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Neuropathy: Causes, Symptoms, Types, and Management

Neuropathy (peripheral neuropathy) is damage to peripheral nerves causing sensory, motor, or autonomic dysfunction. It can be mononeuropathy (single nerve), multiplex, or polyneuropathy (symmetric, length-dependent).

Major Etiologies

  1. Diabetes mellitus: #1 cause. Metabolic (polyol pathway, AGEs, PKC, oxidative stress) + vascular injury. Distal symmetric sensorimotor ± autonomic.
  2. Alcohol: Toxic + nutritional (thiamine). Painful sensory > motor.
  3. Nutritional: B12 deficiency (subacute combined degeneration), B1, B6 (excess), E, copper.
  4. Autoimmune/Inflammatory: GBS, CIDP, vasculitic (PAN, cryoglobulinemia), paraneoplastic, Sjögren's, lupus.
  5. Hereditary: Charcot-Marie-Tooth (CMT1A dup 17p12), HNPP, familial amyloid neuropathy.
  6. Toxic: Chemo (platinum, taxanes, vincristine, bortezomib), heavy metals (lead, arsenic, mercury), medications (metronidazole, isoniazid, linezolid).
  7. Compressive/Traumatic: Carpal tunnel, radiculopathy, thoracic outlet.
  8. Infectious: HIV, Lyme, leprosy, diphtheria, CMV.
  9. Systemic: Amyloidosis, renal/hepatic failure, hypothyroidism, critical illness neuropathy.

    10. Symptoms

    • Sensory: numbness, tingling, burning, pain (neuropathic), allodynia, loss of vibration/position.
    • Motor: weakness, atrophy, fasciculations, cramps, foot drop.
    • Autonomic: orthostatic hypotension, gastroparesis, neurogenic bladder, erectile dysfunction, anhidrosis.

    Diagnosis

    • History, neuro exam (stocking-glove, reflexes, proprioception).
    • NCS/EMG (demyelinating vs. axonal, distribution).
    • Labs: glucose/HbA1c, B12, folate, TSH, SPEP/immunofixation, ANA, ESR, heavy metals, genetic panel.
    • Skin biopsy (small fiber), autonomic testing, nerve biopsy (rare).

    Treatment

    • Etiology-specific: glucose control, B12 replacement, immunosuppression (CIDP), plasmapheresis (GBS), toxin removal.
    • Symptomatic neuropathic pain: gabapentinoids, SNRIs (duloxetine), TCAs, topical lidocaine/capsaicin.
    • Physical therapy, orthotics, fall prevention.
    • Foot care (diabetic): daily inspection, proper footwear, podiatry.

    Early diagnosis prevents irreversible axonal loss. Multidisciplinary care optimizes function.

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