Cerebellar disorders in children âclinical features
12.05.2015 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 • • • • • • Stereotyped side-to-side head shaking Horizontal gaze palsy Bilateral parietal alopecia Ocular motor apraxia Telangiectasias Supranuclear vertical gaze palsy Respiratory abnormalities • • • • ∞ 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…] Joubert, Eisenring, Robb, Andermann Neurology 1969 Montreal Children‘s Hospital [later JBTS3] 1 12.05.2015 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 2 12.05.2015 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 • …….. 3 12.05.2015 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 • • • • 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 4 12.05.2015 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 • • • • 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 5 12.05.2015 Niemann-Pick disease Type C NPC Bone marrow storage cells in Niemann-Pick disease type C „seablue histiocyte“ and „foam cell“ • • • • • 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 6
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