MS
M1403 Very Early Gait Training after Acute Stroke; a
Dose-Escalation Study
Randolph S. Marshall, Ying K. Cheung, Clare Bassile, Laura
A. Evensen, Roujie Chen, Veronica Perez, Ronald M. Lazar
and Bernadette Boden-Albala; New York
T1506 Therapeutic and Preventive Effects of a Novel
AD Vaccine
Carmen Vigo, Ivan Cuevas, Lucia Fernandez, Valter
Lombardi, Richard Manivanh and Ramon Cacabelos;
Sunnyvale, CA and Bergondo, La Coruna, Spain
th
136 Annual Meeting Tuesday,
September 27, 2011
Poster Session
T1507 MoCA vs. MMSE: Patterns of Cognitive
Performance across Adult Lifespan in a Non-Clinical
Sample
Shea Gluhm, Charles Van Liew, Jody Goldstein, Guerry Peavy,
Mark Jacobson, Stephanie Lessig and Jody Corey-Bloom; La
Jolla, CA and San Diego, CA
Posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
T1508 Amyloid Imaging with Florbetapir-PET
Correlates with Cognitive Performance in NonDemented Oldest-Old
Maria M. Corrada, Dana E. Greenia, Chris M. Clark, Carrie
B. Peltz, Mark A. Mintun, Michael J. Pontecorvo, Abhinay D.
Joshi and Claudia H. Kawas; Irvine, CA; Philadelphia, PA
and St. Louis, MI
Dementia and Aging
T1501 Amyloid-Beta Dynamics and Prevention Trials in
Dominantly Inherited Alzheimer’s Disease
Randall J. Bateman and on behalf of the Dominantly
Inherited Alzheimer Network; St. Louis, MO
T1502 Integrating Genome-Wide Association and
Functional Validation To Understand Susceptibility for
Alzheimer’s Pathology
Joshua M. Shulman, Portia I. Chipendo, Lori B. Chibnik,
Brendan T. Keenan, Dong Tran, Matthew A. Huentelman,
Julie A. Schneider, Eric M. Reiman, Denis A. Evans, David
A. Bennett, Mel B. Feany and Philip L. De Jager; Boston,
MA; Chicago, IL and Phoenix, AZ
T1509 FRET Measurements of Ab-Induced Glutamate
Release from Astrocytes
Sara Sanz-Blasco, Juan C. Piña-Crespo, Maria V. Talantova
and Stuart A. Lipton; La Jolla, CA
T1510 Is Poststroke Dementia Related to Amyloid
Deposition and Microglia Activation?
Wolf-Dieter Heiss, Basia Radlinska, Jean-Paul Soucy, Ralf
Schirrmacher, Alexander Thiel and Vladimir Hachinski;
Cologne, Germany; Montreal, QC, Canada and London, ON,
Canada
T1503 Brain Expression Genome-Wide Association
Study (eGWAS) and Alzheimer’s Disease
Nilufer Ertekin-Taner, Fanggeng Zou, High Seng Chai,
Curtis S. Younkin, Julia Crook, V Shane Pankratz,
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T1511 Cycad Methylazoxymethanol Linked to DNA
Damage, Cancer and Neurodegeneration
Glen E. Kisby, Rebecca C. Fry, Michael R. Lasarev, Theodor
K. Bammler, Richard P. Beyer, Mona I. Churchwell, Daniel R.
Doerge, Lisiane B. Meira, Valerie S. Palmer, Ana-Luisa
Ramos-Crawford, Xuefeng Ren, Robert S. Sullivan, Terrance J.
Kavanagh, Leona D. Samson, Helmut Zarbl and Peter S.
Spencer; Portland, OR; Seattle, WA; Cambridge, MA;
Jefferson, AR; Guildford, Kent, United Kingdom; Buffalo, NY;
Piscataway, NJ and Chapel Hill, NC
Stage:
Page: 14
T1520 The First Nationwide Survey of Bardet-Biedl
Syndrome in Japan
Makito Hirano, Toshihide Yamashita, Yasushi Ikuno, Hiromi
Iwahashi, Mitsuru Ohishi, Toshiyuki Mano, Ryu Ishihara, Ichiro
Tanaka, Keiko Yanagihara, Yusaku Nakamura and Susumu
Kusunoki; Sakai, Osaka, Japan; Suita, Japan; Izumi, Japan;
Osaka, Japan; Kashihara, Japan and Osaka Sayama, Japan
T1521 P600 Word Repetition Effect Amplitude
Correlates with Left Hippocampal Volume
John M. Olichney, Rawi Nanakul, Alireza K. Javan, Patrick
E. Adams, Andrea Schneider, Andreea Seritan, Randi J.
Hagerman, Paul J. Hagerman and Susan M. Rivera; Davis,
CA and Sacramento, CA
T1512 Genetic Associations between VPS10 Receptor
Genes and Late-Onset Alzheimer’s Disease
Christiane Reitz, Joseph Lee, Lindsay Farrer, Margaret PericakVance, Jonathan Haines, Ekaterina Rogaeva, Peter St. GeorgeHyslop and Richard Mayeux; New York; Boston; Miami;
Nashville and Toronto, Canada
T1522 Visuospatial Construction Measures and Their
Utility in Identifying Dementia of the Alzheimer’s Type
Bonnie M. Scott, G. Duncan, H. Carlson, Matthew Nance,
Michele K. York, Angela Larery, Josephine Stouter and Adriana
M. Strutt; Houston, TX
T1513 Cardiac Ejection Fraction, Cognitive Function
and Leukoaraiosis in an Elderly Cohort: The
Cardiovascular Health Study
Rebecca F. Gottesman, Salvador Cruz-Flores, Annette
Fitzpatrick, John Gottdiener, Traci Bartz, Richard Kronmal
and W.T. Longstreth, Jr.; Baltimore, MD; St. Louis, MO and
Seattle, WA
T1523 Responder Analysis in a Trial of Once-Daily,
Extended-Release Memantine (28 mg) in Patients with
Moderate to Severe Alzheimer’s Disease
Stephen M. Graham, Suzanne Hendrix, Michael L. Miller,
Vojislav Pejovic and Michael Tocco; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
T1514 Predicting MCI Outcome with Clinically
Available MRI and CSF Biomarkers
David S. Heister, James B. Brewer, Sebastian Magda, Kaj
Blennow and Linda K. McEvoy; La Jolla, CA and Mo¨lndal,
Sweden
T1524 Rates of Cognitive Decline and Alzheimer’s
Disease (AD) Neuropathology in Oldest-Old
Archana B. Balasubramanian, Claudia H. Kawas, Daniel J.
Berlau, Carrie B. Peltz and Marı´a M. Corrada; Irvine, CA
T1515 Light and Electron Microscopic Analysis of FUS
Immunoreactivity in 3 Variants of Tau and TDP-43
Negative Frontotemporal Lobar Degeneration
Keith A. Josephs, Wen-Lang Lin, Joseph E. Parisi, Neil GraffRadford, Ronald C. Petersen and Dennis W. Dickson;
Rochester, MN and Jacksonville, FL
T1525 Cortical Thickness on MR Imaging: Relation to
Cognitive Reserve in Normal Aging and Mild Cognitive
Impairment
Jagan A. Pillai, Linda K. McEvoy, Donald J. Hagler, Jr,
Dominic Holland, Anders M. Dale, David P. Salmon, Douglas
Galasko and Christine Fennema-Notestine; San Diego, CA
T1516 Effects of Once-Daily, Extended-Release
Memantine (28 mg/day) on Cognitive Domains in
Patients with Moderate to Severe Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
T1526 Effects of Once-Daily, Extended-Release
Memantine on Individual Activities of Daily Living in
Patients with Moderate to Severe Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
T1517 Efficacy of Memantine by Baseline Disease
Severity: A Pooled Post-Hoc Analysis of Trials in Mild to
Moderate Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
T1527 Neurophysiologic Markers of Aging-Related
Muscle Weakness
Ela B. Plow, Dina Gohar, Mehmed B. Bayram, Jing Hou,
Alexandria Wyant, Yin Fang, Vlodek Siemionow and Guang
H. Yue; Cleveland, OH
T1518 Clinical Gait Abnormalities and Hippocampal
Morphometry in MCI: Preliminary Results from the
ADNI Study
Vincent S. DeOrchis and Joe Verghese; Bronx, NY
T1528 The Purkinje Cell of the Cerebellar Cortex in
Alzheimer’s Disease
and Stavros J. Baloyannis; Thessaloniki, Greece
T1519 Topography of Cortical Thinning in
PIB-Negative Subcortical Vascular Dementia
Versus Alzheimer’s Disease
Chi Hun Kim, Sang Won Seo, Sung Tae Kim, Jae-Hong Lee,
Jae Seung Kim, Seung Jun Oh, Suk-Hui Kim, Hae Kwan
Cheong, Jong-Min Lee, Seun Jeon and Duk L. Na; Seoul,
Korea and Suwon, Korea
T1529 A Translational Program of BDNF Gene Delivery
for Alzheimer’s Disease
Mark H. Tuszynski, Alan Nagahara, Adrian P. Kells, J.
Bringas, John Forsayeth and Krystopf S. Bankiewicz; La Jolla,
CA and San Francisco, CA
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T1530 Imaging Signatures of Pathology in Behavioral
Variant Frontotemporal Dementia
Jennifer L. Whitwell, Clifford R. Jack, David S. Knopman,
Bradley F. Boeve, Ronald C. Petersen, Joseph E. Parisi, Dennis
W. Dickson and Keith A. Josephs; Rochester, MN and
Jacksonville, FL
Stage:
Page: 15
T1605 Heavily T2-Weighted Magnetic Resonance
Myelography for Post-Lumbar Puncture Headache:
A Pilot Study
Yen-Feng Wang, Jong-Ling Fuh, Jiing-Feng Lirng and
Shuu-Jiun Wang; Taipei, Taiwan
T1531 Improved Statistical Power To Detect Treatment
Effects on Functional Outcomes in Alzheimer’s Disease
(AD) Clinical Trials by Item-Response Theory (IRT)
M. Colin Ard, Douglas R. Galasko and Steven D. Edland; La
Jolla, CA
T1606 Angioplasty and Stenting for the Treatment of
Idiopathic Intracranial Hypertension Associated with
Dural Venous Sinus Stenosis
Parisa P. Javedani**, Jeremy D. Fields, Kenneth C. Liu,
Stanley L. Barnwell and Bryan Petersen; Portland, OR and
Charlottesville, VA
T1532 Neuropathologic Basis of Age-Associated Brain
Atrophy
Deniz Erten-Lyons, Randy Woltjer, Hiroko Dodge, Lisa Silbert
and Kaye Jeffrey; Portland, OR
T1607 Adrenal Insufficiency Presenting as Postural
Tachycardia Syndrome
Darine Kassar and Stanley Iyadurai; Saint Louis, MO
T1608 Prevalence of Chronic Migraine (CM), HeadacheRelated Disability and Sociodemographic Factors in the
US Population: Results from the American Migraine
Prevalence and Prevention (AMPP) Study
Dawn C. Buse, Michael L. Reed, Kristina Fanning,
Aubrey N. Manack, Catherine C. Turkel and
Richard B. Lipton; Bronx, NY; Chapel Hill, NC and
Irvine, CA
T1533 A Long-Term, Open-Label Extension Study
Evaluating the Safety of Extended-Release Memantine
(28 mg) in Patients with Moderate to Severe Alzheimer’s
Disease
Stephen M. Graham and James Perhach; Jersey City, NJ
T1534 A Retrospective Analysis Using Data-Monitoring
Algorithms: What Are the Logical Relationships between
the ADAS-Cog and MMSE?
Christian Yavorsky, Guillermo DiClemente, Mark Opler, Sofija
Jovic, Brian Rothman and Ashleigh DeFries; New York, NY
T1609 Chronic Low Dose Methadone for the
Suppression of Treatment-Refractory Chronic Migraine
Keyvani Madjid and John F. Rothrock; San Diego, CA and
Birmingham, AL
T1535 Withdrawn.
T1536 Case of Bimodal Charles Bonnet Syndrome and
Dementia
Mirret El-Hagrassy and Gokhan Akfirat; New York, NY
T1610 Relationship between High Frequency Nausea
and Treatment Satisfaction in Episodic Migraine (EM):
Results of the American Migraine Prevalence and
Prevention (AMPP) Study
Richard B. Lipton, Michael L. Reed, Kristina M. Fanning and
Dawn C. Buse; Bronx, NY and Chapel Hill, NC
T1537 Lead Exposure Up-Regulated Autophagy
Response in Neuroblastoma SH-SY5Y Cells Via mTOR
Kinase Signaling Pathway
Shun-Sheng Chen, Chueh-Tan Chen and Jiin-Tsuey Cheng;
Kaohsiung, Taiwan
T1611 Frequent Nausea in Episodic Migraine (EM) Is
Common and Associated with Increased Burden: Results
from the American Migraine Prevalence and Prevention
(AMPP) Study
Dawn C. Buse, Michael L. Reed, Kristina M. Fanning and
Richard B. Lipton; Bronx, NY and Chapel Hill, NC
Headache and Pain
T1601 Withdrawn.
T1602 OnbotulinumtoxinA for the Treatment of
Chronic Migraine: Long-Term Outcome
Hanlon T. Christopher, Silvia M. Weibelt,
Diane C. Andress-Rothrock and John F. Rothrock;
Birmingham, AL
T1612 Medical Consultation and Headache-Impact
among Persons with Chronic Migraine (CM) and
Episodic Migraine (EM): Results from the American
Migraine Prevalence and Prevention (AMPP) Study
Aubrey N. Manack, Dawn C. Buse, Daniel Serrano, Sepideh
F. Varon, Catherine C. Turkel and Richard B. Lipton; Irvine,
CA; Bronx, NY and Chapel Hill, NC
T1603 Utility of Orally-Inhaled Dihydroergotamine
When Early Intervention Is Impractical
Shashidhar Kori, Stewart Tepper, Peter J. Goadsby,
Paul Winner, Min Wang and Stephen Silberstein;
Mountain View; Cleveland; San Francisco;
West Palm Beach and Philadelphia
T1613 Unmet Treatment Needs among Episodic
Migraineurs (EM): Results of the American Migraine
Prevalence and Prevention Study (AMPP)
Richard B. Lipton, Dawn C. Buse, Daniel Serrano, Daisy S.
Ng-Mak, Starr H. Pearlman and Michael Reed; Bronx, NY;
Chapel Hill, NC; West Point, PA and Savannah, GA
T1604 Characterization of Intraepidermal Nerve
Fiber Morphology in Pain Associated with Diabetic
Neuropathy and Impaired Glucose Tolerance
Hsinlin T. Cheng, Jacqueline R. Dauch, Gordon A. Smith,
Robinson J. Singleton, Brandon M. Yanik and Eva L.
Feldman; Ann Arbor, MI and Salt Lake City, UT
T1614 Association between Triptan Use and Cardiac
Contraindications in Migraine
Daisy S. Ng-Mak, Valerie P. Pracilio, Stephen Silberstein,
Joseph Couto, Cary Sennett, Mary Hopkins, Jon Bumbaugh
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and Neil Goldfarb; West Point, PA; Philadelphia, PA and
Bowie, MD
Chicago, IL; Oxford, United Kingdom; Birmingham, AL;
London, ON, Canada; Vancouver, BC, Canada; Wayne, NJ;
Berlin, Germany and Montville, NJ
T1615 ‘‘Let-Down Headache’’: Reductions in Stress and
Improvement in Mood Predict Headaches in Persons
with Migraine
Dawn C. Buse, Sheryl R. Haut, Charles Hall, Howard
Tennen, Tiffani DeFreitas, Thomas M. Borkowski and
Richard B. Lipton; Bronx, NY and Storrs, CT
T1703 A Recombinant Human Neuron-Binding IgM
Protects Spinal Cord Axons and Improves Motor
Function in a Murine Model of Multiple Sclerosis
Aleksandar Denic*, Slobodan Macura, Arthur E. Warrington,
Istvan Pirko, Brandon R. Grossardt, Larry R. Pease and Moses
Rodriguez; Rochester, MN
T1616 Assessing the Consistency of LEVADEXTM
(MAP0004, Orally Inhaled Dihydroergotamine)
Pharmacokinetic Parameters in Healthy Volunteers:
Results from 3 Clinical Studies
Amy Forst, Julie Iwashita, Don Kellerman, Shashidhar Kori,
Tracy Thomas and Glyn Taylor; Mountain View;
Merthyr Tydfil, United Kingdom and Radyr,
United Kingdom
T1704 Neuroprotection Mediated through Estrogen
Receptor Alpha in Astrocytes
Rory Spence, Mary Hamby, Elizabeth Umeda, Noriko Itoh,
Sienmi Du, Galyna Bondar, Michael Sofroniew and Rhonda
Voskuhl; Los Angeles, CA
T1705 Genesis of Astrogliosis in an Autoimmune Model
of Multiple Sclerosis
Fuzheng Guo, Yoshiko Maeda, Joyce Ma, Monica Delgado and
David Pleasure; Sacramento, CA
T1617 Migraine Recurrence Rates with Acute Treatment:
Case for Standardizing the Definition
Stewart Tepper, Shashidhar Kori, Peter J. Goadsby, Michel
Ferrari, Richard Lipton, Scott Borland, Min Wang and David
Dodick; Cleveland; Mountain View; San Francisco; Leiden,
Netherlands; Bronx and Scottsdale
T1706 Distinct Features of Neuromyelitis Optica
According to Anti-Aquaporin-4 Antibody IgG Subclass
Noriko Isobe, Tomomi Yonekawa, Takuya Matsushita, Yuji
Kawano, Katsuhisa Masaki, Satoshi Yoshimura and Jun-ichi
Kira; Fukuoka, Japan and Matsuyama, Japan
T1618 Transdermal Sumatriptan for Acute Treatment of
Migraine
and Jerome Goldstein; San Francisco, CA
T1707 Effect of Fingolimod on Relapse Rate by Prior
Treatment Status and Reason for Discontinuation:
FREEDOMS Subgroup Analyses
Marcelo Kremenchutzky, Paul O’Connor, Reinhard Hohlfeld,
Ernst-Wilhelm Radue, Ludwig Kappos, Lixin Zhang-Auberson,
Dieter A. Ha¨ring, Philipp von Rosenstiel, Xiangyi Meng and
Augusto Grinspan; London, ON, Canada; Toronto, ON,
Canada; Munich, Germany; Basel, Switzerland and East
Hanover, NJ
T1619 Dejerine Roussy Syndrome in a Patient with
Sneddon’s Syndrome as an Initial Manifestation
Jennie Luna, Anish Shah, Sourav Sen and Dipak P. Pandya;
Paterson, NJ
T1620 Valproate-Responsive Subclinical Rhythmic
Electrographic Disharges (SREDA) in a Migraineur
Umer Akbar, Bhavpreet Dham, Evren Burakgazi and John
Kelly; Camden, NJ and Washington
T1708 Effect of Fingolimod on Relapse Rate by Prior
Treatment Status and Reason for Discontinuation:
TRANSFORMS Subgroup Analyses
Bhupendra O. Khatri, Jean Pelletier, Ludwig Kappos, HansPeters Hartung, Giancarlo Comi, Frederik Barkhof, Jeffrey
Cohen, Tracy Stites, Xiangyi Meng and Augusto Grinspan;
Milwaukee, WI; Marseille, France; Basel, Switzerland;
Dusseldorf, Germany; San Raffaele, Milan, Italy; Amsterdam,
Netherlands; Cleveland, OH and East Hanover, NJ
T1621 Utriculo-Ocular Counterroll Reflex Disruption in
Skew Deviation
James A. Sharpe, Manokaraananthan Chandrakumar, Alan
Blakeman, Herbert C. Goltz and Agnes M. Wong; Toronto,
ON, Canada
T1622 Superior Semicircular Canal Dehiscence (SSCD)
and Osteoporosis in Elderly Asian Women
Alexander Yu, Douglas L. Teich and Eric T. Wong; Boston,
MA
T1709 Safety Overview of Fingolimod in Relapsing
Multiple Sclerosis: Phase 2 and 3 Studies
Jeffrey A. Cohen, Ludwig Kappos, Gordon Francis, William
Collins, Lixin Zhang-Auberson and Dejun Tang; Cleveland,
OH; Basel, Switzerland and East Hanover, NJ
Neuroimmunology and Demyelinating Disease
T1710 Fingolimod Mechanism of Action (MOA) in
Multiple Sclerosis (MS)
Jerold Chun and Jeffery A. Cohen; La Jolla, CA and
Cleveland, OH
T1701 Antibodies to Metabotropic Glutamate Receptors
in Ophelia Syndrome and Cerebellitis
Eric Lancaster, Eugenia Martinez-Hernandez, Maarten J.
Titulaer, Sarah Wong, Jian Xu, Anis Contractor, Rita BaliceGordon and Josep Dalmau; Philadelphia, PA and Chicago, IL
T1711 Antibodies to the VGKC-Complex Proteins LGI1
and CASPR2 in Acquired Neuromyotonia
Camilla Buckley, Philippa Pettingill, Rosie Pettingill, Matthew
Kiernan, Osamu Watanabe, Sarosh Irani, Patrick Waters and
Angela Vincent; Oxford, United Kingdom; Sydney, Australia
and Kagoshima, Japan
T1702 Mortality Outcomes for Interferon Beta-1b
Versus Placebo 21 Years Following Randomization
Douglas S. Goodin, Anthony T. Reder, George Ebers, Gary
Cutter, Marcelo Kremenchutzky, Joel Oger, Mark Rametta,
Karola Beckmann and Volker Knappertz; San Francisco, CA;
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T1725 Regulation of IL-12 by IL-23 in Bone Marrow
Dendritic Cells
Farinaz Safavi, Patricia Gonnella, Bogojub Ciric,
Abdolmohamad Rostami and Farinaz Safavi; Philadelphia, PA
T1713 Association of MS Susceptibility Variants and
Early Attack Location
Ellen M. Mowry, Jean Pelletier, Maria R. Blasco, Pierre Duquette,
Pablo Villoslada, Pierre-Antoine Gourraud, Irina Malikova,
Christophe Picard, Jamie McDonald, Elaine Roger, Stacy Caillier
and Emmanuelle Waubant; San Francisco; Marseille, France;
Madrid, Spain; Montreal, Canada and Pamplona, Spain
T1726 Clinically Apparent MRI Activity Predicts 2-Year
Outcomes in Patients with RRMS
Thomas Scott, Xiaojun You and Pamela Foulds; Pittsburgh,
PA and Weston, MA
T1727 The Correlation of Brain MRI Lesion Load with
Functional Outcome in Animal Models of MS
Istvan Pirko, Jeffrey Gamez, Moses Rodriguez, Mihajlo
Babovic and Slobodan I. Macura; Rochester, MN and
Northfield, MN
T1714 Osmotic Demyelination Syndrome: Lack of
Association between Outcome and Severity of
Hyponatremia
Jennifer E. Fugate*, Jonathan Graff-Radford and Alejandro A.
Rabinstein; Rochester, MN
T1728 Comparison of CIDP Patients with Normal and
Elevated CSF Protein
YuanYuan Xue and Ericka P. Simpson; Houston, TX
T1715 Correlation of Brain Atrophy, Disability and
Spinal Cord Atrophy in a Murine Model of MS
M Mateo Paz Soldan, Jeffrey D. Gamez, Aaron J. Johnson,
Anne K. Lohrey, Yi Chen and Istvan Pirko; Rochester, MN
and Cincinnati, OH
T1729 Are Anti-TAG-1 Autoantibodies Markers in
Autoimmune Demyelinating Disorders of the PNS and
CNS?
Harry Alexopoulos, Pantelis P. Pavlakis, Domna Karagogeos,
Clementine E. Karageorgiou and Marinos C. Dalakas; Athens,
Greece and Heraklion, Greece
T1716 Anti-NMDA-Receptor Encephalitis: Clinical
Analysis of 457 Patients
Maarten J. Titulaer, Eugenia Martinez-Hernandez, Lindsey
McCracken, Rita Balice-Gordon and Josep Dalmau;
Philadelphia, PA and Barcelona, Spain
T1730 Introduction and Diffusion of Multiple Sclerosis
in the United States
Mitchell T. Wallin and John F. Kurtzke; Washington, DC
T1717 Cigarette Smoke Induces Inflammation and
Oxidative Stress in Brains of Lewis Rats
Ashwani Khanna and Walter Royal, III; Baltimore, MD
T1731 Withdrawn.
T1732 Withdrawn.
T1718 Withdrawn.
T1733 The Relationship between Conduction Block and
Clinical Characteristics in Guillain-Barré Syndrome with
Anti-GM1/GalNAc-GD1a Antibodies
Go Ogawa, Ken-ichi Kaida, Susumu Kusunoki,
Motoi Kuwabara, Fumihiko Kimura and Keiko Kamakura;
Tokorozawa, Saitama, Japan and Osaka-Sayama,
Osaka, Japan
T1719 Differential Sensitivity of Human PBMC Subsets
to Alemtuzumab-Mediated Cytotoxicity
William Siders, Sambasiva Rao, Juanita Campos-Rivera, Jose
Sancho, Paula Boutin, Peter Severy, Johanne Kaplan, Bruce
Roberts and Srinivas Shankara; Framingham, MA
T1720 Transcriptional Profiles Uncover Population
Structure among Multiple Sclerosis Patients
Linda Ottoboni, David Hafler, Howard Weiner and
Philip De Jager; Boston, MA and New Haven, CT
T1734 Withdrawn.
T1735 Randomized, Open-Label Study To Evaluate
Patient-Reported Outcomes (PRO) with Fingolimod
after Changing from Prior Disease-Modifying Therapy
(DMT) for Relapsing Multiple Sclerosis (MS): EPOC
Study Rationale and Design
Luigi M. Barbato, Lesley Schofield, Kevin McCague, Linda
Pestreich, Kathy Tobias and Manoj Malhotra; East Hanover, NJ
T1721 Analysis of Immune Competence Following
Alemtuzumab Treatment in huCD52transgenic Mice
William Siders, Nathalie Chretien, Michael LaMorte, Bruce
Roberts and Johanne Kaplan; Framingham, MA
T1722 Withdrawn.
T1736 Novel Diagnostic Tool for MS
Nancy L. Monson, Ann J. Ligocki, William H. Rounds,
Diane Xiang, Lindsay G. Cowell, Doug Bigwood, Eric
Eastman, Jeffrey L. Bennett, Scott D. Boyd, Andrew Z.
Fire, Elliot M. Frohman and Benjamin M. Greenberg;
Dallas, TX; Gaithersburg, MD; Denver, CO and
Palo Alto, CA
T1723 Withdrawn.
T1724 A Single Dose Escalation Study of the Safety,
Pharmacokinetics, and Pharmacodynamics of
Subcutaneous Pegylated Interferon-Beta in Healthy
Volunteers
Kenneth Grabstein, Aijun Wang, Natalie Winblade Nairn and
Daniel J. Burge; Seattle, WA
T1737 Efficacy of Combination Therapy in Marburg
Variant Type of Multiple Sclerosis
Jennifer Gabbard, Yasmin Bilal and Dipak Pandya; Paterson,
NJ
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T1738 Coma as an Inital Manifestation of Acute
Disseminated Encephalomyelitis
Megan McGarry, Natasha Tilluckdharry and Dipak P.
Pandya; Paterson, NJ
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T1809 Benign-Histology Meningioma with Extracranial
Metastasis
Umer Akbar, Bhavpreet Dham and Melissa Carran; Camden, NJ
Neurovirology
T1739 NMO-IgG in a Patient with Neurosarcoidosis
Lena Derani** and Elham Bayat; Washington, DC
T1901 HIV Associated Neurocognitive Disorder
(HAND) Is Not Associated with Increased Fibrillar
Amyloid Deposits Using 11C-PiB in Middle-Aged HIVþ
Participants
Beau Ances, Jewell Thomas, Tammie Benzinger, Jon Christensen,
Mengesha Teshome, Patricia Aldea, Anne Fagan, David
Holtzman, John Morris and David Clifford; Saint Louis, MO
T1740 Correlates of Dietary Intake in Individuals with
Multiple Sclerosis
Matthew A. Plow, Marcia Finlayson and Chi Cho; Cleveland,
OH and Chicago, IL
Neurooncology
T1801 Comparative Uptake and Cytotoxicity of Anti-Hu
and Anti-Ri Antibodies in Rat Cerebellar Slice Cultures
John E. Greenlee, Susan A. Clawson, Blair Wood, Kenneth E.
Hill and Noel G. Carlson; Salt Lake City, UT
T1902 Modulation of HIV-Tat Neurotoxicity by
Potassium Channel Blockers
Srikant Rangaraju* and Jeffrey A. Rumbaugh; Atlanta, GA
T1802 Cerebrospinal Fluid Chemokine/Cytokine
Biomarkers for Melanoma Brain Metastasis
Edwin Lok, Amy S. Chung, Szexian Lee, Tamar Melman,
Kenneth D. Swanson and Eric T. Wong; Boston, MA
T1903 Varicella Zoster Encephalitis – Relationship
between Viral Load, Time and Outcome
Benedict D. Michael, Mike Griffiths, Anna Stewart, Charlotte
Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen Galbraith
and Tom Solomon; Liverpool, Merseyside, United Kingdom
T1803 Role of p75NTR and Its Signaling Pathways in
Fenretinide (4-hydroxyphenyl Retinamide – 4HPR)
Induced Apoptosis in Neuroblastoma Cells
Veena R. Ganeshan and Nina F. Schor; Rochester, NY
T1904 Acute Varicella Zoster Virus Encephalitis in
Adults – Relationship between Viral Load, Time,
Clinical Features and Outcome
Benedict D. Michael, Michael Griffiths, Anna Stewart, Charlotte
Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen E.
Galbraith and Tom Solomon; Liverpool, United Kingdom
T1804 Relationship between Brain MRI Imaging
Parameters and Molecular Biomarkers as Prognostic
Indicators in Glioblastoma Multiforme
Xiao-Tang Kong, Senxi Du, Beverly D. Fu, Mark E. Linskey
and Daniela Bota; Orange, CA and Irvine, CA
T1905 TLR4 Expression Is Upregulated in
HIV-Associated Neurocognitive Disorder (HAND)
Amir H. Sabouri, Gursharan Chana, Amol Shah, Critian L.
Achim, Ronald J. Ellis, Ian P. Everall and HNRC Group;
La Jolla, CA; Melbourne, Australia and San Diego, CA
T1805 Secondary Intramedullary Spinal Cord NonHodgkin’s Lymphoma
Eoin P. Flanagan, Brian P. O’Neill, Thomas M. Habermann
and B. Mark Keegan; Rochester, MN
T1906 Revisiting Reactivation of Calcified
Neurocysticercosis: Report of Three Recent Cases
Sanjna M. John** and Maria del Pilar Cortes Nino;
Kingston, ON, Canada and Montreal, QC,
Canada
T1806 Case Report: Optic Neuropathy in a Patient with
Glioblastoma Receiving Bevacizumab
Robert A. Fishman, Lara Kunschner and Erik Happ;
Pittsburgh, PA
T1807 Anti-Ri-Associated Paraneoplastic Brainstem
Cerebellar Syndrome with Medically-Intractable Nausea
in a Patient with Large Cell Neuroendocrine Lung
Carcinoma: A Case Report
Amber N. Mitchell, Jessica Levesque and Earl Zimmerman;
Albany, NY
T1907 Clinical Features at Admission in Patients with
Meningeal Cryptococcosis in a Third Level Hospital in
Mexico
Jesus F. Mendoza, Gilberto Vazquez, Jeronimo Rodriguez
and Ildefonso Rodriguez; San Luis Potosı´, San Luis Potosı´,
Mexico
T1808 Glioblastoma Multiforme: A Rare Presentation of
Pineal Tumor with Leptomeningeal Seeding and Future
Directions
Noor Yono, Tulika Ranjan and Rabih Kashouty; Manhasset,
NY, United States Minor Outlying Islands and New York, NY
T1908 The Diagnosis of Tuberculous Meningitis:
A Current Review of the Clinical and Laboratory
Methods
Brian Chisulo, Shan H. Jiang and Yue S. Pan; Guangzhou,
GZ, China
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136th Annual Meeting Sunday,
September 25, 2011 Works in
Progress Poster Session
136th Annual Meeting Monday,
September 26, 2011 Works in
Progress Poster Session
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing
clinical or basic research of an extraordinary nature, which
warrants expediated presentation. These abstracts were
selected based on scientific merit, timeliness, and anticipated interest to the membership. Key aspects of research
must have been conducted after the regular abstract
deadline.
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected
based on scientific merit, timeliness, and anticipated interest
to the membership. Key aspects of research must have been
conducted after the regular abstract deadline.
Behavioral Neurology
Cerebrovascular Disease
M622 New Approaches to Unraveling the Multi-Scale
Neuroanatomical Changes in Williams Syndrome
Ann Lam and Elan L. Ohayon; La Jolla
S141 Polymorphism of Ninjurin2 in Korean
Atherothrombotic Stroke Patients
Dae-il Chang, Sung Hyuk Heo and Hye Ok Kim; Seoul,
Korea
Epilepsy
S142 NMDA Receptor Biomarker for Acute Stroke
Kerstin Bettermann and Svetlana Dambinova; Hershey, PA
and Kennesaw, GA
M725 HLA-B*1502 Genotyping in Carbamazepine and
Phenytoin Induced Stevens-Johnson Syndrome
Sivakumar M. Rajappa and Srinivasan A. Venkatesan;
Chennai, Tamil Nadu, India
S143 Initial Transcranial Doppler Velocity Predicts
Development of Symptomatic Vasospasm in Aneurysmal
Subarachnoid Hemorrhage
Shyam Prabhakaran, Konark Malhotra, Rajeev Garg, Sayona
John, Richard Temes and Viven Lee; Chicago, IL
M726 Filamin A Regulates Neural Progenitor
Proliferation and Brain Size through wee1-Dependent
cdk1 Phosphorylation
Gewei Lian and Volney Sheen; Boston, MA
S144 Relative Change in Transcranial Doppler Velocities
Is Inferior to Absolute Thresholds in Prediction of
Vasospasm after Subarachnoid Hemorrhage
Konark Malhotra, James Connors, Viven Lee and Shyam
Prabhakaran; Chicago, IL
M727 A Moderate-Throughput Screen for
Antiepileptogenic Compounds
Yevgeny Berdichevsky, Yero Saponjian, Michelle Mail and
Kevin J. Staley; Boston, MA
Movement Disorder
M728 Network Structure and Sensitivity to the
Geometry of Stimuli in Epilepsy and Cognition
Elan L. Ohayon, Ann Lam and Terrence J. Sejnowski; La
Jolla, CA
S238 Dopamine Transporter Imaging Predicts Long
Term Outcomes in Parkinson’s Disease
Bernard M. Ravina, Kenneth Marek, Shirley Eberly, David
Oakes and Ira Shoulson; Rochester and New Haven
M729 Hypoglycemia Induced NMDA
Receptor-Dependent Epileptiform Activity
in the Hippocampal CA3 Area Causes Damage
in CA1
Carlos M. Florez, Jane Zhang, Peter Abdemalik,
Liang Zhang and Peter L. Carlen; Toronto, ON, Canada
S239 Time to First Levodopa-Induced Motor
Complication: Results from the STRIDE-PD Study
C. Warren Olanow, Karl Kieburtz, Olivier Rascol,
Werner Poewe, Anthony Schapira, Helena Nissinen,
Mika Leinonen and Fabrizio Stocchi; New York, NY;
Rochester, NY; Toulouse, France; Innsbruck, Austria;
London, United Kingdom; Espoo, Finland; Kista,
Sweden and Rome, Italy
M730 Alzheimer Disease in Lafora Epilepsy
Jesus Machado-Salas, Maria Rosa Avila-Costa, Patricia
Guevara, Jorge Guevara, Reyna M. Duron, Dongsheng Bai,
Miyabi Tanaka and Antonio V. Delgado-Escueta; Los Angeles,
CA and Mexico, Mexico
S240 Acute Effects of Preladenant, a Selective Adenosine
A2A Antagonist, on Dyskinesia and Parkinsonism in
Levodopa-Treated Subjects
Penelope Hogarth, Matthew D. Troyer, Byung S. Park,
Igor D. Grachev, Tatanisha Laguerre, Fengjuan Xuan, Amol
Tendolkar and John G Nutt; Portland, OR and Whitehouse
Station, NJ
M731 Antiepileptic Activity of Intrapulmonary
Midazolam
Ashish Dhir, Dorota Zolkowska and Michael A. Rogawski;
Sacramento and Davis
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M732 Do Brain Volumes in JME (juvenile myoclonic
epilepsy) differ from normal controls?
Neurology Critical Care
John T. Spitz, Long Vu, Lydia Su, Mark A. Mandelkern,
Barbara E. Swartz; Berkely, CA, Irvine, CA, Los Angeles, CA,
Irvine,CA and Newport Beach, CA
M1206 Imaging Biomarkers of Cerebral Edema in
Malignant Infarction
Kevin N. Sheth, Albert J. Yoo, R. G. Gonzalez, W. T.
Kimberly, Zeshan A. Chaudhry, Jordan J. Elm, Sven Jacobson,
Stephen M. Davis, Geoffrey A. Donnan, Gregory W. Albers
and Barney J. Stern; Baltimore, MD; Boston, MA; Charleston,
SC; New York, NY; Carlton South, Victoria, Australia and
Stanford, CA
Neuromuscular Disease
M836 Disrupted Expression of Myogenin in Inclusion
Body Myositis
Akatsuki Kubota, Jun Shimizu, Atsushi Iwata and Shoji Tsuji;
Tokyo, Japan
136th Annual Meeting Tuesday,
September 27, 2011 Works in
Progress Poster Session
M837 Abnormalities of a Novel Autophagy-Associated
Protein, NBR1, in Muscle Fibers of Sporadic InclusionBody Myositis (s-IBM)
Carla D’Agostino, Anna Nogalska, Mafalda Cacciottolo,
W.King Engel and Valerie Askanas; Los Angeles, CA
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected
based on scientific merit, timeliness, and anticipated interest
to the membership. Key aspects of research must have been
conducted after the regular abstract deadline.
M838 Atrophy and Autophagy in Limb Girdle Muscular
Dystrophy and Glycogen Storage Disease Type 2
Corrado I. Angelini, Annachiara Nascimbeni, Marina Fanin
and Marco Sandri; Padova, Italy
M839 Virtual Demyelination in pmp22 Deficiency
Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman,
Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li;
Nashville; San Diego; Cleveland; Zurich, Swaziland and
Nashville, TN
Dementia and Aging
T1538 Proneurogenic Compound Reduces Synaptic
Ab42 Oligomer Levels and Shows Cognitive Benefit in
Alzheimer’s Mouse Model
Sam Gandy, John W. Steele, Charles Glabe, Kai Treuner,
Todd Albert, Carrolee Barlow, Michelle E. Ehrlich and
Soong Ho Kim; New York, NY; Irvine, CA and
San Diego, CA
M840 First in Human Phase 1 Trial of Neural
Progenitor Cells in ALS: Results in the First 12 Patients
Jonathan D. Glass, Nicholas Boulis, Meraida Polak, Crystal
Kelly, Thais Federici, Jane Bordeau, Seward Rutkove, Karl
Johe, Tom Hazel and Eva Feldman; Atlanta, GA; Boston,
MA; Rockville, MD and Ann Arbor, MI
M841 Clinical Development of an Antisense Therapy for
the Treatment of Transthyretin Amyloidosis
Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis
Alvarado andrew Siwkowski, Merrill Benson, Steve Hughes
and Brett Monia; Carlsbad, CA and Indianapolis, IN
T1539 Alzheimer Risk Variant Clusterin (CLU) and
Brain Function during Aging
Madhav Thambisetty, Lori Beason-Held, Michael Kraut,
Michael Nalls, Andrew Singleton, Luigi Ferrucci, Simon
Lovestone and Susan Resnick; Baltimore and London, United
Kingdom
Neurogenetics
T1540 Association of High Density Lipoprotein to
Alzheimer Disease
Ramin Ebrahimi, Naser Ahmahi, Fereshteh Hajsadeghi and
Hormoz Babaei; LA, CA
M1011 EPI-A0001: New Potential Therapy for
Friedreich Ataxia
David R. Lynch, Steve M. Willi, Robert B. Wilson, Karlla W.
Brigatti, Olena Kucheruck, Eric C. Deutsch, William D.
Shrader, Patrice Rioux, Guy Miller, Amale Hawi and Thomas
Sciascia; Philadelphia, PA; Patterson, NY and Mountain View,
CA
T1541 Amyloid-b 42:40 Metabolism Is Altered in
Autosomal Dominant Alzheimer’s Disease (ADAD)
Rachel E. Potter, Vitaliy Ovid, Tom Kasten, Wendy Sigurdson,
Kwasi Mawuenyega, Bruce Patterson, Don Elbert, Scot Fague,
Sumi Chakraverty, Alison Goate, Kevin Yarasheski, John C.
Morris, Tammie Benzinger and Randall J. Bateman; St. Louis,
MO
M1012 Exome Sequencing Identifies a Rare Variant in
the CYP27B1 Gene Associated with Multiple Sclerosis
George C. Ebers and Sreeram V. Ramagopalan; Oxford,
Oxfordshire, United Kingdom
T1542 Acetylated Tau, a Novel Pathological Signature in
Alzheimer’s Disease and Other Tauopathies
David J. Irwin, Todd Cohen, Murray Grossman, Steven E.
Arnold, Sharon X. Xie, Virginia M.Y. Lee and John Q.
Trojanowski; Philadelphia, PA
M1013 Whole Genome Sequencing in Twins Discordant
for 27 Diseases
George C. Ebers and Sreeram V. Ramagopalan; Oxford,
Oxfordshire, United Kingdom
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Headache and Pain
Rizzuto, Hunter R. Underhill, Kenneth R. Maravilla and Lily
K. Jung-Henson; Seattle, WA
T1623 Retrospective Analysis of Major Congenital
Malformations (MCMs) and Oral Clefts (OC) Associated
with In-Utero Topiramate Exposure
Mark W. Green and Arun Bhattachuria; New York, NY and
Yardley, PA
T1744 Skull Is Skull and Not Simply Another Bony
Structure
Tsutomu Nakada, Yuji Suzuki, Yukihiro Nakayama, Vincent
J. Huber and Ingrid L. Kwee; Niigata, Niigata, Japan and
Martinez, CA
Neuroimmunology and Demyelinating Disease
T1745 Characteristics of the Long Latency Vestibular
Electrical Evoked Potential in Control Human Subjects
Benn E. Smith, Michael J. Cevette, Jan Stepanek, Daniela
Cocco, Gaurav Pradhan, Kenneth H. Brookler, Lindsay
Wagner, Sarah Oakley, David A. Zapala and Mark A. Ross;
Scottsdale, AZ and Jacksoville, FL
T1741 Comparison of MRI Techniques for Monitoring
of Multiple Sclerosis
Manuela Vaneckova, Jan Krasensky, Tomas Kalincik, Dana
Horakova, Eva Havrdova and Zdenek Seidl; Prague, Czech
Republic
T1746 Regulatory T Cells Play Contrasting Roles in a
Viral Model for Multiple Sclerosis
Nicholas E. Martinez, Fridrik Karlsson, Fumitaka Sato,
Seiichi Omura, Alireza Minagar, Mathew B. Grisham, and
Ikuo Tsunoda; Shreveport, LA
T1742 Effects of Rituximab on T-Cells in MS
Uma Vinayagasundaram, Ellen M. Mowry, Ian R. Matthews,
Julia Marino and Emmanuelle Waubant; San Francisco, CA
T1743 Fast Macromolecular Proton Fraction (MPF)
Mapping in Multiple Sclerosis (MS)
Vasily L. Yarnykh, James D. Bowen, Bart P. Keogh, Pavle
Repovic, Angeli Mayadev, Beena Gangadharan, Daniel S.
T1747 Idiopathic Relapsing Conus Myelitis
Raghav Govindarajan and Efrain Salgado; Weston, FL
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136th Annual Meeting Sunday,
September 25, 2011 Career
Development Poster Session
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Neuroimmunology and Demyelinating Disease
CD531 TLR9 Processing in Multiple Sclerosis: A New
Immunomodulatory Effect of Interferon-beta
Konstantin E. Balashov, Suhayl Dhib-Jalbut, and Latt Aung;
New Brunswick, NJ
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
Neurogenetics
CD522 Aberrant Channel Subunit Trafficking in the
Neurodegenerative KCNC3R420H SCA13 Phenotype
Michael F. Waters; Gainesville, FL
Epilepsy
CD515 Non-Convulsive Status Epilepticus Is Associated
with Mortality and Worse Short-Term Outcome in
Critically Ill Children
Nicholas S. Abend, Alexis A. Topjian, and Dennis J. Dlugos;
Philadelphia, PA
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136th Annual Meeting Sunday,
September 25, 2011
Poster Session Abstracts
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Dr. Elkind serves as Resident and Fellow Section Editor for
Neurology, for which he receives compensation from the
AAN.
S102. Functional Outcomes in CREST among Patients
with Periprocedural Stroke and Myocardial Infarction
Bart M. Demaerschalk, Robert J. Hye, O.W. Brown, Donald
V. Heck, Irfan Altafullah, Jenifer H. Voeks, George Howard,
James F. Meschia and Thomas G. Brott; Phoenix, AZ; San
Diego, CA; Royal Oak, MI; Winston Salem, NC; Robbinsdale,
MN; Birmingham, AL and Jacksonville, FL
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
Background: Stroke more frequently complicated stenting,
and myocardial infarction (MI) more frequently complicated
endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).
Purpose: To inform debate on importance of these components of the CREST primary endpoint.
Methods: The modified Rankin Scale (mRS), a measure
of function, was assessed at one year, and scales were available for 72 (89%) of the stroke patients and 34 (81%) of
the MI patients.
Results: There was no evidence of a difference in the distribution of mRS (pCMH ¼ 0.61). Complete or nearly complete recovery (mRS 0-1) was achieved for 43 (60%) of the
stroke patients and 23 (68%) of the MI patients. Slight to
severe disability (mRS 2–5) was achieved for 16 (22%) of
the stroke patients and 5 (15%) of the MI patients. Death
occurred in 13 (18%) of the stroke patients and in 6 (18%)
of the MI patients. Disability and death were more frequent
for both the stroke and MI patients compared to those with
neither (p<0.001).
Conclusion: Periprocedural stroke and MI had adverse
and similar outcomes at one-year in CREST. Each is an important complication of carotid revascularization.
Study supported by: The study was funded by the
National Institute of Neurological Disorders and Stroke of
the National Institutes of Health (NS038384) with supplemental funding provided by Abbott Vascular Solutions (formerly Guidant).
Dr. George Howard reports receiving compensation for
activities with Bayer Healthcare and research support from
Amgen and Bayer Healthcare. He is also a consultant to
Abbott for preparation of FDA materials.
Cerebrovascular Disease
S101. Duration of Diabetes and Ischemic Stroke Risk:
The Northern Manhattan Study
Julio R. Vieira*, Chirantan Banerjee, Yeseon P. Moon,
Myunghee C. Paik, Tatjana Rundek, Ralph L. Sacco and
Mitchell S.V. Elkind; New York, NY and Miami, FL
Background: Diabetes increases stroke risk, but whether
time-dependent analyses improve estimates of effect, and
whether duration is important, is less clear. We hypothesized
that diabetes duration independently predicts ischemic
stroke.
Methods: Among 3,298 stroke-free participants, baseline
diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median ¼ 9 years). We fit Cox
proportional hazards models to examine associations
between diabetes duration and ischemic stroke (IS) risk.
Results: Mean age was 69 6 10 years (52% Hispanic,
21% white, and 24% black); 22% were diabetic at baseline
and 11% developed new diabetes. Diabetes at baseline was
associated with IS (adjusted HR ¼ 2.5, 95% CI ¼ 1.9–
3.3), and the magnitude was similar when analyzed as a
time-varying covariate (adjusted HR ¼ 2.4, 95% CI ¼ 1.8–
3.2). Duration of diabetes was associated with IS (adjusted
HR ¼ 1.03 per year with diabetes, 95% CI ¼ 1.02–1.05).
Compared to non-diabetics, those with diabetes for 0–5
years (adjusted HR ¼ 1.7, 95% CI ¼ 1.1–2.7), 5–10 years
(adjusted HR ¼ 1.8, 95% CI ¼ 1.1–3.0), and 10 years
(adjusted HR ¼ 3.3, 95% CI ¼ 2.4–4.5) were at increased
risk. There was a duration threshold effect at 10 years (p
¼ 0.012).
Conclusion: Duration of diabetes is independently associated with ischemic stroke. The risk triples in those with
diabetes 10 years.
Study supported by: This study was supported by NIH/
NINDS (#R37 29993).
Dr. Vieira reports no disclosures. Dr. Banerjee reports no
disclosures. Ms. Moon reports no disclosures. Dr. Paik
reports no disclosures. Dr. Rundek reports no disclosures.
Dr. Sacco discloses receiving research support from the
NIH/NINDS over the last 12 months. Dr. Elkind serves as
a consultant to Bristol-Myers Squibb and Tethys Bioscience,
Inc.; serves on an event adjudication committee for Jarvik
Heart; and serves on speakers’ bureaus for Boehringer-Ingelheim, Inc., Bristol-Myers Squibb/Sanofi Pharmaceuticals
Partnership, and Genentech; and receives research support
from diaDexus, Inc., Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, and the NIH/NINDS [# R01
NS050724 (PI), #NS048134 (PI), # P50 NS049060 (Project PI), # R37 NS029993 (Co-PI), #R01 NS55809 (Co-I)
and #R01 NS062820 (Co-I)]; and has given expert testimony on behalf of Novartis (ZelnormV and stroke litigation) and GlaxoSmithKline (AvandiaV and stroke litigation).
S103. Inhibition and Scavenging of Complement as
Therapeutic Targets in the Mouse Model of Acute
Ischemic Stroke
Xinzhi Chen, Mark P. Mattson and Milan Basta; Baltimore,
MD and Potomac, MD
Complement activation and subsequent generation of harmful fragments plays and important role in the pathogenesis
of acute ischemic stroke (AIS). We investigated the effect of
high dose intravenous immunoglobulin (IVIG), a potent
scavenger of active complement fragments and C1-INH, an
inhibitor of complement pathway cascades in the mouse
model of AIS. Brain injury was induced by 1 hour occlusion
of middle cerebral artery followed by a 72-hour reperfusion.
Both IVIG (Privigen, CSL Behring) and C1-INH (Berinert,
CSL Behring) significantly and in a dose responsive manner
reduced brain infarction size, neurological deficit score and
deposition of C3b fragments at the site of injury when
given 30 minutes before or 1 hour after ischemia. Optimal
dose of IVIG exerted more neuroprotection than the corresponding C1-INH counterpart (85% vs. 48% reduction of
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brain infarction volume and 35% vs. 22% inhibition of
neurological deficit, respectively). Treatment with human serum albumin and vehicles (stabilizing solutions) for IVIG
and C1-INH did not improve the magnitude of brain
injury observed in non-treated controls. Our data suggest
that complement attenuation could be considered as a novel
interventional therapy for AIS.
Study supported by: CSL Behring
Salary and consulting fees.
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210 (1.9%) in group 1, and 2/12 (16.67%) in group 2 (p
¼ 0.036). At 90 days, 44/144 (30.56%) in group 1 had
mRS 0-1, and in group 2, 1/8 (12.5%, p ¼ 0.437).
We found no difference in sICH or clinical outcome in
patients with high INR after IV t-PA. The data is limited
to few patients. Larger prospective studies are needed to
prove safety and efficacy of IV t-PA in those with higher
INR.
S106. Toward a Further Clinical Physiological
Elucidation: Immediate Regression of Leukoaraiosis after
Carotid Artery Revascularization
and Yu-Ming Chuang; New Taipei City, Taiwan
S104. Does ACE (rs4646994) and a ADDUCIN
(rs4961) Gene Polymorphisms Predicts the Recurrence
of Hypertensive Intracerebral Hemorrhage
Usha K. Misra, Jayantee Kalita, Bindu I. Somarajan,
Bishwanath Kumar, Moromi Das and Balraj Mittal;
Lucknow, Uttar Pradesh, India
Background: To correlate leukoaraiosis, cerebral perfusion
and circle of Willis (CoW) flow patterns after carotid artery
revascularization.
Methods: Leukoaraiosis (LA) on fluid attenuation
inversion recovery (FLAIR) magnetic resonance (MR)
images at the levels of the centrum semiovale and those
of the frontal horns at both cerebral hemispheres were
scored in 62 contiguous patients (men/women ¼ 38/24,
mean age ¼ 63.2 þ- 8.4 years, range 44–82) before and
after unilateral carotid artery revascularization (CAS). The
pre-and post-stenting difference of LA scores, CoW flow
pattern on MR angiography and MR perfusion parameters was analyzed.
Results: Post-stenting sum of leukoaraiosis score on
FLAIR imaging was regressed from 9.87þ0.65 to
8.33þ0.72 (P ¼ 0.03). Subjects were assigned to the
complete CoW group (N ¼ 21) vs. the incomplete CoW
group (N ¼ 41). Incomplete CoW group had a higher preoperative LA load and higher interhemispheric asymmetry
index of relative cerebral blood volume (rCBV) which could
be significantly regressed post-operatively.
Conclusions: A perfusion related remodeling of the leukoaraiosis, regarding the factor of CoW configuration was
observed.
Study supported by: CGMH
Objectives: To evaluate ACE and aADDUCIN gene polymorphisms in patients with nonrecurrent and recurrent HICH.
Methods: Out of 350 HICH, 33 (9.4%) patients had recurrence. ACE (rs4646994) and aADDUCIN (rs4961) gene
polymorphisms was done in patients and 198 controls. Risk
factors, clinical, CT, ACE (rs4646994) and aADDUCIN
(rs4961) findings between recurrent and nonrecurrent
HICH were compared.
Results: The stroke risk factors and drug compliance were
similar between the groups. Ganglionic-ganglionic recurrence
was commonest(75.6%) and all had at least one ICH in hypertensive location. DD genotype (OR6.18,95%CI2.9313.02) and D allele (OR2.43,95%CI1.70-3.47) of ACE was
associated with nonrecurrent ICH compared to controls. In
patients with recurrent ICH, DD genotype (OR7.46,95%
CI2.8-19.4) and D allele (OR3.16, 95%CI1.83-5.46) of ACE
and GW (OR3.49,95%CI 1.47-8.28) and WW (OR 2.9,
95%CI
1.40-4.30)
genotype
and
W
allele
(OR7.46,95%CI2.80-19.40) of aADDUCIN were more frequent compared to controls. Recurrent ICH also had higher
frequency of WW genotype (OR9.43,95%CI1.49-59.50) and
W allele (OR2.19,95%CI1.11-4.03) compared to nonrecurrent ICH. Higher frequency of DDþWW (P ¼ 0.008) and
DD/WWþID/GW (P ¼ 0.0001) genotypes were found in
recurrent compared to nonrecurrent ICH.
Conclusion: Variant genotype combinations of ACE and
aADDUCIN render the hypertensive patient vulnerable for
recurrent ICH.
Study supported by: Study is financially suppoerted by
Indian Council of Medical Research, Government of India.
S107. Ischemic Stroke Exome Pilot Study
John W. Cole, Xinyeu Liu, Luke J. Tallon, Lisa K. Sadzewicz,
Oscar C. Stine, Nicole Dueker, Yuching Cheng, Marcella A.
Wozniak, Barney J. Stern, James F. Mitchell, Braxton D.
Mitchell, Steven J. Kittner and Jeffrey R. O’Connell;
Baltimore, MD and Jacksonville, FL
Background: The genetic architecture of ischemic stroke is
complex and likely to include rare or low frequency variants with high penetrance and large effect sizes. Because a
significant portion of human functional variation may
derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human
exome.
Methods: Ten ischemic stroke cases including 8 AfricanAmericans and 2 Caucasians, consisting of 2 dissections, 5
lacunar, and 3 cryptogenic strokes underwent exome capture and sequencing implementing Illumina and Agilent
technology. Whole-genome alignments of the sequence
reads were performed using Burrows-Wheeler Aligner
against NCBI build 36.1 with the resultant exome data
evaluated for capture efficiency and rare variants as associated with stroke.
Results: Sequencing generated an average of 25.5 million read pairs (75bp x 2) and 3.8Gbp per sample. After
passing quality filters, screening the exomes against dbSNP
S105. Risk of Intracerebral Hemorrhage in t-PA Treated
Patients with Elevated INR
William P. Neil, Rema Raman, Ernstrom Karin and Thomas
M. Hemmen; San Diego, CA
Use of Intravenous tissue Plasminogen Activator (IV t-PA)
for stroke is limited to patients with an INR of less than
1.7. Initial guidelines recommended against use of IV t-PA
in patients with an INR >1.4. This was later revised
to >1.7.
We analyzed our database for safety and outcome in
patients with acute ischemic stroke treated with IV t-PA
from 2004–2010. We separated patients into two groups:
those with INR 0.8–1.3, N ¼ 210 (group 1) and those
with INR 1.4 - 1.7, N ¼ 12 (group 2).
Intracerebral hemorrhage occurred in 19/210 (9.05%) in
group 1 and 2/12 (16.67%) in group 2 (p ¼ 0.316). Symptomatic intracerebral hemorrhage (sICH) was found in 4/
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demonstrated an average of 2839 novel SNPs among African-Americans and 1105 among Caucasians. Nine gene
isoforms demonstrated compound heterozygosity across all
ten samples. Additional analyses are ongoing.
Conclusions: We propose that rare coding variants predispose to the risk of ischemic stroke and that exomic-based
analyses are a viable method to identify such variants.
Study supported by: Department of Veterans Affairs
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Results: At admission, the rate of ND was 37.7%, and
RD was 51.9%. The rates of RD were higher among
women on admission than men, 62% versus 37% respectively (p ¼ 0.036). At discharge the rate for ND, and RD
reduced significantly to 44.2%, and 33.7% respectively
(p<0.006).
Conclusion: Treatment and care at the hospital improved
the dipping status. Significant deviation from normal diurnal dipping is a risk for target organ damage and therefore
BP control needs emphasis.
S108. Phosphodiesterase Inhibitors Modulate Human
Brain Microvascular Endothelial Cell Barrier Properties
and Response to Injury
Shuo Liu, Fan Yang, Chuanhui Yu, Annlia Paganini-Hill and
Mark Fisher; Irvine, CA
S110. Preoperative Factors Associated with In-Hospital
Mortality Following Minimally Invasive Hematoma
Aspiration and Thrombolysis for Intracerebral
Hemorrhage
Feng Xu, Zhouping Tang, Huicong Kang, Dengji Pan,
Suiqiang Zhu and Wei Wang; Wuhan, China
Brain microvascular disorders have high prevalence but few
treatment options. To develop new strategies for these disorders, we analyzed effects of phosphodiesterase inhibitors
on human brain microvascular endothelial cells (HBEC).
We modified barrier properties and response to injury of
HBEC with three phosphodiesterase (PDE) inhibitors: cilostazol (PDE-3 inhibitor), rolipram (PDE-4 inhibitor),
and dipyridamole (non-specific PDE inhibitor). Cilostazol
and dipyridamole altered distribution of endothelial Factin. Cilostazol increased expression of tight junction protein claudin-5 by 118 % compared to control (p<.001).
Permeability to albumin was decreased by cilostazol (21%
vs control, p<.05), and permeability to dextran (70Kd)
was decreased by both cilostazol (37% vs control, p<.001)
and dipyridamole (44% vs control, p<.0001). Cilostazol
increased trans-endothelial electrical resistance (TEER) by
111% compared to control after 12 hours (p<.0001). Protein kinase A (PKA) inhibitors H89 and KT5720 attenuated the TEER increase by cilostazol. Using histamine as
standard injury for endothelial monolayers pretreated with
PDE inhibitors, cilostazol maintained higher TEER during
histamine injury. These findings demonstrate distinctive
effects of PDE inhibitors on HBEC. These in vitro findings suggest therapeutic potential of PDE inhibitors in
human brain microvascular disorders.
Study supported by: NIH NS20989 and Otsuka Pharmaceutical Company.
Dr. Fisher has received support from Boehringer-Ingelheim (honoraria, speakers’ bureau, research grant) and
Otsuka Pharmaceutical Company (honoraria, research
grant).
Background and Purpose: Intracerebral hemorrhage (ICH)
is the most fatal and disabling stroke subtype. The minimally invasive hematoma aspiration and thrombolysis has
the most evidence for beneficial effect on the ICH treatment
in the presence of mass-effect. The purpose of this study is
to define reliable predictors of in-hospital risk of death following this promising therapeutic modality.
Method: All consecutive ICH cases treated with the minimally invasive hematoma aspiration and thrombolysis were
prospectively characterized preoperatively from 2007 to
2010 in our division. Mortality was analyzed in relation to
CT findings (hematoma location and volume and ventricular extension) and clinical parameters (age and sex, preoperative level of consciousness and hematoma growth) by the
multiple linear regression statistical method.
Results: One hundred and twenty-nine ICH patients were
enrolled. The overall mortality rate was 13.17%. Multiple
linear regression analysis revealed initial level of consciousness
(B ¼ 0.035, p ¼ 0.002) and intraventricular hematoma (B
¼ 0.176, p ¼ 0.002) were the independent preoperative
prognostic factors associated with in-hospital mortality.
Conclusion: The level of consciousness along with neuroimaging features can help the clinicians to develop the prognosis of ICH patients treated with the minimally invasive
hematoma aspiration and thrombolysis.
Study supported by: Management position
S111. Does Incidental Micro-Hemorrhage, Detected by
Gradient Echo Sequence MRI, Predict Hemorrhagic
Transformation of an Ischemic Stroke?
Konark Malhotra and Yousef M. Mohammad; Chicago, IL
S109. Incidence of Nocturnal Blood Pressure Dipping
during Hospital Admission and Discharge among
African American Stroke Patients
Lien Diep, John Kwagyan, Joseph Kurantsin-Mills, Janaki
Kalyanam, Amy Wong, Kermit Crowder, Bonnie Davis, Leia
Harbour, Jean Edson and Annapurni Jayam-Trouth;
Washington, DC and Baltimore, MD
This is a case-control study. We retrieved data on 529 ischemic stroke patients admitted to Rush University. MRI with
gradient echo sequence was performed on all of the patients.
Using multivariate regression analysis, we assessed the risk
of micro hemorrhage(MH) for the development of hemorrhagic transformation(HT) of ischemic stroke after adjusting
for age, sex, hypertension, diabetes mellitus, and use of
antithrombotics agents prior to the stroke. We had a total
of 529 ischemic stroke patients. 81 patients developed HT
on the gradient echo sequence MRI. Using multivariate
regression analysis, incidental MH was not associated with
increased risk of HT of ischemic stroke (11% and 8.9% in
the cases and control respectively) (p ¼ 0.53). Interestingly,
the intake of anti platelet agents prior to the stroke was
associated with decreased risk of HT (33% and 47% in the
cases and controls respectively (p ¼ 0.02).
Background: Absence of nocturnal dipping in blood pressure (BP) is associated with risk of stroke, and incidence of
target-organ damage. Study examined prevalence of nondipping(ND) and reverse dipping (RD) among African
American acute stroke inpatients.
Methods: We studied 204 patients, 45% males, average
age 56 (610.7) years at Howard University Hospital. Daytime BP was defined as average from 10am to 6pm and
nighttime from 10pm to 6am. Nocturnal BP dipping refers
to 10% fall in average nighttime BP compared to daytime. Non-dipping, and reverse dipping during admission
were compared to that at discharge.
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In this small sample size study, incidental MH as detected
by Gradient Echo Sequence MRI was not associated with
increased risk for HT of ischemic stroke. However, prior
intake of anti-platelet agents was associated with decreased
risk for HT of ischemic stroke.
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S115. Genetic Analysis of Strain-Specific Stroke
Sesceptibility in Mice: How To Classify C57BL/6?
Amy K. Guzik, Sean S. Li, Ira M. Hall, Charles R. Farber,
Brian H. Annex and Bradford B. Worrall; Charlottesville, VA
Preclinical genetic research can identify potential mechanisms and therapeutic targets for ischemic stroke. Many
inbred mouse strains show consistent ischemic susceptibility.
Comparing C57BL/6 to susceptible strains, others have
identifed a chromosome 7 locus. However, we found no differentially expressed genes at this locus when comparing
multiple resistant to susceptible strains. Additionally, in our
literature review, C57BL/6 demonstrate variable vulnerability to MCA occlusion. Thus, we analyzed genomic differences between mouse strains with distinct stroke susceptibilities classifying C57BL/6 as susceptible, resistant, or neither.
Methods: Utilizing the mouse phenome database and literature-derived phenotypes, we compared resistant (129S1/
SvlmJ, DBA/2J, FVB/HJ, NOD/ShiLtJ) and susceptible
(AKR/J, BALB/cByJ, C3H/HeJ) strains. C57BL/6J was
added to resistant and susceptible groupings in separate
comparisons. Results: Comparisons excluding C57BL/6J
demonstrated higher density and percent difference in
genomic regions. Within specific loci of genomic differences, C57BL/6J share some patterns with resistant strains and
others with susceptible strains. Conclusion: These genetic
results mirror conflicting MCAO data, and therefore suggest
uncertain classification of C57BL/6. Among newly identified regions, a chromosome 4 locus encompases 100þ
genes, many we previously implicated in gene expression
experiments, providing promising targets for further
research.
Study supported by: NIH R25 resident training grant,
University of Virginia Internal CTSA pilot grant.
S112. Younger Patients Have Lower Quality of Life after
Intracranial Aneurysm Diagnosis
Nerissa Ko, Richard Hornung, Charles Moomaw, Laura
Sauerbeck and Joseph Broderick; San Francisco, CA and
Cincinnati, OH
Objective: Quality of life (QOL) is an important outcome
in patients with intracranial aneurysm (IA). EuroQol EQ5D is a validated preference-based survey that incorporates
functional, physical, and mental status into a single QOL
value. We measured EQ-5D in subjects with and without
IA in the Familial Intracranial Aneurysm (FIA) Study.
Methods: Within FIA families, subjects with IA were
identified after review of clinical and imaging data. Family
members free of IA entered the study as non-cases. Subjects
who completed the EQ-5D survey 365 6 60 days after diagnosis (75 cases) or study entry (885 non-cases) were
included in the present analysis. Multivariable logistic
regression was performed using the EQ-5D index adjusted
for variables known to affect QOL.
Results: EQ-5D index was significantly lower in subjects
with IA than in those without IA (mean 6 SD 0.84 6
0.19 vs. 0.90 6 0.15, p<0.001), especially within the anxiety/depression component (p<0.001). This difference persisted in the multivariable model, with strong interactions
noted with tobacco use and age<50 years (p ¼ 0.02).
Interpretation: The lower QOL indices in younger IA
patients may reflect the impact of IA diagnosis on mental
status rather than physical/functional disability in this
subgroup
Study supported by: NIH/NINDS R01NS039512
S116. Risk Factor Control in a Phase 3 Carotid
Revascularization Trial
James F. Meschia, Pierre P. Leimgruber, Vito A. Mantese,
Carlos H. Timaran, David Chiu, Bart M. Demaerschalk,
Mary E. Longbottom, Jenifer H. Voeks, George Howard and
Thomas G. Brott; Jacksonville, FL; Spokane, WA; St. Louis,
MO; Dallas, TX; Houston, TX; Phoenix, AZ and
Birmingham, AL
S113. Aggressive Medical Management of Primary
Intracerebral Hemorrhage: Cost/Benefit Analysis
Luis Cava, Diane C. Andress-Rothrock and John F. Rothrock;
Birmingham, AL
Objective: to assess the direct medical cost and clinical outcome associated with aggressive medical management of supratentorial primary intracerebral hemorrhage (PICH).
Methods: We evaluated 150 consecutive cases of supratentorial PICH wherein the patient was intubated and
mechanically ventilated within 24 hours of admission. Clinical outcome and hospital-related direct medical costs were
the primary variables examined.
Results: Of the 150 patients, 66(44%) died in the hospital; intraventicular extension of ICH and age >65 each correlated independently with in-hospital mortality (p<.025).
Of the 84 survivors, 3(3.5%) were discharged to home and
the remainder to an extended care facility. One month following initial admission, 1(.6%) of the 150 patients was independent in routine activities of daily living. The mean
direct cost associated with in-patient management exceeded
$275,000 (range $24,000-$1.5 million).
Conclusion: Aggressive medical management of supratentorial PICH is associated with an unfavorable clinical outcome and represents a particularly poor use of healthcare
resources.
Background: Success of carotid revascularization in preventing stroke must be seen in the context of the success or failure to control traditional risk factors.
Purpose: To describe Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) risk factor control.
Methods: Risk factor intervention was not protocoldriven. Investigators and coordinators counseled patients
and communicated by form-letter with primary physicians, guided by patient-visit results and Guideline statements, with oversight by the CREST PI and Co-PI. Exploratory analyses were performed at baseline and at 36months.
Results: For asymptomatic patients, results at 0- and 36months were 142 and 139mmHg for mean systolic blood
pressure (SBP); 73 and 75mmHg for mean diastolic BP
(DBP); 120 and 112mg/dL for blood glucose; 92 and
87mg/dl for LDL cholesterol; and 24 and 11% for the
active smoking. For symptomatic patients, results were 143
and 136mmHg for SBP; 75 and 74mmHg for DBP; 114
and 114mg/dl for glucose; 102 and 91mg/dl for LDL; and
27 and 12% for active smoking.
S114. Withdrawn
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Conclusion: Traditional stroke risk factors were comparably controlled for asymptomatic and symptomatic patients,
with notable success only in smoking cessation. Protocoldriven approaches merit further study.
Study supported by: This study was supported by the
National Institute of Neurological Disorders and Stroke
(NINDS) and the National Institutes of Health (NIH)
(R01 NS 038384) and supplemental funding from Abbott
Vascular Solutions (formerly Guidant).
Dr. Carlos Timaran reports receiving Speakers’ fees and
Honoraria from Abbott Vascular. Dr. George Howard
reports receiving compensation for activities with Bayer
Healthcare and research support from Amgen and Bayer
Healthcare. He is also a consultant to Abbott for preparation of FDA materials.
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disease (e.g., carotid stenosis). Two independent reviewers
selected studies, with differences adjudicated by a third.
Study characteristics, patient symptoms, and lesion locations
were abstracted.
Results: We identified 414 unique citations, examined
67 full manuscripts, and analyzed 39 studies describing
1214 patients. Principal reasons for abstract exclusion
were non-English language, no confirmed cerebrovascular diagnosis, and not anterior circulation (73%).
Principal reasons for manuscript exclusion were no
reported dizziness and no confirmed cerebrovascular diagnosis (53%). Unbiased studies of dizziness prevalence
in anterior circulation stroke (i.e., dizziness not a mandatory symptom) reported a presenting symptom of
dizziness in 12% (8.4% non-vertiginous, 3.2% vertiginous), syncope in 6.6% of n ¼ 683. Non-vertiginous
symptoms were more commonly reported in right hemispheric lesions (73.9% vs. 26.1%, v2 p<0.001). Typical lesion locations were insula, parietal cortex, and
subcortical white matter.
Conclusions: Contrary to common wisdom, dizziness
and vertigo are presenting symptoms of anterior circulation
vascular disease.
S117. Radiologic Analysis of Thrombolysis-Induced
Intracerebral Hemorrhage and the Role of Early Blood
Pressure Management
Maxim Mokin, Tareq Kass-Hout, Omar Kass-Hout, Robert
Zivadinov and Bijal Mehta; Buffalo, NY
Introduction: The radiographic features of thrombolysisinduced intracerebral hemorrhages (ICH) and factors that
influence early hematoma expansion are not well described.
Methods: We performed volumetric analysis of hematoma volumes in patients who developed ICH from intravenous thrombolysis for acute ischemic stroke. Analysis of covariance was used to evaluate for the effect of baseline blood
pressure (BP) on initial hematoma volume and further
growth.
Results: We found a positive correlation between systolic
BP following thrombolysis and initial hematoma volume (r
¼ 0.46, p ¼ 0.03) but not for the diastolic BP (r ¼ 0.07,
p ¼ 0.40). There was a significant increase in mean hematoma volume expansion when comparing results between
the first and second (median time 9 hours 22 min) CT
study (14.9 6 19.6 cm3 to 26.0 6 26.7 cm3, p ¼ 0.04).
There was also a negative association between the reduction
of systolic BP and hematoma growth (r ¼ 0.67, p ¼
0.02), but no correlation with change in diastolic BP (r ¼ 0.22, p ¼ 0.28).
Conclusion: Thrombolysis-induced ICH undergoes
significant early expansion in size. Systolic BP plays a
role in both initial hematoma development and early
growth.
Dr. Robert Zivadinov received personal compensation
from Teva Neuroscience, Biogen Idec, EMD Serono and
Questcor Pharmaceuticals for speaking and consultant
fees, financial support for research activities from Biogen
Idec, Teva Neuroscience, Genzyme, Questcor Pharmaceuticals, Greatbatch, EMD Serono and Bracco. Dr. Bijal
Mehta received lecturing honoraria from Teva and Biogen
Idec.
S119. The Presence of Intracranial Vascular Calcification
May Protect Against Vasospasm Following Subarachnoid
Hemorrhage
Joya Paul, Mohamed Zghouzi, Yousef Mohammad, Shyam
Prabhakaran, Sudeep Bhabad and Bichun Ouyang;
Chicago, IL
Vasospasm is a serious complication of subarachnoid hemorrhage (SAH). Intracranial vascular calcification (IVC) is
incidentally noted on computerized tomography (CT). Presence of IVC may retard contraction of vascular smooth
muscle and inhibit vasospasm.
In a retrospective single-center study, we reviewed data on
consecutive patients with SAH. Symptomatic vasospasm was
defined as clinical deterioration associated with angiographic
vasospasm requiring intra-arterial treatment. Brain CT
angiogram (CTA) images were evaluated for IVC. Chisquare tests and logistic regression analyses assessed the association between IVC and symptomatic vasospasm and controlled for age, gender, Hunt Hess (HH) score, and Fisher
Grade (FG).
Among 434 patients with SAH, 313 had complete data
(mean age 57; 67% female). IVC was detected in 40% and
20% had symptomatic vasospasm. Only 12.7% of those
with IVC had symptomatic vasospasm versus 25.2% in
those without IVC (OR ¼ 0.430, p ¼ 0.004). Adjusting
for age, gender, HH score, and FG, presence of IVC
showed a trend towards decreased odds of symptomatic vasospasm (adj. OR ¼ 0.534, p ¼ 0.075).
IVC may have a protective effect on symptomatic
vasospasm following SAH. Further study may be
warranted.
S118. Anterior Circulation Stroke Causing Dizziness or
Vertigo: A Systematic Review
Yun Zhou, Seung-hun Lee, Ali S. Saber Tehrani, Karen A.
Robinson and David E. Newman-Toker; Baltimore, MD and
Gwangju, Korea
S120. Stroke Knowledge: A Nation-Wide, Internet-Based
Survey of 11,121 Inhabitants in Japan
Hisanao Akiyama, Kanako Shimizu, Yoshiaki Tokuyama and
Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan
Background: Determine frequency, localization of anterior
circulation stroke causing dizziness/vertigo.
Methods: Systematic review of observational studies.
Search—electronic (MEDLINE) and manual search for English-language studies (1966–2011). Inclusions—dizziness/vertigo/syncope due to anterior circulation stroke or vascular
Objective: To investigate the difference in stroke knowledge
among inhabitants, we performed a nation-wide, internetbased survey.
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Method: The survey was conducted from November,
2010 via internet using structured, self-applicable questionnaire addressed stroke knowledge.
Results: We have valid responses from 11,121 people
aged from 20 to 69 years old throughout all Japanese districts. 66.2% of subjects were no source of informations
about stroke. On the other hand, subjects of remaining
33.8% can get the informations of stroke through mainly
TV (85.2%). They understood the signs of stroke such as
speech disturbance (95.5%). 67% of them request the ambulance and transport to the hospital promptly at the time
of stroke onset but only 22.4% on the occasion of TIA.
Importance of early diagnosis and treatment within 3
hours of onset was well recognized among all age subjects
(75.3%) and significantly associated with calling ambulance quickly when stroke (OR 4.458, 95%CI, 3.897–
5.099, p ¼ 0.000) or TIA (OR 2.331, 95%CI, 1.923–
2.825, p ¼ 0.000) occurred.
Conclusions: Our survey demonstrates that it is important to educate stroke knowledges through TV such as judgment of stroke and calling ambulance when stroke or TIA
occurred.
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hypertension (HTN) are modifiable cardiovascular risk factors with higher prevalence in minorities.
Design: We evaluated patients with acute ischemic
stroke/TIA presenting to Boston Medical Center from 1/
2009-12/2010. Patients were stratified by race (Whites,
Blacks, Other) and insurance status (Medicaid/no insurance,
Medicare, Private). Cardiovascular risk factor control
(HTN, hyperlipidemia, diabetes) was evaluated on
admission.
Results: Among 833 patients (mean age 61yrs, 50.4%
women), 34.8% were white, 45.5% black and 19.7% other
races; 50.4% were insured and 49.6% uninsured. Compared
to white, black and other races were more likely to be uninsured (p<0.001), had higher LDL (p<0.001), HbA1C
(p<0.001), and DBP (p<0.001). Compared to insured
patients, uninsured patients were younger (p ¼ 0.0001),
had higher LDL (p ¼ 0.02), HbA1C (p ¼ 0.02), and DBP
(p ¼ 0.02).
Conclusions: Our findings suggest that race and insurance disparities may influence the control of cardiovascular
risk factors, thereby risk of stroke.
S123. A Population-Based Verbal Autopsy Study of 1250
Stroke Deaths in Bangladesh
Farrah J. Mateen, Nurul Alam, Marco Carone and Robert E.
Black; Baltimore, MD; Dhaka, Bangladesh and Berkeley, CA
S121. Is Anti Epileptic Drug Necessary in Cortical
Venous Thrombosis?
Velmurugendran Cannigaiper Uthamaroyan, Kaushik Sundar,
Meenakshisundaram Umaiorubahan and Shankar
Venkatasubramaniam; Chennai, Tamilnadu, India
Background: Verbal autopsy is an interview-based method
to determine the cause of death in resource-poor regions. A
health and demographic surveillance system has been maintained in Matlab, Bangladesh since 1966 (average population 223,886 in 142 villages).
Methods: All adult deaths (2005–2008) were reviewed
and categorized by medical officers. Risk factors for stroke
deaths were calculated using all adult injury deaths as
controls.
Results: 1250 stroke deaths (51% women; mean age 72
years, range 20–101) occurred out of 4955 total deaths
(population-attributable mortality 25.2%) and were compared to 274 adult injury deaths (47% women, mean age
55.8 years, range 20–100). Risk of stroke death increased
with hypertension (OR ¼ 7.94, 95%CI 4.44-15.54,
p<0.001), diabetes (OR ¼ 2.54, 1.21-6.21, p ¼ 0.02), and
betel consumption (OR 2.36, 1.45–3.80, p<0.001), but
not from heart disease (OR 1.37, 0.45–5.95, p ¼ 0.62),
cigarette smoking (OR ¼ 1.41, 0.82–2.45, p ¼ 0.22),
tobacco powder (OR ¼ 1.15, 0.30–7.64, p ¼ 0.86), or
pipe smoking (OR ¼ 0.94, 0.45–2.18, p ¼ 0.88).
Conclusions: There is a high modifiable burden of risk
factors for adult stroke deaths in rural Bangladesh which
may include betel consumption, a previously unidentified
risk factor for stroke. Endemic hypertension and diabetes
also represent treatable and preventable risk factors.
Study supported by: Dr. Mateen is supported by the
American Academy of Neurology Practice Research Fellowship Grant and The Johns Hopkins Bloomberg School of
Public Health Sommer Scholars Program.
Introduction: Though CVT is associated with seizures,is it
necessary to start AEDs in all patients with CVT?
Aims To study the clinical profile of patients with CVT
and to find out the incidence and etiology of seizures.
Materials and methods: Patients who presented with
signs and symptoms suggestive of CVT were admitted and
brain imaging was done.If CVT was revealed,requisite investigations were done.Patients were then treated and followed
up for a period of one year.
Results: 50 (28 males/22 females) patients were diagnosed
to have CVT.Of these 50 patients 25 of them presented with
Seizures and all these 25 had an infarct/haemorrhage/ infarct
with haemorrhagic transformation in their MRI.
Discussion: We found that 50% of our study patients
had seizures and all of them had an infarct/haemorrhage/or
infarct with haemorrhagic transformation.The patients who
did not have an infarct did not have a seizure and were not
started on AEDs and remain seizure free till date.
Conclusion: Patients with CVT who have no evidence of
parenchymal lesion in the MRI need not be treated with
AEDs as a prophylaxis and a wait and watch strategy can be
followed.
Study supported by: Self
S122. Race and Insurance Disparities in Cardiovascular
Risk Factors Control in Patients with Acute Stroke
Anna M. Cervantes, Jose R. Romero, Helena Lau, Feliks
Koyfman, Aleksandra Pikula, Thanh N. Nguyen, Carlos S.
Kase and Viken L. Babikian; Boston, MA
S124. Heparin-Induced Thrombocytopenia Associated
with Cerebral Venous Sinus Thrombosis Following
Postoperative Enoxaparin Administration in a
64 Year-Old Female
Robert A. Fishman and Ashis Tayal; Pittsburgh, PA
Objective: To investigate racial and socioeconomic disparities in cardiovascular risk factor control at the time of acute
ischemic stroke at an urban hospital.
Background: Racial and socioeconomic inequalities may
play a role in the observed higher frequency and severity of
stroke in minorities. Hypercholesterolemia, diabetes and
Heparin-induced thrombocytopenia (HIT) is a serious platelet dyscrasia that is associated with clinically-significant
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arterial and venous thrombosis. The more common, and
dangerous form of HIT, HIT II, is caused by prothrombotic
anti-heparin/platelet factor PF4 complex antibodies, which
activate platelets, induce their aggregation, and trigger coagulation (1). The consequences, especially if not diagnosed
early, can be devastating, ranging from deep venous
thromboses to myocardial infarctions and strokes. HIT is
most commonly associated with the use of heparin after orthopedic procedures, as compared to cardiovascular surgeries
and medical conditions requiring admission to an intensive
care unit. HIT is much less frequently associated with the
use of low molecular weight heparin, such as enoxaparin
(3). Here, we present the case of a 64 year-old woman who
developed both a lower extremity deep venous thrombosis
and cerebral venous sinus thromboses from the administration of enoxaparin after an orthopedic surgery. Our patient
is only the second reported case of HIT-induced CVST
related to enoxaparin administration. Our poster will
include brain imaging, graphs and tables regarding the clinical case.
Study supported by: Residency Program
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tion. Typical RVAS is known to occur due to compression
of the dominant vertebral artery during contralateral head
rotation, usually at the atlantoaxial joint. A few reports have
described atypical patterns of RVAS, such as compression of
bilateral vertebral artery during unilateral head rotation and
various compression level. The present case shows that dominant vertebral artery can be also compressed by ipsilateral
head tilt in RVAS. A 29-years-old man presented with 8
months history of paroxysmal vertigo induced by head tilt
to the left. The patient reported that tinnitus in both ears
and visual blurring were accompanied by rotatory vertigo.
Leftward head tilt induced mainly downbeat nystagmus
with a small left beating horizontal component. MRI of the
brain was unremarkable and MR angiography showed a
hypoplastic right vertebral artery. Dynamic angiography
documented complete occlusion of the left vertebral artery
at the atlantoaxial junction during leftward head tilt.
S127. A Novel Presentation of Mesodiencephalic
Ischemic Stroke: Case Report and Literature Review
Khalid S. Alqadi, Tariq Alfahad and Kathleen Burger;
Washington, DC
S125. Renal Failure Increases Risk for Intracranial
Hemorrhage Following Stroke
Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and
Rebecca F. Gottesman; Baltimore, MD
Objective: To present and discuss the clinical and image
findings of a novel mesodiencephalic infarct along with its
anatomic and pathophysiologic correlates.
Background: Strokes in the mesodiencephalic junction
can have different presentations due to its complex neural
circuits. Weber’s syndrome from thalamic-midbrain stroke
has been described in the literature in association with facial
palsy, & vertical gaze palsy.
To our knowledge, the combination of Weber’s syndrome,
contralateral facial & pseudoabducens palsies with vertical
gaze palsy have never been described before.
Results: A 45 year old male presented with acute onset
of double vision, speech difficulty and left side weakness.
Neurological exam showed right oculomotor nerve palsy,
left central facial and pseudoabducens palsies with vertical
gaze palsy, and left hemiparesis. His NIH stroke scale was
11. MRI revealed right thalamic infarct extending inferiorly
into the midbrain. MRA of head and neck, and transthoracic echocardiogram were normal.
Conclusions: This case highlights the importance of recognizing the atypical manifestations of strokes in the thalamic midbrain junction. Small vessel stroke at the mesodiencephalic junction can lead to a combination of weber’s
syndrome with contralateral facial and pseudoabducens palsies with vertical gaze palsy.
Background: Anticoagulation is associated with increased
risk of intracranial hemorrhage. Renal failure can lead to
platelet dysfunction, which may increase the risk further.
We followed patients admitted with acute ischemic stroke
who had an indication for anticoagulation, to determine if
renal failure was associated with increased risk for intracranial hemorrhage.
Methods: 63 patients admitted with acute ischemic
stroke and with an indication for anticoagulation were
included. Age-adjusted logistic regression was used to evaluate the association between history of renal failure and glomerular filtration rate (GFR) (>60 (normal), 30–60 (mildly
reduced), <30 (moderately reduced)), and risk for
hemorrhage.
Results: Patients with renal failure of any type were
much more likely to hemorrhage than individuals without
history of renal failure (OR 12.40, 95% CI 1.35–113.36).
Worsening GFR was also highly associated with risk of
hemorrhage. Compared to individuals with normal GFR,
patients with mildly reduced GFR were 1.2 times (OR
1.22, 95% CI 0.09–16.16) and individuals with moderately
reduced GFR were 15 times (OR 15.43, 95% CI 1.98–
120.02; p-trend 0.03) more likely to bleed.
Conclusions: In patients with acute ischemic stroke who
also require anticoagulation, renal insufficiency is associated
with increased risk of intracranial hemorrhage.
Study supported by: The first author, EB Marsh, is supported in part by a NINDS R25 Research Grant- R25
NS065729.
EB Marsh is currently a resident, partially supported by
funding from the R25 Research Grant.
S128. Fatal Postpartum Cerebral Vasoconstriction
Syndrome
Jennifer E. Fugate, Eelco F.M. Wijdicks, Kelly D. Flemming
and Alejandro A. Rabinstein; Rochester, MN
Background: Postpartum cerebral vasoconstriction is typically considered benign and self-limiting. We describe four
fulminant and fatal cases seen in a short time period at one
institution.
Methods: Retrospective case series of patients seen at
Mayo Clinic from August 2009 – October 2010.
Results: Four women ages 15–33 developed acute neurologic deficits 1–8 days after uncomplicated deliveries. One
had history of migraine headaches. Two had uneventful
pregnancies while two had pre-eclampsia. Presenting symptoms included severe headache (n ¼ 3), focal deficit (n ¼
1), seizure (n ¼ 1) and encephalopathy (n ¼ 1). Initial
brain imaging demonstrated ischemia and global edema in
2, lobar hemorrhage in 1, and normal findings in 1. All had
S126. Dominant Vertebral Artery Occlusion during
Ipsilateral Head Tilt
In Soo Moon, Jae-Hwan Choi and Kwang-Dong Choi; Busan,
Korea
Paroxysmal vertigo induced by head rotation occurs in
patients with rotational vertebral artery syndrome (RVAS),
which is characterized by recurrent attacks of vertigo, nystagmus, and ataxia that are mainly induced by head rota-
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rapid deterioration over hours to days with multi-territorial
infarctions and global edema on imaging. All had angiographic findings of diffuse, severe, multifocal arterial narrowings. Aggressive treatment was attempted in most,
including intravenous magnesium, corticosteroids, calcium
channel blockers, balloon angioplasty, vasopressors, and osmotic agents. Despite aggressive measures, all patients suffered fulminant courses ending in death within 8–24 days
after delivery.
Conclusions: Postpartum vasoconstriction can be fatal
with rapid progression of vasoconstriction, ischemia, and
brain edema. Postpartum women with acute neurological
symptoms deserve close monitoring with consideration of
noninvasive cerebrovascular imaging.
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Results: A positive correlation between the volume of infarction measured on MRI and NIHSS at presentation was
found with an R squared value of .12. NIHSS stroke scale
range was 7–32. 11 of 14 patients with infarction volume
of < 30 ml had improved outcome with 1 no change and 2
worsening. Of the 6 with infarction volume > ¼ 30ml and
< ¼ 100ml, 5 improved and 1 had worse outcome. 4
patients had infarction volume > 100 with one improved
and 3 with worse outcome.
Conclusion: High ischemic volume have higher NIHSS
and worse outcome.
Study supported by: USF College of Medicine
S131. Treatment Outside the NINDS Stroke Study
Exclusion Criteria: A Case Report
Nhu T. Bruce and Brett C. Meyer; San Diego, CA
S129. Racial Disparities in Secondary Stroke Prevention
Practices
Pratik Bhattacharya, Seemant Chaturvedi, Flicia Mada, Leeza
Salowich-Palm, Sabrina Hinton, Scott Millis, Sam Watson
and Kumar Rajamani; Detroit, MI and Lansing, MI
Introduction: The original NINDS stroke trial established
IV rt-PA as effective and defined treatment parameters.
Some exclusions were well founded on data, others were
chosen via consensus opinion. Successful use of rt-PA outside of some criteria raises concern over the continued utility of some exclusions. We report an intriguing case where a
patient with prolonged PTT was successfully treated with IV
rt-PA.
Methods: Case report from the University of California,
San Diego
Results: An 86 year old woman with no hematologic history presented with acute ischemic stroke within the 3 hour
window. Given her lack of being on anticoagulants or having hepatic dysfunction, her elevated PTT was felt to be
spurious, and she was treated with rt-PA despite not meeting this inclusion criteria. Patient had significant improvement and work up was positive for a diagnosis of anti-phospholipid antibody syndrome.
Conclusions: rt-PA treatment is effective, though only a
minority of patients is treated. Multiple cohort studies have
shown that deviations from the original exclusions may not
result in worse outcomes for specific exclusion criteria.
Reevaluating the significance and limiting the exclusion criteria may help to increase thrombolytic treatments.
Study supported by: NIH SPOTRIAS
Racial differences in stroke risk, risk factor prevalence and
outcomes are established. We explored racial differences in
secondary stroke prevention practices among stroke patients.
Methods: A retrospective review was conducted on ischemic
stroke patients in 5 JC (Joint Commission) certified and 5
noncertified hospitals. Secondary stroke prevention measures
such as antiplatelet use, statin use, antihypertensives and
smoking cessation steps were assessed. Results: 574 patients
(430 white, 144 African Americans(AA); 47.9% evaluated at
JC certified centers) were included. AA were younger (mean
age 64.4 vs 72.5; p<0.0001) and more likely to have prior
stroke (37.1% vs 27.7%; p ¼ 0.03). More AA were evaluated at JC certified centers(65.3% vs 42.1%; p<0.0001).
AA received stroke education materials(89.9% vs 77.8%; p
¼ 0.002) and were discharged on antiplatelets more often
(95.8% vs 89.5%; p ¼ 0.02). Compliance with secondary
prevention measures was higher in JC certified centers.
Racial disparity in antiplatelet use was present in JC certified centers alone(100%in AA, 91.8% in whites; p ¼
0.005). Patients discharged without antiplatelets from JC
centers were older and more likely to be discharged to a
nursing home. Conclusions: Racial disparities exist in secondary stroke prevention practices (antiplatelet use and stroke
education) even in JC certified centers. Increased awareness
of these differences amongst patients, families and caregivers
could help narrow the disparities.
Study supported by: Blue Cross and Blue Shield Foundation of Michigan.
S132. Size Matters: Predictors of Intracranial
Hemorrhage in Stroke Patients on Anticoagulation
Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and
Rebecca F. Gottesman; Baltimore, MD
Background: Anticoagulation is associated with increased
risk of intracranial hemorrhage. This may be higher in
patients who have had a recent stroke. We followed patients
with acute ischemic stroke who had an indication for anticoagulation, to determine what factors were associated with
increased risk for hemorrhage.
Methods: 63 patients admitted with acute ischemic
stroke and with an indication for anticoagulation were
included. We evaluated risk of hemorrhage associated with
indicators of stroke severity; namely NIH Stroke Scale
(NIHSS) score and infarct size (largest lesion and total
lesion volume), using age-adjusted logistic regression.
Results: Higher NIHSS scores predicted increased risk of
hemorrhage. For every 3 point increase, risk for hemorrhage
increased 51% (OR 1.51, 95% CI 1.01–2.25). Total volume of the infarct also approached statistical significance
(OR 2.6 per larger quartile, 95% CI 0.86–7.56).
Conclusions: In patients with acute ischemic stroke who
also have an indication for anticoagulation, the severity of
S130. Predicting Ischemic Stroke Outcomes Based on
Volume of Lesion
Shazia Z. Choudhary, Jay-Ming Wang, Zahid Choudary,
Michael Sloan, Harry R. Van Loveren, Karen R. Wilson,
Morgan Wang and David A. Decker; Tampa, FL and
Orlando, FL
Hypothesis: Can stroke lesion volume predict ischemic
stroke outcome?
Background: Imaging to diagnose stroke needs development to maximize its potential. We seek to the use stroke
lesion volume to predict ischemic stroke outcome.
Methods: We did a retrospective chart review of 24
patients with hospitalization with ischemic stroke. The volume of the infarction was measured by using (A x B x C) /
2 method. Patient outcomes were measured by linear regression model and data segmentation.
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their stroke, indicated by their NIHSS score and volume of
infarct, is a strong predictor of their risk for hemorrhage.
Study supported by: The first author, EB Marsh, is supported in part by a NINDS R25 Research Grant- R25
NS065729.
EB Marsh is currently a resident, partially supported by
funding from the R25 Research Grant.
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Background: Not all guidelines for stroke are well supported by evidence. We seek to retrospectively study the
effects of MERCI/PENUMBRA stroke interventions and
hemodynamics to see ischemic stroke outcome.
Methods: A retrospective chart review of 24 patients with
hospitalization with ischemic stroke with age range 18 to
90, mean age 70.6, 13 males, and 11 females. The blood
pressure was correlated with ischemic stroke outcome. The
patients undergoing MERCI/PENUMBRA intervention
were analyzed.
Results: We noted a significant positive correlation
between higher blood pressures and worse outcomes in
patients with large volume lesions.
In the 8 patients with MERCI/PENUMBRA intervention, we had 3 with worse outcomes and 5 with improvement at discharge. Of the 3 with worse outcomes, 2 had
large lesions and 1 had a small lesion. The 5 improved outcomes had 3 small lesions and 2 medium lesions. Three of
the five had received IV tPA prior to interventional therapy.
Two did not.
Conclusion: MERCI/PENUMBRA intervention has an
overall positive outcome on patients suffering from ischemic
stroke.
Higher blood pressures predict a worse outcome in
patients with stroke lesions greater than 100 ml.
Study supported by: USF College of Medicine
S133. A Rare Presentation of Anterior and Posterior
Spinal Arteries Ischemia during Dilaysis
Noor Yono, Adrian Marchidann and Rabih Kashouty;
Manhasset, NY and New York, NY
Spinal cord infarction is considered to be a rare event and
usually presents with severe neurological deficits. Multiple
etiologies have been described; however, this is the first case
report of spinal cord infarction in the territory of the anterior and posterior spinal arteries secondary to hypotension
during dialysis. We report a case of a 60 year-old man with
past medical history of severe atherosclerosis, coronary artery
disease and acute kidney failure, who presented with lower
extremity paraplegia during hemodialysis secondary to hypotension. MRI of the spine demonstrated spinal cord infarction starting at the level of T8 and below. Clinical features
suggested that the lesion was an ischemic infarct. In addition to paraplegia, he demonstrated absence of sensation to
dull touch, pin prick, temperature, proprioception and
vibration. Hypotension during dialysis could carry significant risk of spinal cord infarction. This unusual infarction
demonstrates the importance of blood pressure control in
susceptible patients with severe atherosclerotic disease. Physicians should be aware of such complications.
S136. Migraine-Related ICH – A Case Study and Review
Shivani Ghoshal**, Sankalp Gokhale and Louis Caplan;
Boston, MA
54 year-old right-handed male, with a 25-year history of
frequent migraine headache, presented with an episode of
severe migraine headache associated with visual changes;
imaging revealed new left frontal intracranial hemorrhage.
Since then, the patient had two different types of paroxysmal attacks. One consisted of prolonged severe headaches
with multisystem sensory deficits, most consistent with migraine with aura. The second consisted of brief visual and
auditory perseveration, likely representing focal seizures near
the region of ICH. Excluding the initial presentation, the
subsequent episodes left no discernible damage on clinical
exam or imaging. Migraine is a form of vascular headache,
postulated to cause direct vasoconstriction of cerebral vessels. This vasospasm may, in some cases, lead to reperfusion
edema, with intracerebral bleeding to follow. Though migraine-related ischemia has been well-documented, there
have been few noted cases of migraine-related ICH and
none to date in male patients; the association of migraine
and ICH is likely under-recognized and hence underreported. Given the dangers for cerebral hemorrhage, future
migraine treatment may benefit from weighing the risk of
vasoactive agents. We take this opportunity to review the
current literature to provide guidance for improvement in
care.
S134. Neurosarcoidosis: A Case Presentation
Amtul Farheen, Nancy Gadallah, Rony Dekermenjian,
Michael Rosenberg and Sushanth Bhat; Edison, NJ
27 y/o man with no significant medical history woke up
with weakness and parasthesias of his right side. He smoked
1ppd for more than 10yrs. Neurological examination was
significant for decreased power on right side. Right upper
extremity revealed power of 2/5 deltoid, 3/5 bicep/tricep/
brachio, 1/5 intrinsic hand muscles, Right lower extremity
revealed: 4/5 iliopsoas, hams, quads 0/5 dorsi and plantar
flexion 0/5. Sensation was mildly decreased on right side.
Reflexes were asymmetric and increased with upgoing toe
on the right. MRI brain showed small left medullary hyperintensity. Csf had opening Pressure of 23, RBC 222, WBC
7, Prot 57.8, Glucose 65. CSF was negative for gram stain,
protein electrophoresis, oligoclonal bands, and infectious
work up. Csf ACE 0.1. Serum ACE was 109. CT chest
showed mediastinal and bilateral hilar lymphadenopathy.
Mediastinal lymph node biopsy revealed noncaseating granulomas diagnostic of neurosarcoidosis. The patient was
started on iv steroids and was discharged on oral prednisone. He improved clinically and was later almost back to
his baseline.
Although sarcoidosis is rarely confined to the nervous system, its neurological features frequently occur early in the
course of the disease leading to diagnostic confusion.
S137. Stroke as a Complication of Tuberculous
Meningitis
Amtul Farheen, Sumaiya Salim, Zoha Fasih, Rony
Dekermenjian and Sushanth Bhat; Edison, NJ
S135. Stroke Outcomes Based on MERCI/PENUMBRA
Intervention and Hemodynamics
Jay-Ming Wang**, Zahid I. Choudary, Shazia Z. Choudhary,
Michael Sloan, Harry R. Van Loveren, Karen R. Wilson and
David A. Decker; Tampa, FL
A 28 y/o Hispanic man who moved to US from Guatemala
four years before presentation, had no significant past medical history presented with 2 days of progressive confusion
and headache. He reported weight loss, severe cough for few
days with low grade temperatures and night sweats. He
smoked occasionally. On examination he was lethargic and
cachectic, neck stiffness noted, enlarged lymph nodes of the
Hypothesis: What are the effects of MERCI/PENUMBRA
and blood pressure on stroke outcome?
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neck. He was tachycardic and had diminished breath sounds
with bilateral crackles. Neurological examination revealed
normal cranial nerve examination. He moved all extremities
spontaneously. Initial CT head was normal. Lumbar puncture revealed WBC 53 (neutrophils predominantly), RBC 7,
Protein 170, Glucose 7. Sputum was positive for AFB. HIV
testing was negative. He was diagnosed with disseminated
tuberculosis with tuberculous meningitis and started on
antituberculous medications. On the third day of admission
he had decreased movement of the left side of his body and
a repeat CT of his head showed a new infarct in the right
internal capsule.
Vasculitis of the vessels of circle of Willis which may
present as stroke is one of the most dreaded complications
of Tuberculous meningitis.
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Results:7,925 dizzy patient complaints (3% of visits,
weighted 28.3 million) sampled over 13 years. Dizziness
was ‘‘isolated’’ (none, nausea/vomiting, or otologic co-complaints) in 21%; others with dizziness had only neurologic
(10%), only medical (15%), or other (54%) co-complaints.
Cerebrovascular causes were diagnosed in 4.1% (isolated),
10% (neurologic), 0.9% (medical), 3.8% (other), 1.0%
(non-dizzy controls). Neurologic co-symptoms increased
odds (2.57, 95%CI 1.85 to 3.58) and medical co-symptoms
decreased odds (0.21, 95%CI 0.10–0.41) of a cerebrovascular diagnosis relative to isolated dizziness.
Conclusions: ED physicians use associated symptoms to
diagnose dizzy patients. While this reflects an appropriate
assessment of disease probability, it could increase the risk
of stroke misdiagnosis in isolated dizziness or dizziness with
medical symptoms.
Study supported by: This study was supported principally
by the National Institutes of Health, National Center for
Research Resources (NCRR) grant K23 RR 17324-01.
S138. Patterns and Mechanisms of Head-Shaking
Nystagmus in Anterior Inferior Cerebellar Artery
Infarction
Young Eun Huh and Ji Soo Kim; Seongnam-si, Gyeonggi-do,
Korea
S140. Eclamptic Versus Non-Eclamptic PRES (Posterior
Reversible Encephalopathy Syndrome): Comparison of
Clinical Features and Response to Treatment
Pavan Bhargava, Fazeel Siddiqui, Vivek Patel, Rodger J. Elble
and Srikanth Vallurupalli; Springfield, IL
Infarctions involving the anterior inferior cerebellar artery
(AICA) territory give rise to unique clinical features of combined peripheral and central vestibulopathies. Evaluation of
head-shaking nystagmus (HSN) may provide information
on central and peripheral vestibular dysfunction. We analyzed patterns of spontaneous nystagmus (SN) and HSN in
18 patients with acute infarction involving the AICA territory which was confirmed on MRI. Patients also underwent
head impulse and bithermal caloric tests, and pure tone
audiogram. Twelve patients (12/18, 67%) showed unilateral
caloric paresis (n ¼ 11) or abnormal head impulse test (n
¼ 9) on the side of the infarction and most of them (10/
12, 83%) also had acute hearing loss. Fifteen patients
(83%) exhibited HSN, and the horizontal HSN was usually
contralesional (10/14, 71%). However, 9 patients also
showed patterns of central HSN which included perverted
HSN (n ¼ 7), ipsilesional HSN (n ¼ 4), and HSN in the
opposite direction of SN (n ¼ 4). Especially, perverted
HSN was induced in half of the 6 patients without audiovestibular loss. In AICA infarction, HSN was common with
both peripheral and central patterns. Careful evaluation of
HSN may provide clues for AICA infarction in patients
with acute unilateral audiovestibular loss.
Study supported by: This study was supported by grant
of the Korea Health 21 R&D Project, Ministry of Health
& Welfare, Republic of Korea (A080750)
Objective: To examine the hypothesis that eclamptic PRES
responds more rapidly to treatment than non-eclamptic
PRES.
Background: PRES is characterized by reversible vasogenic edema, predominantly in the posterior circulation distribution, and can occur in various clinical settings such as
eclampsia and malignant hypertension. It is unknown
whether clinical, imaging and EEG features differ in
eclamptic versus non-eclamptic PRES.
Design/Methods: Retrospective data including clinical,
EEG and MRI characteristics was collected on patients diagnosed with PRES between January 2003 and June 2010.
Appropriate statistical methods were employed.
Results: 45 episodes of PRES occurred in 43
patients(69% women) with a mean age of 44.5 years(range
9–82). The nine patients with eclampsia had significantly
lower age(25 6 5 yrs vs. 50 6 20 yrs, p ¼ 0.002), shorter
duration of stay following diagnosis(3.1 vs. 7.6 days, p ¼
0.002), less incidence of renal impairment(0% vs. 39%, p
¼ 0.04) and lower likelihood of abnormal EEG finding(33% vs. 85%, p ¼ 0.07) compared to non-eclamptic
PRES. The etiologies of non-eclamptic PRES were hypertension(86%), sepsis(17%), transplant(11%) and connective
tissue disorder(17%).
Conclusions: Eclamptic PRES appears to respond more
rapidly with treatment of the underlying condition than
non-eclamptic PRES, which has a more varied etiology.
S139. Co-Complaints Influence Odds of Stroke
Diagnosis in ED Dizziness
Ali S. Saber Tehrani, Yu-Hsiang Hsieh, Jonathan A. Edlow,
Carlos A. Camargo and David E. Newman-Toker; Baltimore,
MD and Boston, MA
Movement Disorders
Background: Assess impact of co-complaints on stroke
diagnosis in dizziness presentations to US emergency departments (EDs).
Methods: Design—Cross-sectional study of ED visits
from the National Hospital Ambulatory Medical Care Survey. Setting—Weighted sample of US ED visits (1993–
2005). Participants—16 years old; reason-for-visit code
vertigo/dizziness (1225.0). Measures—co-complaints, ICD-9
diagnoses. Co-complaints grouped as otologic (e.g., tinnitus);
neurologic (e.g., weakness); medical (e.g., chest pain); or other
(including multiple co-complaint groups). Diagnoses
grouped using HCUP categories.
S201. Allele Specific RNAi Against Triplet Repeat
Disease-Causing Alleles in Huntington Disease
Hirokazu Furuya, Masaki Takahashi, Shoko Watanabe, Miho
Murata, Ichiro Kanazawa, Keiji Wada and Hirohiko Hohjoh;
Omuta, Fukuoka, Japan and Kodaira, Tokyo, Japan
Suppression of disease-causing alleles is a potential approach
to treatment of intractable diseases caused by dominate-negative alleles, such as triplet repeat diseases. RNAi may be an
applicable tool in medical treatment; however, the identification of nucleotide variations and the design of siRNAs
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conferring disease allele-specific RNAi are quite difficult.
Here we report an innovative procedure that facilitated allele-specific silencing of disease-causing alleles in Huntington disease (HD), a triplet repeat disease. We developed a
pull-down method to rapidly identify coding SNP (cSNP)
haplotypes of triple repeat, disease-causing alleles, and demonstrated disease allele-specific RNAi that targeted cSNP
sites in mutant Huntingtin (HTT) alleles, each of which
possessed a different cSNP haplotype. We examined 5
patients with HD, found heterozygous cSNP sites in two
patients, and successfully suppressed the disease-causing alleles in lymphoblastoid cells derived from the patients by
means of RNAi. Therefore, the methods allow for diseasecausing allele specific silencing targeting disease-linked
cSNP haplotypes of triplet repeat diseases.
Study supported by: This work was supported by research
grants from the Ministry of Health, Labour and Welfare of
Japan
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modified Center for Epidemiologic Studies Depression Scale
at examinations from 1991–1993 in 403 autopsied participants. A score >8 was defined as significant DS. LC neurodegeneration was based on semi-quantitative assessments by
a neuropathologist shielded from clinical information. After
age-adjustment, significant neurodegeneration was observed
in 32.9% of 55 decedents with DS versus 17.8% in 348
without DS (p ¼ 0.010). DS continued to be associated
with LC neuron loss after removing 27 PD or dementia
with Lewy bodies cases (p ¼ 0.044), and after removing 89
cases with any Lewy pathology (p ¼ 0.010). Findings suggest that DS correlate with LC involvement in PD prior to
development of classic motor symptoms as well as in some
individuals without Lewy pathology.
Study supported by: NIA, NIH; NINDS, NIH; Department of Defense; Office of Research and Developement,
Veterans Affairs
S204. MRI in HDLS Shows a Unique Mechanism of
Neuroaxonal Degeneration
C. Sundal*, C. Wider, J.A. Van Gerpen, J. Lash, J.Y.
Garbern, K.J. Schweitzer, J. Aasly, B. Goodman, B.K.
Woodruff, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S.
DeArmond, R. Rademakers, D.W. Dickson, D.F. Broderick, O.
Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville,
FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; San
Francisco, CA; Rochester, MN and Munchen, Germany
S202. Antigen-Sensitized Dendritic Cell Vaccine Against
Human a-Synuclein: A Potential Cell-Based Therapy
Against Parkinson’s Disease
Chuanhai Cao, Xiaoyang Lin, Wang Li, Cai Jianfeng, Li
Kunyu, Song Shijie and Juan Sanchez-Ramos; Tampa
The goal of this study was to develop a cell-based vaccine
directed against human a-synuclein (hAS).
Human recombinant a-synuclein (hrAS) was expressed in
BL21 cells and AS peptides were synthesized based on antigen analysis. Mouse bone marrow-derived dendritic cells
(DCs) were generated ex vivo, sensitized with hrAS or AS
mixed peptides and then delivered i.v. to Tg hAS mice.
Mice vaccinated with DCs sensitized with a peptide mixture
(DC-ASpep) exhibited detectable anti-AS antibody earlier
than mice vaccinated with DC-sensitized with human
recombinant protein (DC-hrAS). With repeated treatments,
antibody levels in the DC-hrAS was higher than in the DCASpep group. AS levels were significantly decreased at both
3rd and 5th treatment compared to the control group. In behavioral tests, treatment groups performed better on the
rotometer than control mice; the DC-ASpep group exhibited the best performance. Among all cytokines measured,
only GM-CSF and IL1a were significantly changed after
treatment, indicating that this treatment method has no
potential to induce inflammation.
Conclusions: AS-sensitized dendritic cell vaccination is
effective, specific, long-lasting and unlike antigen-based vaccines, does not elicit non-specific activation of the immune
system.
Study supported by: Parkinson Study Group and Helen
Ellis Endowed Chair Fund
Background: Hereditary diffuse leukoencephalopathy with
spheroids (HDLS) is an autosomal dominant neurodegenerative disorder with symptomatic disease onset usually in
adult age and with relatively rapid course leading to death
in less than a decade. It is clinically characterized by a constellation of symptoms including personality changes, cognitive dysfunction and motor impairments, often leading to a
clinical misdiagnosis. Neuropathology is characterized by
axonal spheroids. The disease-causing gene is unknown.
Methods: Over the last 7 years, we have collected HDLS
families both retrospectively and prospectively. We performed head magnetic resonance imaging (MRI) studies
with only neuropathological proven HDLS cases/kindreds.
Results: From all 13 families available to us, 14 cases
were studied. 4 had repeated examinations. MRI demonstrated unique distribution of changes in the periventricular,
deep and subcortical white matter of frontal/parietal lobes
and in corpus callosum.
Conclusions: MRI is helpful to substantiate the diagnosis
of HDLS. It will be an important biomarker for HDLS
progression after the gene is identified. It will also be very
useful to follow the patients undergoing future experimental
treatments if such are developed.
Study supported by: C.Sundal supported by research
grants through Gothenburg University, Sweden
S203. Depressive Symptoms and Neurodegeneration in
the Locus Coeruleus: The Honolulu-Asia Aging Study
Ross Webster, Robert D. Abbott, Helen Petrovitch, Kamal H.
Masaki, Caroline M. Tanner, Jane H. Uyehara-Lock and
Lon R. White; Honolulu, HI; Hiroshima, Japan and
Sunnyvale, CA
S205. Appropriate Outcome Measures for Cognitive
Trials in Huntington’s Disease
Jody Corey-Bloom, Jody Goldstein, Shea Gluhm, Charles Van
Liew, Stephanie Lessig, Jagan Pillai and Steven D. Edland; La
Jolla, CA
Depression commonly occurs in Parkinson’s disease (PD),
often pre-dating diagnosis. Lewy pathology in the locus
coeruleus (LC) occurs early in PD and LC neurodegeneration occurs in depressed PD patients. Whether depressive
symptoms (DS) are associated with LC neurodegeneration
prior to onset of classic PD motor features remains unclear.
Our objective is to examine the association of DS and LC
neurodegeneration in decedents from the longitudinal Honolulu-Asia Aging Study. DS were assessed using the 11-item
Suitable measures are needed for clinical trials of therapeutic
agents for cognition in Huntington’s disease (HD). The
Montreal Cognitive Assessment (MoCA), Mini-Mental State
Examination (MMSE), and Mattis Dementia Rating Scale
(DRS) are commonly used cognitive instruments; however,
little is known about longitudinal change on these measures
in HD. We used mixed effects models to analyze MoCA,
MMSE, and DRS scores obtained during 2.5–5 years of
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follow-up of up to 153 subjects with HD. Annual rates of
decline on the MoCA and MMSE were 1.0 and 0.69
points/year, respectively, over 2.5 years of follow-up. Rate of
decline on the DRS was 3.04 points/year in the first 5 years
of observation. For cognitive trials in HD, sample size
requirements (90% power, critical alpha level 0.05) for a 3year trial to detect 50% reduction in mean rate of decline
using the MoCA, MMSE, or DRS would be 106, 173, and
165 subjects/ treatment arm, respectively. We conclude that,
although all three measures decline significantly over time in
an unselected HD population, the MoCA may be a more
efficient instrument for assessing effects of a therapeutic
agent for cognition in HD.
Study supported by: Huntington’s Disease Society of
America and Shiley-Marcos Alzheimer Disease Research
Center NIH P50 AG005131.
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with hallucinations or depression followed by memory
impairment. The younger brother developed levodopa responsive asymmetrical parkinsonism characterized by resting
tremor, rigidity, and bradykinesia during the course of his
illness. The autopsy showed transitional (limbic) type of
Lewy body disease (LBD) in the brother and diffuse LBD
in the older sister, with mild to moderate Alzheimer’s disease pathology (Braak stage II-IV) in both. We will present
our clinicopathologic review with future genealogical and
clinical research planned on this family.
Study supported by: ZKW is partially supported by the
NIH/NINDS 1RC2NS070276, NS057567, P50NS072187,
Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030), and gift
from Carl Edw and Bolch, Jr., and Susan Boss Bolch (MCF
#90052031/PAU #90052). FS is partially supported by
Mayo Clinic Florida (MCF) Research Committee CR programs (MDF #90052018).
S206. Distinctive Neurocognitive Profiles Associated
with Right and Left Motor Symptom Onset in
Parkinson’s Disease
Paul J. Eslinger, Daymond Wagner, Suman Sen, Mechelle M.
Lewis, Guangwei Du, Michele L. Shaffer and Xuemei Huang;
Hershey, PA
S208. Alcohol Consumption and Risk of Parkinson
Disease
Rui Liu, Yikyung Park, Xuemei Huang, Xuguang Guo, Albert
Hollenbeck, Aaron Blair and Honglei Chen; Research Triangle
Park, NC; Rockville, MD; Hershey, PA and Washington, DC
Parkinson’s disease (PD) is commonly diagnosed in patients
presenting with asymmetric motor impairments. However,
the literature remains mixed with regard to the significance
and prognostic value of identifying first-onset motor symptoms particularly for cognitive functioning and progression.
We investigated the hypothesis that asymmetric motor
impairment and attendant dopamine loss are associated with
distinctive right- and left-onset profiles in 36 PD subjects
(21 with right-sided,15 with left-sided motor symptom
onset) and 44 matched healthy controls recruited for longitudinal cognitive and anatomical studies. Although samples
did not differ on screening cognitive measures (Mini-Mental
Status Examination, Montreal Cognitive Assessment), contrasting profiles of neurocognitive impairments were
detected in PD. Specifically, left-sided motor symptoms
were associated with prominent deficits in visuospatial learning and memory, visuospatial speed/accuracy in mirror tracing, and design fluency. In contrast, right-sided motor
symptoms were associated with decline in cognitive flexibility and heightened symptoms of depression. Results support
the hypothesis that asymmetric motor symptoms in PD are
associated with distinctive patterns of early cognitive change
that may require different management approaches. Analyses
are underway to examine the relationship between such cognitive profiles and cortical changes in PD.
Study supported by: National Institutes of Health
Objective: To prospectively examine the association between
overall and individual types of alcohol consumption and
risk of Parkinson disease (PD).
Methods: Participants comprised 1,086 PD cases and
299,684 individuals without PD from the NIH-AARP Diet
and Health Study. Alcohol consumption was assessed in
1995–1996 and PD was diagnosed in 2000–2006.
Results: Total alcohol consumption was not associated
with PD. However, moderate beer consumption was associated with lower risk of PD. After controlling for potential
confounders and other types of alcohol consumption, the
multivariate odds ratio (OR) for beer drinkers was 0.81
(95% confidence interval [CI] 0.70–0.94) for <1 drink/day,
0.76 (0.52–1.11) for 1–1.99 drinks/day, and 0.87 (0.61–
1.24) for 2 drinks/day. For liquor consumption, we found
a monotonic increase in PD risk: ORs (95% CI) were 1.05
(0.91–1.23), 1.19 (0.91–1.56), and 1.39 (1.05–1.84) for
<1, 1–1.99, and 2 drinks/day; p trend <0.01. Results for
wine consumption were less clear, although a lower PD risk
was also observed when comparing drinkers of 1–1.99
drinks/day with nondrinkers.
Conclusions: Our results suggest that beer and liquor
consumption may have opposite associations with PD: moderate beer consumption with lower PD risk and liquor consumption with higher risk.
Study supported by: Supported by the intramural research
program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), and the National
Cancer Institute (Z01 CP010196-02).
S207. The Clinical and Pathological Features of Familial
Parkinsonism with EIF4G1Gene Mutation
Shinsuke Fujioka, Owen A. Ross, Rosa Rademakers, Matthew
J. Farrer, Dennis W. Dickson and Zbigniew K. Wszolek;
Jacksonville, FL and Vancouver, BC, Canada
S209. Hereditary Diffuse Leukoencephalopathy with
Spheroids: An Under-Diagnosed Disease
C. Sundal, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern,
E.A. Shuster, K.J. Schweitzer, J. Aasly, B. Goodman, B.K.
Woodruff, W. Kupsky, A. Tselis, C.W. Christine, M. Baker,
J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W.
Dickson, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden;
Jacksonville, FL; Rochester, NY; Trondheim, Norway;
Scottsdale, AZ; Detroit, MI; San Francisco, CA; Rochester,
MN and Munchen, Germany
Recently, we have performed genome-wide linkage analysis
of several families with autosomal-dominant late-onset parkinsonism and identified mutations in a novel susceptibility
gene for Parkinson’s disease, eukaryotic translation initiation
factor 4-gamma 1 isoform (EIF4G1) on chromosome 3q2627. The missense mutations, EIF4G1 c.2057G>T
(p.G686C) and c.3589C>T (p.R1197W) were identified
together in two siblings of US 331-95 family. We reviewed
available medical records and brain autopsy reports for both
siblings. Mean age at symptomatic onset was 79 years and
mean disease duration was 5.5 years. Both siblings presented
Background: Hereditary diffuse leukoencephalopathy with
spheroids (HDLS) was originally described in a Swedish
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kindred in 1984. An additional 11 kindreds and 8 sporadic
cases have been reported over the years. Inheritance is autosomal dominant. HDLS presents with psychiatric, cognitive
and motor symptoms. A definite diagnosis is made pathologically by demonstrating axonal spheroids. The causative
gene is unknown.
Method: Brains and brain biopsy specimens were collected through world wide collaborations and only those
cases/families demonstrated pathological features of HDLS
were included in our study.
Results: 20 affected individuals were identified in 13 kindreds. During the course of the illness all patients developed
parkinsonian signs along with other classic symptoms of
HDLS. There was no response to levodopa. The mean age
of onset was 45 years (range, 16–68), and mean disease duration was 4 years (range, 1–11).
Discussion and Conclusions: HLDS is an under-diagnosed neurodegenerative condition. Cases are misdiagnosed
as AD, PD, CBD, MS, FTD, FTDP, and others. Finding
the gene for this condition will be of paramount importance
in understanding the neurodegeneration associated with
white matter abnormalities.
Study supported by: C.Sundal supported by research
grants through Gothenburg University, Sweden
Stage:
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hoc analyses revealed older PD onset age in aMCI-SD,
worse MMSE scores in naMCI-MD, and worse H&Y stage
in naMCI-MD. Mean UPDRS motor scores were higher in
both MD subtypes. Axial function differed among groups
with worse scores in naMCI-MD.
Conclusion: Nonamnestic and single domain impairment
predominated. Multiple-domain PD-MCI had worse motor
function. Increased burden of cognitive dysfunction (multiple-domain), rather than deficit type (amnestic/nonamnestic), may be associated with greater motor impairment and
dementia risk.
Study supported by: NIH K23060949, Parkinson’s
Disease Foundation
S212. Loss of Cortical Gray Matter in Parkinson’s
Disease
Suman Sen, Paul J. Eslinger, Daymond Wagner, Guangwei
Du, Mechelle M. Lewis, Michel L. Shaffer and Xuemei
Huang; Hershey, PA
In addition to classic motor dysfunction, Parkinson’s disease
(PD) patients exhibit cognitive deficits that are related to
cortical network dysfunction. To investigate PD changes in
cortical gray matter, high-resolution T1-weighted magnetic
resonance images were acquired from 40 right-handed PD
subjects and compared to 40 age-, gender-, education-, and
handedness-matched healthy controls. Screening cognitive
measures of Mini-Mental Status Examination (p ¼ 0.32) and
Montreal Cognitive Assessment (p ¼ 0.81) were also comparable between groups. Imaging data were analyzed using
voxel-based morphometry (VBM). Permutation-based, nonparametric testing (5000 permutations) was applied within
the framework of a general linear model, adjusting for age
and gender within groups. Group differences were considered
significant at p<0.05 (FWE corrected), after initial clusterforming thresholding at p0.01 (uncorrected). Compared to
controls, PD subjects showed significant loss of gray matter
in the left precentral and paracentral gyri, left superior temporal gyrus, bilateral orbital-frontal cortex, bilateral frontal
poles, precuneus, cuneus, and left occipital cortex. Results
support the conclusion that PD causes significant loss of cortical gray matter in multiple regions outside motor areas. In
addition to confirmation with additional samples, correlation
of the cortical alterations with cognitive, behavioral and other
functional outcomes warrants further investigation.
Study supported by: National Institute of Neurological
Disorders and Stroke (NS060722), General Clinical
Research Center Grant from National Institutes of Health
(M01RR10732), General Clinical Research Center Construction Grant (C06RR016499)
S210. Co-Existing HTT and ATXN8OS Repeat
Expansions and a ‘Face of the Giant Panda’ Sign on
MRI in a Patient with a Complex Movement Disorder
Shin C. Beh, Cherian A. Karunapuzha and Shilpa Chitnis;
Dallas, TX
We present a 66 year old woman with a complex movement
disorder syndrome. The disease began in her mid-fifties with
fidgetiness. She later developed progressive gait ataxia and
chorea. Unintended weight loss, mild dysphagia, depression
and mild memory impairment were also present. Examination revealed square-wave jerks, grimacing, motor impersistence, generalized choreiform movements, hyperreflexia and
an ataxic, choreic gait. Her mother had a similar movement
disorder. In addition to cortical atrophy, T2-weighted brain
MRI demonstrated mesencephalic white matter hyperintensity with areas of hypointensity in the red nuclei, substantia
nigra and superior colliculi taking on the appearance of the
‘‘face of the giant panda’’ sign. Genetic testing revealed coexisting huntingtin and ATXN8OS triplet repeat expansions.
We discuss phenotype-genotype correlation and the unusually
variable phenotypes of spinocerebellar ataxia 8.
S211. Clinical Differences among PD-MCI Subtypes
Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard and
Christopher G. Goetz; Chicago, IL
S213. Association of PSP with Chemical Occupational
Exposure Factors
Irene Litvan, Christopher R. Cunningham, Peter Lees, Leila
Jackson, Jorge Juncos, David Riley, Yvette Bordelon, David
Standaert, Stephen Reich, Alex C. Cambon, Joseph Jankovic,
Deborah A. Hall, Richard Dubinsky, Cassandra Shepherd,
Claire Henchcliffe, Ryan Uitti, Benzi Kluger, David Shprecher,
Connie Marras, Eliza Gallin, James Leverenz and Shesh N.
Rai; Louisville, KY; Baltimore, MD; Cleveland, OH; Atlanta,
GA; Los Angeles, CA; Birmingham, AL; Houston, TX;
Chicago, IL; Kansas City, KS; New York, NY; Jacksonville, Fl;
Boulder, CO; Salt Lake City, UT; Toronto, Canada and
Seattle, WA
Objective: To examine PD-MCI subtypes.
Background: Mild cognitive impairment in PD (PDMCI) may represent a pre-dementia state. MCI subtypes distinguish between amnestic (aMCI) and nonamnestic (naMCI)
phenotypes and single (SD) or multiple-domain (MD)
impairment. Whether PD-MCI subtypes differ in characteristics, progression or neuropathology remains unknown.
Methods: 96 PD-MCI patients (not demented but with zscore of < 1.5 on at least 1 of 5 cognitive domains) were classified as: aMCI-SD, naMCI-SD, aMCI-MD, and naMCI-MD.
Results: Group demographics included: age 71.8 (9.2),
education 14.5 (2.9), PD duration 6.9 (5.2) years; MMSE
26.9 (2.1); UPDRS motor score 31.6 (11.4). In our sample,
25% had aMCI-SD, 44% naMCI-SD, 21% aMCI-MD,
and 10% naMCI-MD. Subtypes differed significantly
regarding age, PD onset age, MMSE, and H&Y stage. Post-
Background: Multicenter case-control study designed to
determine if an association exists between occupational
chemical exposures and PSP.
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Methods: Analysis is based on 199 PSP cases and 129
age-gender and geographically matched controls. Trained
interviewers conducted standardized telephone surveys to
collect information including demographics, residence history, lifetime occupational history and home pesticide use.
An industrial hygienist and toxicologist blinded to whether
data were from cases or controls assessed self-reported exposure to chemicals and determined if the subjects had direct,
indirect or no exposure based on occupational histories.
Odds ratios (OR) and 95% confidence intervals (CI) were
estimated using univariable and multivariable logistic regression adjusting for significant covariates.
Results: PSP cases were significantly more likely to report
exposure to occupational pesticides (OR:2.22; CI:1.15-4.37,
p ¼ 0.015) and organic solvents (OR:1.57; CI:1.05-2.34, p
¼ 0.026) than controls. Using assigned exposures, cases
were significantly more likely to have direct exposure to any
chemical (OR:1.99; CI:1.26-3.16, p ¼ 0.003), and pesticides (OR:2.14; CI:1.06-4.61, p ¼ 0.034).
Conclusions: This is the first epidemiological study to
find a significant association between occupational chemical
exposures and PSP. Future studies should determine which
chemicals are associated with the development of this primary tauopathy and whether genetic and environmental risk
factors interact.
Study supported by: National Institutes of Aging,
National Insitutes of Health
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Objective: To study if STN-DBS or GPi-DBS has different
effects on gait and balance in individuals with PD.
Background: Both STN- and GPi-DBS improve motor
functions in PD. However, their differential benefits on gait
and balance are unclear. Comparison of their effects may
help clinical decisions in choosing the target.
Method: Composite scores of 5-UPDRS items (arising, posture, gait, postural instability, bradykinesia) and 3-item standwalk-sit test of the STN-DBS (N ¼ 25) and GPi-DBS (N ¼
23) groups were compared. Variables during ‘‘off-on’’ (medication-off, stimulation-on), ‘‘off-off’’ and ‘‘on-on’’ were measured.
Result: During ‘‘off-on’’, the sum of 5-item UPDRS
improved by 1.96(p<0.05) in STN-DBS and 1.44(p<0.01)
in GPi-DBS from ‘‘off-off ’’. The 3-item stand-walk-sit
improved by 2.4%, 2.8%, 1.4% in STN-DBS and
14.7%, 12.6%, 16.7% in GPi-DBS. During ‘‘on-on’’, the
sum improved by 4.32(p<0.001) and 3.60(P<0.001); the
stand-walk-sit improved by 39.1%, 25.4%, 70.0% in STNDBS; and 46.1%, 34.6%, 68.9% in GPi-DBS, respectively.
Discussion: Our results suggest that STN-DBS alone was
more beneficial than GPi-DBS on gait performance. After
taking levodopa, both groups had much more improvement,
particularly for freezing episodes. Levodopa remains a gold
standard treatment for PD patients after DBS.
Study supported by: Veterans Affairs salaries
S216. Reliability of Self-Reported Parkinson’s Disease
(PD) Features
Caroline M. Tanner, Cheryl Meng, Ira Shoulson, Anthony E.
Lang, David Oakes, Roger Kurlan, Alberto Ascherio, Flint
Beal, Emily Flagg, Jennifer Harman, Michael Schwarzchild,
James Beck, Bernard Ravina, Kenneth Marek, Shirley Eberly,
Karen Marder and Robin Elliott; Sunnyvale, CA; Washington,
DC; Toronto, ON, Canada; Rochester, NJ; Summit, NJ;
Boston, MA; New York, NY; Cambridge, MA and New
Haven, CT
S214. Psychiatric Co-Morbidities and Mortality among
Hospitalized Parkinson Disease Patients
Nicte Mejia and Zeina Chemali; Boston, MA
Affective and anxiety disorders are determinants of poor
quality of life and survival for Parkinson disease (PD)
patients. Their impact on in-hospital PD mortality has not
been examined.
The study evaluates the effect of depression and anxiety
on in-hospital PD mortality.
PD patients with depression or anxiety would have higher
in-hospital mortality compared to PD patients with no psychiatric co-morbidities. Alcohol or drug use would further
increase mortality. We sampled 1998–2007 HCUP-NIS for
PD, depression, anxiety, alcohol and drug use were identified through ICD-9 codes. All statistical models were
adjusted for age, gender, and race/ethnicity.
3,013,346 collected PD discharges-age 77.9 (SD 9.0
years), 52.8% male, 84% white. Depression identified in
10.6%; anxiety in 4.7%, an underestimate to population
predicted prevalence for those disorders in same settings.
Statistically significant lower mortality was found for PD
patients with known depression (OR ¼ 0.64; p< 0.001) or
anxiety (OR ¼ 0.50; p< 0.001). Substance and alcohol use
were assessed as modifiers.
Depression and anxiety are under-diagnosed in hospitalized PD patients. Contrarily when recognized and appropriately treated, depression and anxiety are associated with
lower in-hospital PD mortality. Alcohol and illicit substances impact negatively on PD outcome.
Study supported by: The authors have no disclosure. Dr.
Nicte Mejia was awarded 2010 AAN Foundation Clinical
Research Training Fellowships
Objective: To determine reliability of self-reported remote
assessments of PD.
Background: In person visits can be costly and impossible for some. Remote assessment may provide a useful
alternative.
Subjects: Participants in both the Longitudinal Assessment and Biomarker Study of PD, LABS-PD (in person
assessments) and Follow-up of Persons with Neurologic Diseases, FOUND (assessments using mailed self-reported
questionnaires.)
Methods: Analogous FOUND and LABS-PD assessments
occurring within 3 months were compared.
Results: During 45.2 months median follow-up, 325/422
subjects completed at least one FOUND assessment within
3 months of a LABS-PD assessment. Exact agreement was
80% for diagnosis, disease features (e.g., tremor, dyskinesias) and PD medication type. For the 19 items in the
UPDRS parts II & IV, agreement was > 70% (8 items:
70–79%, ICC 0.230–0.594; 11 items 80%, ICC 0.230 –
0.676). For the 20 items in the MDS-UPDRS parts I.b. &
II, exact agreement was > 60% (2 items:60 – 69%, ICC
0.215–0.353; 11 items: 70–79%, ICC 0.393 - 0.563; 7
items: 80%, ICC 0.397 – 0.694).
Conclusion: Remote assessment of PD patients using
mailed self-reported questionnaires is a reliable way to collect information on disease status.
Study supported by: Parkinson’s Disease Foundation;
NIH; Cephalon, Inc.; H. Lundbeck A.S.
Dr. Beck and Mr Elliott are employed by the Parkinson’s
Disease Foundation.
S215. Comparison of Subthalamic (STN) and Pallidal
(GPi) Deep Brain Stimulation (DBS) on Gait and
Balance in Patients with Parkinson’s Disease (PD)
Jyhgong Gabriel Hou, Minn Thant, Aliya Sarwar, Linda
Fincher, Monthaporn S. Bryant, Farrah Atassi and Eugene C.
Lai; Houston, TX and Galveston, TX
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S217. First Neurological Examination Can Predict
Course of Parkinson’s Disease (PD)
Ali H. Rajput, Michele L. Rajput and Alex H. Rajput;
Saskatoon, SK, Canada
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Parkinson’s disease (PD). In 2008, Llebaria and colleagues
reported excellent sensitivity and specificity detecting dementia in PD using a DRS total score cutoff of 123. However, this study used a sample with rather low educational
achievement.
Methods: Linear discriminant function analysis was used
cross-validate the 123 cutoff score in a sample of PD
patients with rather high educational.
Results: From a sample of 38 PD patients, 12 were diagnosed with dementia following comprehensive neuropsychological evaluation. A total score cutoff of 123 misidentified
9 patients with dementia (25% sensitivity, 100% specificity). Age and education corrected scaled scores did not
improve overall classification.
Discussion: Results suggest caution in applying DRS-2
total score cutoffs in highly educated patients, and highlight
the importance of comprehensive neuropsychological evaluations for clinical diagnosis of dementia in PD.
Our previous publications concluded that, when the entire
clinical course is considered, the tremor dominant (TD),
mixed (MX), and akinetic/rigid (AR) subtypes of PD have
different pathology and different outcomes. There are no biological markers or early clinical manifestations to distinguish between those phenotypes.
All patients were followed at Movement Disorders Clinic
Saskatchewan and autopsied between 1972 and 2006. Those
with Lewy body PD and no co-morbidity to modify the motor
features were included. Excluded were cases that at baseline
had 15 years or longer duration of PD motor symptoms. The
patients were assessed in the state as they attended our clinic.
We hypothesized that predominant tremor at baseline
would evolve into lifelong TD, predominant akinesia/rigidity into AR and those with equal severity into MX subtypes.
156 PD cases in the study, included 39 AR, 106 MX, and
11 TD subtypes. Mean duration of symptoms at baseline was
4.4 years. 133 (85%) of all – 90% of AR, 88% of MX, and
55% of TD could be accurately identified at baseline.
These observations are helpful for patient care, drug trials
patient selection and for studies of pathophysiology of PD.
Study supported by: Have received honorarium for lectures and meeting participation from Novartis. Have
received travel support to meeting from Teva. Have been
involved in Botulinum toxin study sponsored by Allergan.
Research funding from Curling Classic, Parkinson Society
Saskatchewan, and Greystone Golf Classic.
S220. Impaired Social Problem-Solving in Huntington’s
Disease
Charles Van Liew, Jody Goldstein, Shea Gluhm, Jagan Pillai
and Jody Corey-Bloom; San Diego, CA
Huntington’s disease (HD) is a genetic neurodegenerative
disorder characterized by motor, cognitive, and psychiatric
dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal
relationships, judgment, and independent living. In the current study, we examined social problem-solving (SPS) in
well-characterized HD and at-risk (AR) subjects using the
Social Problem-Solving Inventory-Revised:Long (SPSIR:L)—a 52-item, well-validated, standardized measure of
SPS. Items are aggregated under five subscales (Positive,
Negative, and Rational Problem-Solving; Impulsivity/ Carelessness; and Avoidance). Thirty-five subjects, including 12
HD (mean age ¼ 53, mean CAG ¼ 44) and 23 gene-positive AR (mean age ¼ 41, mean CAG ¼ 42), were compared with two-tailed t-tests on SPSI-R:L scores. HD subjects scored significantly worse on Total SPS (p<.05),
explained by greater Avoidance (p ¼ .01) and Impulsivity/
Carelessness (p<.0001) than AR subjects. Our findings
demonstrate that, as HD progresses, impulsivity and avoidance become more predominant and, inevitably, problematic. We conclude that the SPSI-R provides a promising and
novel means of quantifying psychosocial impairments in
HD. Further studies will be needed to confirm and extend
these findings.
Study supported by: UCSD Shiley-Marcos Alzheimer’s
Disease Research Center, UCSD Huntington’s Disease Society of America Center of Excellence
S218. Difficulty with Balance Occurs Early in PD: It
Isn’t Appreciated Because It’s Not Asked about Nor
Tested For
Abraham N. Lieberman, Samea Husain, Naomi Salins and
Anthony Santiago; Phoenix, AZ
Objective: Devise a question and tests to assess balance
early, before patients fall.
Background: Balance difficulty resulting in falls is a wellrecognized feature late in PD. Less well known is that balance difficulty occurs early in PD.
Method: In addition to questions and testing of gait on
the UPDRS we added a question about balance and 3 simple balance tests. We assessed balance and gait in 102 consecutive non-demented PD patients. The ANOVA analysis
was used for continuous variables and a logistic regression
analysis was used for categorical variables.
Results: Duration of PD in patients who answered ‘‘yes’’
on our balance question was 7.11 (6 4.5) versus 3.95 ( 6
1.79) yrs in patients who answered ‘‘no.’’ This was significant: p< 0.0007. It’s noteworthy that 45% of 62 patients
with PD for 1- 5 yrs had balance difficulty separate from
gait difficulty. There were statistically significant differences
on the tests between patients who complained of balance
difficulty and those who did not.
Conclusions: the balance question and tests provide a
simple way of assessing balance early in PD.
Study supported by: Self supported
S221. Association of Psychological Symptoms with
Impulse-Control Behaviors after Dopamine Agonist
Therapy for Parkinson’s Disease: A Longitudinal Study
Jennifer S. Hui, Steven Cen, Megan Gomez and Lauice Yang;
Los Angeles, CA and Pasadena, CA
Recent evidence suggests that dopamine agonist (DA) therapy in Parkinson’s disease (PD) is associated with the development of ICBs, but no previous longitudinal studies have
examined psychological symptoms associated with ICBs.
Participants (n ¼ 18), recruited from the clinical trial
Boehringer Ingelheim Eye Safety study, were randomized to
pramipexole (9 subjects) or ropinerole (9 subjects). Participants completed the Symptom Checklist-90 Revised (SCL90 R), and a brief, structured interview assessing for ICBs at
baseline, 11 weeks, 6, 12, 18, and 24 months.
S219. Poor Dementia Screening with Mattis Dementia
Rating Scale Cutoffs in Highly Educated Parkinson’s
Disease Patients
Travis H. Turner and Vanessa Hinson; Charleston, SC
Introduction: The Mattis Dementia Rating Scale (DRS) is
widely used to assess cognition and screen for dementia in
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8/18 (44%) subjects developed ICBs. Subjects developing
ICBs showed a significantly higher rate of progression on
the Psychoticism (PSY) (p ¼ 0.004), Paranoid Ideation
(PAR) (P ¼ 0.01), Global Severity Index (GSI)(p ¼ 0.03),
and Positive Symptom Total (PST) (p ¼ 0.01) subscores.
Subjects randomized to pramipexole had a significantly
higher rate of progression on the PAR subscore (p ¼ 0.02).
Careful monitoring of psychological symptoms after initiation of DA therapy may aid in identifying patients at risk
for developing ICBs. Pramipexole may play a role in the
manifestation of ICBs by augmenting certain psychological
symptoms. Clinicians should consider medication effects
when prescribing DA in patients with underlying or progressive psychological distress.
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motor asymmetry were accurate and correlated with their 9HPT scores. This conclusion raises intriguing questions
regarding the progression of these neurodegenerative disorders, and therefore merits further investigation.
Study supported by: Cooper Foundation
S224. Neurotoxin Injection for Treatment of Cervical
Dystonia
Chandler E. Gill, Anna L. Molinari, Neil D. Manus, Michael
W. Pelster, Jason A. Cook, Wallace Title and David Charles;
Maywood, IL; Nashville, TN; Minneapolis, MN and New
Orleans, LA
Botulinum toxin is a first-line treatment for cervical dystonia (CD); onabotulinumtoxinA (BoNT-A), rimabotulinumtoxinB (BoNT-B), and abotulinumtoxinA (BoNT-D) are
available formulations. We conducted a record review and
interview to characterize neurotoxin use and reasons for discontinuation. All patients treated at a university clinic from
1997–2006 were eligible and 70 (54 female) participated.
Age at onset was 44.2 6 16.8 and 47.2 6 14.8 at first
treatment. Initial treatment: BoNT-A (97%), BoNT-B
(1.5%), BoNT-D (1.5%). Following BoNT-A, 33.3%
switched to BoNT-B; of those, 47.6% returned to BoNT-A.
Average starting dose of BoNT-A was 270.4U which
increased by 0.28U per injection (range: 1–39). Average
starting dose of BoNT-B was 11,996U which increased by
113.6U per injection (range: 1–18). 21 patients (30%) discontinued BoNT, and 16 (23%) of these no longer received
any treatment. The most common reason was inadequate
response (primary 4%; secondary 11%); 3 patients developed resistance documented by frontalis or antibody test.
Other reasons were inadequate insurance payment (7%),
travel distance (3%) and side effects (3%). CD patients typically switch between BoNT formulations before discontinuing treatment, and a significant minority discontinue all
care. Efforts to improve treatment of CD should include
education and advocacy to facilitate patient access.
Study supported by: This study was supported by an
unrestricted research grant from Allergan, Inc.
Vanderbilt University has received income from grants and
contracts from Allergan and Medtronic for research led by
Dr. Charles. Dr. Charles has received income from Allergan,
Medtronic, and Pfizer for education and consulting services.
S222. Balance Difficulty in PD Correlates with Step
Length and Velocity
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
Objective: To determine step length and velocity in PD
patients.
Background: PD patients often report balance difficulty
without falls.
Method: In 102 consecutive non-demented PD patients,
we compared patients with reported imbalance without falls
to patients without imbalance as regards age, PD duration,
UPDRS/Pull-Test, BNI Balance Scale, Stride Length and
Velocity. There were no confounding causes of balance or
gait difficulty upon historical review or physical exam.
Results: Patients with balance difficulty had a shorter
stride: 1.72 (60.47) vs 2.16 (60. 27) feet/ step, p <0.0001,
and a slower step velocity of 2.86 (60.93) vs 3.72 (60.75)
feet/ second; a longer duration of PD: 7.2 (6 4.6) vs 4.4
(62.4) yrs, p < 0.008; a worse BNI Balance Score: 7.9
(63.8) vs 2.8(6 2.3), p<0.0001; were older: 70.6 (68.8) vs
64. 6 (69.4) yrs, p < 0.01; had a worse motor UPDRS
score: 19.6 (67.7) vs 14.3(65.8), p < 0.005.
Conclusions: Balance difficulty in PD correlates strongly
with PD duration, BNI Balance Score, step length and step
velocity. The shortened step and slower velocity may reflect
adaptive responses to impaired balance rather than a locomotive dysfunction.
S223. Motor Asymmetry in SCAs
Mitra Assadi, Bhavpreet Dham, Gazelle Zerafati, Jon Veloski
and Paola Leone; Camden, NJ and Philadelphia, PA
S225. The Association between Mediterranean-Type Diet
Adherence and Parkinson’s Disease
Roy N. Alcalay, Yian Gu, Helen Mehia-Santana, Lucien Cote,
Karen S. Marder and Nicholas Scarmeas; New York, NY
Introduction: The spinocerebellar ataxias (SCA) represent a
heterogeneous group of neurodegenerative disorders. Given
the genetic nature of these diseases, symmetric involvement
of the neuroaxis is to be expected in the phenotype.
Methods: 19 right-handed patients with SCA were
recruited into the study as described before (Assadi, JNS
2007). Upper extremity motor coordination was measured
using a timed nine hole peg test (9-HPT) on 3 separate
examinations. The mean scores for the right and left hands
were calculated and compared using a t-test.
Results: Twelve patients reported experiencing more
ataxia on the left side, while one patient perceived the right
side as being more severely affected. For these 13 patients,
the means for the 9-HPT were significantly different
between the right and the left sides (t-test, p< 0.01). In the
six subjects who did not report any motor asymmetry, the
means of the two sides were approximately equal, and no
statistical difference was found.
Conclusions: Motor asymmetries are common in SCAs
and observed in 68% of our cases. Patients’ self-reports of
Objective: Recent studies have investigated the association
between a Mediterranean-type diet (MeDi) and Alzheimer’s
risk, but explorations in relation to Parkinson’s disease (PD)
have been limited. We assessed the association between
MeDi and PD status.
Methods: 280 PD cases (Columbia University) and 199
controls (recruited mostly by random digit-dialing) completed the Willett semi-quantitative food frequency questionnaire. A MeDi adherence score was calculated using a 9point scale. High scores indicate greater adherence to MeDi.
A logistic regression model was computed to assess the association between PD status and MeDi, adjusting for caloric
intake (CaI), age, gender, education and ethnicity. Among
PD cases, we assessed the association between MeDi adherence and age-at-onset using linear regression, adjusted for
CaI, gender, education, ethnicity and disease duration.
Results: PD cases were younger (68yrs vs. 72yrs, p<
0.001) and more educated (14yrs vs. 12yrs, p<0.001) than
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controls. Lower MeDi adherence was associated with higher
odds for PD after adjustment for all covariates (OR per
MeDi point ¼ 0.894, 95%CI ¼ 0.800–0.998, p ¼ 0.045).
Mean age-at-PD-onset was 61.6yrs. Lower MeDi score was
associated with earlier age-at-PD-onset (b ¼ 1.275, p ¼
0.001).
Conclusions: PD patients adhere less than controls to
the MeDi. Dietary behavior may relate to PD risk.
Study supported by: NIH (NS32527 and KL2
RR024157) and the Parkinson’s Disease Foundation
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confounding causes of balance or gait difficulty upon historical review or physical exam.Results: Patients with reported
balance difficulty had a longer duration of PD: 7.2 (6 4.6)
vs 4.4 (6 2.4) yrs, p < 0.008; a worse BNI Balance Score:
7.9 (6 3.8) vs 2.8 (6 2.3), p<0.0001; were significantly
older: 70.6 (6 8.8) vs 64. 6 (6 9.4) yrs, p < 0.01; a worse
motor UPDRS score: 19.6 (6 7.7) vs 14.3 (6 5.8), p <
0.005. Conclusions: Balance difficulty in PD strongly correlates with the BNI Balance Score.
S228. STEADY-PD. Safety and Tolerability of Isradipine
CR in Early Parkinson’s Disease. Interim Tolerability
Data Analysis
Tanya Simuni, Kevin Biglan, David Oakes, Cheryl Deeley,
Irenita Gardiner, Parkinson Study Group and STEADY PD
Investigators; Chicago, IL and Rochester, NY
S226. Autonomic Dysfunction in Early Parkinson’s
Disease
Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song
and P. David Charles; Nashville, TN
Background: Orthostatic hypotension (OH) and suppressed
heart rate (HR) response to standing are frequent symptoms
of autonomic dysfunction (AD) in advanced Parkinson’s
Disease (PD), but their incidence in early PD is unknown.
Methods: 30 Hoehn & Yahr Stage II idiopathic PD subjects underwent a 7 day medication washout. Seated and
standing blood pressure (BP) and HR measurements were
recorded daily. Subjects were divided into 2 groups based
on medication regimen: Group 1 levodopa only (n ¼ 9),
Group 2 dopamine agonist monotherapy or in combination
with levodopa (n ¼ 21).
Results: HR response to standing improved in all 30 subjects during medication washout with an average increase of
2.9 6 7.7 beats/minute (p ¼ 0.03). No subjects exhibited
symptomatic OH. On average, systolic BP (SBP) decreased
by 2.60 mmHg and diastolic BP (DBP) decreased by 3.13
6 9.26 mmHg on Day 8, but these differences were not
significant. Subjects in Group 1 experienced a smaller difference between seated and standing SBP and DBPs on Day 8,
but these differences were also not significant.
Conclusions: In early PD, the normal compensatory
increase in HR upon standing is diminished while SBP and
DBP are unaffected. HR response should be considered
when evaluating AD in early PD.
Study supported by: The clinical trial from which this case
is reported is funded by Medtronic, Inc., by Vanderbilt CTSA
grant 1 UL1 RR024975 from the NCRR-NIH, and by private donations. Medtronic representatives did not take part in
data collection, management, analysis, or interpretation of the
data or in preparation, review, or approval of the manuscript.
Dr. Charles has received personal compensation and Vanderbilt University has received grants to support research
from Medtronic in excess of $10,000. Dr. Charles has also
received funding from Allergan for speaking and consulting
services as well as research grants.
Background: STEADY PD is a multicenter pilot phase II
double blind placebo controlled tolerability and dose finding study of isradipine CR as a disease modifying agent in
patients with early PD.
Objective: To establish a dosage of isradipine CR that is
tolerable and demonstrates preliminary efficacy for future
pivotal efficacy studies. We report results of the prespecified
interim tolerability data analysis.
Methods: Subjects with early PD on no dopaminergic
therapy are radomized 1:1:1:1 to receive isradipine CR
5:10:20mg:placebo for 12 months. The primary outcome of
the study is tolerability of three doses of isradipine with the
tolerability threshold defined as > 30% difference relative to
placebo. The interim tolerability analysis was preplanned after
50 subjects (50%) completed 12 week dose titration phase.
Results: The 20 mg dose was declared intolerable based
on the interim tolerability data reviewed by the Data Safety
Monitoring Board in July 2010. Investigators remained
blinded to the dose assignment.
Conclusion: These results support previously reported
data on the dose dependent tolerability of isradipine in PD.
Final data analysis and dose choice for the pivotal study will
be available Fall 2011.
Study supported by: Michael J. Fox Foundation and
Northwestern Memorial Foundation Dixon Priority
Research Initiative Award
S229. Nigella sativa Oil Controls Astrogliosis and
Reduces Haloperidol-Induced Deficit in Rats
Tafheem Malik**, Darakhshan Jabeen Haleem, Shema Husan,
Shahid Pervez and Tasneem Fatima; Karachi, Sind, Pakistan
and Karachi, Pakistan
The neuropathological status of Haloperidol (HP) induced
Extrapyramidal symptoms (EPS) remains unclear.Evidence
suggested persistent neuronal alterations in the basal ganglia
cause EPS. This study evaluate the possible protective effects
of the Nigella sativa (NS) oil on HP induced neuronal alterations and motor symptoms. EPS was monitored in HP
treated groups and with NS oil alone and with placebo.HP
treated group displayed (p<0.01) high degree of motor
impairment with late appearing vacuous chewing movement.
Striatum (Str) shown grossly disturbed large fraction of
cytoarchitectonic pattern with nerve cell depletion concomitant shrunken cytoplasm, nuclear membrane breakdown and
chromatin disorganization. Scarring was prominent feature
owing profusion of astrogliosis in the dorso - ventro lateral
regions of the caudate putamen and in the core of nucleus
accumbens.Halo and pyknotic neurons were moderate(p<0.05). HP induced neuronal changes were almost
absent in the HP plus NS treated groups. However minor
S227. Balance Difficulty in PD Correlates with the BNI
Balance Scale
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
Objective: To compare PD patients with and without
reported balance difficulty by several variables to assess the
validity of the BNI Balance Scale.
Background: Balance difficulty is a late complication of
PD. We devised a questionnaire and tested 3 tasks to calculate the BNI Balance Scale.
Method: In 102 consecutive non-demented PD patients,
we compared patients with reported balance difficulty without falls to patients without imbalance as regards age, PD
duration,UPDRS/Pull-Test, BNI Balance Scale (one foot
stance, turning 360 degrees, timed-gait). There were no
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astrogliosis with no indication of cell loss and 82% normal
neuronal densities were observed. We conclude that NS may
prevent HP induced neuronal degeneration.We believe that
further preclinical research into the utility of NS may indicate
its usefulness as a protective agent from irreversible EPS.
Study supported by: The University of Karachi, Pakistan.
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Without a biomarker of Parkinson’s disease (PD) progression, we rely on clinical ratings to estimate disease progression. Medication washout may be useful in these ratings.
We are conducting a prospective, blinded, pilot trial of deep
brain stimulation (DBS) in early stage PD subjects aged 50
to 75, Hoehn & Yahr II, without dyskinesias or motor fluctuations, and on PD medications < 4 years. Inpatient medication washout and motor rating is conducted at baseline
and every six months for two years. On Day 1, subjects are
rated ON medication and then medications are withheld
and motor function is rated daily. Thirty subjects were
randomized (15 MED; 15 DBSþMED). Participants are 27
males and 3 females aged 60.3 6 6.6 years at study entry
and taking medication an average of 2.1 6 1.5 years.
UPDRS-III score at baseline Day 1 (ON medication) was
14.9 6 7.9 which increased by 1.7 points per day to 27.0
6 7.9 after one week withdrawal. Median ON Hoehn &
Yahr Score was 2 (Range: 1-2) which remained at 2 after
one week (Range: 2–2.5). Schwab & England ADL score
also did not significantly change (Day 1: 92% 6 5%; Day
8: 89% 6 4%).
Study supported by: The clinical trial from which this
case is presented is supported by Vanderbilt CTSA grant 1
UL1 RR024975 from the National Center for Research
Resources, National Institutes of Health, by a research
grant from Medtronic, Inc., and by gifts from private
donors.
Vanderbilt University has received support from Allergan
and Medtronic for research led by Drs. Charles and Medtronic for researcfh led by Dr. Konrad. Drs. Konrad and
Davis have received personal compensation in the past from
Medtronic for consulting fees or honoraria. Dr. Charles
receives income from Allergan, Medtronic, and Pfizer for
education and consulting services.
S230. Cost-Benefit Assessment of Two Forms of
Botulinum Toxin Type-A in Different Pathologies
Humberto Juarez, Santamaria Salvador, Leticia Hernandez
and Enrique Molina; Mexico City, Mexico, Mexico
Botulinum Toxin Type-A has been successfully used since
20 years in the treatment of different movement disorder
pathologies.The comparison with Merz PharmaV’s Botulinum Toxin Type A regarding its equivalency has not been
trustfully demonstrated.The Social Security Hospitals have a
high captive population for each disease group.In 2008, due
to administrative restructure, a 150 kD assessment of Botulinum Toxin Type-A was initiated.To effectively compare the
potency, efficacy and safety of the new biologic, the same
dilution and application standards were maintained. Video
and photography were taken for all patients with a standard
procedure.From May 2008 to April 2009 the responses of 4
types of 150 kD different batches of the toxin were employed.Comparatively, patients injected with onabotulinumtoxin
A from May 2007 to April 2008 were selected.Our surveillance regarding potency, maximum time effect, and maximum duration was that in all parameters the Botulinum
Toxin Type A at 150 kD was lower and oscillates at 6 weeks
in average for all pathologies.
R
S231. Weight and Height Distribution in Children with
Tourette Syndrome
Katie Kompoliti, Glenn T. Stebbins and Christopher G. Goetz;
Chicago, IL
Objective: To compare height and weight of untreated children with Tourette syndrome (TS) with age and gender
matched controls.
Background: TS children are reported to have lower
height and weight, with normal body mass index (BMI),
indicating a possible dopaminergic over-activity.
Methods: Weight and height of consecutive TS patients
under 20 years were recorded. Patients were considered
untreated if they had never taken medications for tics or TS
co-morbidities. Age and gender standardized weight z-score
and BMI z-scores were compared between the TS group and
the CDC normative data from 2000 using one-sample t-test.
Results: A total of 195 patients (155 males, 40 females),
mean 11.9years (SD 3.5), were included, with 95 never
exposed to medications. Untreated patients had higher
adjusted average weight compared to the CDC sample’s mean
(p ¼ 0.0005), but no difference in height (p ¼ 0.08). Patients
with medication exposure had a higher adjusted weight compared to those never treated but no difference in height.
Conclusion: Un-medicated TS children are heavier than
the general population, arguing against a generalized hyperdopaminergic state. Medication treatment increases weight
further, alerting physicians to monitor weight when treating
TS children.
S233. Gender Differences in the Interleukin-6 G-174C
Polymorphism and the Risk of Parkinson’s Disease
Marta San Luciano, Laurie J. Ozelius, Richard B.. Lipton,
Deborah Raymond, Kaili M. Stanley, Susan B. Bressman and
Rachel Saunders-Pullman; New York, NY and Bronx, NY
Reports of associations between the -174G>C SNP in the
promoter region of the interleukin-6 (IL6) gene and the
1730G>A SNP in the estrogen receptor beta (ESR2) and
PD are conflicting. We investigated the association of both
SNPs in a sample of 121 unrelated Caucasian Parkinson’s
disease (PD) cases and 329 control subjects. The G allele of
the G-174C SNP was more common in the group of men
with PD when compared to controls (p ¼ 0.022), but not
among women with PD or in the overall group. In men,
having the GG genotype increased the risk of PD by over
two fold (OR ¼ 2.11, 95%CI: 1.14–3.89, p ¼ 0.017).
Analysis restricted to young-onset PD cases showed no association. No differences in allele or genotype frequencies
were observed between PD patients and controls for the
ERBeta G-1730A SNP in the overall group or either gender
separately, or between younger onset PD patients and controls. Our data supports a possible inflammatory role in PD
for IL6, and concurs with a prior report linking the G allele
with PD, although a gender effect was not found. These
findings were not replicated in two other samples. The contradictory findings may be explained by ethnic differences
in distribution of IL6 polymorphisms, the existence of other
polymorphisms in tight linkage disequilibrium with the C/
G SNP differentially influencing IL6 expression, methodological differences and sample size considerations, and
inability to capture the complex functional network of
S232. Motor Deterioration after Medication Withdrawal
in Early Parkinson’s Disease
Chandler E. Gill**, Anna L. Molinari, Thomas L. Davis,
Mark Bliton, Stuart G. Finder, Michael G. Tramontana, Peter
E. Konrad and David Charles; Maywood, IL; Nashville, TN
and Los Angeles, CA
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cytokines and chemokines from single gene association studies. Analysis of IL6 SNPs in larger and more diverse populations and sequencing of surrounding regions is recommended to further assess a role for this cytokine in PD.
Study supported by: Dr. San Luciano is supported by an
American Academy of Neurology Foundation Clinical
Research Training Fellowship. Dr. Saunders-Pullman is supported by the Pfizer Society for Women’s Health Research
Scholar Grant for Faculty Development in Women’s Health.
This study was supported by Grant Number K23NS047256
from the National Institute of Neurological Disorders and
Stroke (RSP), the Michael J. Fox Foundation (RSP, SBB),
the Thomas Hartman Foundation (RSP), and The Einstein
Aging Study is funded by the National Institute on Aging
(AG03949, Principal Investigator: R.B. Lipton). This publication was made possible by the CTSA Grant UL1
RR025750 and KL2 RR025749 and TL1 RR025748 from
the National Center for Research Resources (NCRR), a
component of the National Institutes of Health (NIH), and
NIH Roadmap for Medical Research.
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ance Scale. There were no confounding causes of balance or
gait difficulty upon historical review or physical exam.
Results: Patients with reported imbalance without gait
challenges demonstrated postural instability to Pull-Test: odds
ratio 6.00 (95% CL 1.331, 27.047), and one foot stance
instability: odds ratio 5.440 (95% CL 1.217, 24, 321) compared with patients reporting isolated gait difficulty.
Conclusions: Most patients with PD report a balance
difficulty with a co-morbid gait challenge. We believe there
is a subset of patients with subjectively perceived and objectively measurable impaired balance without noticeable gait
challenges that may reflect a distinct circuitry aberration
impacting balance separate from locomotion.
S236. Adult Onset Dopamine Responsive Dystonia
(DRD): Is There a New Gene?
Hossein Ansari, Ludwig Gutmann and Laurie Gutmann;
Morgantown, WV
Background: DRD is a type of inherited dystonia typically
presenting within the first decade of life. Various genes have
been identified for this condition.
Late-onset DRD is very rare and its gene has yet to be
identified.
Case Report: 29 y/o female with severe entire-body and
facial dystonic movements. This was associated with occasional myoclonus. Mental status significantly decreased over
the course of the patient’s nine-week hospitalization.Trials
with different agents (including dopamine depletors) failed.
Upon administration of Levopoda, however, the patient
dramatically improved. After 2 doses, her mental status
completely recovered and abnormal movements significantly
decreased. With continued medication, patient normalized.
Both the patient’s twin and one older sister have a history
of similar movements.
Conclusions: The rarity of late-onset DRD contributes
to its misdiagnosis. Therefore, adult-onset DRD is probably
an under-diagnosed condition with no known gene. We
speculate this patient’s sisters also suffer from DRD.
This family could be a prime case for genetic study used
to identify the potential gene/mutation causing adult DRD.
They are set to participate in a study by the NIH
Undiagnosed Diseases Program.
S234. Serum Cholesterol Is Linked with Nigrostriatal
Iron Deposition in Parkinson’s Disease
Guangwei Du, Mechelle M. Lewis, Michele L. Shaffer,
Honglei Chen, Richard B. Mailman and Xuemei Huang;
Hershey, PA and Research Triangle Park, NC
Higher nigrostriatal iron content has been related to Parkinson’s disease (PD). Higher serum cholesterol levels also have
been suggested to be associated with lower occurrence of PD.
To understand the relationship between serum cholesterol and
nigrostriatal iron content, 3T MRI (T1-, T2-weighted, T2*)
were obtained from 40 PD and 29 matched Controls. Fasting
serum lipid profiles were measured in all subjects. The mean
R2* values of bilateral substantia nigra (SN), caudate, putamen, globus pallidus (GP), and red nucleus (RN) were calculated, and correlated with serum cholesterol levels after controlling for age, gender, and statin usage. In PD, higher serum
cholesterol levels were associated with lower iron content in
SN (R ¼ 0.337, and p ¼ 0.048), striatum (R ¼ 0.403, p
¼ 0.017 for caudate; R ¼ 0.366, p ¼ 0.031 for putamen),
and RN (R ¼ 0.436, p ¼ 0.009), but not GP (R ¼
0.250, p ¼ 0.147). In Controls, higher serum cholesterol
levels were associated with lower iron content in striatum (R
¼ 0.449, p ¼ 0.032 for caudate; R ¼ 0.451, p ¼ 0.027
for putamen), but not associated with the SN (R ¼ 0.096, p
¼ 0.654), RN (R ¼ 0.136, p ¼ 0.526), or GP (R ¼
0.191, p ¼ 0.371) iron levels. Thus, higher serum cholesterol concentrations are associated with lower iron content in
nigrostriatal structures, warranting further studies.
Study supported by: NS060722, and the HMC GCRC
(NIH M01RR10732) and GCRC Construction Grant
(C06RR016499)
S237. Dystonia Induced Mechanical Stress as a Cause of
DBS Extension Fracture and Expulsion
Massimo Mondani, Elisa Petacchi, Roberto Eleopra, Silvia
Molteni, Sabrina Gualdi, Miran Skrap and Andrea
Martinuzzi; Udine, UD, Italy; Conegliano, TV, Italy and
Sesto San Giovanni, MI, Italy
The mechanical failure of the device, especially the most
exposed and longest part connecting the electrode to the
impulse generator (IPG) is a possible adverse eventa in DBS.
We describe a 12 year old child in whom the successful
treatment with GPi DBS for secondary generalized dystonia
repeatedly failed for malfunction of the IPG-electrode connection including one internal fracture diagnosed by electrophysiology, and two aseptic scar breakage leading to expulsion of a 5 cm long stretch of the left extension and
removal of the entire left implant.
The study of the pattern of child’s movements and of the
extension position along the left mastoid and neck revealed
a region of mechanical stress on the left extension which
was eluded by the right one thanks to its obliquity in
respect to the axis of the prevalent neck movements.
When implanting dystonia patients with DBS, especially
when they are children and present neck dyskinesias, one
S235. Balance Difficulty Differs from Gait Difficulty in
PD
Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan
and Anthony Santiago; Phoenix, AZ
Objective: To compare reported balance difficulty from gait
difficulty in PD.
Background: Patients with PD often report imbalance
without gait challenges.
Method: In 102 consecutive non- demented PD patients,
we compared 13 patients with reported imbalance without
gait impairment with 22 patients with isolated gait difficulty
as regards age, PD duration, UPDRS/Pull-Test, BNI Bal-
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should avoid positioning the IPG extension parallel to the
major axis of the prevalent movement. A slight obliquity of
the extension may suffice in preventing failures leading to
suspension of an otherwise efficacious treatment.
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Conclusions: Patients with PNES in our study population reported a higher frequency of NREM parasomnias
compared to epilepsy patients, and a much higher frequency
compared to general prevalence estimates. Parasomnias
should always be considered in the differential of paroxysmal nocturnal events in these patients.
Study supported by: Self Supported
Sleep Disorders and Circadian Rhythm
S301. Endogenous GABAA Receptor Enhancement
Modulates Vigilance in the Primary Hypersomnias
David B. Rye, Kathy Parker, Lynn Marie Trotti, Paul S.
Garcia, James C. Ritchie, Michael J. Owens, Leslie Morrow,
Donald L. Bliwise and Andrew Jenkins; Atlanta, GA;
Rochester, NY and Chapel Hill, NC
S303. Endothelial Function in Patients with Obstructive
Sleep Apnea
Kanika Bagai, James Muldowney, Yanna Song, Lily Wang,
Douglas E. Vaughan and Beth A. Malow; Nashville, TN and
Chicago, IL
Background: Obstructive sleep apnea (OSA) is implicated in the
pathogenesis of stroke, although mechanisms need clarification.
Methods: Severity of OSA [apnea-hypopnea index (AHI)
of 5 or greater] was defined by overnight polysomnography.
Endothelial function testing was done using flow mediated
dilatation and computerized arterial pulse waveform analysis
in 17 patients with OSA and 17 normal controls.
Results: The mean AHI (6 standard deviation) in the
OSA group was 18.68(25.48) and in the non-OSA group was
0.84 (0.80). Using a linear regression model, with AHI as the
main effect, and age as covariates, there was a trend towards
greater mean velocity change with higher AHIs (p ¼ 0.06).
Conclusions: The severity of OSA selectively affects the
percent velocity change after reactive hyperemia as measured
by flow mediated dilation. Consistent with prior studies with
altered endothelial function in OSA patients, our results show
a trend towards significant difference in the markers of endothelial function as measured by brachial artery flow- mediated
dilatation testing. One reason for the less dramatic difference
noted in our study may be because we included patients with
mild OSA, as compared with other studies which included
patients with moderate to severe OSA.
Study supported by: Supported in part by Vanderbilt
CTSA grant 1 UL1 RR024975 from NCRR/NIH.
Primary hypersomnias lack an etiology or rational treatments.
We investigated biological and neurobehavioral markers in 31
such cases. Plasma and CSF assays ruled out sedative-hypnotic
use, neurosteroid or gamma-aminobutryic acid (GABA)
excess, pathological amino acid profiles, and hypocretin-1 deficiency. We tested for GABA-ergic activity employing ligand
binding assays and electrophysiological recordings of cells
expressing recombinant GABAA receptors. CSF from 31
hypersomnolent and 16 control patients all enhanced a1b2c2s
GABAA receptors. The magnitude of enhancement in hypersomnolent subjects exceeded that of controls (89% 6 46.5 vs
41.4% 6 5.7, t ¼ 5.39, P < 0.001). Pharmacological profiling suggested that enhancement was due to an allosteric modulator unique to affected versus control CSF. Enhancement
did not require a functional BZD binding site, was selective
for a 2 > a1 receptors and negligible at a 4 receptors, and
was reversible with benzodiazepine antagonist flumazenil. Flumazenil normalized vigilance in seven index cases. Inhibitory
GABAA receptor enhancement occurs by way of a positive allosteric modulator unique to patients with a primary hypersomnia. This altered biology is antagonized in vitro and in
vivo by flumazenil and identifies a novel pathophysiology to
primary hypersomnolence.
Study supported by: Woodruff Health Sciences Center
Fund and USPHS grants NS055015 and NS055015-03S1
(D.B.R), NS-050595 (D.L.B), and GM073959 (A.J).
Education
S302. Frequency of Parsaomnias in Patients with
Non-Epileptic Seizures
Mitchell G. Miglis, Michael Boffa, Sujata Thawani, Alcibiades
Rodriguez and Anuradha Singh; New York, NY
S401. The Effectiveness of Education Intervention on
Health Knowledge among Neurological Patients
Mercedes Jacobson and Polina Pomerants; Philadelphia, PA
Objective: To assess the impact of education intervention
on patient’s health literacy in outpatient neurology
setting.
Background: Inadequate health knowledge is a strong indicator for higher risk of non-compliance, poor self-management, and negative health outcomes.
Methods: A single-blind randomized study was conducted.
Designed using Ask Me 3 principles, a questionnaire was
administered to study group before and a week after onsite
education intervention and to demographically matched control group a week after intervention. Performance was scored
on consistency between subjects’ responses and congruence
with information from subjects’ medical charts.
Results: Control and study group population (N ¼ 118)
consisted of unemployed (84%) middle-aged adults (44.2
þ/ 12.4) who are legally disabled (66%) and lack postsecondary education (82%). Study subjects retained more
health information (0.19þ/ 0.08, p<0.0001) after education intervention and scored higher in their overall knowledge of medical condition (0. 11þ/ 0.44, p< 0.0001)
and medications (0.30þ/ 0.50, p <0.0001) than control
subjects.
Objective: To assess frequency of parasomnias in patients
with Psychogenic Non-Epileptic Seizures (PNES)
Background: PNES have been associated with a history
of psychosocial stresssors, an association that has also been
suggested for some parasomnias. There is little data on frequency of parasomnias in patients with PNES.
Design/Methods: We selected a cohort of patients (n ¼
9) with vEEG-confirmed PNES from our Epilepsy Unit
and administered sleep questionnaires (Epworth, Munich
Parasomnia Scale) on follow-up visits and phone interviews.
An age-matched group of patients with vEEG-confirmed
epilepsy (n ¼ 9) were interviewed for comparison. Participants were scored on responses relating to twenty-one parasomnias. Responses of PNES and epilepsy patient were
compared (Chi square analysis, SPSS v16).
Results: PNES patients reported a higher frequency of
NREM parasomnias when compared to epilepsy patients,
notably hypnic jerks (77.8% vs. 11.1%, p ¼ 0.004), rhythmic foot movements (55.6% vs. 0%, p ¼ 0.023), exploding
head syndrome (44.4% vs. 0% p ¼ 0.023), and bruxism
(66.7% vs. 0%, p ¼ 0.003).
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versus 15/20, 75%, p ¼ 0.045). The percentage who felt all
important data were being transmitted increased from 49%
(16/33) to 80% (16/20, p ¼ 0.041). Overall satisfaction
(scale 1–10) increased from 6.2þ/1.6 to 7.4þ/1.3 (p ¼
0.002).
Interpretation: Structured sign-out results in improved
communication skills, and may improve patient safety and
quality of care.
Conclusions: Statistically significant improvement in
health knowledge resulted from education intervention using
Ask Me 3 tool. Patient education with attention to health
literacy should be employed in neurology teaching clinics to
improve patients’ adherence to treatment and comprehension of health information.
S402. Teleneurology in Leading U.S. Medical
Institutions
Benjamin P. George**, Nicholas J. Scoglio, Jason I. Reminick,
Kevin M. Biglan and E. Ray Dorsey; Rochester, NY and
Baltimore, MD
S404. Improved Scores on the AAN Resident Inservice
Training Examination (RITE) after Lecture Curriculum
Intervention
L. John Greenfield, Vicki Ramsey-Williams, Theresa Marshall
and Boyd Koffmann; Toledo, OH and Little Rock, AR
Objective: Telemedicine is used for the care of neurological
conditions yet little is known about the details of telemedicine use in neurology departments. The study purpose is to
determine current teleneurology opinions and practices
among neurologists at leading U.S. medical institutions.
Methods: A survey on teleneurology was performed
among neurologists at the top 50 hospitals in neurology
based on U.S. News and World Report. The survey was
sent to department chairs, faculty involved in teleneurology,
or department administrators. Respondents indicated level
of telemedicine use by department, current applications, and
opinions of telemedicine.
Results: The initial response rate was 32% (16 institutions, 18 responses). 50% of respondents were neurology
faculty, the remaining were department chairs (33%) and
department administrators (17%). 69% of institutions provide telemedicine; of those, all use telemedicine for stroke,
18% for movement disorders, and 9% for neuroimmunology. 45% of institutions using telemedicine services initiated
services within the last year, and 60% of institutions not
providing telemedicine have plans to within a year. Additionally, 61% of respondents find telemedicine to be equal
to the in-person care model.
Conclusions: There is increasing use and acceptance of
teleneurology by neurologists at leading U.S. medical
institutions.
Objective: Determine whether curriculum intervention has
a positive impact on resident education as measured by
RITE scores.
Background: Performance on the RITE predicted scores
on the ABPN Part I board examination, and has been used to
assess readiness to take ABPN Part I (Goodman et al. 2002).
Methods: Retrospective analysis of RITE and USMLE
scores for 3 years preceding and following curriculum intervention, which consisted of realigning the didactic syllabus
with the subject areas of the ABPN (Neurology) exam, and
pre-and post-lecture quizzes.
Results: All neurology residents at the Medical College of
Ohio/University of Toledo between 2003 and 2010 were
included. The mean percent of correct answers on the RITE
significantly improved from prior to 2007 (55.561.4, n ¼
30) to 2007 and after (61.361.6, n ¼ 27, p<0.01). Prior
to 2007, resident RITE percentile scores improved more
from PGY2 to PGY3 (8.5 6 1.7, n ¼ 8) than from PGY3
to PGY4 (3.0 6 2.2, n ¼ 7), but after 2007 increases were
seen at both stages (9.0 6 2.2, n ¼ 8; 8.9 6 0.9, n ¼ 7).
USMLE scores were also higher after 2007, and correlated
with RITE scores.
Conclusions: Our data support curriculum intervention
to improve resident education as measured by RITE.
S405. Evidence Based Medicine(EBM) in the 2nd Year
Neurosciences Curriculum
Michael J. Schneck and Edward Neafsey; Maywood, IL
S403. Standardized Sign-Out Improves Communication
Skills
Brian D. Moseley, Jonathan H. Smith, Gloria E. DiazMedina, Mateo Paz Soldan, Meredith Wicklund, Radhika
Dhamija, Haatem Reda, Michael F. Presti and Jeffrey W.
Britton; Rochester, MN
Objective: EBM is an increasingly emphasized part of student education but integration in basic science courses is
not common. We attempted to create an EBM module in
the Loyola neuroscience course to teach clinical decisionmaking based on neuroanatomical principles.
Methods: An introductory lecture on EBM was followed
by small group review of the NASCET and ACAS trials and
recommendaitons about 3 carotid case scenarios. Students
were assessed by small group reports and final exam multiple test questions. Based on initial class experience, module
changes were made in subsequent years. We describe our experience for years 2007–2010.
Results: Multiple test EBM answers were in line with
general neuroscience test results (mean 80%). Small group
responses were more variable Additionally,student assessment
of the module was less positive (mean 3.5/5).
Discussion: Reviewing the limited success of EBM in the
neuroscience course, we hypothesized we were less successful
because students lacked both general clinical experience and
factual information about EBM practice. Based on our
observations, EBM modules are more likely to succeed as
part of the 3rd & 4th year neuroscience clerkships after a
more robust general epidemiology and EBM course in preclinical years.
Objective: Unstructured handoffs are vulnerable to communication failures. We implemented standardized sign-out on
our inpatient Neurology services and assessed its effect on
communication skills.
Methods: Residents spent the first half of their rotations
utilizing unstructured sign-out. They switched to a structured sign-out system (using the Situation-BackgroundAssessment-Recommendation format) during the second
half. We analyzed survey responses before and after implementation to evaluate for an effect.
Results: We documented improvements in many variables, including being told: pertinent past medical history
(14/33, 42% versus 14/20, 70%, p ¼ 0.088); pending laboratory studies/tests (26/33, 79% versus 19/20, 95%, p ¼
0.234); recommendations for how to handle nursing/pharmacy calls (12/33, 36% versus 12/20, 60%, p ¼ 0.154);
and up-to-date code status (14/33, 42% versus 14/20, 70%,
p ¼ 0.088). Residents utilizing structured sign-out were significantly more likely to share test results with patients/family prior to shift changes (22/33, 67% versus 18/20, 90%, p
¼ 0.037) and update our electronic service list (13/33, 39%
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S406. Adapting a Teaching Hospital Inpatient Neurology
Service to New Duty Hour Requirements: The
Washington University Adult Neurology Experience
Robert Bucelli and Barbara J. Snider; Saint Louis, MO
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ance on the clerkship and grade. Students were surveyed via
zoomerang after completing their clerkship. Grades had not
been assigned before evaluation, though students had
received feedback from attendings and the clerkship director
about floor performance. Attitudes towards night call, specific floor attendings, lecturers, and a clinical examination
were numerically and qualitatively assessed. Histograms will
be presented. Spearman rank correlations will be performed
to relate student feedback ratings with their floor performance scores, clinical examination score, shelf performance,
and overall grade. A Wilcoxon analysis will compare students assigning either extreme high/low feedback ratings and
grades, shelf score, and clinical examination performance.
Forty-six evaluations have to date been collected. Collection
will continue until shortly before the meeting at which
point the data will be analyzed.
New duty hour regulations for ACGME accredited residency training programs will go into effect July 1, 2011.
The complexity of neurological disorders makes balancing
duty hours with educational and patient care goals particularly challenging for inpatient neurology services at teaching
hospitals. The Washington University/Barnes Jewish Hospital (WU/BJH) Adult Neurology residency convened a workgroup of residents and faculty to create a rotation system
designed to ease compliance with the proposed duty hour
rules. This system was instituted July 1, 2010. We used a
combination of local and national surveys of residents,
patient satisfaction scores, and hospital quality data to assess
whether this change altered duty hour compliance, resident
satisfaction, patient satisfaction or patient outcomes. Our
experience demonstrates the inherent difficulties in monitoring the effects of duty-hour driven changes in resident
schedules and suggests that these changes may have unexpected negative effects on other aspects of residency education and patient care. Future adjustments will require resident feedback and patient care metrics to best balance
resident education/quality of life and patient care responsibilities while maintaining compliance with program
requirements.
136th Annual Meeting Monday,
September 26, 2011
Poster Session
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
S407. Translational Research in Neuro-AIDS and Mental
Health
Amanda Brown, Valerie Wojna, Bruce Shiramizu, Avindra
Nath and Justin C. McArthur; Baltimore, MD; San Juan, PR
and Honolulu, HI
Behavioral Neurology
M601. Behaviorally-Driven Anatomical Mapping of
Hemispatial Neglect
Alex R. Carter, Mark P. Mcavoy, Serguei V. Astafiev, Jennifer
Rengachary, Daniel L.W. Pope, Abraham Z. Snyder, Kristi
Zinn, Nick Metcalf, Gordon L. Shulman and Maurizio
Corbetta; Saint Louis, MO
HIV infection of the CNS frequently results in neuropsychiatric complications and is a major cause of disability. Despite effective antiretroviral treatment, nearly 80% of
patients have asymptomatic cognitive impairment. HIV disproportionately affects racial/ethnic minorities and several
barriers must be overcome for a significant impact on this
illness to be realized. A better understanding of how social,
cultural and genetics impact the pathophysiology of disease
and the development of new therapies is needed. Another
barrier is the dearth of scientists from racial/ethnic minority
groups in the field of Neuro-AIDS research. The R25 program was designed to address these barriers by 1) supporting the education and training of minority graduate students, fellows and junior faculty and individuals who are
not members of minority groups but are engaged in NeuroAIDS disparity related research through a web-based didactic course; 2) to promote innovative Neuro-AIDS research,
through pilot grants and 3) to provide long-term mentoring
relationships to further career development. Since program
inception 12 university partnerships have formed, 127 trainees have completed the course, 8 trainees were research
scholars and/or received pilot grants, 11 independent grants
were obtained by trainees, and more than 50 manuscripts
have been published.
Study supported by: 5R25MH080661, The National
Institutes of Mental Health
Objective: A wide range of lesions have been associated
with hemispatial neglect. Some heterogeneity may be attributable to the use of varying tests. We used a single computerized test with high sensitivity for deficits in both topdown control of attention and reorientation to salient stimuli to predict which brain regions are more likely damaged
in subjects with those deficits after right hemispheric stroke.
Methods: Reaction times and accuracy were measured in
61 right hemisphere stroke patients using a computerized
Posner reaction time task. Stroke lesions were quantified by
MRI. Behavioral scores and lesion data were entered into a
novel voxel-wise logistic regression analysis.
Results: Two distinct patterns were observed. Impaired
target detection in the contralesional visual field predicted
damage to the subcortical paraventricular white matter
underlying the middle frontal and inferior frontal gyri.
However, impaired shifting of attention predicted damage
to more cortical regions between the inferior parietal lobule
and the temporo-parietal junction complex.
Interpretation: Lesions of long-range fronto-parietal
white matter tracts may be associated with deficits in the
maintenance of spatial representations; in contrast ventral
parietal lesions may be associated with deficits in phasic
reorientation of attention.
Study supported by: This study was supported by the
National Institute of Mental Health [R01 HD061117-05A2
to M.C.; 1K08NS064365-01A1 to A.R.C.], the Robert
S408. Relationship between Medical Student Feedback
and Grading
and James M. Stankiewicz; Boston, MA
It is common for students to be asked for feedback in order
to foster clerkship improvement. It is less clear whether
medical student feedback is ultimately related to perform-
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Wood Johnson Foundation Amos Medical Faculty Development Program [65592 to A.R.C.].
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cal and research activities of the Neurology Department of
the University Hospital of Crete.
M604. Motor Chunking Is Correlated with
Sensorimotor Cortex and Striatum Activation
Nicholas Wymbs and Scott T. Grafton; Santa Barbara, CA
M602. Markers of Celiac Disease and Gluten Sensitivity
in Patients with Cerebellar Ataxia
Caroline Tan, Peter H. Green, Khalaf O. Bushara, Donald D.
Kasarda, Ejaz Shamim, Norman Latov, Mark Hallett and
Armin Alaedini; New York, NY; Minneapolis, MN; Albany,
CA and Bethesda, MD
Motor chunking facilitates the production of everyday
movements by combining discrete motor elements into
well-integrated units of behavior. We hypothesized that sensorimotor cortex and corresponding basal ganglia projection
areas are essential for chunking. Healthy participants learned
a motor sequencing task during fMRI scanning. Instructed
to respond as quickly as possible, participants translated
sequences from a pseudo-musical tablature displaying a series of twelve ‘notes’ on a four-lined staff to one of four
response keys. Using multislice graph analysis, an unbiased
estimator identified chunks on a trial-by-trial basis for a set
of three extensively trained sequences (189 trials/sequence)
performed over the course of three scanning sessions. A
‘chunking score’ based on the element-to-element variance
within each chunk was used to determine the strength of
overall chunking for each trial and then entered as a covariate in the estimation of BOLD. Consistent with our predictions, we found activity in contralateral sensorimotor cortex
and posterior putamen correlated with chunking strength,
independent of movement speed or reaction time. Disruption of this circuit may result in deficits of concatenating
complex serial actions into contiguous behavior and explain
some symptoms of subcortical apraxia or Parkinson disease.
Study supported by: Supported by PHS grant NS44393
and contract no. W911NF-09-D-0001 from the U. S.
Army Research Office.
Celiac disease is an autoimmune enteropathy resulting from
sensitivity to wheat gliadin and related cereal proteins. A
link between celiac disease and cerebellar ataxia has been
postulated, based primarily on reports of increased anti-gliadin antibodies among patients with ataxia. Serum specimens
from 21 patients with cerebellar ataxia and elevated antigliadin antibody titer, 20 celiac disease patients, and 20
healthy subjects were assessed for antibodies to deamidated
gliadin peptides and transglutaminase 2 (TG2) by ELISA.
The anti-gluten antibody response was further characterized
through examination of reactivity towards chromatographically separated gliadin and glutenin protein fractions by immunoblotting. In contrast to the celiac disease group, there
was not a significant association between the anti-gliadin
immune response and anti-TG2 or anti-deamidated gliadin
antibodies in the ataxia group. Characterization of antibody
specificity revealed differential reactivity towards specific
gluten protein fractions between ataxia and celiac disease
patients. The findings indicate that the mechanism and profile of the elevated antibody response to gluten in patients
with cerebellar ataxia is significantly different from those in
celiac disease patients.
M605. Areas of Ischemia Associated with ‘‘Frontal Lobe’’
Task Failure
Yessenia Gomez and Argye E. Hillis; Baltimore, MD
M603. Early Signs of Cognitive Impairment among
Multiple Sclerosis Patients with Clinically Isolated
Syndrome
Theodora Panou, Vasileios Mastorodemos, Efrosyni Papadaki,
Panagiotis G. Simos and Andreas Plaitakis; Heraklion, Greece
and Rethymnon, Greece
Hypothesis: Measures of ‘‘frontal lobe function’’ evaluate
broad functional networks including left frontal, temporal,
and parietal cortex.
Methods: We identified acute areas of ischemia associated
with impaired performance on Trail Making, Phonemic
Word Fluency (word generation in 1 minute), and word
span, in 95 patients with acute left hemisphere ischemic
stroke within 48 hours of onset. DWI and PWI were evaluated for infarct or hypoperfusion in 14 Brodmann areas
(4,6,10,11,44, 45,21,22,38,37,39,40,18,19). ANOVA was
used to identify areas where ischemia was associated with
mean decrement in performance.
Results: Patients with ischemia (DWI or PWI abnormality) in BA 6, 44, 45 (posterior frontal), 21, 22, 37 (temporal), 39 or 40 (inferior parietal) had significantly impaired
performance on word span (p ¼ .03-.001). Patients with ischemia in BA 4, 6, 21, 22, 37 and 39 had impaired performance on word fluency. Only patients with ischemia in
BA 37 had impaired Trail Making, but many could not complete the task. Lowest word span scores were associated with
ischemia in BA 45 (mean 1.0 6 0); lowest word fluency
were associated with ischemia in BA 21 (mean 4.7 6 3.9).
Conclusion: Word fluency and span tasks are sensitive
but not specific for frontal lesions.
Study supported by: NIH R01 DC05375
The study investigates primary and secondary verbal memory and motor/executive functions (response inhibition and
strategy shifting ability) in multiple sclerosis (MS) patients
with clinically isolated syndrome (CIS). We studied 44 CIS
patients and compared them to 49 patients with relapsing
remitting MS (RR-MS) displaying mild disability and to a
large cohort of age- and education level-matched healthy
volunteers. Results showed that both CIS and RR-MS
patients evidenced a disproportionate impairment in the immediate and delayed recall of the second (as compared to
the first) of two short narratives of the Logical Memory
WMS-III subtest, and reduced performance on the Memory
for Digits-Forward. Performance of either group on the executive tasks was not impaired, showing evidence of a
reversed speed-accuracy trade-off. Illness duration emerged
as a significant predictor of memory and executive task performance. Clinical, psychoemotional, and brain imaging
findings were also examined as potential correlates of cognitive deficits and disease progression among CIS patients.
These findings may signify early-onset decline of specific
cognitive functions in CIS, which merits regular follow-up
assessments and monitoring of psychoemotional adaptation
and everyday functioning.
Study supported by: This Research Project was partially
supported by the Association for Research and Treatment of
Neurologic Disorders of Crete (‘‘EY ZHN’’), which is philanthropic (non-profit) organization that supports the clini-
M606. Thalamic Atrophy in Gastric Bypass Patients
with Cognitive Complaints
Jonathan Graff-Radford, Jennifer Whitwell, Max R. Trenerry,
J.E. Ahlskog, Michael D. Jensen, Clifford R. Jack, Jr. and
Keith A. Josephs; Rochester, MN
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Background: Gastric bypass patients are at risk for developing neurological complications, often from nutritional deficiencies. We have noticed a series of patients presenting for
cognitive complaints that developed after gastric bypass,
without any identifiable etiology. We set out to determine
whether such patients have any focal brain atrophy that
could account for the complaints.
Methods: Retrospective case series to identify patients (n
¼ 10) with cognitive complaints following gastric bypass
that had a volumetric MRI. Voxel-based morphometry and
atlas-based parcellation were used to assess patterns of grey
matter volume loss in all patients compared to a group of
10 age and gender-matched controls, and a group of 10
controls matched by body mass index before surgery.
Results: Patients underwent gastric bypass at a median
age of 54. Cognitive complaints began at a median age of
57. All were taking multi-vitamins with nine receiving vitamin B12. Formal neuropsychometric testing revealed only
minor impairments. No nutritional abnormalities were identified. Focal thalamic atrophy was identified in the gastric
bypass patients when compared to controls.
Conclusions: Patients with cognitive complaints after
gastric bypass surgery have focal thalamic brain atrophy that
could account for the cognitive impairment.
Study supported by: KAJ is funded by the NIH grant
R01 DC010367 (PI), the Dana Foundation (PI) and the
Morris K. Udall PD Research Center of Excellence NIH/
NINDS P50 NS40256 (Co-investigator).
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with the disorder present a variety of psychiatric symptoms
including obsessive compulsion, general anxiety, specific
phobia, and depression. However, it is unknown the extent
to which these behavioral problems are related to cognitive
ability or hypersocial behaviors in WS. Thus, this study
aimed to examine the relationships among cognitive ability
(Verbal, Performance, Full IQ), psychiatric symptoms, and
social behaviors (social-emotionality, social approach) in WS
versus typical development (TD). A cognitive battery
(WISC, WASI, WAIS), Brief Symptom Inventory and Salk
Institute Sociability Questionnaire were administered to 41
WS and 31 TD participants. Results suggest that verbal
intelligence is predictive of greater psychiatric symptoms
(e.g., somatization, interpersonal sensitivity, paranoid ideation, psychoticism) in WS but not in TD. Interestingly,
greater reported psychiatric symptoms in WS were associated with poorer socio-emotionality (i.e., emotion recognition, desire to please) but not with approach behavior, while
no significant correlations between social and psychiatric
measures were observed in TD. Possible role of cognition in
psychiatric ailments and social outcomes of WS will be
discussed.
Study supported by: Grant P01-HD033113-13
M609. Human Brain Mapping at the Single Cellular
Level: Neuronal and Area Specific Differences in Health
and Diseases
Ryan P. Moore, Irisa Mahaparn, Eliezer Masliah and Pavel V.
Belichenko; La Jolla, CA
M607. Parietal Lobe Lesions Affect the Generation of
Antisaccades
James A. Sharpe, Ping Cheng and Moshe Eizenamn; Toronto,
ON, Canada
The Human Brain Mapping Project is an ongoing effort to
characterize neural circuitry at the level of single cells (Belichenko and Dahlstrom, 1994). Lucifer yellow microinjection and high resolution confocal microscopy imaging were
employed to reveal disparities in dendritic geometry of von
Economo neurons (VENs) vs. pyramidal neurons in the cingular cortex complemented with bilateral analysis of speech
areas to find morphological substrates for the speech area
asymmetry. For the VENs, significant differences were
revealed in spine density (p<0.01), spine head area (p ¼
0.04), and cell shape. Left and right speech area 44 and 45
were distinguished by bigger neuronal size (p<0.05), by
greater synaptophysin immunoreactivity (p<0.05), and by
greater density of parvalbumin positive neurons (p<0.05) in
the speech dominant hemisphere. The results indicate foci
for more myopic biochemical analysis in the hope of expediting further characterization both within cell types (VENs
vs. pyramidal neurons) as well as between hemispheres
(speech areas 44 and 45 asymmetry). Clinical significance of
our data includes autistic spectrum disorder (Rett syndrome), a range of diseases presenting with alexithymia
including schizophrenia and agenesis of the corpus
callosum.
Antisaccades are directed away from visual targets, requiring
suppression of reflexive saccades toward a target. Impaired
antisaccade generation has been attributed to frontal lobe
damage. The role of the parietal lobe is not established. We
studied antisaccade generation by magnetic search coil technique in 13 patients (age 45 6 7 years) with unilateral focal
parietal lobe lesions (9 tumors; 5 vascular lesions), and in
10 age-matched controls.
Patients were instructed to make horizontal antisaccades
away from a 100ms target flashed randomly 10 degrees to
the right or left of center. The task was to look 10 opposite
to the target flash.
The patient group made antisaccades in only 49.7 6
32.7% of contraversive trials (visual target flash ipsilateral to
lesions) and 49.6 6 38.4% of ipsiversive trials. In the other
trials they made reflexive saccade errors toward the target
flash. The control group made antisaccades in 82.8 6
13.7% of trials. Eight patients showed subnormal antisaccade generation. Their imaged lesions overlapped in parietal
lobe white matter.Generation of voluntary saccades is
impaired by parietal lobe lesions. Antisaccades provide a
means of measuring voluntary saccade function of the parietal lobes independent of visual guidance.
Study supported by: Canadian Institutes of Health
Research (CIHR)
M610. Cognitive and Behavioral Differences between
ADHD Populations (Inattentive Type Versus ADHD
Plus) Using Neuropsychological Testing and SelfReported Symptoms in Diagnosed Population from
Years 1991–2008
Barbara C. Fisher, Danielle M. Garges and Stephany Fulda;
Shelby Township, MI and Munich, Germany
M608. Cognitive Ability Correlates of Psychiatric and
Social Behaviors in Williams Syndrome
Rowena Ng, Anna Ja¨rvinen-Pasley and Ursula Bellugi; San
Diego, CA
Introduction: Investigate relationship between Inattentive
Type ADHD and ADHD Plus using neuropsychological
tests, self-reported anxiety and hyperactivity in a clinic
population.
Method: 1332 adults referred for ADD/ADHD testing
(15–50 years, 831 males); 74% with diagnosed ADHD
Williams syndrome (WS) is a genetic disorder characterized
with cognitive impairment, a gregarious personality and significant anxiety. Research on WS indicates that individuals
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(Inattentive Type) and 24% with ADHD plus additional
disorder (i.e. sleep apnea; brain dysfunction excluded). Neuropsychological tests included Trail Making Tests (A and B)
and SDMT-W. Self-report measures assessed hyperactivity
and anxiety (PPCA, PHCA, PBC, PCC).
Results: Hyperactivity (> 45%) and anxiety (> 50%)
were frequent with no significant difference between
ADHD and ADHD plus. We found a significant relationship between hyperactivity and anxiety. Individuals who
reported yes to one or both anxiety items had higher hyperactivity scores than those who said no to both items.
ADDþ performed worse on all neuropsychological tests (p
< 0.001 for all comparisons).
Conclusions: Findings indicate ADHD (Inattentive
Type) and ADHDþ can be differentiated on cognitive
measures, but not on self-reported symptoms of anxiety and
hyperactivity as these co-morbid factors are highly prevalent
in both populations.
Study supported by: Personally funded and donated time
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tor and unrelated pictures (p < .05). Controls and PPAnonSV patients had more fixations to the competitor than
the unrelated pictures in the Coordinate condition only (p
< .05). In contrast, SV patients had more fixations to the
competitor in both the coordinate and associative conditions
(p < .05).
These results suggest that deficits in PPA-SV at least partially stem from increased semantic interference (i.e. coordinate and associative) over the time-course of lexical
processing.
Study supported by: NIDCD RO1 DC 05375
M613. Differences in Time Interval Distributions Reveal
Controlled and Automatic Contributions to Cued Word
Retrieval
Kyongje Sung, Erin J. Pickett, Kerry Ledoux, Tracy D.
Vannorsdall, Mohammad Elsayed, Nia M. Billings, Jessica
Silva, David J. Schretlen and Barry Gordon; Baltimore, MD
Category-cued word retrieval is generally thought to entail
the automatic activation of related concepts, guided by controlled switching among subcategories. The same mechanisms are thought to characterize letter-cued word retrieval,
but with greater reliance on controlled than automatic processes. We examined the distributions of time intervals
between successively generated words during letter- and category-cued retrieval tasks for evidence of these different
mechanisms. Sixty-one healthy adults performed two category-cued word fluency tasks (animals and supermarket
items) and two letter-cued word fluency tasks (‘p’ and ‘s’).
Word outputs were categorized using the methods described
in Ledoux et al. (2009) and the time intervals between
words were measured. For category-cued word production,
exponential distributions provided excellent fits for time
interval distributions. However, for letter-cued words, different types of distributions (e.g., ex-Gaussian) were required
in order to fit the time intervals. This discrepancy supports
the hypothesis that letter- and category-cued word fluency
tasks invoke fundamentally different cognitive mechanisms.
This implies that different neuroanatomic structures might
subserve lexical retrieval under these constraints, a conclusion that garners some support from disassociations in
verbal fluency that characterize various degenerative conditions and focal lesions.
Study supported by: This research was supported by the
Therapeutic Cognitive Neuroscience Gift Fund and by the
NIMH grants MH60504 and MH43775.
M611. The Use of Quetiapine in Agitated Patients with
Acquired Brain Injury: A Case Control Study
Sara Piccoli, Gabriella Paparella, Alec Vestri and Andrea
Martinuzzi; Pieve di Soligo, TV, Italy
Background: Experimental studies on neurocognitive effects
of quetiapine showed improvements of cognitive functions
in psychiatric patients. Patients with Acquired Brain Injury
(ABI) often present behavioral disturbances (BD) requiring
drug treatment which might impair responsiveness and cognition. The use of quetiapine may provide in these patients
adequate control of BD without cognitive side effects.
Methods: 40 consecutive ABI patients (LCF 4–6) attending intensive neurorehabilitation were recruited, 20 of
whom with BD scored by Aggressive Behaviour Scale (ABS)
requiring medical treatment, and 20 with ABS score <21
not requiring medication. Patients with BD were treated
with quetiapine. The changes after 3 months of neurorehabilitation in cognitive functioning and autonomy in ADL
(LCF and FIM) in patients receiving quetiapine were
compared with those observed in the patients not treated
with it.
Results: ABS score was significantly reduced in patients
receiving quetiapine LCF and FIM improved at similar
extent in both groups.
Conclusions: Quetiapine provides effective control of
BD in ABI patients without interfering with cognitive and
functional aspects.
M614. Gender Differences across the Lifespan in
Neuropsychological Testing Performance in ADHD
Population from the Years 1991–2008
Barbara C. Fisher, Danielle M. Garges and Stephany Fulda;
Shelby Township, MI and Munich, Germany
M612. On-Line Lexical-Semantics in the Semantic
Variant of Primary Progressive Aphasia
David S. Race and Argye E. Hillis; Baltimore, MD
Patients with the semantic variant of primary progressive
aphasia (PPA-SV) have semantic deficits in language. In a
word-picture matching study, we used eye-tracking to investigate whether PPA-SV patients suffer from lexical-semantic
interference during target selection.
Participants selected one of four pictures (target, competitor, two unrelated) upon hearing its name. The target-competitor relation was either: coordinate (bee-mosquito), associative (cow-farm), or linguistic (butter-fly). We measured
accuracy and proportion of fixations to each picture (which
should increase with its level of semantic activity). PPA-SV
performance was compared with PPA-nonSV and controls.
Accuracy scores were high for controls (98%), PPAnonSV (93%), and PPA-SV (91%). For each condition, all
groups had more fixations to the target than to the competi-
Introduction: Explore differences between males and
females (adolescents and adults) in neuropsychological testing performance in diagnosed ADHD population.
Method: A total of 673 adults and adolescents, from age
15 to 73 years were included (419 males) with diagnosed
ADHD (Inattentive Type; brain dysfunction/referrals
excluded).
Results: Females of all ages performed worse than males
on all four trials of PASAT. Significant interaction of
depression and gender found with females without depression performing better on Stroop than males without
depression and no gender differences for subjects with
depression; also depressed females performed worse than
non-depressed females, with no difference for males. Males
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and females did not differ in performance on SDMT and
Trail Making Tests.
Conclusions: Gender differences are present across lifespan on tasks of information processing (PASAT). Depression moderates performance on tasks assessing distractibility
(Stroop) to a greater degree for females than males. Significant gender differences did not occur systematically on
SDMT and Trail Making Tests, which involve speeded performance and whole brain functioning.
Study supported by: Personally funded
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formance on the FAB compared with the MMSE, consistent
with frontal-subcortical dysfunction in depression.
Study supported by: University of Colorado Denver
School of Medicine.
M617. Attention Deficit Hyperactivity Disorder in
Depressed Adults
Ildefonso Rodrı´guez Leyva, Rube´n Haro SIlva and Ana A.
Renterı´a Palomo; San Luis Potosi, San Luis Potosi, Mexico
Objective: Attention deficit hyperactivity disorder (ADHD)
is now recognized as a common disorder, as well as in
children and adults. ADHD has an estimated prevalence of
3–5% in adults. Evidence points to an increased rate of
a co-morbidity in adult ADHD patients. The most common are disorders of the affective area, including depression.
We investigated the comorbidity between these two
conditions.
Methods: Two questionnaires were applied, the first is
the Hamilton Depression Scale D and the second is the
Adult Self-Assessment Scale (EAVA), developed by the
working group on adult ADHD, which includes the New
York University Medical Center, Harvard Medical School
and Massachusetts General Hospital.
Results: 50 patients, 42 women and 8 men. 74% had
some level of depression. 18% had criteria for ADHD
(12% inattentive, 6% impulsive). By correlating the scale of
Hamilton with the score of EAVA, results that in patients
with ADHD and depression, impulsive symptom severity
decreased in proportion to the degree of depression.
Conclusions: In patients with ADHD and depression,
the intensity of the symptoms of inattention and not those
of impulsiveness, are related in proportion to the degree of
comorbid depression measured by the Hamilton Scale.
M615. Hazard Perception in Cognitively Impaired Older
Drivers
Nazan Aksan, Monica Lees, John D. Lee, Shaun Vecera and
Matthew Rizzo; Mountain View, CA; Madison, WI and Iowa
City, IA
Aging and neurological impairment reduce situation awareness and increase injury risk as in falls and car crashes. Hazard perception ability (HPA) is important to driver safety
and can be indexed by reaction time (RT) to traffic scenarios (Horswill & McKenna, 2004; Horswill et al., 2008).
Declines in HPA correlate with reductions in Useful Field
of View (UFOV), a measure of spatial area within which
individuals can detect visual stimuli (Ball & Rebok, 1994).
We examined whether vehicular warning systems can
improve RT in HPA paradigms in elderly drivers with and
without UFOV deficits. 27 of 51 elderly (67-87yrs without
neurodegenerative disease, min MMSE ¼ 25) were randomly assigned to receive auditory/visual warnings in a simulator while watching video scenarios and 10 of those had
deficits in UFOV. Warnings improved RTs slightly
(300msec) and a large difference of 1sec in RTs were noted
between those with and without UFOV deficits. Warnings
did not differentially improve RTs of those with deficits.
However, they improved sensitivity, d’, of elderly without
deficits more than those with deficits. Findings imply warning systems do not provide uniform benefits to elderly
drivers.
Study supported by: NIH R01 HL091917
M618. Cognition and EEG Abnormalities in NonEpileptic AD(H)D/LD Patients with and without AntiEpileptic Drug/Stimulant Therapy
Brittany M. DiVito, Heather A. Koch, Spencer A. Leblang,
Erik C. Bakken and Drake D. Duane; Scottsdale, AZ and
Tempe, AZ
Background: Epileptiform EEG abnormalities of unknown
but non-epileptic clinical significance are not rare in developmental disorders of attention and learning (ADD/LD).
The fate of these EEG patterns, their correlation with behavioral manifestations and effects of AED therapy is
unknown.
Methods: Retrospective analysis of 56 non-epileptic
ADD/LD with an initial Dysrhythmia Grade II or III EEG
(Mayo Clinic classification) and subsequent EEG later for
developmental dx, cognitive test profile, noting if stimulant,
AED, both or none were employed.
Results: Baseline Abnormal EEG-M38/F18, mean age 10
5/12 years, Dx:AD(H)D-47, LD-40, both-32
EEG and cognitive improvement in at least 1 of 5 cognitive tests: F/U EEG Nl-50%; F/U EEG Abn-52%
In both, proof reading and verbal learning most apt to
improve, rarely computerized attention
Rx and cognitive improvement (cumulative score 5
tests): No Rx-11, Stim-20, AED-12, Both-23
Conclusions: In AD(H)D/LD with Abn EEG:
M616. Differentiation of Alzheimer’s Disease and
Depression with Standard Cognitive Measures
Meredith C. Frederick**, Stefan Sillau, David B. Arciniegas,
C. Alan Anderson, Katherine L. Howard and Christopher M.
Filley; Aurora, CO and Denver, CO
Objective: Alzheimer’s disease (AD) and depression can
both present with cognitive impairment. To compare the
neurobiology of these disorders, we assessed patients with
AD and depression using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB).
Methods: Medical records were reviewed of 475 consecutive patients seen at a behavioral neurology clinic over 34
months. From this group, patients with AD (n ¼ 59) and
depression (n ¼ 44) were selected after receiving a consensus diagnosis by three physicians certified in Behavioral
Neurology & Neuropsychiatry (DBA, CAA, CMF). MMSE
and FAB data were analyzed using Z-score transformation.
Results: AD patients performed significantly worse than
those with depression on both the MMSE (z-scores 3.93
vs. 0.05, p < 0.0001) and FAB (3.1 vs. 1.0, p ¼
0.009). Patients with depression scored significantly worse
on the FAB than the MMSE (p ¼ 0.0003). AD patients
performed equally poorly on both tests.
Conclusions: The MMSE and FAB may assist in the differentiation of AD and depression. Whereas both measures
were abnormal in AD, depressed patients had poorer per-
-Normalization of EEG has no general correlation with
improved cognition. When cognition is improved, it is most
often in verbal learning/memory/proof reading not computerized attention tasks.
-Irrespective of follow up EEG, cognition is most apt to
improve when both an AED and stimulant are employed.
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M619. Evolution of EEG Abnormalities in Non-Epileptic
AD(H)D/LD Patients with and without Anti-Epileptic
Drug/Stimulant Therapy
Heather A. Koch, Brittany M. DiVito, Spencer A. Leblang,
Erik C Bakken and Drake D. Duane; Scottsdale, AZ and
Tempe, AZ
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M621. Cruetzfeldt-Jakob Disease Presenting as a Rapidly
Progressing Dementia with Non-Convulsive Status
Epilepticus
Natasha Tilluckdharry, Megan McGarry and Dipak P.
Pandya; Paterson, NJ
Background Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by the accumulation of misfolded prion proteins in the brain. Although rare, it is the
most common prion body disease. Clinical manifestations
include rapidly progressive dementia, behavioral changes,
extrapyramidal signs, akinetic mutism and myoclonus. We
report a unique case of CJD with nonconvulsive status
epilepticus.
Case Report: 73 year old woman was admitted with a
rapidly progressive dementia of one year. The patient was
noted to have intermittent jerky movements, decreased
responsiveness and mutism. Physical examination revealed
vegetative mental state, whole body stiffness, myoclonic
jerks and right sided rigidity. Electroenchephalogram (EEG)
demonstrated generalized periodic,rhythmic and lateralized
complexes. Magnetic Resonance Imaging (MRI) of the brain
revealed global cerebral atrophy. CSF evaluation showed
presence of 14-3-3 protein and extremely high levels of Tau
protein. The brain biopsy was refused by family.
Conclusion The clinical triad of rapid progressive dementia, myoclonus, akinetic mutism in conjunction with EEG
and CSF findings are usually conclusive for CJD. Brain biopsy is the diagnostic choice with histopathologic findings
of spongiform changes, cortical neuronal loss and abnormal
deposition of prion protein. Nonconvulsive status epilepticus is usually a rare finding with CJD.
Background: Epileptiform EEG abnormalities of non-epileptic clinical significance are not rare in developmental disorders of attention and learning (ADD/LD). The fate of
these EEG patterns and their evolution over time with or
without AED therapy is unknown.
Methods: Retrospective analysis of 56 non-epileptic
ADD/LD with initial Dysrhythmia Grade II or III EEG
(Mayo Clinic classification) and subsequent EEG later for
developmental dx, noting if stimulant, AED, both or none
were employed. Population was contrasted with 56 control
ADD/LD with normal EEG.
Results: Baseline Nl EEG- M38/F18, mean age 10 9/12
years, Dx: AD(H)D-49, LD-50, Both-43
Baseline Abn EEG- M38/F18, mean age 10 5/12 years,
Dx: AD(H)D-47, LD-40, Both-32
Follow Up EEG: interval mean 3 9/12 years (range 8/12
to 15 years)
Nl- 25(45%) No Rx-3, Stim-5, AED-8, Both-9
Abn- 31(55%) No Rx-9, Stim-11, AED-4, Both-7
Conclusions: In AD(H)D/LD with abnormal EEG:
-Diagnosis distribution is similar to normal EEG.
-Whether on or off AED Rx, EEG abnormalities often
persist, but less often if AED in use.
M620. Transection of CA3 Does Not Affect Memory
in Rats
Mohamad Z. Koubeissi, Saifur Rashid, Gemma Casadesus,
Joseph LaManna, Kui Xu, Hans Luders and Dominique
Durand; Cleveland, OH
Epilepsy
M701. Controlled Cortical Impact in Adult Rats and
Posttraumatic Seizures and Epilepsy
Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller, Bo Lu
and Zakaria Mtchedlishvili; Pittsburgh, PA and Philadelphia,
PA
Objective: To investigate the effect of CA3 transections on
memory in rats.
Rationale: Longitudinal hippocampal pathways are
needed for seizure synchronization, and their transection
may abolish seizures. However, the effect of such transection
on memory is unknown.
Methods: Sprague-Dawley Rats (247–285g) were used.
A stereotactic knife was implanted 4mm ventrally, 3.3mm
posterior and 4.0mm lateral to bregma, targeting CA3.
The knife was protruded from its sheath to transect CA3.
Sham surgery (n ¼ 4), unilateral (n ¼ 5), and bilateral (n
¼ 5) CA3 transections were made. Novel object recognition (NOR) and Morris water maze (MWM) tests were
started 18 days later. Cut locations were confirmed by cresyl-violet staining.
Results: For MWM, the ratio of the amount of time
spent in the target quadrant to that spent in the other three
quadrants showed no difference between groups. For NOR,
discrimination scores were also not different between controls and transected animals. Histology confirmed the locations of transections in the CA3 region.
Conclusion: Normal performance in NOR and MWM
does not appear to require intact transmission throughout
the whole length of CA3.
Significance: Since CA3 transections do not interfere
with memory function, they may be tried for treatment of
temporal lobe epilepsy.
Study supported by: Dr. Durand is supported by the
National Institute of Health (5R01NS032845-13,
5R01NS060757-03, and 5R01NS064157-02) and the
COULTER Foundation
The CCI model of TBI has been used in mice and immature rats to model posttraumatic epilepsy. We used young
adult rats and long-term video and video-EEG with cortical
and hippocampal electrodes to investigate posttraumatic epileptogenesis and associated neuropathological changes. A
total of 28,956 hours of monitoring was obtained from 128
CCI-injured and 15 sham-operated animals. Class 3–5 provoked seizures occurred in 7/72 (9.7%) animals video-monitored for 1 week immediately after CCI. Epileptic seizures
occurred in 26/118 (22%) animals monitored beyond 1
week post-CCI. Class 3–5 seizures occurred in 19 animals;
ictal discharges appeared generalized at onset or from the
contralateral frontal cortex. Nonconvulsive seizures occurred
in 7 animals characterized by motor arrest or no behavioral
change associated with continuous 1-2 Hz high amplitude
spikes or spike-waves averaging 26.2 6 2.8 seconds. No
control animal had seizures. CCI resulted in severe cortical
and subcortical injury and alterations in NeuN and GFAP
staining. Timm staining showed mossy fiber sprouting in
the inner molecular layer of the dentate gyrus of epileptic
and nonepileptic animals. These results indicate that the
CCI model can be used in adult animals to investigate
mechanisms underlying posttraumatic epileptogenesis.
Study supported by: Pennsylvania Department of Health
Research Formula Fund RFA 01-07-26 and Epilepsy Foundation Research Grant (ZM)
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M702. Serotonin 1A Receptors and Memory in
Temporal Lobe Epilepsy
William H. Theodore, Edythe Wiggs, Ashley Martinez, Irene
Dustin, Omar Khan, Shmuel Appel, Patricia Reeves-Tyer and
Susumu Sato; Bethesda
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Objective: Periventricular nodular heterotopia (PNH) are
associated with epilepsy and dyslexia. Evidence suggests that
heterotopia have a functional role and connectivity defects
may be important in this disorder. We investigated the restingstate functional connectivity of heterotopic nodules in PNH.
Methods: Eleven subjects were studied using functional
connectivity MRI with bold oxygenation level-dependent
(BOLD) imaging acquired during rest. The functional correlation between heterotopic nodules and other brain voxels
was systematically identified and relationships to clinical
measures analyzed.
Results: Forty-three of 45 heterotopia (96%) showed
functional correlation with discrete regions of overlying cortex (mean peak coefficient 0.61). Nodules also demonstrated
correlation with contralateral cortex (62%), other nodules
(51%), ipsilateral nonoverlying cortex (42%), and basal ganglia/cerebellum (13%). The peak degree of connectivity
between heterotopia and other gray matter regions was significantly related to epilepsy duration.
Interpretation: Nearly all heterotopia in PNH are functionally connected to overlying cortex, and the strength of
aberrant connectivity increases with duration of epilepsy.
Along with prior evidence that cortico-cortical tract defects
underlie dyslexia in this disorder, these results suggest that
altered connections are a critical substrate for neurological
dysfunction in brain malformations.
Study supported by: NIH/NINDS, Epilepsy Foundation,
William F. Milton Fund
Memory deficits are common in patients with temporal lobe
epilepsy (TLE). Previous PET studies have shown reduced
mesial temporal 5HT1A receptor binding. We studied 40
patients (24 male; mean age 34.5). Seizure diagnosis and
focus localization were based on ictal Video-Electoencephalographic recording. Patients had Weschler Adult Intelligence
Score III, Weschler Memory Score III, Beck Depression inventory, and interictal PET with [18F]FCWAY, a highly specific 5HT1A ligand. MRI partial volume correction for hippocampal atrophy and tracer plasma free fraction (f1)
measurement were used to obtain [18F]FCWAY volume of
distribution (V/f1). V/f1 was significantly lower ipsilateral
than contralateral to the epileptic focus (73.7 þ/ 27.3 versus 95.4 þ/ 28. We found a significant relation between
left hippocampal FCWAY V/f1 and delayed auditory memory score (r ¼ 0.41; p <0.02). The side of the seizure focus
was not significant. There was a significant inverse relation
between BDI and FCWAY V/f1 ipsilateral to the epileptic
focus (r ¼ 0.38; p<0.02), but no relation between BDI and
auditory memory. Reduced left hippocampal 5-HT1A receptor binding may play a role in memory impairment in TLE.
Study supported by: NINDS NIH Division of Intramural
Research
M703. Ictal Hypoxemia Is Associated with Cardiac
Repolarization Abnormalities
Lisa M. Bateman, Franchette Pascual, Michael Lee, Chin-Shang
Li and Masud Seyal; Sacramento, CA and Los Angeles, CA
M705. JAK/STAT Inhibition Slows the Progression of
Temporal Lobe Epilepsy in an Animal Model
Heidi L. Grabenstatter, Yasmin Cruz Del Angel, Marco I.
Gonzalez, Yogendra H. Raol, Shelley J. Russek and Amy R.
Brooks-Kayal; Aurora, CO and Boston, MA
Background: Peri-ictal hypoxemia occurs in 1/3 of patients
with intractable localization-related epilepsy. Cardiac repolarization abnormalities also occur during seizures. The relationship between these changes is unknown.
Methods: We analyzed 37 seizures with oxygen desaturations (DESAT) and 19 seizures without desaturations
(NODESAT) in 17 consecutive patients undergoing videoEEG telemetry. Consecutive QT and RR intervals were
measured for 1 minute prior to seizure onset (PRE), during
the period of hypoxemia in DESAT and two minutes after
seizure onset in NODESAT. QTc was calculated using
Hodges formula. QTd was the difference between the longest and shortest QT for PRE and DESAT/NODESAT.
Results: Prolonged QTc was more likely during DESAT
than PRE (OR 10.64;95% CI 4.75–27.98,p<0.0001), as
was shortened QTc (OR 1.65;95% CI 1.42–
1.92,p<0.0001). DESAT QTd was significantly associated
with desaturation nadir (p ¼ 0.025) and desaturation duration (p < 0.0001) but not seizure duration (p ¼ 0.079).
Prolonged QTc was more likely during DESAT than
NODESAT (OR 4.30;95% CI 2.56–7.39,p<0.0001), as was
shortened QTc (OR 2.13;95% CI 1.84–2.46,p<0.0001).
Conclusions: Peri-ictal shortening and prolongation of
QTc and increases in QTd are associated with depth and
duration of hypoxemia. These findings may be related to
the pathophysiology of SUDEP.
In the rat pilocarpine model of Temporal Lobe Epilepsy
(TLE), status epilepticus (SE) decreases transcription of the
GABA-A receptor a1 subunit (GABARa1) in hippocampal
dentate gyrus (DG) and may be critical for epileptogenesis.
Decreased transcription of GABARa1 results from JAK/
STAT pathway activation which increases inducible cAMP
early repressor, and subsequently downregulates GABARa1.
To investigate the utility of JAK/STAT inhibitors to prevent
epileptogenesis after SE, a novel inhibitor of STAT3 activation, WP1066, was administered to rats at the onset of SE.
WP1066 (50 mg/kg i.p.) administered at onset of and 1
hour into pilocarpine-induced SE reduced STAT3 phosphorylation in DG by 45%. Continuous video-EEG monitoring for two weeks demonstrated that administration of
WP1066 significantly reduced the total time spent in SE
and impeded the progressive increase in spontaneous seizures over time compared to SE rats treated with vehicle. Latency to first seizure was not affected. Conclusions: Treatment with JAK/STAT inhibitors at the time of SE reduces
the severity and duration of SE and slows the progression of
epilepsy inherent to post-SE models, suggesting that JAK/
STAT inhibitors may be disease modifying.
Study supported by: NIH NS R01051710 (to ABK and SJR),
Epilepsy Foundation (to HLG), and CURE (to ABK and SJR)
M706. Long-Term Changes in mGluR-Mediated
Long-Term Depression Following a Single Episode
of Early Life Seizures in Rats
Paul B. Bernard, Anna Castano and Tim A. Benke;
Aurora, CO
M704. Gray Matter Heterotopia in an Epileptic Brain
Malformation Are Functionally Connected to Overlying
Cortex
Joanna A. Christodoulou, Linsey M. Walker, Stephanie N.
Del Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E.
Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA
and Haifa, Israel
Previous research in our lab has indicated that following a
single episode of early life seizures (ELS), rats display
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increased LTD (long term depression) and cognitive deficits
at maturity (PND 60þ). These changes occur in the absence of pronounced hippocampal injury. We speculate that
increased LTD expression may be responsible for the
observed learning abnormalities. LTD induction can be
mediated by two distinct mechanisms, NMDA receptor
(NR) dependent and metabotropic glutamate receptor
(mGluR) dependent. The NR-mediated and mGluR-mediated forms are differentiated by the effectiveness of different
chemical and electrical LTD inducing stimulation paradigms. Using these paradigms, we found that alterations in
LTD following ELS are the result of changes exclusively in
mGluR-mediated LTD. Furthermore, we found that ELS
results in abnormal signaling consistent with that mediated
by the Fragile X Mental Retardation Protein (FMRP) to
result in increased mGluR-mediated LTD, with similarities
to that found in genetic disruption of FMRP. Expression of
proteins associated with mGluR-mediated LTD and FMRP
signaling were also altered in a consistent fashion, suggesting
a mechanism for the observed changes in LTD and possible
targets for therapeutic intervention.
Study supported by: NIH-NINDS, Epilepsy Foundation,
The Childrens Hospital Research Institute
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were defined anatomically a priori and functioned as seeds
in a functional connectivity analysis. Results indicate that
TLE exerts a complex effect on the functional connections
of the medial temporal region. Intrahemispheric coupling
between the hippocampal head and entorhinal cortex was
surprisingly stronger in TLE patients (p<.05), which may
have either compensatory or pathologic significance. While
cross-hemispheric coupling between hippocampi was weaker
than controls (p<.05), even in patients there was strong
interhemispheric connectivity, suggesting partially preserved
function in the affected hippocampus. Tracking the amount
of preserved connectivity in the individual patient may help
predict risk of postsurgical functional decline.
Study supported by: NIH/NCRR Washington University
ICTS Grant Number UL1 RR024992
M709. Mice Deficient in SNAREs/SNARE Regulators
Predict Kindling Phenotype
John T. Slevin, Elena E. Matveeva, Sidney W. Whiteheart,
Greg A. Gerhardt and Thomas C. Vanaman; Lexington, KY
Alterations in neurosecretory machinery may play a role in
kindling epileptogenesis. Neurotransmitter (NT) release
requires fusion of vesicle and plasma membranes, initiated
by the formation of a stable complex (7SC) of SNARE proteins. 7SC is composed of VAMP-2 from the synaptic vesicle and syntaxin 1 & SNAP-25 from the neuronal active
zone. There are alterations of SNARE Regulators and permanent accumulation of 7SC in hippocampus ipsilateral to
the kindling stimulus. We have begun to characterize epileptogenicity of mice deficient in neurosecretory proteins. To
fully kindle, the VAMP-2þ/ mouse requires 150% the AD
stimulus and >2.5 as many stimuli as the wild-type animal.
One month after full kindling 7SC asymmetry is present in
both. VAMP-2 reduction correlates with reduced glutamate
release in hippocampal CA3. Tomosyn, as a place-holder for
the v-SNARE, may be a negative regulator of NT release;
we predicted that tomosyn/ mice would be kindling-sensitive. In preliminary studies these mutants required half as
many stimuli and 2/3 the AD current to fully kindle, compared to wild type. Transgenics with reduced levels of
SNAREs/SNARE Regulators may be useful to determine if
alterations in neurosecretory machinery can lead to changes
in epileptogenesis.
Study supported by: Department of Veterans Affairs
M707. Heterozygous Loss of the Epilepsy-Associated
GABAA Receptor a1 Subunit Causes Spontaneous EEG
Spike Discharges in Two Mouse Strains
Fazal M. Arain and Martin J. Gallagher; Nashville, TN
Autosomal dominant juvenile myoclonic epilepsy and absence epilepsy are associated with missense (A322D) and
frameshift (S326fs328X) mutations in the GABAA receptor
a1 subunit. Although both mutations substantially reduce
a1 subunit protein expression in vitro, previous studies
failed to detect seizures in heterozygous a1 subunit knockout (GABRA1 KO) mice. Here, we performed video-EEG
studies in wild type and heterozygous GABRA1 KO mice in
the seizure-resistant C57BL/6 and susceptible DBA/2J
strains. Consistent with previous results, both strains of wild
type mice had a low incidence of spike discharges (SD), and
this baseline incidence was greater in DBA/2J (7 6 4 SD/
hr) than C57BL/6 (2 6 1 SD/hr) mice. Heterozygous
GABRA1 KO caused an ethosuximide-sensitive increase in
SD incidence to 14 6 3 SD/hr in DBA/2J mice and 12 6
3 SD/hr in C57BL/6 mice. The typical SD duration was
brief (1–3 seconds) and no definite associated behavior
changes were observed. Therefore, heterozygous loss of a1
subunit produces thalamocortical hypersynchrony in vivo
and likely represents a principle mechanism by which the
A322D and S326fs328X mutations cause seizures.
Study supported by: National Institute Of Neurological
Disorders And Stroke R01NS064286
M710. Pharmacokinetic Equivalence between
Immediate-Release and Extended-Release Topiramate
Lawrence J. Lambrecht, Wesley M. Todd and Mark B.
Halvorsen; Maple Grove, MN
Decreased absorption in the presence of food and plasma
fluctuations can negatively affect antiepileptic drug therapy.
Food has no effect on the absorption of immediate-release
topiramate (TPM-IR) but twice-daily dosing is recommended to minimize fluctuations. Recently, an extendedrelease topiramate formulation (USL255) was developed
that displays improved pharmacokinetic (PK) characteristics
based on single-dose and modeled steady-state data.
Equivalence of exposure between USL255 and TPM-IR,
and the effect of food on the USL255 PK profile, were
determined in a Phase I, randomized, 3-way crossover study.
Equivalence criteria were 90% confidence interval of the
ratios of the geometric least-squares means for AUC0-t,
AUC0-1, and Cmax within the range 0.8–1.25. Similar criteria were established for determining the food effects. Tmax
and t1/2 were also determined for each treatment.
M708. Regional Network Disruption in Temporal Lobe
Epilepsy
Luigi Maccotta* and Edward Hogan; St. Louis, MO
Medial temporal cortex forms a network of connections
with both the contralateral medial temporal lobe and with
extratemporal brain regions. It is unclear how temporal lobe
epilepsy (TLE) affects these connections, and whether the
effect is pathologic/dysfunctional or compensatory. We
investigated the functional connections of the medial temporal region with contralateral temporal and extratemporal
brain regions in TLE patients using resting state fMRI.
Twenty-three TLE patients underwent resting-state BOLD
fMRI. Seizure localization was based on video-EEG.
Healthy controls served as comparison. Regions of interest
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TPM exposure was equivalent between USL255 and
TPM-IR; furthermore, USL255 displayed a lower Cmax and
later Tmax than TPM-IR. While bioavailability of USL255
was unaffected by food, Tmax was delayed by 4 hours with
food as compared with the fasted condition.Single-dose
USL255 demonstrated equivalent TPM exposure and a lack
of food effect analogous to TPM-IR dosed twice-daily, suggesting that USL255 may provide a once-daily alternative to
TPM-IR.
Study supported by: Upsher-Smith Laboratories, Inc.
All authors are employees of Upsher-Smith Laboratories,
Inc. (study sponsor)
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lowing suppression of the GABAB receptors, an effect that
may contribute to antiepileptic properties of the drug.
Thus, GABAB receptor antagonists reduce pro-epileptic activity in DS model mice.
Study supported by: Down syndrome research and treatment foundation (DSRTF); Larry L. Hillblom Foundation
M713. Lacosamide: Long-Term Safety and Efficacy in
Partial-Onset Seizures
William Rosenfeld, Nathan B. Fountain, Gintaras Kaubrys,
Elinor Ben-Menachem, Cindy McShea, Jouko Isojarvi and
Pamela Doty; St. Louis; Charlottesville; Vilnius, Lithuania;
Go¨teborg, Sweden and Raleigh
M711. Cingulate Epilepsy, Reporting 3 Clinical and
Electrophysiologic Subtypes with Surgical Outcomes
Mhd Rafeed Alkawadri, Norman K. So, Paul C. Van Ness
and Andreas V. Alexopoulos; Cleveland, OH and Dallas, TX
Long-term (8 years exposure) safety and efficacy of the
antiepileptic drug (AED) lacosamide were evaluated from a
completed open-label extension (SP615; NCT00552305) in
partial-onset seizures.
Patients enrolled following double-blind or open-label
lacosamide trials. Dosage adjustment of lacosamide (100800mg/day) and/or concomitant AEDs occurred to optimize tolerability and seizure reduction. Treatment-emergent
adverse events (TEAEs), vital signs, body weight, clinical
laboratory data, electrocardiograms, and seizure frequency
from subject diaries were evaluated.
Of 370 enrolled patients, 77%, 51%, and 39% had >1,
>3, or >5 years lacosamide exposure, respectively (median
modal dose 400mg/day). Common TEAEs (15%) were
dizziness, headache, nausea, diplopia, fatigue, upper respiratory tract infection, nasopharyngitis, contusion, and coordination abnormal. Discontinuations due to TEAEs were
12.7%; only dizziness and convulsion led to discontinuation
in 1% of patients. Median 28-day seizure frequency was
12.0 at Baseline of previous trials; median percent reduction
from Baseline was 50.8% across Treatment, and was 47.3%,
56.8% and 65.2%, respectively, for 1-year, 3-year and 5year completers. The 50% responder rate was 51.2%
across Treatment, and was 48.8%, 57.2% and 63.4% for 1year, 3-year and 5-year completers, respectively.
Long-term adjunctive lacosamide treatment was generally well
tolerated, reduced seizure frequency and maintained efficacy.
Study supported by: UCB Inc.
Elinor Ben-Menachem, within the past year, has had contracted research, consulting, speaking, and teaching, relationship with UCB. Cindy McShea and Jouko Isojarvi are
employed by UCB BioSciences Inc. Pamela Doty is
employed by UCB BioSciences, Inc. as a Principal Clinical
Program Director for Lacosamide Epilepsy. As Principal
Clinical Program Director, she receives stock option grants.
William Rosenfeld is a principal investigator and has
received research support from UCB for participating in
double-blind and open-label studies. William Rosenfeld is
on the UCB speaker’s bureau.
Objective: To characterize epilepsy arising from the cingulate gyrus.
Design/Methods: We describe 14 cases of lesional cingulate gyrus epilepsy treated surgically. The cases were identified from the Cleveland clinic and the UTSouthwestern epilepsy monitoring unit databases 1992–2009.
Results: All 14 cases had cingulate epilepsy confirmed by
MRI lesions and remarkable improvement after surgery.
They were divided into 3 groups based on the anatomical
location and the semiology. In the posterior cingulate group
4 of 4 cases had clinical or electrophysiologic findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a ‘‘typical’’ (BANCAUD,
1992) group: 6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or
interictal personality changes; and an ‘‘atypical’’ group: 4
cases presenting with simple motor seizures and a tendency
for more frequent generalization and less favorable surgical
outcome. The pathology of the atypical cases was
astrocytoma.
Conclusions: Posterior cingulate gyrus epilepsy presents
with electroclinical findings that are suggestive of temporal
lobe epilepsy and can be considered an example of ‘‘pseudotemporal epilepsy’’. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology.
M712. GABAB Receptor Antagonists Reduce ProEpileptic Activity in Hippocampal Slices of Ts65Dn
Mice, a Genetic Model of Down Syndrome
Alexander M. Kleschevnikov, Brett Rasmuss, Pavel V.
Belichenko and William Mobley; La Jolla, CA
Epilepsy is a known co-morbidity of Down syndrome (DS).
GABAB receptor antagonists have been proposed recently as
medicines for improving memory in DS. We examined
effects of GABAB antagonists on pro-epileptic properties in
Ts65Dn mouse model of DS. In a high-potassium in vitro
model of epilepsy, elevation of extracellular [Kþ] provoked
seizures in the dentate gyrus in slices from both Ts65Dn
and 2N (control) mice. The frequency of seizures was significantly greater in Ts65Dn (0.47 6 0.03 Hz vs. 0.33 6
0.06 Hz, p ¼ 0.013), while the amplitude did not differ (p
¼ 0.45). GABAB antagonist CGP52432 reduced the amplitude of seizures more considerably in Ts65Dn than in 2N
slices (63.5 6 4.6% vs. 80.2 6 8.1%, p ¼ 0.033). The frequency of seizures was not affected (p > 0.4). GABAB
antagonists reduced also ratio of amplitudes of population
spikes (PSA2/PSA1) evoked by paired stimuli. This result
suggests an increase in the feedback inhibitory efficiency fol-
M714. Lacosamide: Long-Term Safety in Partial-Onset
Seizures
Robert F. LeRoy, Gregory Krauss, Nathan B.. Fountain,
Deanne Dilley, O’Neill D’Cruz and Pamela Doty; Dallas, TX;
Baltimore, MD; Charlottesville, VA and Raleigh, NC
Long-term safety of the antiepileptic drug (AED) lacosamide was evaluated in an open-label extension trial SP926
(NCT00655486).
Eligible participants were enrolled from IV infusion trial
SP925 (NCT00655551). Investigators could adjust lacosamide oral tablet (100–800mg/day) and/or concomitant AED
dosage to optimize treatment. Safety assessments included
adverse events (AEs), ECGs and clinical laboratory data.
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Of the 97 enrolled patients, 58.8% and 38.1% had
>12- and >18-months of lacosamide exposure, respectively. The median modal lacosamide dose was 500mg/day.
TEAEs (incidence 15%) included dizziness (44.3%), diplopia (17.5%), and vomiting (16.5%); most were mild/
moderate in intensity. Only one serious AEs (SAEs)
occurred in >1 patient (convulsion, n ¼ 2). One patient
discontinued due to SAEs (arrhythmia supraventricular
and atrial fibrillation) and continued commercial lacosamide after treatment of the SAEs. One TEAE led to discontinuation in >1 patient (dizziness, n ¼ 3). Median
clinical laboratory values remained within normal range;
changes from Baseline were not of clinical relevance. Small
increases in mean PR interval and QRS duration were consistent with the known lacosamide safety profile and did
not vary with lacosamide exposure.
Safety evaluations indicate long-term lacosamide administration (100–800mg/day) is generally well tolerated as adjunctive treatment for patients with partial-onset seizures.
Study supported by: UCB Inc.
Dr. RF LeRoy has a significant financial relationship with
UCB, the sponsor of the study which generated this
abstract. He participated in funded research as an investigator in study SP926 and other UCB funded studies as well
as a speaker for the Vimpat Speaker ProgramHe has participated in UCB sponsored advisory boards for Vimpat. Dr. G
Krauss has received research support from UCB S.A., Johnson & Johnson Inc., SK-Biosciences Corporation, Eisai Inc.,
Sepracor Inc., and Icagen, Inc., and has served as a paid
consultant for Eisai Inc. and UCB S.A. Deanne Dilley: Employee, UCB BioSciences, Inc. O’Neill D’Cruz: Employee,
UCB BioSciences, Inc. Pamela Doty is employed by UCB
BioSciences, Inc. as Principal Clinical Program Director for
Lacosamide Epilepsy. As a Principal Clinical Program Director, she receives stock option grants
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M717. Status Epilepticus: An Independent Predictor of
Poor Survival after Anoxic Brain Injury
Jennie Luna, Nelly Awkar, Megan McGarry, Deepthi
Karanam and Dipak P. Pandya; Paterson, NJ
Introduction: Evaluation of prognosis in Anoxic brain
injury is a very difficult task due to lack of clinical and biological markers. The delay in neurological recovery is a poor
prognostic sign. Status epilepticus (SE) may present in up
to one third of patients with cardiac arrest. We report the
significance of SE and myoclonic status as an independent
clinical marker in anoxic brain injury.
Methods: After IRB approval, we studied adult patients
with SE in anoxic brain injury. Status epilepticus was
defined with clinical history and EEG findings. Patients
without EEG findings were excluded. Total 48 patients were
identified.
Results: 20/48(41%) had SE. 16/20(80%) expired and 4/
20(20%) survived. A 15% of the patients with SE had
anoxic myoclonus with 100% mortality. All SE patients
were comatose. Patients with SE, 60% reported duration of
CPR 10 minutes. The other 40% had unknown duration.
All our study patients were resistant to antiepileptic
medications.
Conclusion: Status epilepticus was present in 41% of
patients and anoxic myoclonic status remains a grave prognostic sign for any survival. Overall, comatose mental status
with SE or anoxic myoclonus remains an independent clinical marker for poor outcome.
M718. Periodic Lateralized Epileptiform Discharges
(PLEDs)-Rhythmic Discharges (RDs) in Anoxic
Encephalopathy
Sushanth Bhat, Sombabu Maganti, Eli S. Neiman, Divya
Gupta and Sudhansu Chokroverty; Edison, NJ
Objective: To describe an unusual EEG pattern of stereotypical PLEDs coupled with RDs in anoxic encephalopathy.
Case Discussion: Following cardiac arrest, a comatose 79
year-old woman had left facial twitching, sluggish pupils,
absent corneal’s/Doll’s eyes reflexes and no withdrawal to
stimuli. Facial twitching subsided with intravenous levetiracetam. CT scan of the head showed cerebral atrophy. An
EEG showed right anterior/midtemporal PLEDs with slowsharp morphology recurring at 0.3–0.5 Hz, coupled with a
9 Hz RD from the same area every 24–29 seconds and lasting 5.5–7 seconds, not evolving into electrographic seizures
and unchanged in morphology or frequency. There was no
clinical/EEG background change to noxious stimulation.
Discussion: PLEDs may be PLEDS-proper or PLEDSplus (associated with RDs). Both may occur with acute cerebral lesions, with PLEDs-plus more likely to be associated
with seizures. However, focal and chronic lesions more often
produce PLEDs-proper.
The presented case is unusual, with no evolution of the
PLEDs- RDs complex into electrographic seizures; such a
pattern has not been described in acute, diffuse cortical injury
such as anoxic encephalopathy, where BiPLEDs would be
expected. Our EEG findings are reminiscent of those in isolated cortex in an animal model (Kristiansen, 1949).
M715. Withdrawn
M716. Computational Models of Ligand-Gated Receptor
Function Characterize Anticonvulsant Drug Actions at
GABAergic and Glutamatergic Synapses
and David E. Naylor; Torrance, CA
Many neurological drugs act on inhibitory GABAergic or
excitatory glutamatergic receptors. Little is known about the
direct effects of endogenous ligand or drug exposure on
receptors in situ, and even less about broader pharmacological effects on normal or pathological circuit activity. Here,
computational models of receptors characterize drug actions
on multiple scales from submillisecond transmitter release,
diffusion and uptake at single synapses to near seconds of
residual receptor desensitization after multisynaptic
synchronized release. GABA-A and NMDA receptor-kinetic
models at synaptic and extrasynaptic sites in dentate gyrus
granule cells are optimized to fit inhibitory and excitatory
postsynaptic currents (PSCs) as well as evoked paired-pulse
and tonic current responses after ligand and drug exposure.
Synaptic GABA-A receptors over-exposed to GABA paradoxically show rapid downregulation/amplitude reduction
from receptor desensitization. Hi-frequency 200Hz pulsatile
release of GABA for 400 ms (as with epileptic fast ripples)
also degrades synaptic inhibition, and recovery from desensitization is prevented by 0.5 to 2 Hz interictal-like discharges. Subsequent model fits of IPSCs/EPSCs after exposure to anticonvulsant agents quantify and optimize the
effects of single and combination agents on receptor
properties.
M719. Periodic Lateralizing Epileptiform Discharges
(PLEDs) Causing Persistent Magnetic Resonance
Imaging (MRI) Changes in Ipsilateral Thalamus
Umang Shah, Umer Akber and Chunyang Wang; Camden, NJ
Objective: To recognize PLEDs as potential cause of persistent MRI changes in ipsilateral thalamus.
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Background: Transient diffusion weighted image (DWI)
abnormalities in ipsilateral thalamus following status epilepticus are well-recognized, but persistent changes in fluidattenuated inversion recovery (FLAIR) and T2-weighted
images (T2WI) are rare.
Design/methods: We report a patient who had persistent
ipsilateral signal change in thalamus after complex partial
status epilepticus and PLEDs.
Results: Case: A 56 year-old woman presented with
recurrent partial seizures involving the right arm and change
in mental status. Electroencephalography revealed PLEDs in
the left temporal lobe causing partial status epilepticus. Immediate brain MRI was normal but repeat MRI ten days
later showed a focus of increased signal on FLAIR and
T2WI in the left posterolateral thalamus. No abnormal
enhancement was seen. Follow-up MRI one-month later
demonstrated a persistent area of signal abnormality in the
left thalamus.
Discussion: Thalamic role in ictal events is unclear, but
afferent and efferent cortical-interconnections may explain
thalamic involvement in epileptic activity, which is generally
considered a cortical phenomenon. Although DWI thalamic
abnormalities are reported after status epilepticus, persistent
FLAIR and T2WI signal is rare.
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of the disease. Status epilepticus has not been reported as a
clinical manifestation in Sneddon’s Syndrome.
Results: A 68 year old man with history of hypertension
admitted with confusion, decrease responsivessness and subtle
left sided weakness. He had non-itchy skin rash and mild left
sided paresis. His laboratory tests showed thrombocytopenia,
Hepatitis C, positive antiphospholipid antibodies. MRI
showed acute right middle cerebral artery distribution infarct.
EEG showed Periodic Lateralized Epileptiform Discharges
from right hemisphere with changing morphology and evolving in nature. Patient was treated with antiepileptic medications, intravenous immunoglobulins, antiplatelet agents, statin
and ACE inhibitors. His acute condition was improved and
he was discharged to rehabilitative facility.
Conclusions: Most cases of Sneddon’s syndrome are sporadic. It is unclear whether the status epilepticus is due to
acute brain injury, from antiphospholipid antibodies or
from inflammatory mediators.
M722. Status Epilepticus Secondary to Milk Alkali
Syndrome Induced by Hypercalcemia (Oral Antacids)
Rabih Kashouty, Noor Yono and Mershed Al Samara;
Manhattan, NY; Manhasset, NY and Southfield, MI
Milk-alkali syndrome is mainly caused by the ingestion of
large amounts of calcium and absorbable alkali. This syndrome can lead to metastatic calcification, renal failure and
metabolic alkalosis secondary to hypercalcemia. Hypercalcemia is rarely a cause of seizure activity. Very few case reports
have been published linking seizure to hypercalcemia, but
only one recent case report about mesial temporal sclerosis
relates the seizure activity to Milk-alkali syndrome. This is
the first report regarding seizures associated with excess calcium carbonate intake without evidence of mesial temporal
sclerosis. The patient described in this article, suffered from
status epilepticus most likely secondary to hypercalcemia.
Evaluations for malignancy, thyroid, and parathyroid dysfunctions were non conclusive, therefore hypercalcemia in
our patient was attributed to milk-alkali syndrome given the
history of the prolonged calcium carbonate intake.
M720. Ammoniacal Encephalopathy Presenting as
Complex Partial Seizure-Like Episodes: A Case Series
Darine Kassar and Stanley Iyadurai; Saint Louis, MO
Objective: To report a series of cases with hyperammonemia, presenting as seizure-like episodes.
Background: Seizures are caused due to several causes.While accumulation of ammonia is a common cause of
encephalopathy, it is also known to cause a broad spectrum
of neurological manifestations. Seizures have not been
reported in association with chronic hyperammonemia.
Methods: Case Series
Case report: Index case: A 53-year old man with chronic
hepatitis C presented with confusional episodes associated
with stereo-typed movements. Physical examination revealed
psychomotor slowing. Routine serological and CSF evaluations were normal, except elevated ammonia (177 mmol/l).
A diagnosis of ammoniacal encephalopathy was made. The
patient was started on lactulose therapy with improvement.
Four other patients with similar history, presentation, and
elevated ammonia levels were seen. Complete resolution of
symptoms were observed with treatment of hyperammonemia with lactulose in these patients.
Conclusion: Here we present a series of patients with
episodes of various neurologic dysfunctions. The only metabolic abnormality that was identified was an elevated ammonia level. We believe that his seizure-like episodes are associated with hyperammonemia. To our knowledge, this is the
first report that links complex partial seizure-like episodes to
hyperammonemia.
M723. A Case of Magnesium-Responsive Paraneoplastic
Non-Convulsive Status Epilepticus
Robert K. Shin, Anna V. Rosenbaum and Nicholas Frost;
Baltimore, MD
Objective: We present a case of paraneoplastic non-convulsive status epilepticus resistant to multiple AEDs that
resolved with magnesium.
Background: Paraneoplastic syndromes affecting the
nervous system have been described in association with
numerous cancers, some presenting as limbic encephalites
associated with seizures, including an encephalitis in young
women with ovarian teratoma associated with anti-NMDA
receptor antibodies.
Results: A 57-year old female with clear cell ovarian cancer became unresponsive following a one week prodrome of
increasing confusion and forgetfulness. EEG demonstrated
non-convulsive status epilepticus. Imaging, serum and CSF
studies were non-diagnostic. Over a course of two weeks, she
did not respond to multiple anti-epileptic medications and
continued to have up to 30 seizures daily. IV magnesium was
administered, and the following morning she was alert, oriented and able to converse with her husband.
Conclusions: While magnesium is routinely used to treat
seizures in obstetrics, its use in neurology is uncommon.
Given that it is a known NDMA inhibitor, it may represent
M721. Status Epilepticus as an Initial Manifestation of
Sneddon’s Syndrome
Anish Shah, Saurav Sen, Jennie Luna and Dipak P. Pandya;
Paterson, NJ
Background: Sneddon’s Syndrome is a rare progressive noninflammatory vasculopathic disease affecting small and medium size arteries in conjunction with ischemic cerebrovascular disease, possibly livedo reticularis in absence of well
recognizable connective tissue disease stigmata. It may associate with hepatitis C, thrombocytopenia and positive antiphospholipid antibodies. Seizures are rare during the course
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wild-type nerves (4 mice), and minimal in pmp22þ//
pak1/ nerves (2 mice). Pak1/ mice developed no
phenotype up to 22 month old. Taken together, ablation of
PAK1 activity partially suppresses tomaculous formation
and myelin leakage in the pmp22þ/ nerves. Reversal of
the tomaculous abnormality would improve the security of
action potential propagation.
Study supported by: NIH
a useful treatment option, particularly in cases of paraneoplastic seizures.
Study supported by: Study is a case report. There are no
sponsors or affilitations associated with it. No individual
associated with this case report (or their relatives) has a relevant financial interest relating to the support of the abstract.
M724. Withdrawn
M804. Zebrafish Models of Amyotrophic Lateral
Sclerosis
Stacey A. Sakowski, J. Simon Lunn, Angela S. Busta, Carey
Backus, Sang Su Oh, James J. Dowling and Eva L. Feldman;
Ann Arbor, MI
Neuromuscular Disease
M801. Nicotinamide Mononucleotide (NMN) Treatment
of Diabetic Neuropathy
Ankit Sura, Mitch Onken, Krish Chandrasekaran, Helen Chen
and James W. Russell; Baltimore, MD
Amyotrophic lateral sclerosis (ALS) involves the degeneration and loss of motor neurons (MNs). Zebrafish provide
and ideal system to investigate cellular mechanisms and
potential treatments for ALS onset and progression. Transient genetic manipulation of zebrafish to express mutant
forms of SOD1 associated with familial forms of ALS
results in early defects in MN outgrowth and axonal branching. Growth factor signaling, which activates neuroprotective
pathways, can be easily upregulated in zebrafish embryos
and rescues these early defects, validating the model for
therapeutic discovery. Stable transgenic zebrafish lines
expressing mutant SOD1 enable further characterization of
the consequences of ALS disease progression. Behavioral
monitoring reveals late onset muscle weakness and decreased
activity in transgenic ALS zebrafish with disease progression.
Examination of MNs and zebrafish morphology reveals a
loss of neuromuscular junctions and alterations in MN
innervations patterns with ALS progression. Finally, MN
cell loss is evident later in the course of disease. This
sequence of events provides insight into the mechanisms of
MN degeneration in transgenic ALS zebrafish, and validates
the zebrafish as a novel model for mechanistic discovery and
therapeutic development for ALS.
Study supported by: Study supported by the A. Alfred
Taubman Medical Research Institute and the Program for
Neurology Research & Discovery. SAS supported by the
NIH (T32 NS007222-28).
Nicotinamide adenine dinucleotide (NAD) is a critical
metabolite in energy metabolism and mitochondrial (Mt)
electron transfer. Nicotinamide mononucleotide (NMN) is a
direct substrate for generation of NAD. A decreased NAD
level in diabetes may increase the severity of diabetic neuropathy. We determined if NMN prevented the development of diabetic neuropathy. Adult rats were made diabetic
with streptozotocin. NMN was injected every second day.
There were 4 treatment groups: (1) non-diabetic control
with vehicle (2) diabetic (3) diabetic þ 50 mg/kg NMN (4)
diabetic þ 100 mg/kg NMN. The Von Frey monofilament
sensory withdrawal threshold was normalized in diabetic rats
treated with 50 mg/kg or 100 mg/kg NMN for a period of
2 months from the onset of diabetes (n ¼ 6 rats/group,
P<0.05 for 100 mg/kg NMN treated compared to diabetic
rats). NMN treatment also prevented sciatic motor conduction velocity slowing and diabetic loss of skin Intraepidermal nerve fibers in the hind-limb paw (P<0.01). Addition
of NMN to adult mouse DRG dissociated cultures also
reduced glucose-induced generation of reactive oxygen species (ROS). NMN effectively reduces the severity of experimental diabetic neuropathy and reduces generation of ROS.
Study supported by: Juvenile Diabetes Foundation,
Department of Veterans Affairs, NIH
M802. Withdrawn
M805. ALS-Like Spinal Cord Pathology in Transgenic
Mice with a Mutation in the Valosin-Containing Protein
Gene
Hong Z. Yin, Tahseen Mozaffar, Virginia E. Kimonis and
John H. Weiss; Irvine, CA
M803. Tomaculous Formation in HNPP
Jun Li, Zahara M. Jaffer, Xuebao Zhang, Qing Yan, Michael
E. Shy, Ueli Suter, Jonathan Chernoff and Jiasong Guo;
Nashville, TN; Philadelphia; Nashville; Detroit and Zurich,
Swaziland
Kimonis et al. identified a human genetic syndrome, Inclusion Body Myopathy associated with Paget’s disease of the
bone and frontotemporal dementia (IBMPFD), and subsequently found it to be associated with mutations in the
valosin-containing protein (VCP) gene (Watts, Nature
genetics 2004). A knock-in VCP mouse model of IBMPFD
(R155H) developed by this group exhibited muscle, bone
and brain pathology characteristic of the human disease,
including TDP-43 positive inclusions (Badadani, PLoS
One. 2010). Recent studies have extended the list of diseases
associated with VCP mutations to include ALS (Johnson,
Neuron 2010). We have thus undertaken studies of spinal
cord pathology in heterozygous R155H mice. Preliminary
examinations of 18–24 month old R155H mice show degenerative changes in ventral horn motor neurons (MNs),
and increased astrocyte activation. In addition, we find evidence for TDP-43 positive cytosolic inclusions in many
damaged MNs. These studies suggest that the R155H VCP
mouse may provide a valuable new animal model for ALS,
Heterozygous deletion of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP) with a pathological hallmark of tomacula. Because p21-activated kinase
(PAK1) regulates polarized membrane extension of cells, we
have tested a hypothesis whether the PAK1 plays a role in
the formation of tomacula. The pmp22þ/ mouse of
HNPP was crossbred with pak1 knockout mice (pak1/)
to generate double-knockouts. The sciatic nerves at the age
of one month were analyzed by teased nerve fiber study.
The percentages of paranodes with tomacula was 29 6
19% in pak1þ/þ/pmp22þ/ mice (n ¼ 6) vs 9 6 10% in
pak1//pmp22þ/ mice (n ¼ 8), which was statistically
significant (p<0.05). Moreover, we tested permeability of
tomaculous membrane by incubating sciatic nerves (total 10
mice) with a fluorescent dye (wt ¼ 332kd; Sigma). Fluorescence was visible in about a half of paranodal tomacula of
pmp22þ/ nerves (4 mice), but absent in all paranodes of
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which reproduces key aspects of human disease, including
the presence of MN cytosolic aaggregates, and pronounced
astrocytic as well as MN pathology.
Study supported by: NIH grant NS36548
M808. Novel Demonstration of ConformationallyModified Tau in Sporadic Inclusion-Body Myositis (sIBM) Muscle Fibers. Possible Importance to s-IBM
Pathogenesis
Anna Nogalska, Carla D’Agostino, King W. Engel and Valerie
Askanas; Los Angeles, CA
M806. Reevaluating Disease Progression in
Facioscapulohumeral Dystrophy
Jeffrey M. Statland*, William B. Martens, Kathryn R. Wagner,
John Kissel, Shree Pandya, Michael P. McDermott and Rabi
Tawil; Rochester, NY; Baltimore, MD and Columbus, OH
Molecular phenotype of s-IBM muscle fibers, the most
common myopathy of older persons, has similarities to Alzheimer-disease (AD) brain, including intra-muscle-fiber
accumulations of Ab42 and its oligomers, and large clusters
of paired-helical filaments (PHFs) immunoreactive with various antibodies recognizing phosphorylated tau (p-tau).
In AD brain, conformational changes of tau, including its
modifications detectable with specific antibodies TG3,
Alz50 and MC1, are early and important modifications
leading to tau’s abnormal folding and assembly into PHFs.
We have now identified conformationally modified tau (ctau) in 13 s-IBM muscle biopsies by a) light-and electronmicroscopic immunohistochemistry, b) immunoblots, and c)
dot-immunoblots, using TG3, Alz50 and MC1 antibodies.
Interestingly, in the very atrophic degenerating fibers, TG3
co-localized with PHF-1 antibody recognizing p-tau, considered a later change in the PHFs formation; however, most
of TG3-positive inclusions in non-atrophic fibers were
PHF-1 immunonegative. None of the 12 disease- and normal-control muscle biopsies contained c-tau or PHF-1 immunoreactive tau. This first demonstration of c-tau in sIBM suggests that, because of its abundance in non-atrophic
muscle fibers, c-tau might play an early role in s-IBM PHF
formation and thus be pathogenically important.
Study supported by: MDA
Background: Recent breakthroughs in the molecular pathophysiology of Facioscapulohumeral dystrophy (FSHD) have
identified potential therapeutic targets. Consequently, an
accurate understanding of disease progression in FSHD is
crucial for the design of future clinical trials.
Methods: Data from 164 subjects in 2 negative clinical
trials and 1 natural history study were combined to examine
disease progression in FSHD. All studies utilized the same
techniques for manual muscle testing (MMT) and quantitative myometry (QMT). Both techniques yield a total
strength score that can be followed over time as an indicator
of disease progression.
Results: Whereas, natural history data showed a statistically significant decrease in strength by both QMT and
MMT at 1 year, combined data from all 3 studies demonstrated a reduced estimate of loss of strength for both techniques at 1 year, which was no longer significant for QMT.
Comparing natural history to combined clinical trial data
suggested this reduced estimate of disease progression was
due to a placebo effect, most noticeable at 6 months.
Conclusions: Contrary to estimates based only on natural
history data, treatment durations of longer than 1 year will
be required to demonstrate arrest of disease progression in
future FSHD therapeutic trials.
M809. Anti-Ganglioside Antibodies Mimic CNS
Inhibitors of Axon Regeneration
Kazim Sheikh and Gang Zhang; Houston, TX
Anti-ganglioside antibodies (Abs) are strongly associated
with axonal forms of Guillain Barré syndrome (GBS). Several studies indicate that GBS patients with anti-ganglioside
Abs directed against GM1, GD1a, or ganglioside complexes
have poor prognosis and/or incomplete recovery. We
recently demonstrated that experimental monoclonal and
GBS patient derived anti-ganglioside Abs can inhibit regeneration of injured axons in an animal model suggesting that
Ab-mediated inhibition of nerve repair is one mechanism of
delayed recovery. We have now established motor and sensory primary neuronal culture models to examine the cellular and molecular mechanisms of this Ab-mediated inhibition of axon regeneration. We found that GBS patient’s
anti-ganglioside Abs can inhibit neurite outgrowth in primary neuronal cultures. This Ab-mediated inhibition of
neurite outgrowth involves the activation of small GTPase
RhoA and downstream effector ROCK pathway and this
activation is through the engagement of specific cell surface
gangliosides by Abs. In summary, these studies directly link
patient autoantibodies to an intracellular inhibitory signaling
pathway that is also central to inhibitory signaling induced
by almost all CNS inhibitors of axon regeneration. Our
results support the hypothesis that specific anti-ganglioside
Abs mimic intracellular signaling induced CNS inhibitors of
axon regeneration.
Study supported by: NIH/NINDS
M807. Dysferlin (DYSF) Is Absent from the
Muscle-Fiber Sarcolemma in Various Neuromuscular
Diseases, and in Sporadic Inclusion-Body Myositis
(s-IBM) It Forms Cytoplasmic Inclusions Colocalizing
with Amyloid-b42 (Ab42)
Mafalda Cacciottolo, Anna Nogalska, Carla D’Agostino,
W King Engel and Valerie Askanas; Los Angeles, CA
DYSF is a transmembrane protein participating in muscle
plasmalemma repair. In normal human biopsies, DYSF is
present at the muscle-fiber sarcolemma. In dysferlinopathies
– autosomal-recessive muscle diseases caused by mutations
in the DYSF gene – DYSF is immunohistochemically absent
from the sarcolemma, and is absent or prominently
decreased by immunoblots. Immunohistochemically-absent
DYSF at the sarcolemma is sometimes considered ‘‘diagnostic’’ of dysferlinopathies. However, sarcolemmal absence of
DYSF, and a cytoplasmic ‘‘neolocalization’’, was previously
reported in some sarcoglyconopathies and DMD patients.
We now report absence of DYSF at the sarcolemma of
virtually all muscle fibers of 4 ALS, 4 peripheral neuropathy,
5 s-IBM, and 1 polymyositis biopsies. In s-IBM, vacuolated,
very abnormal muscle fibers often had DYSF-immunoreactive cytoplasmic inclusions that colocalized with Ab42. Four
age-matched controls had normal sarcolemmal DYSF distribution. By immunoblots, DYSF levels were comparable in
all biopsies. Thus: a) immunolocalization of DYSF cannot
be a diagnostic criterion of dysferlinopathy; b) Ab42 might
be a novel binding partner of DYSF, and in that complex
DYSF might contribute to the s-IBM pathogenesis.
Study supported by: MDA
M810. Evaluating Mechanoreceptors in Glabrous Skin in
Diabetic Neuropathy
Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier;
Nashville, TN
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Meissner corpuscles (MCs) and their myelinated afferents
are found only in glabrous skin. We hypothesized that alterations in MCs occur in diabetic neuropathy and correlate
with other measures of axonal loss. Immunohistochemistry
was performed on 2 and 3 mm skin punches from the index
finger and distal leg, respectively. Four diabetic patients
(ages 45–75), with neuropathy confirmed by exam and
nerve conduction studies and four control patients (aged
35–50), were studied. Average Meissner corpuscle density
(MCD) in control patients was 15.3 6 7.1 MCs/ mm2
with significant reductions observed in two patients (3.3,
6.2 MCs/ mm2) with near normal or higher density in two
other patients (11.1, 28.1 MCs/mm2), suggestive of proliferation. MCs in diabetics often displayed abnormal morphology. Density of intrapapillary myelinated endings (IME)
correlated with MCD in all patients (r ¼ 0.97). Diabetic
patients’ intraepidermal nerve fiber density (IENFD) in the
distal leg was 4.2 6 5.9 fibers/mm, compared to 13.7 6
1.3 in controls. IME density did not correlate with IENFD,
suggesting that these populations of fibers are independently
affected by hyperglycemia. Glabrous skin biopsies afford
evaluation of mechanoreceptors which are important in
studying pathophysiology of diabetic neuropathy.
Study supported by: Supported by NINDS K23
NS056009 (A.C. P.), NINDS R01NS066927-01(J.L.), Vanderbilt CTSA grant 1 UL1 RR024975.
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ALS patients. Methods: Fifteen patients with definite or
probable ALS fulfilled the El Escorial revised criteria, and 15
age- and sex-matched controls underwent cervical cord 1HMRS. A volume of interest with dimensions of approximately
6.08.040.0 mm (19.2 mL) was located along the main
axis of C1-C3 cord on T2-weighted images. N-acetyl-aspartate (NAA), choline-containing compounds (Cho), creatine
plus phosphocreatine (Cr) and myo-Inositol (m-Ins) were
determined. ALS functional rating scale (FRS) and forced
vital capacity (FVC) were assessed monthly. Electromyography was performed. Results: NAA/Cr was decreased significantly (p<0.05) and m-Ins/Cr was increased significantly
(p<0.05) in ALS patients compared to controls. NAA/m-Ins
was associated with decline of FRS score and FVC, and electromyogram, including ongoing denervation and reduced
amplitudes of compound muscle action potential in the limb
muscles. Conclusion: Our data indicated significant changes
of NAA/Cr and m-Ins/Cr in the cervical cord. Significant
relationships were found between NAA/m-Ins, clinico-respiratory deterioration and axonal damages on electromyography.
Thus, cervical cord 1H-MRS could have benefits for a predictive marker of disease progression in ALS patients.
M813. Localization of FIG4 in the Nervous System
Jiasong Guo, Qing Yan and Jun Li; Nashville, TN
Recessive mutations of FIG4 cause CMT4J with a phenotype resemble amyotrophic lateral sclerosis. Localization of
FIG4 in the nervous system remains unknown. We have
investigated this issue in rats. FIG4 expression in the CNS
was robust embryonically by western blot but low in the
adulthood. Using immunohistochemistry at P7-20, FIG4
was localized in cortical/spinal neurons, but hardly detectable in astrocytes. By P30, FIG4 immunoreactivity declined
to a minimal level; however, was still conspicuous in the
myelin (oligodendrocytes and Schwann cells) and sensory
neurons of dorsal root ganglion. For the sub-cellular localization, FIG4 signals appeared to be partially overlapped
with late-endosomes/lysosomes, but not overlapped with mitochondria, Golgi complex, early endosome or endoplasmic
reticulum. Taken together, these findings are in line with
our recent study that has demonstrated prominent vacuolated endo-/lysosomes in the sensory neurons and abnormal
lysosomal storage in the spinal motor and cortical neurons
in FIG4 null mice (Katona et al, EJN 2011).
Study supported by: MDA and VA RR&D
M811. Amiodarone Associated Myopathy. A Report
of 4 Cases
Eoin P. Flanagan, Charles M. Harper, Erik K. St. Louis,
Michael H. Silber, Ronald C. Petersen and Keith A. Josephs;
Rochester, MN
Myopathy is a known side effect of amiodarone. However,
the characteristic features and outcome are not widely
known. We identified 4 patients from 1996 – 2010 at our
institution with electrophysiologically confirmed myopathy
and a final diagnosis of presumed amiodarone induced myopathy. The median age was 71 years (range, 67–75) and all
had an insidious onset. Initial presenting symptoms
included: lower extremity weakness, 3; and swallowing difficulty, 1. Amiodarone was begun a median time of 20.5
months (range, 1–36) before symptom onset. Laboratory
features included elevations in: creatine kinase, 2; myoglobin, 2; and aldolase, 1. EMG demonstrated short duration
motor unit potentials in proximal muscles in all four
patients and features of myonecrosis were seen in two. Muscle biopsies performed in two patients demonstrated severe
necrotic myopathy with tubular aggregates in one and
vacuolated atrophic fibers in the other. All 3 patients with
follow up available improved after discontinuation of amiodarone, but in two the recovery was prolonged (>6 months)
and incomplete. Amiodarone induced myopathy appears to
affect mostly proximal muscles with variable electrophysiological and pathological findings. Discontinuation of amiodarone is associated with improvement, but recovery may be
prolonged and incomplete.
M814. High Frequency Chest Wall Oscillation
(HFCWO) in Amyotrophic Lateral Sclerosis (ALS)
Patients Decreases Respiratory Infections Requiring
Antibiotics and/or Hospitalization: A Pre-Post
Observational Study
Benjamin R. Brooks, Velma L. Langford, Amber L. Ward,
Nicole M. Williams, Mindy S. Nichols, Elena Bravver and
Scott C. Lindblom; Charlotte, NC
Background: Respiratory care in ALS patients with increasing restricted pulmonary function requires attention to
clearing pulmonary secretions. Lange, et al., 2006 demonstrated respiratory function improvement but did not show
an effect of HFCWO on infection rate.
Objective: To evaluate in an ALS Clinic setting whether
there is a decrease in the prevalence of infections requiring
antibiotics and/or hospitalization following HFCWO.
Methods: The prevalence of infections was calculated retrospectively for the period from ALS diagnosis to and prospectively from the point of initiating HFCWO in ALS
patients based on vital capacity and clinical respiratory
M812. Cervical Cord 1H-Magnetic Resonance
Spectroscopy (1H-MRS) in Amyotrophic Lateral Sclerosis
(ALS): Relationship to Clinoco- Electrophysiological
Dysfunction
Ken Ikeda, Yasuhiro Yoshii, Kiyoko Murata, Riya Nagata,
Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo,
Japan
Background: To examine whether clinico-electrophysiological
aspects are related to spinal cord dysfunction on 1H-MRS in
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parameters. Mean infection rate 6 standard deviation(SD)before and after HFCWO was compared with paired, unpaired two-tailed t-tests and Wilcoxan rank tests.
Results: ALS patients[36]patients pre-HFCWO had 0.07
6 0.13(SD)infections/month which reduced to 0.02 6
0.06 infections/[t test p ¼ 0.0638; Wilcoxon ranked test p
¼ 0.0415]. Compliance in each patient compared well with
the mean national compliance assessed by Hill-Rom in neuromuscular disease.
Conclusion: HFCWO significantly reduces the perpatient infection rate in ALS patients. Observational studies
employing pre-post-intervention design can provide important clinically meaningful information supporting certain respiratory interventions in ALS patients.
Study supported by: Carolinas ALS Research Fund of the
Carolinas Healthcare Foundation and Hill-Rom
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weekly, continuing for 6 yrs, arrested progression and sustained partially-improved strength, breathing and swallowing. In 3/10, added rituximab, 375mg/m2 q2wksx4 loading,
plus q12-6wks maintenance, produced further increased
strength, regained ability to walk independently 150ft, climb
stairs, turn in bed, shower standing, and drive a car. This
benefit from the continuing IVIG-plus-rituximab therapy
emphasizes treatability of the AORMS and suggests a dysimmune pathogenesis. His concurrent CIDP-like aspect
may be relevant to his beneficial response. (Interestingly,
experimentally, tenotomy can produce rods (Engel et al,
‘66).)
M817. Geographic Trends of ALS in Minnesota
Eric J. Sorenson and Lisa Kronk; Rochester, MN and
Minneapolis, MN
Background: This study examined geographic trends of
ALS across Minnesota and assessed the completeness of ALS
case ascertainment within the ALS association’s database
(Minnesota/North Dakota chapter).
Methods: The ALS association’s database was queried for
deaths during 2009 in Minnesota with the county of residence recorded for each. 2009 census data was recorded for
each Minnesota county with an incidence rate calculated for
each county and for Minnesota overall. A chi-squared analysis compared incidence rates among the 88 counties.
Results: 97 deaths occurred from a population of
5,266,203, giving an incident rate of 1.8 cases per 100,000
person-years (95% CI from 1.5 to 2.2). This agreed with
incidence rates from Olmsted County of 1.7 per 100,000
person-years suggesting that the ALS Association’s database
has near complete case ascertainment throughout Minnesota. County incidence rates varied from 0 to 12.7 per
100,000 person-years. However, comparison across counties
failed to demonstrate any significant differences (p ¼ 0.42).
Conclusions: No significant geographic trends were identified among the counties in Minnesota suggesting the clustering of cases in some counties is likely due to random case
aggregation. The ALS association’s database proved effective
at near complete case ascertainment in the state of
Minnesota.
Study supported by: ALS Association
M815. Dominant Cardiomyopathy and Very Distal
Myopathy with Rod, Myofibrillar and AVSF
Myopathology
Stanley J. Iyadurai, Chris Weihl, Bob Baloh and Alan
Pestronk; St. Louis, MO
We describe a multigenerational family with a distal myopathy with unusual features. The syndrome segregated by history as a dominantly-inherited disorder with affected family
members of both sexes. Four affected patients without cardiac pacing died before age 40. Two affected patients with
cardiac pacing were examined in their fifth decade. Symmetric weakness was most severe in intrinsic muscles of the
hands and feet, averaging less than 10% of normal. Intrinsic
muscles of the hands and feet were severely atrophic. Proximal muscle strength was normal. Tendon reflexes and sensation were normal. Serum CK was less than 250. EMG
revealed a distal-predominant, irritable myopathy. Nerve
conduction studies were normal. Muscle ultrasound showed
a distal myopathy involving the hands and legs. Muscle biopsy showed varied fiber size, splitting, rods, desmin aggregates, and vacuoles containing granular debris with rims
staining for sarcolemmal proteins, including dystrophin, sarcoglycans and caveolin. Distinctive features include very distal weakness and wasting, early sudden death, and myopathology with rods, myofibrillar changes in addition to
AVSFs. Genotyping will be required to further define the
identity of this distal myopathy syndrome.
Study supported by: Department of Neurology and Psychiatry, Saint Louis University, St. Louis, MO.
M818. Clinical Features Associated with Fine Specificity
of IgG Anti-GQ1b Antibodies
Susumu Kusunoki, Seiko Suzuki, Masami Ueda and Motoi
Kuwahara; Osaka-Sayama, Osaka, Japan
M816. Adult-Onset Rod Myopathy Syndrome
(AORMS): Sustained Benefit from IVIG Plus Rituximab
Shalini Mahajan, King W. Engel, Valerie Askanas,
Indermohan Luthra and Varun Gupta; Los Angeles, CA and
Rancho Mirage, CA
Anti-GQ1b IgG antibodies are present in most cases of
Fisher syndrome (FS), Bickerstaff brainstem encephalitis
(BBE), and Guillain-Barré syndrome (GBS) with ophthalmoplegia. Anti-GQ1b antibodies frequently bind to GT1a,
but the relative binding activities with the GQ1b and GT1a
antigens vary. Some anti-GQ1b antibodies have higher activity against a mixture of GQ1b and phosphatidic acid
(GQ1b/PA). We investigated anti-GQ1b IgG-positive cases
including FS (n ¼ 197), BBE (n ¼ 20), GBS (n ¼ 78) and
atypical FS (n ¼ 52) to see whether diversity in the fine
specificity of IgG anti-GQ1b antibodies is related with variations in clinical features. Higher antibody activity with
GQ1b compared to GT1a (GQ1b>GT1a) was significantly
more frequent in BBE and FS than in GBS (p<0.01), and
higher antibody activity with GQ1b compared to GQ1b/PA
(GQ1b>GQ1b/PA) was significantly more frequent in BBE
than in FS (p<0.01). A significantly higher anti-GT1a antibody titer and rate of GT1a>GQ1b were found in patients
with bulbar palsy (p<0.01). The anti-GQ1b/PA antibody
AORMS (Engel WK,’66), is a rare, progressive, myopathy
associated with intrafiber rods, often monoclonal gammopathy (MG), 6 dysschwannian neuropathy, and often fatal.
Patients were unresponsive to anti-dysimmune therapies,
including rituximab (Keller CE,’06). We report successful
treatment of a 55yr old AORMS patient. Before treatment,
he had for 1yr, sub-acute, progressively severe proximal limb
and neck weakness, and dysphagia. Tendon reflexes were
absent, vibratory and pinprick sensations decreased. Serum:
IgG-kappa MG, normal CK. CSF: protein elevated, 59/45.
NCVs: dyschwannian (demyelinating) neuropathy. EMG:
fibrillations and brief small abundant motor-units. Muscle
biopsy: groups of trichrome-red intrafiber rods, and a few
small angular fibers. Rx: IVIG, 0.4 gm/kg infusions twice-
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titer was significantly higher in patients with ophthalmoplegia (p<0.01) and in those with ataxia (p<0.01). Thus, the
fine specificity of IgG anti-GQ1b antibodies may be associated with clinical features in each patient.
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screening (including Sjogren’s and anti-ganglioside antibodies) was uninformative. Electrophysiology revealed motor
neuronopathy involving 3–4 body segments and sensory
neuropathy. Blink reflexes in four and autonomic testing in
two were abnormal. In 3 patients, nerve biopsies showed
non-specific axonal degeneration/regeneration. Four patients
failed immunotherapy. One autopsy examination revealed
loss of spinal motor neurons.
This disorder, distinct from sporadic bulbar-onset ALS
resembles FOSMN, but with dementia and/or chorea. We
are applying new genomics tools to study this unique
patient group.
Study supported by: National Institues of Health (NIH)Intramural Program
M819. Amyotrophic Lateral Sclerosis [ALS] Dashboard:
Cognitive, Behavioral, Bulbar, Respiratory, Arm, Leg
Domain-Specific Disease Staging – Statistically
Significant Larger Proportion of Stage 3 Behavioral,
Bulbar, Arm and Leg, but Not Cognitive or Re
Benjamin R. Brooks, Mohammed S. Sanjak, Elena Bravver,
William L. Bockenek, Urvi G. Desai, Scott C. Lindblom,
Thomas J. Paccico, Nicole M. Williams, Mindy S. Nichols,
Amber L. Ward, Kathryn A. Wright, Mifflin O’Neill, Velma
L. Langford, Kristy Walgren, Priscilla Russo, Anne Blythe and
Heather Oplinger; Charlotte, NC
M821. Update on a Phase 1 Study of ISIS 333611 in
Familial ALS Due to SOD1 Mutations
Timothy M. Miller, Richard Smith, Swati Aggarwal, Alan
Pestronk, William David, Jeffrey Rothstein, Ericka Simpson,
Benjamin Brooks, Isaac Bakst, Patricia Andres, Peggy Allred,
Katie Alexander, Kathie Bishop, C.F. Bennett and Merit
Cudkowicz; St. Louis, MO; La Jolla, CA; Boston, MA;
Baltimore, MD; Houston, TX; Charlotte, NC and
Carlsbad, CA
Background: ALS Dashboard is a new tool for analyzing
disease severity within a single patient and across different
patients defining involvement over 6 domains on a per
patient basis.
Methods: ALS patients [199/263] at first clinic visit were
categorized as El Escorial Criteria clinically definite (EECD)
only [90] or Awaji clinically definite only (AwCD) [109]
and staged according to the ALS Dashboard criteria. Comparisons of stage 3 disease in each domain by EECD/
AwCD criteria were conducted by chi-square test with Yates
correction and confirmed with Fisher’s exact test.
Results: At first clinic visit in EECD/AwCD ALS stage
3 cognitive disease was similar [8.9%/13.8%; p ¼ 0.3968],
stage 3 pseudobulbar affect [11.1%/2.8%; p ¼ 0.0369],
stage 3 depression [25.6%/10.0%; p ¼ 0.0070], stage 3
bulbar dysfunction [45.6%/13.8%; p ¼ 0.0001], stage 3
arm dysfunction [35.6%/8.3%; p ¼ 0.0001], stage 3 leg
dysfunction [55.6%/33.9%; p ¼ 0.0036]were statistically
significantly increased and stage 3 respiratory dysfunction
was identical [7.8%/4.6%; p ¼ 0.5209].
Conclusions: Disease severity in some domains, segregates differently with a higher proportion of stage 3 disease in EECD ALS. The proportion of stage 3 disease
ranks similarly: leg >arm >bulbar >depression
>pseudobulbar affect.
Study supported by: Carolinas ALS Research Fund of the
Carolinas Healthcare Foundation
Objective: To evaluate the safety, tolerability, and pharmacokinetics of intrathecal infusion of ISIS 333611, an antisense oligonucleotide inhibitor of SOD1 mRNA.
Background/Methods: Mutations in SOD1 cause 20%
of familial ALS. In animal models, ISIS 333611 distributed widely in the brain and spinal cord, decreased
SOD1 mRNA, and prolonged survival. A randomized,
placebo controlled Phase 1 safety trial of ISIS 333611 is
underway. In Cohort 1, ISIS 333611 (0.15 mg) was
infused intrathecally over 12 hours in 6 SOD1-positive
ALS patients (2 patients received vehicle control). Safety
measures and neurological exams were assessed during the
infusion and after 1, 8 and 29 days. CSF and plasma
drug levels were measured. This completes 1 of 4
cohorts, each with increasing dose and similar active:placebo ratio.
Results: No serious adverse events occurred and common
adverse events are consistent with procedure-related findings.
Changes in neurological exams are consistent with ALS.
CSF and plasma drug levels are consistent with levels predicted from preclinical studies. An update on the SOD1
antisense program will be provided.
Conclusion: In Cohort 1, ISIS 333611 was well tolerated
and CSF drug levels are as predicted.
Study supported by: ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals
M820. A New Phenotype in Neurodegeneration:
Trigeminal Sensory Deficits Preceding Rostro-Caudal
Progressive Motor and Sensory Neuronopathy, Chorea
and Dementia
Camilo Toro, Justin Y. Kwan, Tanya J. Lehky, Bryan J.
Traynor, Catherine A. Groden, Rena A. Godfrey, Michele E.
Nehrebecky, Wiggs A. Edythe and Gahl William; Bethesda,
MD
M822. Retrospective Analysis of a Cohort of Non
Systemic Vasculitic Neuropathy
Raghav Govindarajan, Jagadish B. Agadi, Anita Mahadevan
and S.K. Shankar; Weston, FL and Bangalore, India
We describe five adults with a slowly progressive bulbaronset ALS like phenotype but preceded by trigeminal sensory symptoms, with or without late development of chorea
and dementia. Age of onset was 53–69 years; disease duration was 5–12 years.
Three women and two men experienced facial/oral sensory disturbance involving the unilateral infra-orbital area
(3), tongue, or lips 6–18 months before bulbar motor deficits. At evaluation, all had impaired cornea reflexes, facial/
oral hypoesthesia or anesthesia extending to posterior scalp
plus truncal and shoulder weakness, while lower limb
strength was relatively preserved. Three patients had frontotemporal dysfunction and two had chorea. Neuroimaging,
CSF examinations, metabolic, toxic and immunological
Background: Nonsystemic vasculitic neuropathy (NSVN) is
an infrequent neuropathy without systemic manifestations.
Only few studies have reported the clinicopathologic spectrum. Fewer have looked into the treatment aspects.
Methods: Nerve biopsies done over 10 years were
reviewed. Patients who met criteria for NSVN at time of diagnosis and in whom 6 month follow-up was available were
included. They were treated with steroid therapy (ST) or
with steroids and azathioprine-combination therapy (CT).
Independent T-tests were performed for age, duration of
symptoms prior to therapy and improvement in Prineas
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disability score (PDS) between groups. Differences between
pre and post-therapy PDS within groups were analyzed by
paired T-tests and Chi-Square.
Results: 21 cases were in the series with 12 males and 9
females.Sensori-motor asymmetric axonopathy was seen in
71%. Biopsy showed microvasculitis in 52%. 12 were
treated with ST, 7 with CT,2 opted out. CT was superior in
improving disability (1.57 vs. 1.08 p < 0.05). CT was 14
times more likely to improve PDS by more >2 units (p ¼
0.01). The percentage of improvement did not significantly
differ between them (paired T-test 50% vs.42% p ¼ 0.37).
Conclusion: NSVN is an asymmetric sensory predominant axonopathy. Combination therapy may be superior to
steroids alone in improving disability.
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gene protein level from ALS muscles showed no obvious
difference compared to controls.
Conclusions: The up-regulation of the above genes in
the muscles of ALS patients relative to MMN and controls
discovered previously by our microarray analysis is reproducible and statistically significant. Further studies are necessary to evaluate the identified genes in larger patient
groups and different tissues.
Study supported by: This work was supported by grants
from the Muscular Dystrophy Association and the Horace
Havemeyer Neuromuscular Research Fund.
M825. Small-Fiber Polyneuropathy (SFPN) Can Cause
Chronic Pain and Somatic Complaints in Youth
and Anne Louise Oaklander; Boston, MA
M823. Optimizing a Hospital Discharge Database for
Passive Surveillance of Guillain-Barre Syndrome (GBS)
Christopher D. Lee and Timothy F. Jones; Nashville, TN
Patients with unexplained diffuse pain and multisomatic
complaints are enigmatic and hard to treat, with pediatric
cases especially concerning. An index youth with chronic
pain from steroid-responsive SFPN prompted record analysis from 41 consecutive young patients with widespread
pain and/or multisomatic complaints; age-matched volunteers provided controls. Age of onset averaged 13y; 73%
were female. Most were seriously ill; 71% were hospitalized
and 1 died. Half reported preceding injuries or infections.
29% had other autoimmune illnesses. 98% had chronic
pain and 98% had somatic symptoms, often cardiovascular
and/or gastrointestinal. Abnormal fatigue, headaches, and
sweating each affected more than half. Sensory abnormalities were present in 71% and erythromelalgia in 28%.
94% of 33 autonomic-function tests were abnormal, 6%
borderline, and most skin (25) and 2/2 nerve biopsies
implicated SFPN. Etiologic testing spotlighted only
immune markers (in 86%). Many symptoms became manageable once explained as neuropathic. Corticosteroids or
IVIG helped 70% of 14 treated. This characterizes a disabling illness, juvenile-onset SFPN, sometimes caused by
organ-specific autoimmunity. This verifiable and treatable
diagnosis merits consideration in youngsters with syndromes of widespread pain and multisystem complaints, eg
fibromyalgia, chronic fatigue, POTS, and seronegative
Lyme.
Study supported by: NINDS, Dept. of Defense, Bradley
family foundation, Curvey family foundation
The 2009–2010 H1N1 pandemic influenza immunization
program prompted a nationwide active surveillance effort to
determine the risk of GBS following vaccination. Active surveillance is unsustainable in the long-term. Therefore, we
sought to optimize a statewide hospital discharge database
to evaluate its utility for GBS surveillance, compared to
active surveillance data.
We examined data from all patients discharged from Tennessee hospitals with an ICD-9 code for GBS, from 2000–
2010. A total of 2659 cases with Tennessee residency were
identified. Of these, 1098 (41%) were excluded due to a
prior hospitalization with a GBS diagnosis in the database.
Annual incident cases ranged from 143 to 161 (mean
adjusted incidence calculated as 1.41 per 100,000 individuals). Variation in annual case tallies was significantly narrowed with this method, compared to aggregate ICD-9
totals. We calculate capability of detecting an increase in
GBS cases with an effect size of 1.20. Sensitivity compared
to active surveillance was 0.81. Positive predictive value was
0.45.
Although incidence calculations are overestimated, an
optimized hospital discharge database shows low variation
and is capable of detecting small increases in GBS cases.
Such a database can be useful for long-term surveillance.
M824. Gene Expression Analysis in Patients with
Amyotrophic Lateral Sclerosis and Multifocal Motor
Neuropathy
Alexander Shtilbans, Soon Gang Choi, Mary E. Fowkes, Greg
Khitrov, Mona Shahbazi, Jess Ting, Stuart C. Sealfon and
Dale J. Lange; New York, NY
M826. Median Nerve Ultrasound in Diabetic PN with
and without Carpal Tunnel Syndrome
Anhar Hassan, Andrea Leep Hunderford, James Watson,
Andrea Boon and Eric Sorenson; Rochester, MN
Background: Gold standard diagnosis for carpal tunnel syndrome (CTS) is nerve conduction study (NCS). However
sensitivity decreases in peripheral neuropathy (PN). Ultrasound detects median nerve enlargement but its utility in
coexistent PN is unknown.
Methods: Case-control study enrolling diabetic PN
patients (NCS-proven) referred to our EMG lab, with or
without clinical symptoms of CTS. Demographics, CTS
symptom score, median and ulnar NCS are recorded and
correlated with blinded median and ulnar nerve ultrasound
cross-sectional areas (CSA).
Results: Full data to be presented. Six patients (100%
male; 2 cases, 4 controls) are enrolled so far: age 50.5 years
(range 35–68), with diabetes duration 106.5 months (10–
300) and PN 13.5 months (0–93). Median nerve CSA was
significantly larger (p ¼ 0.03) in CTS cases, and median
antidromic sensory distal latency was significantly prolonged
(p ¼ 0.04). There was no significant difference in diabetes
Objectives: To confirm the previously identified gene
expression pattern in muscles from patients with Amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy
(MMN) compared to controls.
Methods: RNA extracted from skeletal muscles of 3-ALS,
3-MMN and 3-control patients were subjected to RT-PCR
confirmation analysis based on the previously published genome-wide microarray gene expression data (Shtilbans et al,
Ann Neurol.,2009). Four additional ALS patients and four
new controls were also used.
Results: Validation analysis of the most significant expression pattern differences confirmed our previous microarray
data for leucine-rich repeat kinase-2 (LRRK-2), follistatin,
collagen type XIX alpha-1, ceramide kinase-like and sestrin3 which were overexpressed only in the ALS group.
CXorf64 was increased in ALS and decreased in MMN
compared to controls. Western blot analysis of LRRK-2
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(p ¼ 0.13) or PN duration (p ¼ 0.16); neurophysiologic
PN severity (p ¼ 0.18); median motor (p ¼ 0.14) or sensory palmar NCS (p ¼ 0.05).
Conclusions: In diabetic patients with peripheral neuropathy, median nerve CSA appears significantly enlarged with
coexistent clinical CTS. If findings are confirmed, median
nerve ultrasound may be a useful addition to NCS.
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Conclusion: In our study there were no significant benefits to MRN over EMG in radiculopathy diagnosis.
M829. Denervation Causes Lower Expression of Heat
Shock Protein 27 in Regenerating Skeletal Muscle
Takahiro Jimi, Yoshihiro Wakayama and Hajime Hara;
Yokohama, Japan
We have studied changes of gene expression in denervated
skeletal muscles and found a remarkably increased expression of genes relating to quality control. Denervation results
in the incomplete regeneration of skeletal muscles. So we
examined the mRNA expression of heat shock protein 27
(HSP 27) in regenerating rat muscles in innervated and denervated conditions. We made rat regenerating muscles by
injection of bupivacaine in both extensor digitorum longus
(EDL) muscles. At the same time of injection, right sciatic
nerve was removed. At 1, 2, 4, and 6 weeks after surgery,
both EDL muscles were excised from five rats. The concentrations of HSP 27 mRNA were estimated by real-time
PCR analysis. The mRNA level in the innervated condition
was rapidly increased (ten times) at 1 week after surgery,
and gradually decreased to the original level, whereas the
increase in the denervated condition was mild (four times)
and delayed (at two weeks). Thus, we speculated that denervation causes some effects on the regeneration of skeletal
muscles, and the lower expression of proteins relating to
quality control may be involved in the incomplete regeneration under denervation of skeletal muscle.
M827. Subacute Paraneoplastic Motor Neuronopathy
with Ri Immunoeactivity and Breast Cancer: A
Clinicopathologically Studied Patient
and David S. Younger; New York, NY
A 49 year old woman had fatigue, cramps, and leg twitching in February 2010, four months before noting a breast
mass. Lumpectomy in June 2010 showed stage II invasive
ductal breast cancer, and estrogen and progesterone receptor positivity. Examination showed leg weakness, atrophy,
and widespread twitching. Initial EMG/NCS showed
motor predominant polyneuropathy of the legs with
demyelinating features and persistent fasciculation. MRI of
the brain, spinal cord, and cerebrospinal fluid showed no
evidence of metastases. Blood studies showed positive
ANNA-2 (Ri) titer 1:7680 from an extensive panel of paraneoplatic autoantibodies. Intravenous immunoglobulin
(IVIg) was followed by combination chemotherapy. Followup EMG/NCS showed persistent motor polyneuropathy and fascicuation with resolution of demyelinating features. Prophylactic radiotherapy was well tolerated. She
continued to decline whereupon followup EMG/NCS in
February 2011showed motor neuropathy with active leg fibrillation and fasciculation. Sural nerve and soleus muscle
biopsy were consistent with subacute motor neuronopathy.
CSF evidenced Ri immunoreactivity using purified human
recombinant antigen and Western blot analysis. Whole
body PET/CT showed no evidence of malignancy. This is
the first report of subacute motor neuronopathy in association with the Ri (ANNA-2) antibody.
M830. Rapid Magnetic Stimulation Versus Conventional
Physiotherapy in Bell’s Palsy
Devathasan Gobinathan and Lea Dosado; Singapore,
Singapore
We compared the use of rapid magnetic stimulation (RMS)
therapy in 23 subjects with 22 others who elected conventional electrical, muscle stimulation (CS) treatment and acupuncture. All patients had acyclovir for 7 days with varying
dose of steroids. After one year the parameters assessed were
the strength of frontalis, orbicularis oculis, zygomaticus,
orbicularis oris and for autonomic dysfunction–score 2
being normal, 1 partial recovery and 0 no recovery or distressing. Patients did their own scoring.
RMS was administered in 1 or 2 sessions ten times or
days during the acute phase at 15Hz, 1500 pulses, 5 second
pause, 50 in each of 30 trains at strength of 30 to 35A/us.
Stimulation sites were at the mastoid and more distally at
the facial area over the affected muscles away from the eye
globe.
Significant difference was noted in favor of RMS ( p <
0.004, t ¼ 7.1, df ¼ 21 mean score RMS ¼ 9.9 and CS ¼
6.0).
High dose steroids may have introduced a bias element
in favor of the RMS group as they received much less
steroids.
Study supported by: NIL
M828. Magnetic Resonance Neurography Versus
Electromyography for the Diagnosis of Radigulopathy
Youssef A. Dakka, Andrew Biondo, John Corrigan, Shehanaz
Ellik and Ximena Arcilla-Londono; Detroit, MI
Introduction: Evaluation of spinal nerve disorders relies on
an accurate history, examination, MRI, MR Neurography
and EMG/NCS. The purpose of our study was (a) to determine if MRN could detect radiculopathies earlier than
EMG.
Methods: Inclusion criteria included adults with cervical
radiculopathy, MRN and EMG studies. Exclusion criteria
included peripheral neuropathy, muscle disease, diabetes or
tumor. Of the 438 patients reviewed, 64 patients were
included. Symptoms, time course, MRN/EMG findings and
consistency of MRN/EMG results with clinical findings
were obtained retrospectively. The patient population was
subdivided into males/females and symptom duration < or
> 2 months. McNemars test and Generalized Estimating
Equation Model were used. Interaction was evaluated at the
significance level of 0.10.
Results: Differences in agreement between MRN and
EMG were 23.5% for females and 6.7% for males. For
those with <2 months duration, the difference in agreement
between MRN and EMG was 4.7% while for those with >
2 months duration, it was 20.9%. However, because of the
small sample size, the power to detect these differences was
reduced and they were not statistically significant.
M831. Establishing a Rare Disease Center in China: The
Periodic Paralysis Program
Qing Ke, Benyan Luo, Ming Ming, Michael Hanna, Jacob
Levitt, Barbara Herr and Robert C. Griggs; Hang Zhou, Zhe
Jiang, China; Rochester, NY; London, United Kingdom and
New York, NY
Objective: To establish a rare disease referral center in China.
Methods: Analyze ways periodic paralysis (PP) patients
reached Chinese centers and compare this process with US
and UK approaches.
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Results: 116 patients were evaluated with PP in two center (Beijing and Hangzhou) from 2003–2009. Only 20%
patients were local, the remaining patients traveled distances
without referrals from other areas. The deciding factor in
seeking care largely depended on patients’ choice. In contrast, at University of Rochester Medical Center, over 90%
of patients are referred from physicians throughout the
country by virtue of published information concerning physician expertise or on the basis of referrals from a patient
advocacy group. In UK, a single center, supported by the
National Health Service, provides assessment and genetic
testing for all patients in the country.
Conclusions: Currently, PP patients in China are practising self-referral to a larger center for medical care. Most of
them are evaluated in brief outpatient visits. With the rapid
development of computer access and expertise coupled with
a website locating one or more centers, patients in the country will be able to identify specific specialty centers.
Study supported by: NIH F05NS065682
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signal alteration in left mid anterior spinal cord from C 3C7. Electrodiagnostic testing revealed normal nerve conduction studies. EMG showed positive sharp waves, fibrillation
potentials and motor unit action potentials of increased amplitude and duration with reduced recruitment in almost all
of the muscles in left upper extremity.
Monomelic amyotrophy is a rare disorder presenting with
atrophy and weakness restricted to one limb. The benign
nature of Monomelic amyotrophy helps distinguish it from
other lower motor neuron disorders like ALS.
M834. Botulism: A Case Report
Peter Struck, Amtul Farheen and Sushanth Bhat; New
Brunswick and Edison, NJ
A 3 month old boy presented with 15 days of constipation
and 5 days of progressive generalized weakness. Parents
noted weak cry, poor appetite, lethargy, and generalized
muscle weakness. No respiratory or ocular symptoms were
reported. No history of sick contacts. The baby was full
term, born by c-section but otherwise healthy. On examination facial weakness, weak gag,head lag and diffuse hypotonia were noted. There were no focal motor deficits. Deep
tendon reflexes were 1 in bilateral upper extremities and 2þ
in lower extremities. Babinski was positive bilaterally. Blood
tests including CBC, CMP, UA, Newborn Screen were normal. Motor nerve conduction studies revealed normal conduction velocity, slightly decreased amplitudes. RNS of right
median nerve at 3 Hz showed 9 % decrement and at 20 Hz
showed 30 % increment. EMG showed fibrillations at rest,
short duration low amplitude MUAPs. Stool revealed botulinum toxin. Baby was diagnosed to have botulism and was
treated with Baby Botulism Immunoglobulin. After treatment patient was noted to have a stronger cry, improved
appetite and improved weakness.
The diagnosis of botulism should be considered in infants
and children with hypotonia. The detection of toxin in the
stool and EMG are diagnostic.
M832. Effect of Fatigue on Pulmonary Function Studies
in ALS Patients
Kathleen S. Alfuth, Ericka P. Simpson and Aparajitha K.
Verma; Houston, TX
Objective: To measure change in pulmonary function tests
(PFTs) as relates to time of day and fatigue in ALS patients.
Methods: Cross-sectional cohort study evaluating %
change in PFTs from early to late-day and correlation with
fatigue severity scale (FSS), disability (ALSFRS-r), bulbar
compromise (ALSFRS-r bulbar subscale). PFT measures
include forced vital capacity (FVC), maximal inspiratory
pressure (MIP), maximal expiratory pressure (MEP) at times
T1 and T2 (5–9hrs after T1) in sitting and supine positions.
Results: Eight patients were recruited [age 56.9 6 7.9
yrs, 75% female, 25% bulbar onset, FSS 42.3 6 14.7,
ALSFRS 35.5 6 8.1, ALSFRS-r bulbar 12.8 6 1.7]. Highest of three recorded attempts were used to calculate average
change between T1 and T2. FVCsitting -13% 6 27%; FVCsupine -13% 6 28%; MIPsitting þ7% 6 14%; MIPsupine -9%
6 20%; MEPsitting -3 6 17%; MEPsupine þ7% 6 29%.
Correlation analysis showed a trend association with increasing fatigue (FSS) and decrease in MIPsupine (p ¼ 0.13).
Conclusion: Preliminary data suggests PFTs in ALS may
significantly change from early to late-day and this may correlate with fatigue. This study is ongoing to determine significance of the results and possible impact upon
management.
Study supported by: Methodist Neurological Institute
Employment
M835. A Novel Pentameric Thiophene Derivative (pFTAA) Strongly Highlights Clusters of Paired Helical
Filaments Containing Phosphorylated Tau in Sporadic
Inclusion-Body Myositis (s-IBM) Muscle Fibers
There´se Klingstedt, Anna Nogalska, Cristiane Blechschmidt,
Stefan Prokop, Frank L. Heppner, King W. Engel, Valerie
Askanas and Peter K.R. Nilsson; Linko¨ping, Sweden; Los
Angeles and Berlin, Germany
p-FTAA is a fluorescent amyloid-specific ligand that can be
used for the detection of protein aggregates in vivo as well
as pre-fibrillar and fibrillar species in vitro. The probe spectrally discriminate amyloid-beta (Ab) plaques and phosphorylated tau (p-tau)-containing neurofibrillary tangles in Alzheimer’s disease (AD) brain.
Muscle biopsies of s-IBM, the most common muscle disease of older persons, have several pathologic similarities
with the AD brain, including intra-muscle fiber accumulations of Ab and p-tau-containing clusters of paired helical
filaments (PHFs). We now report that in all 6 s-IBM muscle biopsies studied, fluorescence evaluation of p-FTAA
staining, using excitation 450–490 nm and emission 520
nm, revealed a strong and specific signal from inclusions
positive with AT100 antibody recognizing p-tau and p62
antibody indicating clusters of PHFs. All 12 normal and
disease-control muscle biopsies were negative.
Our study demonstrates a novel staining method for
detection of p-tau inclusions in s-IBM muscle fibers. The
quick staining protocol together with the high signal-to-
M833. Monomelic Amyotrophy – A Rare Case
Presentation
Amtul Farheen, Manpreet Multani, Aiesha Ahmed, Raji
Grewal and Raji Grewal; Edison, NJ
A 26 year-old right handed Indian man presented with
weakness and atrophy of the left upper extremity over seven
years. He denied pain, numbness, diplopia, dysphagia, ptosis, muscle cramps, fasciculations and neck pain. There was
no history of febrile illness, poliomyelitis, and exposure to
toxins or heavy metals. On examination there was atrophy
of entire left upper extremity and weakness (power of 4/5)
of left deltoid, biceps, triceps, and wrist flexion and extension, and hand muscles. Motor exam was normal in other
extremities. Sensation and cranialnerve examination were
normal. Serum electrolytes, thyroid panel, ESR, CPK, HIV
were normal. MRI of C-spine showed vertically oriented
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noise ratio makes this probe an excellent tool for the diagnosis of s-IBM.
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Both genotype and allele frequency of ACE and
aADDUCIN however were not different between patients
with and without ECMRA or ICMRA abnormality after
adjustment of putative stroke risk factors.
Conclusions: ACE DD genotype and D allele and
aADDUCIN GW genotype and W allele were associated
with IS compared to controls but not related to IC or
ECMRA abnormalities.
Study supported by: Study financially supported by Indian council of medical research, Governmernt of India
Neurogenetics
M1001. Withdrawn
M1002. Clinico-Genetic Characterization of a Large
Italian Cohort with Primary Spastic Paraplegia
Andrea Martinuzzi, Mariateresa Bassi, Grazia D’Angelo, Sara
Bonato, Gabriella Paparella, Olimpia Musumeci,
Mariagiovanna Rossetto, Marianna Fantin, Francesca Peruch,
Alessia Arnoldi, Claudia Crimella, Erika Tenderini, Paolo
Bonanni, Vanessa Casanova, Giovanni Meola, Giacomo Comi,
Antonio Toscano and Nereo Bresolin; Conegliano, TV, Italy;
Bosisio Parini, LC, Italy; Messina, Italy and Milano, Italy
M1004. Generation and Characterization of MeCP2_270
Mutant Mice
Chiranjeevi Bodda, Karolina Can, Liakath Ali Kifayathulla,
Hope Yao Agbemenyah and Ashraf U. Mannan; Goettingen,
Germany
MeCP2 is a transcription factor that binds to methylated
target DNA sequence. Loss-of-function mutations in
MECP2 gene is the main cause for Rett syndrome (RTT).
The R270X is one of the most frequent recurrent MECP2
mutations among RTT cohorts. The R270X mutation
resides within the TRD-NLS region of MeCP2 and causes a
severe clinical phenotype with increased mortality as compared to other mutations. To evaluate the functional role of
R270X mutation, we first generated a transgenic mouse
model expressing MeCP2_270 (human mutation equivalent)
by BAC recombineering. The generated transgenic mice
were crossed with Mecp2 knockout mice to produce
Mecp2_R270X knockin mice. The expression pattern of
MeCP2_270 was similar to that of endogenous MeCP2.
Strikingly, MeCP2_270 localizes in the nucleus, contrary to
the conjecture that the R270X could cause disruption of the
NLS. Quantitative expression analysis of MeCP2 target
genes revealed a similar trend in gene regulation pattern as
observed in knock-out mice, however the level of differential
regulation was variable. At the present, we are performing
behavioral analysis to characterize the phenotype of the
mice. Also, we are evaluating neuronal parameters to determine impairment in neuron development/differentiation
and synaptic network dysfunction.
Study supported by: DFG-Research Center Molecular
Physiology of the Brain. Germany
Background: Diagnostic definition of hereditary spastic
paraplegias (HSPs) is complicated by the wide genetic
heterogeneity.
Objectives: Establish in a large cohort of Italian HSP
patients the relative frequency of the various forms, providing indications for an efficient diagnostic algorhythm.
Methods: 478 index cases (72 familial, 98 pure, 380
complicated) HSP were clinically and molecularly assessed.
Results: 80 cases were molecularly defined. SPG4 was
the most frequent form (55%), followed by SPG11 (16.6%)
SPG7 (9%), SPG10 (8,8% ) and 5 (5.1%). SPG3a and
SPG31 were rarer (2.5%). No mutations were identified in
SPG6, 8, 13, 20, 21, 35, 48. There was wide inter and
intrafamilial variation. Neurophysiology showed invariably
increased central conduction time at lower limbs. Axonal
polyneuropathy was detected in some SPG3a, 5, 10, 11, 17
and SPG4 (15%). MRI showed abnormalities in SPG 5,
10, 11 and 15.
Conclusion: Frequency of SPG forms within this cohort
of Italian HSPs confirms the prevalence of SPG4, reveals
the recurrence of SPG11 and 7 and the low frequency of
SPG3a and 31. Once SPG4 and SPG11 are excluded, family history, neurophysiology and neuroimaging may direct
the choice of genetic testing.
Study supported by: Italian Ministry of Health
M1003. A Study of ACE and ADD1 Gene
Polymorphism in Extra and Intracranial Atherosclerosis
in Patients with Ischemic Stroke
Jayantee Kalita, Usha K. Misra, Sunil Kumar, Bishwanath
Kumar, Bindu I. Somarajan and Balraj Mittal; Lucknow,
Uttar Pradesh, India
M1005. Identification of Epigenomic Modifications as
Biomarkers for Amyotrophic Lateral Sclerosis
Claudia Figueroa-Romero, Junguk Hur, Yu Hong, John S.
Lunn, Crystal Pacut, Colin E. Delaney, Raymond Yung, Brian
Callaghan and Eva L. Feldman; Ann Arbor, MI
ALS is a progressive and terminal neurodegenerative disease
leading to irreversible motor neuron degeneration. The high
incidence of sporadic ALS (sALS) suggests that long-term
influences of environmental factors on the genome may
have a major impact in disease development. We hypothesize that epigenetic modifications play a key role in the
pathogenesis of sALS. DNA from postmortem spinal cord
(SC) tissue from sALS patients/controls was subjected to an
epigene discovery phase. We identified 4,080 autosomal
CpG sites with a significantly different methylation status in
sALS compared to control (False Discovery Rate < 5%).
The biological functions of ‘extracellular region’, ‘defense
response’ and ‘immune response’ were highly associated
with these differentially methylated sites. Furthermore, differential expression of six genes involved in human cytokine
activity was observed in ALS/control human lymphocytes
and/or SC. We have identified methylation profiles in diseased tissue, which might parallel those in blood as
Objective: To evaluate the hypertensive gene (ACE and
aADDUCIN) and MR angiography (MRA) abnormality in
patients with ischemic stroke (IS).
Method: 151 patients with MRI proven IS were subjected to clinical and biochemical stroke risk factors evaluation. Both intra(IC) and extracranial(EC) MRA were done
and more than 50% stenosis was considered significant.
ACE and aADDUCIN gene polymorphism was done in
patients and 188 controls.
Results: The patients’ median was 60years and 26.5%
were females. MRA was abnormal in 77.5%; ECMRA in
58.3% and ICMRA in 66.7%. The conventional risk factors
were not different between the patients with and without
MRA abnormalities. Presence of DD genotype
(OR3.86,95%CI0.78-2.28,P ¼ 0.0001) and aADDUCIN
GW genotype (OR2.05, 95%CI1.28-3.27,P ¼ 0.003)
increased the risk of IS significantly compared to controls.
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epigenetic biomarkers of sALS. This could enable early-stage
diagnosis and therapeutic interventions to increase survival
outcomes in sALS patients.
Study supported by: The A. Alfred Taubman Medical
Research Institute.
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Mayo Clinic Florida (MCF) Research Committee CR programs (MDF #90052018).
M1008. Aberrant Methylation by Mutations of DNA
Methyltransferase 1 Cause Peripheral and Central
Axonal Degeneration
Christopher J. Klein, Maria V. Botuyan, Yanhong Wu,
Christopher J. Ward, Garth A. Nicholson, Simon Hammans,
Hiromitch Yamanishi, Adam R. Karpf, Douglas C. Wallace,
Mariella Simon, Cecilie Lander, Julie M. Cunningham, Glenn
E. Smith, William J. Litchy, Benjamin Boes, Elizabeth J.
Atkinson, Sumit Middha, P. James Dyck, Joseph E. Parisi,
Georges Mer, David I. Smith and Peter J. Dyck; Rochester,
MN; Sydney, Australia; Southampton, United Kingdom;
Hyogo, Japan; Buffalo, NY; Irvine, CA; Herston, Australia
and Indianapolis, IN
M1006. A Drosophila Model of Williams Syndrome
Ralph J. Greenspan and Jenee Wagner; La Jolla, CA
Social cognition is a major frontier in neuroscience, and
Williams Syndrome (WS) is a condition affecting social cognition associated with hemizygous deletions of 28 genes
on human chromosome 7. The genetics of WS is apparently
simple, consisting of a deletion of a defined chromosome
segment, but complex because the deletions remove a block
of genes, thus obscuring the contributions of interactions
among subsets of the genes. These interactions are directly
addressable in Drosophila, where ten of the genes in WS
deletions have bona fide homologs in Drosophila, and one
more has a more distant homolog, and all have extant mutant alleles.
We are mapping the gene network interactions affected
by different combinations of WS homologs in the fruit fly,
capitalizing on the extensive conservation with humans of
their genes and gene networks. Results from these experiments indicate that fly homologs of LIMK1 and CLIP190,
among others, have substantial effects on behavior individually, but their contributions are not additive in combination
with other WS genes. This non-linearity is reflected in the
effects of these manipulations on gene network activities.
Supported by NSF IOS-0840717 and NIH
1R21EY020629-01 grants to R.J.G.
Study supported by: NIH, NSF
DNA methyltransferase 1 (DNMT1) is an essential component of genomic methylation. Neural gene expression, DNA
mismatch repair and cell cycle regulation are all influenced
by DNA methylation. Here we show mutations in DNMT1
cause both central and peripheral axonal degeneration in
one form of hereditary sensory and autonomic neuropathy
with dementia and hearing loss. Two American, one European and one Japanese kindreds were studied. Next generation sequencing was utilized to identify two DNMT1 mutations, c.A1484G(p.Y495C) in American and Japanese
kindreds and c.1470TCC-1472ATA(p.D490E-P491Y) in a
European kindred. All mutations are within the DNA targeting sequence domain of DNMT1. Functional analysis
shows premature degradation and reduced methyltransferase
activity. Mutant proteins lost heterochromatin binding ability during the G2 cell cycle, leading to global hypomethylation measured by mass spectrometry analysis. Methylation
of satellite 2 repetitive elements is preferentially decreased.
Global hypomethylation and regional hypermethylation is
shown in affected persons, a pattern commonly seen in
unregulated cancer cells, suggesting post mitotic neural cells
may undergo axonal degeneration by loss of cell cycle arrest.
The discovered mutations in DNMT1 provide a new framework for the study of neurodegenerative diseases.
Study supported by: NINDS K08 award
M1007. Clinical and Pathological Features of Progressive
Supranuclear Palsy with Family History
Shinsuke Fujioka, Avi Algom, Audrey Strongosky, Dennis W.
Dickson and Zbigniew K. Wszolek; Jacksonville, FL
Objective: To compare the clinical and pathological characteristics of progressive supranuclear palsy (PSP) patients
with and without a family history of parkinsonism or PSP.
Methods: We reviewed autopsy case records from Mayo
Clinic Florida Brain Bank to retrieve PSP cases with positive
family history of neurodegenerative disease, defined as PSP
or parkinsonism, as well as PSP cases without a family history of neurologic disease.
Results: This study was based on 375 pathologically confirmed PSP cases, of which 56 had a family history of PSP
or parkinsonism. Among these, 19 patients had multiple
affected family members with PSP, parkinsonism, or other
neurodegenerative conditions, such as dementia or tremor.
There was a trend (p ¼ 0.128) for PSP with a positive family history to have more atypical clinical features and diagnoses other than PSP, such as corticobasal syndrome or
frontotemporal dementia. They also tended (p ¼ 0.131) to
have more frequent atypical PSP pathology.
Conclusion: PSP patients with a positive family history
share many clinical and pathologic features with PSP
patients without family history, but in general they tend to
be atypical in clinical presentation and in final pathology.
Study supported by: ZKW is partially supported by the
NIH/NINDS 1RC2NS070276, NS057567, P50NS072187,
Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030), and gift
from Carl Edw and Bolch, Jr., and Susan Boss Bolch (MCF
#90052031/PAU #90052). FS is partially supported by
M1009. Common and Distinct Associations of HLADRB1 and -DPB1 Alleles with Neuromyelitis Optica and
Multiple Sclerosis in Japanese
Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Tomomi
Yonekawa, Katsuhisa Masaki and Jun-ichi Kira; Fukuoka,
Japan
Background: A distinctive association between human leukocyte antigen (HLA) gene alleles and each clinical subtype,
opticospinal multiple sclerosis (OSMS) and conventional
MS (CMS), has been reported in Asians. However, patients’
sample sizes were relatively small in the previous studies.
OSMS is now suggested to be the same as a relapsing form
of neuromyelitis optica (NMO) in Westerners.
Objective: To clarify the association of HLA-DRB1 and DPB1 alleles with NMO and non-NMO MS phenotypes in
a large series of Japanese patients.
Methods: Genotyping of HLA-DRB1 and -DPB1 alleles
was performed in 288 MS patients including 83 who fulfilled the NMO criteria, and 367 healthy controls (HCs).
Results: DRB1*0901 frequency was significantly lower in
both NMO (pcorr ¼ 0.0003, OR:0.133, 95%CI:0.048–
0.374) and non-NMO MS patients (pcorr<0.0001,
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OR:0.301, 95%CI:0.181–0.499) as compared with HCs.
Susceptibility alleles for non-NMO MS are DRB1*0405
(pcorr ¼ 0.0189, OR:1.867, 95%CI:1.300–2.683) and
DPB1*0301 (pcorr ¼ 0.0022, OR:3.328, 95%CI:1.747–
6.337) while those for NMO are DRB1*1602 (pcorr ¼
0.0028,
OR:12.942,
95%CI:3.355–49.923)
and
DPB1*0501 (pcorr ¼ 0.0265, OR:2.608, 95%CI:1.412–
4.816).
Conclusion: There is a common resistant DRB1 allele
between NMO and non-NMO MS while susceptibility alleles are distinct between the two conditions in Japanese.
Study supported by: This work was supported in part by
the Health and Labour Sciences Research Grant on Intractable Diseases (H20-Nanchi-Ippan-016) from the Ministry of
Health, Labour and Welfare, Japan, and the grant-in-aid (B;
no. 22390178) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
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rHIgM12 co-localized with microtubules and was co-immunoprecipitated with b3-tubulin. rHIgM12 promoted tyrosination of a-tubulin. Finally, rHIgM12 enhanced polarized
axon outgrowth when presented as substrate. Our results
indicate that there exists a repertoire of natural IgMs with
the potential to regulate membrane lipid and microtubule
dynamics required for axonal outgrowth. These findings
also identify a bioactive molecule that may be utilized to
treat neurologic diseases.
Study supported by: This work was supported by grants
from the NIH (R01 GM092993, R01 NS024180, R01
NS03219, R01 NS048357) and the National Multiple Sclerosis Society (CA 1011-A8). We also acknowledge with
thanks support from the Applebaum and Hilton Foundations and the Minnesota Partnership Award for Biotechnology and Medical Genomics.
M1102. Computed Tomography Characteristics of
Pediatric Traumatic Brain Injury
Korak Sarkar and Kia Shahlaie; Sacramento
M1010. Computer Simulations of Striatal Atrophy and
Age at Onset of Huntington’s Disease
Steven D. Edland and Jagan Pillai; La Jolla, CA
Little is known about the differences in CT findings
between adult and pediatric TBI populations. A retrospective analysis of 1206 consecutive non-penetrating TBI
patients treated at a Level 1 trauma center from August
2008 to January 2011 was performed. Admission CT scan
were evaluated for skull fractures, ICH, midline shift, and
basal cistern compression. Of 1206 patients in our registry
349(28.5%) were pediatric. Demographics and injury severity distribution were similar between the two populations
(p> 0.05). The distribution of CT findings, however, was
significantly different. Pediatric TBI patients were more
likely to be associated with skull fractures (57.0% vs 23.4%)
and EDH (17.2% vs 9.7%), and less likely to be associated
with contusion, SDH, SAH, or basal cisterns compression
(p<0.05). Despite similarities in demographic characteristics
and clinical severity between adult and pediatric TBI, there
were significant differences in the pattern of CT findings.
These findings may reflect differences in anatomy (skull
fractures), biomechanical forces during injury (ICH patterns), or intracranial compliances (mass effect). These differences may have a significant impact on clinical trial
design and treatment strategies for patients in different age
groups.
Beyond polyglutamine repeat length on the huntingtin
gene, little is known about predictors of age at onset of first
symptoms of Huntington’s disease (HD). Cajevec et al.
(Neurogenetics, 2006) proposed that variability in age at
onset given repeat length could be explained by the random
nature of striatal cell loss under the ‘‘one-hit’’ model of HD
neurodegeneration proposed by Clarke et al. (Nature,
2000). Alternatively, the rate of neuronal loss in HD could
vary person to person due to environmental and background
genetic influences affecting rate of neuronal loss or affecting
susceptibility to the extent of cell loss. To investigate this,
we simulated striatal neuron loss in HD as proposed by
Cajevec et al. and under these alternative models. We found
that stochastic cell death is unlikely to explain an appreciable fraction of variability in age at onset, while models
with random rates of neuronal loss and susceptibility recapitulated empirical HD survival distributions perfectly. We
conclude, contrary to Cajevec et al., that age at onset is a
valuable phenotypic endpoint for investigations of environmental and background genetic factors affecting the expression of HD.
Study supported by: NIH/NIA AG00513 and
AG034439.
M1103. Neurological Outcome Scale for Traumatic
Brain Injury: Predictive Validity and Sensitivity to
Change
Paolo Moretti, Stephen R. McCauley, Elisabeth A. Wilde,
James N. Scott and Guy L. Clifton; Houston, TX and Calgary,
AB, Canada
Trauma/Injury
M1101. A Human Natural IgM Drives Axon Outgrowth
Xiaohua Xu, Arthur Warrington, Brent Wright, Allan Bieber,
Virginia Van Keulen, Larry Pease and Moses Rodriguez;
Rochester, MN
The Neurological Outcome Scale for Traumatic Brain Injury
(NOS-TBI) is a measure assessing neurological functioning
in TBI. We hypothesized the NOS-TBI would be more sensitive to change than other well-established measures, demonstrate predictive validity, and relate to initial Marshall CT
classification. We analyzed data from the National Acute
Brain Injury Study: Hypothermia II trial (n ¼ 98). Patients
were 16–45 years with severe TBI assessed at 1, 3 and 6
months post-injury. For analysis of validity, Spearman correlations were performed comparing the NOS-TBI to Glasgow Outcome Scale (GOS) and GOS-Extended (GOS-E),
Disability Rating Scale (DRS), and Marshall CT classification. Sensitivity to change was analyzed using the Wilcoxon
signed-rank sum test of subsamples demonstrating no
We demonstrate that a human natural IgM, HIgM12 promotes axonal outgrowth by mechanisms coupling lipid raft
to microtubule dynamics. Serum-derived human IgMs have
been shown to support neurite extension of primary cerebellar granule neurons. In the current study with primary hippocampal neurons, we showed that a recombinant form of
one of these IgMs, rHIgM12 regulated kinetics of membrane lipids. rHIgM12 bound to neuron surfaces and
induced clustering of cholesterol and ganglioside, GM1.
Following membrane association, rHIgM12 segregated into
two pools, one associated with lipid raft fractions, and the
other with detergent insoluble pellet composed of cytoskeletons. Moreover, rHIgM12 affected microtubule dynamics.
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change in GOS or GOS-E between 3 and 6 months. The
1- and 3-month NOS-TBI correlated with the 3- and 6month GOS, GOS-E and DRS (all p<.002), and Marshall
CT correlated with 6-month NOS-TBI (p<.03). NOS-TBI
demonstrated higher sensitivity than GOS or GOSE (p
.02). The NOS-TBI demonstrates predictive validity and
higher sensitivity to change than existing TBI measures; it
may enhance prediction of outcome in clinical practice and
measurement of outcome in research.
Study supported by: National Institute of Neurological
Disorders and Stroke NS043353
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0.033). Patients reported that only 17.4% (19/109) of injuries occurred during exercise.
Conclusions: Risk factors for injury include male gender,
living longer with MS, being younger and having the diagnosis of primary progressive MS, respectively.
Study supported by: University of Massachusetts Medical
School
M1106. Raising the Dead: Barriers to Therapeutic
Hypothermia Post Cardiac Arrest
and Mark Andrews; Palo Alto, CA
Induction of therapeutic hypothermia (TH) in post cardiac
arrest patients has been shown to be neuroprotective and
may yield additional therapeutic benefits including
decreased mortality. Despite better outcome data, the existence of physician order protocols, and readily available
state-of-the-art equipment, early induction of therapeutic
hypothermia is often started late in the hospital continuum
of care. Unlike other interventions shown to improve postarrest outcomes (early bystander CPR, early defibrillation,
and early advanced cardiac life support), early induction of
therapeutic hypothermia is a hospital-based strategy requiring the integration and cooperation of multiple practitioners
and multiple departments for successful implementation.
Approaching the issue from this multidisciplinary perspective led me to survey over a 100 practitioners in a large,
university-based hospital setting in order to identify experiences, knowledge, and barriers to inducing therapeutic
hypothermia early in the care continuum. Few of the
respondents reported experiences with TH and most
reported a lack of standardized protocols, unclear orders,
and technical difficulties with cooling equipment as the
most common barriers to induction.
M1104. Determination of Awareness in Patients with
Severe Brain Injury Using EEG Spectral Analysis
Andrew M. Goldfine, Jonathan D. Victor, Mary M. Conte,
Jonathan C. Bardin and Nicholas C. Schiff; New York, NY
and White Plains, NY
Recent studies using functional MRI (fMRI) and eventrelated potentials (ERP) demonstrate that some severely
brain-injured patients retain a range of cognitive functions
despite minimal or no behavioral evidence of awareness.
However, fMRI is impractical for bedside use and ERPs
may fail to detect responses that are delayed or not tightly
synchronized to a stimulus. We investigated whether electroencephalographic (EEG) spectral analysis could identify
behaviorally covert responses to command in three patients
with severe brain injury, ranging from minimally conscious
state (MCS) to locked-in-state (LIS). We first demonstrated
that EEG spectral analysis could denote performance of a
motor and navigation imagery tasks in healthy controls. As
patterns of signal change were inconsistent between controls,
we defined a positive outcome in patients as consistent spectral changes across task performances. Using this outcome
measure, one patient in MCS and one in LIS demonstrated
evidence of motor imagery. Patterns of spectral power and
cross-channel coherence varied across subjects, representing
different local and widespread cortical networks involved in
task performance. We conclude that EEG spectral analysis is
a promising versatile tool for bedside testing of awareness in
patients with severe brain injury.
Study supported by: NIH-NICHD 51912, the James S
McDonnell Foundation, and Weill-Cornell CTSC UL
1RR02499
M1107. Abnormal Oculomotor Function among BlastInjured Combat Veterans
Bruce P. Capehart, Adam Mehlenbacher, Carol SmithHammond, Dale Bass and James Burke; Durham, NC
Dysfunctional saccades and smooth pursuit have been
reported after blunt traumatic brain injury (TBI). These
tests of oculomotor function could assist in the diagnosis of
TBI after exposure to significant blast injuries. We report
results of saccade and smooth pursuit testing for blastexposed combat veterans who did not have a prior history
of blunt TBI. These results show abnormalities in both saccades and smooth pursuit. These tests should be further
investigated for use as screening and/or diagnostic assessment when blast-related TBI is a possible diagnosis.
M1105. Orthopedic Injuries in Multiple Sclerosis
Patients: Analysis of the Incidence of Injury in This
Vulnerable Population
Daniel Mandell** and William Tosches; Worcester, MA
Background: Because of the high degree of disability in
multiple sclerosis (MS) patients, minimizing injury occurrence is essential for preserving quality of life.
Objectives: By establishing relative risks of particular
injuries in different subsets of MS patients and analyzing
when the injuries occurred following diagnosis, we aim to
provide information to encourage injury prevention.
Methods: A questionnaire of 40 fill in the blank or multiple choice questions was administered to previously diagnosed MS patients. Results: The years following MS diagnosis with the highest injury rates (injuries/people years lived)
were 25 years or more (.0594 injuries/year, 95% CI [0.0771
- 0.0449]). People below the age of 40 have nearly a
doubled risk of injury compared to people above the age of
40 (p ¼ .0331). Primary progressive MS patients had the
greatest past incidence of fractures, 55.6% (5/9) (FFH p ¼
Neurology Critical Care
M1201. Withdrawn
M1202. Predictors of Outcome in Prolonged Refractory
Status Epilepticus
Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M.
Wijdicks and Alejandro A. Rabinstein; Rochester, MN
To determine predictors of outcome in refractory status epilepticus (RSE) we retrospectively analyzed all episodes of
RSE treated between 1999 and 2011 at Mayo Clinic. RSE
was defined as generalized convulsive or non-convulsive status epilepticus that continued clinically or electrographically
despite initial first and second line therapies. We identified
55 episodes of RSE in 46 patients aged 50 6 17.9 years.
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IT injections were given to all patients (mean ¼ 6.4, range
1–14), median dose 4mg (range 1.2mg-4mg). No intracranial complications were observed by neuroimaging. No
patient developed infectious ventriculitis. 2 patients had
CSF cloudiness immediately after injection, but no infection
occurred. 1 patient had yellow nicardipine crystals that
came out of external ventricular drain after repeated
injections.
Conclusion: IT-nicardipine at dose ranges of 1.2mg to
4mg may be safe for treating vasospasm after aSAH. Further
study is needed for dose-finding and assessing efficacy.
Induction of anesthetic coma was necessary in 49/53 SE
incidents. Patients required anesthetic agents for 9.6 (4, 0–
60) days. Eighteen died, withdrawal of support preceded
death in 13. Compared to a pre-morbid modified Rankin
scale (MRS) of (2.09 6 1.6) 27 patients alive at 3–6
months following hospital discharge had a MRS of (3.81 6
1.52) (p<0.0001) and 20 patients alive at 9–12 months
had a MRS of (3.3 6 1.83) (p<0.0005). Asystole
(p<0.0098), cardiac arrhythmias requiring treatment
(p<0.0540), pulmonary edema (p<0.0498) and longer duration of mechanical ventilation (p<0.0492) were associated
with in-hospital death. Mortality was similar to other published series of RSE. Despite prolonged anesthetic coma,
patients who survive RSE may have acceptable outcomes. In
this RSE series, the largest single center series reported thus
far, cardiopulmonary complications were the main predictors of mortality.
M1205. Acute Bacterial Meningitis as a Possible Cause
of Severe Dysautonomia Leading to Death
Yadira Velazquez-Rodriguez, Umer Akbar and Evren
Burakgazi-Dalkili; Camden, NJ
Objective: To recognize the possibility of pneumococcal
meningitis causing severe dysautonomia leading to death.
Background: Episodes of autonomic instability with dystonia (PAID) are known to result from multiple intracranial
processes, however pneumococcal meningitis as a cause is
under-recognized.
Design/Methods: We describe a case of severe autonomic
instability in a patient with acute bacterial meningitis.
Results: Case: A 76 year-old woman with fever and
altered mental status was diagnosed with acute pneumococcal meningitis. Antibiotic therapy improved her mentation, however few days later, she developed episodes of
unresponsiveness with dilated, asymmetric and sluggish
pupils, shivering, generalized tremors, hypertension and
tachycardia followed by episodes of severe hypotension,
bradycardia and asystole eventually leading to her death.
These episodes were not responsive to conventional resuscitative measures.
Conclusions: The inflammatory reactions that accompany infections have been implicated in autonomic dysfunction. Our case suggests that PAID is a spectrum-disease rather than a syndrome with distinct criteria. PAID
was recognized in patients with central nervous system disorders, particularly traumatic brain injury, but to our
knowledge, it has never been reported to occur from pneumococcal meningitis and with such severity resulting in
patient’s death.
M1203. Refractory Status Epilepticus and Heart Damage
– A Warning for Neurologists
Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M.
Wijdicks and Alejandro A. Rabinstein; Rochester, MN
To determine the incidence of neurocardiogenic injury in
refractory status epilepticus (RSE) we reviewed all episodes
treated between 1999 and 2011 at Mayo Clinic. RSE was
defined as generalized convulsive or non-convulsive SE that
continued despite initial therapies. We identified 55 episodes in 46 patients aged 50 6 17.9 years. Induction of
anesthetic coma was necessary in 49/53 cases. Patients
required anesthetic agents for 9.6 (4, 0–60) days. Eighteen
patients had troponin levels drawn at onset of SE (mean
0.1 6 0.19 ng/mL). Electrocardiogram findings at onset of
SE included: ST elevation (6.98%), ST depression
(4.65%), T wave inversion (4.65%), LVH (6.98%), nonspecific ST changes (54.55%). Cardiac arrhythmias
included: asystole (11.54%), ventricular tachycardia/fibrillation (7.69%), atrioventricular block (3.85%), atrial fibrillation/flutter (7.69%), paroxysmal supraventricular tachycardia (1.92%), sinus bradycardia (46%), sinus tachycardia
(75%). Intervention was required for cardiac arrhythmias
in 22.45%. One patient met criteria for non ST elevation
myocardial infarction (NSTEMI). Pulmonary edema was
present in 35%. Six of 24 patients evaluated with echocardiograms during and after SE had stress-induced cardiomyopathy with resolution after SE. We conclude that adrenergically-driven neurogenic cardiopulmonary injury is
common in RSE. These disturbances may require specific
treatment and are often reversible.
Pediatric Neurology
M1301. Diffusion Tensor MRI Tractography Reveals
Altered Brainstem Fiber Connections Accompanying
Agenesis of the Corpus Callosum
Juebin Huang, Jian Chen, Haipeng Cai, Robert P. Friedland,
Mohamad Z. Koubeissi, David H. Laidlaw and Alexander P.
Auchus; Jackson, MS; Hattiesburg, MS; Louisville, KY;
Cleveland, OH and Providence, RI
M1204. Safety and Feasibility of Intrathecal Nicardipine
for Vasospasm after Subarachnoid Hemorrhage
William D. Freeman, Sothear Luke, Christina Campbell, Dan
Jackson and James F. Meschia; Jacksonville, FL
Introduction: Delayed arterial vasospasm (VSP) is a major
cause of ischemic stroke after aneurysmal subarachnoid
hemorrhage (aSAH). We hypothesize intra-thecal (IT) nicardipine would be safe and feasible for treating vasospasm.
Methods: Retrospective chart review of consecutive
aSAH patients admitted to the Neurosciences ICU at
Mayo Clinic Florida from January 2009 to March 2011.
Data collection included: age, sex, Fisher grade, and IT nicardipine dosing. Assessment of safety included post-injection intracranial bleeding (per CT or MRI) and infectious
ventriculitis.
Results: 12 patients (11 women; mean age, 49 yrs [range,
27–67 yrs]) with aSAH were treated with IT-nicardipine. 77
Introduction: Agenesis of Corpus Callosum (ACC) is a developmental anomaly wherein interhemispheric cerebral
fibers fail to cross into the contralateral hemisphere. Using
Diffusion Tensor MRI Tractography (DTT), we report two
ACC cases with altered brainstem fiber connections involving middle cerebellum peduncles and transverse pontine
fibers.
Cases: Case 1: A 22 year-old woman with seizures, mental retardation and behavioral abnormalities. Case 2: A 50
year-old man with syncope, cognitive impairments and
bilateral palmomental responses.
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Imaging Procedures: Whole brain DTT was performed
using streamtube tracing and culling techniques. DTT of a
normal subject was obtained as a control.
Results: Conventional brain MRI displayed complete absence of the corpus callosum in both cases. Whole brain
DTT showed no corpus callosum fibers crossing the midline
in either ACC case. Instead, robust fiber bundles passing
through middle cerebellum peduncles via transverse pontine
fibers were seen.
Conclusion: DTT was useful in visualizing expected and
unexpected alterations of white matter fiber connections in ACC.
Study supported by: National Science Foundation
(1017921,1018769, 1016623)
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ease. The significance of the Macro-CK in relation to the
Leukoencephalopathy in this patient or the frequency of this
association is completely unknown.
Study supported by: Supported by The William Pilcher
Endowment for Pediatric Neurology
M1304. Pharmaceuticals in the Environment: A Focus
on Neurological Medications
and Ilene Ruhoy; Seattle, WA
Pharmaceutical residues in the environment have been an
issue of increasing interest amongst environmental scientists,
toxicologists, and policy makers. Physicians have recently
expressed concern regarding the potential ill effects on
humans from chronic exposures to these active pharmaceutical residues (APIs).
Research has demonstrated the potential for neurological
effects from exposure to the multitude of pharmaceutical
residues identified in our environment, specifically in our
water systems. Studies in aquatic organisms have revealed
altered brain size, poor neuronal growth, and neuropathy. In
addition, many of the pharmaceuticals that have been identified are centrally acting. Carbamazepine is one drug of significant concern in that it is largely refractory to most treatment technologies and indeed it has been identified in all
water sampling studies. Benzodiazepines are another common culprit that are found with increasing frequency and
are ubiquitous in its prescription patterns.
This presentation will discuss the known and unknown
with regards to medications commonly prescribed in the
neurological setting and environmental presence. It will correlate research on aquatic wildlife with the potential for
human health effects from exposures to these medications
and will recommend actions to minimize human exposures.
M1302. Neurofibromatosis 1 (NF1) Vasculopathy in
Children – An Emerging Entity
Partha S. Ghosh, A.D. Rothner and Manikum Moodley;
Cleveland, OH
Objective: Vasculopathy in children with NF1.
Methods: Retrospective review of children with NF1
from 2000- 2010 at Cleveland Clinic. NF1 associated vasculopathy divided into: (1) Cerebrovascular, (2) Cardiovascular (3) Other.
Results: Of 398 patients, 26 (6.5%) had vasculopathy.
Group1: Ten (2.5%) had cerebrovascular abnormalities
(mean age 12.8 years; 5 males). Presentation- headache
(4), seizures (1), asymptomatic (5): all had normal neurological examination. MRA brain: Moyamoya disease-4, stenosis/occlusion of Internal carotid artery-3, Middle cerebral
artery stenosis-2, Posterior cerebral artery stenosis-1. Ischemic changes noted in 1. On follow-up (mean 5.2 years);
1 died of brain tumor, others did not develop stroke. One
had encephaloduromyosynangiosis for moyamoya.
Group2: Fifteen (3.7%) had cardiovascular abnormalities
(mean age 6.6 years; 8 males). Presentation: hypertension (2),
shortness of breath (2), chest pain (1), syncope (1), murmur
(6). Cardiac lesions: Pulmonary stenosis-5, Coarctation-4, mitral-valve prolapse-1, supra-valvular aortic stenosis-1, anomalous right coronary artery-1, pulmonary artery hypoplasia-1.
On follow-up (mean 4.6 years), 3 had surgical procedures.
Group3: Two girls had renal artery stenosis (RAS); 1 with
coarctation. Both were hypertensive: 1 underwent RAS repair.
Conclusion: Children with NF1 should be carefully
screened for vasculopathy.
Rehabilitation and Regeneration
M1401. Human Induced Pluripotent Stem Cell-Derived
Neural Progenitor Grafting into Rat Hippomcapus
Alison L. Althaus, Yu Liu, Duriel Hardy and Jack M. Parent;
Ann Arbor, MI
Induced pluripotent stem cells (iPSCs) offer potential
advantages as a neural progenitor cell (NPC) source for regenerative therapy, including readily available supply, vast
differentiation potential and autologous grafts that obviate
the need for immunosuppression. To begin developing
iPSC-based transplantation therapy, we injected human
iPSC-derived NPCs into neonatal rat hippocampus to determine their differentiation potential. We also examined how
the degree of in vitro differentiation influenced graft behavior. GFP- or mCherry-labeled human iPSCs were neurally
differentiated and transplanted (10^5 cells) into postnatal
day 4 rat hippocampus either at the primitive neural rosette
stage or after 3-day neurosphere differentiation. Grafts were
examined after 2, 4 or 8 weeks by immunostaining for
human nuclear antigen or GFP/mCherry and neuronal or
glial markers. Grafts generated GFAPþ glia and TuJ1þ
neurons at all time points. Neural rosette grafts tended to
form large neural tube-like structures that deformed host tissue. Neurosphere grafts dispersed more widely and gave rise
to mature-appearing neurons, some of which expressed a pyramidal cell marker (Tbr1). These findings suggest that
iPSCs autografts may be useful for treating brain disorders.
Further work is needed to determine optimal NPC differentiation states for grafting.
Study supported by: NIH NS065450
M1303. Macro CK-1 a Cause of Spuriously Elevated CK
Associated with Leukoencephalopathy in an Infant
and John B. Bodensteiner; Phoenix, AZ
Macro CK-1 is a complex formed by the Creatine Kinase isoenzyme BB and monoclonal IgG. The complex is not formed
by abnormal CK enzyme but by an autoimmune reaction
and occurs in about 1% of patients studied. First identified
as a cause of spurious elevation of the total CK in patients
suspected of myocardial infarction in the 1970s the test has
been largely replaced by the measurement of Troponin levels.
We present an infant with delayed milestones and persistently
elevated CK measurements (1000–4000 IU) normal EMG
and brisk DTRs. Suspicion that this was not a myopathy
prompted the measurement of CK isoenzymes and brain
imaging which showed the presence of Macro CK-1 and
extensive signal abnormality of the cerebral white matter.
Macro CK-1 has been associated with cancer, infection, myositis and heart disease, not described in association with leukoencephalopathy or in infants. Macro CK-1 may be a cause
of elevated total CK in patients without primary muscle dis-
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136th Annual Meeting Tuesday,
September 27, 2011
Poster Session
M1402. Local Molecular Manipulation and Peripheral
Nerve Regeneration
Douglas W. Zochodne, Kimberly J. Christie,
Christine A. Webber, Chu Cheng and Jose A.
Martinez; Calgary, AB, Canada and Edmonton,
AB, Canada
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
NOTE: An asterisk designates a resident/fellow travel award
winner. Two asterisks represent a medical student travel award
winner.
Regeneration of peripheral neurons following injury or
neuropathy is more challenging than usually assumed. We
describe new molecular players that may offer insights into
early axon outgrowth, the initiating step in regeneration.
After complete nerve transection, axon outgrowth requires
an intimate molecular exchange with partnering Schwann
cells (SCs). Using an accessible conduit to connect the
stumps of transected peripheral nerves in rats, we show
that several forms of intervention, including local siRNA
knock down, can alter regenerative outcome: (i) CGRP, an
axonally synthesized peptide, signals local SCs to proliferate in order to support axon growth: knockdown interrupts
regeneration. (ii) PTEN, a tumour suppressor molecule, is
a regenerative roadblock that attenuates growth factor support of regeneration: knockdown dramatically enhances
axon outgrowth. (iii) DCC and Unc5H are netrin facilitatory and inhibitory developmental pathfinding receptors
respectively that are re-expressed in regenerating adult SCs:
DCC knockdown attenuates adult regeneration whereas
Unc5H knockdown enhances it. Local molecular manipulation can have significant impacts on the critical initiating
step of peripheral nerve regeneration by eliminating roadblocks or upregulating growth signals. The approach may
offer new forms of intervention for irreversible peripheral
nerve lesions.
Study supported by: Canadian Institutes of Health
Research, Alberta Heritage Foundation for Medical
Research
Dementia and Aging
T1501. Amyloid-Beta Dynamics and Prevention Trials in
Dominantly Inherited Alzheimer’s Disease
Randall J. Bateman and on behalf of the Dominantly
Inherited Alzheimer Network; St. Louis, MO
Amyloid-beta is a key pathologic protein in Alzheimer’s disease(AD) and extensive research has started an era of clinical
trials targeting amyloid-beta. Understanding the dynamics
of amyloid-beta formation and clearance in the human
CNS and the processes that lead to clinical disease are essential to design better clinical trials. Developing efforts to prevent AD in autosomal dominant mutation carriers may test
the amyloid hypothesis, determine the timing of treatment,
and lead the way to AD prevention.
Amyloid-beta production and clearance rates were measured with stable isotope labeling kinetics. The Dominantly
Inherited Alzheimer’s Network interim findings of clinical,
cognitive, MRI, PET, CSF, and blood biomarkers were analyzed with respect to the expected age of onset.
Amyloid-beta clearance rate is decreased by 30% in AD
compared to controls. Changes in clinical, cognitive, MRI,
PET, CSF, and blood biomarkers in autosomal dominant
AD indicate the pathophysiologic cascade begins up to 20
years before the expected age of onset.
The pathophysiologic changes of AD can be specifically
measured and targeted for clinical trials. Autosomal dominant AD prevention trials offer a unique opportunity to
lead the way to effective treatments for all AD.
Study supported by: NIH K-23-AG03094601, NIH R01-NS065667, NIH 3P-01-AG02627603S1 (FACS), NIH
1U-01-AG03243801 (DIAN), ADRC (P50 AG05681-22),
HASD (P01 AG03991-22), WU CTSA award (UL1
RR024992),
Mass
Spectrometry
Resource
(NIH
RR000954), Eli Lilly research collaboration
R.J.B. is a co-founder of a company (C2N Diagnostics)
that has licensed a Washington University patent on some
of the technology described in this abstract.
M1403. Very Early Gait Training after Acute Stroke; a
Dose-Escalation Study
Randolph S. Marshall, Ying K. Cheung, Clare Bassile, Laura
A. Evensen, Roujie Chen, Veronica Perez, Ronald M. Lazar
and Bernadette Boden-Albala; New York
Intensive rehabilitation within days of stroke may benefit
from an altered inhibition/disinhibition environment which
promotes neuroplasticity. Conversely, early rehab may be
impeded by excitotoxicity, medical co-morbidities, logistics
of diagnostic testing, and low motivation.
We used a stepwise sequential probability ratio test
(sSPRT) with 6 tiers to determine the maximal tolerated
dose of standard gait training at 24–96 hours after ischemic
or hemorrhagic stroke. A multidisciplinary acute stroke/
rehab team assessed cardiac and neurological safety outcomes. Inclusion criteria: NIHSS leg motor or ataxia 1
and prestroke Rankin 3.
After 28 patients the study met the sSPRT algorithm
requirements of dose-escalation to the highest tier, with 5 of
6 patients completing 60 min/day at 24–96 hours. Safety
outcomes included 3 cardiac withdrawals (2 patients at tier
3, 1 at tier 6), and 3 fatigue withdrawals (1 at tier 4, 1 at
tier 5, 1 at tier 6). One patient failed to complete his
assigned dose because of sedation for diagnostic testing.
These preliminary data suggest that very early rehabilitation with gait training is safe and feasible beginning
24–48 hours after stroke. Further study is required to establish efficacy of early rehabilitation intervention in
acute stroke.
Study supported by: This work was supported by a Pilot
Grant Award through Columbia University’s CTSA.
T1502. Integrating Genome-Wide Association and
Functional Validation To Understand Susceptibility for
Alzheimer’s Pathology
Joshua M. Shulman, Portia I. Chipendo, Lori B. Chibnik,
Brendan T. Keenan, Dong Tran, Matthew A. Huentelman,
Julie A. Schneider, Eric M. Reiman, Denis A. Evans, David
A. Bennett, Mel B. Feany and Philip L. De Jager; Boston,
MA; Chicago, IL and Phoenix, AZ
Gene discovery in Alzheimer’s disease (AD) is limited by etiologic heterogeneity of dementia in cases and subclinical
disease in controls. We have implemented a novel strategy
using quantitative AD pathology as an outcome for genome-wide association (GWA) analysis. Candidate susceptibility genes were subsequently tested for functional
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validation in a Drosophila model, based on transgenic
expression of human Tau. In a pilot study of 227 subjects,
6 out of 15 genomic regions associated with AD pathology
contained genes showing interactions with Tau neurotoxicity
in vivo. In the full cohort of 651 autopsies, GWA identified
a variant in PFTK1 (rs11563839) associated with neurofibrillary tangle burden (p ¼ 6106), and this polymorphism was also related to episodic memory decline (p ¼
0.004) in 1600 prospectively-followed, elderly subjects. Significantly, in Drosophila, we find that both gain- and lossof-function of the PFTK1 ortholog, Eip63E, is associated
with suppression and enhancement of Tau toxicity, respectively. Interestingly, PFTK1 encodes a cell cycle-related kinase strongly expressed in adult brain. Our strategy of integrating a GWA scan for pathologic phenotypes with
functional validation in a model organism is likely to be a
powerful approach for gene discovery in AD.
Study supported by: National Institutes of Health/National
Institute on Aging, Massachusetts Alzheimer’s Disease Research
Center, the Harvard NeuroDiscovery Center, and the Clinical
Investigator Training Program: Beth Israel Deaconess Medical
Center–Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co.
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T1504. Insulin-Like Growth Factor 1 (IGF-1) and Risk
of Alzheimer’s Disease: The Framingham Study
Andrew J. Westwood*, Alexa S. Baiser, Ramachandran S.
Vasan, Tamara B. Harris, Ronenn Roubenoff, Aleksandra
Pikula, Rhoda Au, Charles DeCarli, Philip A. Wolf and
Sudha Seshadri; Boston, MA; Framingham, MA; Bethesda,
MD and Sacremento, CA
Objective: To relate serum IGF1 to risk of Alzheimer’s disease (AD) and to brain volumes in a dementia-free community sample.
Background: IGF1 may be a biological link between lifestyle and risk of AD; exercise elevates and hyperinsulinemia
depresses circulating IGF1. IGF1 levels correlate positively
with cognition in older men and lower levels are reported in
mouse models of AD.
Method: Framingham participants (N ¼ 648, mean age
79 6 4 yrs, 63% women) who had serum IGF1 measured
(radioimmunoassay, coefficient of variation 4%) in 1990-94
were followed prospectively for incident AD. Dementia-free
survivors (N ¼ 161) underwent brain MRI in 1999–2005.
Results: Mean IGF1 levels were 143 6 60lg/L. We
observed 105 cases of incident AD over a mean follow-up
of 9 6 4 years. In multivariable models adjusted for age-,
sex-, APOE, plasma homocysteine and waist-hip ratio, each
standard deviation increase in baseline IGF1 was associated
with a 23% lower risk of AD (HR ¼ 0.77,95%CI:0.620.96;p ¼ 0.019). Persons with IGF1 levels in the lowest
quartile had lower brain volumes (b 6 SD ¼ 0.6 6 0.28;
p ¼ 0.033) cross-sectionally, and a 80% greater risk of
developing AD (HR ¼ 1.80,95%CI:1.19–2.71;p ¼ 0.005)
compared to others.
Conclusions: Higher IGF1 levels may protect from clinical AD and subclinical brain atrophy.
Study supported by: This work was supported by the Framingham Heart Study’s National Heart, Lung, and Blood
Institute contract (N01-HC-25195) and by grants from the
National Institute of Neurological Disorders and Stroke
(R01 NS17950 to P.A.W.) and from the National Institute
on Aging (R01 AG16495 to P.A.W., AG08122 to P.A.W.,
AG033193 to S.S., AG031287 to S.S., AG033040 to
P.A.W., P30AG013846 to S.S.). Dr. Roubenoff is an employee of Biogen Idec, Inc, but reports no conflict of interest with the subject of this paper
T1503. Brain Expression Genome-Wide Association
Study (eGWAS) and Alzheimer’s Disease
Nilufer Ertekin-Taner, Fanggeng Zou, High Seng Chai, Curtis
S. Younkin, Julia Crook, V Shane Pankratz, Mariet Allen,
Minerva M. Carrasquillo, Christopher N. Rowley, Otto
Pedraza, Morad Ansari, Caroline Hayward, Igor Rudan,
Harry Campbell, Ozren Polasek, Nicholas D. Hastie, Asha A.
Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li
Ma, Kimberly G. Malphrus, Ryan Palusak, Sarah Lincoln,
Gina Bisceglio, Constantin Georgescu, Christopher P. Kolbert,
Jin Jen, Zbigniew Wszolek, Maria Barcikowska, Sigrid B.
Sando, Jan Aasly, Kevin Morgan, Clifford Jack, Ronald C.
Petersen, Neill R. Graff-Radford, Alan Wright, Dennis W.
Dickson and Steven G. Younkin; Jacksonville, FL; Rochester,
MN; Edinburgh, United Kingdom; Split, Croatia; Zagreb,
Croatia; Warsaw, Poland; Trondheim, Norway and
Nottingham, United Kingdom
Genetic variants that modify brain gene expression may also
influence risk for CNS diseases, including Alzheimer’s disease (AD). We performed an eGWAS of 24,526 transcript
levels measured in the cerebella of 197 ADs and 177 nonADs with 313,330 SNP genotypes. After elimination of
probes with a known SNP within their sequence, cis-SNP/
transcript level associations were sought. Corrections were
made for technical and biological variables. Significant cerebellar associations were also tested in the temporal cortex of
198 ADs and 193 non-ADs. Cerebellar expression was detectable for 69% of all transcripts. After accounting for
technical variance, cis-SNPs explained 5–85% of the variance of >1,600 transcripts. There was an excess of significant associations. Substantial number of cis-SNP/transcript
associations were significant in both ADs and non-ADs
with similar direction and magnitude of effects. Many top
cerebellar cis-SNPs were also detectable in the temporal cortex with similar effect sizes. We demonstrate that genetic
factors influence brain expression for many genes, replicably
across disease pathologies and tissue regions. eGWAS may
be an excellent approach to identify candidate functional
genetic variants implicated in AD. Top cis-SNPs are investigated for association with AD and its endophenotypes
including plasma amyloid-b.
Study supported by: R01 AG018023, P50 AG016574
T1505. Components of Blood Pressure and Progression
of Cerebral Leukoaraiosis: The ARIC Study
Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker,
Josef Coresh, Clifford R. Jack, Jr., David S. Knopman,
Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and
Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC;
Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle,
WA and Jackson, MS
Background: The contribution of blood pressure (BP) components to the burden and progression of cerebral white
matter hyperintensity (WMH) is poorly understood. We
evaluated these associations in the population-based Atherosclerosis Risk in Communities (ARIC) cohort.
Methods: 983 participants each underwent 2 brain MRIs
10 years apart. Systolic (SBP) and diastolic BP (DBP) were
measured at 4 study visits. Four BP components were examined as predictors of WMH progression: 1) mean arterial
pressure (MAP); 2) pulse pressure (PP); 3) orthostatic hypotension (OH); and 4) 10-year change in BP.
Results: Baseline (preceding MRI #1) MAP value predicted WMH progression (OR 1.39 (1.20–1.62), per 10
mm Hg increase), but PP did not. Presence of OH did not
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predict WMH progression, but OH severity did (OR 1.21
(1.02–1.42) per 10 mm Hg SBP decrease). Change in DBP
over 10 years had a U-shaped relationship with WMH progression: extreme increases and decreases, independent of
antihypertensive use, were both associated with greater
WMH progression (p ¼ 0.007).
Discussion: WMH progression is significantly predicted
by MAP and extent of orthostatic SBP reduction. Significant
changes over time in DBP, whether positive or negative, predict WMH progression, cautioning against simplified interpretations of blood pressure associations.
Study supported by: The Atherosclerosis Risk in
Communities Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute
contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN2
68201100009C, HHSN2682011000010C, HHSN2682011
000011C, HHSN2682011000012C).
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Wilcoxon Signed Ranks Tests. We found that, for the total
sample, there were significant differences between MoCA
and MMSE with regard to total score (p<0.001), in addition to visuospatial (p ¼ 0.002), language (p<0.001), and
memory (p<0.001) domains. Although mean MMSE scores
declined only modestly across the decades, the decline in
mean MoCA scores was more dramatic. There were no consistent domain differences between the MoCA and MMSE
during the 3rd, 4th and 5th decades; however, significant
differences with regard to memory and language (p<0.01–
p<0.001) emerged in the 6th through 9th decades. We conclude that the MoCA may be more sensitive than the
MMSE at detecting age-related decrements in cognitive performance, even in non-clinical adult populations.
Study supported by: Huntington’s Disease Society of
America (HDSA) and Shiley Marcos Alzheimer’s Disease
Research Center NIH P50 AG005131
T1508. Amyloid Imaging with Florbetapir-PET
Correlates with Cognitive Performance in
Non-Demented Oldest-Old
Maria M. Corrada, Dana E. Greenia, Chris M. Clark, Carrie
B. Peltz, Mark A. Mintun, Michael J. Pontecorvo, Abhinay D.
Joshi and Claudia H. Kawas; Irvine, CA; Philadelphia, PA
and St. Louis, MI
T1506. Therapeutic and Preventive Effects of a Novel
AD Vaccine
Carmen Vigo, Ivan Cuevas, Lucia Fernandez, Valter
Lombardi, Richard Manivanh and Ramon Cacabelos;
Sunnyvale, CA and Bergondo, La Coruna, Spain
A vaccine consisting of b-amyloid peptide (Ab) delivered in
a liposomal matrix composed of phosphatidylcholine: phosphatidylglycerol:
cholesterol:
sphingosine-1-phosphate
(EB101) was administered intraperitoneally for seven
months to double transgenic mice (B6C3-Tg (APPswe,PSEN1dE9)), before or after the AD pathology was developed. Ab plaques and neurofibrillary tangles were quantified
by ELISAs and brain histology using specific antibodies. Basal immunological interaction between the T-cells in the
affected hippocampal area and other immune activation
markers, including glial fibrillary acidic protein (GFAP)
(astroglia) and CD-45 (B-cells) were also studied. Both preventive and therapeutic vaccination with EB101 resulted in
a marked inhibition of Ab deposits (from 60 to 90%), a
reduction of neurofibrillary tangles (70 to 90%) and almost
completely suppression of reactive gliosis as measured by
GFAP immunoreactivity, consistent with a marked decrease
in amyloidosis-induced inflammation. No external neurological deficits were observed as a result of EB101 immunization (limb paralysis or brain atrophy). Cognitive tests in
these animals treated with EB101 also show a dramatic
improvement in learning and psychomotor activity. The
present results indicate that the immunization with EB101
prevents and reverses AD neuropathology and underlined
inflammation, thus warranting further studies.
Study supported by: Euroespes Foundation
We examined the association between amyloid imaging with
florbetapir F18 positron emission tomography (PET) and
cognitive performance in non-demented oldest-old.
Thirteen non-demented oldest-old subjects received a
florbetapir-PET scan within 3 months of neuropsychological
testing, which included the Modified Mini-Mental State
Exam (3MS), California Verbal Learning Test (CVLT) 10minute delay, Boston Naming Test, and Trails A and B.
Scans were analyzed with a semiautomated quantitative
analysis of the cortical to cerebellar signal ratio (SUVr) on
the average of 6 cortical brain regions (frontal, temporal, parietal, anterior and posterior cingulate, and precuneus).
Participants were 9 women and 4 men with an average age
of 94.2 years (range:90–99). Eight participants were diagnosed
as cognitively normal and 5 had cognitive impairment but did
not meet dementia criteria. CVLT scores correlated significantly with the average SUVr (Pearson corr ¼ 0.64, p ¼
0.03) and 3MS scores trended towards a significant correlation
with the average SUVr (Pearson corr ¼ 0.54, p ¼ 0.07).
This preliminary study suggests that greater amyloid burden is associated with poorer cognition, especially memory,
in non-demented oldest-old participants. Amyloid imaging
may identify oldest-old individuals at increased risk of
developing Alzheimer’s disease.
Study supported by: NIH grant RO1AG21055 and Avid
Radiopharmaceuticals, Inc.
Dr. Kawas and Ms. Grenia received a grant from Avid
Radiopharmaceuticals (awarded to UCI) for their participation in this study. Dr. Clark, Dr. Mintun, Dr. Pontecorvo,
and Mr. Joshi are employees of Avid Radiopharmaceuticals,
a wholly owned subsidiary of Eli Lilly.
T1507. MoCA vs. MMSE: Patterns of Cognitive
Performance across Adult Lifespan in a Non-Clinical
Sample
Shea Gluhm, Charles Van Liew, Jody Goldstein, Guerry Peavy,
Mark Jacobson, Stephanie Lessig and Jody Corey-Bloom; La
Jolla, CA and San Diego, CA
T1509. FRET Measurements of Ab-Induced Glutamate
Release from Astrocytes
Sara Sanz-Blasco, Juan C. Piña-Crespo, Maria V. Talantova
and Stuart A. Lipton; La Jolla, CA
The Mini Mental State Examination (MMSE) is the most
commonly used brief cognitive screening instrument; however, the Montreal Cognitive Assessment (MoCA) may be
more sensitive to early cognitive dysfunction. The present
study sought to compare age-related decline on these measures across the adult lifespan in a non-clinical sample. Performance on the MMSE and MoCA of 202, presumably
normal, community-dwelling participants ranging in age
from 20–89, divided by decade, were compared with
Recent failures of clinical trials for Alzheimer’s disease (AD)
using anti-amyloid b-peptide (Ab) approaches suggest that
it may be necessary to attack downstream targets in the Ab
cascade. To elucidate such targets, we studied the effect of
Ab on astrocytes. Astrocytes are known to modulate
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neuronal excitability and synaptic transmission. Here, we
used the glutamate sensing fluorescent reporter (SuperGluSnFR) developed by Roger Tsien’s laboratory to perform
sensitive optical measurements of glutamate release in
response to Ab. This probe provides both a temporal and
quantitative fluorescent readout of glutamate concentration
by imaging FRET-dependent changes. We transfected HEK293T cells with SuperGluSnFr, and then co-cultured these
‘glutamate-sensing cells’ with astrocytes. Nanomolar concentrations of oligomerized (but not non-oligomerized) Ab
induced release of several hundred-micromolar glutamate
from astrocytes. These levels of glutamate can cause synaptic
loss and excitotoxic damage to neurons. Taken together with
prior studies, our work suggests that the neurotoxic effects
of Ab may be mediated at least in part by local release of
glutamate from astrocytes. Additionally, we found that
newer congeners of memantine (called NitroMemantines)
are able to prevent toxic glutamatergic effects of Ab to a
greater degree than memantine itself.
Study supported by: NIH and ADAMAS Pharmaceuticals, Inc.
Stuart Lipton is the named inventor on patents for memantine and NitroMemantine for neurodegenerative disorders
that are licensed to Forest Laboratories, Inc. and ADAMAS
Pharmaceuticals, Inc., respectively. Concerning memantine,
Dr. Lipton participates in a Royalty Sharing Agreement
administered by his former institution, Harvard Medical
School/Children’s Hospital, Boston.
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Guam ALS-PD Complex (tauopathy) is linked epidemiologically to cycasin, methylazoxymethanol (MAM) glucoside, a
neurotoxin, carcinogen and genotoxin. MAM produces O6methylguanine (O6-mG) DNA lesions that are repaired by
O6-mG methyltransferase (MGMT). We asked whether
MAM-induced DNA damage in MGMT-deficient
(Mgmt/) mouse brain (a model of the young adult
human brain) activates signal transduction pathways perturbed in neurodegenerative disease. Brain transcriptional
profiles of young adult Mgmt/and wild-type mice were
determined at intervals after a single systemic dose of MAM
or vehicle. Mgmt/ mice treated with MAM vs. vehicle
showed 362 differentially expressed genes, of which 57 were
highly correlated with O6-mG levels. Sixty of 153 modulated genes correlated with O6-mG when the response of
wild-type vs. Mgmt/ mice to MAM vs. vehicle was
determined. Top associations were with neurological disease,
psychological disorders, cancer, and genetic disorders. Prominent MAM-modulated brain KEGG pathways included
Wnt-beta-catenin, which is perturbed in Alzheimer Disease
(AD) and in MAM-induced colorectal carcinoma. Thus,
MAM modulates pathways common to cancer (in cycling
cells) and cell degeneration (in non-cycling neurons). Exposure to environmental MAM-like genotoxins (e.g., nitrosamines) may have relevance to the etiology of other tauopathies, notably AD.
Study supported by: National Institutes of Environmental
Health Sciences: ES11384, ES11399, ES011387 and
ES07033.
T1510. Is Poststroke Dementia Related to Amyloid
Deposition and Microglia Activation?
Wolf-Dieter Heiss, Basia Radlinska, Jean-Paul Soucy, Ralf
Schirrmacher, Alexander Thiel and Vladimir Hachinski; Cologne,
Germany; Montreal, QC, Canada and London, ON, Canada
T1512. Genetic Associations between VPS10 Receptor
Genes and Late-Onset Alzheimer’s Disease
Christiane Reitz, Joseph Lee, Lindsay Farrer, Margaret PericakVance, Jonathan Haines, Ekaterina Rogaeva, Peter St. GeorgeHyslop and Richard Mayeux; New York; Boston; Miami;
Nashville and Toronto, Canada
Amyloid deposition typical for Alzheimer’s Disease might be
a predisposing factor for poststroke dementia and might be
aggravated by inflammation accompanying ischemic changes.
The relationship between amyloid deposition, inflammatory
reaction and development of poststroke dementia is studied in
5 patients with first supratentorial ischemic stroke by MRI (at
2 weeks and 5 – 7 months) and PET with 11C-PIB for amyloid imaging and with 11C-PK 11195 for inflammation at 6
months, the clinical course is followed for 12 months.
Preliminary results indicate a significant increase in global
PIB uptake (SUVR > 1.5) in the entire cortex compared to
cerebellum. This amyloid deposition usually was asymmetric
with peak values in prefrontal (SUVR ¼ 2.29 6 0.325) or
parieto-temporal areas (SUVR ¼ 2.02 6 0.202). Increased
PK-uptake as a marker of microglia activation was found in
areas around the infarct, but also in connecting fiber tracts
and distant from the ischemic lesion.
These preliminary data demonstrate amyloid deposition
and increased microglia activation in patients after stroke.
The relationship between these two pathological processes
and their impact on the development and progression of
cognitive impairment will be further investigated.
Background: Genetic and functional studies showed that
genetic variation in SORL1 and SORCS1 is associated with
LOAD risk by modulating secretase processing of APP.
Consequently, underexpression of SORL1 or SORCS1 leads
to Ab overexpression and increased LOAD risk. We
hypothesized that also genetic variation in the homologs
SORCS2 and SORC3 is associated with LOAD.
Methods: First, we analyzed associations between genetic
variation in SORCS2 and SORCS3 and LOAD risk in several independent datasets. Then, we compared SORCS2
and SORCS3 expression levels in brain regions from LOAD
cases and controls, and performed cell biological experiments exploring the effect of both genes on APP processing.
Results: Consistent with SORL1 and SORCS1, inherited
variants in SORCS2 and SORCS3 were associated with
LOAD risk. In addition, both genes were underexpressed in
amygdala tissue from LOAD brains compared to control
brains. Finally, we found evidence that - similar to SORL1
and SORCS1- both SORCS2 and SORCS3 may influence
APP processing by modulating gamma secretase processing
of APP.
Conclusions: In addition to SORL1 and SORCS1, also
variants in SORCS2 and SORCS3 may play a role in the
pathogenesis of LOAD through an effect on APP processing.
Study supported by: R37-AG15473 (Mayeux), P01AG07232 (Mayeux), R01-AG09029 (Farrer), R01AG025259 (Farrer), P30-AG13846 (Boston University Alzheimer’s Disease Research Center grant), K23AG034550
(Reitz). R01-AG027944 (Pericak-Vance), R01-AG019757
(Pericak-Vance)
T1511. Cycad Methylazoxymethanol Linked to DNA
Damage, Cancer and Neurodegeneration
Glen E. Kisby, Rebecca C. Fry, Michael R. Lasarev, Theodor
K. Bammler, Richard P. Beyer, Mona I. Churchwell, Daniel R.
Doerge, Lisiane B. Meira, Valerie S. Palmer, Ana-Luisa
Ramos-Crawford, Xuefeng Ren, Robert S. Sullivan, Terrance J.
Kavanagh, Leona D. Samson, Helmut Zarbl and Peter S.
Spencer; Portland, OR; Seattle, WA; Cambridge, MA;
Jefferson, AR; Guildford, Kent, United Kingdom; Buffalo, NY;
Piscataway, NJ and Chapel Hill, NC
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T1513. Cardiac Ejection Fraction, Cognitive Function
and Leukoaraiosis in an Elderly Cohort: The
Cardiovascular Health Study
Rebecca F. Gottesman, Salvador Cruz-Flores, Annette
Fitzpatrick, John Gottdiener, Traci Bartz, Richard Kronmal
and W.T. Longstreth, Jr.; Baltimore, MD; St. Louis, MO and
Seattle, WA
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AG024904). ADNI is funded by the National Institute on
Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering PharmaAG,Bristol-Myers Squibb, Eisai Global Clinical Development,
Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co.,
Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc,
F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and
Wyeth, as well as non-profit partners the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation, withparticipation from the U.S. Food and Drug Administration. Private
sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The
grantee organization is the Northern California Institute for
Research and Education, and the study is coordinated by the
Alzheimer’s Disease Cooperative Study at the University of
California, San Diego. ADNI data are disseminated by the
Laboratory for Neuro Imaging at the University of California,
Los Angeles. This research was also supported by NIH grants
P30 AG010129, K01 AG030514, and the Dana Foundation.
None of the study sponsors had any role in the design and
conduct of the current study, nor in data analysis, interpretation, preparation, review or approval of the manuscript.
L. McEvoy’s spouse is President, CorTechs Labs, Inc. La Jolla,
CA; Sebastian Magda is an employee of CorTechs Labs, Inc.
Background: Heart failure has been associated with cognitive dysfunction. To explore mechanism, we examined associations among ejection fraction (EF), cognition, and MRIdefined white matter hyperintensity (WMH) in the Cardiovascular Health Study (CHS), a longitudinal cohort study
of participants 65 years old.
Methods: We included 1972 CHS participants who underwent echocardiography, 2 brain MRIs 5 years apart, and cognitive assessments concurrent with the MRIs. Linear regression
models including vascular risk factors, demographics, and EF
(normal or impaired) were used to evaluate these outcomes:
WMH grade on a 10-point scale, progression of WMH by
1 grade, and change in cognitive performance on the 100point modified Mini-Mental State examination (3MS) and
Digit Symbol Substitution test (DSST).
Results: EF independently predicted WMH grade at the second MRI (p ¼ 0.05) and WMH progression (OR 1.61, 95%
CI 1.07–2.43). Worse EF independently predicted more decline
in 3MS (p ¼ 0.02) and DSST (p ¼ 0.02), but these relationships were partially attenuated with WMH grade as a covariate.
Conclusions: In an elderly population, EF predicts volume and progression of WMH. EF also predicts cognitive
performance, but this may be partially mediated through
effects on the white matter.
Study supported by: NIH/ NHLBI (not to the first / corresponding author directly)
T1515. Light and Electron Microscopic Analysis of FUS
Immunoreactivity in 3 Variants of Tau and TDP-43
Negative Frontotemporal Lobar Degeneration
Keith A. Josephs, Wen-Lang Lin, Joseph E. Parisi, Neil GraffRadford, Ronald C. Petersen and Dennis W. Dickson;
Rochester, MN and Jacksonville, FL
Background: The majority of frontotemporal lobar degenerations (FTLD) can be classified as tau or TDP-43 immunoreactive. Three rare variants were unclassified until recent
evidence demonstrated FUS immunoreactivity: neuronal intermediate filament inclusion disease (NIFID), atypical
FTLD with ubiquitin-immunoreactive inclusions (aFTLDU) and basophilic inclusion body disease (BIBD).
Aim: To assess the immunohistochemical profile of
NIFID, aFTLD-U and BIBD.
Methods: Light, electron and immunoelectron microscopic analysis of 15 cases of NIFID (n ¼ 5), aFTLD-U (n
¼ 8) and BIBD (n ¼ 2).
Results: All aFTLD-U and BIBD, and 3/5 NIFID cases
were FUS immunoreactive. One FUS-negative NIFID case
showed TDP-43 immunoreactivity. Electron microscopic
examinations revealed FUS-immunoreactive granulofilament
cytoplasmic inclusions in all aFTLD-U and BIBD cases,
and in the FUS-positive NIFID cases. Granulofilament
inclusions in the TDP-43 positive NIFID case were FUS
negative, yet TDP-43-immunoreactive. Compact hyaline
inclusions in all 5 NIFID cases were FUS-negative.
Conclusions: Unlike in aFTLD-U and BIBD, FUS immunoreactivity in NIFID is variable and is limited to only certain
types of inclusions, arguing against the notion that FUS is the
primary pathological process in NIFID. Furthermore, TDP43 immunoreactivity and NIFID are not mutually exclusive.
Study supported by: NIH R01-AG037491
T1514. Predicting MCI Outcome with Clinically
Available MRI and CSF Biomarkers
David S. Heister, James B. Brewer, Sebastian Magda, Kaj
Blennow and Linda K. McEvoy; La Jolla, CA and Mo¨lndal,
Sweden
Cerebrospinal fluid (CSF) measures and medial temporal
lobe atrophy (MTLA) on structural magnetic resonance
images (MRIs) each predict decline to Alzheimer’s disease
(AD), but how such measures can be used clinically to
improve predictive prognosis is unclear.193 MCI participants
were separated into risk groups (high/low) based on MTLA,
quantified from FDA-approved software for volumetric imaging of MRIs, or based on cerebrospinal fluid (CSF) levels of
total tau and Ab 1–42. Participants were also stratified into
groups based on the combination of MTLA and CSF risk
measures. Cox hazards models were used to assess group hazard ratios (HR) of converting to AD. MCI individuals with
high atrophy or high CSF risk showed significantly greater
hazard of AD conversion than those with low risk for each
measure (HR: 3.52–4.20). Combining atrophy and CSF risk
information substantially improved predictive ability. Individuals with both risk factors showed a significantly higher HR
(13.68) than those with neither risk factor. Using both measures, 80% of high-risk individuals developed AD in 3 years
compared to 10% of low-risk individuals. Clinically available
CSF and MRI measures can be combined to significantly
improve predictive prognosis in MCI.
Study supported by: L.K.M. is supported by NIA
K01AG029218; J. B.B. is supported by NINDS
K02NS067427. Data collection and sharing for this project
was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01
T1516. Effects of Once-Daily, Extended-Release
Memantine (28 mg/day) on Cognitive Domains in
Patients with Moderate to Severe Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
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In this post hoc analysis of a 24-week, randomized, placebocontrolled trial (MEM-MD-50, NCT00322153) in ChEItreated patients with moderate to severe Alzheimer’s disease
(AD), we examined the effects of a new, extended-release
(ER) formulation of memantine (28 mg, once daily) on
individual SIB domains, as well as on aggregated domains
defined previously (Schmitt, 2006). Treatment groups were
compared in terms of mean change from Baseline at Endpoint for nine SIB domains (Social Interaction, Memory,
Orientation, Language, Attention, Praxis, Visuospatial Ability, Construction, and Orienting to Name) and combinations of domains aggregated using a face-valid approach
into three higher-order subscales: MEMORY, LANGUAGE,
and PRAXIS. Significant advantage of memantine ER over
placebo was observed for the domains of Memory (OC, P
¼ 0.021; LOCF, P ¼ 0.016), Language (OC, P ¼ 0.003;
LOCF, P ¼ 0.004), Attention (OC, P ¼ 0.014; LOCF, P
¼ 0.003), Praxis (OC, P ¼ 0.015; LOCF, P ¼ 0.002), Orientation (LOCF, P ¼ 0.043), and Construction (OC, P ¼
0.042), and for all three higher-order subscales (MEMORY:
OC, P ¼ 0.002; LOCF, P ¼ 0.003; LANGUAGE: OC,
LOCF, P ¼ 0.003; PRAXIS: OC, P ¼ 0.012; LOCF, P ¼
0.004). In conclusion, memantine ER treatment may be
associated with significant improvements on several cognitive domains, including memory, language, praxis, and
attention.
Study supported by: Forest Research Institute
Michael Tocco and Stephen M. Graham are employees of
Forest Research Institute, Inc. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor
to several pharmaceutical companies, including Forest
Research Institute, Inc. Michael L. Miller and Vojislav
Pejovic are employees of Prescott Medical Communications
Group, an independent contractor to several pharmaceutical
companies, including Forest Research Institute, Inc.
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Drs. Stephen Graham and Michael Tocco are employed
by Forest Research Institute. Dr. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor
to several pharmaceutical companies, including Forest
Research Institute, Inc. Drs. Michael L. Miller and Vojislav
Pejovic are employees of Prescott Medical Communications
Group, an independent contractor to several pharmaceutical
companies, including Forest Research Institute, Inc.
T1518. Clinical Gait Abnormalities and Hippocampal
Morphometry in MCI: Preliminary Results from the
ADNI Study
Vincent S. DeOrchis and Joe Verghese; Bronx, NY
Objective: To examine whether clinical gait abnormalities
could identify aMCI subjects with reduced hippocampal
volume and increased risk of cognitive decline.
Methods: The population for this study included subjects
with aMCI diagnosed using established criteria and with
neuroimaging enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Hippocampal volume was
assessed in 370 aMCI subjects using semiautomated voxel
based morphometry available on the ADNI website. The
association of gait abnormalities, as diagnosed by study
clinicians, with hippocampal volume was assessed using linear regression adjusted for age, gender, education and total
brain volume.
Results: Subjects mean age was 72.8 years, average education was 15.4 years and 62.3% were women. The mean
hippocampal volume was 3188.77 þ/ 562.27mm3 on the
right and 3145.28 þ/ 549.78mm3 on the left. Clinical
gait abnormalities were diagnosed in 35 (9.3%) subjects and
were associated with right hippocampal volume (estimate
264.646, 95% CI: 443.4 to 85.8, p ¼ 0.004), but
not the left (p ¼ 0.053). Adding MMSE or memory test
scores to the final model did not change the significance of
association.
Conclusions: Our preliminary study supports gait abnormalities as a clinical marker of worse hippocampal morphology in aMCI.
T1517. Efficacy of Memantine by Baseline Disease
Severity: A Pooled Post-Hoc Analysis of Trials in Mild to
Moderate Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
T1519. Topography of Cortical Thinning in PIBNegative Subcortical Vascular Dementia Versus
Alzheimer’s Disease
Chi Hun Kim, Sang Won Seo, Sung Tae Kim, Jae-Hong Lee,
Jae Seung Kim, Seung Jun Oh, Suk-Hui Kim, Hae Kwan
Cheong, Jong-Min Lee, Seun Jeon and Duk L. Na; Seoul,
Korea and Suwon, Korea
Several randomized, placebo-controlled trials have demonstrated benefits of memantine in patients with moderate to
severe Alzheimer’s disease (AD); trials in mild to moderate
AD have yielded less consistent results. The dementia severity range in which memantine may provide benefits should
be determined with greater precision. In this post-hoc analysis, we pooled 713 memantine-treated (20 mg/day) and 559
placebo-treated patients from three randomized trials in
mild to moderate AD (MMSE range: 10–23). For each
baseline MMSE value, mean change from baseline was estimated for measures of cognition (ADAS-cog), function
(ADCS-ADL23), global status (CIBIC-Plus), and behavior
(NPI). Furthermore, data (intent-to-treat population,
observed cases) were analyzed by means of a mixed model
with quadratic terms for time and baseline MMSE. Memantine treatment was associated with significant benefits versus
placebo within the MMSE range of 12–20 for the ADAScog, 15–18 for the ADCS-ADL, and 10–17 for the CIBICPlus; no significant differences between groups were
observed for the NPI. In conclusion, memantine treatment
may be associated with significant cognitive, functional, and
global benefits in patients with MMSE scores corresponding
to the early moderate stage of AD.
Study supported by: Forest Research Institute
Objective: To determine the existence of cortical atrophy in
Subcortical Vascular Dementia (SVaD) with negative 11CPittsburgh compound B (PIB) PET scan and to compare
the topography of cortical thinning between PIB (-) SVaD
and Alzheimer’s disease (AD).
Methods: Cortical thickness in 24 patients with PIB (-)
SVaD, 81 clinically probable AD subjects with minimal ischemia, and 72 normal cognitive controls (NC) was measured using a surface-based morphometric method. The
results were compared and mapped onto a 3D brain
surface.
Results: Compared with NC, significant cortical thinning
of PIB (-) SVaD was noted in a widespread area including
frontal, temporoparietal, medial frontal, posterior cingulate
cortices, and ligual gyri. Compared with AD, PIB (-) SVaD
demonstrated cortical thinning in bilateral perisylvian area,
ligual gyri, and right medial frontal lobe. Compared with
PIB (-) SVaD, AD showed significant cortical atrophy in
bilateral medial temporal lobes and precuneus.
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Results: Across our mixed sample of subjects (n ¼ 33;
21 with Fragile X-associated Tremor Ataxia Syndrome, 12
normal controls, mean age ¼ 65, mean MMSE ¼ 27), a
significant correlation (r ¼ 0.38, p ¼ 0.029) was present
between P600 repetition effect amplitude and left, but not
right, hippocampal volume. Linear regression models found
that subsequent cued recall was predicted by left hippocampal volume and age. In contrast, free recall correlated with
P600 repetition effect amplitude (rho ¼ .49, p ¼ 0.004)
only.
Conclusion: P600 word repetition effect correlates with
left hippocampal volume. These two measures appear complementary and predict different aspects of memory
performance.
Study supported by: National Institutes of Health Roadmap Interdisciplinary Research Consortium Grant [Grant
Numbers UL1DE019583 (NIDCR), RL1AG032115], NIH
Grant R01-AG18442, California Alzheimer’s Disease
Program
Randi Hagerman receives research support from Neuropharm, Seaside therapeutics, Forest, Johnson and Johnson
and Roche and consultation with Novartis for fragile X
research studies.
Interpretation: Small vessel disease without amyloid burden may lead to substantial cortical atrophy. PIB (-) SVaD
demonstrated characteristic cortical thinning in bilateral
perisylvian area, ligual gyri, and the right medial frontal
lobe.
Study supported by: The Korea Healthcare Technology
R&D Project, Ministry for Health, Welfare & Family
Affairs, Republic of Korea (A050079), grants from the Asan
Institute for Life Sciences (2006-159), and the Conversing
Research Center Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (2009-0081959)
T1520. The First Nationwide Survey of Bardet-Biedl
Syndrome in Japan
Makito Hirano, Toshihide Yamashita, Yasushi Ikuno, Hiromi
Iwahashi, Mitsuru Ohishi, Toshiyuki Mano, Ryu Ishihara,
Ichiro Tanaka, Keiko Yanagihara, Yusaku Nakamura and
Susumu Kusunoki; Sakai, Osaka, Japan; Suita, Japan; Izumi,
Japan; Osaka, Japan; Kashihara, Japan and Osaka Sayama,
Japan
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by mental impairment, rod-cone dystrophy, polydactyly, central obesity, hypogonadism, and renal
abnormalities. The causative genes have been identified as
BBS1-14 genes encoding proteins that maintain cilia function, but more than 20% of patients have no mutations
identified. This disease is extremely rare in Japan, where
only a few patients have been reported. We conducted the
first nationwide survey of this disease in 2010. We summarized clinical and genetic information of newly identified
patients and previously reported patients. We found that
rare liver fibrosis was detected in 20% of patients, while
only 30% of patients had apparent renal abnormalities,
thought to be a universal symptom. DNA array analysis
(BBS1-10,12) was performed in 9 patients with clinically
definite or possible BBS, but no known mutations were
identified. However, cultured fibroblasts from two patients
had reduced protein levels of BBS6 without any coding
mutations, suggesting abnormalities in transcription/translation or protein instabilities affected by other regulatory proteins. In conclusion, we speculate that clinical symptoms
and genetic background of BBS in Japan may differ from
those in the Western countries.
Study supported by: Health and Labour Science Research
Grants in Japan (Research in intractable diseases)
T1522. Visuospatial Construction Measures and Their
Utility in Identifying Dementia of the Alzheimer’s Type
Bonnie M. Scott, G. Duncan, H. Carlson, Matthew Nance,
Michele K. York, Angela Larery, Josephine Stouter and Adriana
M. Strutt; Houston, TX
Objectives: To examine the psychometric properties and
clinical utility of three visuospatial-construction (VC) measures in differentiating Mild Cognitive Impairment (MCI)
and Alzheimer’s disease (AD).
Background: Assessment of VC deficits aid clinicians in
distinguishing AD from other forms of dementia and determining the patient’s functional status. However, there is currently no research comparing the psychometric properties of
commonly employed VC measures with MCI subtypes and
varying stages of AD.
Methods: 37 MCI and 126 AD patients completed the
Beery-Buktenica Developmental Test of Visual Motor Integration (Beery), Rey-Osterrieth Complex Figure Test (ReyO), and the Block Design subtest of the WAIS-III.
Results: Age and education significantly differed between
groups, and were therefore utilized as covariates. ANCOVAs
revealed significant between group differences (p<0.001)
across the three outcome measures. While the Rey-O demonstrated the highest sensitivity (76.2%), the Beery yielded
a greater specificity (94.6%). Additional statistics will be
presented for the VC measures by subgroups (e.g. amnestic
vs non-amnestic; mild and moderate AD).
Discussion: Considering the significant differences
between the VC capacities of patients with and without
neurodegenerative conditions, identification of the most
statistically sound instrument in assessing VC is warranted.
T1521. P600 Word Repetition Effect Amplitude
Correlates with Left Hippocampal Volume
John M. Olichney, Rawi Nanakul, Alireza K. Javan, Patrick
E. Adams, Andrea Schneider, Andreea Seritan, Randi J.
Hagerman, Paul J. Hagerman and Susan M. Rivera; Davis,
CA and Sacramento, CA
Background: Prior work has shown that hippocampal volume and certain ERP components (e.g. P600 repetition
effect) can be predictors of memory ability. However, the
relationship between hippocampal volume and electrophysiological measures of human memory remains unclear.
Objective: To define the relationship between P600 word
repetition effect amplitude and hippocampal volume. We
hypothesized they would be moderately correlated, with
each variable independently predicting verbal memory.
Methods: 32 channel ERP data was recorded during a
category decision task. Structural 3T MRI was acquired
(Siemens Trio) and hippocampal volumes measured on 3D
MPRAGE sequences.
T1523. Responder Analysis in a Trial of Once-Daily,
Extended-Release Memantine (28 mg) in Patients with
Moderate to Severe Alzheimer’s Disease
Stephen M. Graham, Suzanne Hendrix, Michael L. Miller,
Vojislav Pejovic and Michael Tocco; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
This post hoc analysis explored therapeutic responses in a
24-week, randomized, placebo-controlled trial of once-daily,
extended-release (ER) memantine (28 mg) in ChEI-treated
patients with moderate to severe AD. For each efficacy
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measure (SIB, ADCS-ADL19, NPI, CIBIC-Plus), 5 response
levels were defined, based on change scores attained at Endpoint by the 10th, 25th, 50th, 75th, and 90th percentile of
placebo-treated patients. The proportions of memantineand placebo-treated patients attaining each response level
(or better) were compared using Fisher’s exact test. For each
outcome measure, the proportion of memantine-treated
patients numerically exceeded that of placebo-treated
patients at all response levels. On the SIB, the memantine
group was significantly superior at the 90th percentile level
(improvement >11 points; P ¼ 0.003), on the NPI at the
90th percentile level (improvement 17 points; P ¼ 0.018)
and the 75th percentile level (improvement 8 points; P ¼
0.016), and on the CIBIC-Plus at the 75th percentile level
(score <3: P ¼ 0.023). No significant between-group differences were observed on the ADCS-ADL19. In conclusion,
memantine ER provided consistent benefits on the SIB,
NPI, and CIBIC-Plus, particularly among patients who
experienced relatively high levels of improvement.
Study supported by: Forest Research Institute
Michael Tocco and Stephen M. Graham are employees of
Forest Research Institute, Inc. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor
to several pharmaceutical companies, including Forest
Research Institute, Inc. Michael L. Miller and Vojislav
Pejovic are employees of Prescott Medical Communications
Group, an independent contractor to several pharmaceutical
companies, including Forest Research Institute, Inc.
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Resistance to cognitive decline from neuropathology is
postulated to occur due to cognitive reserve (CR). We
examined whether baseline regional cortical thickness and
rate of regional atrophy are structural markers for CR. We
hypothesized that higher education, a proxy for CR, would
be related to greater cortical thickness in areas related to literacy or intellectual ability in healthy controls and individuals with mild cognitive impairment (MCI) from the Alzheimer’s Disease Neuroimaging Initiative. Cortical thickness in
these regions was compared between high (>18 yrs) and
low education (<13 yrs) subgroups among controls and
MCI individuals separately. Unexpectedly, high education
was related to thinner cortices at baseline for controls in lateral occipital and temporal regions and for MCI in the left
inferior parietal region after controlling for age and sex. In
MCI, the difference in cortical thickness persisted after controlling for disease severity. Pre-existing thinner cortex in the
high education group was not associated with a higher atrophy rate than that observed in the low education group.
Cortical thickness in areas related to intellectual ability or
literacy therefore may not be a persistent marker of CR.
Study supported by: Supported by grants from the
National Institute of Aging (AG031224; K01AG029218)
and the National Center for Research Resources (#U24
RR021382).
A.M.D. is a founder of and holds equity interest in CorTechs Labs, Inc, La Jolla, Calif, and serves on its Scientific
Advisory Board. The terms of this arrangement have been
reviewed and approved by the University of California, San
Diego, Calif, in accordance with its conflict of interest policies. The spouse of L.K.M. is president of CorTechs Labs,
Inc, La Jolla, Calif.
T1524. Rates of Cognitive Decline and Alzheimer’s
Disease (AD) Neuropathology in Oldest-Old
Archana B. Balasubramanian, Claudia H. Kawas, Daniel J.
Berlau, Carrie B. Peltz and Marı´a M. Corrada; Irvine, CA
Objective: To examine if rates of cognitive decline vary by
level of AD neuropathology in oldest-old.
Methods: Participants were 68 autopsied individuals
from The 90þ Autopsy Study, a population-based longitudinal study of people aged 90 and older. Participants were
non-demented at baseline and had 3 or more visits. Global
cognition was assessed using the Mini-Mental State Exam
(MMSE). Participants were categorized as having low or
high AD neuropathology based on plaques (CERAD staging: Low ¼ 0-A, High ¼ B-C) and tangles (Braak staging:
Low ¼ 0-III, High ¼ IV-VI). Random effects models were
used to estimate rates of cognitive decline in people with
low or high AD neuropathology.
Results: Rates of cognitive decline did not differ by level
of AD neuropathology. Individuals with low plaques
declined 0.63 points/year on the MMSE, whereas individuals with high plaques declined 0.50 points/year (p ¼ 0.43).
Individuals with low tangles declined 0.66 points/year on
the MMSE, whereas individuals with high tangles declined
0.48 points/year (p ¼ 0.26).
Conclusion: AD neuropathology is not associated with
differing rates of cognitive decline in the oldest-old. Other
factors such as health, lifestyle or other brain pathology may
contribute to rates of cognitive decline in the oldest-old.
Study supported by: NIH grants R01AG21055 and
P50AG16573
T1526. Effects of Once-Daily, Extended-Release
Memantine on Individual Activities of Daily Living in
Patients with Moderate to Severe Alzheimer’s Disease
Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav
Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake
City, UT and Chicago, IL
In this post hoc study of a 24-week, randomized, placebocontrolled trial (MEM-MD-50, NCT00322153) in ChEItreated patients with moderate to severe Alzheimer’s disease
(AD), we examined the effects of a new, extended-release
(ER) memantine formulation (28 mg, once daily) on individual items and on factor-derived subscales from the 19item AD Cooperative Study Activities of Daily Living scale
(ADCS-ADL19). A significant advantage of memantine ER
over placebo was observed at study Endpoint (OC analysis)
for ADL items of eating (P ¼ 0.024), clearing the table (P
¼ 0.010) and finding belongings (P ¼ 0.029); no other
items demonstrated significant between-group differences. A
factor analysis yielded 4 subscales: Basic ADLs (eating, walking, toileting, bathing, grooming, dressing), Higher-Level
Functions (using telephone, conversing, clearing the table,
finding belongings, obtaining beverage, disposing of litter),
Praxis (turning faucet on, off, turning light on, off ), and
Autonomy (watching TV, travelling, being left alone). At
study Endpoint, the memantine ER group significantly outperformed the placebo group on the Higher-Level Functions
subscale (OC, P ¼ 0.011; LOCF, P ¼ 0.026; MMRM, P
¼ 0.008). In conclusion, treatment with memantine ER
may be associated with improvements in ADLs related to
higher cognitive processing.
Study supported by: Forest Research Institute
Michael Tocco and Stephen M. Graham are employees of
Forest Research Institute, Inc. Suzanne Hendrix is an
T1525. Cortical Thickness on MR Imaging: Relation to
Cognitive Reserve in Normal Aging and Mild Cognitive
Impairment
Jagan A. Pillai, Linda K. McEvoy, Donald J. Hagler, Jr,
Dominic Holland, Anders M. Dale, David P. Salmon,
Douglas Galasko and Christine Fennema-Notestine; San Diego,
CA
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employee of Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest
Research Institute, Inc. Michael L. Miller and Vojislav
Pejovic are employees of Prescott Medical Communications
Group, an independent contractor to several pharmaceutical
companies, including Forest Research Institute, Inc.
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T1529. A Translational Program of BDNF Gene
Delivery for Alzheimer’s Disease
Mark H. Tuszynski, Alan Nagahara, Adrian P. Kells, J.
Bringas, John Forsayeth and Krystopf S. Bankiewicz; La Jolla,
CA and San Francisco, CA
Nervous system growth factors have extensive effects on neuronal function and survival. Nerve growth factor (NGF) prevents the death and stimulates the function of basal forebrain
cholinergic neurons in correlational models of Alzheimer’s disease (AD), and is in a Phase 2 multi-center clinical trial using
AAV2 gene delivery. Separately, Brain-Derived Neurotrophic
Factor (BDNF) influences the survival and function of entorhinal cortical and hippocampal neurons in several animal
models of AD, including transgenic mutant APP-expressing
mice; aged rats and lesioned rats; and aged and lesioned primates. These effects occur independent of beta amyloid load.
We are examining the safety and tolerability of BDNF gene
delivery to the entorhinal cortex in rodent and primate dose
escalation, safety and tolerability studies. Successful completion of these studies will lead to a Phase I trial of AAV2BDNF gene delivery to target short term memory loss in Alzheimer’s disease. The translation of this clinical program will
require development and utilization of real-time, MRI-guided
AAV2 vector delivery with gadoteridol co-infusion to track
and confirm vector distribution to the intended target.
Study supported by: NIH, VA, Alz Assoc, Shiley Family
Foundation
T1527. Neurophysiologic Markers of Aging-Related
Muscle Weakness
Ela B. Plow, Dina Gohar, Mehmed B. Bayram, Jing Hou,
Alexandria Wyant, Yin Fang, Vlodek Siemionow and Guang
H. Yue; Cleveland, OH
Age-related muscle weakness is usually ascribed to peripheral
factors, such as loss and change of muscle fibers. Recent evidence demonstrates that central neural drive diminishes
with age, but its relation to strength remains unclear. We
investigated the cortical neurophysiologic markers of agerelated muscle weakness using Transcranial Magnetic Stimulation (TMS). Ten healthy elderly (76.3 6 2.6yrs) and 15
young individuals (22.3 6 0.9yrs) were enrolled. Measures
included left elbow flexion strength, size of muscle evoked
potential (MEP) following suprathreshold TMS delivered to
Right Motor Cortex (RM1), size of RM1 map of left biceps
brachii (BB) muscle, and inter-hemispheric inhibition (IHI)
exerted upon RM1. Results demonstrate that elderly, compared to the young, were weaker (83.4 6 8.4N vs.105.9 6
8.3N, p ¼ 0.04), possessed smaller RM1 map of BB (717.8
6 150.8sq. mm vs.1034.4 6 116.1sq. mm, p ¼ 0.05) and
showed stronger IHI (79.9 6 6.3% vs. 63.5 6 6.2%, p ¼
0.04), although their size of MEP was larger (1.1 6 0.2mV
vs. 0.4 6 0.1mV, p ¼ 0.02). Stronger IHI was associated
with smaller RM1 map of BB (r ¼ 0.38, p ¼ 0.05) and
poor strength (r ¼ 0.36, p ¼ 0.06). Thus, although compensatory processes ensue in the muscle, age-related weakness persists. Reduced motor cortical maps and stronger inhibition from ipsilateral motor areas may explain weakness
in the elderly; interventions modulating these cortical factors
may improve strength.
Study supported by: National Institutes of Health R01
NS035130
T1530. Imaging Signatures of Pathology in Behavioral
Variant Frontotemporal Dementia
Jennifer L. Whitwell, Clifford R. Jack, David S. Knopman,
Bradley F. Boeve, Ronald C. Petersen, Joseph E. Parisi, Dennis
W. Dickson and Keith A. Josephs; Rochester, MN and
Jacksonville, FL
Background: Behavioral variant frontotemporal dementia
(bvFTD) is pathologically heterogeneous. The most common pathologies underlying bvFTD are Pick’s disease (PiD),
corticobasal degeneration (CBD), and FTLD-TDP type 1.
We aimed to determine whether patterns of atrophy on
imaging differed across these pathologies in bvFTD.
Methods: We identified 15 bvFTD subjects that had a
volumetric MRI and a pathological diagnosis of PiD (n ¼
5), CBD (n ¼ 5) or FTLD-TDP type 1 (n ¼ 5). Voxelbased morphometry was used to assess patterns of atrophy
in each group compared to 20 controls.
Results: All groups showed frontal grey matter loss,
although specific patterns of atrophy differed across groups.
The PiD group showed widespread frontal loss with involvement of the anterior temporal lobes. The CBD group
showed less severe loss predominantly involving posterior lateral and medial superior frontal lobe. The FTLD-TDP group
showed widespread loss in frontal, temporal and parietal
lobes. Greater parietal loss was observed in FTLD-TDP compared to both other groups, and greater anterior temporal
loss was observed in PiD compared to CBD.
Conclusions: Atrophy patterns in bvFTD vary according
to pathology and may therefore be helpful in predicting
these underlying pathologies.
Study supported by: NIH grants R01 DC10367, R01
AG037491, R21 AG38736, R01 AG11378 and P50 AG16574.
T1528. The Purkinje Cell of the Cerebellar Cortex in
Alzheimer’s Disease
and Stavros J. Baloyannis; Thessaloniki, Greece
Alzheimer’s disease is a heterogeneous neurodegenerative disorder, characterized by progressive memory loss, affective
and behavioural changes.We studied the morphological findings of the cerebellar cortex, in twenty early cases of Alzheimer’s disease using electron microscopy and silver impregnation techniques. The Purkinje cells showed morphological
alterations concerning dendritic profiles and axonic collaterals. Loss of dendritic branches was marked in Purkinje cells
of the vermis. Large number of spines was lost in most of
Purkinje cells. Axonic collaterals were also lost. The thick
axonic network around the initial part of Purkinje cell
axons, disappeard. The electron microscopy revealed morphological alterations of the mitochondria in the perikaryon,
the dendritic processes and the axon of Purkinje cells. Fragmentation of the cisternae of Golgi apparatus was prominent.The loss of dendritic spines resulted in a dramatic
decrease of the synapses in the molecular layer. However a
tendency for regeneration of the spines was noticed, through
a limited number of unattached spines. The synaptic alteration of the Purkinje cell emphasizes the importance of synaptic loss for the clinical and pathological profile of the
disease,
T1531. Improved Statistical Power To Detect Treatment
Effects on Functional Outcomes in Alzheimer’s Disease
(AD) Clinical Trials by Item-Response Theory (IRT)
M. Colin Ard, Douglas R. Galasko and Steven D. Edland; La
Jolla, CA
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patients with AD (MMSE 3–18; N ¼ 166) who were
titrated or switched immediately to memantine ER, and
MEM-MD-54, a 28-week OLEX of a pivotal, 24-week,
randomized, placebo-controlled trial of memantine ER
(MEM-MD-50; NCT00322153) in patients with AD
(MMSE 3–14; N ¼ 677). All patients from Study MEMMD-54 and most patients from MEM-MD-51 were taking
a ChEI at Baseline, which continued throughout this study.
Sixty-six patients received memantine during this trial; 44
(66.7%) completed the study, and 8 (12.1%) discontinued
due to an AE. A total of 50 (75.8%) patients experienced a
treatment-emergent AE, including UTI (13.6%), agitation
(12.1%), aggression (10.6%), exacerbation of AD (9.1%),
and anemia, constipation, weight decrease, and back pain
(7.6% each); 17 (25.8%) experienced a serious AE. In conclusion, treatment with once-daily, memantine ER (28 mg)
for up to two years is well tolerated in patients with moderate to severe Alzheimer’s disease.
Study supported by: Forest Laboratories, Inc.
Drs. Stephen Graham and James Perhach are employed
by Forest Research Institute.
The Alzheimer’s Disease Cooperative Study-Activities of
Daily Living (ADCS-ADL) scale assesses an individual’s
ability to perform a range of everyday tasks and is frequently used as an endpoint in clinical trials for AD. While
the ADCS-ADL has excellent face validity as a measure of
the functional impact of AD, the manner in which it is constructed presents several challenges for longitudinal data
analysis, including the use of different rating scales across
items, item-specific gender and/or lifestyle biases, differences
in the complexity or difficulty of indicated activities, and
missing data at the item level. IRT constitutes a family of
quantitative models that assume that responses on specific
items are jointly probabilistically determined by item characteristics and underlying subject-level trait(s), and are well
suited to handling item heterogeneity and missing data.
Using data from an ADCS clinical trial of 409 mild to
moderate AD patients we found that ADCS-ADL scores
constructed from IRT-based re-weighted item scores displayed increased sensitivity to change and improved statistical power as an outcome measure in clinical trials.
Study supported by: NIH/NIA AG010483 (SDE),
AG005131 (SDE, DG), and AG034439 (MCA, SDE).
T1534. A Retrospective Analysis Using Data-Monitoring
Algorithms: What Are the Logical Relationships between
the ADAS-Cog and MMSE?
Christian Yavorsky, Guillermo DiClemente, Mark Opler, Sofija
Jovic, Brian Rothman and Ashleigh DeFries; New York, NY
T1532. Neuropathologic Basis of Age-Associated Brain
Atrophy
Deniz Erten-Lyons, Randy Woltjer, Hiroko Dodge, Lisa Silbert
and Kaye Jeffrey; Portland, OR
Background: The ADAS-Cog and MMSE are standard
instruments in Alzheimer’s disease trials. The Critical Path
Institute Online Data Repository (CODR) includes results
of AD trials submitted by 11 sponsors. However, reliability
and validity problems exist with clinician administered
measures. Data-monitoring uses relationships between
instruments to address this. We assessed the likelihood of
error in assessments if they fell outside expected correlations
between the ADAS-Cog and MMSE, and examined whether
errors could have been detected by data-monitoring.
Methods: Correlations of total ADAS-Cog and MMSE
scores from AD patients in 11 trials were compared with
known correlations. Assessments that fell out of previously
reported ranges were evaluated using data-monitoring
algorithms.
Results: The correlation between MMSE and ADAS-Cog
was .780 (p<.01), agreeing with the literature and used to
establish an expected range. Nearly half (47%) of the sample
fell out of the expected range. 90% of these contained one
or more potential errors.
Conclusions: The ADAS-Cog and MMSE scores that fell
out of range were more likely to contain error that those that
did not. Because these contained one or more item-level inconsistencies, data-monitoring would have detected this in-study.
Study supported by: ProPhase LLC
One or more authors are employed by ProPhase LLC.
Objective: To examine the association between postmortem
neuropathologic measures and antemortem brain atrophy in
aging.
Background: Better understanding of the neuropathologic basis of age-related brain atrophy is needed to differentiate disease processes from normal aging, and to optimize
use of brain volume as an outcome in Alzheimer disease
prevention studies.
Methods: Seventy-three participants of a longitudinal aging
study were followed until death. All subjects had 2 MRI
scans, with the last scan within 36 months of death, and cognitive evaluations within 24 months of death. The association
between antemortem rate of ventricular volume expansion over
time and three postmortem measures:neurofibrillary tangles
(NFTs), neuritic plaques (NPs) and infarcts (large vessel and
lacunar) was examined using a mixed-effects model adjusting
for age at death, APOE e4 presence and cognitive status.
Results: Presence of infarcts, high NFT and NP scores
were significantly associated with higher rate of ventricular
enlargement regardless of cognitive status. e4 carriers also
had a significantly higher rate of ventricular enlargement.
Conclusion: These results suggest that brain atrophy, as
indexed by ventricular enlargement, is a marker of accruing
age-associated neuropathology independent of presence of
cognitive impairment.
Study supported by: Merit Review Grant & Research Career Development Award, Office of Research and Development, Department of Veterans Affairs, National Institutes of
Health (AG08017, MO1 RR000334)
T1535. Withdrawn
T1536. Case of Bimodal Charles Bonnet Syndrome and
Dementia
Mirret El-Hagrassy and Gokhan Akfirat; New York, NY
T1533. A Long-Term, Open-Label Extension Study
Evaluating the Safety of Extended-Release Memantine
(28 mg) in Patients with Moderate to Severe
Alzheimer’s Disease
Stephen M. Graham and James Perhach; Jersey City, NJ
Case: 72 year old hearing impaired male with glaucoma, aggression toward hallucinations. Visual hallucinations followed blindness. He saw silent children, animals for months, recently heard
familiar music. Sometimes had insight. Was admitted to Medicine after trying to fight with images for first time.
Positive findings: disorientation, impaired short term memory,
calculation. Anemia, prerenal acute kidney injury. No history of
This study (MEM-MD-82) was a 52-week, multicenter,
open-label extension (OLEX) of two previous trials of a 28mg, once-daily, memantine extended-release (ER) formulation: MEM-MD-51, a 52-week, open-label dosing trial in
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dementia. Denied images, mentioned spirits, paranoid about
witchcraft to make him look mad and get him locked up, implying pension would be stolen. He was hydrated, given Aricept,
Seroquel, became calmer. He was discharged with diagnosis of
Alzheimer’s dementia, bimodal CBS (Charles Bonnet Syndrome), possible resolved delirium and dehydration.
Discussion: CBS involves complex visual hallucinations
with partial or full insight; auditory variant rarely reported
with visual, both associated with sensory deprivation.
Patients often hide hallucinations, as our patient did. Management includes anticonvulsant, antipsychotic, and antidepressant trials, also reassurance, increasing sensory stimulation and socialization.
CBS was suggested as early marker for dementia, particularly Alzheimer’s and Lewy Body dementias.
Conclusion: Suggest screening blind or deaf patients for
CBS; closely follow for signs of dementia if positive. Further
studies to ascertain positive predictive value and if earlier diagnosis leads to improved outcomes.
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in headache days/month, we continued to treat and follow
123 consecutive patients for at least 2 years (mean 2.76
years; range 24 months-61 months).
Results: Ten subjects (8%) eventually worsened despite
continued treatment and relapsed to CM. Thirty-one subjects (25%) were able to stop onabotA therapy and remain
largely free of headache for >6 months (mean sets of injections required: 4.8; range 2–8). Eighty-two (67%) remained
responders but required ongoing injection therapy throughout the study period (at intervals ranging from 3 months to
6 months; mean 3.4 months). Out of 1,142 sets of injections, there was one serious adverse event (status migrainosus, requiring brief hospitalization).
Conclusion: Most CM patients who initially respond to
treatment with onabotA will maintain that response for at
least 2 years, and a substantial minority will be able to discontinue treatment and do well without prophylactic therapy. Long-term therapy with onabotA for CM is associated
with a very low incidence of SAEs.
Member, Allergan Physician Advisory Board; Consultant,
Allergan
T1537. Lead Exposure Up-Regulated Autophagy
Response in Neuroblastoma SH-SY5Y Cells Via mTOR
Kinase Signaling Pathway
Shun-Sheng Chen, Chueh-Tan Chen and Jiin-Tsuey Cheng;
Kaohsiung, Taiwan
T1603. Utility of Orally-Inhaled Dihydroergotamine
When Early Intervention Is Impractical
Shashidhar Kori, Stewart Tepper, Peter J. Goadsby, Paul
Winner, Min Wang and Stephen Silberstein; Mountain View;
Cleveland; San Francisco; West Palm Beach and Philadelphia
Objective: To study the signal transduced interaction
between b-amyloid accumulation and autophagy response of
lead exposured neuroblastoma SH-SY5Y cells.
Background: Cellular necrosis, apoptosis, and b-amyloid
deposition frequently occur after chronic lead exposure, resulted
in the amyloid-b formed during autophagic turnover of APPrich organelles supplied by both autophagy and endocytosis.
Therefore, the new perspective was tried to prove the role of
autophagy on amyloidogensis disorders of lead exposure.
Methods: SH-SY5Y neurons were exposed with low concentration lead, and enhanced autophagy process was
observed by western blot. The APP-mRNA levels, intracellular and secreted isoforms of APP, the mRNA levels, cell
viability and b-amyloid production were also measured.
Results: After lead exposure, SH-SY5Y cells were enhanced
by their autophagy responses through increased LC3II from
LC3I cleavage. Lead exposure also induced neuronal death by
b-amyloid deposition. During autophagy process, neuronal
death was accompanied with other autophagic characteristics
as accumulation of the autophagosome and protein degradation regulated negatively by the mTOR kinase signaling.
Conclusion: The autophagy processes have shown that
enhancing chronic lead exposure in neurons is accompanied
by accumulation of the autophagosome and protein degradation which regulated negatively via mTOR kinase signaling.
Study supported by: National Science Council, Taiwan
Background: Well-controlled studies have demonstrated
substantial reductions in triptan efficacy with delayed migraine treatment, and surveys have revealed some patient reluctance to treat migraines early, leading to treatment failure
and dissatisfaction.
Methods: This post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study of orally-inhaled
DHE compared 2-hour pain-relief(PR) and pain-free(PF)
rates among patients treating migraine within 1 hour, 1–4
hours, 4–8 hours, or >8 hours of its start.
Results: Of 903 patients randomized, 771 treating a single
attack were included in the efficacy analysis. Two-hour PF
and PF rates were: 66% and 38% (inhaled DHE) and 41%
and 13% (placebo) when treated within 1 hour of migraine
start; 60% and 28% (inhaled DHE) and 35% and 10% (placebo) when treated within 1–4 hours; 53% and 22% (inhaled
DHE) and 30% and 8% (placebo) when treated within 4–8
hours; and 49% and 19% (inhaled DHE) and 24% and 9%
(placebo) when treated >8 hours after start.
Conclusions: This analysis demonstrated the efficacy of
orally inhaled DHE in moderate/severe acute migraine, even
when administered >8 hours after migraine start. Inhaled
DHE may help many migraineurs who are unable to treat
migraine early.
Study supported by: This study was sponsored by MAP
Pharmaceuticals. Dr Kori is a full-time employee of MAP
Pharmaceuticals. Dr Tepper, Dr Goadsby, Dr Winner and
Dr Silberstein have consulted for MAP Pharmaceuticals.
Shashi Kori, MD is a full-time employee of MAP
Pharmaceuticals.
Headache and Pain
T1601. Withdrawn
T1602. OnbotulinumtoxinA for the Treatment of
Chronic Migraine: Long-Term Outcome
Hanlon T. Christopher, Silvia M. Weibelt, Diane C. AndressRothrock and John F. Rothrock; Birmingham, AL
T1604. Characterization of Intraepidermal Nerve Fiber
Morphology in Pain Associated with Diabetic
Neuropathy and Impaired Glucose Tolerance
Hsinlin T. Cheng, Jacqueline R. Dauch, Gordon A. Smith,
Robinson J. Singleton, Brandon M. Yanik and Eva L.
Feldman; Ann Arbor, MI and Salt Lake City, UT
Background: The long-term clinical outcomederived from
treatment of chronic migraine (CM) with onabotulinumtoxinA (onabotA) is unknown.
Methods: From a series of CM patients treated twice
with onabotA who experienced a 50% or greater reduction
Neuropathic pain is a common symptom associated with diabetes and. Measurement of intraepidermal nerve fiber
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density (IENFD) in distal skin samples is a standard
method for the diagnosis of diabetic neuropathy (DN).
IENFD, however, is not considered a good indicator for the
diagnosis of painful diabetic neuropathy (PDN). To evaluate
the use of skin biopsy to study neuropathic pain in PDN,
we studied the IENFD and nerve morphology in skin samples from: normal control, diabetic control, PDN, and DN.
Skin samples from both the distal leg and proximal thigh
were examined. Quantification of IENFD demonstrated no
significant difference between PDN and DN. Morphological
studies on these skin samples demonstrated the presence of
axonal swellings or microneuromas, round shape nerve segments in PDN. The microneuroma densities in the proximal thigh of PDN are significantly higher than that of the
DN. In summary, IENFD does not have a diagnostic value
for PDN. In contrast, the microneuroma densities in proximal skin samples could be used as an indicator for PDN.
Study supported by: NIH
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dural venous sinus stenosis of the dominant venous outflow
system (gradient 10 mmHg).
Results: Thirteen cases were identified (all female; mean
39 years); all failed medical therapy and 5/13 failed surgical
intervention. Technical success was achieved in 13/13 without
major peri-procedural complications. The mean pre-procedural gradient across the venous stenosis was reduced from
23mmHg to 4mmHg post-procedure. Headache resolved or
improved in 9/13. Papilledema resolved in 12/13 and
improved in 1/13. Among the 9 patients with angiographic
follow-up, there were no instances of restenosis.
Conclusions: Venous sinus stenting can achieve a high
degree of technical success and safety with excellent clinical
outcomes. Our series suggests that angioplasty and stenting
may be considered as an alternative to current surgical therapies in patients with IIH and dural venous sinus stenosis.
Study supported by: This study was unfunded and no
individuals other than the authors have contributed to the
preparation of this manuscript.
T1605. Heavily T2-Weighted Magnetic Resonance
Myelography for Post-Lumbar Puncture Headache:
A Pilot Study
Yen-Feng Wang, Jong-Ling Fuh, Jiing-Feng Lirng and
Shuu-Jiun Wang; Taipei, Taiwan
T1607. Adrenal Insufficiency Presenting as Postural
Tachycardia Syndrome
Darine Kassar and Stanley Iyadurai; Saint Louis, MO
Objectives: To report a case of adrenal insufficiency presenting as Postural Tachycardia Syndrome (POTS).
Background: POTS is a disorder of unknown etiology
characterized by orthostatic intolerance and excessive
tachycardia.
POTS is believed to be caused by central hypovolemia.
Adrenal insufficiency has not been described before as an
etiology for POTS.
Methods: Case report
Case report: We report a case of a 20 year-old woman
who presented for migraine headache. Headaches improved
after hydration and treatment. She returned to emergency
room 2 weeks after discharge, with dizziness and recurrent
falls associated with loss of consciousness that occurred
while she attempted to stand.
Physical examination showed orthostatic tachycardia. Tilt
table test was positive. A diagnosis of POTS was made.
No major improvement was noticed with fluid hydration
and treatment with fludrocortisone. Additional work up
showed low morning cortisol level. A diagnosis of adrenal
insufficiency was made and patient was placed on prednisone with relief of her symptoms.
Conclusion: POTS remains a diagnosis of exclusion. Here
we report the first case of POTS associated with adrenal insufficiency, which was successfully treated with prednisone.
Given the right clinical setting, checking cortisol level should
be a consideration in evaluation for an etiology for POTS.
Objective: To investigate the utility of heavily T2-weighted
magnetic resonance myelography (HT2W MRM) in postlumbar puncture (LP) headache (PLPH).
Background: PLPH occurs in about one third of patients
receiving diagnostic LPs. HT2W MRM was proved comparable to computed tomographic myelography in localizing
CSF leaks in spontaneous intracranial hypotension.
Methods: We prospectively enrolled inpatients with indications for diagnostic LPs. Whole-spine axial HT2W
MRMs were carried out after LPs. PLPH was diagnosed
according to the ICHD-2 criteria.
Results: Sixteen patients (3M/13F, age 45.9 6 14.6
years, range 24–82) were recruited. Five patients (31.3%)
(1M/4F) developed PLPH. Twelve patients (75%) had postLP CSF leakage, and all of them had CSF leaks along the
nerve roots. Of these patients, four (33.3%) had epidural
CSF collections, and five (41.7%) had lumbosacral retrospinal CSF collections. All of the patients with PLPH had
CSF leaks along the nerve roots, but only 41.7% of the
patients with CSF leakage developed PLPH.
Conclusion: HT2W MRM was sensitive in detecting
CSF leaks after LP. Although CSF leakage after LPs was
common, it was not the only determinant in the development of PLPH.
Study supported by: Taipei Veterans General Hospital
The authors are employees of Taipei Veterans General
Hospital.
T1606. Angioplasty and Stenting for the Treatment of
Idiopathic Intracranial Hypertension Associated with
Dural Venous Sinus Stenosis
Parisa P. Javedani**, Jeremy D. Fields, Kenneth C. Liu,
Stanley L. Barnwell and Bryan Petersen; Portland, OR and
Charlottesville, VA
T1608. Prevalence of Chronic Migraine (CM),
Headache-Related Disability and Sociodemographic
Factors in the US Population: Results from the American
Migraine Prevalence and Prevention (AMPP) Study
Dawn C. Buse, Michael L. Reed, Kristina Fanning, Aubrey N.
Manack, Catherine C. Turkel and Richard B. Lipton; Bronx,
NY; Chapel Hill, NC and Irvine, CA
Introduction: Lumboperitoneal shunt, ventriculoperitoneal
shunt, and optic nerve sheath fenestration are accepted surgical therapies for medically refractory idiopathic intracranial
hypertension (IIH). Stenting of stenotic venous sinuses has
emerged as a potential therapy.
Methods: We retrospectively reviewed all cases of dural
stents for IIH at our institution. Eligibility criteria included
medically refractory IIH with documented papilledema and
Objective: Estimate the prevalence of CM in the US population by sociodemographics and headache-related disability.
Methods: In 2004 surveys were mailed to 120,000 US
households; 162,756 individuals aged 12 returned surveys;
28,621 reported severe headache. CM was defined as
ICHD-2 migraine with headache frequency 15 headache
days/month. Crude and sociodemographically adjusted prevalence ratios (PRs) were generated.
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Results: 19,189 individuals (11.8%) met ICHD-2 criteria
for migraine (17.3% of females; 5.3% of males); 0.9% met
criteria for CM (1.3% of females; 0.5% of males). Prevalence was highest in males and females aged 40–49. When
compared with persons aged 12–17, adjusted PRs in the
40–49 age group were as follows: females 4.71 (95% CI
3.24–6.83), males 3.31 (95% CI 1.99 ¼ 5.49.) Rates of
CM were inversely correlated with annual household
income. Severe-headache related disability was reported by
38.0% of CM vs. 9.5% of EM respondents.
Conclusions: Prevalence of CM in the US was 0.9%,
and was highest in adjusted models among females, in midlife, and households with the lowest income. Severe headache-related disability was most common among persons
with CM.
Study supported by: The AMPP was funded through a
grant to the National Headache Foundation by OrthoMcNeil Neurologics, Inc., Titusville, New Jersey with supplemental funding by Allergan Inc., Irvine, CA.
Drs. Buse, Lipton, Serrano, and Reed have received consulting funds and/or research support from Allergan. Drs.
Manack and Turkel are full time employees of Allergan.
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Results: Among 6,559 respondents with EM, 49.7%
reported nausea half the time with headache, which was
associated with greater symptomology including unilateral
pain, pulsating pain, pain worsened by activity, photophobia, phonophobia, osmophobia, loss of appetite, neck pain
and sinus pain (all p<.001). Respondents with frequent
nausea reported greater dissatisfaction with medication effectiveness, side effects and overall satisfaction, and were more
likely to report that headache medication(s) interfered with
work, household work, and family social and leisure activities (all p<.001).
Conclusions: Persons who frequently experience nausea
with headache also have greater odds of experiencing other
headache symptoms as well as more dissatisfaction with several aspects of their current medication(s).
Study supported by: The AMPP is funded through a
research grant to NHF from Ortho-McNeil Neurologics,
Inc., Titusville, NJ. Supplemental funding provided by
NuPathe, Inc. Conshohoken, PA.
Drs. Buse, Reed, Fanning and Lipton have received
research support from NuPathe, Inc.
T1611. Frequent Nausea in Episodic Migraine (EM) Is
Common and Associated with Increased Burden: Results
from the American Migraine Prevalence and Prevention
(AMPP) Study
Dawn C. Buse, Michael L. Reed, Kristina M. Fanning and
Richard B. Lipton; Bronx, NY and Chapel Hill, NC
T1609. Chronic Low Dose Methadone for the
Suppression of Treatment-Refractory Chronic Migraine
Keyvani Madjid and John F. Rothrock; San Diego, CA and
Birmingham, AL
Objective: to determine the safety and effectiveness of
methadone administered chronically to patients with treatment-refractory chronic migraine (TRCM).
Methods: We administered low dose (range 2.5–10 mg
TID) methadone to a series of patients with TRCM. A positive treatment response was defined as a 50% or greater
reduction in headache days/month during the 3rd treatment
month relative to the baseline pre-treatment month, with
that response maintained for at least 6 months. At 6 months
we attempted to taper all responders off methadone.
Results: We treated 130 subjects, and 57 (44%) achieved
a positive response. We followed all responders for a mean
of 27 months (range 13–57 months). Only 5 patients (4%
of the total and 7% of responders) eventually were able to
discontinue methadone without relapsing to CM within 30
days. There was one serious adverse event (death due to
overdose of oxycodone and alprazolam).
Conclusions: While chronic administration of low dose
methadone may achieve remission of TRCM to episodic
migraine in a significant minority of patients so treated, discontinuation of treatment typically is associated with rapid
relapse to CM.
Objective: To characterize headache-burden and sociodemographics by nausea status among persons with EM.
Methods: Respondents to the 2009 AMPP survey who
met criteria for EM (ICHD-2 criteria and <15 headache
days/month) rated nausea occurring with severe headache:
none of the time, rarely, < half the time, or half the
time. Chi-square was used to compare sociodemographics.
Ordinal logistic regression adjusting for sociodemographics
yielded odds ratios (OR) and 95% confidence internals (CI)
for headache-related disability (MIDAS) and headacheimpact (HIT-6).
Results: Among 6,559 respondents with EM, 49.7%
reported nausea half the time with severe headache, with
higher frequency in females (52.6%) vs. males (39.3%,
p<.001), and among persons on occupational ‘‘disability’’/
medical leave (62.5%) vs. persons employed full-time
(46.7%, p<.001). Individuals with frequent nausea were
almost twice as likely to experience greater headache-related
disability (OR ¼ 1.94, CI 1.68–2.24), almost four times
more likely to report ‘‘severe pain’’ with headache (OR ¼
3.71, CI 3.28–4.18), greater impairment in daily activities,
desire to lie down, tiredness, irritability and difficulty concentrating (all p<.001).
Conclusion: Frequent nausea was strongly associated
greater headache-related disability and headache-impact.
Study supported by: The AMPP is funded through a
research grant to NHF from Ortho-McNeil Neurologics,
Inc., Titusville, NJ. Supplemental funding provided by
NuPathe, Inc. Conshohoken, PA.
Drs. Buse, Reed, Fanning and Lipton have received
research support from NuPathe, Inc.
T1610. Relationship between High Frequency Nausea
and Treatment Satisfaction in Episodic Migraine (EM):
Results of the American Migraine Prevalence and
Prevention (AMPP) Study
Richard B. Lipton, Michael L. Reed, Kristina M. Fanning and
Dawn C. Buse; Bronx, NY and Chapel Hill, NC
Objective: Report headache symptomology and satisfaction
with medications among persons with EM by headacherelated nausea status.
Methods: Respondents to the 2009 AMPP survey who
met criteria for EM (ICHD-2 criteria and <15 headache
days/month) reported nausea occurring with severe headache: none of the time, rarely, < half the time, or half
the time. Ordinal logistic regression was used adjusting for
sociodemographics, and odds ratios with 95% confidence
internals were generated.
T1612. Medical Consultation and Headache-Impact
among Persons with Chronic Migraine (CM) and
Episodic Migraine (EM): Results from the American
Migraine Prevalence and Prevention (AMPP) Study
Aubrey N. Manack, Dawn C. Buse, Daniel Serrano, Sepideh
F. Varon, Catherine C. Turkel and Richard B. Lipton; Irvine,
CA; Bronx, NY and Chapel Hill, NC
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Objective: Compare patterns of medical consultation and
headache-impact in persons with migraine in the general
population.
Methods: The AMPP study is a longitudinal, population
study of persons with severe headache. 2009 survey respondents who met ICHD-2 criteria for migraine (CM [15
headache days/month] or EM [<15 headache days/month])
were compared on self-reported visits to healthcare professionals (HCPs) and/or facilities for headache in the preceding 12 months and headache-impact (HIT-6). Descriptive
statistics summarize data and t-tests were utilized to compare HIT-6 scores.
Results: 27,253 questionnaires were fielded; 20,107 were
returned. 373 respondents met criteria for CM and 6,796
for EM. 48.5% of CM and 24.5% of EM respondents
reported 1 visit to a HCP/facility for headache. CM suffers were more likely to consult both PCPs (CM ¼ 34.1%,
EM ¼ 15.8%) and specialists (CM ¼ 15.8%, EM ¼
5.6%). Among both groups, headache-impact was greater
among those who consulted neurologists/headache specialists
(CM mean HIT-6 score: 66.7 vs. 64.5; p <0.001; EM
Mean HIT-6 score: 63.6 vs. 57.3, p<0.001).
Discussion: Persons with CM consult HCPs more frequently, particularly specialists. Specialist visits are related to
greater headache-impact.
Study supported by: The AMPP Study is funded through
a research grant to the NHF from Ortho-McNeil Neurologics, Inc., Titusville, NJ Additional analyses and abstract
preparation were supported by Allergan Inc., Irvine, CA.
Drs. Buse, Lipton, Serrano, and Reed have received consulting funds and/or research support from Allergan. Drs.
Manack and Turkel are full-time employees of Allergan.
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the National Headache Foundation from Ortho-McNeil
Neurologics, Inc., Titusville, NJ. Additional analyses and
manuscript preparation were supported by Merck Sharp &
Dohme Corp., West Point, PA.
Dr. Ng-Mak is an employee of Merck Sharp & Dohme Corp.
T1614. Association between Triptan Use and Cardiac
Contraindications in Migraine
Daisy S. Ng-Mak, Valerie P. Pracilio, Stephen Silberstein,
Joseph Couto, Cary Sennett, Mary Hopkins, Jon Bumbaugh
and Neil Goldfarb; West Point, PA; Philadelphia, PA and
Bowie, MD
Objectives: This study assessed the association between triptan use and the presence of cardiac contraindications within
an insured migraine population.
Background: Migraine is associated with cardiovascular
diseases. The vasoconstrictive mechanism of triptans poses
safety concerns for migraine patients with cardiovascular diseases and/or risk factors.
Methods: Ten representative health plans were randomly
selected from the MedAssurant MORE2 RegistryTM. Approximately 2.5 million lives (ages 18–64) were covered during
the measurement year (2009). Migraine patients were identified by a visit with a migraine diagnosis found in claim/encounter data, or if they had 2 episodes of headache seven
or more days apart, or had at least one prescription for a migraine drug or migraine analgesic. Cardiac contraindications
for triptans were defined as at least one prescription or medical claim indicating a cardiac contraindication.
Results: 121,286 (4.9%) migraineurs were identified. Of
the migraineurs in the sample, 38% had one or more prescriptions for a triptan and 8% had a cardiac contraindication. Twenty-two percent of those with a cardiac contraindication had a triptan prescription during 2009 (24% of
those 18–49 and 21% 50–64 years of age).
Conclusion: This study demonstrates potential concerns
regarding pharmacotherapy for migraine. More than 20% of
migraine patients with cardiac contraindications had prescriptions for triptans filled in 2009. While we recognize
that triptans remain the gold standard for acute migraine
treatment, their high utilization (21%) especially among the
50–64 year old population with cardiac contraindications
and who may be exposed to other risks, is concerning and
deserves further study.
Study supported by: This study was sponsored by Merck
Sharp & Dohom Corp.
Dr. Ng-Mak is an employee of Merck Sharp & Dohme
Corp.
T1613. Unmet Treatment Needs among Episodic
Migraineurs (EM): Results of the American Migraine
Prevalence and Prevention Study (AMPP)
Richard B. Lipton, Dawn C. Buse, Daniel Serrano, Daisy S.
Ng-Mak, Starr H. Pearlman and Michael Reed; Bronx, NY;
Chapel Hill, NC; West Point, PA and Savannah, GA
Background: Low triptan persistency and low-moderate satisfaction with migraine therapy suggest that there are unmet
treatment needs.
Objectives: To define ‘‘unmet treatment needs’’ and examine the prevalence and characteristics of EM in the general
population having the unmet needs.
Methods: The AMPP is a longitudinal population-based
study. EM were assessed based on 5 categories of unmet
needs: 1. Dissatisfaction with current treatment; 2. Moderate/severe headache-related disability; 3. Excessive use of
opioids/barbiturates; 4. Recurrent use of the emergency
department (ED) or urgent care clinic (UCC) for headache;
and 5. Use of triptans despite a history of cardiovascular
(CVD) events.
Results: Of 5,591 EM, 2,274 (40.7%) demonstrated at
least one unmet needs. 1,467 (26.2%) had 1 unmet need,
while 807 (14.4%) had 2 unmet needs. Among those
with 1 unmet need, 851(37.4%) were dissatisfied with
treatment, 1,069(47.0%) had moderate/severe headacherelated disability, 728 (32.0%) excessively used opioid or
barbiturate, 129 (5.7%) had 2 visits/year to the ED/
UCC for headache, and 595 (26.2%) were using triptans
despite a history of CVD events.
Conclusions: These results demonstrated that unmet
needs in migraine exist despite available therapies for EM.
Study supported by: The American Migraine Prevalence
and Prevention Study is funded through a research grant to
T1615. ‘‘Let-Down Headache’’: Reductions in Stress and
Improvement in Mood Predict Headaches in Persons
with Migraine
Dawn C. Buse, Sheryl R. Haut, Charles Hall, Howard
Tennen, Tiffani DeFreitas, Thomas M. Borkowski and Richard
B. Lipton; Bronx, NY and Storrs, CT
Objective: To examine if relaxation following stress
increases the probability of headache in persons with migraine (i.e., ‘‘let-down headache’’).
Methods: 20 headache clinic patients (ICHD-2 diagnoses
of migraine, age 18, 3–10 migraine attacks and <15 headache days/month) entered data using a palm-pilot at multiple
pre-set and random times daily. The 4-item Perceived Stress
Scale (PSS, range 4–20) and mood (ratings of happy, sad,
relaxed, nervous, lively and bored from 0–100) were assessed.
Logit-normal random effects models taking account withinperson correlation were used to estimate odds of headache.
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Results: 17 patients entered 30 days of data (192 headache attacks [mean ¼ 5.5]). Lower PSS was associated with
higher odds ratios (ORs) for headache within 12 hours (OR
[95% CI] ¼ 1.81 [1.13, 2.91] per 4-unit difference on
PSS). Improvement in mood was significantly associated
with headache occurrence within 12, 18, and 24 hours for
happy (ORs ¼ 1.20, 1.20, and 1.18, and relaxed ORs ¼
1.26, 1.17, and 1.14. Increases of >10 points were associated with headache occurrence within 12 hours for happy
OR ¼ 2.73 and relaxed OR ¼ 2.31.
Conclusions: Reduced perceived stress and increased feelings of happiness and relaxation were associated with
increased odds of headache.
Study supported by: This study was supported by an investigator initiated grant from ENDO Pharmaceuticals,
Chadds Ford, PA.
Drs. Buse and Lipton have acted as consultants and/or
received research support from Endo Pharmaceuticals.
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Background: Recurrence-rates highlight an important clinical problem in acute treatment of migraine, although endpoint definitions differ widely.
Methods: A phase 3 study post-hoc analysis comparing
orally-inhaled dihydroergotamine (DHE) with placebo using
four published recurrence-rate definitions. These were: (a)
numerator ¼ subjects with 2-hour pain relief (PR) and
moderate/severe pain during 2–24 or 2–48 hours, denominator ¼ subjects with 2-hour PR; (b) numerator ¼ same as
a plus subjects with PR using rescue medication during 2–
24 or 2–48 hours, denominator ¼ same as a; (c) numerator
¼ same as a, denominator ¼ subjects in mITT population;
and (d) numerator ¼ same as b, denominator ¼ same as c.
Results: Of 903 subjects randomized, 792 experiencing/
treating a qualifying migraine comprised the efficacy analysis. Recurrence-rates during 2–24 hours were 6.5%, 22.4%,
3.8%, and 13.2% with DHE and 15.3%, 39.4%, 5.3%,
and 13.6% with placebo for definitions a, b, c, and d. Recurrence-rates during 2–48 hours were 10.3%, 30.2%,
6.1%, and 17.7% with DHE and 18.2 %, 41.6%, 6.3%,
and 14.4% with placebo for definitions a, b, c, and d.
Conclusions: Migraine recurrence-rates vary widely in
definition, which can be misleading. A standardized definition would help facilitate clinical discussions. In this analysis, DHE recurrence-rates were low, regardless of definition.
Study supported by: This study was sponsored by MAP
Pharmaceuticals. Dr Kori is a full time employee of MAP
Pharmaceuticals. Dr Tepper, Dr Goadsby, Dr Lipton and
Dr Dodick have consulted for MAP Pharmaceuticals.
Shashi Kori, MD is a full-time employee of MAP
Pharmaceuticals.
T1616. Assessing the Consistency of LEVADEXTM
(MAP0004, Orally Inhaled Dihydroergotamine)
Pharmacokinetic Parameters in Healthy Volunteers:
Results from 3 Clinical Studies
Amy Forst, Julie Iwashita, Don Kellerman, Shashidhar Kori,
Tracy Thomas and Glyn Taylor; Mountain View; Merthyr
Tydfil, United Kingdom and Radyr, United Kingdom
Background: Rapid, consistent drug absorption is important for effectively treating migraine acutely. MAP0004, a
novel, orally inhaled dihydroergotamine (DHE), has shown
efficacy in treating migraine acutely. Data from pharmacokinetic studies were analyzed for consistency, adequacy, and
speed of DHE absorption through inhalation.
Methods: Three studies compared MAP0004 1.0mg
nominal with 1.0mg of intravenous (IV) DHE, assessing
pharmacokinetic differences between smokers and nonsmokers, effect of co-administration of ketoconazole on
MAP0004, and acute effects of MAP0004 on pulmonary artery pressure.
Results: MAP0004 delivered DHE rapidly in all studies
(mean Tmax, 7–11 minutes). Peak plasma concentrations of
DHE were consistent across studies in non-smokers (Cmax
geometric mean, 2475–2551 pg/mL). MAP0004 Cmax values were substantially lower than IV values (average,
45,000pg/mL) but higher than intranasal (1,004pg/mL).
Cmax and clearance did not vary significantly based on lung
function, age, or weight across studies. Co-administration of
ketoconazole did not significantly impact DHE pharmacokinetics after MAP0004 administration. 80 -hydroxy-dihydroergotamine concentrations after MAP0004 administration
were low (average Cmax, <100pg/mL). No unique
MAP0004 tolerability issues were observed.
Conclusions: Across studies, MAP0004 administration
showed consistent DHE pharmacokinetics and rapid absorption via pulmonary administration.
Study supported by: This study was sponsored by MAP
Pharmaceuticals. Amy Forst, Don Kellerman and Shashidhar
Kori are full-time employees of MAP Pharmaceuticals. Glyn
Taylor is a consultant for MAP Pharmaceuticals.
Amy Forst, Don Kellerman and Shashidhar Kori are fulltime employees of MAP Pharmaceuticals.
T1618. Transdermal Sumatriptan for Acute Treatment of
Migraine
and Jerome Goldstein; San Francisco, CA
Migraine is a widespread neurologic disorder characterized by
episodes of headache accompanied by photophobia, phonophobia, gastrointestinal symptoms and, often, cutaneous allodynia. Symptoms can vary considerably, but gastrointestinal
disturbances are common. Current pharmacotherapy for migraine includes analgesics, nonsteroidal anti-inflammatory
drugs, and 5HT-agonists in various oral, nasal spray, and subcutaneous formulations. Among the 5HT-agonists, sumatriptan is the most frequently prescribed, but its therapeutic limitations (ie, poor absorption, low bioavailability, adverse events)
cause some migraineurs to delay or avoid treatment and may
lead to suboptimal outcomes. Transdermal sumatriptan
(ZelrixV) is a new, single-use, disposable patch that delivers
sumatriptan via iontophoresis, a less invasive method for systemic delivery. Pharmacokinetic data indicate that transdermal
sumatriptan delivery is fast, consistent, and predictable. Results
from well-controlled clinical studies demonstrate significant
superiority versus placebo within 1 hour post-activation for
pain relief (P ¼ 0.0135) and nausea-free (P ¼ 0.0251); at 2
hours post-activation, transdermal sumatriptan significantly
outperformed placebo for pain-free (P ¼ 0.009), pain relief (P
¼ 0.0135), photophobia-free (P ¼ 0.0028), phonophobia-free
(P ¼ 0.0002), and migraine-free (P ¼ 0.0135). Transdermal
sumatriptan is well tolerated, and reported adverse events are
mostly mild, transient application site reactions. This article
reviews the evidence supporting the efficacy and safety of transdermal sumatriptan for acute treatment of migraine.
R
T1617. Migraine Recurrence Rates with Acute
Treatment: Case for Standardizing the Definition
Stewart Tepper, Shashidhar Kori, Peter J. Goadsby, Michel
Ferrari, Richard Lipton, Scott Borland, Min Wang and David
Dodick; Cleveland; Mountain View; San Francisco; Leiden,
Netherlands; Bronx and Scottsdale
T1619. Dejerine Roussy Syndrome in a Patient with
Sneddon’s Syndrome as an Initial Manifestation
Jennie Luna, Anish Shah, Sourav Sen and Dipak P. Pandya;
Paterson, NJ
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Introduction: Dejerine Roussy Syndrome(DRS) usually
results from damage to sensory pathways from thalamus to
spinal cord. It may occur after stroke, multiple sclerosis, after trauma or in brain tumor involving thalamus. Occurrence of DRS in a patient with Sneddon’s syndrome has not
been reported. We report a patient diagnosed with Sneddon’s syndrome presenting with central pain syndrome.
Case Report: 69 year-old man with hypertension, hepatitis C, right posterior cerebral artery stroke presented with
left hemi body severe pain. He was diagnosed with Sneddon’s syndrome nine months ago. His pain was severe,
burning in nature, tearing and excruciating deep pressure
pain involving left face, and left hemibody. He had left
sided spastic hemiparesis and hyperesthesia and tenderness
to touch. He was treated with all neuropathic medications
and narcotic medications without significant success.
Conclusion: DRS can be long lasting or even life long
occurs immediately or years after a stroke. The exact pathogenesis is unknown, it could be related with inflammatory
mediators and pain peptides by denervated nerves. To the
best of our knowledge, occurrence of DRS in Sneddon’s
syndrome has not been reported in the literature.
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skew from brainstem or cerebellar lesions, and 18 controls.
Patient group mean OCR gain was significantly reduced in
both torsional directions. OCR gains were asymmetric
between eyes and between directions in 16 patients. The
hypotropic eye incyclotorting gain was lower than the
hypertropic eye excyclotorting gain after head roll toward
the hypotropic eye in 17 patients.
The reduced static OCR gain and interocular and directional gain asymmetries provide evidence of disruption of
utriculo-ocular pathways in the pathogenesis skew deviation.
Study supported by: Canadian Institutes of Health
Research (CIHR)
T1622. Superior Semicircular Canal Dehiscence (SSCD)
and Osteoporosis in Elderly Asian Women
Alexander Yu, Douglas L. Teich and Eric T. Wong; Boston,
MA
SSCD is associated with vertigo caused by the absence of bone
overlying the SSC. This opening acts as a third window for
the vestibular system, resulting in vertigo that is triggered by
sound (Tullio phenomenon) or external pressure exerted on
the canal (Hennebert sign). Four elderly Asian women were
evaluated for dizziness/vertigo in a community health clinic.
Their age, 57–85, was significantly older than the median age
of 40 originally reported for SSCD. They all complained of
motion-induced vertigo without nausea or vomiting. Their
cerebellar examinations were normal. Only one had inducible
vertigo on Dix-Hallpike maneuver, and none had Tullio phenomenon or Hennebert sign. SSCD was confirmed in all cases
by high-resolution CT, with longitudinal areas of dehiscence
along the long axis of SSC, ranging from 0.4 to 3.0 mm, as
seen on Poschl view. They also suffered from osteopenia or
osteoporosis in the axial skeleton, as confirmed by bone density tests. SSCD may be associated with osteoporosis in elderly
Asian woman without Tullio phenomenon or Hennebert sign.
Further research is needed to determine the relationship of
age, race, osteoporosis risk, and the development of SSCD.
Study supported by: Chinese Center of Long Island
T1620. Valproate-Responsive Subclinical Rhythmic
Electrographic Disharges (SREDA) in a Migraineur
Umer Akbar, Bhavpreet Dham, Evren Burakgazi and John
Kelly; Camden, NJ and Washington
Objective: To report SREDA and its response to valproate
in a patient with migraine headache.
Background: The electroencephalogram (EEG) findings
in migraine are typically non-specific, such as ictal and
inter-ictal diffuse and focal slowing. More specific EEG
findings in migraine are diffuse and focal slowing in theta
and delta frequencies and decreased alpha activity with
increased response to photic stimulation.
Design: We report the case of SREDA during a migraine
headache, improving after valproate administration.
Case: A 45 year-old Caucasian female with catamenial
migraines was admitted for dizziness, fogginess, and refractory
migraines. Magnetic resonance imaging revealed deep white matter changes consistent with history of recurrent migraines. An
otherwise unremarkable EEG showed intermittent episodes of
SREDA in wakefulness and drowsiness. Valproate was initiated
and repeat EEG two-weeks later showed no evidence of SREDA.
Discussion: SREDA is an infrequent EEG pattern which
occurs predominantly in adults after hyperventilation. It is
generally thought to be benign with little clinical significance and has been noted in conditions as diverse as vascular events, syncope, transient global amnesia and epilepsy.
Response to valproate confirms the electrical mechanism of
migraines and suggests SREDA’s potential causal relationship with migraines.
Neuroimmunology and Demyelinating Disease
T1701. Antibodies to Metabotropic Glutamate Receptors
in Ophelia Syndrome and Cerebellitis
Eric Lancaster, Eugenia Martinez-Hernandez, Maarten J.
Titulaer, Sarah Wong, Jian Xu, Anis Contractor, Rita BaliceGordon and Josep Dalmau; Philadelphia, PA and Chicago, IL
Objective: The Ophelia syndrome is a presumed autoimmune disorder characterized by severe but treatment-responsive limbic encephalitis, in association with Hodgkin’s lymphoma. We aimed to determine the target autoantigen.
Methods: Imunohistochemistry on brain tissue and cultures of rat hippocampal neurons was used to demonstrate
antibodies. Immunoprecipitation, mass spectrometry, and
mGluR5 knock outs served to identify the antigen.
Results: Patient’s serum had antibodies that reacted with
the hippocampus and cell surface of live, cultured neurons,
immunoprecipitated mGluR5, and specifically labeled cells
transfected with mGluR5. Reactivity of patient’s serum, but
not control individuals, was abrogated in brain of mGluR5null mice, further confirming the specificity of the antibodies. Parallel studies with mGluR1, a receptor closely related
to mGluR5, lead us to identify a case with cerebellar ataxia
and mGluR1 antibodies. Despite the high homology of
these receptors, each patient’s antibodies were specific for
one type of receptor and a distinct syndrome, resembling
the phenotype of genetic deletion of each receptor.
T1621. Utriculo-Ocular Counterroll Reflex Disruption
in Skew Deviation
James A. Sharpe, Manokaraananthan Chandrakumar, Alan
Blakeman, Herbert C. Goltz and Agnes M. Wong; Toronto,
ON, Canada
Lateral head tilt activates the utricles to evoke a static ocular
counterroll reflex (OCR) of torsional eye motion. Damage
to utriculo-ocular reflex pathways with an abnormal static
OCR might be the mechanism of skew deviation, a vertical
strabismus caused by supranuclear lesions.
OCR gains, the change in torsional eye position/change
in head position after sustained passive lateral head tilt of
20 , were recorded using search coils in 18 patients with
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Conclusions: Antibodies to mGluR1 and mGluR5 should be
considered in patients with cerebellitis and the Ophelia syndrome. Recognition is important because these disorders respond
to immunotherapy. Our findings facilitate this diagnosis.
Study supported by: Dr. Lancaster has a training grant
from Talecris; his contribution to the current work was supported by a Dana Foundation Neuro-immunology Award.
Dr. Martinez-Hernandez has a grant from the Fondo de
Investigaciones Sanitarias, FIS, Spain (FI08/00285). Dr. Titulaer is supported by a KWF fellowship 2009–4451 of the
Dutch Cancer Society. Dr. Dalmau receives royalties from
the editorial board of Up-To-Date; from Athena Diagnostics
for a patent for the use of Ma2 as autoantibody test. Dr.
Dalmau has received a research grant from Euroimmun, and
his contribution to the current work was supported in part
by grants from the National Institutes of Health and
National Cancer Institute (grant RO1CA89054). Drs. Dalmau and Balice-Gordon were supported by 1RC1NS06820401, and a McKnight Neuroscience of Brain Disorders award.
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outgrowth. We generated a recombinant form, rHIgM12, with
identical properties. Intracerebral infection with Theiler’s Murine Encephalomyelitis Virus (TMEV) of susceptible mouse
strains causes chronic demyelinating disease with progressive
axonal loss and neurologic dysfunction similar to progressive
forms of multiple sclerosis. We studied the effects of rHIgM12
on motor function of TMEV-infected mice by recording spontaneous nocturnal activity continuously over several weeks using
AccuScan activity boxes. Compared to control IgM- and salinetreated mice, rHIgM12-treated mice showed improved motor
function which became statistically significant at 9 days post
treatment (p ¼ 0.038 and p ¼ 0.043, respectively) until the
end of experiment (56 days). To assess axonal integrity we performed retrograde-labeling, a technique that relies on anatomically continuous and functionally preserved axons. rHIgM12treated mice had more retrograde-labeled brainstem neurons, as
compared to saline-treated controls. This study supports the hypothesis that peripheral treatment with a neuron-binding IgM
not only protects spinal cord axons in vivo but also influences
functional motor improvement.
Study supported by: This work was supported by grants from
the NIH (R01 GM092993, R01 NS024180, R01 NS03219,
R01 NS048357) and the National Multiple Sclerosis Society
(CA 1011-A8). We also acknowledge with thanks support from
the Applebaum and Hilton Foundations and the Minnesota
Partnership Award for Biotechnology and Medical Genomics.
A patent for the use of rHIgM12 antibody has been issued
to the Mayo Clinic and Foundation. Therefore some of the
authors may receive financial compensation in the future.
T1702. Mortality Outcomes for Interferon Beta-1b
Versus Placebo 21 Years Following Randomization
Douglas S. Goodin, Anthony T. Reder, George Ebers, Gary
Cutter, Marcelo Kremenchutzky, Joel Oger, Mark Rametta,
Karola Beckmann and Volker Knappertz; San Francisco, CA;
Chicago, IL; Oxford, United Kingdom; Birmingham, AL;
London, ON, Canada; Vancouver, BC, Canada; Wayne, NJ;
Berlin, Germany and Montville, NJ
Objective: To assess the effect of interferon beta-1b (IFNB1b) 250 lg on mortality outcomes in multiple sclerosis
(MS).
Methods: Originally 372 patients were randomized to either IFNB-1b 50 lg (n ¼ 125), IFNB-1b 250 lg (n ¼
124), or placebo (n ¼ 123), and remained on assigned
treatment for a median 3.8 years (maximum 5.1 years),
before licensed treatment became available. The primary
outcome variable in this 21 year follow-up study was allcause mortality and the secondary cause-specific mortality.
Results: At 21.1 years (median), vital status information
was available for 366/372 (98.4%) of patients; of whom, 81
(22.1%, 81/366) were deceased. Original randomization to
IFNB-1b 250 lg showed a significant reduction in all-cause
mortality versus placebo (log-rank test, P ¼ 0.0272) and
risk of death was reduced by 39.3%. Cause of death data
was assessed for 75% of deaths; of which, 50/61 (82%)
were MS-related. Most of the excess mortality rate in placebo was MS-related.
Conclusions: With near-complete ascertainment and over
21 years of observation time, a substantial survival advantage was seen for patients receiving early IFNB-1b treatment
versus placebo. Most of this striking difference appears to be
due to MS-related deaths.
Study supported by: Bayer HealthCare Pharmaceuticals,
Montville, NJ, USA.
Prof Douglas Goodin has received honoraria from Bayer
HealthCare Pharmaceuticals for consulting fees and honoraria for speaking.
T1704. Neuroprotection Mediated through Estrogen
Receptor Alpha in Astrocytes
Rory Spence, Mary Hamby, Elizabeth Umeda, Noriko Itoh,
Sienmi Du, Galyna Bondar, Michael Sofroniew and Rhonda
Voskuhl; Los Angeles, CA
Estrogen has well documented neuroprotective effects in
central nervous system (CNS) disorders such autoimmune
inflammation, traumatic injury, stroke, and neurodegenerative diseases, but the underlying mechanisms are uncertain,
because diverse cell types express estrogen receptors in the
immune system and CNS. We selectively deleted estrogen
receptor alpha (ERa) from either astrocytes or neurons using
well-characterized Cre-loxP systems for conditional gene
knockout in mice. We found that signaling through ERa in
astrocytes, but not in neurons, is essential for the neuroprotective effects of systemic treatment with ERa ligand on
clinical function, CNS inflammation and axonal loss during
experimental autoimmune encephalomyelitis. Our findings
reveal a novel cellular mechanism for estrogen-mediated
neuroprotective effects by signaling through astrocytes and
have implications for understanding the pathophysiology of
sex hormone effects in diverse CNS disorders.
Study supported by: National Multiple Sclerosis Society
(RRV), Adelson Medical Research Foundation (RRV and
MVS), NIH NINDS grants NS 062117 (RRV) and
NS057624 (MVS), Skirball Foundation, Hilton Foundation,
and Sherak Family Foundation.
T1705. Genesis of Astrogliosis in an Autoimmune Model
of Multiple Sclerosis
Fuzheng Guo, Yoshiko Maeda, Joyce Ma, Monica Delgado and
David Pleasure; Sacramento, CA
T1703. A Recombinant Human Neuron-Binding IgM
Protects Spinal Cord Axons and Improves Motor
Function in a Murine Model of Multiple Sclerosis
Aleksandar Denic*, Slobodan Macura, Arthur E. Warrington,
Istvan Pirko, Brandon R. Grossardt, Larry R. Pease and Moses
Rodriguez; Rochester, MN
Astrogliosis is a prominent feature of multiple sclerosis
(MS). We employed genetic fate-mapping and bromodeoxyuridine (BrdU) labeling to evaluate the cellular origins of reactive astroglia in spinal cords of mice with experimental
Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite
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autoimmune encephalomyelitis (EAE) induced by immunization with myelin oligodendrocyte glycoprotein peptide 35–55
(MOG peptide). We found that oligodendroglial progenitor
cells (OPCs) were stimulated to proliferate early in the course
of MOG peptide EAE, and that many of these OPCs differentiated to oligodendroglia, but that OPC generation of
astroglia was a rare event. Spinal cord ependymal cells, which
have been reported to give rise to astroglia following spinal
cord trauma, did not generate either OPCs or astroglia during MOG peptide EAE. Instead, virtually all reactive astroglia, identifiable by their expressions of nestin and vimentin
in addition to glial fibrillary acidic protein, arose from resident spinal cord astroglia. In spinal cord white matter, astroglial proliferation increased overall astroglial numbers. In gray
matter, in contrast, reactive astrogliosis was not accompanied
by astroglial hyperplasia. Our study provides the first comprehensive view of the cellular origins of astrogliosis during
an autoimmune demyelinative disorder.
Study supported by: This work was supported by the
Shriners Hospitals for Children, the California Institute for
Regenerative Medicine (CIRM), NMSS and NINDS
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Fingolimod (FTY720) is a sphingosine-1-phosphate receptor
modulator for the treatment of relapsing-remitting multiple
sclerosis. In the phase 3 FREEDOMS study, fingolimod
0.5-mg once daily reduced annualized relapse rate (ARR) by
56% vs. placebo at 24 months (p<0.001). The effect of fingolimod on ARR in patient subgroups was evaluated in the
intent-to-treat population using a negative binomial regression model adjusting for treatment (overall results), or treatment and subgroup (subgroup results). In the overall population, the ARR treatment ratio (fingolimod 0.5 mg [ARR
¼ 0.21] vs. placebo [ARR ¼ 0.48]) was 0.44 (95% confidence interval [CI]: 0.36–0.55). Likewise, ARR ratios were
0.36 (CI: 0.27–0.49) for treatment-naı̈ve (n ¼ 244, fingolimod 0.5 mg; n ¼ 249, placebo) and 0.54 (CI: 0.39–0.73)
for previously treated (n ¼ 181, fingolimod; n ¼ 169, placebo) subgroups. Additionally, the ARR ratio favored fingolimod regardless of prior treatment with interferon (yes:
ARR ratio ¼ 0.53, CI: 0.37–0.77 [n ¼ 127, fingolimod; n
¼ 115, placebo]; no: ARR ratio ¼ 0.39, CI: 0.30–0.51 [n
¼ 298, fingolimod; n ¼ 303, placebo]) and discontinuation
due to lack of efficacy (yes: ARR ratio ¼ 0.31, CI: 0.16–
0.60 [n ¼ 41, fingolimod; n ¼ 38, placebo]; no: ARR ratio
¼ 0.46, CI: 0.37–0.58 [n ¼ 384, fingolimod; n ¼ 380,
placebo]). Fingolimod consistently reduced the ARR vs. placebo in all subgroups.
Study supported by: Novartis Pharma AG, Basel,
Switzerland
Dr. Kremenchutzky and the London MS Clinic have
received operational funding from the MS Society of Canada, and research support as well as consulting/speaker’s fees
from many sources including the endMS research and training network, the Research Scientific Foundation of the MS
Society of Canada, Bayer, Berles, Bio-MS, Biogen Idec,
Boehringer-Ingelheim, Bristol-Myers Squibb, Elan, EMD
Serono, Eli Lilly, Genzyme, GSK, GW, Novartis, PDL, Parexel, Quintiles, Roche, sanofi-aventis, Schering, Teva, and
UCB Pharma. Dr. O’Connor has received consulting fees
from Novartis, sanofi-aventis, Roche, Biogen Idec, Bayer,
EMD Serono, Teva Neurosciences, Eli Lilly, Opexa Therapeutics, Celgene, Glemark, and Actelion. He has received
honoraria from Biogen Idec, EMD Serono, and Novartis.
Dr. Hohlfeld has recieved consulting fees, honoraria and
grant support from Novartis, Biogen-Idec, Merck-Serono,
Teva, sanofi-aventis, and Bayer. Dr. Radue has received lecuture fees from Actelion, Bayer Schering, Biogen Idec, and
others, and have been exclusively used for research funding
at the Medical Image Analysis Center Basel. Dr. Kappos has
participated as principal investigator, member or chair of
planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and
other neurological diseases. The sponsoring pharmaceutical
companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer
Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC
Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis,
Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche,
Teva, UCB and Wyeth. He has also lectured at medical conferences or in public on various aspects of the diagnosis and
management of multiple sclerosis. In many cases these talks
have been sponsored by non-restricted educational grants
from one or another of the above listed companies. Honoraria and other payments for all these activities have been
exclusively used for funding of research of his department.
Research and the clinical operations (nursing and patient
care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these
T1706. Distinct Features of Neuromyelitis Optica
According to Anti-Aquaporin-4 Antibody IgG Subclass
Noriko Isobe, Tomomi Yonekawa, Takuya Matsushita, Yuji
Kawano, Katsuhisa Masaki, Satoshi Yoshimura and Jun-ichi
Kira; Fukuoka, Japan and Matsuyama, Japan
Objective: To clarify the clinical features of neuromyelitis
optica (NMO) according to anti-aquaporin-4 (AQP4) antibody IgG subclass.
Methods: We developed a quantitative flow cytometric
assay for each anti-AQP4 antibody IgG subclass, and
assessed 142 patients with multiple sclerosis (MS), 29 with
neuromyelitis optica (NMO) fulfilling the 1999 criteria, 19
with recurrent/longitudinally extensive myelitis, 86 with
other inflammatory or non-inflammatory neurological diseases, and 28 healthy controls.
Results: Anti-AQP4 antibody IgG was detected in 46
patients, among whom 35 fulfilled either the 1999 or 2006
NMO criteria, 9 had recurrent/longitudinally extensive spinal cord lesions, and two showed MS-like features. IgG1, 2,
3 and 4 anti-AQP4 antibodies were detected in 97.8, 39.1,
13.0 and 8.7% of patients, respectively. In patients not
receiving corticosteroids, the levels of IgG1 anti-AQP4 antibody correlated positively with disease duration, while those
of IgG2 antibodies correlated negatively with maximum spinal cord lesion length. IgG2 anti-AQP4 antibody carriers
showed a younger age of onset, longer disease duration and
lower Progression Index than those of other subclasses.
Conclusion: IgG1 anti-AQP4 antibody levels increase
with disease duration, while IgG2 antibodies are seen in relatively benign cases with a younger onset age.
Study supported by: The Health and Labour Sciences
Research Grant on Intractable Diseases (H20-Nanchi-Ippan016) from the Ministry of Health, Labour and Welfare, Japan,
and the grant-in-aid (B; no. 22390178) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
T1707. Effect of Fingolimod on Relapse Rate by Prior
Treatment Status and Reason for Discontinuation:
FREEDOMS Subgroup Analyses
Marcelo Kremenchutzky, Paul O’Connor, Reinhard Hohlfeld,
Ernst-Wilhelm Radue, Ludwig Kappos, Lixin Zhang-Auberson,
Dieter A. Ha¨ring, Philipp von Rosenstiel, Xiangyi Meng and
Augusto Grinspan; London, ON, Canada; Toronto, ON,
Canada; Munich, Germany; Basel, Switzerland and East
Hanover, NJ
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companies and by grants from the Swiss MS Society, the
Swiss National Research Foundation, the European Union,
the Gianni Rubatto, Novartis and Roche Research Foundations. Dr. Zhang-Auberson, Dr. Häring, Dr. von Rosenstiel,
Dr. Meng, and Dr. Grinspan are employees of Novartis.
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care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these
companies and by grants from the Swiss MS Society, the
Swiss National Research Foundation, the European Union,
the Gianni Rubatto, Novartis and Roche Research Foundations. Dr. Hartung has received consulting fees Bayer
HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi-Aventis. He has received honoraria
from Bayer HealthCare, Biogen Idec, Genzyme, Merck
Serono, Novartis, Roche, Teva, and sanofi-aventis. Dr.
Comi has received honoraria from Teva, Novartis, Biogen,
Lilly, Merck Serono, and Bayer-Schering. Dr. Barkhof have
received consulting fees from Bayer-Schering, Merck Serono,
Synthon, Novartis, UCB, Biogen Idec, and Roche. He has
received honoraria from sanofi-aventis, Genzyme, and
Serono Symposia. Dr. Cohen has received consulting fees
from Biogen Idec, Elan, Lilly, Novartis, and Teva. Dr. Stites,
Dr. Meng, and Dr. Grinspan are employees of Novartis.
T1708. Effect of Fingolimod on Relapse Rate by Prior
Treatment Status and Reason for Discontinuation:
TRANSFORMS Subgroup Analyses
Bhupendra O. Khatri, Jean Pelletier, Ludwig Kappos, HansPeters Hartung, Giancarlo Comi, Frederik Barkhof, Jeffrey
Cohen, Tracy Stites, Xiangyi Meng and Augusto Grinspan;
Milwaukee, WI; Marseille, France; Basel, Switzerland;
Dusseldorf, Germany; San Raffaele, Milan, Italy; Amsterdam,
Netherlands; Cleveland, OH and East Hanover, NJ
In the phase 3 TRANSFORMS study of relapsing–remitting
multiple sclerosis patients, fingolimod (FTY720) 0.5-mg
once-daily significantly reduced annualized relapse rate
(ARR) vs. once-weekly intramuscular interferon (IFN)b-1a
30 lg by 52% at 1 year (p<0.001). Using a negative binomial regression model, effects of fingolimod on ARR were
evaluated in various patient subgroups (intent-to-treat population). ARR was lower with fingolimod 0.5 mg than with
IFNb-1a in both treatment-naive (ARR ratio ¼ 0.14, fingolimod [n ¼ 183] vs. 0.31, IFNb-1a [n ¼ 183]) and previously treated (ARR ratio ¼ 0.26, fingolimod [n ¼ 246] vs.
0.52, IFNb-1a [n ¼ 248]) patient subgroups. ARR treatment ratios (fingolimod 0.5 mg vs. IFNb-1a) favored fingolimod regardless of prior treatment with IFN (yes: ARR ratio ¼ 0.42, confidence interval [CI]: 0.29–0.62 [n ¼ 218,
fingolimod; n ¼ 206, IFNb-1a]; no: ARR ratio ¼ 0.57, CI:
0.37–0.87 [n ¼ 211, fingolimod; n ¼ 225, IFNb-1a]) or
glatiramer acetate (yes: ARR ratio ¼ 0.72, CI: 0.40–1.30 [n
¼ 56, fingolimod; n ¼ 66, IFNb-1a]; no: ARR ratio ¼
0.44, CI: 0.32–0.60 [n ¼ 373, fingolimod; n ¼ 365,
IFNb-1a]) and regardless of whether patients discontinued
study for lack of efficacy (yes: ARR ratio ¼ 0.43, CI: 0.19–
0.95 [n ¼ 41, fingolimod; n ¼ 45, IFNb-1a]; no: ARR ratio ¼ 0.50, CI: 0.37–0.67 [n ¼ 388, fingolimod; n ¼ 386,
IFNb-1a]). In TRANSFORMS, fingolimod improved ARR
in the subgroups analyzed.
Study supported by: Novartis Pharma AG, Basel,
Switzerland
Dr. Khatri is a consultant or does speaking for Teva,
Bayer, Pfizer, Medtronics, Biogen Idec, Serono, and Novartis. He does receive compensation from them. Dr. Pelletier
has received consulting fees from Novartis, Bayer Schering,
Merck Serono, sanofi-aventis, and Teva. Dr. Kappos has
participated as principal investigator, member or chair of
planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and
other neurological diseases. The sponsoring pharmaceutical
companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer
Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC
Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis,
Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche,
Teva, UCB and Wyeth. He has also lectured at medical conferences or in public on various aspects of the diagnosis and
management of multiple sclerosis. In many cases these talks
have been sponsored by non-restricted educational grants
from one or another of the above listed companies. Honoraria and other payments for all these activities have been
exclusively used for funding of research of his department.
Research and the clinical operations (nursing and patient
T1709. Safety Overview of Fingolimod in Relapsing
Multiple Sclerosis: Phase 2 and 3 Studies
Jeffrey A. Cohen, Ludwig Kappos, Gordon Francis, William
Collins, Lixin Zhang-Auberson and Dejun Tang; Cleveland,
OH; Basel, Switzerland and East Hanover, NJ
Fingolimod (FTY720) is a sphingosine-1-phosphate receptor
modulator approved in the US for relapsing multiple sclerosis. Safety data from phase 2 and 3 studies were assessed
using 2 analysis groups: Group A (FREEDOMS; n ¼
1272) included patients receiving fingolimod 1.25-mg or
0.5-mg once-daily, or placebo; Group B (all studies; N ¼
2615) included patients receiving fingolimod in phase 2 and
3 (TRANSFORMS/FREEDOMS) studies and ongoing
extensions. In Group A, serious adverse event (AE) rates
were 10.1% with fingolimod 0.5 mg, 11.9% with 1.25 mg,
and 13.4% with placebo; corresponding rates of AEs leading
to discontinuation were 7.5%, 14.2%, and 7.7%. Group B
results were similar, with higher rates of AEs leading to discontinuation with fingolimod 1.25 mg. Overall infection
rates were 68.5–71.5% in the fingolimod groups vs. 72%
with placebo (Group A). Malignancy rates were 0.9% in
both fingolimod groups vs. 2.4% with placebo in Group A
and 1.4% with fingolimod 0.5 mg and 1.1% with 1.25 mg
in Group B. Macular edema was uncommon, dose-dependent, and generally resolved upon treatment discontinuation.
The safety profile of fingolimod has been well characterized,
with a better benefit-risk profile observed with the 0.5-mg
dose.
Study supported by: Novartis Pharma AG, Basel,
Switzerland
Dr. Cohen has received consulting fees from Biogen Idec,
Elan, Lilly, Novartis, and Teva. Dr. Kappos has participated
as principal investigator, member or chair of planning and
steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for
these trials include Actelion, Advancell, Allozyne, BaroFold,
Bayer Health Care Pharmaceuticals, Bayer Schering Pharma,
Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly,
Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB and
Wyeth. He has also lectured at medical conferences or in
public on various aspects of the diagnosis and management
of multiple sclerosis. In many cases these talks have been
sponsored by non-restricted educational grants from one or
another of the above listed companies. Honoraria and other
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payments for all these activities have been exclusively used
for funding of research of his department. Research and the
clinical operations (nursing and patient care services) of the
MS Center in Basel have been supported by non-restricted
grants from one or more of these companies and by grants
from the Swiss MS Society, the Swiss National Research
Foundation, the European Union, the Gianni Rubatto,
Novartis and Roche Research Foundations. Dr. Francis, Dr.
Collins, Dr. Zhang-Auberson, and Dr. Tang are employees
of Novartis.
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itive with the cell based assays: eight for both CASPR2-Abs
and LGI1-Abs, four only for CASPR2-Abs, two only for
LGI1-Abs. In addition, ten of the 48 VGKC-complex-Ab
negative sera had CASPR2-Abs. These results indicate that
patients with neuromyotonia can have both CASPR2 and
LGI1 antibodies. Moreover, the presence of CASPR2
antibodies in 20% of the patients negative for VGKC-Abs
by radioimmunoassay suggests that the cell-based assays
may make a useful addition to the investigation of
neuromyotonia.
Study supported by: Medical Research Council of Great
Britain and NIHR Oxford Biomedical Research Centre
Angela Vincent, Sarosh Irani and Patrick Waters may in
the future receive royalties from use of the LGI1 and
CASPR2 antibodies for diagnosis of neuromyotonia and
other diseases
T1710. Fingolimod Mechanism of Action (MOA) in
Multiple Sclerosis (MS)
Jerold Chun and Jeffery A. Cohen; La Jolla, CA and
Cleveland, OH
Fingolimod, the first oral MS therapy, is thought to mediate
its effects through actions of its metabolite, fingolimodphosphate, on sphingosine-1-phosphate (S1P) receptors on
T-lymphocytes. This interaction produces ‘‘functional antagonism’’ of the receptor subtype S1P1 on CCR7-positive Tcells (naı̈ve, activated, central memory), whereby S1P1 is
internalized and degraded, receptor signalling is lost, and
egress from lymphoid organs is inhibited. Fingolimod exposure leaves CCR7-negative effector memory T-cells comparatively unaffected. In MS, the net effect is a relative preservation of immune surveillance, while proinflammatory
subsets are prevented from reaching the CNS. Additionally,
accumulating data support a distinct, nonmutually exclusive
mechanism involving direct S1P-receptor modulation on
CNS cells. To address this issue, studies in EAE-challenged
mice have been pursued using a conditional-null mutation
resulting in a lack of S1P1 in neurons and glia. This mutant
demonstrated attenuated disease severity and loss of fingolimod efficacy despite maintaining immunologic effects on
peripheral blood lymphocytes. Loss of fingolimod efficacy
was apparent in astrocyte, but not neuronal, S1P1-null
mutants. Additional data in this model will be discussed
towards considering fingolimod as having a dual MOA
involving S1P-receptor modulation in not only the immune
system but also the CNS.
Study supported by: NIH and Novartis Pharma AG,
Basel, Switzerland
Dr. Chun has received consulting fees from Novartis and
Ono; lecture fees from Novartis; and research support from
Novartis and Pfizer. Dr. Cohen has received consulting fees
from Biogen Idec, Elan, Lilly, Novartis, and Teva.
T1712. Withdrawn
T1713. Association of MS Susceptibility Variants and
Early Attack Location
Ellen M. Mowry, Jean Pelletier, Maria R. Blasco, Pierre
Duquette, Pablo Villoslada, Pierre-Antoine Gourraud, Irina
Malikova, Christophe Picard, Jamie McDonald, Elaine Roger,
Stacy Caillier and Emmanuelle Waubant; San Francisco;
Marseille, France; Madrid, Spain; Montreal, Canada and
Pamplona, Spain
Background: The anatomic location of early MS relapses
within the central nervous system is predicted by the first
attack location. We sought to determine if genetic polymorphisms associated with multiple sclerosis (MS) susceptibility
are associated with attack location.
Methods: 17 well-documented MS susceptibility polymorphisms were genotyped in 354 white, non-Hispanic
patients seen within a year of MS onset. Their association
with the CNS location of the first two MS attacks was
assessed.
Results: The IL12A polymorphism was associated with
increased odds of both attacks involving the spinal cord
(OR ¼ 2.4, 95% CI 1.3, 4.3, p ¼ 0.003). The IL7R polymorphism was associated with reduced odds of both attacks
involving the brainstem/cerebellum (OR ¼ 0.2, 95% CI
0.0, 0.9, p ¼ 0.042). There was a strong trend for an association of EVI5 with reduced odds of both attacks featuring
optic neuritis. Several other genes showed trends for association with attack locations.
Conclusions: Some of the MS susceptibility genes predict
MS attack location. This finding may lead to improved
understanding of MS pathogenesis and treatment.
Study supported by: National Multiple Sclerosis Society
T1711. Antibodies to the VGKC-Complex Proteins LGI1
and CASPR2 in Acquired Neuromyotonia
Camilla Buckley, Philippa Pettingill, Rosie Pettingill, Matthew
Kiernan, Osamu Watanabe, Sarosh Irani, Patrick Waters and
Angela Vincent; Oxford, United Kingdom; Sydney, Australia
and Kagoshima, Japan
T1714. Osmotic Demyelination Syndrome: Lack of
Association between Outcome and Severity of
Hyponatremia
Jennifer E. Fugate*, Jonathan Graff-Radford and Alejandro A.
Rabinstein; Rochester, MN
VGKC-complex-Abs are found in neuromyotonia, Morvan’s
syndrome, or limbic encephalitis. It is now clear that
VGKC-complex-Abs are mainly directed against proteins
that are complexed with VGKCs in the brain, particularly
LGI1 (mainly limbic encephalitis) and CASPR2 (mainly
Morvans syndrome and neuromyotonia), but these antibodies have not been studied in detail in neuromyotonia
patients. 68 sera from patients with neuromyotonia from
centers in Kagoshima and Sydney (29 females, 39 males,12
to 85 years) were assayed using cell-based assays for antibodies to LGI1 and CASPR2. 20/68 (30%) sera were positive
for VGKC-complex-Abs (106–1560 pM) including three of
the four with Morvans syndrome. 14 of these sera were pos-
Objective: Little is known about outcome predictors in osmotic demyelination syndrome (ODS), though one study
identified that severity of hyponatremia is an independent
predictor. We aimed to characterize clinical and radiographic
features of patients with ODS and identify variables that
predict outcome.
Methods: A retrospective study of patients with ODS
identified by a search of Mayo Clinic medical records from
1999–2010. Patients were diagnosed by clinical and
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of patients had 3 of the following: psychiatric symptoms,
speech disorder, seizures, dyskinesias, decreased consciousness, autonomic instability, or hypoventilation. Treatment
included tumor removal when appropriate, and immunotherapy (91%). At the time of analysis, full recovery/minimal symptoms (back to all activities) have occurred in
57.3% of the patients, mainly in those with teratoma
(66.7% vs 48.8%); 6% died. The frequency of relapses varied according to the response to initial immunotherapy;
87% of relapses occurred in patients without teratoma.
Conclusions: Anti-NMDA-receptor encephalitis is a
severe but treatable disorder of predominantly young individuals. Prompt diagnosis and treatment are important to
improve outcome. In addition to the above, detailed analysis
of the frequency of relapses, immunotherapy, timing of recovery, and prognostic factors will be provided.
Study supported by: The current work is supported in
part by grants from the National Institutes of Health and
National Cancer Institute RO1CA89054 (Dalmau),
1RC1NS068204-01 (Balice-Gordon and Dalmau), and a
McKnight Neuroscience of Brain Disorders award (BaliceGordon and Dalmau).
Dr. Titulaer is supported by a KWF fellowship 2009–
4451 of the Dutch Cancer Society; Dr. Martinez-Hernandez
has a grant from the Fondo de Investigaciones Sanitarias,
FIS, Spain (FI08/00285); Dr. Dalmau receives royalties
from the editorial board of Up-To-Date; from Athena Diagnostics for a patent for the use of Ma2 as autoantibody test.
Dr. Dalmau holds a patent application for the use of
NMDA receptor as autoantibody test. Dr. Dalmau has
received a research grant from Euroimmun.
radiographic features. Medical charts were reviewed. Favorable outcome was defined by Modified Rankin Scale (mRS)
2.
Results: Of 24 patients, 14 (48%) had central pontine
myelinolysis and 10 (42%) extrapontine myelinolysis. Hyponatremia was documented in 18 (75%) with mean sodium nadir of 114 mmol/L. Favorable outcome was seen in
15 (63%) at mean follow-up 3 years. Initial brain MRI was
normal in 21%. The following variables were assessed: age
(p ¼ 0.40), gender (0.68), sodium level (p ¼ 0.30), albumin (p ¼ 0.12), extrapontine involvement (p ¼ 1.00),
GCS (p ¼ 0.33), alcoholism (p ¼ 1.00), and sepsis (p ¼
0.17). None were predictive of outcome.
Conclusions: Functional outcome in ODS is not associated with severity of hyponatremia. Serial brain imaging is
of value as a substantial proportion of patients have normal
initial MRIs.
T1715. Correlation of Brain Atrophy, Disability and
Spinal Cord Atrophy in a Murine Model of MS
M Mateo Paz Soldan, Jeffrey D. Gamez, Aaron J. Johnson,
Anne K. Lohrey, Yi Chen and Istvan Pirko; Rochester, MN
and Cincinnati, OH
Disability progression in MS remains incompletely understood. Unlike lesional measures, CNS atrophy has strong
correlation with disability. TMEV infection in SJL mice is
an established model of progressive MS. We utilized in vivo
MRI to quantify brain and spinal cord atrophy in this
model and analyzed the temporal relationship between atrophy and disability.
Infected and control mice were followed for 12 months.
Disability was assessed monthly using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular
volume and C4-5 cord cross-sectional area measurements
were performed using Analyze 10. At three months, brain
atrophy reached statistical significance (p ¼ 0.009). In contrast, disability did not differ until four months post infection (p ¼ 0.0032). Cord atrophy reached significance by
eight months (p ¼ 0.0088). By 12 months, brain atrophy
resulted in 111.8% increased ventricular volume (p ¼
0.000031), while spinal cord cross-sectional area was 25%
reduced (p ¼ 0.0013) in cases.
Our results suggest that significant brain atrophy precedes
and predicts the development of disability, while spinal cord
atrophy occurs late and correlates with severe disability. The
observed temporal relationship establishes a framework for
mechanisms of disability progression and enables further
investigations of their underlying substrate.
Study supported by: National MS Society Pilot Project
Grant, NIH/NINDS R01 NS 058698
T1717. Cigarette Smoke Induces Inflammation and
Oxidative Stress in Brains of Lewis Rats
Ashwani Khanna and Walter Royal, III; Baltimore, MD
Cigarette smoke (CS) exposure is a risk factor for developing multiple sclerosis. We examined this effect by analyzing
brains from Lewis rats exposed to CS from 4 cigarettes /
day for 30 days using a system developed to simulate
human smoking behavior. Using quantitative PCR, we
observed an increase in IFN-c, TNF-a, TGF-b, IL-10, IL6, IL-17, IL-18 and IL-23 and in MCP-1/CCL2, MIP-1a/
CXCR3 and SDF-1a/CXCL12 gene expression in the rat
brains. Also gene expression for p22phox, NOX-4, dual oxidase and Nfr2 was increased whereas thioredoxin gene
expression was decreased. Immunocytochemical analysis of
the brains from the rats showed, compared to rats not
exposed to CS, increased staining for CD4, TNF-a, IFNc, class II MHC, ED1, Nrf2 and GFAP. Double immunofluorescence staining demonstrated cytoplasmic localization
of Nrf2 in astrocytes from rats exposed to CS whereas nuclear localization was observed for non-exposed rats. These
studies, therefore, demonstrate that CS exposure can result
in increased brain immune cell trafficking, pro-inflammatory responses and oxidative stress. This model may be
useful for elucidating mechanisms related to the link
between CS and MS and for developing effective treatment
strategies for the diseases.
T1716. Anti-NMDA-Receptor Encephalitis: Clinical
Analysis of 457 Patients
Maarten J. Titulaer, Eugenia Martinez-Hernandez, Lindsey
McCracken, Rita Balice-Gordon and Josep Dalmau;
Philadelphia, PA and Barcelona, Spain
Introduction: Anti-NMDA-receptor encephalitis is the
most common and best characterized antibody-mediated encephalitis. We provide the clinical features and follow-up of
457 patients.
Methods: Analysis of demographics, onset, syndrome,
treatment, and outcome at 24 months.
Results: 84% were female. Median age was 21 years
(range 1–85; 39% 18 and 4.3% 45 years). 45% had a
tumor (94% teratomas, 5.7% other). 62% of females >18
years had ovarian teratoma(s), versus 35% 18 years. 84%
T1718. Withdrawn
T1719. Differential Sensitivity of Human PBMC Subsets
to Alemtuzumab-Mediated Cytotoxicity
William Siders, Sambasiva Rao, Juanita Campos-Rivera, Jose
Sancho, Paula Boutin, Peter Severy, Johanne Kaplan, Bruce
Roberts and Srinivas Shankara; Framingham, MA
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Alemtuzumab(monoclonal antibody)currently in clinical
trials for treatment of MS,recognizes CD52antigen
expressed on lymphocytes&most myeloid cells. Its cytotoxic effects are reportedly influenced by density ofCD52antigen on target cells. Using alemtuzumab in polychromatic flow cytometry assay,we examined levels
ofCD52expression on 20distinct subsets of lymphoid
&myeloid cells in peripheral blood mononuclear
cells(PBMCs)from 11 healthy donors. Data demonstrated
subsets of PBMCs express differing levels ofCD52. Quantitative analysis showed memory B-cells&myeloid dendritic
cells(mDCs)display highest number while natural killer
(NK) cells&plasmacytoid DCs have lowest number of CD52
molecules per cell amongst lymphoid&myeloid cell populations,respectively. To test significance of differential CD52expression on sensitivity of PBMC subsets to alemtuzumabmediated cytotoxicity, we developed flow cytometry-based,
complement-dependent cytotoxicity(CDC) assay allowing for
simultaneous assessment of total number of dead cells&identification of phenotypes of surviving cells amongst PBMCs.
Results from 4donors indicated, amongst lymphocytes, alemtuzumab-mediated profound cytotoxic effects on B-and Tcells with minimal effect on NKcells, correlating with density
ofCD52 on these cells. Despite CD52 levels comparable to
lymphocyte subsets, mDCs&monocytes were less susceptible
to alemtuzumab-mediated CDC indicating antigen density
alone doesn’t define susceptibility. Additionally, mDCs&monocytes expressed significantly higher levels of complement
inhibitory proteins(CIPs) compared to lymphocyte subsets
which may contribute to their resistance to alemtuzumabmediated CDC. Overall, results show while density of CD52
antigen can influence cell susceptibility to alemtuzumabmediated CDC, factors such as, level of CIP expression, may
also have an impact.
Study supported by: Genzyme
All authors received financial compensation (including
stock) as employees of Genzyme.
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T1721. Analysis of Immune Competence Following
Alemtuzumab Treatment in huCD52transgenic Mice
William Siders, Nathalie Chretien, Michael LaMorte, Bruce
Roberts and Johanne Kaplan; Framingham, MA
Alemtuzumab (humanized monoclonal antibody) currently
in clinical trials for treatment of MS, results in the overall
depletion of lymphocyte subsets followed by extended period of repopulation. The goal, to evaluate functionality of
lymphocytes following treatment, was accomplished by
treating human CD52 (huCD52) transgenic mice w/alemtuzumab & evaluating ability of remaining T-lymphocytes
to respond to polyclonal stimulation. While lymphocytes
from animals treated with alemtuzumab are present in
lower numbers, they retain ability to proliferate in response
to T-cell receptor (TCR) ligation & produce similarTh1,
Th2, & Th17 family cytokines compared to lymphocytes
from untreated animals. Comparison of TCR Vbeta families represented in alemtuzumab-treated & untreated animals demonstrated no differences in diversity of T-cell repertoire. We next evaluated ability of alemtuzumab-treated
animals to generate de novo & recall immune responses to
adenovirus serotype2( Ad2). Animals were injected with
Ad2 at various timepoints relative to treatment &evaluated
for Ad2-specificT-cell frequency by IFNgamma ELIspot &
development of antibodies to Ad2. This demonstrated animals immunized as early as 7 days developed detectable
frequencies of antigen specific T-cells. Recall responses
were unaffected in animals which memory responses were
allowed to develop prior to treatment. These studies demonstrate alemtuzumab therapy doesn’t impact functional
activity of remaining T-cells &doesn’t severely affect ability
of host to generate functional T- and B-cell responses to
foreign antigen.
Study supported by: Genzyme
All authors receive financial compensation from Genzyme
(including stock) as employees.
T1722. Withdrawn
T1720. Transcriptional Profiles Uncover Population
Structure among Multiple Sclerosis Patients
Linda Ottoboni, David Hafler, Howard Weiner and Philip De
Jager; Boston, MA and New Haven, CT
T1723. Withdrawn
There is extensive heterogeneity among subjects with multiple
sclerosis (MS) in terms of their disease course and treatment
response. Here, we explore the structure of the MS subject
population using RNA expression profiles derived from peripheral blood mononuclear cells of 398 subjects. These subjects were untreated (n ¼ 148), treated with glatiramer acetate
(GA) (n ¼ 101) or treated with interferon beta (IFNb) (n ¼
143). We find the expected expression profile associated with
IFNb treatment but find no significant difference in gene
expression with GA treatment. Using unsupervised clustering,
we define 2 subsets of untreated subjects, with enhanced type
I interferon response gene expression in the smaller group and
enhanced lymphocyte activation pathway gene expression in
the larger group. This population structure is preserved in the
GA subjects (Kappa coefficient ¼ 0.83) and IFNb subjects
(Kappa ¼ 0.82). Retrospective data suggest that the smaller
group is more likely to have an clinical or MRI event after
sampling (p ¼ 0.02). We therefore report the identification of
a gene expression profile discriminating 2 subsets of MS subjects and further report that this architecture captures a previously reported T cell gene expression signature associated with
high-risk CIS subjects (Corvol et al. PNAS 2008).
Study supported by: Affymetrix Inc. - donation of microarrays and processing
T1724. A Single Dose Escalation Study of the Safety,
Pharmacokinetics, and Pharmacodynamics of
Subcutaneous Pegylated Interferon-Beta in Healthy
Volunteers
Kenneth Grabstein, Aijun Wang, Natalie Winblade Nairn and
Daniel J. Burge; Seattle, WA
Purpose: A single-ascending dose study was conducted in
healthy volunteers (HV) to establish the safety, tolerability,
pharmacokinetic (PK) and pharmacodynamic (PD) profile
of AZ01 (PEGylated interferon-beta). Methods: Eight HV
in each of 5 escalation cohorts received one subcutaneous
dose of AZ01 or placebo (6:2) at doses from 100mg to
10mg. Safety, PK and PD parameters were evaluated.
Results: The AE profile of AZ01 was consistent with that
expected with IFN-beta therapy, especially in the 10mg
group. Events included injection site reactions, headache,
myalgia, chills, fatigue, nausea, and fever. No SAEs or AEs
leading to discontinuation occurred. No laboratory parameter, vital sign measurement, or ECG was determined by the
Investigator to be clinically significant. PK and PD analyses
indicate a sustained exposure and response to single doses of
AZ01, lasting about 14 days. Conclusion: Single subcutaneous AZ01 doses of up to 10mg were well tolerated by HV.
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The prolonged PK and PD may allow dosing at greater
intervals than with currently available interferon therapies.
Less frequent injections are likely to decrease injection site
reactions and flu-like symptoms and improve compliance.
Study supported by: Allozyne Inc.
Salaries, stock options, consulting fees
Stage:
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nir; research support from Biogen Idec, Teva, Novartis, the
National MS Society, Pittsburgh Foundation, and Allegheny-Singer Research Foundation. XY and PF: employees
of Biogen Idec.
T1727. The Correlation of Brain MRI Lesion Load with
Functional Outcome in Animal Models of MS
Istvan Pirko, Jeffrey Gamez, Moses Rodriguez, Mihajlo Babovic
and Slobodan I. Macura; Rochester, MN and Northfield, MN
T1725. Regulation of IL-12 by IL-23 in Bone Marrow
Dendritic Cells
Farinaz Safavi, Patricia Gonnella, Bogojub Ciric,
Abdolmohamad Rostami and Farinaz Safavi; Philadelphia, PA
We previously demonstrated MS-related MRI features
including brain atrophy, spinal cord atrophy, lesional T1
hypointensity and gray matter T2 hypointensity in Theiler’s
Murine Encephalitis Virus-based MS models. A common
characteristic of most MS models is the relative paucity of
brain compared to spinal cord lesions. In MS, brain lesion
load and disability correlation remains controversial, with
most studies demonstrating weak but some showing moderate to strong correlation. We hereby describe two different
models of brain lesion development and their correlation
with rotarod detectable disability. In interferon-c receptor
deficient mice of 129 (A) or C57BL6/J (B) background, we
observed different patterns of lesion formation: in model
(A) lesion development was close to linear and showed
strong correlation with disability (r ¼ 0.96, p ¼
0.00002). In model (B), biphasic lesion development was
demonstrated: early (<4weeks) and unusually large periventricular lesion formation was followed by lesion development similar to the pattern in model (A), and only beyond
week 4 was a strong MRI-disability correlation observed in
this model (r ¼ 0.92, p ¼ 0.02).These models demonstrate different patterns of lesion formation and correlation
with disability and may allow for investigations of the MRIclinical paradox.
Study supported by: NIH NINDS R01 NS58698, Mayo
Clinic Department of Neurology Intramural Research Funds
Th1 and Th17 cells play important roles in the pathogenesis
of Experimental Autoimmune Encephalomyelitis and other
autoimmune models. IL-12 and IL-23 are heterodimeric
cytokines produced mostly by dendritic cells (DCs) that
promote development of Th1 and Th17 cells, respectively.
Understanding the mechanisms that regulate production of
these cytokines should advance our knowledge of the pathogenesis of Multiple Sclerosis (MS) and could lead to novel
treatments for this disease. To test the effect of IL-23 on IL12 production, Bone Marrow Dendritic cells(BMDCs) from
IL-23p19 KO and WT mice were used. BMDCs were
stimulated with LPS and mouse recombinant IL-23 (5 ng/
ml) and IL-12p70 and IL-12p35 expression were measured
after 6 and 24 hrs. WT DCs stimulated with both LPS and
LPSþIL-23 secreted significantly larger quantities of IL12p70 (p< 0.01) compared to IL-23p19 KO cells. RT-PCR
analysis also showed significantly higher expression of IL12p35 mRNA in WT DCs treated with either LPSþIL-23
or LPS (p < 0.01 ). Our observations indicate that the
expression of IL-12 is regulated by IL-23 in vitro.Finding
similar regulatory mechanisms in vivo should increase our
understanding of the role of these cytokines in the pathogenesis of autoimmunity.
Study supported by: NIH grant number RO1NS046782
T1726. Clinically Apparent MRI Activity Predicts 2-Year
Outcomes in Patients with RRMS
Thomas Scott, Xiaojun You and Pamela Foulds; Pittsburgh,
PA and Weston, MA
T1728. Comparison of CIDP Patients with Normal and
Elevated CSF Protein
YuanYuan Xue and Ericka P. Simpson; Houston, TX
Background: Several studies report clinically apparent and
clinically silent MRI lesions predict disease worsening in
patients on IFNb-1a. The magnitude of risk, especially with
clinically silent activity, remains uncertain.
Methods: SENTINEL enrolled patients with > ¼ 12
months of prior IFNb-1a treatment who continued with or
without addition of natalizumab. MRI scans at baseline and
year 1 were compared for new lesions. New lesions as a risk
for clinical activity (relapses or progression) between years 1
and 2 were examined.
Results: New MRI and clinical activity in year 1 was
associated with increased risk for relapse or progression in
year 2 (P<0.0001 and P ¼ 0.0016). Clinical activity in
year 1, even without new MRI activity, showed increased
risk for the same outcomes (P<0.0004). From a logistic
regression, patients with > ¼ 2 new MRI lesions and no
clinical activity in year 1 demonstrated a trend to be more
likely to have clinical activity in year 2 compared with similar patients with <2 new lesions in year 1 (OR ¼ 1.562,
CI 0.889, 2.743), P ¼ 0.1208).
Conclusion: Clinically apparent but not clinically silent
MRI activity predicted disease worsening over 2 years. Longer studies are needed to confirm results.
Study supported by: Biogen Idec Inc.
TS: consultant fees and honoraria from Biogen Idec,
Teva, Novartis, Pfizer, Athena Diagnostics, Acorda, and Ave-
Background: Elevated CSF protein with leukocyte count
<10/mm3 is a supportive criterion of chronic inflammatory
demyelinating polyradiculoneuropathy (CIDP). However,
protein content can be normal in a part of these patients.
Objective: To analysis the difference of electrophysiological
patterns and clinical features in CIDP patients with or without protein elevation. Methods: Detailed electrophysiological
findings, clinical features and CSF changes were reviewed in
patients with CIDP. Result: Of 35 patients, 26 had elevated
CSF protein and 9 were unchanged. There was no statistical
difference between these groups for age (Pearson corr:
0.179), gender (Pearson corr: 0.065), response to therapy,
comorbdity, and outcome (Pearson correlation 0.197). Of
the 9 patients with normal CSF protein, there was a strong
correlation with an axonal pattern on electrophysiological
examination (Pearson correlation 0.692; pvalue). Conclusion:
CIDP patients with normal CSF protein are indistinguishable from CIDP with elevated protein with the exception of
an axonal pattern on EMG/NCV. Although these patients
had an equal response to therapy, further data will be collected to determine whether other factors are associated with
normal CSF protein and treatment outcomes.
Study supported by: The Methodist Hospital Neurological Institute
Salaries
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T1729. Are Anti-TAG-1 Autoantibodies Markers in
Autoimmune Demyelinating Disorders of the PNS and
CNS?
Harry Alexopoulos, Pantelis P. Pavlakis, Domna Karagogeos,
Clementine E. Karageorgiou and Marinos C. Dalakas; Athens,
Greece and Heraklion, Greece
Stage:
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T1733. The Relationship between Conduction Block
and Clinical Characteristics in Guillain-Barré Syndrome
with Anti-GM1/GalNAc-GD1a Antibodies
Go Ogawa, Ken-ichi Kaida, Susumu Kusunoki, Motoi
Kuwabara, Fumihiko Kimura and Keiko Kamakura;
Tokorozawa, Saitama, Japan and Osaka-Sayama, Osaka,
Japan
There is evidence of anti-TAG-1 autoantibodies (TAG-1
is involved in the development of axonal connections),
being associated with autoimmune syndromes of the
CNS. Anti-TAG-1 antibodies have been found both in
multiple sclerosis and in autoimmune limbic encephalitis. Also, polymorphisms in the TAG-1 gene influence
treatment response in chronic inflammatory demyelinating polyradiculoneuropathy. We wanted to investigate
whether anti-TAG-1 autoantibodies are present in
CIDP.
We tested serum samples from 12 patients with autoimmune demyelinating neuropathy (8 with CIDP, 2 with
CIDP and CNS demyelination, 2 with MMN), 9 with
Sjögren’s syndrome-associated axonal polyneuropathy and
50 with relapsing–remitting MS. We established a cell-based
assay previously used to detect anti-TAG-1 autoantibodies
in LE. Briefly, either the FNIII or the IgC2 domains of
TAG-1 were expressed in HEK cells and were incubated
with patient sera. Antibody binding was visualized using a
secondary anti-human fluorescent antibody.
No positive staining was detected in any of the patients
with autoimmune peripheral neuropathies or with RRMS.
Our results suggest that neither anti-TAG-1 autoantibodies
are a marker for demyelination in PNS or CNS nor TAG-1
is a candidate autoantigen in CIDP or MS.
Study supported by: Special Research Account, National
and Kapodistrian University of Athens
Patients with Guillain-Barré syndrome (GBS) with antibodies to a ganglioside complex GM1/GalNAc-GD1a frequently show motor conduction block (CB) at the intermediate portion of peripheral nerves. Clinical data of 57
patients with anti-GM1/GalNAc-GD1a-IgG were studied to
elucidate the association between CB and clinical and electrophysiological characteristics. Thirty patients (male/female,
19/11) had CB, classified as CB(þ) (mean age, 43.1 6
17.7 y/o), and 27 patients (male/female, 10/17) did not,
classified as CB(-) (mean age, 46.8 6 16.5 y/o). Males are
significantly more in the CB(þ). Both groups presented frequent preceding respiratory infection, infrequent cranial and
sensory nerve disturbances, and were equal in the disability
at the nadir. Twenty of 25 non-ambulatory patients could
walk within three months, with no difference between both
groups. The 17 CB(þ) patients were electrodiagnostically
classified into acute inflammatory demyelinating polyneuropathy, one of whom changed to acute motor axonal neuropathy later. Serial electrophysiological results suggested
Wallerian degeneration only in one and no evident remyelination. In view of the rapid recovery and lack of remyelination, axonal conduction failure with little pathological
changes may be major mechanism in anti-GM1/GalNAcGD1a antibody-associated nerve dysfunction.
T1734. Withdrawn
T1730. Introduction and Diffusion of Multiple Sclerosis
in the United States
Mitchell T. Wallin and John F. Kurtzke; Washington, DC
T1735. Randomized, Open-Label Study To Evaluate
Patient-Reported Outcomes (PRO) with Fingolimod
after Changing from Prior Disease-Modifying Therapy
(DMT) for Relapsing Multiple Sclerosis (MS): EPOC
Study Rationale and Design
Luigi M. Barbato, Lesley Schofield, Kevin McCague, Linda
Pestreich, Kathy Tobias and Manoj Malhotra; East Hanover,
NJ
Epidemiological evidence suggests that multiple sclerosis has
spread from an origin in northwestern Europe. How and
when it came to the US has not been well defined. Nationwide morbidity data here have arisen primarily from the
military-veteran populations of our several wars. Prevalence
rates for draftees rejected because of MS for military service
in World War I provide its earliest distribution. Small numbers of cases required combination of states of residence
into 23 areas. Prevalence rates for the 255 cases in these
areas showing a strikingly high rate in area P, comprising
Wisconsin and Minnesota. These states were settled in the
mid-19th century mainly by immigrants from south-central
Norway and Sweden. Their original Scandinavian residences
were principally in the high-risk areas for MS in both countries. When compared with two later military-veteran series,
one from World War II and the Korean Conflict, the other
from Vietnam and later service to 1994, a continuing spread
from this north mid-western focus was seen. MS appears to
have been introduced into the US in the mid-19th by immigrants from Scandinavia to Wisconsin and Minnesota, with
later diffusion throughout the land.
Study supported by: VA Merit Review Grant Program &
National MS Society
The efficacy and safety profiles of fingolimod (FTY720)
have been well characterized in phase 2 and 3 studies; however, limited data exist on PRO. The EPOC study is evaluating PRO and safety in relapsing–remitting MS patients
who have received 6 months’ treatment with a single
approved DMT and are randomized 3:1 to receive oncedaily fingolimod 0.5 mg with no washout or to continue
standard DMT (interferon-b-1a, interferon-b-1b, or glatiramer acetate) for 6 months, followed by a 3-month openlabel extension, in which the DMT group can change to
fingolimod with no washout. The primary endpoint is
change in patient-reported treatment satisfaction using the
global satisfaction subscale of the Treatment Satisfaction
Questionnaire for Medication (TSQM). Secondary endpoints are safety/tolerability, changes in physician-reported
Clinical Global Impression-Improvement, and changes in
the following PRO: Fatigue Severity Scale; Beck Depression
Inventory-II; activities of daily living using the Multiple
Sclerosis Activities Scale (PRIMUS-Activities); effectiveness,
side effects, and convenience subscales of the TSQM; and
the Short-Form 36 Health Survey-v2-acute. The study is
enrolling at approximately 175 US centers.
T1731. Withdrawn
T1732. Withdrawn
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Study supported by: Novartis Pharma AG, Basel,
Switzerland
Dr. Barbato, Dr. Schofield, Dr. McCague, Dr. Pestreich,
Dr. Tobias, and Dr. Malhotra are employees of Novartis.
Stage:
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T1738. Coma as an Inital Manifestation of Acute
Disseminated Encephalomyelitis
Megan McGarry, Natasha Tilluckdharry and Dipak P.
Pandya; Paterson, NJ
Background: Acute Disseminated Encephalomyelitis
(ADEM) is a monophasic autoimmune demyelinating disease. Clinical manifestations include an altered behavior,
headache, seizures and coma. We report a unique case which
was presented as a coma an initial manifestation of ADEM.
Case Report 21 year old woman was found unconscious
with severe metabolic acidosis, renal failure requiring urgent
dialysis and ventilatory support. Magnetic Resonance Imaging (MRI) of the brain showed extensive T2 signal in the
periventricular area, deep white matter and bilaterally in the
basal ganglia and hippocampus with enhancement. Her
CSF studies were unremarkable. She was treated with pulse
dose of solumedrol. Because of lack of initial response, she
was treated with eight cycles of plasmapheresis. She recovered completely from illness. She had several follow up
MRIs with significant improvement. Her neuropsychological
evaluations showed significant improvement and currently
she is pursuing higher studies without any difficulties.
Conclusion: Based on our literature, this is the first case
of coma patient as an initial manifestation of ADEM. Our
patient has complete recovery of physical and neurcognitive
symptoms which make onliest clinical features and outcome.
We think that prompt and aggressive management may
improve outcome from catastrophic neurological sequel.
T1736. Novel Diagnostic Tool for MS
Nancy L. Monson, Ann J. Ligocki, William H. Rounds, Diane
Xiang, Lindsay G. Cowell, Doug Bigwood, Eric Eastman,
Jeffrey L. Bennett, Scott D. Boyd, Andrew Z. Fire, Elliot M.
Frohman and Benjamin M. Greenberg; Dallas, TX;
Gaithersburg, MD; Denver, CO and Palo Alto, CA
Multiple Sclerosis (MS) is the leading disease of the central
nervous system and a significant, costly cause of disability in
young adults. Patients at risk for MS often present with a
single demyelinating event, typically called a ‘‘clinically isolated syndrome’’ (CIS) and present a challenging diagnostic
and therapeutic dilemma. The community has an urgent
need to develop tools that would assist in identifying
patients who would develop MS in the future, since treatment with the appropriate immunomodulatory agents early
in the disease course can delay long-term disability. Our laboratory has identified a completely novel type of biomarker,
based on a pattern of antibody gene mutations (i.e. antibody gene signature or ‘‘AGS’’) that is exclusive to MS
patients. In fact, the AGS demonstrated utility as a molecular diagnostic tool in a small cohort of patients who presented with optic neuritis (and were thus at risk to develop
MS) with a sensitivity of 100%, specificity of 67%, positive
predictive value of 89%, negative predictive value of 100%,
and accuracy of 91%. Our current cohort, which includes
both patients who presented with optic neuritis and patients
that presented with transverse myelitis, has an increased accuracy of 94%.
Study supported by: National MS Society
T1739. NMO-IgG in a Patient with Neurosarcoidosis
Lena Derani** and Elham Bayat; Washington, DC
Neurosarcoidosis is a rare manifestation of sarcoidosis in
which inflammation and abnormal deposits occur in the
nervous system. Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that primarily targets the spinal cord and optic nerves. NMO-IgG (anti-aquaporin-4) is
considered to be a sensitive and specific marker for NMO.
However, NMO-IgG has also been found in patients with
NMO spectrum disorders (NMOSD), paraneoplastic disease
and systemic lupus erythematosus. We present the first
reported case of NMO-IgG positivity in a patient with neurosarcoidosis but no evidence of NMO. We discuss autoimmunity in neurosarcoidosis, the specificity of NMO-IgG
and its likelihood in autoimmune diseases, and the possibility of concomitant neurosarcoidosis and neuromyelitis
optica. We suggest the possibility that NMO-IgG is a nonspecific indicator of autoimmunity present in patients with
other autoimmune disorders, including neurosarcoidosis. We
remind neurologists that patients who test positive for
NMO-IgG do not necessarily carry the diagnosis of NMO
or NMOSD, despite the documented specificity and sensitivity of NMO-IgG for these diseases. Further studies are
needed to investigate the positive predictive value of NMOIgG and the prevalence of positive NMO-IgG in the normal
population and in patients with autoimmune diseases.
T1737. Efficacy of Combination Therapy in Marburg
Variant Type of Multiple Sclerosis
Jennifer Gabbard, Yasmin Bilal and Dipak Pandya; Paterson,
NJ
Background: Marburg variant type of MS is a very rare
form of disease which commonly consider fatal after weeks
to months. The variant forms of multiple sclerosis are very
rare and tend to have a rapid deteriorating course. We
report an unusual case of Marburg variant MS, who
responded to various combination therapy favourably.
Results: 18-year-old male presented with imbalance,
wide based gait and dizziness. His physical examination
showed nystagmus, no signs of optic neuropathy, dysmetria, hyperreflexia and sustained clonus. The MRI brain
showed extensive demyelinating plaques in periventricular
white matter, brainstem and various areas of brain. The
imaging findings were not consistent with Neuromyelitis
optica. The patient was initally treated with pulse doses
methylprednisone and plasmapheresis. Because of persisting clinical symptoms and imaging findings, patient was
treated with induction doses of mitoxanthrone and interferone beta-1b. The patient had near complete resolution
of his clinical symptoms and significant MRI
improvement.
Conclusions: Combination acute therapies like plasmapheresis and mitoxanthrone may reduce inflammatory cytokins in acute course of disease and may result in improvement. More multicenter clinical trial may help to
understand nature of disease and management options.
T1740. Correlates of Dietary Intake in Individuals with
Multiple Sclerosis
Matthew A. Plow, Marcia Finlayson and Chi Cho; Cleveland,
OH and Chicago, IL
Since the multiple sclerosis (MS) population has a similar
life expectancy as the general population and is characterized
by impairments that can interfere with healthy eating habits,
malnutrition, vitamin deficiencies, and obesity are prevalent
problems among MS patients. However, few studies have
been conducted to provide clinicians with evidence-based
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approaches to support MS patients in developing healthy
eating habits. Thus, the purpose of this study was to identify modifiable factors that predict dietary intake. Using
data from an on-line validated survey of 271 MS patients, a
stepwise multiple regression model was used to determine
the relative importance of personal characteristics, symptoms, functional limitations, and coping skills in influencing
dietary intake. Over 50% of the sample was overweight/
obese. Four variables made the model: self-efficacy (b ¼
0.51), physical activity (b ¼ 0.14), pessimism (b ¼ 0.13),
age (b ¼ 0.12), and coping skills (b ¼ 0.10), which
explained 40.5% of the variance in intake. Neither symptoms nor functional limitations significantly predicted
intake. This is the first study to document a relationship
between self-efficacy, coping skills, and nutritional habits in
a large generalizable sample of MS patients. Future research
should examine the effectiveness of efficacy-enhancing nutritional interventions that focus on improving coping skills.
Study supported by: This work was supported through
the National Multiple Sclerosis Society (NMSS) post-doctoral training grant. The information presented in this
abstract does not necessarily reflect the position, ideas, or
opinions of the NMSS
Stage:
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CSF with distinct chemokine/cytokine profiles. Cluster 1
had the shortest time from initial melanoma diagnosis to
brain metastasis (mean 7.5 months, P ¼ 0.0278). MIP-1b
and IP-10 were elevated while GRO-a, IL-8, and Eotaxin
were suppressed. Cluster 3 was associated with a shortened
time from brain metastasis to death (mean 5.5 months, P ¼
0.0714). Prior biologics treatment also correlated with the
shortest time interval from brain metastasis to death (mean
5.9 months, P ¼ 0.0396). In cluster 3, MIP-1a was elevated, while GRO-a, MPIF-1, MIG, and IL-1b were suppressed. Cluster 4 was associated with a trend for prolonged
overall survival (mean 78.0 months, P ¼ 0.0847). This cluster also had the longest survival from date of biologics treatment to death (mean 58.5 months, P ¼ 0.0132). Cluster 4
had elevated MPIF-1 while GRO-a, IL-8, IP-10, MDC, IL5, MIG, and IL-1b were suppressed. Specific cytokine/chemokine profiles measured in the CSF of melanoma patients
may have prognostic and predictive value for melanoma
brain metastasis.
Study supported by: A Reason To Ride research fund.
T1803. Role of p75NTR and Its Signaling Pathways in
Fenretinide (4-hydroxyphenyl Retinamide – 4HPR)
Induced Apoptosis in Neuroblastoma Cells
Veena R. Ganeshan and Nina F. Schor; Rochester, NY
Neurooncology
T1801. Comparative Uptake and Cytotoxicity of AntiHu and Anti-Ri Antibodies in Rat Cerebellar Slice
Cultures
John E. Greenlee, Susan A. Clawson, Blair Wood, Kenneth E.
Hill and Noel G. Carlson; Salt Lake City, UT
Objective: To understand the role of p75NTR and its signaling pathways in Fenretinide(4-hydroxyphenyl retinamide4HPR)-induced apoptosis and determine if JNK phosphorylation mediates this effect in neuroblastoma cells.
Background: 4HPR is well tolerated in clinical trials and
causes apoptosis by increasing oxidative stress(OS) in cancer
cells. p75NTR has pro and anti-apoptotic functions
depending on the cell milieu and type.
Methods: S-type neuroblastoma cells (SH-EP1) transfected with varying amounts of p75NTR are used in the
4HPR-concentration experiments. 4HPR treatment results
in changes in JNK phosphorylation and OS, which are
recorded using western blotting and fluorescent microscopy.
Results: 4HPR treatment reduces viability in SH-EP1
and SK-N-SH cells within 24(15%)-72 hrs(40%) and causes
an increase in mitochondrial O2- production. A sustained
increase in Akt phosphorylation occurs in SH-EP1 cells
with lower p75NTR levels. Within 1hr of 4HPR treatment,
JNK phosphorylation increases by 100–150% in SH-EP1
cells with lower levels of p75NTR.
Conclusion: JNK phosphorylation appears to be protective against 4HPR-induced apoptosis. This will facilitate the
development of combination chemotherapeutics for residual
disease treatment and recurrence by increasing OS and
enhancing response to conventional chemotherapeutics.
Study supported by: Studies presented in this abstract
were funded by grants to Nina F. Schor from the
National Cancer Institute (CA07429), the National Institute of Neurologic Disorders and Stroke (NS038569),
and the William H. Eilinger Endowment for Pediatric
Research of the Golisano Children’s Hospital at the University of Rochester Medical Center. These organizations
played no role in the interpretation of the data or the
substance of the review presented herein. Veena R. Ganeshan is a doctoral student in the Integrated Graduate Program in Neuroscience of the University of Rochester
School of Medicine and Dentistry. Neither of the authors
have conflicts of interest of relevance for this abstract. No
additional individuals played any role in the production
of this abstract.
Anti-Hu and anti-Ri antibodies label different neuronal antigens in western blots. However, both recognize intracellular
antigens present in essentially all neurons. At autopsy, brains
of patients with anti-Hu antibody show neuronal destruction.
In contrast, anti-Ri antibody is less clearly associated with
neuronal death, and patients with anti-Ri antibodies may
respond to treatment. To study the effects of these two antibodies on living neurons, we incubated rat cerebellar slice
cultures with either anti-Hu or anti-Ri antibodies and followed these cultures over time using TUNEL and FLICA
methods to detect apoptosis, and uptake of SYTOX green to
detect non-apoptotic cell death. Both anti-Hu and anti-Ri
antibodies accumulated in essentially all neurons. Anti-Hu
antibodies caused apoptosis within 72–96 hours in neurons
throughout the cerebellum. In contrast, cells accumulating
anti-Ri antibodies remained viable for over 200 hours, without evidence of apoptosis or necrotic cell death. Neurons in
general may be able to internalize antibodies. Anti-Hu
appears to be specifically cytotoxic, whereas anti-Ri appears
less able to affect neuronal viability and may predominantly
cause neuronal dysfunction rather than death.
Study supported by: United States Department of Veterans Affairs
T1802. Cerebrospinal Fluid Chemokine/Cytokine
Biomarkers for Melanoma Brain Metastasis
Edwin Lok, Amy S. Chung, Szexian Lee, Tamar Melman,
Kenneth D. Swanson and Eric T. Wong; Boston, MA
Because immunoregulatory chemokines and cytokines may
modulate the biology of melanoma brain metastasis, we
measured 26 of them in the CSF from 22 patients using
multiplexed ELISA. Clustergram revealed segregation of
non-disease controls from 5 identifiable clusters of patient
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T1804. Relationship between Brain MRI Imaging
Parameters and Molecular Biomarkers as Prognostic
Indicators in Glioblastoma Multiforme
Xiao-Tang Kong, Senxi Du, Beverly D. Fu, Mark E. Linskey
and Daniela Bota; Orange, CA and Irvine, CA
Stage:
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lished Bevacizumab side effects include hypertension,
delayed/impaired wound healing, gastrointestinal perforation
and proteinuria. Recently a small number of case reports
have reported six cases of optic neuropathy following Bevacizumab treatment for GBM.
We report here a case of a 24 year old woman with Neurofibromatosis type I (NF-1) and right Thalamic GBM
(WHO grade IV), who developed a severe, subacute optic
neuropathy during treatment with Bevacizumab and Irinotecan for recurrent GBM following standard initial chemo
radiotherapy with temozolamide. Following 4 cycles of salvage chemotherapy using Bevacizumab/Irinotecan, the
patient developed diffuse blurring of vision, which progressed over 3-4 weeks-eventually resulting in total
blindness.
Six weeks following cessation of Bevacizumab the patient’s
vision improved with return of light perception, and eventual return of baseline vision. Our completed poster will
include a summary of our case, MRI images of the tumor,
and results of ophthalmologic examination during and following Bevacizumab treatment.
Study supported by: Residency program
The purpose of this study is to explore the relationship
between the potential MRI prognostic indicators and the
molecular biomarkers in order to better evaluate the prognosis of the patients with GBM.
Molecular biomarkers were determined using Immunohistochemistry. MIPAV software was used to quantify the volume of MRI parameters.
Of the seventeen specimens that eventually included, 10
had high and 6 low levels of MGMT expression; 5 were
negative and 11 positive for EGFR wt amplification; 12
negative and 5 positive for EGFRvIII expression; 14 had
PTEN loss and 3 had intact PTEN. The vasogenic edema
were more significant in the low MGMT expression group
(P ¼ 0.04). The necrosis were larger in the group of non
EGFR wt amplification (P ¼ 0.03) and the total volume of
tumor involvement was significantly more in EGFRvIII variant expression group (P ¼ 0.0072). Our data suggest that
the volume of vasogenic edema, necrosis and total tumor
involvement are related to low MGMT level, lack of EGFR
wt amplification, and increased EGFRvIII expression as
prognostic indicators. Definitely, more cases will be added
to the study to confirm the findings and to evalute the clinical prognosis.
T1807. Anti-Ri-Associated Paraneoplastic Brainstem
Cerebellar Syndrome with Medically-Intractable Nausea
in a Patient with Large Cell Neuroendocrine Lung
Carcinoma: A Case Report
Amber N. Mitchell, Jessica Levesque and Earl Zimmerman;
Albany, NY
T1805. Secondary Intramedullary Spinal Cord NonHodgkin’s Lymphoma
Eoin P. Flanagan, Brian P. O’Neill, Thomas M. Habermann
and B. Mark Keegan; Rochester, MN
Paraneoplastic neurologic syndromes are rarely the first
manifestations of occult malignancies, which if left
untreated, often lead to significant morbidity and mortality.
The presence of onconeural antibodies supports the paraneoplastic diagnosis, but is not absolutely essential. Anti-Ri
autoantibodies are commonly associated with breast and
small cell lung cancers. There are cases of anti-Ri paraneoplastic cerebellar degeneration reported, but none describe
associated severe nausea and emesis as the major presenting
and enduring symptoms. Here, we report a case of a 75year-old female with medically-intractable nausea, vomiting,
diplopia, and vertigo for three months. Physical exam
revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Serum was
Anti-Ri antibody positive. Computed tomography identified
a 2.5 cm by 2.2 cm lung mass, and histopathology revealed
large cell neuroendocrine carcinoma with smaller portions
of adenocarcinoma. Post-lobectomy, the patient clinically
improved. This is the first report of paraneoplastic brainstem cerebellar syndrome involving anti-Ri positivity from
neuroendocrine tumor of the lung with nausea and vertigo
as the major features and with improvement after tumor
resection.
Intramedullary spinal cord metastases are rare and associated
with poor long-term survival. We present the clinical characteristics and outcome of secondary intramedullary spinal
cord non-Hodgkin’s lymphoma (NHL) in 7 patients seen at
Mayo Clinic from 1996–2010. All patients had myelopathy
and imaging evidence of intramedullary spinal cord involvement of pathologically confirmed systemic NHL (B-cell, 6;
T-cell, 1). Spinal cord NHL was diagnosed by: CSF cytology, 4; PET hypermetabolism, 2; or MRI features alone, 1.
In two, myelopathy was the initial presentation of systemic
NHL and in the remainder the median time from NHL diagnosis to intramedullary involvement was 8 months (range,
1–58). Median age was 60 years (range, 41–81) and 4 were
wheelchair-dependent at diagnosis. MRI spine lesions (Thoracic, 3; Cervical, 3; or both, 1) were typically gadolinium
enhancing, expansile and associated with PET hypermetabolism. Two had leptomeningeal involvement and 4 had coexisting brain lesions. Six of the seven were treated: intravenous methotrexate, 3; radiation, 2; and R-CHOP, 1. Four
improved (mild, 3; marked, 1) following treatment. The
median survival was 11.5 months (range, 1–28). Secondary
intramedullary spinal cord NHL appears to have longer survival than intramedullary metastases from most other
cancers.
T1808. Glioblastoma Multiforme: A Rare Presentation
of Pineal Tumor with Leptomeningeal Seeding and
Future Directions
Noor Yono, Tulika Ranjan and Rabih Kashouty; Manhasset,
NY, United States Minor Outlying Islands and New York, NY
T1806. Case Report: Optic Neuropathy in a Patient with
Glioblastoma Receiving Bevacizumab
Robert A. Fishman, Lara Kunschner and Erik Happ;
Pittsburgh, PA
Glioblastoma Multiforme (GBM) is the most common primary malignancy of the Central Nervous System. Pineal
GBM with leptomeningeal seeding is an exceedingly rare tumor. Only 18 cases have been reported in the literature. We
present a case of pineal gland GBM with leptomeningeal
disease treated with combination chemotherapy. A 55-yearold man presented with progressive headache, peduncular
Bevacizumab is a humanized monoclonal antibody developed to target and subsequently block vascular endothelial
growth factor received FDA approval for single agent treatment of recurrent Glioblastoma multiforme in 2009. Estab-
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hallucinations and perinaud syndrome. Brain MRI showed a
heterogeneously enhancing pineal mass measuring 2.1 cm
with hydrocephalus and infiltration into the midbrain and
thalamus. The pathology was consistent with GBM with
Ki-67 labeling index of 30–50%. Brain and total spine MRI
showed diffuse linear leptomeningeal disease. Chemotherapy
with Temozolomide was started on day 1st. Two high-volume lumbar punctures with intrathecal Methotrexate were
performed. Within 24 hours following the first Methotrexate treatment, the patient showed significant improvement.
Initial lumbar puncture showed markedly elevated protein
count of 2856. He was further treated with Avastin every 2
weeks and monthly Temozolomide. Recent CSF protein has
improved to 315 and the pineal mass size has decreased to
0.9mm after four months of starting treatment.
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mographic variables amongst groups. An ANOVA assessed
11
C-PiBregional differences.
Results: Symptomatic AD were older (p < 0.001), had
lower CSF Ab42 (p < 0.001), and had higher CSF tau levels
(p < 0.001). Regardless of degree of impairment, HIVþ
participants had no increased 11C-PiB. Mean and regional
binding potentials were elevated for symptomatic AD participants (p <0.0001).
Conclusions: HIVþ participants, even with HAND, do
not exhibit increased 11C-PiB while symptomatic AD individuals have increased fibrillar Ab42 deposition. Observed dissimilarities between HAND and AD may reflect differences
in Ab42 metabolism. 11C-PiB may provide a diagnostic biomarker for distinguishing symptomatic AD from HAND.
Study supported by: ADRC Pilot Grant (3255
P50AG05681), NIMH (K23MH081786), NINR (R01NR
012657), Dana Foundation (DF10052), ARRS Scholar Award,
NIH P01-AG026276, and NIH PO1-AG03991
T1809. Benign-Histology Meningioma with Extracranial
Metastasis
Umer Akbar, Bhavpreet Dham and Melissa Carran;
Camden, NJ
T1902. Modulation of HIV-Tat Neurotoxicity by
Potassium Channel Blockers
Srikant Rangaraju* and Jeffrey A. Rumbaugh; Atlanta, GA
Objective: To recognize extracranial dissemination from a
meningioma
Background: Meningiomas are regarded as benign
tumors, as malignant histology is uncommon and extracranial metastasis is an extremely rare occurrence.
Design: We report a case of a histologically-benign meningioma with metastasis to the lungs.
Case: A 36 year-old male with symptomatic epilepsy presented with a breakthrough seizure. Patient had a meningioma resection in 1998. Few months later, imaging revealed
recurrent tumor which was treated with 48 Gy of radiation.
Routine chest x-ray followed by computed tomography scan
confirmed multiple scattered round nodules, averaging
between 1 to 1.5 cm. Fine-needle aspiration showed clusters
of meningothelial cells consistent with metastasis from the
recurrent intracranial tumor.
Discussion: Majority of meningiomas are benign (grade
I), while few are atypical (grade II) and malignant (grade III)
histology is rare. Aggressive behavior and metastatic potential
is mainly seen in atypical and malignant histologic subtypes.
With a metastasis rate of 0.1%, meningiomas are seldom
seen extracranially. Very rarely, the metastasizing meningioma
is of benign histology. Certain tumor tendencies for aggressive behavior have been observed and are discussed.
HIV-Tat is released by HIV-infected cells and activates
NMDA receptors on neurons leading to calcium influx. As
intracellular calcium concentrations rise, the calcium gradient decreases and limits further calcium entry.Voltage-sensitive(Kv) and calcium-activated(SK) potassium channels open
in response to depolarization and calcium flux thereby
restoring the ionic gradient needed for sustained calcium
entry. This dysregulation of calcium homeostasis triggers
secondary neurotoxic cascades resulting in cell death.
Kv(Kv1.2, 1.3, 2.1) and SK channels are expressed in large
numbers by cortical neurons. We hypothesized that blockade of potassium channels may reduce Tat-neurotoxicity by
preventing restoration of calcium gradients. Fetal rat cortical
neurons were exposed to Tat (400 nM) and potassium channel blockers: Tetraethylammonium (TEA, non-specific Kv
blocker), 4-Aminopyridine (4-AP, Kv1 and Kv2 blocker)
and Apamin (SK blocker). Neurotoxicity was determined by
the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 12 hours. Tat neurotoxicity (p ¼
0.0005 compared to untreated controls) was abolished by 4AP at 0.5 mM (p ¼ 0.0005) and 1mM (p ¼ 0.0003) and
reduced by TEA (100 microM, p ¼ 0.03) and Apamin
(50nM, p ¼ 0.01). Our results suggest that potassium channels play a role in Tat-neurotoxicity. Kv and SK potassium
channels may represent novel therapeutic targets in HIVneurodegeneration.
Study supported by: Emory University Internal funding.
Neurovirology
T1901. HIV Associated Neurocognitive Disorder
(HAND) Is Not Associated with Increased Fibrillar
Amyloid Deposits Using 11C-PiB in Middle-Aged HIVþ
Participants
Beau Ances, Jewell Thomas, Tammie Benzinger, Jon
Christensen, Mengesha Teshome, Patricia Aldea, Anne Fagan,
David Holtzman, John Morris and David Clifford; Saint
Louis, MO
T1903. Varicella Zoster Encephalitis – Relationship
between Viral Load, Time and Outcome
Benedict D. Michael, Mike Griffiths, Anna Stewart, Charlotte
Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen
Galbraith and Tom Solomon; Liverpool, Merseyside, United
Kingdom
Objectives: Diagnostic challenges exist for differentiating
HIV associated dementia (HAD) from Alzheimer disease
(AD). Similar abnormalities in brain amyloid-b42 (Ab42)
metabolism occur for both. We evaluated if 11C-Pittsburgh
compound B (11C-PiB) discriminates AD from HAND.
Methods: In this case-control study 16 HIVþ (11 cognitively normal, 5 HAND) and 19 HIV- (8 cognitively normal, 11 symptomatic AD) participants were assessed using
11
C-PiB, clinical exam, and cerebrospinal fluid (CSF) testing. v2 and t-tests investigated differences in clinical and de-
Background: Varicella zoster virus (VZV) is a common
cause of encephalitis with a wide spectrum of morbidity and
mortality. The pathophysiology remains poorly understood
and few prognostic markers are available. A few studies have
attempted to use the viral load of the cerebrospinal fluid
(CSF) to investigate this, with contradictory results. These
have not been conducted in context of time.
Objectives: To determine the CSF viral load in VZV encephalitis in relation to time and outcome.
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Study Design: The regional virology database was
screened to identify VZV positive CSF over 5years. Viral
load was determined by quantitative-polymerase chain reaction (qPCR).
Results: 608 patients were screened, 36 had VZV qPCR
performed, 12 were positive and had encephalitis. There was a
strong negative correlation between time to LP and viral load
(tau b ¼ 0.59, p ¼ 0.036). There was no significant difference in viral load between those with good and poor outcome.
Conclusions: CSF viral load appears to more closely
relate to time to LP than outcome. Timing of LP should be
included in future studies to investigate the role of the viral
load in the pathophysiology and prognosis of encephalitis.
Study supported by: Study funded by the National Institute for Health Research (NIHR-UK) Biomedical Research
Centre.
for lipopolysaccharide (LPS), within post-mortem brain tissue from HIV positive subjects (n ¼ 15) and HIV negative
subjects (n ¼ 10) via quantitative real time PCR (qRTPCR) and immunohistochemistry (IHC). We also assessed
cognitive brain functions in 7 domains and their correlation
with TLR4 mRNA expression. We found TLR4 expression
was significantly higher in HIV positive subjects than HIV
negative controls (p<0.05). IHC demonstrated that TLR4
expression was upregulated in HAND brains, and TLR4positive cells in the cortex were significantly smaller in HIV
positive subjects (p<0.05). Higher TLR4 mRNA expression
was associated with impaired motor function among HIV
positive subjects (p<0.05). These findings suggest that
TLR4 signaling may play a role in HIV neuropathogenesis
and suggest new strategies for therapeutic intervention.
Study supported by: NIH R21 Grant
T1904. Acute Varicella Zoster Virus Encephalitis in
Adults – Relationship between Viral Load, Time,
Clinical Features and Outcome
Benedict D. Michael, Michael Griffiths, Anna Stewart,
Charlotte Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller,
Sareen E. Galbraith and Tom Solomon; Liverpool, United
Kingdom
T1906. Revisiting Reactivation of Calcified
Neurocysticercosis: Report of Three Recent Cases
Sanjna M. John** and Maria del Pilar Cortes Nino; Kingston,
ON, Canada and Montreal, QC, Canada
Background: Neurocysticercosis (NCC) is a CNS infection
with significant associated morbidity in the form of acquired
epilepsy. The final stage of disease is cyst calcification, originally thought to represent disease resolution and cessation of
active symptoms. Recent studies have suggested that calcified
NCC is a chronic condition with intermittent symptom exacerbation and imaging findings during symptom recurrence.
Methods: We did a retrospective chart review and imaging analysis of patients seen with reactivation of calcified
NCC at the Montreal Neurological Institute between 2007
and 2010.
Findings: 2/3 of patients presented with neurological
symptoms other than seizures, and 2/3 of patients presented
with multiple calcified cysts. All patients had edema and
hypodensity on imaging around at least one calcified lesion
during symptom exacerbation.
Interpretation: Our findings were generally consistent
with prior literature, however, seizure was not the predominant clinical presentation as has been reported. Perilesional
edema was seen on imaging in all patients and could be
used as a reliable sign of symptom recurrence.
Background: Varicella zoster virus (VZV) is a common
cause of viral encephalitis with a wide spectrum of outcomes. The pathophysiology remains poorly understood and
few prognostic markers exist. A few studies have used viral
load, determined by quantitative polymerase chain reaction
(qPCR) of cerebrospinal fluid (CSF), to investigate this,
with contradictory results. However, these have not assessed
this in the context of time.
Objectives: To determine the viral load in VZV encephalitis in relation to time and outcome.
Study Design: The Liverpool Specialist Virology laboratory was screened to identify patients with VZV-positive
CSF over 5years. Viral load was determined. Poor outcome
was defined as moderate disability-death (Glasgow outcome
score [GOS]2-5) and high viral load as (>5104GEq/ml).
Results: Of 608 screened; 36 had VZV-PCR; 12 were
positive. There was a strong negative correlation between
time from symptoms to LP and viral load (tau b ¼ 0.59,
p ¼ 0.036). There was no difference in viral load between
those with good and poor outcome.
Conclusions: In VZV encephalitis, viral load appears to
better relate to time. Timing should be included in future
studies aiming to relate viral load to outcome.
Study supported by: This study recieved support from
the National Institute for Health Research Biomedical
Research Centre on Infectious Diseases. The authors have
no other conflicts of interest to declare
T1907. Clinical Features at Admission in Patients with
Meningeal Cryptococcosis in a Third Level Hospital in
Mexico
Jesus F. Mendoza, Gilberto Vazquez, Jeronimo Rodriguez and
Ildefonso Rodriguez; San Luis Potosı´, San Luis Potosı´, Mexico
Introduction: Meningeal cryptococcosis (MC) is caused by
Cryptococcus species.
In Mexico, treatment is limited because 5-fluocytocine is
unavailable.
Objectives: To determine the presenting clinical features
of patients diagnosed with meningeal cryptococcosis in a
third level hospital in Mexico.
Methods: Retrospective review of medical records of
patients with diagnosis of MC.
Results: We found 4 HIV possitive patients. Symptom
onset to admision was longer than two weeks in 5 patients.
Clinical characteristics: headache 87.5%, cognitive
impairment, nausea/vomiting and meningismus 62.5%
each, fever and cranial nerve affection 37.5% each, wakefullnes alterations in 25%.
CSF findings: Positive india ink 75%, low glucose 75%, linfocytosis 62.5%, high protein level 62.5%, positive culture 50%.
T1905. TLR4 Expression Is Upregulated in HIVAssociated Neurocognitive Disorder (HAND)
Amir H. Sabouri, Gursharan Chana, Amol Shah, Critian L.
Achim, Ronald J. Ellis, Ian P. Everall and HNRC Group; La
Jolla, CA; Melbourne, Australia and San Diego, CA
Despite the introduction of highly active antiretroviral therapy (HAART), HIV associated neurocognitive disorders
(HAND) remain a significant cause of morbidity. In a previous investigation, we have demonstrated that the gene
expression of a number of proteins related to the innate
immune system toll-like receptor (TLR) signaling pathway
correlate strongly with HIV associated neurodegeneration,
most significantly TLR3 and 4. In this study, we examined gene expression of TLR4, the major signaling receptor
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All patients recieved treatment with Amphotericine B and
fluconazole.Only half completed the induction phase as
recommended.
Discussion: Clinical presentation, CSF findings of
patients presenting with MC in our hospital do not differ
from what has been reported in the medical literature. This
findings confirms the need to mantain a high suspicion
index of CM in immunocompromised or immunocompetent patients with suggestive clinical picture.
Special attention must be paid to appropiate treatment schemes
in the future to achieve better outcomes in this population.
Study supported by: The authors declare no conflict of
interest. None of the authors recieved any financial benefits
from the study.
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considered in the diagnosis of tuberculous meningitis
(TBM). In compiling this review, we searched electronic
data bases in PubMed, Science Direct, Biomedical Central and Google Scholar. Firstly, we evaluate the more
traditional diagnostic methods which have been commonly applied in the diagnostics of tuberculosis (TB).
The role of direct cerebrospinal fluid (CSF) examination
for acid-alcohol fast bacilli, CSF culture for Mycobacterium tuberculosis, and detection of mycobacterial nucleic
acid in the CSF is evaluated. We also consider the role
of brain imaging and chest X-ray. Secondly, the review
evaluates the current evidence on the role of some newly
prospective diagnostic techniques and the coverage is
given to the role of CSF adenosine deaminase activity,
Gen Probe amplified Mycobacterium tuberculosis direct
test, microscopic observation drug susceptibility
(MODS) culture technique, ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay
(ELISpot assay) and enzyme-linked immunosorbent assay
(ELISA) in the diagnosis of TBM.
Study supported by: This was a self-financed study.
T1908. The Diagnosis of Tuberculous Meningitis: A
Current Review of the Clinical and Laboratory Methods
Brian Chisulo, Shan H. Jiang and Yue S. Pan; Guangzhou,
GZ, China
This review traces our understanding of the clinical
manifestations and the laboratory methods commonly
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136th Annual Meeting Sunday,
September 25, 2011 Works in
Progress Poster Session Abstracts
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predictive value of 78% at a cutoff point of 0.5 lg/l. Preliminary results suggest a significant correlation (rs¼0.8)
between NR2 peptide levels and lesion size.
Conclusion: The NR2 peptide is a sensitive and specific
biomarker for IS. Increased NR2 peptide levels can identify
patients with acute IS and correlate with findings on neuroimaging studies.
Study supported by: Department of Defense Grant
(DM090557: VALIDATION OF AMPA RECEPTOR
PEPTIDE ASSAY TO IMPROVE DIAGNOSTIC CERTAINTY OF MILD TRAUMATIC BRAIN INJURY),
USAMRAA
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected
based on scientific merit, timeliness, and anticipated interest
to the membership. Key aspects of research must have been
conducted after the regular abstract deadline.
S143. Initial Transcranial Doppler Velocity Predicts
Development of Symptomatic Vasospasm in Aneurysmal
Subarachnoid Hemorrhage
Shyam Prabhakaran, Konark Malhotra, Rajeev Garg, Sayona
John, Richard Temes and Viven Lee; Chicago, IL
Cerebrovascular Disease
We reviewed 350 consecutive SAH patients with aneurysmal
source, who had TCD within 3 days of admission and survived at least 7 days. We recorded initial flow velocity (IFV)
of the MCA by TCD. Using survival analysis and Cox proportional hazard models, we evaluated initial TCD velocity
at baseline as a predictor of symptomatic MCA vasospasm
and calculated hazard ratios (HR). Among 195 patients who
met inclusion criteria, 43(22%) developed symptomatic
MCA vasospasm. Median values from admission for: TCD
monitoring¼1 day, vasospasm ¼ 6 days and initial MCAMFV ¼ 68cm/sec. In multivariable analysis, initial MCAMFV >75 cm/s was strongly predictive of symptomatic
MCA vasospasm. The 3, 7, 10, and 14-day risks of symptomatic MCA vasospasm were 0.9%, 9.4%, 14.8%, and
14.8% for those with initial MCA-MFV <75 cm/s compared to 5.1%, 21.8%, 31.2%, and 33.0% for those with
initial MCA-MFV >75 cm/s (log-rank test: P ¼ 0.001).
Elevated initial TCD velocity may provide a useful marker
for those at high-risk for symptomatic vasospasm. The risk
of vasospasm in those with elevated MCA velocity > 75
cm/s was significantly higher, occurring earlier and for a
longer period, than in those without.
S141. Polymorphism of Ninjurin2 in Korean
Atherothrombotic Stroke Patients
Dae-il Chang, Sung Hyuk Heo and Hye Ok Kim;
Seoul, Korea
Recently, in a genome-wide association study, the singlenucleotide polymorphisms (SNPs) rs12425791 and
rs11833579 of ninjurin2 (NINJ2) were reported to be associated with atherothrombotic stroke. However, this finding
has not been validated in Korean population yet. We therefore investigated an association between atherothrombotic
stroke and SNPs of NINJ2 in 200 patients and 295 control
subjects. Allelic discrimination assay was used. The A allele
of rs11833579 increased stroke risk significantly (p ¼
0.003, 1.50 (95% CI, 1.15 to 1.96), respectively). The A allele frequencies were higher in stroke patients with hypertension than in control subjects with hypertension (p ¼
0.042 and p ¼ 0.001, respectively) in both SNPs of NINJ2
(rs12425791 and rs11833579). Also, the A allele was more
frequent in stroke patients with hyperlipidemia than in control subjects with hyperlipidemia (p ¼ 0.010 and p ¼
0.005, respectively) in both. In addition, the A allele was
more frequent in stroke patients with diabetes than in control subjects with diabetes (p ¼ 0.008, respectively) in SNPs
rs11833579. In conclusion, SNPs of NINJ2 (rs12425791
and rs11833579) confer a substantial genetic risk factor for
atherothrombotic stroke in our population.
S144. Relative Change in Transcranial Doppler Velocities
Is Inferior to Absolute Thresholds in Prediction of
Vasospasm after Subarachnoid Hemorrhage
Konark Malhotra, James Connors, Viven Lee and Shyam
Prabhakaran; Chicago, IL
S142. NMDA Receptor Biomarker for Acute Stroke
Kerstin Bettermann and Svetlana Dambinova; Hershey, PA
and Kennesaw, GA
We reviewed 350 consecutive SAH patients with aneurysmal
source, who underwent serial TCD monitoring and survived
at least 7 days. We recorded initial flow velocity(IFV) upto
14 days, maximal flow velocity of middle cerebral artery
(MCA), relative flow changes (MFV/IFV) >3, absolute
maximal Lindegaard ratio (LR) >6, mean MCA maximum
flow velocity (MFV) >175 cm/s, and MFV >200 cm/s.
Among 211 patients selected, 48 (23%) developed symptomatic MCA vasospasm. Area under the ROC curve (AUC)
was: MCA-MFV >175 ¼ 0.80, MFV >200 ¼ 0.73, LR
>6 ¼ 0.71, and MFV/IFV >3 ¼ 0.60. The best characteristics were observed for MFV >175 cm/s or maximal LR
>6 as: AUC ¼ 0.81; while sensitivity, specificity and negative predictive value were: 81%, 81% and 94%, respectively;
the positive likelihood ratio was 4.1. MFV/IFV >3 performed the worst. MFV >175 cm/s and/or Lindegaard ratio
>6 accurately predict symptomatic MCA vasospasm. Presence of either/both abnormalities in first 14 days after SAH
increases the likelihood of symptomatic MCA vasospasm by
Background: The NR2 peptide, a breakdown product of
brain specific NMDA receptors, is released into the bloodstream during cerebral ischemia and can be used as a marker
for acute ischemic stroke (IS). Performance characteristics
and critical values of the NR2 peptide in acute IS patients
presenting within 24h of symptom onset are analyzed.
Methods: NR2 peptide levels are correlated with neurological status and results of advanced neuroimaging studies.
Plasma NR2 peptide concentrations are determined by plotting their absorbance values on a calibration curve constructed from the absorbance units of each calibrator and
their known concentrations.
Results: Controls and individuals with vascular risk factors have NR2 peptide concentrations below 0.25 and 0.3
lg/l, respectively. Acute IS patients have significantly higher
NR2 peptide levels (>0.5 lg/l) compared to all control
groups (p<0.0001). Test sensitivity for IS is 98% with a
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>4 fold. Other thresholds including relative change from
baseline appear inferior to these absolute thresholds.
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ing-off in 32.8%. The development of motor complications
was predicted by younger age of onset, higher Unified Parkinson’s Disease Rating Scale Part II score, region (North
America), and gender in addition to levodopa dose. There
was no difference in the LC and LCE groups.
Conclusion: The development of levodopa-induced
motor complications is dose-related (higher with increasing
doses), supporting using the lowest levodopa dose that provides satisfactory clinical control.
Study supported by: This analysis was supported by an
unrestricted grant from Novartis Pharma AG and Orion
Pharma.
C. Warren Olanow has served as a consultant for Teva
Neuroscience, Lundbeck, Boehringer Ingleheim, Novartis
Pharmaceuticals Orion Pharma, Abbot,Solvay, Merck
Serono, Ipsen, and the welding defense industry, and has
stock options in Ceregene and Clintrex. Karl Kieburtz as
received research grants from Amarin, Boehringer-Ingelheim, Medivation and Neurosearch, and received consultancies fees from Abbott, Antipodean, Boehringer-Ingelheim,
Ceregene, Eisai, FoldRx, Lilly, Merz, Novartis Pharmaceuticals, Pfizer, Prestwick, Teva, Schering-Plough, Schwarz,
UCB, Vernalis and Welding. Olivier Rascol has served as a
consultant for Orion Pharma, Novartis Pharmaceuticals,
Teva-Lundbeck, and served on scientific advisory board for
Bial, Boerhinger Ingelheim Eisai, GSK, Impax, Lundbeck,
Merck Serono, Merz Pharmaceutical, Oxford Biomedica,
Schering-Plough, Servier, Abbott, Teva, UCB, Xenoport.
Werner Poewe has received consultancy and lecture fees
from Astra Zeneca, Teva, Novartis Pharmaceuticals, GSK,
Boehringer-Ingelheim, UCB, Orion Pharma, Merck Serono
and Solvay-Abbott in relation to clinical drug development
programmes for PD. Anthony Schapira has served on advisory boards and as a speaker for Orion Pharma and Novartis Pharmaceuticals. He has served as a consultant and
speaker for Boehringer Ingelheim, GSK, Teva-Lundbeck and
Merck Serono. Helena Nissinen is a full-time employee of
Orion Pharma Mika Leinonen is a former employee of
Orion Pharma and a full-time employee of 4Pharma AB,
which received funding from Orion Pharma to carry out
the statistical analysis for the study. Fabrizio Stocchi has
received research grants from Novartis Pharmaceuticals,
GSK and Vernalis, and has served as a consultant for Novartis Pharmaceuticals, Lundbeck, TEVA, GSK, Vernalis,
Serono, Schering Plough and IPX.
Movement Disorder
S238. Dopamine Transporter Imaging Predicts Long
Term Outcomes in Parkinson’s Disease
Bernard M. Ravina, Kenneth Marek, Shirley Eberly, David
Oakes and Ira Shoulson; Rochester and New Haven
Objective: Our objective is to measure the prognostic value
of dopamine transporter (DAT) imaging for motor and
non-motor outcomes in PD.
Methods: We prospectively evaluated a PD cohort after
enrollment in a de novo PD clinical trial with motor, cognitive, and behavioral measures. DAT imaging with [123I][b]CIT (b-CIT) and SPECT was performed at baseline and after 22 months.
Results: Four hundred and ninety-one (91%) of 537 subjects had evidence of dopamine deficiency consistent with
PD. The cohort was followed for 5.5 (0.8) years and had a
diagnosis of PD for 6.3 (1.2) years. Lower striatal binding
of b-CIT at baseline was independently associated with significantly higher risk for important clinical milestones and
measures of PD severity, including motor related disability,
falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for DAT imaging compared to
the top quartile had an odds ratio (95% CI) of 3.5 (1.7,
6.9) for cognitive impairment and 12.8 (2.6, 61.8) for
psychosis.
Conclusions: Near the time of PD diagnosis, DAT imaging with b-CIT and SPECT is an independent predictor of
clinically important motor and non-motor long term
outcomes.
Study supported by: This study was sponsored by the
National Institute of Neurological Disorders and Stroke
(NINDS) (5U01NS050095), Department of Defense
(DOD) Neurotoxin Exposure Treatment Parkinson’s
Research Program (W23RRYX7022N606), Michael J Fox
Foundation (MJFF), Parkinson’s Disease Foundation (PDF),
Cephalon Inc, and Lundbeck Inc.
S239. Time to First Levodopa-Induced Motor
Complication: Results from the STRIDE-PD Study
C. Warren Olanow, Karl Kieburtz, Olivier Rascol, Werner
Poewe, Anthony Schapira, Helena Nissinen, Mika Leinonen
and Fabrizio Stocchi; New York, NY; Rochester, NY; Toulouse,
France; Innsbruck, Austria; London, United Kingdom; Espoo,
Finland; Kista, Sweden and Rome, Italy
S240. Acute Effects of Preladenant, a Selective Adenosine
A2A Antagonist, on Dyskinesia and Parkinsonism in
Levodopa-Treated Subjects
Penelope Hogarth, Matthew D. Troyer, Byung S. Park, Igor D.
Grachev, Tatanisha Laguerre, Fengjuan Xuan, Amol Tendolkar
and John G Nutt; Portland, OR and Whitehouse Station, NJ
Introduction: The STRIDE-PD study compared initiation
of levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in PD patients.
Objective: Determine the effect of levodopa dose on development of motor complications.
Methods: A total of 745 patients participated in a 134–
208-week, double-blind trial, with 3-monthly assessments of
dyskinesia and wearing-off. Based on nominal levodopa
dose per day, patients were divided into four groups: <400
mg (19.7%), 400 mg (46.3%), >400–600 mg (26.6%),
and >600 mg (7.4%). Dose response was analyzed using
log-rank test. Predictive factors for first motor complication
were screened using multivariate analysis.
Results: A dose response was observed between levodopa
dose and first motor complication (p<0.001); with a frequency of 31.3, 57.1, 65.7 and 81.8% in Groups 1–4,
respectively. Dyskinesia developed first in 18.5% and wear-
Background/Objective:
Selective antagonism of striatal adenosine A2A receptors
is proposed to augment the effects of levodopa in Parkinson
disease (PD) and may do so without worsening dyskinesia.
We investigated the acute effects of preladenant on dyskinesia, parkinsonism and safety in patients with advanced
PD.
Methods:
Design: Single-dose, randomized, double-blind, placebocontrolled, 3-period crossover.
Population: PD fluctuators with dyskinesia(n ¼ 12).
Intervention: 10mg and 100mg of preladenant and placebo plus two-hour levodopa infusion.
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Outcome measures: Dyskinesia score(primary); fingertapping and walking speed, tremor score and blood
pressure(secondary).
Analysis: Area Under Curve statistical paradigm
Results: Single doses of 100mg of preladenant increased
levodopa-induced dyskinesia compared to placebo(p ¼
0.003). Single doses of 10mg were not statistically significantly different from placebo(p ¼ 1.00). We found a trend
suggesting a dose-response for dyskinesia, and observed dyskinesia in 4 of 12 subjects prior to levodopa infusion. Neither dose significantly improved any measure of parkinsonism. The drug was generally well-tolerated.
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Conclusions: This proof of concept study does not support the hypothesis that A2A antagonists augment the
effects of levodopa without increasing dyskinesia. Our
results suggest that a supratherapeutic dose of preladenant
may be pro-dyskinetic, perhaps independently of levodopa,
in PD patients with pre-existing dyskinesias.
Study supported by: Merck & Co, Inc
Presenting author Hogarth and co-authors Nutt & Park
received salary support from payments made by the sponsor
to OHSU for contracted research design and execution services. Co-authors Troyer, Laguerre, Grachev, Xuan, and Tendolkar are/were employees of the sponsor.
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136th Annual Meeting Monday,
September 26, 2011 Works in
Progress Poster Session
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phenytoin therapy. Purified DNA were used for HLAB*1502 typing by Sequence Specific Oligopeptide method
using Polymerase Cahin Reaction.
Results: Out of 136 patients on CBZ, HLA-B*1502
were detected in 22 and 19 developed SJS/TEN. In 50
patients on Phenytoin, HLA-B*1502 were detected in six
patients and four had SJS. The mean duration from exposure to SJS was 14 days.
Conclusion: There is a high prevalence of HLA-B*1502
in South Indians on Carbamazepine and Phenytoin
(18.66%). There was a strong association of HLA-B*1502
allele and the developmment of SJS in South Indians, with
the Positive Predictive Value for Carbamazepine and Phenytoin being 86% and 66.67% respectively.
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected
based on scientific merit, timeliness, and anticipated interest
to the membership. Key aspects of research must have been
conducted after the regular abstract deadline.
M726. Filamin A Regulates Neural Progenitor
Proliferation and Brain Size through wee1-Dependent
cdk1 Phosphorylation
Gewei Lian and Volney Sheen; Boston, MA
Behavioral Neurology
M622. New Approaches to Unraveling the Multi-Scale
Neuroanatomical Changes in Williams Syndrome
Ann Lam and Elan L. Ohayon; La Jolla
Mutations in the actin binding filamin A (FlnA) gene cause
the human disorder periventricular heterotopia (PH). FlnAdependent regulation of cytoskeletal dynamics is thought to
direct neural progenitor migration and proliferation. Here
we show that late embryonic FlnA null mice exhibit a
reduction in brain size, impairments in neural progenitor
proliferation, and decline in neural progenitor numbers over
time. The drop in the progenitor population is not attributable to changes in cell fate specification through altered
asymmetric versus symmetric cell divisions, but to prolonged cell cycle duration. Suppression of FlnA leads to
impaired degradation of cyclin b1-related proteins, thereby
delaying the onset and progression through mitosis. We find
that the cdk1 kinase wee1 binds FlnA, demonstrates
increased expressions levels after loss of FlnA function, and
is associated with increased phosphorylation of cdk1. Phosphorylation of cdk1 inhibits activation of anaphase promoting complex degradation system, which is responsible for
cyclin b1 degradation and progression through mitosis. Collectively, our results demonstrate a molecular mechanism
whereby FlnA impairs G2 to M phase entry, leading to cell
cycle prolongation, impaired neural progenitor proliferation,
and reduced brain size.
Study supported by: This work was supported in part by
the National Institutes of Health NS063997-01 to VLS.
This work was also supported in part by the Empire State
Stem Cell Fund through the New York State Department of
Health Contract #C024324 to VLS. The opinions expressed
here are solely those of the author and do not necessarily
reflect those of the Empire State Stem Cell Board, the New
York State Department of Health, or the State of New York.
VLS is a Doris Duke Clinical Scientist Developmental
Award Recipient.
In this study we explore novel multi-scale approaches to
investigate the role of neuroanatomy in cognitive phenotypes by imaging the distribution of metalloproteins across
scales in Williams Syndrome tissue. Synchrotron-based rapid
scanning imaging was used at whole hemisphere levels and
resolutions of up to 10 microns to co-localize elements in
postmortem samples of Williams Syndrome and typicaldeveloping individuals in prefrontal, temporal and occipital
cortex. Comparisons between- and within-subjects revealed
differences between brain areas in elemental distributions.
For example, initial scans showed the expected high levels of
iron in nuclei such as the substantia nigra and prominent
zinc florescence along white matter tracts. To increase the
resolution by a factor of 20, microprobe imaging was then
used attaining resolutions as high as 0.5 microns. This
microprobe analysis of 50–100 micron thick cortical sections showed the co-localization of iron, zinc and calcium
in and around cell-like structures. The combination of these
two synchrotron-based techniques thus enables the study of
biologically relevant elements in postmortem brain tissue
across large areas, while allowing for the co-registering of
elements at high resolutions at the cellular level in regions
of interest.
Study supported by: NIH
Epilepsy
M725. HLA-B*1502 Genotyping in Carbamazepine and
Phenytoin Induced Stevens-Johnson Syndrome
Sivakumar M. Rajappa and Srinivasan A. Venkatesan;
Chennai, Tamil Nadu, India
Objective: To study the association of HLA-B* 1502 allele
in epileptic patients with carbamazepine and phenytoininduced Stevens Johnson Syndrome (SJS) in South Indian
patients.
Background: SJS and Toxic Epidermal Necrolysis (TEN)
are severe cutaneous adverse drug reactions caused by carbamazepine (CBZ) and phenytoin. A strong association has
been reported between human leucocyte antogen HLAB*1502 and carbamazepine-induced SJS in Han Chinese
patients.
Design/Methods: Single center, prospective cross sectional study. After an informed consent, 7 ml of EDTA
blood were collected from 100 patients on CBZ and 50 on
M727. A Moderate-Throughput Screen for
Antiepileptogenic Compounds
Yevgeny Berdichevsky, Yero Saponjian, Michelle Mail and
Kevin J. Staley; Boston, MA
Epilepsy is a frequent complication of traumatic, infectious
and ischemic brain injury. The time interval between injury
and epilepsy provides a tremendous opportunity for diseasemodifying therapies. Development of these therapies is limited by inadequate knowledge of the pathophysiology of epileptogenesis, the long time intervals required to observe
changes in experimental epileptogenesis, and difficulties
quantifying epileptogenesis.
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To address these difficulties we have developed a moderate-throughput drug screen for antiepileptogenic agents
comprised of arrays of organotypic hippocampal brain slices
that develop robust spontaneous electrographic seizure activity within two weeks in vitro. Seizure activity is quantified
either electrographically or metabolically as cumulative lactate production over two weeks in vitro. Neuroprotection is
quantified as cumulative lactate dehydrogenase release over
two weeks in vitro.
Using these techniques we have screened 50 compounds
from the NINDS Custom Compounds Collection in less
than 4 months. Most anticonvulsants demonstrated neither
antiepileptogenic nor significant chronic anticonvulsant
effects, although acute anticonvulsant effects were readily
observable. With other compounds we have resolved chronic
anticonvulsant or antiepileptogenic activities (which are
indistinguishable in the first-level screen) evidenced by
decreased lactate with no increase in LDH, as well as neuroprotective activity, evidence by reduction in LDH.
Study supported by: NIH (NINDS)
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seizures. It was common to observe spreading depressionlike events (SD) and irreversible synaptic failure in the CA1
region following the seizure activity originated in CA3 (8/
12). SD also occasionally occurred in the CA3 area (3/12)
following a SD event in the CA1 region. Hypoglycemic
seizures required glutamatergic activity and NMDA receptor
blockade prevented the hypoglycemia-induced seizures and
SDs.
Conclusions: Hypoglycemia-induced seizures in the hippocampus start in the CA3 region and cause SD and synaptic failure in the CA1 region. Activation of NMDA receptors is the key factor for the initiation of seizures and
development of brain failure during severe hypoglycemia.
Study supported by: JDRF
M730. Alzheimer Disease in Lafora Epilepsy
Jesus Machado-Salas, Maria Rosa Avila-Costa, Patricia
Guevara, Jorge Guevara, Reyna M. Duron, Dongsheng Bai,
Miyabi Tanaka and Antonio V. Delgado-Escueta; Los Angeles,
CA and Mexico, Mexico
Here we describe temporal progression of tau and amyloid
pathology and subtypes of Lafora bodies (LB) in a Laforindeficient (epm2a/) mice model. Wild type and
epm2a/ mice were sacrificed at different ages. Histological and immuonocytochemical techniques were used. We
found in epm2a/ mice that neurofibrilary tangles appear
at 11 days-old while senile plaques are abundant at 6
months. Type I LB are abundant inside neurons, type II LB
are confined to neuron somata. Type I LB appear at 1
month while type II LB with an external rim staining for
Neurofilament L, appear at 3 to 5 months. Both types of
LB increase in size and number with age but show regional
differences. Diencephalon has meager or no LB, cell death
and neurofibrillary tangles. All three features are abundant
in hippocampus, amygdala, cerebellum, and in greatest
amount in pons. Our results indicate that Lafora Disease is
both a neurodegenerative disease and a glycogen metabolism
disorder. We hypothesize that laforin deficiency upregulates
tau protein kinase I/glycogen synthase kinase 3beta forming
tau, amyloid and polyglucosan bodies. Our findings are critical for future experiments on disease mechanisms and
therapies for both Lafora disease and Alzheimer disease.
Study supported by: National Institutes of Health
[1RO1NS055057], Chelsea’s Hope Foundation for Lafora
Disease and Programa de Apoyo a Proyectos de Investigación
e
Innovación
Tecnológica-DGAPA
UNAM
[IN214609, and PAPCA 2010-2011]
M728. Network Structure and Sensitivity to the
Geometry of Stimuli in Epilepsy and Cognition
Elan L. Ohayon, Ann Lam and Terrence J. Sejnowski; La
Jolla, CA
What modulates a brain’s sensitivity to stimuli? This question is central to the study of reflex epilepsies and cognition.
Previously we have shown that network structure can affect
the persistence of complex activity. Here we use computational models to demonstrate how anatomical changes can
modulate sensitivity to initial conditions such as perceptual
stimuli. Models consisted of large spatial networks with up
to 20,000 spiking units with inhibitory and excitatory populations. Network structure was adjusted by randomly adding
or removing cells at 5% increments. Simulations showed
that homogeneous networks (density ¼ 1.0) were least likely
to maintain activity with either single or distributed stimuli.
In contrast, heterogeneous networks became more sensitive
to a variety of stimuli (e.g., over 95% persistence at density
¼ 0.6). Interestingly, the self-propagating responses generated in heterogeneous networks could be ‘‘grafted’’ back
onto the homogenous networks and continue propagating.
These experiments illustrate that changes in anatomy
can modulate responses to stimulus geometry thereby helping explain how neurodegeneration and trauma might lead
to changes in sensitivity and the lowering of seizure threshold. The findings also illustrate how network structure
might modulate responses to stimuli in attention and
cognition.
Study supported by: NIH
M731. Antiepileptic Activity of Intrapulmonary
Midazolam
Ashish Dhir, Dorota Zolkowska and Michael A. Rogawski;
Sacramento and Davis
M729. Hypoglycemia Induced NMDA ReceptorDependent Epileptiform Activity in the Hippocampal
CA3 Area Causes Damage in CA1
Carlos M. Florez, Jane Zhang, Peter Abdemalik, Liang Zhang
and Peter L. Carlen; Toronto, ON, Canada
Midazolam is a short-acting central/peripheral benzodiazepine receptor modulator. It is widely used as an intravenous
sedative and a fast-acting anticonvulsant to abort status epilepticus. In the present study, we sought to characterize
intrapulmonary route to deliver midazolam for providing
fast and potent antiepileptic action. Further, we explored
the involvement of both central and peripheral benzodiazepine receptors in its mechanism of anticonvulsant action.
Intraperitoneal administration of midazolam at 250–5000
lg/kg protected mice against pentylenetetrazol, picrotoxin
and kainic acid-induced convulsions. Similarly, the intratracheal route of midazolam administration demonstrated anticonvulsant activity but at much lower doses (25–100 lg/
kg); the maximum anticonvulsant action was observed
Seizures are the most common clinical presentation of severe
hypoglycemia in neonates. We characterized a new in vitro
model for the study of hypoglycemia-induced seizures using
mouse hippocampal thick slices. Changing the glucose concentration to 1mM produced seizures in 88% of the preparations. Isolation experiments revealed that CA3, less susceptible for hypoglycemia induced synaptic failure than CA1, is
the epileptogenic area. The CA3 network showed decreased
interneuronal activity and increased frequency and energy
transfer of the pyramidal cell activity prior to the onset of
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between 5–15 minutes. The anticonvulsant action of intratracheal midazolam (100 lg/kg) in PTZ i.v. seizure model
was reversed by pre-administration of flumazenil (5 mg/kg.,
i.p.), a centrally acting benzodiazepine receptor antagonist.
Finasteride (100 mg/kg., i.p.), a 5-alpha reductase inhibitor
and neurosteroid synthesis inhibitor partially blocked the
anticonvulsant action of midazolam in PTZ seizure threshold model. Furthermore, the anticonvulsant action of intraperitoneal midazolam was reversed by PK-11195, a peripheral benzodiazepine receptor antagonist. In conclusion, the
intrapulmonary midazolam provides fast and potent anticonvulsant action and involves both central and peripheral
receptors in its mechanism of action.
Study supported by: Epilepsy Laboratory
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Results: Biopsied samples from IBM patients showed
lower expression of myogenin than those from IIM patients,
in immunohistochemistry (IBM 4.761.4 cells/100myofibers, IIM 7.363.7, p ¼ 0.0352), Western blot (IBM
0.04860.030 (relative amount to actin), IIM 0.09060.056,
p ¼ 0.0297), and real-time RT-PCR (IBM 10.668.5 (relative amount to b-actin), IIM 19.6611.7, p ¼ 0.0344).
Immunohistochemistry of biopsied samples from IBM
patients also revealed that myogenin was aberrantly
expressed within degenerative myofibers, and was aggregated
in Ab-positive inclusion bodies.
Conclusion: Disrupted expression of myogenin may
reflect impaired regeneration in IBM.
Study supported by: Grants-in Aid for Scientific Research
and Health and Labour Sciences Research Grants for
Research on Intractable Diseases from the Ministry of
Health, Labour and Welfare of Japan, and Grants-in Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
M732. Do Brain Volumes in JME (juvenile myoclonic
epilepsy) differ from normal controls?
John T. Spitz, Long Vu, Lydia Su, Mark A. Mandelkern,
Barbara E. Swartz; Berkely, CA, Irvine, CA, Los Angeles, CA,
Irvine,CA and Newport Beach, CA
M837. Abnormalities of a Novel Autophagy-Associated
Protein, NBR1, in Muscle Fibers of Sporadic InclusionBody Myositis (s-IBM)
Carla D’Agostino, Anna Nogalska, Mafalda Cacciottolo,
W.King Engel and Valerie Askanas; Los Angeles, CA
Background: JME is a form of generalized epilepsy that
accounts for 7% of all epilepsies. The natural history of
JME and its brain morphology is explored in this study.
Methods: We compared the volumes of 11 regions of interest (frontal and subcortical) and grey matter density
between 17 JME subjects (33.8 þ/ 10.4 years) with sex
and age-matched controls (35.4 þ/ 11.7) using automated
and manual volumetric procedures and voxel based morphometry (VBM). Regional volumes were normalized to
whole brain volumes prior to statistical analyses.
Results: Initial analysis of the volumetric data using ttests with Bonferroni correction found no significant differences between the JME and controls. However, individual
subjects with JME were more likely to have regions larger
than control mean volumes than visa versa using VBM and
volumetry (p ¼ .04, Binomial test, VBM). Additionally,
both VBM and manual volumetric analysis found the left
thalamus larger in JME subjects. These results will be
expanded using ANCOVA and/or MANCOVA analyses to
control for a number of covariates: duration of epilepsy, sex,
seizure control and medications for final presentation. Discussion will emphasize the growing literature in this area.
Study Supported By: Veteran’s Administration Merit
Review Program 821/103.
Intra-muscle fiber accumulation of ubiquitinated protein
aggregates containing several conformationally modified proteins, including amyloid-b and phosphorylated tau, is characteristic of the pathologic phenotype of s-IBM, the most
common degenerative myopathy of older persons. Impaired
protein-degradation, involving both the 26S proteasome and
autophagic-lysosomal pathways, we previously demonstrated
in s-IBM muscle. NBR1 is a ubiquitin-binding scaffold-protein importantly participating in autophagic degradation of
ubiquitinated proteins. Abnormalities of p62, another ubiquitin-binding protein, were previously described in s-IBM.
Abnormalities of NBR1 have not been reported in s-IBM.
We have now identified in 14 s-IBM muscle biopsies
that NBR1, by: a) immunohistochemistry, was strongly
accumulated within s-IBM muscle-fiber aggregates, where
it closely co-localized with p62 and phosphorylated tau;
b) immunoblots, was increased 3x, p< 0.01; and c) immunoprecipitation, was associated with p62. By real-time PCR,
NBR1 mRNA was increased 2x, p< 0.01. None of the 15
disease- and normal-control muscle biopsies had any NBR1
abnormality.
This first demonstration of NBR1 abnormalities in sIBM: a) further suggests that abnormalities of the autophagic-lysosomal pathway may be critically involved in the sIBM pathogenesis, and b) indicates a potential therapeutic
focus.
Study supported by: Muscular Dystrophy Association
Neuromuscular Disease
M836. Disrupted Expression of Myogenin in Inclusion
Body Myositis
Akatsuki Kubota, Jun Shimizu, Atsushi Iwata and Shoji Tsuji;
Tokyo, Japan
Background: Inclusion body myositis (IBM) is a chronic
progressive inflammatory myopathy, with degenerative pathology. Immunosuppressive therapies are ineffective to
IBM, unlike other idiopathic inflammatory myositis (IIM).
Muscle regeneration is also impaired in IBM, but the mechanism remains undetermined. Myogenin is one of the myogenic regulatory factors, and plays an essential role in maturation of myogenic cells.
Purpose: We evaluated expression of myogenin in biopsied muscles from IBM and IIM patients.
Materials and methods. We analyzed biopsied samples
from 11 IBM and 19 IIM patients. We quantified myogenin-positive cells by immunohistochemistry, myogenin protein by Western blot, and myogenin mRNA by real-time
reverse transcription PCR (RT-PCR).
M838. Atrophy and Autophagy in Limb Girdle Muscular
Dystrophy and Glycogen Storage Disease Type 2
Corrado I. Angelini, Annachiara Nascimbeni, Marina Fanin
and Marco Sandri; Padova, Italy
Few studies have investigated atrophy/autophagy gene
expression in LGMDs and GSD type 2, to study the fate of
misfolded proteins in ubiquitin-proteasome system and recovery in autophagy-lysosome pathway after Enzyme
Repacement Therapy (ERT).
We investigated gene expression from 40 muscle biopsies
of LGMD 2A, 20 LGMD 2B and 12 GSD type 2, both infantile and late onset. We found evidence of activation of
molecular pathways with upregulation of autophagy-related
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genes: BNIP3 and p62 in Pompe, of atrophy-related genes
atrogin-1 and MuRF-1 in LGMD 2A (calpainopathy) and
in LGMD 2B (dysferlinopathy). In one infantile, one juvenile and one adult GSD type 2 cases a second biopsy was
done after ERT and analysed for morphology and gene
markers: in the second biopsy we observed after ERT
reduced vacuolated fibers and decreased autophagy related
markers.
Our study in GSD type 2 recognises an important contribution of autophagic process in the development of muscle
pathology, after ERT autophagy markers are considerably
decreased as well as vacuolisation of muscle fibers. Our
observations in LGMDs are new and support future therapeutic interventions to rescue muscle atrophy.
Study supported by: Telethon, Eurobobank.
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events attributable to the cellular injections. We are using
clinical evaluation, strength testing, and electrical impedence myography to monitor progression of disease. Following FDA review and approval of safety data from the
first 12 patients we will move to injections into the cervical
spinal cord.
Study supported by: Neuralstem, Inc.
M841. Clinical Development of an Antisense Therapy
for the Treatment of Transthyretin Amyloidosis
Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis
Alvarado, Andrew Siwkowski, Merrill Benson, Steve Hughes
and Brett Monia; Carlsbad, CA and Indianapolis, IN
Transthyretin (TTR)-associated amyloidosis is a late-onset
autosomal-dominant genetic disease. Mutations in TTR
destabilize TTR tetramer thereby inducing the formation of
amyloid fibrils. This disease mainly affects peripheral nerves
as in familial amyloidotic polyneuropathy (FAP) or heart as
in familial amyloid cardiomyopathy (FAC). Circulating
TTR is predominantly produced by the liver, and the only
available treatment as of June 2011 is orthotopic liver transplantation. Using antisense technology, we identified an
antisense oligonucleotide, ISIS-TTRRx, for the treatment of
TTR-associated amyloidosis. When tested in a human TTR
transgenic mouse model, ISIS-TTRRx showed a dose-dependent reduction of human TTR at both the mRNA and protein
levels. In cynomolgus monkeys, ISIS-TTRRx treatment produced a time-dependent reduction in plasma TTR levels. After 12 weeks of treatment, liver TTR mRNA and plasma
TTR protein levels were reduced by 80%. We also observed
a significant decrease in plasma RBP4 levels correlating with
TTR reduction. ISIS-TTRRx treatment was well tolerated in
both rodents and monkeys and produced a PK/PD profile
consistent with prior experience using this chemistry platform. ISIS-TTRRx is currently under evaluation in a Phase I
clinical trial, with the first cohort dosed in May 2011.
Study supported by: Isis Pharmaceuticals
Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis
Alvarado, Steve Hughes and Brett Monia are all employees
at Isis Pharmaceuticals
M839. Virtual Demyelination in pmp22 Deficiency
Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman,
Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li;
Nashville; San Diego; Cleveland; Zurich, Swaziland and
Nashville, TN
Safety factor for action potential propagation in pmp22þ/
nerves appears impaired (Bai et al, J Neurosci 2010). The
present study investigates mechanisms responsible for the
impairment. Fluorescent dyes with different molecular sizes
were injected into sciatic nerves. After 4-hour incubation,
sciatic nerves were teased into individual nerve fibers, and
examined under fluorescence microscopy. Fluorescence was
of strong intensity in about a half of paranodal tomacula of
pmp22þ/ nerves (15 mice), but absent or minimal in the
paranodes of wild-type nerves (11 mice). This finding suggests that myelin is abnormaly leaky, and may result in excessive outward current. Application of potassium channel
blocker, 4AP, to reduce outward current improved the amplitude of motor response during nerve stimulation. Western
blot and immunohistochemistry revealed alterations of tight
junction protein assembly, a potential molecular mechanism
for the myelin leakage.
Conclusions: Our results show excessive leakage in
pmp22þ/ myelin in the absence of demyelination. This
leakage is functionally similar to demyelination. These findings not only reveal novel mechanism for conduction block
but also establish new therapeutic approach for this disease.
Study supported by: NIH
Neurogenetics
M1011. EPI-A0001: New Potential Therapy for
Friedreich Ataxia
David R. Lynch, Steve M. Willi, Robert B. Wilson, Karlla W.
Brigatti, Olena Kucheruck, Eric C. Deutsch, William D.
Shrader, Patrice Rioux, Guy Miller, Amale Hawi and Thomas
Sciascia; Philadelphia, PA; Patterson, NY and Mountain View,
CA
M840. First in Human Phase 1 Trial of Neural
Progenitor Cells in ALS: Results in the First 12 Patients
Jonathan D. Glass, Nicholas Boulis, Meraida Polak, Crystal
Kelly, Thais Federici, Jane Bordeau, Seward Rutkove, Karl
Johe, Tom Hazel and Eva Feldman; Atlanta, GA; Boston,
MA; Rockville, MD and Ann Arbor, MI
This study tested the ability of EPI-A0001(previously called
A0001) (a-tocopherol quinone), to improve in vitro measures, glucose metabolism and neurological function in Friedreich ataxia. We used an in vitro assay of cell rescue followed by a double blind, placebo controlled trial of 2 doses
of EPI-A0001 in 30 adults. The primary clinical trial outcome was disposition index, a measure of diabetic tendency,
from an IVGTT, evaluated 4 weeks after treatment. Secondary neurologic measures included the Friedreich ataxia rating
scale (FARS).
EPI-A0001 inhibited cell death in FRDA models in vitro.
For the clinical trial, mean GAA repeat length was 699, and
mean age was 31. Four weeks after treatment initiation,
changes in disposition index between subjects treated with
EPI-A0001 and placebo were not statistically significant. In
contrast, a dose dependent improvement in FARS score was
Twelve patients with ALS were injected into the lumbar
spinal cord with fetal-derived neural stem cells. The design
is one of ‘‘escalating risk’’, where each group of patients is
progressively less impaired. The first 6 patients were nonambulatory, 3 were supported by mechanical ventilation.
The first 3 patients received 5 unilateral injections at L2L4, and the next 3 received 5 injections bilaterally. Patients
7–12 were ambulatory and had vital capacities > 60 %
predicted. Patients 7–9 received 5 unilateral injections, and
patients 10–12 received bilateral injections. Each injection
was 10 ll of 10,000 cells/ll; patients received either
500,000 or 1 million cells through 5 or 10 injections,
respectively. There have been two deaths, one which was
unrelated to either ALS or the clinical trial. The surgical
procedure was well tolerated. There have been no adverse
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found. Patients on placebo improved 2.0 FARS points while
patients on low dose EPI-A0001 improved by 4.9 points (p
¼ 0.04) and patients on high dose improved by 6.1 points
(p<0.01).
Although EPI-A0001 did not alter disposition index, it
caused a dose dependent improvement in neurologic function. Longer studies will assess the reproducibility and persistence of neurologic benefit.
Study supported by: Penwest/Endo Pharmaceuticals, Edison Pharmaceuticals
Drs. Sciascia and Hawi are former employees of Penwest
Pharmaceuticals. Drs Miller and Shrader are current
employees of Edison pharmaceuticals. Dr Rioux is a former
employee of Edison pharmaceuticals
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slowly progressive sensory neuropathy and spinal stenosis
but also for many degenerative conditions of other organs
including osteoarthritis.
Their whole genome was sequenced and was found to be
identical for all exons. Further studies of whole genome
methylation sequencing using two completely different
methodologies confirmed 141 sites which were significantly
different at a genome-wide level. The results of these studies
carried out on CD4 positive T-lymphocytes, were confirmed
in epithelial cells from buccal smear, implicating a germ line
origin for these changes.
There are two common features among the 27 conditions
present in one but not in the other monozygotic twin.
These findings highlight the importance of epigenetic alterations in the development of the common degenerative diseases of man.
Study supported by: This study was supported by grant
funding from the MS Society of the UK and the Scientific
Foundation of the Canadian MS Society.
M1012. Exome Sequencing Identifies a Rare Variant in
the CYP27B1 Gene Associated with Multiple Sclerosis
George C. Ebers and Sreeram V. Ramagopalan; Oxford,
Oxfordshire, United Kingdom
Background: Multiple sclerosis (MS) is a complex neurological disease. We previously described the ascertainment of
43 Canadian families with 4 or more individuals with MS.
Genetic linkage analysis and genotyping of candidate genes
in these families has not fully explained familial disease clustering although alleles of GWAS genes are overrepresented.
Methods: Whole exome sequencing was performed to
further understand heightened prevalence of MS in these
families.
Findings: Forty-three individuals with MS (one/family)
were sequenced. On average over 58000 variants were identified in each individual. Searching for rare variants in
known or candidate MS susceptibility genes led to identification of a rare loss-of- function variant in the CYP27B1
gene. This variant in 2716 parent-affected child trios
showed significant association to MS P ¼ 6105. Further
genotyping of other variants in over 11,000 individuals
showed that rare CYP27B1 variants conferred significant
risk of MS, Peto odds ratio ¼ 4.1 (95% confidence interval
1.5–11.1).
Interpretation: Causative role for CYP27B1 in MS risk
is supported. CYP27B1 encodes the vitamin D activating 1alpha hydroxylase enzyme. A role for vitamin D in MS
pathogenesis is strongly implicated. We show the utility of
using extreme multicase families to identify rare variants.
Study supported by: This study was supported by grant
funding from the MS Society of the United Kingdom and
the Scientific Foundation of the Canadian MS Society.
Neurology Critical Care
M1206. Imaging Biomarkers of Cerebral Edema in
Malignant Infarction
Kevin N. Sheth, Albert J. Yoo, R. G. Gonzalez, W. T.
Kimberly, Zeshan A. Chaudhry, Jordan J. Elm, Sven Jacobson,
Stephen M. Davis, Geoffrey A. Donnan, Gregory W. Albers
and Barney J. Stern; Baltimore, MD; Boston, MA; Charleston,
SC; New York, NY; Carlton South, Victoria, Australia and
Stanford, CA
Objective: 70% of patients with malignant infarction die
secondary to cerebral edema. A fundamental challenge is the
lack of a validated imaging marker for brain edema. We
hypothesized that MRI hemisphere and ventricle volumes
reliably change over the first five days in patients with malignant edema.
Methods: We conducted a retrospective analysis of the
EPITHET study MRI’s at stroke onset and at 3–5 days. We
selected patients with an acute diffusion weighted imaging
volume 82cc, which is highly predictive for malignant
edema. The involved hemisphere and ipsilateral ventricle
were manually outlined, and volumes were measured using
Analyze software.
Results: 12 patients, with a mean age of 71 and mean
NIHSS score of 19, were included in the analysis,. The
mean (6SD) increase in ipsilateral hemisphere brain volume
was 81.5cc (629.0cc) with a corresponding decrease in ventricular volume of 9.2cc (64.7cc) (both p<0.0001). Concordance correlations for baseline and follow-up measurements were 0.9470 (95%CI: 0.8411–0.9830) and 0.9319
(95%CI: 0.7978–0.9782).
Conclusions: MRI-based metrics of cerebral edema are
responsive to change and have a high inter-rater agreement.
These data suggest their potential utility as a biomarker for
novel therapies that prevent malignant edema.
Study supported by: National Institutes of Health, Remedy Pharmaceuticals
Remedy Pharmaceuticals has provided funding for a 10
patient pilot study for intravenous glyburide in malignant
infarction. This study is ongoing and a precursor to application for NIH.
M1013. Whole Genome Sequencing in Twins Discordant
for 27 Diseases
George C. Ebers and Sreeram V. Ramagopalan; Oxford,
Oxfordshire, United Kingdom
An apparently unique pair of monozygous twins was identified. They had long been thought to be fraternal because of
striking differences in birthweight, appearance and health.
However a history was elicited of their having been told
they were born in the same sac. Finally at age 61 suspicions
were raised when it was noted their handprints were
identical.
They were discordant for many neurological conditions
including precocious puberty, migraine, essential tremor,
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136th Annual Meeting Tuesday,
September 27, 2011 Works in
Progress Poster Session
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positron emission tomography measurements of rCBF were
available at baseline and up to 7 annual follow-up visits in 88
cognitively normal older individuals in whom genome-wide
genotyping data were collected. Cognitively normal carriers
of the risk allele of the rs11136000 SNP in CLU show significant and dose-dependent longitudinal increases in resting
state rCBF in brain regions intrinsic to memory processes.
We propose that these increments in rCBF over time represent compensatory changes in neuronal activity required to
maintain normal cognition during aging in at-risk individuals, and that their eventual failure in some may mark the
transition from normal aging to Alzheimer’s disease.
Study supported by: NIA Intramural Research Program
WIP posters will be displayed in Elizabeth A-E of the
Manchester Grand Hyatt from 10:00 am – 7:00 pm,
with authors present from 6:00 pm – 7:00 pm.
The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected
based on scientific merit, timeliness, and anticipated interest
to the membership. Key aspects of research must have been
conducted after the regular abstract deadline.
T1540. Association of High Density Lipoprotein to
Alzheimer Disease
Ramin Ebrahimi, Naser Ahmahi, Fereshteh Hajsadeghi and
Hormoz Babaei; LA, CA
Dementia and Aging
T1538. Proneurogenic Compound Reduces Synaptic
Ab-42 Oligomer Levels and Shows Cognitive Benefit
in Alzheimer’s Mouse Model
Sam Gandy, John W. Steele, Charles Glabe, Kai Treuner, Todd
Albert, Carrolee Barlow, Michelle E. Ehrlich and Soong Ho
Kim; New York, NY; Irvine, CA and San Diego, CA
Background: Alzheimer’s disease (AD) is a devastating progressive neurologic disorder with increasing prevalence. Little data exists regarding association of HDL-c to AD. This
study evaluates the association of different HDL-c levels
with AD.
Methods: This study consists of 2144 Veterans with AD
and 16175 without AD. VA electronic medical records from
veterans were used to evaluate the presence or absence of
AD, HDL levels and risk factors. HDL-c was classified as
HDL-c <40 mg/dl, 40–50 mg/dl and >50 mg/dl. Conditional logistic regression analysis was employed to assess the
association of lower levels of HDL-c with AD.
Results: The mean age was 7966 years. After adjustment
for risk factors, odds ratio of AD was 2.20 (95% CI 2.09–
2.31, p ¼ 0.0001) for those with HDL-c of 40–50 mg/dl and
2.89 (95% CI 2.75–3.05, p ¼ 0.0001) for those with HDL-c
<40 mg/dl, as compared to subjects with HDL-c>50 mg/dL.
Conclusion: There is a strong association between lower
levels of HDL-c and AD. Furthermore, population attribution risk of lower levels of HDL-c for new AD is very high;
warranting future studies evaluating the role of specific lipid
therapy to improve HDL-c levels to potentially decreased
future development of AD.
Study supported by: Self
Group II metabotropic glutamate receptors (Gp II mGluR)
trigger production of Ab peptides from isolated synaptic terminals, and synaptic Ab42 generation is selectively suppressed by Gp II mGluR antagonists. Gp II mGluR antagonists also stimulate hippocampal neurogenesis and enhance
cognition. Pilot studies were performed in old (18 mo) and
young (6 mo) Dutch APP693Q x PS1D Exon 9 bigenic
mice. After 3 wk oral BCI-838 treatment of 18 mo-old
mice, levels of prefibrillar A11-immunoreactive Ab oligomers were decreased in hippocampi from treated mice (p 0.01). In young Dutch APP693Q x PS1D Exon 9 mice,
fibrillar OC-immunoreactive Ab oligomer levels were
decreased in the treated young mice (p 0.01). Some
Dutch APP693Q and wildtype littermates were given BCI838 p.o. for 3 mo. BCI-838 treatment was associated with
improved memory in cued fear conditioning (p ¼ 0.01
TgþVeh vs TgþBCI-838). A trend toward reduced anxiety
was also observed (p ¼ 0.086 for TgþVeh vs TgþBCI838). GpII mGluR antagonists are promising compounds
for prevention or treatment of AD because of their unique
synaptic Ab42- and Ab-oligomer-lowering activity coexisting
with pro-cognitive and pro-neurogenic activities.
Study supported by: P01 AG10491
Carrolee Barlow is CSO at BrainCells. Todd Albert and
Kai Treuner are staff scientists at BrainCells.
T1541. Amyloid-b 42:40 Metabolism Is Altered in
Autosomal Dominant Alzheimer’s Disease (ADAD)
Rachel E. Potter, Vitaliy Ovid, Tom Kasten, Wendy Sigurdson,
Kwasi Mawuenyega, Bruce Patterson, Don Elbert, Scot Fague,
Sumi Chakraverty, Alison Goate, Kevin Yarasheski, John C.
Morris, Tammie Benzinger and Randall J. Bateman; St. Louis,
MO
T1539. Alzheimer Risk Variant Clusterin (CLU) and
Brain Function during Aging
Madhav Thambisetty, Lori Beason-Held, Michael Kraut,
Michael Nalls, Andrew Singleton, Luigi Ferrucci, Simon
Lovestone and Susan Resnick; Baltimore and London, United
Kingdom
We hypothesized that ADAD is caused by mutations that
lead to higher production rates for amyloid-beta (Ab) 42
compared to Ab40. We measured Ab isoform production
and clearance rates in ADAD participants to determine the
effects of mutations which invariably lead to AD. Presenilin
1 mutation carriers (46.2yrs 6 15.8 (N ¼ 7)), and related
non-carriers (52.0yrs 6 20.5 (N ¼ 7)) completed Ab stable
isotope labeling 13C6-Leu kinetic studies of cerebrospinal
fluid, and PET PIB imaging. Differences in the Ab42 relative to Ab40 labeling curves were specifically altered in
mutation carriers versus non-carriers. Newly generated Ab42
was detected before Ab40 or 38, and there were differences
in area under the curve analyses. These findings support
prior in vitro studies that Ab42 is overproduced relative to
other Ab isoforms. Ab isoform production and clearance
Recent genome wide association studies have identified common risk variants for Alzheimer’s disease (AD), although
these exert small effects and are, by themselves, unlikely to be
of clinical utility in risk prediction. However, these genetic
risk variants may reveal mechanisms involved in the transition from normal aging to cognitive impairment. We examined the effect of the recently discovered AD risk variant
rs11136000 single nucleotide polymorphism in the clusterin
gene (CLU) on longitudinal changes in resting state regional
cerebral blood flow (rCBF) during normal aging. 15O-water
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may be used to define the therapeutic effectiveness of treatments which target abnormal Ab metabolism in AD.
Study supported by: This work was supported by a grant
from NIH (no. P01AG026276), an anonymous foundation,
Eli Lilly research, the Knight Initiative for Alzheimer’s
Research, and the James and Elizabeth McDonnell Fund for
Alzheimer’s Research. R.J.B. is a cofounder of a company
(C2N Diagnostics) that has licensed a pending Washington
University patent on the technology described in this article.
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Results: MCM rates were 4.11%, 4.02% and 4.15% for
TPM, migraineurs, and APMD-treated migraineurs, respectively. Relative risks (95% CI) for TPM vs. migraineurs and
APMD-treated migraineurs were 1.02 (0.73–1.45) and 0.99
(0.68–1.45), respectively. OC rates were 0.26%, 0.17%, and
0.37% for the TPM, migraineurs, and APMD-treated
migraineurs, respectively. Relative risks (95% CI) for TPM
vs. migraineurs and APMD-treated migraineurs were 1.50
(0.37–6.19) and 0.69 (0.15–3.12), respectively.
Conclusions: TPM exposure did not significantly
increase the rates of OC or MCM.
Study supported by: Vivus, Inc.
T1542. Acetylated Tau, a Novel Pathological Signature
in Alzheimer’s Disease and Other Tauopathies
David J. Irwin, Todd Cohen, Murray Grossman, Steven E.
Arnold, Sharon X. Xie, Virginia M.Y. Lee and John Q.
Trojanowski; Philadelphia, PA
Neuroimmunology and Demyelinating Disease
T1741. Comparison of MRI Techniques for Monitoring
of Multiple Sclerosis
Manuela Vaneckova, Jan Krasensky, Tomas Kalincik, Dana
Horakova, Eva Havrdova and Zdenek Seidl; Prague, Czech
Republic
The microtubule-binding protein, tau, is the major component of neurofibrillary inclusions characteristic of Alzheimer’s
disease (AD) and related tauopathies. Recently, we reported
that the acetylation of tau at lysine residue 280 (ac-K280) is
a novel, pathological post-translational modification. Here,
we performed detailed immunohistochemistry (IHC) to further characterize tau ac-K280 expression in tauopathies.
Ac-K280 tau IHC was conducted on 30 postmortem central nervous system (CNS) regions from AD (n ¼ 10), corticobasal degeneration (CBD; n ¼ 5), and progressive
supranuclear palsy (PSP; n ¼ 5) patients. Ac-K280-immunoreactive (Ir) tau pathology was compared to multiple
well-characterized tau epitopes.
All cases showed significant CNS ac-K280-Ir tau pathology in a distribution pattern similar to hyperphosphorylated-tau. In AD cases, the majority of ac-K280-Ir tau pathology was in intracellular, thioflavin-S (ThS) positive tau
inclusions, and also ThS negative tau pathology in CBD
and PSP. Ac-K280-Ir was present throughout all stages of
AD pathology, but more prominent in later stages.
Ac-K280-Ir is a pathological modification of tau that
may contribute to neurodegeneration by augmenting losses
of normal tau properties, as well as toxic gains of function.
Thus, inhibiting tau acetylation could be a disease modifying drug discovery target for tauopathies.
Study supported by: NIH grants: T32-AG000255 Training in Age-Related Neurodegenerative Diseases and P30
AG010124-20 Alzheimer’s Disease Core Center grant.
Goal: To compare contemporary MRI measures for prediction of future clinical disability in multiple sclerosis patients
by analysis of our MRI data (brain atrophy, T2 lesion volume, T1 lesion volume and corpus callosum atrophy).
Methods: Long term (7-year) longitudinal MRI data of
178 patients were analyzed Area of corpus callosum, T2
lesion volume, T1 lesion volume, brain parenchymal fraction and brain atrophy were measured. Clinical disability
was assessed with Expanded Disability Status Scale (EDSS).
Patients were divided in two groups: clinically stable and
those with sustained progression during seven years.
Results: Statistically significant correlation of future clinical
disability (as characterized by EDSS score) with brain atrophy
and corpus callosum atrophy was found. In this retrospective
study, clinically stable patients were distinguished from
patients with sustained progression in less than 1 year using
the corpus callosum atrophy (probability over 98%) and after
3 years using the brain atrophy (with probability of 96%).
Conclusions: We have shown that the corpus callosum
atrophy is a superior marker of disease progression compared to the brain atrophy, which was considered to be its
most significant marker.
Supported by Biogen Idec Inc. and the grants
MZOVFN2005, MSM 0021620849.
Study supported by: Supported by Biogen Idec Inc. and
the grants MZOVFN2005 and MSM 0021620849.
Headache and Pain
T1742. Effects of Rituximab on T-Cells in MS
Uma Vinayagasundaram, Ellen M. Mowry, Ian R. Matthews,
Julia Marino and Emmanuelle Waubant; San Francisco, CA
T1623. Retrospective Analysis of Major Congenital
Malformations (MCMs) and Oral Clefts (OC) Associated
with In-Utero Topiramate Exposure
Mark W. Green and Arun Bhattachuria; New York, NY and
Yardley, PA
Objective: To examine rituximab effect on T-cell subsets.
Background: Rituximab, an anti-CD20 antibody, profoundly depletes circulating B-cells. It is unclear how it
impacts T-cells. Methods: In a retrospective study of
patients who received >1 rituximab infusions at UCSF MS
center, within-patient pre- and post-infusion (mean duration
¼ 7 months) lymphocyte counts for the first rituximab
course were compared. Results: Of 119 patients who
received rituximab, 56 (45 MS, 10 NMO, 1 other indication) had both pre- and post-infusion labs. The mean (þ
SD) absolute count of CD19þ B-cells dropped from 273
(þ 25) pre- vs. 59 (þ17) post-rituximab (p <0.0001). The
overall (CD3þ; 1322 þ 104 vs. 1047 þ 62; p ¼ 0.009),
CD4þ (907 þ 75 vs. 717 þ 44; p ¼ 0.0124), and CD8þ
(409 þ 39 vs. 313 þ 23; p ¼ 0.004) T-cell counts dropped
after rituximab. At follow-up, 15 of 67 (22%) had a CD4
Purpose: To analyze the prevalence of malformations
among infants born to women exposed to topiramate.
Methods: This study used retrospective data from Wolters-Kluwer Pharma Solutions that followed patients’ Pharmacy and Medical Claims (1/2003–12/2010) to identify
infants exposed to topiramate during pregnancy (n ¼ 778).
Probable exposure during pregnancy was refined using data
on script fill date/supply, infant birth date, and ICD-9
codes for birth term.
Control cohorts included women with diagnosis of migraine without epilepsy (n ¼ 26,920) and a subset exposed
to acute-preventive migraine drugs (APMD) during pregnancy (n ¼ 2,964). Topiramate was excluded from both
groups. All cohorts excluded known or suspected teratogens.
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count below 500, and 4 (6%) had a CD4 count below 200.
NK cell number (CD56þ, CD16-) tended to increase postinfusion (182 þ 13 vs. 199 þ 14; p ¼ 0.2). Impact of retreatment is being analyzed. Conclusions: Rituximab induces long-term T-cell reduction, whose impact is unclear.
Study supported by: Research grant from Roche
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marrow space of the skull involves aquaporin water
channels.
Study supported by: Grants from the Ministry of Education, Culture, Sports, Science, and Technology (Japan) and
University of Niigata.
T1743. Fast Macromolecular Proton Fraction (MPF)
Mapping in Multiple Sclerosis (MS)
Vasily L. Yarnykh, James D. Bowen, Bart P. Keogh, Pavle
Repovic, Angeli Mayadev, Beena Gangadharan, Daniel S.
Rizzuto, Hunter R. Underhill, Kenneth R. Maravilla and Lily
K. Jung-Henson; Seattle, WA
T1745. Characteristics of the Long Latency
Vestibular Electrical Evoked Potential in
Control Human Subjects
Benn E. Smith, Michael J. Cevette, Jan Stepanek, Daniela
Cocco, Gaurav Pradhan, Kenneth H. Brookler, Lindsay
Wagner, Sarah Oakley, David A. Zapala and Mark A. Ross;
Scottsdale, AZ and Jacksoville, FL
MPF mapping is a new quantitative imaging method, which
determines relative concentration of macromolecular protons
involved into the magnetization transfer effect. Literature suggests strong correlations between MPF and myelin content in
neural tissues. We recently developed a fast 3D MPF mapping
technique for clinical applications, which utilizes two images
(with and without off-resonance saturation), and complimentary T1, B0, and B1 maps, providing whole-brain coverage,
1.51.54mm3 resolution, and <15 min total acquisition
time on a 3T MRI scanner. In this ongoing study, MPF maps
were obtained from 9 healthy controls, 18 relapsing-remitting
(RRMS) patients, and 3 secondary-progressive (SPMS)
patients. Whole-brain MPF histogram analysis was performed
to quantitatively characterize individual MPF distributions in
white matter (WM) and gray matter (GM). Group comparisons (independent t-test) revealed significant decreases of mean
MPF in MS vs. controls and in SPMS vs. RRMS for both
WM (P<0.001) and GM (P<0.04). Mean MPF in WM and
GM demonstrated significant correlations with EDSS (r ¼
0.55 and 0.56, P<0.01) and MSFC (r ¼ 0.78 and 0.68,
P<0.001) scores. In summary, MPF can be used as a prospective quantitative imaging biomarker of demyelination, which
captures pathological changes in both WM and GM.
Study supported by: National Institutes of Health: NIH
R21EB009908
Dr. Yarnykh is the PI of the above NIH grant, and his
salary is funded in part by this award.
Introduction: A human vestibular electrical evoked potential (VEEP) technique has recently been reported.
Objective: To report a unique long latency waveform
associated with the human VEEP which has novel electrical
properties.
Methods: Control ears (n ¼ 23) were studied with bipolar mastoid electrical stimulation. Evoked potentials were
produced using currents from 1 to 25mA, recording over
Cz-A1/2.
Results: In neurologically normal controls, mastoid stimulation at 2.5mA yielded Cz-A1/2 late responses of median
amplitude 61lV (range 1.6–104; SD 25) and median latency 10.2ms (range 6.0–13.3; SD 4.9). These responses
progressively increased in latency from 8.6 to 22.6ms (mean
latency increase of 1.3ms/mA) as current strength was
increased in 10 steps (1mA/step) from threshold current levels in all 5 subjects studied in this way.
Conclusions: (1) The VEEP technique produces late
responses in neurologically normal adults, (2) these
response latencies increase with increasing current strength
as reported in animals, (3) the current strength-response
pattern of human VEEP late responses may reflect inhibition of descending vestibular efferent pathways or alternative as yet undiscovered mechanism(s), and (4) future studies are needed to define the nature and origin of the VEEP
in health and disease.
Study supported by: Mayo Foundation
T1744. Skull Is Skull, and Not Simply Another Bony
Structure
Tsutomu Nakada, Yuji Suzuki, Yukihiro Nakayama, Vincent
J. Huber and Ingrid L. Kwee; Niigata, Niigata, Japan and
Martinez, CA
T1746 Regulatory T Cells Play Contrasting Roles in a
Viral Model for Multiple Sclerosis
Nicholas E. Martinez, Fridrik Karlsson, Fumitaka Sato,
Seiichi Omura, Alireza Minagar, Mathew B. Grisham, and
Ikuo Tsunoda; Shreveport, LA
Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a viral model for multiple
sclerosis (MS). Regulatory T cells (Tregs) can suppress experimental autoimmune encephalomyelitis, an autoimmune
model for MS by modulating pathogenic Th1 and Th17
immune responses. While these findings imply that Tregs
could also be beneficial in MS, we hypothesized that Tregs
can be a double-edged sword in TMEV-IDD. In viral infections, although Tregs can prevent immune-mediated pathology, Tregs can suppress anti-viral immune responses, leading
to more active viral replication and/or viral persistence. We
injected TGF-b induced Tregs (iTregs) into TMEV-infected
SJL/J mice on days 0 (early) or 35 (late). The early iTreg
injection group developed more severe motor disturbances 1
week post infection (p.i.). The exacerbation of acute disease
is most likely due to suppression of anti-viral immune
responses in the central nervous system, facilitating viral replication. In contrast, late iTreg injection reduced inflammatory demyelination during the chronic phase of infection (2
months p.i.), which could be due to suppression of
Aquaporin-4 (AQP-4) is a membrane protein in the
aquaporin family of water transporters. It is widely
expressed in the astrocyte system of the brain. Evidence
continues to accumulate that AQP-4 is actively involved
not only in vital physiological brain functions such as
neural-flow coupling, but also in the pathophysiology of
various brain diseases. In the process of developing clinical AQP-4 positron emission tomography (PET) for the
brain, we identified various AQP-4 inhibitors. Among
these, TGN-020 (2-nicotinamido-1,3,4-thiadiazole), was
found to be suitable for AQP-4 PET in spite of its partial co-affinity for aquaporin-1. Subsequent human PET
images obtained utilizing 11C-TGN-020 appropriately
demonstrated specific distribution of AQP-4 within
human brain in vivo. The study, however, unexpectedly
exhibited very strong uptake of 11C-TGN-020 within
the diploic space of the skull. Other bony structures, by
contrast, showed virtually no uptake. Aeration represents
a unique characteristic of the skull of ‘‘heavy brain’’ animals. The study strongly suggests that drying of the
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immunopathology. Therefore, iTregs could play contrasting
roles depending upon the stage of virus-mediated demyelinating diseases.
Study supported by: National Center for Research
Resources of the National Institutes of Health.
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tially with repeat imaging 5 days from symptom onset
revealing a conus myelitis (CM).
Case report: A 42-year-old female woke up with UR,
which progressed to an ascending FP without a sensory
level. MRI of spinal axis w/wo was normal. Lumbar
puncture revealed 0 WBC, 1 RBC, normal protein,
glucose and negative immune markers (IgG Index and
oligoclonal bands). EMG was normal. MRI of the lumbar spine repeated 5 days later revealed CM. Extensive
infectious, inflammatory and autoimmune work up
including NMO was negative. Brain MRI w/wo was
normal as were VEPs. She had a relapse 3 months after
the initial bout.
Conclusion: Idiopathic CM appears to be a rare clinical
entity, which can have protean manifestations requiring a
high index of clinical suspicion and a thorough systematic
workup.
Study supported by: None
T1747 Idiopathic Relapsing Conus Myelitis
Raghav Govindarajan and Efrain Salgado; Weston, FL
Background: Idiopathic acute transverse myelitis (TM)
involves the thoracic cord. In rare cases conus might be the
only site involved. Bladder symptoms can be a presenting
feature without an obvious sensory level. Imaging studies
might remain inconclusive thus posing a diagnostic challenge. Relapses in TM are rare and even more so restricted
to the conus. We report a case of a 42 year-old female who
presented with urinary retention (UR) that progressed to a
flaccid paraplegia (FP). Imaging studies were negative ini-
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136th Annual Meeting Sunday,
September 25, 2011 Career
Development Poster Session
Abstracts
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in gene expression, differential display microarray data was
analyzed.
Results: Immunocytochemistry of KCNC3R420H mutant
allele revealed perinuclear clumping and aggregation. Evidence
for precise trans-Golgi localization was obtained by high FRET
efficiency in the KCNC3R420H cells co-stained for 58K and
KCNC3. Immunogold EM revealed KCNC3R420H failed to
be delivered to the plasma membrane, though intracellular
accumulation of KCNC3R420H was observed in swollen, distorted Golgi depleted of Golgi-derived vesicles. Microarray
data revealed significant expression differences between the mutant and wildtype cultures in genes involved in Golgi processing and ubiquitination pathways.
Conclusions: Our results establish the likelihood of protein aggregation and aberrant intracellular trafficking localized to the trans-Golgi network as a pathogenic mechanism
in the neurodegenerative form of SCA13. KCNC3 channels
are expressed in Purkinje cells and the hippocampus and are
critical for the properties of bursting neurons.
Study supported by: K23; American Academy of Neurology clinical research training fellowship
Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with
authors present from 6:00 pm – 7:00 pm.
CD515. Non-Convulsive Status Epilepticus Is Associated
with Mortality and Worse Short-Term Outcome in
Critically Ill Children
Nicholas S. Abend, Alexis A. Topjian and Dennis J. Dlugos;
Philadelphia, PA
Objective: Determine whether non-convulsive seizures
(NCS) and non-convulsive status epilepticus (NCSE) were
associated with higher mortality and worse short-term
outcome.
Methods: Critically ill children with acute encephalopathy underwent EEG monitoring. EEGs scored as no seizures, NCS, or NCSE. Co-variates included age, etiology of
acute encephalopathy, and EEG background. Outcomes
were mortality and change in Glasgow Outcome Scale
(GOS) from admission to ICU discharge. Chi-squared analysis and multi-variable logistic regression were used to evaluate for associations.
Results: 200 children underwent cEEG. NCS occurred
in 84 (42%) of which 43 (22%) had NCSE. 83 (41%) had
a decrease in GOS of which 36 (18%) died. In multi-variate
analysis NCSE was associated with mortality (OR 3.05,
p¼0.04) and change in GOS (OR 15.5, P<0.001) while
NCS was not associated with mortality (OR 1.2, p¼0.76)
or change in GOS (OR 1.5, p¼0.45).
Conclusions: NCSE, but not NCS, is associated with
worse short-term outcomes in critically ill children with
acute encephalopathy. Further investigation is needed to
determine whether this association is causal, persists in the
long-term, and whether identification and management of
NCS improves outcome.
Study supported by: NIH K12-NS049453
CD531. TLR9 Processing in Multiple Sclerosis: A New
Immunomodulatory Effect of Interferon-beta
Konstantin E. Balashov, Suhayl Dhib-Jalbut and Latt Aung;
New Brunswick, NJ
Background: Viral pathogens, e.g., Epstein-Barr DNA virus
have been implicated in the pathogenesis of multiple sclerosis(MS). Toll-like receptor(TLR)9 is the only TLR able to recognize viral DNA. TLR9 protein has to be cleaved from the
N-terminal to become functional(processed TLR9). TLR9 is
highly expressed in plasmacytoid dendritic cells(pDCs).
Methods: pDCs were separated from healthy donors and
MS patients. TLR9 gene expression was assessed by oligonucleotide microarrays. Unprocessed(135kDa) and processed(65kDa) TLR9 protein expression were studied by Western blot. Cytokine production by activated pDCs was
measured by Multi-Analyte Profiling.
Results: After treatment with IFN-beta, pDCs developed
decreased ability to produce IFN-alpha, IL-6 and TNFalpha in response to TLR9 agonists as compared to the
same patients prior to treatment. IFN-beta treated patients
had levels of both TLR9 gene expression and the fulllength(unprocessed) TLR9 protein similar to untreated
patients and healthy donors. However, pDCs separated
from IFN-beta treated patients(n¼11), had significantly
reduced levels of the processed TLR9 protein
(0.89760.0639 relative units) as compared to untreated
patients(1.44560.106, n¼14, p¼0.0004).
Conclusion: Our findings suggest a novel immunomodulatory mechanism of IFN-beta. Modulation of TLR9 protein processing may contribute to decreased frequency of
clinical exacerbations in IFN-beta treated MS patients.
Study supported by: NIH, NMSS, Bayer Healthcare
Dr. Balashov and Dr. Dhib-Jalbut served as consultants
for Bayer Healthcare in the past.
CD522. Aberrant Channel Subunit Trafficking in the
Neurodegenerative KCNC3R420H SCA13 Phenotype
Michael F. Waters; Gainesville, FL
Background: Potassium channels influence many aspects of
electrical excitability and mutations in their genes have been
described in neurological diseases. We previously reported
that the KCNC3R420H mutation leads to a neurodegenerative phenotype.
Methods: Cell were transfected with constructs expressing
wild-type and mutant KCNC3 alleles. Localization experiments were performed utilizing immunocytochemistry and
electron microscopy. To assess mutant-mediated alterations
111
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ABSTRACT AUTHOR INDEX
Arnoldi, Alessia
M1002
Artibee, Kay
M810
Asadollahi, Marjan
T1732
Ascherio, Alberto
S216
Askanas, Valerie
M807, M808,
M816, M835
Assadi, Mitra
S223
Astafiev, Serguei V.
M601
Atassi, Farrah
S215
Atkinson, Elizabeth J.
M1008
Au, Rhoda
T1504
Auchus, Alexander P.
M1301
Awkar, Nelly
M717
Azimi, Amirreza
T1722
Babikian, Viken L.
S122
Babovic, Mihajlo
T1727
Backus, Carey
M804
Bagai, Kanika
S303
Baiser, Alexa S.
T1504
Baker, M.
S204, S209
Bakken, Erik C.
M618, M619
Bakst, Isaac
M821
Balasubramanian, Archana B.
T1524
Balice-Gordon, Rita
T1701, T1716
Baloh, Bob
M815
Baloyannis, Stavros J.
T1528
Bammler, Theodor K.
T1511
Banerjee, Chirantan
S101
Bankiewicz, Krystopf S.
T1529
Barbato, Luigi M.
T1735
Barcikowska, Maria
T1503
Bardin, Jonathan C.
M1104
Barkhof, Frederik
T1708
Barnwell, Stanley L.
T1606
Bartz, Traci
T1513
Bass, Dale
M1107
Bassi, Mariateresa
M1002
Bassile, Clare
M1403
Basta, Milan
S103
Bateman, Lisa M.
M703
Bateman, Randall J.
T1501
Bayat, Elham
T1739
Bayram, Mehmed B.
T1527
Beal, Flint
S216
Beck, James
S216
Beckmann, Karola
T1702
Beh, Shin C.
S210
Belichenko, Pavel V.
M609,
M712
Bellugi, Ursula
M608
Benke, Tim A.
M706
Aasly, J.
S204, S209
Aasly, Jan
T1503
Abbott, Robert D.
S203
Abolfazlee, R.
S114, T1732
Achim, Critian L.
T1905
Adams, Patrick E.
T1521
Agadi, Jagadish B.
M822
Agbemenyah, Hope Yao M1004
Aggarwal, Swati
M821
Ahlskog, J.E.
M606
Ahmed, Aiesha
M833
Akbar, Umer
M1205, T1620,
T1809
Akber, Umer
M719
Akfirat, Gokhan
T1536
Akiyama, Hisanao
S120
Aksan, Nazan
M615
Al Samara, Mershed
M722
Alaedini, Armin
M602
Alam, Nurul
S123
Alcalay, Roy N.
S225
Aldea, Patricia
T1901
Alexander, Katie
M821
Alexopoulos, Andreas V.
M711
Alexopoulos, Harry
T1729
Alfahad, Tariq
S127
Alfano, Lindsay N.
M802
Alfuth, Kathleen S.
M832
Algom, Avi
M1007
Alkawadri, Mhd Rafeed
M711
Allen, Mariet
T1503
Allred, Peggy
M821
Alqadi, Khalid S.
S127
Altafullah, Irfan
S102
Althaus, Alison L.
M1401
Amini Harandi, Ali S114, T1712,
T1718, T1722, T1723,
T1731, T1732, T1734
Ances, Beau
T1901
Andersen, O.
S204, S209
Anderson, C. Alan
M616
Andres, Patricia
M821
Andress-Rothrock, Diane C.
S113, T1602
Andrews, Mark
M1106
Annex, Brian H.
S115
Ansari, Hossein
S236
Ansari, Morad
T1503
Appel, Shmuel
M702
Arain, Fazal M.
M707
Arcilla-Londono, Ximena M828
Arciniegas, David B.
M616
Ard, M. Colin
T1531
Ben-Menachem, Elinor
M713
Bennett, C.F.
M821
Bennett, David A.
T1502
Bennett, Jeffrey L.
T1736
Benzinger, Tammie
T1901
Berlau, Daniel J.
T1524
Bernard, Bryan
S211
Bernard, Paul B.
M706
Beyer, Richard P.
T1511
Bhabad, Sudeep
S119
Bhargava, Pavan
S140
Bhat, Sushanth
M718, M834,
S134, S137
Bhattacharya, Pratik
S129
Bieber, Allan
M1101
Biglan, Kevin
S228
Biglan, Kevin M.
S402
Bigwood, Doug
T1736
Bilal, Yasmin
T1737
Billings, Nia M.
M613
Biondo, Andrew
M828
Bisceglio, Gina
T1503
Bishop, Kathie
M821
Black, Robert E.
S123
Blair, Aaron
S208
Blakeman, Alan
T1621
Blasco, Maria R.
T1713
Blechschmidt, Cristiane
M835
Blennow, Kaj
T1514
Bliton, Mark
S232
Bliwise, Donald L.
S301
Blythe, Anne
M819
Bockenek, William L.
M819
Bodda, Chiranjeevi
M1004
Boden-Albala, Bernadette M1403
Bodensteiner, John B.
M1303
Boes, Benjamin
M1008
Boeve, Bradley F.
T1530
Boffa, Michael
S302
Bonanni, Paolo
M1002
Bonato, Sara
M1002
Bondar, Galyna
T1704
Boon, Andrea
M826
Bordelon, Yvette
S213
Borkowski, Thomas M.
T1615
Borland, Scott
T1617
Bota, Daniela
T1804
Botuyan, Maria V.
M1008
Boutin, Paula
T1719
Boyd, Scott D.
T1736
Bravver, Elena
M814, M819
Brennan, K.C.
T1601
Bresolin, Nereo
M1002
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Catellier, Diane J.
T1505
Cava, Luis
S113
Cen, Steven
S221
Cervantes, Anna M.
S122
Chai, High Seng
T1503
Chana, Gursharan
T1905
Chandrakumar,
Manokaraananthan
T1621
Chandrasekaran, Krish
M801
Chang, Bernard S.
M704
Charles, David
S224, S232
Charles, P. David
S226
Chaturvedi, Seemant
S129
Chemali, Zeina
S214
Chen, Chueh-Tan
T1537
Chen, Helen
M801
Chen, Honglei
S208, S234
Chen, Jian
M1301
Chen, Roujie
M1403
Chen, Shun-Sheng
T1537
Chen, Xinzhi
S103
Chen, Yi
T1715
Cheng, Chu
M1402
Cheng, Hsinlin T.
T1604
Cheng, Jiin-Tsuey
T1537
Cheng, Ping
M607
Cheng, Yuching
S107
Cheong, Hae Kwan
T1519
Chernoff, Jonathan
M803
Cheung, Ying K.
M1403
Chibnik, Lori B.
T1502
Chipendo, Portia I.
T1502
Chisulo, Brian
T1908
Chitnis, Shilpa
S210
Chiu, David
S116
Cho, Chi
T1740
Choi, Jae-Hwan
S126
Choi, Kwang-Dong
S126
Choi, Soon Gang
M824
Chokroverty, Sudhansu
M718
Choudary, Zahid
S130
Choudary, Zahid I.
S135
Choudhary, Shazia Z.
S130,
S135
Chretien, Nathalie
T1721
Christensen, Jon
T1901
Christie, Kimberly J.
M1402
Christine, C.W.
S204, S209
Christodoulou, Joanna A.
M704
Christopher, Hanlon T.
T1602
Chuang, Yu-Ming
S106
Chun, Jerold
T1710
Chung, Amy S.
T1802
Churchwell, Mona I.
T1511
Ciric, Bogojub
T1725
Bressman, Susan B.
Brewer, James B.
Bringas, J.
Britton, Jeffrey W.
S233
T1514
T1529
M1202,
M1203, S403
Broderick, D.F.
S204
Broderick, Joseph
S112
Brooks, Benjamin
M821
Brooks, Benjamin R.
M814,
M819
Brooks-Kayal, Amy R.
M705
Brott, Thomas G.
S102, S116
Brown, Amanda
S407
Brown, O.W.
S102
Bruce, Nhu T.
S131
Bryant, Monthaporn S.
S215
Bucelli, Robert
S406
Buckley, Camilla
T1711
Buckley, Charlotte T1903, T1904
Bumbaugh, Jon
T1614
Burakgazi, Evren
T1620
Burakgazi-Dalkili, Evren M1205
Burge, Daniel J.
T1724
Burger, Kathleen
S127
Burke, James
M1107
Buse, Dawn C.
T1608, T1610,
T1611, T1612, T1613,
T1615
Bushara, Khalaf O.
M602
Busta, Angela S.
M804
Cacabelos, Ramon
T1506
Cacciottolo, Mafalda
M807
Cai, Haipeng
M1301
Caillier, Stacy
T1713
Callaghan, Brian
M1005
Camargo, Carlos A.
S139
Cambon, Alex C.
S213
Campbell, Christina
M1204
Campbell, Harry
T1503
Campos-Rivera, Juanita
T1719
Can, Karolina
M1004
Cannigaiper Uthamaroyan,
Velmurugendran
S121
Cao, Chuanhai
S202
Capehart, Bruce P.
M1107
Caplan, Louis
S136
Carlson, H.
T1522
Carlson, Noel G.
T1801
Carone, Marco
S123
Carran, Melissa
T1809
Carrasquillo, Minerva M. T1503
Carter, Alex R.
M601
Casadesus, Gemma
M620
Casanova, Vanessa
M1002
Case, Amanda
M1001
Castano, Anna
M706
Stage:
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Clark, Chris M.
Clark, K. Reed
Clawson, Susan A.
Clifford, David
Clifton, Guy L.
Cohen, Jeffery A.
Cohen, Jeffrey
Cohen, Jeffrey A.
Coker, Laura H.
Cole, John W.
Collins, William
Comi, Giacomo
Comi, Giancarlo
Conte, Mary M.
Contractor, Anis
Cook, Jason A.
Corbetta, Maurizio
Coresh, Josef
Corey-Bloom, Jody
T1508
M802
T1801
T1901
M1103
T1710
T1708
T1709
T1505
S107
T1709
M1002
T1708
M1104
T1701
S224
M601
T1505
S205, S220,
T1507
Corrada, Maria M.
T1508,
T1524
Corrigan, John
M828
Cote, Lucien
S225
Couto, Joseph
T1614
Cowell, Lindsay G.
T1736
Crimella, Claudia
M1002
Crook, Julia
T1503
Crowder, Kermit
S109
Cruz Del Angel, Yasmin
M705
Cruz-Flores, Salvador
T1513
Cudkowicz, Merit
M821
Cuevas, Ivan
T1506
Cunningham,
Christopher R.
S213
Cunningham, Julie M.
M1008
Cutter, Gary
T1702
D’Agostino, Carla M807, M808
Dakka, Youssef A.
M828
Dalakas, Marinos C.
T1729
Dale, Anders M.
T1525
Dalmau, Josep
T1701, T1716
D’Angelo, Grazia
M1002
Das, Moromi
S104
Dauch, Jacqueline R.
T1604
David, William
M821
Davis, Bonnie
S109
Davis, Thomas L.
S232
D’Cruz, O’Neill
M714
De Jager, Philip
T1720
De Jager, Philip L.
T1502
DeArmond, S.
S204, S209
DeCarli, Charles
T1504
Decker, David A.
S130, S135
Deeley, Cheryl
S228
DeFreitas, Tiffani
T1615
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Elble, Rodger J.
Eleopra, Roberto
El-Hagrassy, Mirret
Elkind, Mitchell S.V.
Ellik, Shehanaz
Elliott, Robin
Ellis, Ronald J.
Elsayed, Mohammad
Engel, King W.
M808,
S140
S237
T1536
S101
M828
S216
T1905
M613
M816,
M835
Engel, W. King
M807
Ertekin-Taner, Nilufer
T1503
Erten-Lyons, Deniz
T1532
Eslinger, Paul J.
S206, S212
Etemadifar, Masoud
T1732
Evans, Denis A.
T1502
Evensen, Laura A.
M1403
Everall, Ian P.
T1905
Faezi, Sholeh
T1731
Fagan, Anne
T1901
Fallah, A.
T1712, T1723
Fang, Yin
T1527
Fanning, Kristina
T1608
Fanning, Kristina M.
T1610, T1611
Fantin, Marianna
M1002
Farber, Charles R.
S115
Farheen, Amtul
M833, M834,
S134, S137
Farrer, Lindsay
T1512
Farrer, Matthew J.
S207
Fasih, Zoha
S137
Fatima, Tasneem
S229
Feany, Mel B.
T1502
Feldman, Eva L. M804, M1005,
T1604
Fennema-Notestine,
Christine
T1525
Fernandez, Lucia
T1506
Ferrari, Michel
T1617
Fields, Jeremy D.
T1606
Figueroa-Romero, Claudia M1005
Filley, Christopher M.
M616
Fincher, Linda
S215
Finder, Stuart G.
S232
Finlayson, Marcia
T1740
Fire, Andrew Z.
T1736
Fisher, Barbara C. M610, M614
Fisher, Mark
S108
Fishman, Robert A. S124, T1806
Fitzpatrick, Annette
T1513
Flagg, Emily
S216
Flanagan, Eoin P. M811, T1805
Flanigan, Kevin M.
M802
Flemming, Kelly D.
S128
Forsayeth, John
T1529
DeFries, Ashleigh
T1534
Dekermenjian, Rony S134, S137
del Pilar Cortes
Nino, Maria
T1906
Del Tufo, Stephanie N.
M704
Delaney, Colin E.
M1005
Delgado, Monica
T1705
Demaerschalk,
Bart M.
S102, S116
Denic, Aleksandar
T1703
DeOrchis, Vincent S.
T1518
Derani, Lena
T1739
Desai, Urvi G.
M819
Dham, Bhavpreet S223, T1620,
T1809
Dhamija, Radhika
S403
Diaz-Medina, Gloria E.
S403
Dickson, D.W.
S204, S209
Dickson, Dennis W.
M1007,
S207, T1503,
T1515, T1530
DiClemente, Guillermo
T1534
Diep, Lien
S109
Dilley, Deanne
M714
DiVito, Brittany M. M618, M619
Dodge, Hiroko
T1532
Dodick, David
T1617
Doerge, Daniel R.
T1511
Dominantly Inherited
Alzheimer Network
T1501
Dorsey, E. Ray
S402
Dosado, Lea
M830
Doty, Pamela
M713, M714
Dowling, James J.
M804
Du, Guangwei S206, S212, S234
Du, Senxi
T1804
Du, Sienmi
T1704
Duane, Drake D. M618, M619
Dubinsky, Richard
S213
Dueker, Nicole
S107
Duncan, G.
T1522
Duquette, Pierre
T1713
Durand, Dominique
M620
Dustin, Irene
M702
Dyck, P. James
M1008
Dyck, Peter J.
M1008
Eastman, Alison J.
M1001
Eastman, Eric
T1736
Eberly, Shirley
S216
Ebers, George
T1702
Edland, Steven D.
M1010,
S205, T1531
Edlow, Jonathan A.
S139
Edson, Jean
S109
Edythe, Wiggs A.
M820
Eizenamn, Moshe
M607
Stage:
Page: 114
Forst, Amy
Foulds, Pamela
Fountain, Nathan B.
T1616
T1726
M713,
M714
Fowkes, Mary E.
M824
Francis, Gordon
T1709
Frederick, Meredith C.
M616
Freeman, William D.
M1204
Friedland, Robert P.
M1301
Frohman, Elliot M.
T1736
Frost, Nicholas
M723
Fry, Rebecca C.
T1511
Fu, Beverly D.
T1804
Fugate, Jennifer E. S128, T1714
Fuh, Jong-Ling
T1605
Fujioka, Shinsuke M1007, S207
Fulda, Stephany
M610, M614
Furuya, Hirokazu
S201
Gabbard, Jennifer
T1737
Gabrieli, John D.E.
M704
Gadallah, Nancy
S134
Galasko, Douglas
T1525
Galasko, Douglas R.
T1531
Galbraith, Sareen
T1903
Galbraith, Sareen E.
T1904
Gallagher, Martin J.
M707
Gallin, Eliza
S213
Gamez, Jeffrey
T1727
Gamez, Jeffrey D.
T1715
Ganeshan, Veena R.
T1803
Garbern, J.Y.
S204, S209
Garcia, Paul S.
S301
Garden, Gwenn A.
M1001
Gardiner, Irenita
S228
Garges, Danielle M.
M610,
M614
George, Benjamin P.
S402
Georgescu, Constantin
T1503
Gerhardt, Greg A.
M709
Ghaffarpour, Majid
T1732
Ghaffar-Pour, Majid
S114
Gharagozli, Kourosh
T1731
Ghareghozli, Kourosh
T1718
Ghargozlee, Kourosh
T1732
Ghosh, Partha S.
M1302
Ghoshal, Shivani
S136
Ghragozlee, Kourosh
S114
Gill, Chandler E.
S224, S232
Gluhm, Shea
S205, S220,
T1507
Goadsby, Peter J. T1603, T1617
Gobinathan, Devathasan
M830
Godfrey, Rena A.
M820
Goetz, Christopher G. S211, S231
Gohar, Dina
T1527
Gokhale, Sankalp
S136
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Hafler, David
T1720
Hagerman, Paul J.
T1521
Hagerman, Randi J.
T1521
Hagler, Jr, Donald J.
T1525
Haines, Jonathan
T1512
Haleem, Darakhshan Jabeen S229
Hall, Charles
T1615
Hall, Deborah A.
S213
Hall, Ira M.
S115
Hallett, Mark
M602
Halvorsen, Mark B.
M710
Hamby, Mary
T1704
Hammans, Simon
M1008
Hanna, Michael
M831
Happ, Erik
T1806
Hara, Hajime
M829
Harbour, Leia
S109
Hardy, Duriel
M1401
Häring, Dieter A.
T1707
Harman, Jennifer
S216
Haro SIlva, Rubén
M617
Harper, Charles M.
M811
Harris, Tamara B.
T1504
Hart, Ian J.
T1903, T1904
Hartung, Hans-Peters
T1708
Hasegawa, Yasuhiro
S120
Hassan, Anhar
M826
Hastie, Nicholas D.
T1503
Hatemian, A.
S114
Haut, Sheryl R.
T1615
Hayward, Caroline
T1503
Heck, Donald V.
S102
Heiss, Wolf-Dieter
T1510
Heister, David S.
T1514
Hemmen, Thomas M.
S105
Henchcliffe, Claire
S213
Hendrix, Suzanne
T1516,
T1517, T1523,
T1526
Heppner, Frank L.
M835
Hernandez, Leticia
S230
Herr, Barbara
M831
Heshmat, Ramin
T1722
Hill, Kenneth E.
T1801
Hillis, Argye E.
M605, M612,
S125, S132
Hinson, Vanessa
S219
Hinton, Sabrina
S129
Hirano, Makito
T1520
HNRC Group
T1905
Hocker, Sara
M1202, M1203
Hogan, Edward
M708
Hohjoh, Hirohiko
S201
Hohlfeld, Reinhard
T1707
Holland, Dominic
T1525
Hollenbeck, Albert
S208
Goldfarb, Neil
T1614
Goldfine, Andrew M.
M1104
Goldman, Jennifer G.
S211
Goldstein, Jerome
T1618
Goldstein, Jody
S205, S220,
T1507
Goltz, Herbert C.
T1621
Gomez, Megan
S221
Gomez, Yessenia
M605
Gonnella, Patricia
T1725
Gonzalez, Marco I.
M705
Goodin, Douglas S.
T1702
Goodman, B.
S204, S209
Gordon, Barry
M613
Gottdiener, John
T1513
Gottesman, Rebecca F.
S125,
S132, T1505,
T1513
Gourraud, Pierre-Antoine T1713
Govindarajan, Raghav
M822
Grabenstatter, Heidi L.
M705
Grabstein, Kenneth
T1724
Graff-Radford, Jonathan M606,
T1714
Graff-Radford, Neil
T1515
Graff-Radford, Neill R.
T1503
Grafton, Scott T.
M604
Graham, Stephen M.
T1516,
T1517, T1523,
T1526, T1533
Green, Peter H.
M602
Greenberg, Benjamin M. T1736
Greenfield, L. John
S404
Greenia, Dana E.
T1508
Greenlee, John E.
T1801
Greenspan, Ralph J.
M1006
Grewal, Raji
M833
Griffiths, Michael
T1904
Griffiths, Mike
T1903
Griggs, Robert C.
M831
Grinspan, Augusto
T1707,
T1708
Groden, Catherine A.
M820
Grossardt, Brandon R.
T1703
Gu, Yian
S225
Gualdi, Sabrina
S237
Guo, Fuzheng
T1705
Guo, Jiasong
M803, M813
Guo, Xuguang
S208
Gupta, Divya
M718
Gupta, Varun
M816
Gutmann, Laurie
S236
Gutmann, Ludwig
S236
Guzik, Amy K.
S115
Habermann, Thomas M. T1805
Hachinski, Vladimir
T1510
Stage:
Page: 115
Holtzman, David
T1901
Hong, Yu
M1005
Hopkins, Mark
T1903, T1904
Hopkins, Mary
T1614
Hornung, Richard
S112
Hou, Jing
T1527
Hou, Jyhgong Gabriel
S215
Howard, George
S102, S116
Howard, Katherine L.
M616
Hsieh, Yu-Hsiang
S139
Huang, Juebin
M1301
Huang, Xuemei
S206, S208,
S212, S234
Huentelman, Matthew A. T1502
Huh, Young Eun
S138
Hui, Jennifer S.
S221
Hur, Junguk
M1005
Husain, Samea
S218
Husan, Shema
S229
Hussain, Tiki S222, S227, S235
Hye, Robert J.
S102
Ikeda, Ken
M812
Ikuno, Yasushi
T1520
Irani, Sarosh
T1711
Ishihara, Ryu
T1520
Isobe, Noriko
M1009, T1706
Isojarvi, Jouko
M713
Itoh, Noriko
T1704
Iwahashi, Hiromi
T1520
Iwasaki, Yasuo
M812
Iwashita, Julie
T1616
Iyadurai, Stanley
M720, T1607
Iyadurai, Stanley J.
M815
Jack, Clifford
T1503
Jack, Clifford R.
T1530
Jack, Jr., Clifford R.
M606,
T1505
Jackson, Dan
M1204
Jackson, Leila
S213
Jacobson, Mark
T1507
Jacobson, Mercedes
S401
Jaffer, Zahara M.
M803
Jankovic, Joseph
S213
Järvinen-Pasley, Anna
M608
Javan, Alireza K.
T1521
Javedani, Parisa P.
T1606
Jayadev, Suman
M1001
Jayam-Trouth, Annapurni
S109
Jeffrey, Kaye
T1532
Jen, Jin
T1503
Jenkins, Andrew
S301
Jensen, Michael D.
M606
Jeon, Seun
T1519
Jianfeng, Cai
S202
Jiang, Shan H.
T1908
Jimi, Takahiro
M829
115
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Kim, Chi Hun
T1519
Kim, Jae Seung
T1519
Kim, Ji Soo
S138
Kim, Suk-Hui
T1519
Kim, Sung Tae
T1519
Kimonis, Virginia E.
M805
Kimura, Fumihiko
T1733
Kira, Jun-ichi
M1009, T1706
Kisby, Glen E.
T1511
Kissel, John
M806
Kittner, Steven J.
S107
Klein, Christopher J.
M1008
Kleschevnikov, Alexander M.
M712
Klingstedt, Therése
M835
Kluger, Benzi
S213
Knappertz, Volker
T1702
Knopman, David S.
T1505,
T1530
Ko, Nerissa
S112
Koch, Heather A. M618, M619
Koffmann, Boyd
S404
Kolbert, Christopher P.
T1503
Kompoliti, Katie
S231
Kong, Xiao-Tang
T1804
Konrad, Peter E.
S232
Korczyn, Amos D.
T1535
Kori, Shashidhar
T1603,
T1616, T1617
Koubeissi, Mohamad Z.
M620,
M1301
Koyfman, Feliks
S122
Krauss, Gregory
M714
Kremenchutzky, Marcelo T1702,
T1707
Kronk, Lisa
M817
Kronmal, Richard
T1513
Kumar, Bishwanath M1003, S104
Kumar, Sunil
M1003
Kunschner, Lara
T1806
Kunyu, Li
S202
Kupsky, W.
S209
Kurantsin-Mills, Joseph
S109
Kurlan, Roger
S216
Kurtzke, John F.
T1730
Kusunoki, Susumu
M818,
T1520, T1733
Kuwabara, Motoi
T1733
Kuwahara, Motoi
M818
Kwagyan, John
S109
Kwan, Justin Y.
M820
Lai, Eugene C.
S215
Laidlaw, David H.
M1301
LaManna, Joseph
M620
Lambrecht, Lawrence J.
M710
LaMorte, Michael
T1721
John, Sanjna M.
Johnson, Aaron J.
Jones, Timothy F.
Josephs, Keith A.
T1906
T1715
M823
M606, M811,
T1515, T1530
Joshi, Abhinay D.
T1508
Jovic, Sofija
T1534
Ju, Y. Sungtaek
T1601
Juarez, Humberto
S230
Juncos, Jorge
S213
Kaida, Ken-ichi
T1733
Kalita, Jayantee
M1003, S104
Kalyanam, Janaki
S109
Kamakura, Keiko
T1733
Kanazawa, Ichiro
S201
Kang, Huicong
S110
Kano, Osamu
M812
Kaplan, Johanne T1719, T1721
Kappos, Ludwig T1707, T1708,
T1709
Karageorgiou, Clementine E.
T1729
Karagogeos, Domna
T1729
Karanam, Deepthi
M717
Karimi, Mehdi
S114
Karin, Ernstrom
S105
Karpf, Adam R.
M1008
Karunapuzha, Cherian A.
S210
Kasarda, Donald D.
M602
Kase, Carlos S.
S122
Kashouty, Rabih
M722, S133,
T1808
Kaspar, Brian
M802
Kassar, Darine
M720, T1607
Kass-Hout, Omar
S117
Kass-Hout, Tareq
S117
Katzir, Tami
M704
Kaubrys, Gintaras
M713
Kavanagh, Terrance J.
T1511
Kawabe, Kiyokazu
M812
Kawano, Yuji
T1706
Kawas, Claudia H. T1508, T1524
Ke, Qing
M831
Keegan, B. Mark
T1805
Keenan, Brendan T.
T1502
Kellerman, Don
T1616
Kells, Adrian P.
T1529
Kelly, John
T1620
Kelly, Kevin M.
M701
Khan, Omar
M702
Khanna, Ashwani
T1717
Kharlamov, Elena A.
M701
Khatri, Bhupendra O.
T1708
Khitrov, Greg
M824
Kiernan, Matthew
T1711
Kifayathulla, Liakath Ali M1004
Stage:
Page: 116
Lancaster, Eric
T1701
Lander, Cecilie
M1008
Lang, Anthony E.
S216
Lange, Dale J.
M824
Langford, Velma L. M814, M819
Larery, Angela
T1522
Lasarev, Michael R.
T1511
Lash, J.
S204, S209
Latov, Norman
M602
Lau, Helena
S122
Lazar, Ronald M.
M1403
Leblang, Spencer A. M618, M619
Ledoux, Kerry
M613
Lee, Christopher D.
M823
Lee, Jae-Hong
T1519
Lee, John D.
M615
Lee, Jong-Min
T1519
Lee, Joseph
T1512
Lee, Michael
M703
Lee, Seung-hun
S118
Lee, Szexian
T1802
Leep Hunderford, Andrea M826
Lees, Monica
M615
Lees, Peter
S213
Lehky, Tanya J.
M820
Leimgruber, Pierre P.
S116
Leone, Paola
S223
LeRoy, Robert F.
M714
Lessig, Stephanie
S205, T1507
Leverenz, James
S213
Levesque, Jessica
T1807
Levitt, Jacob
M831
Lewis, Mechelle M. S206, S212,
S234
Li, Chin-Shang
M703
Li, Jun
M803, M810, M813
Li, Sean S.
S115
Li, Wang
S202
Lieberman, Abraham S222, S227,
S235
Lieberman, Abraham N.
S218
Ligocki, Ann J.
T1736
Lin, Wen-Lang
T1515
Lin, Xiaoyang
S202
Lincoln, Sarah
T1503
Lindblom, Scott C. M814, M819
Linskey, Mark E.
T1804
Lipton, Richard
T1617
Lipton, Richard B. S233, T1608,
T1610, T1611, T1612,
T1613, T1615
Lipton, Stuart A.
T1509
Lirng, Jiing-Feng
T1605
Litchy, William J.
M1008
Litvan, Irene
S213
Liu, Kenneth C.
T1606
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Marsh, Elisabeth B. S125, S132
Marshall, Randolph S.
M1403
Marshall, Theresa
S404
Martens, William B.
M806
Martinez, Ashley
M702
Martinez, Jose A.
M1402
Martinez-Hernandez, Eugenia
T1701, T1716
Martinuzzi, Andrea
M611,
M1002, S237
Masaki, Kamal H.
S203
Masaki, Katsuhisa M1009, T1706
Masliah, Eliezer
M609
Mastorodemos, Vasileios
M603
Mateen, Farrah J.
S123
Matsushita, Takuya
M1009, T1706
Mattson, Mark P.
S103
Matveeva, Elena E.
M709
Matyushov, Alexei
M1201
Mayeux, Richard
T1512
McArthur, Justin C.
S407
Mcavoy, Mark P.
M601
McCague, Kevin
T1735
McCauley, Stephen R.
M1103
McCracken, Lindsey
T1716
McDermott, Michael P.
M806
McDonald, Jamie
T1713
McEvoy, Linda K.
T1514,
T1525
McGarry, Megan M621, M717,
T1738
McShea, Cindy
M713
Mehia-Santana, Helen
S225
Mehlenbacher, Adam
M1107
Mehta, Bijal
S117
Meira, Lisiane B.
T1511
Mejia, Nicte
S214
Melman, Tamar
T1802
Mendell, Jerry R.
M802
Mendoza, Jesus F.
T1907
Meng, Cheryl
S216
Meng, Xiangyi
T1707, T1708
Meola, Giovanni
M1002
Mer, Georges
M1008
Meschia, James F. M1204, S102,
S116
Metcalf, Nick
M601
Meyer, Brett C.
S131
Meysamie, A.
T1712
Michael, Benedict D.
T1903,
T1904
Middha, Sumit
M1008, T1503
Miglis, Mitchell G.
S302
Miller, Alistair
T1903, T1904
Miller, Eric R.
M701
Liu, Rui
S208
Liu, Shuo
S108
Liu, Xinyeu
S107
Liu, Yu
M1401
Llinas, Rafael H.
S125, S132
Lohrey, Anne K.
T1715
Lok, Edwin
T1802
Lombardi, Valter
T1506
Longbottom, Mary E.
S116
Longstreth, Jr., W.T.
T1513
Lowes, Linda P.
M802
Lu, Bo
M701
Luders, Hans
M620
Luke, Sothear
M1204
Luna, Jennie
M717, M721,
T1619
Lunn, J. Simon
M804
Lunn, John S.
M1005
Luo, Benyan
M831
Luthra, Indermohan
M816
Ma, Joyce
T1705
Ma, Li
T1503
Maccotta, Luigi
M708
Macura, Slobodan
T1703
Macura, Slobodan I.
T1727
Mada, Flicia
S129
Madjid, Keyvani
T1609
Maeda, Yoshiko
T1705
Maganti, Sombabu
M718
Magda, Sebastian
T1514
Maghzi, Amir Hadi
T1732
Mahadevan, Anita
M822
Mahajan, Shalini
M816
Mahaparn, Irisa
M609
Maharjan, Sooraj
T1503
Mailman, Richard B.
S234
Malhotra, Konark
S111
Malhotra, Manoj
T1735
Malik, Tafheem
S229
Malikova, Irina
T1713
Malow, Beth A.
S303
Malphrus, Kimberly G.
T1503
Manack, Aubrey N.
T1608,
T1612
Mandell, Daniel
M1105
Mandrekar, Jay M1202, M1203
Manivanh, Richard
T1506
Mannan, Ashraf U.
M1004
Mano, Toshiyuki
T1520
Mantese, Vito A.
S116
Manus, Neil D.
S224
Marchidann, Adrian
S133
Marder, Karen
S216
Marder, Karen S.
S225
Marek, Kenneth
S216
Marras, Connie
S213
Stage:
Page: 117
Miller, Michael L. T1516, T1517,
T1523, T1526
Miller, Timothy M.
M821
Millis, Scott
S129
Ming, Ming
M831
Mintun, Mark A.
T1508
Misra, Usha K.
M1003, S104
Mitchell, Amber N.
T1807
Mitchell, Braxton D.
S107
Mitchell, James F.
S107
Mittal, Balraj
M1003, S104
Mobley, William
M712
Moeller, Thomas
M1001
Mohammad, Yousef
S119
Mohammad, Yousef M.
S111
Mokin, Maxim
S117
Molina, Enrique
S230
Molinari, Anna L.
S224, S226,
S232
Molteni, Silvia
S237
Mondani, Massimo
S237
Monson, Nancy L.
T1736
Moodley, Manikum
M1302
Moomaw, Charles
S112
Moon, In Soo
S126
Moon, Yeseon P.
S101
Moore, Ryan P.
M609
Moretti, Paolo
M1103
Morgan, Kevin
T1503
Morris, John
T1901
Morrison, Richard S.
M1001
Morrow, Leslie
S301
Moseley, Brian D.
S403
Moshirzadeh, Sasan
T1718
Mosley, Thomas H.
T1505
Mowry, Ellen M.
T1713
Mozaffar, Tahseen
M805
Mtchedlishvili, Zakaria
M701
Muldowney, James
S303
Multani, Manpreet
M833
Murata, Kiyoko
M812
Murata, Miho
S201
Musumeci, Olimpia
M1002
Myers, Iliza
M810
Na, Duk L.
T1519
Nafissi, Shahriar
T1722
Nagahara, Alan
T1529
Nagata, Riya
M812
Nair, Asha A.
T1503
Nakamura, Yusaku
T1520
Nanakul, Rawi
T1521
Nance, Matthew
T1522
Nath, Avindra
S407
Naylor, David E.
M716
Neafsey, Edward
S405
Nehrebecky, Michele E.
M820
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Parent, Jack M.
M1401
Parisi, J.E.
S204, S209
Parisi, Joseph E. M1008, T1515,
T1530
Park, Yikyung
S208
Parker, Kathy
S301
Parkinson Study Group
S228
Pascual, Franchette
M703
Patel, Vivek
S140
Pati, Sandipan
M715, M1201
Paul, Joya
S119
Pavlakis, Pantelis P.
T1729
Paz Soldan, M Mateo
T1715
Paz Soldan, Mateo
S403
Pazdera, Ladislav
M724
Pearlman, Starr H.
T1613
Pease, Larry
M1101
Pease, Larry R.
T1703
Peavy, Guerry
T1507
Pedraza, Otto
T1503
Pejovic, Vojislav T1516, T1517,
T1523, T1526
Pelletier, Jean
T1708, T1713
Pelster, Michael W.
S224
Peltier, Amanda C.
M810
Peltz, Carrie B.
T1508, T1524
Perez, Veronica
M1403
Perhach, James
T1533
Pericak-Vance, Margaret
T1512
Peruch, Francesca
M1002
Pervez, Shahid
S229
Pestreich, Linda
T1735
Pestronk, Alan
M815, M821
Petacchi, Elisa
S237
Petersen, Bryan
T1606
Petersen, Ronald C.
M811,
T1503, T1515, T1530
Petrovitch, Helen
S203
Pettingill, Philippa
T1711
Pettingill, Rosie
T1711
Phibbs, Fenna T.
S226
Picard, Christophe
T1713
Piccoli, Sara
M611
Pickett, Erin J.
M613
Pikula, Aleksandra S122, T1504
Pillai, Jagan M1010, S205, S220
Pillai, Jagan A.
T1525
Piña-Crespo, Juan C.
T1509
Pirko, Istvan
T1703, T1715,
T1727
Plaitakis, Andreas
M603
Pleasure, David
T1705
Plow, Ela B.
T1527
Plow, Matthew A.
T1740
Polasek, Ozren
T1503
Pomerants, Polina
S401
Neil, William P.
Neiman, Eli S.
Newman-Toker, David E.
S105
M718
S118,
S139
Ng, Rowena
M608
Ng-Mak, Daisy S. T1613, T1614
Nguyen, Thanh N.
S122
Nguyen, Thuy
T1503
Nichols, Mindy S. M814, M819
Nicholson, Garth A.
M1008
Nilsson, Peter K.R.
M835
Nogalska, Anna
M807, M808,
M835
Nourian, A.
S114, T1732
Oakes, David
S216, S228
Oaklander, Anne Louise
M825
O’Connell, Jeffrey R.
S107
O’Connor, Paul
T1707
Ogawa, Go
T1733
Oger, Joel
T1702
Oh, Sang Su
M804
Oh, Seung Jun
T1519
Ohishi, Mitsuru
T1520
Olichney, John M.
T1521
O’Neill, Brian P.
T1805
O’Neill, Mifflin
M819
Onken, Mitch
M801
Opler, Mark
T1534
Oplinger, Heather
M819
Ottoboni, Linda
T1720
Ouyang, Bichun
S119
Owens, Michael J.
S301
Ozelius, Laurie J.
S233
Paccico, Thomas J.
M819
Pacut, Crystal
M1005
Paganini-Hill, Annlia
S108
Paik, Myunghee C.
S101
Pakdaman, Hosein
T1734
Pakdaman, Hossein S114, T1712,
T1722, T1723, T1731, T1732
Pakdaman, Hossien
T1718
Pakdaman, Reza T1712, T1723
Palmer, Valerie S.
T1511
Palusak, Ryan
T1503
Pan, Dengji
S110
Pan, Di
S222, S227, S235
Pan, Yue S.
T1908
Pandya, Dipak
T1737
Pandya, Dipak P. M621, M717,
M721, T1619, T1738
Pandya, Shree
M806
Pankratz, V. Shane
T1503
Panou, Theodora
M603
Papadaki, Efrosyni
M603
Paparella, Gabriella
M611,
M1002
Stage:
Page: 118
Pontecorvo, Michael J.
T1508
Pope, Daniel L.W.
M601
Prabhakaran, Shyam
S119
Pracilio, Valerie P.
T1614
Prakash, Neal
T1601
Presti, Michael F.
S403
Prokop, Stefan
M835
Rabinstein, Alejandro A. M1202,
M1203, S128, T1714
Race, David S.
M612
Rademakers, R.
S204, S209
Rademakers, Rosa
S207
Radlinska, Basia
T1510
Radue, Ernst-Wilhelm
T1707
Rahimian, E.
T1723
Rai, Shesh N.
S213
Rajamani, Kumar
S129
Rajput, Alex H.
S217
Rajput, Ali H.
S217
Rajput, Michele L.
S217
Raman, Rema
S105
Rametta, Mark
T1702
Ramos-Crawford, Ana-Luisa
T1511
Ramsey-Williams, Vicki
S404
Rangaraju, Srikant
T1902
Ranjan, Tulika
T1808
Rao, Sambasiva
T1719
Raol, Yogendra H.
M705
Rashid, Saifur
M620
Rasmuss, Brett
M712
Ravina, Bernard
S216
Raymond, Deborah
S233
Reda, Haatem
S403
Reder, Anthony T.
T1702
Reed, Michael
T1613
Reed, Michael L. T1608, T1610,
T1611
Reeves-Tyer, Patricia
M702
Reich, Stephen
S213
Reiman, Eric M.
T1502
Reitz, Christiane
T1512
Reminick, Jason I.
S402
Ren, Xuefeng
T1511
Rengachary, Jennifer
M601
Renterı́a Palomo, Ana A. M617
Riley, David
S213
Ritchie, James C.
S301
Rivera, Susan M.
T1521
Rizzo, Matthew
M615
Roberts, Bruce
T1719,
T1721
Robinson, Karen A.
S118
Rodriguez, Alcibiades
S302
Rodriguez, Ildefonso
T1907
Rodriguez, Jeronimo
T1907
118
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Santiago, Anthony
S218, S222,
S227, S235
Sanz-Blasco, Sara
T1509
Sarkar, Korak
M1102
Sarwar, Aliya
S215
Sato, Susumu
M702
Sauerbeck, Laura
S112
Saunders-Pullman, Rachel S233
Scarmeas, Nicholas
S225
Schiff, Nicholas C.
M1104
Schirrmacher, Ralf
T1510
Schneck, Michael J.
S405
Schneider, Andrea
T1521
Schneider, Julie A.
T1502
Schofield, Lesley
T1735
Schor, Nina F.
T1803
Schretlen, David J.
M613
Schwarzchild, Michael
S216
Schweitzer, K.J.
S204, S209
Scoglio, Nicholas J.
S402
Scott, Bonnie M.
T1522
Scott, James N.
M1103
Scott, Thomas
T1726
Sealfon, Stuart C.
M824
Sen, Saurav
M721
Sen, Sourav
T1619
Sen, Suman
S206, S212
Sennett, Cary
T1614
Seo, Sang Won
T1519
Seritan, Andreea
T1521
Serrano, Daniel
T1612, T1613
Seshadri, Sudha
T1504
Severy, Peter
T1719
Seyal, Masud
M703
Shaffer, Michel L.
S212
Shaffer, Michele L.
S206, S234
Shah, Amol
T1905
Shah, Anish
M721, T1619
Shah, Umang
M719
Shahbazi, Mona
M824
Shahbegi, Said
S114
Shahbeigi, Saeed
T1734
Shahkarami, Mohammad Amir
T1722
Shahlaie, Kia
M1102
Shamim, Ejaz
M602
Shankar, S.K.
M822
Shankara, Srinivas
T1719
Sharpe, James A. M607, T1621
Sharrett, A. Richey
T1505
Sheikh, Kazim
M809
Shepherd, Cassandra
S213
Shibata, Dean K.
T1505
Shijie, Song
S202
Shimizu, Kanako
S120
Shin, Robert K.
M723
Rodriguez, Moses
M1101,
T1703, T1727
Rodrı́guez Leyva, Ildefonso M617
Roeber, S.
S204, S209
Rogaeva, Ekaterina
T1512
Roger, Elaine
T1713
Romero, Jose R.
S122
Rosales, Xiomara Q.
M802
Rose, Kathryn M.
T1505
Rosenbaum, Anna V.
M723
Rosenberg, Michael
S134
Rosenfeld, William
M713
Ross, Owen A.
S207
Rossetto, Mariagiovanna M1002
Rostami, Abdolmohamad T1725
Rothman, Brian
T1534
Rothner, A.D.
M1302
Rothrock, John F.S113, T1602,
T1609
Rothstein, Jeffrey
M821
Roubenoff, Ronenn
T1504
Rounds, William H.
T1736
Rowley, Christopher N.
T1503
Royal, III, Walter
T1717
Rudan, Igor
T1503
Ruhoy, Ilene
M1304
Rumbaugh, Jeffrey A.
T1902
Rundek, Tatjana
S101
Russek, Shelley J.
M705
Russell, James W.
M801
Russo, Priscilla
M819
Rye, David B.
S301
Saber Tehrani, Ali S. S118, S139
Sabouri, Amir H.
T1905
Sacco, Ralph L.
S101
Sadzewicz, Lisa K.
S107
Safavi, Farinaz
T1725
Sahenk, Zarife
M802
Sahraian, Mohammad
T1732
Sahraian, Mohammad Ali
T1712, T1723
Sakowski, Stacey A.
M804
Salami, Shiva
T1722
Salim, Sumaiya
S137
Salins, Naomi
S218, S222,
S227, S235
Salmon, David P.
T1525
Salowich-Palm, Leeza
S129
Salvador, Santamaria
S230
Samadpour, Reza
T1731
Samson, Leona D.
T1511
San Luciano, Marta
S233
Sanchez-Ramos, Juan
S202
Sancho, Jose
T1719
Sando, Sigrid B.
T1503
Sanjak, Mohammed S.
M819
Stage:
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Shiramizu, Bruce
S407
Shojaee, Maziar
T1731
Shojaei, Maziar
T1718
Shoulson, Ira
S216
Shprecher, David
S213
Shtilbans, Alexander
M824
Shulman, Gordon L.
M601
Shulman, Joshua M.
T1502
Shuster, E.A.
S209
Shy, Michael E.
M803
Siddiqui, Fazeel
S140
Siders, William
T1719, T1721
Siemionow, Vlodek
T1527
Silber, Michael H.
M811
Silberstein, Stephen
T1603,
T1614
Silbert, Lisa
T1532
Sillau, Stefan
M616
Silva, Jessica
M613
Simon, Mariella
M1008
Simos, Panagiotis G.
M603
Simpson, Ericka
M821
Simpson, Ericka P.
M832,
T1728
Simuni, Tanya
S228
Singh, Anuradha
S302
Singleton, Robinson J.
T1604
Skrap, Miran
S237
Slevin, John T.
M709
Sloan, Michael
S130, S135
Smith, David I.
M1008
Smith, Glenn E.
M1008
Smith, Gordon A.
T1604
Smith, Jonathan H.
S403
Smith, Richard
M821
Smith-Hammond, Carol M1107
Snider, Barbara J.
S406
Snyder, Abraham Z.
M601
So, Norman K.
M711
Sofroniew, Michael
T1704
Solomon, Tom
T1903, T1904
Somarajan, Bindu I.
M1003,
S104
Song, Yanna
S226, S303
Sorenson, Eric
M826
Sorenson, Eric J.
M817
Soucy, Jean-Paul
T1510
Spence, Rory
T1704
Spencer, Peter S.
T1511
St. George-Hyslop, Peter T1512
St. Louis, Erik K.
M811
Standaert, David
S213
Stankiewicz, James M.
S408
Stanley, Kaili M.
S233
Statland, Jeffrey M.
M806
STEADY PD Investigators S228
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Toscano, Antonio
Tosches, William
Tramontana, Michael G.
Tran, Dong
Traynor, Bryan J.
Trenerry, Max R.
Trotti, Lynn Marie
Tselis, A.
Tufail, Yusuf
M715,
Turkel, Catherine C.
M1002
M1105
S232
T1502
M820
M606
S301
S209
M1201
T1608,
T1612
Turner, Travis H.
S219
Tuszynski, Mark H.
T1529
Tyler, William J. M715, M1201
Ueda, Masami
M818
Uitti, Ryan
S213
Umaiorubahan,
Meenakshisundaram
S121
Umeda, Elizabeth
T1704
Uyehara-Lock, Jane H.
S203
Vallurupalli, Srikanth
S140
Van Gerpen, J.A.
S204, S209
Van Keulen, Virginia
M1101
Van Liew, Charles
S205, S220,
T1507
Van Loveren, Harry R.
S130, S135
Van Ness, Paul C.
M711
Vanaman, Thomas C.
M709
Vannorsdall, Tracy D.
M613
Varon, Sepideh F.
T1612
Vasan, Ramachandran S. T1504
Vaughan, Douglas E.
S303
Vazquez, Gilberto
T1907
Vecera, Shaun
M615
Velazquez-Rodriguez,
Yadira
M1205
Veloski, Jon
S223
Venkatasubramaniam,
Shankar
S121
Verghese, Joe
T1518
Verma, Aparajitha K.
M832
Vestri, Alec
M611
Victor, Jonathan D.
M1104
Vieira, Julio R.
S101
Vigo, Carmen
T1506
Villoslada, Pablo
T1713
Vincent, Angela
T1711
Viollet-Callendret, Laurence
M802
Voeks, Jenifer H.
S102, S116
von Rosenstiel, Philipp
T1707
Voskuhl, Rhonda
T1704
Vysata, Oldrich
M724
Wada, Keiji
S201
Wagner, Daymond
S206, S212
Stebbins, Glenn T.
S211, S231
Stern, Barney J.
S107
Stewart, Anna
T1903, T1904
Stine, Oscar C.
S107
Stites, Tracy
T1708
Stouter, Josephine
T1522
Strongosky, Audrey
M1007
Struck, Peter
M834
Strutt, Adriana M.
T1522
Sullivan, Robert S.
T1511
Sundal, C.
S204, S209
Sundar, Kaushik
S121
Sung, Kyongje
M613
Sura, Ankit
M801
Suter, Ueli
M803
Suzuki, Seiko
M818
Swanson, Kenneth D.
T1802
Tabasi, M.
S114
Tabatabae, Al
S114
Takahashi, Masaki
S201
Talantova, Maria V.
T1509
Tallon, Luke J.
S107
Tan, Caroline
M602
Tanaka, Ichiro
T1520
Tang, Dejun
T1709
Tang, Zhouping
S110
Tanner, Caroline M. S203, S216
Tawil, Rabi
M806
Tayal, Ashis
S124
Taylor, Glyn
T1616
Teich, Douglas L.
T1622
Tenderini, Erika
M1002
Tennen, Howard
T1615
Tepper, Stewart
T1603, T1617
Teshome, Mengesha
T1901
Thant, Minn
S215
Thawani, Sujata
S302
Theodore, William H.
M702
Theriot, Jeremy J.
T1601
Thiel, Alexander
T1510
Thomas, Jewell
T1901
Thomas, Tracy
T1616
Tilluckdharry, Natasha
M621, T1738
Timaran, Carlos H.
S116
Ting, Jess
M824
Title, Wallace
S224
Titulaer, Maarten J.
T1701,
T1716
Tobias, Kathy
T1735
Tocco, Michael
T1516, T1517,
T1523, T1526
Todd, Wesley M.
M710
Toga, Arthur W.
T1601
Tokuyama, Yoshiaki
S120
Toro, Camilo
M820
Stage:
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Wagner, Jenee
M1006
Wagner, Kathryn R.
M806
Wakayama, Yoshihiro
M829
Walgren, Kristy
M819
Walker, Linsey M.
M704
Wallace, Douglas C.
M1008
Wallin, Mitchell T.
T1730
Wang, Aijun
T1724
Wang, Chunyang
M719
Wang, Jay-Ming
S130, S135
Wang, Lily
S226, S303
Wang, Min
T1603, T1617
Wang, Morgan
S130
Wang, Shuu-Jiun
T1605
Wang, Wei
S110
Wang, Yen-Feng
T1605
Ward, Amber L.
M814, M819
Ward, Christopher J.
M1008
Warrington, Arthur
M1101
Warrington, Arthur E.
T1703
Watanabe, Osamu
T1711
Watanabe, Shoko
S201
Waters, Patrick
T1711
Watson, James
M826
Watson, Sam
S129
Waubant, Emmanuelle
T1713
Webber, Christine A.
M1402
Webster, Ross
S203
Weibelt, Silvia M.
T1602
Weihl, Chris
M815
Weiner, Howard
T1720
Weiss, John H.
M805
Werner, Perla
T1535
Westwood, Andrew J.
T1504
White, Lon R.
S203
Whiteheart, Sidney W.
M709
Whitfield-Gabrieli, Susan M704
Whitwell, Jennifer
M606
Whitwell, Jennifer L.
T1530
Wicklund, Meredith
S403
Wider, C.
S204, S209
Wiggs, Edythe
M702
Wijdicks, Eelco F.M.
M1202,
M1203, S128
Wilde, Elisabeth A.
M1103
William, Gahl
M820
Williams, Nicole M.
M814,
M819
Wilson, Karen R.
S130, S135
Winblade Nairn, Natalie T1724
Winner, Paul
T1603
Wojna, Valerie
S407
Wolf, Philip A.
T1504
Woltjer, Randy
T1532
Wong, Agnes M.
T1621
Wong, Amy
S109
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Xu, Xiaohua
M1101
Xue, YuanYuan
T1728
Yamanishi, Hiromitch
M1008
Yamashita, Toshihide
T1520
Yan, Qing
M803, M813
Yanagihara, Keiko
T1520
Yang, Fan
S108
Yang, Lauice
S221
Yanik, Brandon M.
T1604
Yavorsky, Christian
T1534
Yin, Hong Z.
M805
Yonekawa, Tomomi
M1009,
T1706
Yono, Noor M722, S133, T1808
York, Michele K.
T1522
Yoshihiro, Anna
M715, M1201
Yoshii, Yasuhiro
M812
Yoshimura, Satoshi M1009, T1706
You, Xiaojun
T1726
Younger, David S.
M827
Wong, Eric T.
T1622, T1802
Wong, Sarah
T1701
Wood, Blair
T1801
Woodruff, B.K.
S204, S209
Worrall, Bradford B.
S115
Wozniak, Marcella A.
S107
Wright, Alan
T1503
Wright, Brent
M1101
Wright, Kathryn A.
M819
Wszolek, Z.K.
S204, S209
Wszolek, Zbigniew
T1503
Wszolek, Zbigniew K.
M1007,
S207
Wu, Yanhong
M1008
Wyant, Alexandria
T1527
Wymbs, Nicholas
M604
Xiang, Diane
T1736
Xu, Feng
S110
Xu, Jian
T1701
Xu, Kui
M620
Stage:
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Younkin, Curtis S.
Younkin, Steven G.
Yu, Alexander
Yu, Chuanhui
Yue, Guang H.
Yung, Raymond
Zarbl, Helmut
Zerafati, Gazelle
Zghouzi, Mohamed
Zhang, Gang
Zhang, Xuebao
Zhang-Auberson, Lixin
Zhou, Yun
Zhu, Suiqiang
Zimmerman, Earl
Zinn, Kristi
Zivadinov, Robert
Zochodne, Douglas W.
Zou, Fanggeng
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T1503
T1503
T1622
S108
T1527
M1005
T1511
S223
S119
M809
M803
T1707,
T1709
S118
S110
T1807
M601
S117
M1402
T1503
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WIP AUTHOR INDEX
Fanin, Marina
M838
Federici, Thais
M840
Feldman, Eva
M840
Ferrucci, Luigi
T1539
Florez, Carlos M.
M729
Gandy, Sam
T1538
Gangadharan, Beena
T1743
Garg, Rajeev
S143
Glabe, Charles
T1538
Glass, Jonathan D.
M840
Goate, Alison
T1541
Gonzalez, R. G.
M1206
Govindarajan, Raghav
T1747
Grachev, Igor D.
S240
Green, Mark W.
T1623
Grisham, Mathew B.
T1746
Grossman, Murray
T1542
Guevara, Jorge
M730
Guevara, Patricia
M730
Guo, Jiasong
M839
Guo, Shuling
M841
Hajsadeghi, Fereshteh
T1540
Havrdova, Eva
T1741
Hawi, Amale
M1011
Hazel, Tom
M840
Heo, Sung Hyuk
S141
Hogarth, Penelope
S240
Horakova, Dana
T1741
Huber, Vincent J.
T1744
Hughes, Steve
M841
Irwin, David J.
T1542
Iwata, Atsushi
M836
Jacobson, Sven
M1206
Johe, Karl
M840
John, Sayona
S143
Jung-Henson, Lily K.
T1743
Kalincik, Tomas
T1741
Karlsson, Fridrik
T1746
Kasten, Tom
T1541
Kelly, Crystal
M840
Keogh, Bart P.
T1743
Kieburtz, Karl
S239
Kim, Hye Ok
S141
Kim, Soong Ho
T1538
Kimberly, W. T.
M1206
Krasensky, Jan
T1741
Kraut, Michael
T1539
Kubota, Akatsuki
M836
Kucheruck, Olena
M1011
Kwee, Ingrid L.
T1744
Laguerre, Tatanisha
S240
Lam, Ann
M622, M728
Lee, Virginia M.Y.
T1542
Abdemalik, Peter
Ackermann, Elizabeth
Ahmahi, Naser
Albers, Gregory W.
Albert, Todd
Alvarado, Luis
Angelini, Corrado I.
Arnold, Steven E.
Askanas, Valerie
Avila-Costa, Maria Rosa
Babaei, Hormoz
Bai, Dongsheng
Barlow, Carrolee
Bateman, Randall J.
Beason-Held, Lori
Benson, Merrill
Benzinger, Tammie
Berdichevsky, Yevgeny
Bettermann, Kerstin
Bhattachuria, Arun
Booten, Sheri
Bordeau, Jane
Boulis, Nicholas
Bowen, James D.
Brigatti, Karlla W.
Brookler, Kenneth H.
Cacciottolo, Mafalda
Carlen, Peter L.
Cevette, Michael J.
Chakraverty, Sumi
Chang, Dae-il
Chaudhry, Zeshan A.
Cocco, Daniela
Cohen, Todd
Connors, James
D’Agostino, Carla
Dambinova, Svetlana
Davis, Stephen M.
Delgado-Escueta, Antonio
M729
M841
T1540
M1206
T1538
M841
M838
T1542
M837
M730
T1540
M730
T1538
T1541
T1539
M841
T1541
M727
S142
T1623
M841
M840
M840
T1743
M1011
T1745
M837
M729
T1745
T1541
S141
M1206
T1745
T1542
S144
M837
S142
M1206
V.
M730
Deutsch, Eric C.
M1011
Dhir, Ashish
M731
Donnan, Geoffrey A.
M1206
Duron, Reyna M.
M730
Eberly, Shirley
S238
Ebers, George C. M1012, M1013
Ebrahimi, Ramin
T1540
Ehrlich, Michelle E.
T1538
Elbert, Don
T1541
Elisman, Mark
M839
Elm, Jordan J.
M1206
Engel, W.King
M837
Fague, Scot
T1541
Lee, Viven
S143, S144
Leinonen, Mika
S239
Li, Jun
M839
Lian, Gewei
M726
Lovestone, Simon
T1539
Lynch, David R.
M1011
Machado-Salas, Jesus
M730
Mail, Michelle
M727
Malhotra, Konark
S143, S144
Maravilla, Kenneth R.
T1743
Marek, Kenneth
S238
Marino, Julia
T1742
Martinez, Nicholas E.
T1746
Matthews, Ian R.
T1742
Mawuenyega, Kwasi
T1541
Mayadev, Angeli
T1743
McIntyre, Cameron
M839
Miller, Guy
M1011
Minagar, Alireza
T1746
Monia, Brett
M841
Morris, John C.
T1541
Mowry, Ellen M.
T1742
Nakada, Tsutomu
T1744
Nakayama, Yukihiro
T1744
Nalls, Michael
T1539
Nascimbeni, Annachiara
M838
Nissinen, Helena
S239
Nogalska, Anna
M837
Nutt, John G
S240
Oakes, David
S238
Oakley, Sarah
T1745
Ohayon, Elan L.
M622, M728
Olanow, C. Warren
S239
Omura, Seiichi
T1746
Ovid, Vitaliy
T1541
Park, Byung S.
S240
Patterson, Bruce
T1541
Poewe, Werner
S239
Polak, Meraida
M840
Potter, Rachel E.
T1541
Prabhakaran, Shyam S143, S144
Pradhan, Gaurav
T1745
Rajappa, Sivakumar M.
M725
Ramagopalan, Sreeram V.
M1012, M1013
Rascol, Olivier
S239
Ravina, Bernard M.
S238
Repovic, Pavle
T1743
Resnick, Susan
T1539
Rioux, Patrice
M1011
Rizzuto, Daniel S.
T1743
Rogawski, Michael A.
M731
Ross, Mark A.
T1745
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Rutkove, Seward
Salgado, Efrain
Sandri, Marco
Saponjian, Yero
Sato, Fumitaka
Schapira, Anthony
Sciascia, Thomas
Seidl, Zdenek
Sejnowski, Terrence J.
Sheen, Volney
Sheth, Kevin N.
Shimizu, Jun
Shoulson, Ira
Shrader, William D.
Sigurdson, Wendy
Singleton, Andrew
Siwkowski, Andrew
Smith, Benn E.
Sosinsky, Gina
Spitz, John T.
Staley, Kevin J.
Steele, John W.
Stepanek, Jan
Stern, Barney J.
Stocchi, Fabrizio
Suter, Ueli
Suzuki, Yuji
Tanaka, Miyabi
Temes, Richard
Tendolkar, Amol
Thambisetty, Madhav
Treuner, Kai
Trojanowski, John Q.
Troyer, Matthew D.
Tsuji, Shoji
Tsunoda, Ikuo
M840
T1747
M838
M727
T1746
S239
M1011
T1741
M728
M726
M1206
M836
S238
M1011
T1541
T1539
M841
T1745
M839
M732
M727
T1538
T1745
M1206
S239
M839
T1744
M730
S143
S240
T1539
T1538
T1542
S240
M836
T1746
Stage:
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Underhill, Hunter R.
T1743
Vaneckova, Manuela
T1741
Venkatesan, Srinivasan A. M725
Vinayagasundaram, Uma T1742
Wagner, Lindsay
T1745
Wang, Lily
M839
Waubant, Emmanuelle
T1742
Willi, Steve M.
M1011
Wilson, Robert B.
M1011
Xie, Sharon X.
T1542
Xuan, Fengjuan
S240
Yan, Qing
M839
Yarasheski, Kevin
T1541
Yarnykh, Vasily L.
T1743
Yoo, Albert J.
M1206
Zapala, David A.
T1745
Zhang, Jane
M729
Zhang, Liang
M729
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ABSTRACT SUBJECT INDEX
A
Cortical Dysplasia (CD)
M704
Cytokines M1005, S202, T1717, T1725, T1802, T1908
Cytotoxicity
T1509, T1737, T1902
Acute Cerebral Ischemia M721, S102, S105, S109, S116,
S118, S120, S121, S128, S136, T1619
Acute Ischemic Stroke
S102, S103, S105, S109, S114,
S116, S117, S120, S122, S124, S125, S127,
S129, S130, S131, S132, S135
Acute Neuropathies M818, M822, M823, M825, M827,
M830, T1733
Affective Functioning
M608, M617, M819, S203
Alzheimer’s Disease (AD) M616, M808, M1001, T1501,
T1502, T1503, T1504, T1506, T1508, T1509,
T1512, T1514, T1516, T1517, T1518, T1521,
T1522, T1523, T1524, T1525, T1526, T1528,
T1529, T1531, T1532, T1533, T1534, T1535, T1901
Amyotrophic Lateral Sclerosis (ALS)
M804, M805,
M807, M813, M817, M821, M824,
M829, M1005
Antibodies M602, M809, M818, M822, M825, M1101,
S202, T1506, T1701, T1703, T1706, T1711,
T1716, T1719, T1721, T1729, T1733,
T1736, T1739, T1801, T1908
Apoptotic Cell Death
T1537, T1801, T1803
Astrocytes
M1004, T1506, T1509, T1704,
T1705, T1710
Atherosclerosis
M1003
Attention-Deficit/Hyperactivity Disorder M610, M614,
M617, M618, M619
Autoimmune Demyelination
M1105, M1303, T1704,
T1713, T1729, T1731, T1732, T1734, T1738
D
Deep Brain Stimulation
M1201, S215, S232, S237
Delirium
T1536
Dementia
M621, M820, M1008, S201, S219, T1504,
T1510, T1518, T1519, T1521, T1521, T1522,
T1525, T1531, T1536
Demyelination
M822, T1705, T1712, T1713, T1714,
T1715, T1718, T1722, T1723, T1727
Diabetic Neuropathy M801, M810, M822, M826, T1604
Down Syndrome (DS)
M712
Drosophila
M1006, T1502
E
Epilepsy
M620, M701, M702, M703, M704, M707,
M708, M710, M711, M713, M714, M715,
M716, M717, M718, M719, M722, S302, T1906
Epilepsy Model
M701, M705, M706, M707, M709,
M712, M716, M720
Epileptic Seizures
M621, M701, M711, M716, M717,
M719, M721, M722, M723, M1202, M1203
Epileptogenesis
M618, M619, M701, M705, M707,
M709, M712, M716, M718
Experimental Autoimmune Encephalomyelitis
(EAE)
T1704, T1705, T1725
B
Brain Imaging
M601, M606, M704, M719, M1103,
M1104, M1301, S117, S119, S125, S128,
S132, S140, S204, S212, T1510, T1513, T1514,
T1518, T1525, T1527, T1532, T1601, T1619,
T1714, T1715, T1804, T1906, T1908
Brain Ischemia
M605, M1201, M1204, S103, S106,
S114, S115, S126, T1519
Brain Mapping
M601, M604, M605, M609, M708,
M724, S109, T1527, T1601
F
fMRI
Frontotemporal Dementia (FTD)
M604, M708
M612, M819,
T1515, T1530
G
Gene Expression
M705, M707, M824, M829, M1003,
M1004, S104, S115, T1503, T1511, T1512,
T1520, T1720, T1804
Gene Regulation M705, M821, M1001, M1004, M1008
Gene Therapy
S201, T1529
Genetic Mutations M709, M803, M813, M815, M1002,
M1004, M1006, M1007, M1008, S107,
S115, S201, S207, S233, T1502, T1512,
T1520, T1713, T1736
Gilles de la Tourette Syndrome (GTS)
S231
Glioblastoma Multiforme T1804, T1806, T1806, T1808
C
Cell Death
M717, M812, M1106, S114, T1528,
T1537, T1801
Cerebrospinal Fluid (CSF)
M821, S134, S301, T1501,
T1514, T1738, T1802, T1903, T1904, T1907, T1908
Chronic Inflammatory Demyelinating
Polyradiculoneuropathy (CIDP)
T1728, T1729
Cognitive and Neurobehavioral Status
Examination (CNS)
M607, M613, M617
Cognitive Dysfunction
M601, M603, M604, M605,
M606, M609, M611, M612, M613, M620,
M621, M706, M712, M720, M1006, S204,
S205, S206, S209, S211, S214, S219, S407,
T1507, T1520, T1522, T1536, T1901
Cognitive Outcomes M603, M613, M615, M618, M619,
M702, M819, M1103, S205, S212, S301, S401,
S406, T1507, T1508, T1513, T1524, T1534, T1738
Consciousness
M721, M1104, S110, S140, S301
H
Headache
M825, T1601, T1603, T1605, T1606, T1607,
T1608, T1610, T1611, T1612, T1613, T1614,
T1615, T1616, T1617, T1618, T1619
HIV
S407, T1901, T1902, T1905
Huntington’s Disease
M1010, S201, S205, S210, S220
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I
O
Interferon Treatments
T1702, T1722, T1724
Interferons
M1001, T1722, T1726
Intracerebral Haemorrhage (ICH)
M1003, S104, S105,
S110, S111, S113, S117, S124, S125,
S128, S132, S136
Ischemia
S124, S126, S133
Oligodendrocyte
T1705, T1710
Other
M608, M608, M608, M616, M617, M618,
M619, M710, M715, M722, M723, M723,
M724, M806, M809, M811, M811, M820,
M823, M823, M824, M825, M826, M834,
M1005, M1007, M1102, M1102, M1102,
M1104, M1107, M1107, M1205, M1301,
M1302, M1303, M1304, M1401, M1402,
M1402, M1402, S101, S102, S110, S112, S113,
S116, S118, S118, S123, S125, S128, S129, S132,
S133, S133, S134, S138, S139, S139, S139, S140,
S140, S202, S210, S210, S214, S217, S217, S217,
S223, S223, S224, S224, S224, S224, S225, S226,
S226, S229, S232, S236, S236, S236, S401, S401,
S403, S404, S405, S405, S408, T1501, T1501,
T1503, T1504, T1508, T1515, T1537, T1537,
T1602, T1606, T1607, T1609, T1619, T1620,
T1622, T1701, T1701, T1714, T1716, T1716,
T1716, T1724, T1725, T1727, T1730, T1739,
T1739, T1802, T1803, T1805, T1805, T1805,
T1805, T1807, T1807, T1807, T1807, T1808,
T1808, T1808, T1809, T1809, T1809, T1902,
T1903, T1903, T1904, T1906, T1906, T1907, T1907
L
L-Dopa Therapy
Levodopa
Lewy Bodies (LB)
Limbic Encephalitis
S215
S232, S236
S207
T1701
M
Magnetic Resonance Imaging (MRI)
M612, M719,
M721, M828, M1301, S106, S204, S212, S234,
T1504, T1505, T1514, T1519, T1521, T1525,
T1530, T1532, T1605, T1726, T1727,
T1737, T1738
Magnetic Resonance Spectroscopy (H-MRS)
M812
Migraine
S136, T1601, T1602, T1603, T1608, T1609,
T1610, T1611, T1612, T1613, T1614,
T1615, T1616, T1617, T1618, T1620
Morvan Syndrome
T1711
Motoneuron Disease
M804, M805, M812, M813,
M814, M817, M819, M820, M832,
M833, M1002, T1511
Multiple Sclerosis (MS) M603, M1009, M1105, T1621,
T1702, T1703, T1704, T1707, T1708,
T1709, T1710, T1712, T1713, T1715, T1717,
T1718, T1719, T1720, T1721, T1722, T1723,
T1724, T1725, T1726, T1727, T1729, T1730,
T1731, T1732, T1734, T1735, T1736,
T1737, T1740
Muscular Dystrophies
M806, M807
Myelin
M803
Myelin Oligodendrocyte Glycoprotein (MOG)
T1737
Myoclonus
M621, M717
Myopathic Syndrome
M815, M816
Myopathy
M802, M806, M807, M808, M811,
M815, M816, M829, M835
P
Parkinson’s Disease (PD) M604, S202, S203, S206, S207,
S208, S211, S212, S214, S215, S216, S217,
S218, S219, S221, S222, S225, S226, S227,
S228, S232, S233, S234, S235, T1511, T1535
Periodic Paralysis
M831
PET
M702, T1508, T1510, T1519, T1901
Pharmacokinetics
M710, S230, T1724
R
Reactive Oxygen Species (ROS)
M801, T1803
S
Sleep Disorders and Circadian Rhythm S301, S302, S303
Stroke
M601, M1003, M1101, M1204, M1403, S101,
S102, S103, S105, S107, S108, S109, S110, S115,
S116, S122, S123, S124, S127, S130, S131,
S133, S135, S137, S402, T1510, T1621
Subarachnoid Hemorrhage
M1102, M1204, S119
Subthalamic Nucleus (STN) Stimulation
S215
N
Neurodegenerative Diseases M805, M808, M812, M813,
M817, M820, M821, M832, M1005, M1007,
M1008, M1101, S203, S204, S207, S209,
S210, S213, S214, S220, S223, S229, S234,
T1503, T1511, T1515, T1530, T1532, T1740
Neurofibromatosis Type1
M1302, T1806
Neurogenesis
M803, M1401
Neuroleptics (NLs)
M611, S229
Neuromyelitis Optica (NMO)
M1009, T1706, T1739
Neuroprotection
M801, M803, M829, S114,
S229, T1509, T1529, T1902
Neurotrophin
T1529, T1803
T
Tau
M808, M1007, T1502, T1530
Temporal Lobe Epilepsy (TLE)
M702, M708,
M709, M711
Triptans
T1613, T1614, T1618
V
Visual Cortex
Visual Function
M607
M607, M615, M1107, T1536, T1806
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WIP SUBJECT INDEX
L
A
Acute Cerebral Ischemia
Acute Ischemic Stroke
Affective Functioning
Alzheimer’s Disease (AD)
Lafora Disease
L-Dopa Therapy
S142
M1206, S142
M622, T1745
M730, T1538, T1539,
T1540, T1541, T1542
T1541
T1744
S141
T1742
Alzheimer’s Disease Mutants
Astrocytes
Atherosclerosis
Autoimmune Demyelination
M
Magnetic Resonance Imaging (MRI)
Migraine
Multiple Sclerosis (MS)
Muscular Dystrophies
Myelin
Myoclonus
Myopathy
B
Brain Imaging
M622, M1206, S143, S144, S238,
T1539, T1741, T1743, T1744
M1206, S142
M622, T1745
M727, M729, T1539, T1541
Brain Ischemia
Brain Mapping
Brain Metabolism
M730
S240
M1206, T1741,
T1743
T1623
M1012, T1741, T1742, T1743
M838
M839, T1745
M730
M836, M837, M838
N
Neurodegenerative Diseases
M840, M841, T1538,
T1542
Neurogenesis
M726, M839, T1538, T1744
Neuromyelitis Optica (NMO)
T1742
Neuroprotection
M727, M1011
C
Cell Death
Cerebrospinal Fluid (CSF)
Cognitive Outcomes
M728, M1011
T1541
M728, S238
O
D
Other
Dementia
Demyelination
T1538
M839, T1741, T1742, T1743
M622, M725, M731, M836, M837, M840,
M841, M1011, M1012, M1013, S141, S239,
S240, T1540, T1623, T1745
P
E
Epilepsy
Epilepsy Model
Epileptic Seizures
Epileptogenesis
Parkinson’s Disease (PD)
PET
Pharmacokinetics
Pompe Disease
M726, M727, M731, M732
M728, M729, M730, M731
M729
M727, M728, M729
S238, S239, S240
T1539, T1744
M841, S240
M838
R
F
Frontotemporal Dementia (FTD)
Reactive Oxygen Species (ROS)
T1542
M1011
S
G
Gene Expression
Gene Regulation
Genetic Mutations
Single Photon Emission Computed Tomography S238
Stroke
S141, S142, S143, S144
Subarachnoid Hemorrhage
S143, S144
M838, S141
M726, M1013
M726, M839, M841
H
T
Headache
Tau
S143, S144, T1623
M837, T1542
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