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Outline - Intention
Cerebellar disorders in children –
clinical features
Eugen Boltshauser
Pediatric Neurology - Emeritus
Children’s Hospital Zürich Switzerland
• NOT to present «mainstream» signs of cerebellar dysfunction
• Provide hints to less common presentation of
cerebellar malformations – degenerations
• Comment on presentation of
non-progressive congenital ataxia
ESMRN Meeting 2015 Porto
Hints to cerebellar malformations - degenerations
• Respiratory abnormalities
• Horizontal head titubation
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Stereotyped side-to-side head shaking
Horizontal gaze palsy
Bilateral parietal alopecia
Ocular motor apraxia
Telangiectasias
Supranuclear vertical gaze palsy
Respiratory abnormalities
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Episodes of tachypnea (apnea)
Awake state > asleep
No respiratory distress, no cynosis
Spontaneous improvement with increasing age
 Think Joubert syndrome
prevalence ~ 40% in neonatal period
DD Episodic hyperpnea seen in other syndromes
– distinction not problematic
Lighthouse in Denmark
[ e.g. Rett, Pitt-Hopkins…]
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Joubert, Eisenring,
Robb, Andermann
Neurology 1969
Montreal Children‘s
Hospital
[later  JBTS3]
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Boltshauser et al
Neuropediatrics 1981
Horizontal head titubation
Dev Med Child Neurol 2014
Polygraphic study, age 2 days – apnea of 40 seconds, asleep, pulse rate constant
Horizontal head titubation
• 13 patients reported
• Age at recognition 2 weeks to 6 months
• Independent from ocular apraxia
• Age at disappearance 3 months to 7 years
• Potential early benign presentation of JS
• Head titubation present only awake
• Recognition allows targeted investigations – avoids unnecessary tests
• Different from other abnormal head movements (Table in article)
Abnormal head movements
Information collected from
Direct observation
video review
Parental questionnaire
Think rhombencephalosynopsis
• Persistent stereotyped figure-8 and side-to-side head shaking
• (vertical)
• Age at recognition > 1 year
• May persist into adult life
• Aggravating factors fatigue, excitement
• Less if visually attentive
50/59 – abnormal head movements
Recognition important – not to assume
- stereotyped manner
- «psychological» disorder
Movement Disorders 2013;28:2019
Includes instructive supplemental videos
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Sagittal view - Rhombencephalosynapsis - 2 different patients
Rhombencephalosynpasis
PLUS high prevalence of aqueductal stenosis,
absence of septum pellucidum,
other associated anomalies
Horizontal gaze palsy
Think : Horizontal Gaze Palsy and Progressive Scoliosis HGPPS
HGPPS
Horizontal Gaze Palsy and Progressive Scoliosis –
Mutationen ROBO3
 Axonal guidance disorder
• Abnormalities may be obvious already in second year
• Cognition not affected
Haller, Wetzel, Lütschg
Neuroradiology 2008
MRI
Tractography
f MRI
Neurophysiology
Butterfly - lower brain stem
Abnormal guidance in brain stem
Eur J Paed Neurol
2013;17:675
Note
Concave brainstem in
sagittal view
• Joubert syndrome
• PTCD Pontine Tegmental Cap Dysplasia
• ROBO3
• Tubulinopathies (some)
• ….
• Congenital mirror movements
• Pontine malformation, undecussated pyramidal tracts, and regional
polymicrogyria: a new syndrome. (Single case, # known mutations)
Irahara et al, Pediatr Neurol 2014
• ……..
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Bilateral parietal / temporal alopecia
Think Gomez-Lopez-Hernandez syndrome
Eur J Med Genet 2008
• Alopecia easily missed !
• Alopecia is congenital !
Memo
All patients sporadic – no familal cases on record
Eur J Pediatr 2010
6 patients Armenia + Switzerland
Ocular motor apraxia
Terminology
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Ocular motor apraxia
Ocular apraxia
[Oculomotor apraxia]
Congenital ocular motor apraxia
Ocular motor apraxia
• Persuit movements intact
• Vestibulo-ocular reflex intact
• Inability to initiate voluntary saccades in horizontal plane
• May initially mimic visual impairment
• Compensatory «strategies» evolve in first months
- head thrusts
- blinking with change of gaze direction
• Improves with age
 infantile-onset saccade initiation delay
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Ataxia Ocular Apraxia Syndromes
AOA 1 versus AOA 2
AOA Typ 2 = SCAR1
Terms «historical» basis
1988 Aicardi et al
Ann Neurol
Ataxia-ocular apraxia: a syndrome mimicking ataxia telangiectasia
• AOA 1: (9q13 / Aprataxin)
• AOA 2: (9q34 / Senataxin)
• AOA 3:
• AOA 4:
(Saudi Arabia pedigree, OMIM #615217)
(8 Portuguese families, PNKP gene)
• Onset mean 7 years
• 90% ocular apraxia
• 90% albumin decreased
• Onset mean 15 years
• 50% ocular apraxia
• AFP 2-4 x erhöht, CK ↑
Myocardium not affected
MRI pure cerebellar atrophy
Polyneuropathy ++
senso-motor + axonal
Telangiectasias
«Congenital» ocular apraxia
Later onset ocular apraxia («acquired»)
• Isolated (Cogan 1952)
• Joubert syndrome
• M. Gaucher type 3
• Various CNS malformations
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AT Louis-Bar
AOA syndromes
Leigh-like diseases
Bifrontal lesions
• Reported inconsistently in other
genetic disorders
[PCH1, H-ABC, GRID2, Cohen,
CACNA1A, Vit E deficiency…]
10 year old boy, progressive ataxia
• Late manfistetation of Ataxia Telangiectasia Louis-Bar (AT)
• Onset of AT usually in infancy with ataxia
• Good screening «tool» - marked elevation (>10 norm) of Alfpha Feto-Protein
• MRI pure cerebellar atrophy
• Typical – late onset ocular apraxia (> 4 years)
Supranuclear vertical palsy (downgaze > upgaze)
Think M. Niemann-Pick disease type C
• Horizontal gaze not affected
• Slow persuit movements intact
• Vertical saccades impaired
• # vertical upgaze palsy
• Possible early complaint – difficulties going donwstairs
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Niemann-Pick disease Type C NPC
Bone marrow storage cells in Niemann-Pick disease type C
„seablue histiocyte“ and „foam cell“
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Prevalence 1:120’000
Autosomal recessive – 2 genes (NPC1, NPC2)
Pathogenesis intracellular cholesterol trafficking….
Onset variable, mostly first decade
Manifestations
increased prevalence of icterus prolongatus
motor: «clumsiness», ataxia
cognitive decline ev. seizures, cataplexy
supranuclear vertical gaze impairment
• Look for
splenomegaly
vertical gaze (spec. downgaze)
Non-progressive congenital ataxias
• Most prevalent cerebellar dysfunction
• Not an entity (clinical, imaging, genetic)
• Underrecognised – lack of awareness
- Neuroimaging often normal
- Not listed in classifications of cerebellar disorders
- Clinical situation may be dominated by non-motor
problems ( dg as mental retardation, CP, autism…)
• Ataxia is not „congenital“
• Longterm prognosis determined by cognitive abilities
Congenital Ataxia – change of profile over time
Early Presentation
Longterm Problems
Hypotonia
Delayed motor milestones
Delayed language milestones
Ataxia
Behaviour
Cognitive impairment
(Seizures)
(Spastic dystonic component)
Early presentation of congenital ataxia
• Hypotonia
• Delayed motor milestones
• Delayed language milestones (often)
[ ataxia is not „congenital“ – „misnomer“ – „free interval“]
Nonspecific
DD
Variant (buttom shuffler)
Neuromuscular disorder
Syndromic (i.e. neurofibromatosis type 1)
„Developmental delay“
Cerebellar cognitive affective syndrome
Based on observations in adults with acquired disorders
• Cerebellar stroke
• Cerebellitis
• Benign cerebellar tumors ( ≠ radiotp, chemotp)
Concept extended to paediatric cerebellar disorders
acquired and „developmental“
• Benign tumors
• Congenital ataxia
• Cerebellar malformations
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