What are the causes and symptoms of progressive cerebellar atrophy in young adults?

Progressive Cerebellar Atrophy in Young Adults: Causes and Symptoms

Progressive cerebellar atrophy in young adults is most commonly caused by inherited spinocerebellar ataxias (autosomal dominant) and Friedreich ataxia (autosomal recessive), though acquired causes including tumors, inflammatory disorders, and metabolic conditions must be systematically excluded. 1, 2

Primary Causes

Inherited/Genetic Causes (Most Common in Young Adults)

Spinocerebellar ataxias (SCAs) represent the predominant autosomal dominant cause, characterized by genetically heterogeneous neurodegenerative disorders with variable phenotypic expression and progressive cerebellar hemispheric and vermian volume loss. 1, 2, 3

Friedreich ataxia is the major autosomal recessive cerebellar ataxia, typically presenting with progressive symptoms and associated spinal cord involvement. 1, 2

Ataxia-telangiectasia presents with progressive cerebellar ataxia accompanied by characteristic telangiectasias (visible dilated blood vessels). 2

Acquired Causes Requiring Urgent Exclusion

• Cerebellar tumors and brain stem gliomas are collectively common causes of chronic progressive ataxia and must be ruled out early, as they directly impact mortality. 1
• Inflammatory disorders can cause progressive cerebellar degeneration. 1
• Metabolic disorders may underlie progressive atrophy in specific cases. 1
• Paraneoplastic syndromes can cause progressive cerebellar degeneration even in young adults. 3

Clinical Symptoms and Examination Findings

Core Motor Symptoms

Widened-based gait with truncal instability is the hallmark presentation, particularly prominent with cerebellar vermian pathology. 2, 4

Dysmetria manifests as overshooting or undershooting during finger-to-nose and heel-to-shin testing. 4

Dysdiadochokinesia (impaired rapid alternating movements) is characteristic. 4

Dyssynergia (loss of coordinated multi-joint movements) becomes evident as the disease progresses. 4

Speech and Oculomotor Symptoms

Dysarthria with scanning or ataxic speech pattern develops as cerebellar degeneration advances. 4

Ocular dysmetria (saccadic overshooting) and nystagmus are common oculomotor findings. 4

Critical Distinguishing Feature

Unsteadiness does NOT significantly worsen with eye closure, which is the key feature distinguishing cerebellar ataxia from sensory ataxia—this means the Romberg test remains negative in pure cerebellar disease. 2, 4

Associated Symptoms in Specific Conditions

• Spinal cord signs (motor spasticity, sensory changes) may accompany spinocerebellar ataxias, warranting spine imaging. 1, 4
• Cognitive and behavioral deficits including executive dysfunction, visuospatial impairment, and inappropriate behavior can occur but are often overlooked without formal testing. 3
• Hearing loss with slowly progressive ataxia suggests superficial siderosis. 4

Diagnostic Approach

Initial Imaging

MRI of the head without IV contrast is the preferred initial imaging modality to detect cerebellar atrophy, signal changes, and exclude structural lesions like tumors. 2, 4

MRI of the complete spine may be necessary when spinocerebellar ataxias are suspected or when spinal cord signs are present. 1

Important Imaging Considerations

Early imaging in hereditary cerebellar ataxias may be normal or subtly abnormal, with imaging abnormalities becoming more apparent on follow-up due to the progressive nature of these disorders. 1

Progressive cerebellar hemispheric and vermian volume loss is the characteristic finding, with associated signal abnormality and atrophy of the spinal cord in certain conditions. 1, 5

Additional findings may include thinning of the corpus callosum, enlarged ventricles, cortical atrophy, and white matter signal changes depending on the specific etiology. 5, 6

Genetic Testing

Genetic testing for repeat expansions is essential, as common autosomal dominant and recessive ataxias are due to genetic repeat expansions. 7

Common Pitfalls to Avoid

Do not mistake weakness or hypotonia for ataxia, which requires careful examination to distinguish. 4

Do not overlook "pseudoataxia" from functional disorders, which can mimic organic cerebellar disease. 4

Do not assume all progressive ataxia is benign hereditary disease—always exclude tumors, inflammatory conditions, and paraneoplastic syndromes first, as these are treatable and affect mortality. 1, 3

Do not rely solely on initial imaging—serial imaging may be necessary to demonstrate progression in hereditary ataxias where early scans appear normal. 1