What is the general diagnostic approach to polyneuropathy?

Diagnostic Approach to Polyneuropathy

The diagnosis of polyneuropathy should be based upon a combination of clinical symptoms, signs, and electrodiagnostic criteria, with subsequent laboratory testing to identify the underlying etiology. 1

Clinical Assessment

• Evaluate for characteristic symptoms of polyneuropathy including distal paresthesias, numbness, pain, cramps, and weakness that typically begin symmetrically in the toes and feet, later progressing to fingertips 2

• Physical examination should focus on:

  • Distal sensory loss (particularly vibration and pinprick sensation) 3
  • Reduced or absent ankle reflexes 3
  • Distal muscle weakness and wasting 2, 4
  • Gait abnormalities (wide-based, unsteady) 2
  • Autonomic signs (orthostatic hypotension, skin changes) 2, 5

• Combining ankle reflex examination with either vibration or pinprick sensory testing provides the highest sensitivity (88%) for diagnosing polyneuropathy 3

Electrodiagnostic Studies

• Nerve conduction studies and electromyography are essential to:
  • Confirm the diagnosis of polyneuropathy 1
  • Distinguish between axonal and demyelinating patterns 6
  • Separate sensorimotor from pure sensory neuropathies 6
  • Document the severity and distribution of nerve involvement 7

Laboratory Testing

• Screening laboratory tests should be performed for all patients with confirmed polyneuropathy (Level C) 1

• The highest-yield screening tests include:

  • Blood glucose (elevated in approximately 11% of polyneuropathy cases) 1
  • Serum B12 with metabolites (methylmalonic acid and homocysteine) (abnormal in 3.6-8% of cases) 1
  • Serum protein immunofixation electrophoresis (abnormal in approximately 9% of cases) 1
  • Complete blood count 1
  • Erythrocyte sedimentation rate 1
  • Comprehensive metabolic panel (renal and liver function) 1
  • Thyroid function tests 1

• If routine blood glucose testing is normal, consider testing for impaired glucose tolerance in patients with distal symmetric sensory polyneuropathy (Level C) 1

Special Considerations for Specific Polyneuropathy Types

Small Fiber Polyneuropathy

• When small fiber polyneuropathy is suspected (prominent pain, burning sensations, autonomic symptoms with minimal motor findings):
  • Skin biopsy with intraepidermal nerve fiber density measurement is recommended 2, 5
  • Conventional nerve conduction studies may be normal 2

Autonomic Neuropathy

• For suspected autonomic involvement:
  • Perform autonomic testing including heart rate variability to deep breathing and Valsalva maneuver 8, 5
  • Use a battery of validated autonomic tests rather than a single test for highest diagnostic accuracy 5
  • Testing should be performed in a controlled environment (temperature 21-23°C) after appropriate patient preparation (fasting, avoiding caffeine) 8

Hereditary Neuropathy

• Consider genetic testing when:
  • Patient exhibits a hereditary neuropathy phenotype (Level C) 1
  • There is a family history of neuropathy 1
  • Initial genetic testing should focus on CMT1A duplication/HNPP deletion, Cx32 (GJB1), and MFN2 mutations 1

Streamlining the Diagnostic Approach

• In patients with typical polyneuropathy symptoms and certain conditions (diabetes mellitus, renal failure, HIV infection, alcoholism, or use of potentially neurotoxic drugs), extensive additional testing may be unnecessary 6
• Cerebrospinal fluid analysis has low diagnostic yield except in suspected demyelinating polyneuropathies 1
• Nerve biopsy should be reserved for cases where vasculitis or other specific inflammatory conditions are suspected 2

Common Pitfalls to Avoid

• Relying solely on laboratory tests without clinical correlation (laboratory tests alone have only a 37% diagnostic yield) 1
• Failing to test for B12 deficiency with metabolites, as serum B12 levels in the low-normal range (200-500 pg/dL) may still indicate deficiency 1
• Overlooking impaired glucose tolerance in patients with normal fasting blood glucose 1
• Performing autonomic testing during acute illness, stressful conditions, or without appropriate medication washout 8
• Dismissing the possibility of polyneuropathy when only sensory symptoms are present 4, 3