What tests and assessments should be included in a diagnostic panel for peripheral neuropathy?

Comprehensive Diagnostic Panel for Peripheral Neuropathy

A comprehensive diagnostic panel for peripheral neuropathy should include clinical assessment of both small and large fiber function, laboratory testing for common etiologies, and specialized testing when indicated by clinical presentation. 1

Initial Clinical Assessment

History and Symptom Evaluation

• Onset and progression pattern (acute, subacute, chronic)
• Distribution of symptoms (length-dependent, asymmetric, multifocal)
• Quality of symptoms (burning, tingling, numbness, pain)
• Exacerbating and alleviating factors
• Family history of neuropathy
• Medication history (chemotherapeutics, antibiotics)
• Comorbidities (diabetes, thyroid disease)
• Alcohol consumption
• Occupational exposures to toxins

Physical Examination Components

1. Small-fiber function assessment:

   • Pinprick sensation
   • Temperature sensation
   • Assessment for autonomic symptoms (orthostatic dizziness, dry skin) 1

2. Large-fiber function assessment:

   • Vibration sensation using 128-Hz tuning fork 1, 2
   • Deep tendon reflexes
   • Proprioception

3. Protective sensation assessment:

   • 10-g monofilament testing (critical for identifying ulceration risk) 1

4. Vascular assessment:

   • Pulse examination (dorsalis pedis and posterior tibial arteries)
   • Capillary refill time
   • Assessment for dependent rubor or elevation pallor 1

First-Line Laboratory Testing

• Complete blood count
• Comprehensive metabolic panel
• Fasting blood glucose and HbA1c
• Vitamin B12 level
• Thyroid-stimulating hormone (TSH) 3
• Erythrocyte sedimentation rate (ESR)
• Serum protein electrophoresis with immunofixation

Second-Line Laboratory Testing (Based on Clinical Suspicion)

• Vitamin deficiencies (B1, B6, E, folate)
• Heavy metal screening
• HIV testing
• Hepatitis panel (B and C)
• Lyme disease serology
• Cryoglobulins and cold agglutinins 1
• Anti-myelin associated glycoprotein (anti-MAG) antibodies 4
• Anti-ganglioside antibodies (including anti-GM1) 1, 4
• Vasculitis panel (ANA, ANCA, RF)
• Oral glucose tolerance test (for prediabetes)

Electrodiagnostic Studies

• Nerve conduction studies (NCS) to differentiate:
  • Axonal vs. demyelinating neuropathy
  • Sensory vs. motor involvement
  • Symmetric vs. asymmetric patterns 5
• Electromyography (EMG) to assess:
  • Active denervation
  • Chronic reinnervation
  • Distribution of involvement

Specialized Testing (When Indicated)

• Skin biopsy with intraepidermal nerve fiber density:

  • Particularly valuable for small fiber neuropathy when NCS is normal 6

• Quantitative sensory testing:

  • For objective assessment of sensory thresholds
  • Useful for small fiber neuropathy 4

• Autonomic function testing:

  • Heart rate variability
  • Orthostatic blood pressure
  • Sudomotor function 6

• Cerebrospinal fluid analysis:

  • For suspected inflammatory neuropathies
  • Particularly for Guillain-Barré syndrome and CIDP 3

• Nerve biopsy:

  • Reserved for cases where diagnosis remains unclear
  • Consider for suspected vasculitis, amyloidosis, or atypical presentations 7

• Genetic testing:

  • For suspected hereditary neuropathies
  • Family history of neuropathy
  • Early-onset or slowly progressive cases 5

Clinical Pitfalls and Caveats

1. Diabetic neuropathy is a diagnosis of exclusion - other treatable neuropathies may coexist with diabetes 1

2. Up to 50% of diabetic peripheral neuropathy may be asymptomatic - screening is essential to prevent complications 1

3. Noncompressible arteries (ABI >1.40) require toe pressure/toe-brachial index measurements instead of standard ABI 1

4. Electrodiagnostic testing may be normal in small fiber neuropathy - consider skin biopsy in these cases 6

5. Avoid unnecessary specialized testing when clinical presentation and basic testing provide clear diagnosis 7

6. Remember that peripheral neuropathy may be the presenting feature of systemic diseases like diabetes, thyroid disorders, or malignancy 3

By following this systematic diagnostic approach, clinicians can efficiently identify the underlying cause of peripheral neuropathy and implement appropriate treatment strategies to reduce morbidity and improve quality of life.