What is the differential diagnosis for cerebellar ataxia?

Differential Diagnosis for Cerebellar Ataxia

The differential diagnosis for cerebellar ataxia is extensive and should be systematically categorized by time course (acute vs. chronic), etiology (acquired vs. inherited), and age of presentation to guide efficient workup and management. 1

Acute/Subacute Cerebellar Ataxia

Vascular Causes

• Posterior circulation stroke (cerebellar infarction or hemorrhage) is a critical acute cause requiring immediate recognition 1
• Vertebrobasilar insufficiency can present with episodic or progressive ataxia 1

Infectious/Inflammatory Causes

• Acute cerebellitis presents with truncal ataxia, dysmetria, and headache; severe cases may develop altered consciousness, increased intracranial pressure, hydrocephalus, or herniation 1
• Bacterial cerebellitis may occur with cerebritis and meningitis 1
• Postinfectious cerebellar ataxia is the most common cause of acute ataxia in children, accounting for approximately 50% of pediatric emergency presentations 1
• Miller Fisher syndrome (Guillain-Barré variant) presents with the classic triad of ataxia, areflexia, and ophthalmoplegia 1

Demyelinating Diseases

• Multiple sclerosis can cause cerebellar ataxia when plaques affect the cerebellum or cerebellar pathways 1
• Acute disseminated encephalomyelitis (ADEM) may present with ataxia 1

Toxic/Metabolic Causes

• Chronic ethanol abuse is a common cause of cerebellar atrophy and ataxia 1
• Metronidazole toxicity shows increased T2 signal and reduced diffusivity in the dentate nuclei on MRI; brainstem and corpus callosum can also be affected 1
• Methanol toxicity and heroin use can cause cerebellar damage 1
• Mercury poisoning (Minamata disease) causes cortical or cerebellar lesions and atrophy 1
• Vitamin E deficiency is associated with cerebellar atrophy and ataxia 1
• Opiate and solvent abuse can result in cerebellar atrophy and infarction 1

Neoplastic/Paraneoplastic Causes

• Posterior fossa mass lesions (primary or metastatic, intra-axial or extra-axial) must be excluded in ataxia evaluation 1
• Isolated frontal lobe and thalamic mass lesions may present with gait and limb ataxia 1
• Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute or acute onset of gait and limb ataxia, dysarthria, and ocular dysmetria; associated with antibodies against intracellular antigens and commonly linked to SCLC, breast, ovarian, and testicular cancers with poor prognosis 1, 2
• Lhermitte-Duclos disease is considered a neoplasm or hamartoma with association to Cowden disease 1

Immune-Mediated Causes

• Non-paraneoplastic autoimmune cerebellar syndromes are associated with antibodies to neuronal surface antigens and are generally responsive to immunotherapy with better prognosis than paraneoplastic syndromes 2
• Neuro-Behçet disease and other vasculitides can lead to chronic ataxia 1

Other Acquired Causes

• Superficial siderosis presents with slowly progressive ataxia and hearing loss due to recurrent subarachnoid hemorrhage causing hemosiderin deposition 1

Chronic/Progressive Cerebellar Ataxia

Hereditary Ataxias - Autosomal Dominant

• Spinocerebellar ataxias (SCAs) represent a genetically heterogeneous group with variable phenotypic expression 1
• Episodic ataxias present with intermittent symptoms 1

Hereditary Ataxias - Autosomal Recessive

• Friedreich ataxia is a major autosomal recessive cerebellar ataxia 1
• Ataxia-telangiectasia presents with cerebellar ataxia and characteristic telangiectasias 1
• Niemann-Pick disease type C includes ataxia as a component 1
• Neuro-ferritinopathy can present with ataxia 1

Hereditary Ataxias - X-linked

• Fragile X-associated tremor/ataxia syndrome (FXTAS) is an important X-linked cause 1

Hereditary Ataxias - Mitochondrial

• Mitochondrial disorders can cause cerebellar atrophy in childhood and adults 1

Other Genetic Syndromes

• Christianson syndrome includes ataxia as a feature 1
• Huntington disease may present with ataxia 1

Congenital Malformations

• Chiari I malformation can present with posterior fossa symptoms including ataxia 1
• Cerebellar hypoplasias or agenesis are congenital causes 1
• Rhombencephalosynapsis is a rare cerebellar malformation 1
• Joubert syndrome presents with characteristic cerebellar vermian hypoplasia 1

Degenerative Causes

• Multiple system atrophy (MSA) includes cerebellar ataxia as part of its presentation 1
• Sporadic adult-onset ataxias represent a heterogeneous group including toxic/nutritional, immune-mediated, infectious, and degenerative etiologies 1

Metabolic/Storage Disorders

• Neuronal ceroid lipofuscinosis can cause cerebellar atrophy in childhood 1
• GM2 gangliosidosis may present with cerebellar atrophy 1

Diagnostic Approach by Time Course

For Acute Ataxia (hours to days)

• Prioritize exclusion of stroke, hemorrhage, infection, and toxic causes as these are potentially life-threatening and treatable 1
• MRI head without IV contrast is the preferred initial imaging modality 1, 3
• Consider contrast-enhanced MRI if inflammatory or neoplastic causes are suspected 3

For Chronic Ataxia (>2 months)

• Focus on inherited causes, degenerative disorders, and structural abnormalities 1
• MRI head without IV contrast remains the preferred imaging to detect cerebellar atrophy, structural abnormalities, and signal changes 1, 3
• Diagnosis relies on combination of history, thorough neurologic examination, imaging, and confirmatory laboratory/genetic testing 1

Key Clinical Distinctions

Cerebellar vs. Sensory Ataxia

• Cerebellar ataxia shows unsteadiness that does NOT significantly worsen with eye closure, distinguishing it from sensory ataxia 3
• Truncal ataxia is particularly common with cerebellar vermian pathology 1, 3

Age-Specific Considerations

• In children, postinfectious cerebellar ataxia is most common for acute presentations 1
• In adults, the differential broadens significantly to include toxic, degenerative, and neoplastic causes 1

Critical Pitfalls to Avoid

• Do not delay imaging in suspected acute stroke; follow stroke protocols immediately 1
• Do not overlook toxic causes (especially alcohol, medications like metronidazole) as these are reversible 1
• Do not miss paraneoplastic syndromes in subacute presentations; consider malignancy screening 1, 2
• Do not forget that genetic testing is increasingly available and cost-effective for hereditary ataxias 4, 5
• Be aware that conventional neuroimaging may be unremarkable in early disease, particularly in genetic ataxias 1