Cerebellar Disorders Differential Diagnosis

ACUTE—MINUTES TO HOURS

Ischemic stroke and hemorrhage start abruptly. Both worsen clinically over hours if cerebellar edema develops. Note the “posterior fossa mantra” of acute cerebellar and brainstem injury—headache, nausea, vomiting, and vertigo, with or without ataxia, dysarthria, diplopia, and nystagmus. Neurologic examination lateralizes to side of injury.

Acute cerebellitis occurs more commonly in children than adults, starting more abruptly than postinfectious cerebellitis; both produce a pancerebellar syndrome.

Thiamine deficiency produces Wernicke encephalopathy, a triad of ataxia, confusion, and oculomotor disturbances that is a medical emergency requiring immediate repletion of vitamin B₁.

SUBACUTE—DAYS TO WEEKS

Paraneoplastic immune-mediated Purkinje cell attack from remote tumors (lung, breast, ovary) may develop acutely over days, producing a pancerebellar syndrome.

Cerebellar tumors (benign or malignant) worsen over weeks to months but occasionally present acutely with obstructive hydrocephalus.

Other focal lesions include abscesses, multiple sclerosis, progressive multifocal leukoencephalopathy (PML), and rhombencephalitis. Alcoholic cerebellar atrophy (anterior superior vermis) may present subacutely, as can cerebellar leukoencephalopathy from inhaled solvents and heroin, and Creutzfeldt-Jakob disease, with ataxia, dementia, and myoclonus.

INSIDIOUS, CHRONIC PROGRESSION—MONTHS TO YEARS

Neurodegenerative disorders start insidiously, progressing over years or decades. Autosomal dominant (AD) ataxic disorders pass down through generations. AD spinocerebellar ataxias (SCAs) typically manifest during adulthood. SCA 1 and SCA 3 have extrapyramidal, corticospinal and peripheral nerve lesions. SCA 2 has slowed eye movements, and extrapyramidal features in younger patients. SCA 3 is prevalent in Portuguese Azorean communities; younger patients have dystonia. SCA 5 and 6 are purely cerebellar. SCA 7 has visual failure from rod-cone macular dystrophy. SCA 8 includes mild chorea. SCA 10 occurs associated with epilepsy in families with Native American ancestry. SCA 17 resembles Huntington disease, with cognitive failure and choreoathetosis. Dentatorubropallidoluysian atrophy causes myoclonus, dystonia, and cognitive decline; it is uncommon outside Japan. Currently, there are more than 35 SCAs (NIH website – GeneTests, www.ncbi.nlm.nih.gov/sites/GeneTests).

Episodic ataxias (EA) are AD. EA1, a potassium channelopathy starts in childhood, producing brief duration ataxic episodes and myokymia. EA2 is a calcium channelopathy; attacks last for days, sometimes with migraine. The gene causing EA2 is associated with familial hemiplegic migraine and SCA6. Both EAs improve with acetazolamide.

Autosomal recessive disorders (AR) manifest in one generation, usually in childhood. Parents are asymptomatic; nonsibling family history is unrevealing. Friedreich ataxia is the most common AR cerebellar disorder, with ataxia, peripheral neuropathy, cardiomyopathy, scoliosis, and diabetes. Hearing and visual impairment occur late. Occasionally, it begins in adulthood, resembling SCAs. Ataxia telangiectasia often manifests before telangiectasias develop; features include recurrent infections from immunoglobulin IgA deficiency and radiation sensitivity with risk of neoplasia. Ataxia with oculomotor apraxia types 1 and 2 include peripheral neuropathy, choreiform movements, and cognitive difficulties. French Canadians experience AR cerebellar ataxia (ARCA) type 1 progressing over decades and AR spastic ataxia of Charlevoix-Saguenay starting in childhood. ARCA-2 (ataxia with coenzyme Q10 deficiency) and ataxia with vitamin E deficiency are treatable.

Hereditary spastic paraplegias are AD or AR. Myelopathy may be accompanied by ataxia and dysmetria.

Mitochondrial encephalomyopathies cause ataxia and complex clinical constellations. Most are AR or obey mitochondrial maternal inheritance. Mitochondrial recessive ataxia syndromes (MIRAS) caused by mutations in polymerase gamma cause ataxia, neuropathy, and hearing loss, particularly in Scandinavian families. Fragile X–associated tremor ataxia syndrome is an X-linked polyglutamine disorder causing ataxia, tremor, cognitive failure, and erectile dysfunction.

Sporadic ataxias include multiple system atrophy, a synucleinopathy with cerebellar ataxia or parkinsonism, autonomic dysfunction (postural hypotension, erectile dysfunction, urinary incontinence), and rapid eye movement (REM) sleep behavior disorder. Idiopathic late-onset cerebellar ataxia (ILOCA) describes adults older than 50 years with isolated cerebellar degeneration.

Isolated downbeat nystagmus points to lesions at the cervicomedullary junction or lobules IX/X. Rarely, this heralds a neurodegenerative disorder. Palatal tremor occurs with SCA 20.

Many disorders of infancy and childhood have cerebellar malformations or disruptions—hypoplasia, agenesis, megacerebellum, Chiari, and Dandy-Walker malformations.

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