What is the next step in managing an elderly male with peripheral neuropathy, predominantly large fiber, and mild proprioceptive ataxia, with absent ankle jerks and no history of diabetes?

Workup for Large-Fiber Peripheral Neuropathy in Non-Diabetic Patient

The next step is to obtain comprehensive laboratory testing to identify treatable causes, including complete blood count, comprehensive metabolic profile, vitamin B12 level, thyroid-stimulating hormone, serum protein electrophoresis with immunofixation, and erythrocyte sedimentation rate. 1, 2

Diagnostic Rationale

This patient presents with classic large-fiber neuropathy (absent ankle jerks, proprioceptive ataxia, paresthesias) without diabetes, and initial paraneoplastic and vasculitic workups are negative. Peripheral neuropathy is a diagnosis of exclusion, and identifying treatable causes is the priority. 3, 4

Essential Laboratory Testing

The initial workup should systematically evaluate the most common treatable causes:

• Complete blood count and comprehensive metabolic profile to assess for renal disease, hepatic dysfunction, and hematologic abnormalities 1, 2
• Vitamin B12 level - nutritional deficiencies are among the most common treatable causes of large-fiber neuropathy 3, 1, 2
• Thyroid-stimulating hormone - hypothyroidism is a well-established treatable cause 3, 1, 2
• Serum protein electrophoresis with immunofixation - essential to screen for monoclonal gammopathy and multiple myeloma, which can cause large-fiber predominant neuropathy 3, 2
• Erythrocyte sedimentation rate - helps identify inflammatory or systemic conditions 1

Additional Considerations Based on Clinical Context

If initial testing is unrevealing, consider:

• Electrodiagnostic studies (nerve conduction studies and electromyography) to differentiate axonal versus demyelinating neuropathy and assess severity 1, 2, 5
• Referral to neurology is warranted when clinical features are atypical or diagnosis remains unclear after initial workup 3, 4
• Lumbar puncture with cerebrospinal fluid analysis if chronic inflammatory demyelinating polyneuropathy (CIDP) is suspected, particularly with demyelinating features on electrodiagnostic studies 1
• Genetic testing for hereditary neuropathies if family history is suggestive or other causes are excluded 2, 5

Common Pitfalls to Avoid

• Do not assume idiopathic neuropathy without completing the full treatable causes workup - 25-46% of cases remain idiopathic only after comprehensive evaluation 2
• Large-fiber predominant neuropathy with proprioceptive ataxia should raise suspicion for vitamin B12 deficiency, hypothyroidism, or paraproteinemic neuropathy - these require specific testing 3, 1
• Asymmetric presentation or significant autonomic involvement warrants more aggressive workup and earlier neurologist referral 4
• Even with negative paraneoplastic antibodies, serum protein electrophoresis is still essential as monoclonal gammopathy can cause neuropathy through non-paraneoplastic mechanisms 3, 2

Treatment Considerations Pending Workup

While awaiting diagnostic results:

• Symptomatic treatment with pregabalin, duloxetine, or gabapentin can be initiated for neuropathic pain if present 4, 6
• Daily foot examination and proper footwear to prevent complications from sensory loss 3, 6
• Restrict to non-weight-bearing activities if foot injury or open sore develops 3