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Ataxia
Anatomy of Ataxia: Cerebellar Modules
Spinocerebellum
- Involves the limbs and trunk.
- Primarily involves the anterior lobe and vermis.
- The spinocerebellum receives its name from its major input fibers: the spinocerebellar tracts and, as we can imagine, plays a major role in postural stability.
Pontocerebellum
- Involves the arms.
- Primarily derives from the posterior lobe.
- It is geared towards fine motor movements, which are typically goal-oriented (it primarily acts through the corticopontocerebellar pathway).
- See Incoordination
Vestibulocerebellum
- Involves the face.
- Primarily derives from the flocculonodular lobe.
- It is important for equilibrium and eye movements.
Ataxia in relation to Alcohol Toxicity
Acute Alcohol Toxicity
- Acute alcohol intoxication causes toxicity to the entire cerebellum:
- Spinocerebellar toxicity causes truncal ataxia.
- Pontocerebellar toxicity causes incoordination.
- Vestibulocerebellar toxicity causes nystagmus.
Genetic Ataxia Syndromes
Autosomal Recessive:
- Friedreich's ataxia (FA): notably manifests with arreflexia (from the neuropathic component) but also pathologic reflexes (eg, Babinski sign).
- Remember that this mixed pattern can also present in subacute combined degeneration from Vitamin B12 deficiency: ataxia (from dorsal column degeneration), pathologic reflexes (from the myelopathy), arreflexia (from neuropathy).
- Ataxia with Vitamin E Deficiency: far more rare than FA but presents similarly, and, importantly, vitamin E repletion can halt the progression of the disease.
Autosomal dominant:
- Spinocerebellar ataxias (SCAs): generally we divide these into the pure cerebellar disorders and the ataxias with extra-cerebellar signs, as well (see below for details).
- Episodic ataxias: notably causes ataxia attacks. There are currently 7 types of episodic ataxia, but, importantly, EA1 and EA2 respond to pharmacological treatment (Both respond to acetazolamide, EA2 also responds to dalfampridine (4-aminopyridine), which we use in multiple sclerosis).
X-linked disorders:
- Mitochondrial disorders (eg, MERRF)
- Fragile X-tremor/ataxia
- X-linked adrenoleukodystrophy
Sporadic:
- As an example, multiple systems atrophy (MSA) - an atypical parkinsonian disorder that involves autonomic dysfunction + cerebellar disease or parkinsonism.
SPINOCEREBELLAR ATAXIAS
- There are greater than 30 SCAs, so we'll limit our review to the most common: SCAs 1, 2, 3, 6, 7, and DRPLA, which account for 50 – 75% of the cases, worldwide, and all of which are expanded exon-coding CAG repeat disorders. The SCAs comprise a variety of autosomal dominant mutations in addition to the expanded exon-coding CAG repeat mutations (eg, non-coding region expansion mutations and other conventional mutations).
- We'll categorize these into their Harding Classification of Autosomal Dominant Cerebellar Ataxias (ADCA I – III) to help group them by their clinical phenotypes.
ADCA 1
ADCA 1 are ataxias that also share any of the following features: ophthalmoplegia with or without optic atrophy, extrapyramidal features, dementia, extrapyramidal features, and/or amyotrophy.
- SCA1 manifests with ataxia along with, most notably, pyramidal tract signs and slowing of saccades to the point of ophthalmoplegia.
- SCA2 has a similar clinical phenotype to SCA1 but with slow saccades early-on.
- SCA3 (Machado-Joseph disease) is the most common SCA, worldwide, and, in addition to ataxia, notably, has features of levodopa-responsive parkinsonism (making it key part of the atypical parkinsonism differential), brainstem and ophthalmologic signs, amyotrophy, and polyneuropathy.
- DRPLA (Dentatorubral-Pallidolusian Atrophy), which, as a simplification, we can think of as Japanese Huntington's disease with atrophy of the brainstem and cerebellum, since most cases are from Japan and because of the overlap in symptomatology, and because the atrophy in HD it is the caudate whereas in DRPLA it is the brainstem and cerebellum. However, there are notable differences in the disorders that are beyond our scope, here.
ADCA 2
ADCA 2 is most easily thought of as ADCA 1 plus pigmentary retinal degeneration
- SCA7 most notably presents with severe visual loss from maculopathy, along with numerous other signs similar to SCAs 1 – 3.
ADCA 3
ADCA 3 is a pure cerebellar syndrome (with later age of onset, typically)
- SC6 presents as a benign, slowly progressive ataxia, typically in the 50s to 60s; accordingly the pathology is confined to the cerebellum.