What laboratory studies and diagnostic examinations should be performed in a 67‑year‑old man with insidious, progressively worsening ataxia?

Laboratory Studies and Diagnostic Examinations for Progressive Ataxia in a 67-Year-Old Man

MRI of the brain without and with IV contrast is the primary imaging study required to evaluate for structural lesions, cerebellar degeneration, and other intracranial processes that could cause progressive ataxia in this patient. 1

Initial Imaging Studies

Brain Imaging (First Priority)

• MRI brain without and with IV contrast is the gold standard for evaluating progressive ataxia, as it provides superior visualization of the posterior fossa, cerebellum, and brainstem compared to CT 1

• MRI can identify:

  • Posterior fossa mass lesions (primary or metastatic tumors) 1
  • Cerebellar atrophy patterns suggesting neurodegenerative disorders 1
  • Demyelinating diseases (multiple sclerosis, acute disseminated encephalomyelitis) 1
  • Superficial siderosis (hemosiderin deposition from recurrent subarachnoid hemorrhage) 1
  • Vascular lesions including infarctions 1
  • Inflammatory processes (cerebellitis, vasculitis) 1

• Advanced MRI sequences should include susceptibility-weighted imaging or gradient echo T2-weighted sequences to detect blood products in superficial siderosis 1

Spinal Imaging (If Indicated by Examination)

• MRI complete spine should be performed if clinical examination suggests spinal cord involvement (weakness, hyperreflexia, spasticity, sensory loss) 1
• MRI spine evaluates for:
  • Spinal cord compression from degenerative changes 1
  • Inflammatory/demyelinating diseases affecting the cord 1
  • Nutritional deficiencies causing myelopathy (B12, copper deficiency) 1
  • Vascular lesions (spinal dural arteriovenous fistulae) 1

Essential Laboratory Studies

Blood Tests for Treatable Causes

Based on the differential diagnosis of progressive ataxia, the following laboratory studies should be obtained 1, 2, 3:

Metabolic and Nutritional:

• Vitamin B12 level (deficiency causes myelopathy and ataxia) 1
• Vitamin E level (deficiency associated with cerebellar atrophy) 1
• Copper and ceruloplasmin levels (copper deficiency causes myelopathy) 1
• Thyroid function tests (hypothyroidism can cause ataxia) 3
• Comprehensive metabolic panel (electrolytes, glucose, renal/hepatic function) 3

Toxic/Substance-Related:

• Alcohol level and liver function tests (chronic ethanol abuse causes cerebellar degeneration) 1
• Heavy metal screening if exposure suspected (mercury, lead) 1
• Medication review for cerebellar-toxic drugs (metronidazole, phenytoin, lithium) 1

Infectious/Inflammatory:

• Complete blood count with differential 3
• Erythrocyte sedimentation rate and C-reactive protein 3
• Antinuclear antibody and rheumatologic panel if vasculitis suspected 1
• Syphilis serology (neurosyphilis can cause ataxia) 1
• HIV testing 3

Paraneoplastic:

• Paraneoplastic antibody panel (anti-Yo, anti-Hu, anti-Ri, anti-Tr) for paraneoplastic cerebellar degeneration 1
• Cancer screening appropriate for age and risk factors (chest imaging, tumor markers) 1

Cerebrospinal Fluid Analysis (If Indicated)

CSF studies should be obtained if infectious, inflammatory, or paraneoplastic causes are suspected 1, 3:

• Cell count and differential
• Protein and glucose
• Oligoclonal bands (for demyelinating disease) 1
• 14-3-3 protein and RT-QuIC if Creutzfeldt-Jakob disease suspected 1
• Infectious studies (bacterial culture, viral PCR panels) 3
• Paraneoplastic antibodies 1

Genetic Testing (If Hereditary Ataxia Suspected)

• Genetic testing for spinocerebellar ataxias (SCAs) should be considered, particularly if family history is positive or other causes are excluded 1, 4
• Common SCAs to test include SCA1, SCA2, SCA3, SCA6, SCA7 1
• Friedreich ataxia genetic testing if onset before age 25 or appropriate phenotype 1, 2
• Fragile X-associated tremor/ataxia syndrome (FXTAS) testing 1

Additional Diagnostic Studies

Electrodiagnostic Studies

• Nerve conduction studies and electromyography if peripheral neuropathy suspected (sensory loss, hyporeflexia, weakness) 5
• Helps distinguish sensory ataxia from cerebellar ataxia 1

Electroencephalography

• EEG if Creutzfeldt-Jakob disease suspected (periodic sharp wave complexes) 1

Clinical Pitfalls to Avoid

• Do not rely on CT head alone for evaluating progressive ataxia, as it has poor sensitivity for posterior fossa pathology and subtle cerebellar changes 1
• Do not miss treatable causes: Vitamin deficiencies, hypothyroidism, and paraneoplastic syndromes require specific laboratory testing that may not be included in routine panels 1, 3
• Consider age-appropriate malignancy screening: In a 67-year-old with progressive ataxia, paraneoplastic cerebellar degeneration must be excluded with appropriate antibody testing and cancer screening 1
• Genetic testing may be positive even without family history: Sporadic cases of SCA can occur, and family history may be negative due to incomplete penetrance or unrecognized mild symptoms in relatives 4