Cerebellum

Tim McDowellJanuary 26, 2011

Anatomy

• Midline vermis + 2 cerebellar hemispheres– Anterior (I-V) and posterior (VI-IX) lobes divided

by primary fissure– Flocculonodular lobe (X), seperated by

posterolateral fissures

• Cortex folded into folia

Anatomy

Deep Nuclei

• Fastigial– stance and gait, controls muscles only in the modes of

sitting, standing, and walking

• Globose + Emboliform– segmental reflexes, speeds the initiation of

movements triggered by somatosensory cues that guide the response, stops unwanted and promotes wanted oscillations, stabilizes holds

• Dentate– Fine dexterity

Functional Anatomy

• Archicerebellum– flocculonodular lobe– connections with the vestibular system, inputs from

areas of the brain concerned with eye movements

• Paleocerebellum– vermis of the anterior lobe, the pyramis, the uvula,

and the paraflocculus – Spinal cord inputs, controls muscle tone + axial and

limb movements

Functional Anatomy

• Neocerebellum– middle portion of the vermis and most of the

cerebellar hemispheres – planning and initiation of movements, regulation

of fine limb movements

Functional Anatomy

• Organized into Midline, Intermediate and lateral zones– Midline project to fastigial nuclei– Intermmediate project to nucleus interposed– Lateral project to dentate

Cerebeller Cortex

• 3 Layers: – Granular– Purkinje– Molecular

• 5 Cell types:– Basket, stellate, Purkinje, granule, and Golgi

Physiology

Ascending Fibres:• Mossy

– Diffuse projections through granule cells to multiple Purkinje cells

• Climbing– Terminal fibers of olivocerebellar tracts, multiple

synaptic contacts per Purkinje cell

• Multilayered– Afferents from hypothalamus, raphe n, locus ceruleus

Physiology

Descending Fibres:• Purkinje Fibres

– Project from Purkinje cells in Purkinje layer to deep cerebellar nuclei, inhibitory

• Deep nuclei then send excitory signals to their efferent connections

Physiology

• Stellate cells and basket cells cause lateral inhibition of Purkinje cells– Modulation in spatial resolution

• Golgi cells inhibit granular cells– Modulation in temporal resolution

Afferent and Efferents

• Superior Cerebellar Peduncle (brachium conjunctivum)– Connects with midbrain

• Middle Cerebellar Peduncle (brachium pontis)– Connects with pons

• Inferior Cerebellar Peduncle (restiform body)– Connects with medulla

Superior Cerebellar Peduncle

Afferent:•Ventral spinocerebellar tract, transmits proprioceptive and exteroceptive information from levels below the midthoracic cord.•Tectocerebellar tract, arising in the superior and inferior colliculi

ocarries auditory and visual information.•Trigeminocerebellar tract, proprioceptive fibers from the mesencephalon and tactile information from the chief sensory nucleus of the trigeminal nerve•The cerulocerebellar tract, fibers from the nucleus ceruleus

Superior Cerebellar Peduncle

Efferent: (most prominent)• Dentatorubral tract, output to the contralateral red

nucleus• Dentatothalamic tract, output to the contralateral

ventrolateral nucleus of the thalamus• Uncinate bundle of Russell, output to the vestibular

nuclei and reticular formation

Middle Cerebellar PeduncleAfferent fibers: (only)

• Pontocerebellar (corticopontocerebellar) tract, arises in contralateral pontine gray matter

oTransmits impulses from the cerebral cortex to the intermediate and lateral zones of the cerebellum

Inferior Cerebellar Peduncle

Afferent:• Dorsal spinocerebellar tract, originating in the dorsal nucleus

of Clarke (T1–L2), carries proprioceptive and exteroceptive information mostly from the trunk and ipsilateral lower extremity

• Cuneocerebellar 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 nerve

Efferent:• fastigiobulbar tract -(through Juxtarestifrom body),

cerebellovistibular• cerebelloreticular pathways

Vascular Supply

• PICA– From 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 Supply• AICA

– above 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

• SCA– distal 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 Syndromes

PICA (40%)

•Proximal (usually in vertebral arteries)

•Wallenberg syndrome

•Distal:

•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 syndrome• Contralateral 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 Syndromes

• Watershed (20%)– Etiologies: focal hypoperfusion secondary to

occlusive disease in vertibobasilar vessels, emboli, intercranial atheroma, global hypoperfusion

– Physical findings variable

Stroke Syndromes

• PICA vs SCA– SCA has less frequent vertigo and H/A, both with

gait disturbance– SCA typically more benign clinically

• Always need to be aware of possible herniation (tonsillar or transtentorial) with cerebellar stroke

Clinical Features• Ataxia

– Dysmetria, dysdiadokinesis, rebound, truncal, gait, localization dependent

• Hypotonia, pendular reflexes– neocerebellum

• Intention Tremor– Dentate nucleus, rubro-olivo-cerebellar circuit

Clinical Features• Dysarthria

– Scanning speech, agrammatism, involovemnet of tongue representation in cerebellum (L paravermal)

• Nystagmus– PAN, Rebound, Gaze evoked, downbeat (post.

midline)• Abnormal Saccades

– Square-wave jerks, macro square-wave jerks– Occular dysmetria

• Difficult to localize eye movement abnormalities between cerebellum and brainstem

Acute Ataxia Episodic/Recurrent Ataxia

Causes of Chronic Ataxia

Idiopathic (“acute cerebellar ataxia”)Metabolic   Hypoglycemia   Hyponatremia   Hyperammonemia   Biotinidase deficiency   Wernicke's encephalopathyInfections   Bacterial meningitis   Viral meningitis   Brainstem encephalitisToxinsTrauma (battered child)HydrocephalusCerebellar lesions   Neoplasm (primary or metastatic)   Infarct   HemorrhageNeuroblastomaPolyradiculoneuropathy   GBS   Fisher variant of GBS   Tick paralysis“Labyrinthitis”Brainstem tumorsMultiple sclerosis

Channelopathies Episodic ataxia Type 1 Episodic ataxia Type 2 Paroxysmal choreoathetosis with episodic ataxia Periodic vestibulocerebellar ataxiaFamilial hemiplegic migraineBasilar artery migraineBenign paroxysmal vertigo of childhoodEpilepsy (post-ictal state)ToxinsMetabolic Hypoglycemia Hyperammonemia Organic acid disorders Hartnup disease Hyperpyruvic acidemias Pyruvate decarboxylate deficiency Refsum disease Porphyria Leigh syndrome Maple syrup urine disease Congenital lactic acidosisDominant paroxysmal ataxia

Fixed 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.) γ-glutamyl-cysteine synthetase deficiency Triosephosphate isomerase deficiency Chediak-Higashi diseaseAutosomal 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 18–21 (not yet published, but registered) SCA 22 SCA 25Autosomal 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-Sjögren 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 xanthomatosisOther inherited disorders Sphingolipidoses Ceroid-lipofuscinosisX-Linked spinocerebellar ataxiaAcquired 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-Sträussler-Scheinker disease

Video Cases• The 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 mother’s 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 mother’s 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 Ataxia Episodic/Recurrent Ataxia

Causes of Chronic Ataxia

Idiopathic (“acute cerebellar ataxia”)Metabolic   Hypoglycemia   Hyponatremia   Hyperammonemia   Biotinidase deficiency   Wernicke's encephalopathyInfections   Bacterial meningitis   Viral meningitis   Brainstem encephalitisToxinsTrauma (battered child)HydrocephalusCerebellar lesions   Neoplasm (primary or metastatic)   Infarct   HemorrhageNeuroblastomaPolyradiculoneuropathy   GBS   Fisher variant of GBS   Tick paralysis“Labyrinthitis”Brainstem tumorsMultiple sclerosis

Channelopathies Episodic ataxia Type 1 Episodic ataxia Type 2 Paroxysmal choreoathetosis with episodic ataxia Periodic vestibulocerebellar ataxiaFamilial hemiplegic migraineBasilar artery migraineBenign paroxysmal vertigo of childhoodEpilepsy (post-ictal state)ToxinsMetabolic Hypoglycemia Hyperammonemia Organic acid disorders Hartnup disease Hyperpyruvic acidemias Pyruvate decarboxylate deficiency Refsum disease Porphyria Leigh syndrome Maple syrup urine disease Congenital lactic acidosisDominant paroxysmal ataxia

Fixed 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.) γ-glutamyl-cysteine synthetase deficiency Triosephosphate isomerase deficiency Chediak-Higashi diseaseAutosomal 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 18–21 (not yet published, but registered) SCA 22 SCA 25Autosomal 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-Sjögren 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 xanthomatosisOther inherited disorders Sphingolipidoses Ceroid-lipofuscinosisX-Linked spinocerebellar ataxiaAcquired 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-Sträussler-Scheinker disease

References

• Blumenfeld• Brazis

Thanks