CerebellumTim McDowellJanuary 26, 2011

AnatomyMidline vermis + 2 cerebellar hemispheresAnterior (I-V) and posterior (VI-IX) lobes divided by primary fissureFlocculonodular lobe (X), seperated by posterolateral fissuresCortex folded into folia

Anatomy

Deep NucleiFastigialstance and gait, controls muscles only in the modes of sitting, standing, and walking Globose + Emboliformsegmental reflexes, speeds the initiation of movements triggered by somatosensory cues that guide the response, stops unwanted and promotes wanted oscillations, stabilizes holds DentateFine dexterity

Functional AnatomyArchicerebellumflocculonodular lobeconnections with the vestibular system, inputs from areas of the brain concerned with eye movements Paleocerebellumvermis of the anterior lobe, the pyramis, the uvula, and the paraflocculus Spinal cord inputs, controls muscle tone + axial and limb movements

Functional AnatomyNeocerebellummiddle portion of the vermis and most of the cerebellar hemispheres planning and initiation of movements, regulation of fine limb movements

Functional AnatomyOrganized into Midline, Intermediate and lateral zonesMidline project to fastigial nucleiIntermmediate project to nucleus interposedLateral project to dentate

Cerebeller Cortex3 Layers: GranularPurkinjeMolecular5 Cell types:Basket, stellate, Purkinje, granule, and Golgi

PhysiologyAscending Fibres:MossyDiffuse projections through granule cells to multiple Purkinje cellsClimbingTerminal fibers of olivocerebellar tracts, multiple synaptic contacts per Purkinje cellMultilayeredAfferents from hypothalamus, raphe n, locus ceruleus

PhysiologyDescending Fibres:Purkinje FibresProject from Purkinje cells in Purkinje layer to deep cerebellar nuclei, inhibitory Deep nuclei then send excitory signals to their efferent connections

PhysiologyStellate cells and basket cells cause lateral inhibition of Purkinje cellsModulation in spatial resolutionGolgi cells inhibit granular cellsModulation in temporal resolution

Afferent and EfferentsSuperior Cerebellar Peduncle (brachium conjunctivum)Connects with midbrainMiddle Cerebellar Peduncle (brachium pontis)Connects with ponsInferior Cerebellar Peduncle (restiform body)Connects with medulla

Superior Cerebellar PeduncleAfferent:Ventral spinocerebellar tract, transmits proprioceptive and exteroceptive information from levels below the midthoracic cord.Tectocerebellar tract, arising in the superior and inferior colliculi carries auditory and visual information.Trigeminocerebellar tract, proprioceptive fibers from the mesencephalon and tactile information from the chief sensory nucleus of the trigeminal nerveThe cerulocerebellar tract, fibers from the nucleus ceruleus

Superior Cerebellar PeduncleEfferent: (most prominent)Dentatorubral tract, output to the contralateral red nucleusDentatothalamic tract, output to the contralateral ventrolateral nucleus of the thalamusUncinate bundle of Russell, output to the vestibular nuclei and reticular formation

Middle Cerebellar PeduncleAfferent fibers: (only) Pontocerebellar (corticopontocerebellar) tract, arises in contralateral pontine gray matterTransmits impulses from the cerebral cortex to the intermediate and lateral zones of the cerebellum

Inferior Cerebellar PeduncleAfferent:Dorsal spinocerebellar tract, originating in the dorsal nucleus of Clarke (T1L2), carries proprioceptive and exteroceptive information mostly from the trunk and ipsilateral lower extremityCuneocerebellar tract, originating in the external arcuate nucleus, which transmits proprioceptive information from the upper extremity and neck.Olivocerebellar tract, which carries somatosensory information from the contralateral inferior olivary nuclei.

Inferior Cerebellar Peduncle

Vestibulocerebellar tract, transmits information from vestibular receptors on both sides of the body.Reticulocerebellar tract, arises in the lateral reticular and paramedian nuclei of the medulla.Arcuatocerebellar tract, arises from the arcuate nuclei of the medulla oblongata.Trigeminocerebellar tract, arises from the spinal and main sensory nuclei of the trigeminal nerveEfferent:fastigiobulbar tract -(through Juxtarestifrom body), cerebellovistibularcerebelloreticular pathways

Vascular SupplyPICAFrom intracranial vertebral artery, supplies the lateral medullary tegmentum, inferior cerebellar peduncle, the ipsilateral portion of the inferior vermis, and the inferior surface of the cerebellar hemisphere Medial branch supplies dorsolateral medulla and medial cerebellum, lateral branch supplies inferiopostalateral

Vascular SupplyAICAabove the origin of the basilar artery, supplies the anterior petrosal surface of the cerebellar hemisphere, flocculus, lower portion of the middle cerebellar peduncle, and lateral pontomedullary tegmentum SCAdistal segment of the basilar artery just below the terminal bifurcation into the paired PCAs, and supplies the upper surface of the cerebellar hemisphere, ipsilateral portion of the superior vermis, most of the dentate nucleus, upper portion of the middle cerebellar peduncle, superior cerebellar peduncle, and lateral pontine tegmentum

Stroke SyndromesPICA (40%)Proximal (usually in vertebral arteries)Wallenberg syndromeDistal: Medial branch occlusion will cause acute vertigo and truncal ataxia Lateral branch occlusion :unsteadiness, limb ataxia, and dysmetria without dysarthria

Stroke SyndromesAICA (5%)Prominent vertigo, nausea, vomiting, and nystagmus (vestibular nuclei)Ipsilateral facial hypalgesia and thermoanesthesia, and corneal hypesthesia (trigeminal spinal nucleus and tract)Ipsilateral Horner syndromeContralateral trunk and extremity hypalgesia and thermoanesthesia (lateral spinothalamic tract).Ipsilateral ataxia and asynergia (middle cerebellar peduncle and cerebellum).Ipsilateral deafness and facial paralysis (lateral pontomedullary tegmentum).

Stroke SyndromesSCA (35%)Vertigo and vomiting (vestibular nuclei and connections)Nystagmus (MLF and cerebellar pathways)Ipsilateral Horner syndrome Ipsilateral ataxia and asynergia (superior cerebellar peduncle and cerebellum)Ipsilateral intention tremor (dentate nucleus and superior cerebellar peduncle)Contralateral trunk and extremity hypalgesia and thermoanesthesia (lateral spinothalamic)Contralateral hearing impairment (crossed fibers of the lateral lemniscus)Contralateral fourth nerve palsy (pontine tectum)

Stroke SyndromesWatershed (20%)Etiologies: focal hypoperfusion secondary to occlusive disease in vertibobasilar vessels, emboli, intercranial atheroma, global hypoperfusionPhysical findings variable

Stroke SyndromesPICA vs SCASCA has less frequent vertigo and H/A, both with gait disturbanceSCA typically more benign clinicallyAlways need to be aware of possible herniation (tonsillar or transtentorial) with cerebellar stroke

Clinical FeaturesAtaxiaDysmetria, dysdiadokinesis, rebound, truncal, gait, localization dependentHypotonia, pendular reflexesneocerebellumIntention TremorDentate nucleus, rubro-olivo-cerebellar circuit

Clinical FeaturesDysarthriaScanning speech, agrammatism, involovemnet of tongue representation in cerebellum (L paravermal)NystagmusPAN, Rebound, Gaze evoked, downbeat (post. midline)Abnormal SaccadesSquare-wave jerks, macro square-wave jerksOccular dysmetriaDifficult to localize eye movement abnormalities between cerebellum and brainstem

Acute AtaxiaEpisodic/Recurrent AtaxiaCauses of Chronic AtaxiaIdiopathic (acute cerebellar ataxia) Metabolic Hypoglycemia Hyponatremia Hyperammonemia Biotinidase deficiency Wernicke's encephalopathy Infections Bacterial meningitis Viral meningitis Brainstem encephalitis Toxins Trauma (battered child) Hydrocephalus Cerebellar lesions Neoplasm (primary or metastatic) Infarct Hemorrhage Neuroblastoma Polyradiculoneuropathy GBS Fisher variant of GBS Tick paralysis Labyrinthitis Brainstem tumors Multiple sclerosisChannelopathies Episodic ataxia Type 1 Episodic ataxia Type 2 Paroxysmal choreoathetosis with episodic ataxia Periodic vestibulocerebellar ataxia Familial hemiplegic migraine Basilar artery migraine Benign paroxysmal vertigo of childhood Epilepsy (post-ictal state) Toxins Metabolic Hypoglycemia Hyperammonemia Organic acid disorders Hartnup disease Hyperpyruvic acidemias Pyruvate decarboxylate deficiency Refsum disease Porphyria Leigh syndrome Maple syrup urine disease Congenital lactic acidosis Dominant paroxysmal ataxiaFixed deficit Cerebral palsy Malformations (i.e., Dandy-Walker, Chiari, rhomboencephalosynapsis, cerebellar agenesis, hypoplasia of the cerebellar vermis, familial agenesis of the cerebellar vermis, pontocerebellar hypoplasia, Joubert's syndrome, cerebellar cortical malformations, macrocerebellum, etc.) -glutamyl-cysteine synthetase deficiency Triosephosphate isomerase deficiency Chediak-Higashi disease Autosomal dominant SCA1 SCA2 SCA3 (MJD) SCA4 SCA5 SCA6 DRPLA SCA7 (Ataxia/retinal degeneration) SCA8 SCA 9 (not assigned) SCA 10 SCA 11 SCA 12 SCA 13 SCA 14 SCA 15 (genetic locus not yet identified) SCA 16 SCA 17 SCA 1821 (not yet published, but registered) SCA 22 SCA 25 Autosomal recessive Friedreich's ataxia Early onset cerebellar ataxia with retained muscle stretch reflexes Ataxia with vitamin E deficiency Ataxia with oculomotor apraxia With hypogonadism With myoclonus (Ramsay Hunt syndrome) Infantile onset spinocerebellar ataxia With pigmentary retinopathy With optic atrophy mental retardation (including Behr syndrome) With cataract and mental retardation (Marinesco-Sjgren syndrome) With childhood deafness With extrapyramidal features Autosomal recessive late onset cerebellar ataxia Autosomal recessive spastic ataxia of Charleroix-Saguenay Ataxia telangiectasia Wilson's disease Refsum's disease Bassen-Kornzweig disease (abetalipoproteinemia) Spinocerebellar ataxia with axonal neuropathy Inborn errors of metabolism Cerebrotendinous xanthomatosis Other inherited disorders Sphingolipidoses Ceroid-lipofuscinosis X-Linked spinocerebellar ataxia Acquired diseases Hypothyroidism Drugs or toxins Multiple sclerosis Neoplasms Hamartomatous malformations (i.e., dysplastic gangliocystoma or Lhermitte-Duclos disease) Erdheim-Chester disease Paraneoplastic cerebellar degeneration (anti-Yo, anti-Hu, anti-Ri, anti-Tr, anti-CV2, antibody-negative) Autoimmune cerebellar ataxia Creutzfeldt-Jakob disease Gerstmann-Strussler-Scheinker disease

Video CasesThe presentation of MJD/SCA3 varies greatly but always includes ataxia. This affected mother and daughter both suffer from mild, progressive gait ataxia accompanied by mild scanning dysarthria, mild incoordination, and, in the mothers case, ophthalmoparesis noted on lateral gaze. They represent an unusual pair of cases because their disease repeat lengths were classified by the gene testing service as intermediate size alleles of indeterminate significance. Their repeats (54 and 52, respectively) were slightly smaller than the accepted repeat range of >56; in contrast, normal repeats are 42 or smaller for this gene. The ataxic presentation in this mother-daughter pair illustrates that intermediate repeat lengths can in fact cause disease. When interpreting the significance of repeat lengths in dynamic repeat diseases, the clinician should use clinical judgment to help determine whether those uncommon repeat lengths falling within a gray area are actually the cause of disease.SCA6 is a relatively pure cerebellar ataxia that usually begins in midlife. Many cases are sporadic, ie, occur in the absence of a known family history. In addition to describing so well her disease onset, progression, and current symptoms, this patient relates how it became clear, in retrospect, that her mothers gait problems and cerebellar disease were not due to chemotherapy, as had been assumed. The examination illustrates common features of SCA6, including scanning dysarthria, end-gaze nystagmus, and gait ataxia greater than appendicular ataxia.

Summary Slide

Acute AtaxiaEpisodic/Recurrent AtaxiaCauses of Chronic AtaxiaIdiopathic (acute cerebellar ataxia) Metabolic Hypoglycemia Hyponatremia Hyperammonemia Biotinidase deficiency Wernicke's encephalopathy Infections Bacterial meningitis Viral meningitis Brainstem encephalitis Toxins Trauma (battered child) Hydrocephalus Cerebellar lesions Neoplasm (primary or metastatic) Infarct Hemorrhage Neuroblastoma Polyradiculoneuropathy GBS Fisher variant of GBS Tick paralysis Labyrinthitis Brainstem tumors Multiple sclerosisChannelopathies Episodic ataxia Type 1 Episodic ataxia Type 2 Paroxysmal choreoathetosis with episodic ataxia Periodic vestibulocerebellar ataxia Familial hemiplegic migraine Basilar artery migraine Benign paroxysmal vertigo of childhood Epilepsy (post-ictal state) Toxins Metabolic Hypoglycemia Hyperammonemia Organic acid disorders Hartnup disease Hyperpyruvic acidemias Pyruvate decarboxylate deficiency Refsum disease Porphyria Leigh syndrome Maple syrup urine disease Congenital lactic acidosis Dominant paroxysmal ataxiaFixed deficit Cerebral palsy Malformations (i.e., Dandy-Walker, Chiari, rhomboencephalosynapsis, cerebellar agenesis, hypoplasia of the cerebellar vermis, familial agenesis of the cerebellar vermis, pontocerebellar hypoplasia, Joubert's syndrome, cerebellar cortical malformations, macrocerebellum, etc.) -glutamyl-cysteine synthetase deficiency Triosephosphate isomerase deficiency Chediak-Higashi disease Autosomal dominant SCA1 SCA2 SCA3 (MJD) SCA4 SCA5 SCA6 DRPLA SCA7 (Ataxia/retinal degeneration) SCA8 SCA 9 (not assigned) SCA 10 SCA 11 SCA 12 SCA 13 SCA 14 SCA 15 (genetic locus not yet identified) SCA 16 SCA 17 SCA 1821 (not yet published, but registered) SCA 22 SCA 25 Autosomal recessive Friedreich's ataxia Early onset cerebellar ataxia with retained muscle stretch reflexes Ataxia with vitamin E deficiency Ataxia with oculomotor apraxia With hypogonadism With myoclonus (Ramsay Hunt syndrome) Infantile onset spinocerebellar ataxia With pigmentary retinopathy With optic atrophy mental retardation (including Behr syndrome) With cataract and mental retardation (Marinesco-Sjgren syndrome) With childhood deafness With extrapyramidal features Autosomal recessive late onset cerebellar ataxia Autosomal recessive spastic ataxia of Charleroix-Saguenay Ataxia telangiectasiaWilson's disease Refsum's disease Bassen-Kornzweig disease (abetalipoproteinemia) Spinocerebellar ataxia with axonal neuropathy Inborn errors of metabolism Cerebrotendinous xanthomatosis Other inherited disorders Sphingolipidoses Ceroid-lipofuscinosis X-Linked spinocerebellar ataxia Acquired diseases Hypothyroidism Drugs or toxins Multiple sclerosis Neoplasms Hamartomatous malformations (i.e., dysplastic gangliocystoma or Lhermitte-Duclos disease) Erdheim-Chester disease Paraneoplastic cerebellar degeneration (anti-Yo, anti-Hu, anti-Ri, anti-Tr, anti-CV2, antibody-negative) Autoimmune cerebellar ataxia Creutzfeldt-Jakob disease Gerstmann-Strussler-Scheinker disease

ReferencesBlumenfeldBrazis

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