Workup for Bilateral Lower Extremity Neuropathy
The comprehensive workup for bilateral lower extremity neuropathy should include a thorough clinical assessment, laboratory testing, electrodiagnostic studies, and in select cases, specialized imaging or biopsy to identify the underlying cause and guide appropriate treatment.
Initial Clinical Assessment
History
- Symptom characteristics: pain, burning, numbness, tingling, weakness
- Symptom pattern: symmetric vs. asymmetric, distal vs. proximal, progression rate
- Medical history: diabetes, alcohol use, thyroid disease, cancer, HIV, autoimmune conditions
- Medication history: chemotherapeutic agents, other neurotoxic drugs
- Family history: hereditary neuropathies
- Occupational/environmental exposures: toxins, heavy metals
Physical Examination
- Neurological assessment:
- Sensory testing: temperature, pinprick, vibration, pressure sensation
- Motor strength evaluation
- Deep tendon reflexes, especially ankle reflexes
- Proprioception
- Vascular assessment:
- Pulse palpation (femoral, popliteal, dorsalis pedis, posterior tibial)
- Inspection for trophic changes, ulcers, or gangrene
- Auscultation for femoral bruits
Laboratory Testing
First-Line Tests
- Complete blood count
- Comprehensive metabolic panel
- Fasting blood glucose and HbA1c
- Thyroid-stimulating hormone (TSH)
- Vitamin B12 level
- Serum protein electrophoresis and immunofixation
- Erythrocyte sedimentation rate (ESR)
Second-Line Tests (Based on Clinical Suspicion)
- Vitamin B6 and folate levels
- Autoimmune markers: ANA, ESR, CRP, ANCA, anti-smooth muscle, SSA/SSB
- Hepatitis B, C, and HIV testing
- Lyme disease testing
- Paraneoplastic antibody panel (e.g., anti-Hu/ANNA-1)
- Heavy metal screening
- Genetic testing for hereditary neuropathies
Electrodiagnostic Studies
- Nerve conduction studies (NCS) to differentiate:
- Axonal vs. demyelinating neuropathy
- Sensory vs. motor vs. sensorimotor neuropathy
- Severity assessment
- Electromyography (EMG) to evaluate:
- Denervation patterns
- Chronicity of neuropathy
Additional Specialized Testing (When Indicated)
For Small Fiber Neuropathy
- Skin biopsy for intraepidermal nerve fiber density assessment
For Inflammatory Neuropathies
- Lumbar puncture with CSF analysis (cell count, protein, glucose)
For Anatomical Abnormalities
- MRI of spine to rule out compressive lesions
- MRI of plexus if plexopathy is suspected
For Vasculitic Neuropathy
- Nerve biopsy (rarely needed)
For Diabetic Neuropathy
- Cardiac autonomic neuropathy screening:
- Heart rate variability testing
- Postural hypotension testing
- Ambulatory blood pressure monitoring
Disease-Specific Considerations
For Suspected Diabetic Neuropathy
- Comprehensive foot examination
- Assessment for autonomic neuropathy
- Screening for peripheral arterial disease with ABI measurement 1
For Suspected Peripheral Arterial Disease
- Ankle-brachial index (ABI)
- Toe-brachial index (TBI) if ABI >1.40
- Duplex ultrasound for anatomical and hemodynamic assessment
- Consider CT angiography or MR angiography if revascularization is being considered 1
For Suspected Immune-Mediated Neuropathy
- Anti-ganglioside antibody testing (for GBS variants)
- Consider IVIG or plasmapheresis for treatment in severe cases 1
Common Pitfalls to Avoid
- Failing to rule out compressive lesions (e.g., lumbar stenosis, nerve root compression)
- Missing diabetes as the underlying cause (most common treatable etiology)
- Overlooking medication-induced neuropathies
- Not considering small fiber neuropathy when NCS are normal
- Neglecting to screen for peripheral arterial disease in patients with neuropathy
Early identification of the underlying cause is crucial as many neuropathies are treatable or reversible if addressed promptly. The workup should be guided by the clinical pattern of neuropathy, with recognition that patients with peripheral neuropathy and concurrent peripheral arterial disease are at significantly higher risk for amputation, revascularization, and death 2.