Download Cerebellum

Cerebellum
Tim McDowell
January 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 Peduncle
Afferent 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 Syndromes
AICA (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 Syndromes
SCA (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
Idiopathic (“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 sclerosis
Episodic/Recurrent
Ataxia
Channelopathies
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 ataxia
Causes of Chronic Ataxia
Fixed deficit
Cerebral palsy
Malformations (i.e., DandyWalker, 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.) γglutamyl-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 18–21 (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-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
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 LhermitteDuclos 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-SträusslerScheinker disease
Video Cases
SCA6 is a relatively “pure” cerebellar ataxia that usually begins in midlife. Many
•cases
The are
presentation
of MJD/SCA3
greatly
always
includes
sporadic, ie,
occur in thevaries
absence
of a but
known
family
history.ataxia.
In
addition
to describing
soand
welldaughter
her disease
onset,
progression,
current gait
This affected
mother
both
suffer
from mild, and
progressive
symptoms,
this patient relates
it became
clear, inmild
retrospect,
that her and,
ataxia accompanied
by mildhow
scanning
dysarthria,
incoordination,
mother’s
gait problems
cerebellar disease
were
due gaze.
to chemotherapy,
in the mother’s
case,and
ophthalmoparesis
noted
onnot
lateral
They
as had been assumed. The examination illustrates common features of SCA6,
represent an unusual pair of cases because their disease repeat lengths
including scanning dysarthria, end-gaze nystagmus, and gait ataxia greater
were classified by the gene testing service as “intermediate size alleles of
than appendicular ataxia.
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.
Acute Ataxia
Idiopathic (“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 sclerosis
Episodic/Recurrent
Ataxia
Channelopathies
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 ataxia
Causes of Chronic Ataxia
Fixed deficit
Cerebral palsy
Malformations (i.e., DandyWalker, 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.) γglutamyl-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 18–21 (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-Sjögren syndrome)
With childhood deafness
With extrapyramidal features
Autosomal recessive late onset
cerebellar ataxia
Summary Slide
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 LhermitteDuclos 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-SträusslerScheinker disease
References
• Blumenfeld
• Brazis
Thanks