Peripheral Neuropathy

Definition

Disease of the peripheral nerves producing sensory, motor or autonomic deficit. Patterns include length dependent polyneuropathy, mononeuropathy and mononeuritis multiplex.

Aetiology

  • Diabetes mellitus is the commonest acquired cause
  • Alcohol, B12 deficiency, hypothyroidism, renal failure and chemotherapy
  • Hereditary motor and sensory neuropathy, see Charcot-Marie-Tooth disease
  • Inflammatory causes include Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy
  • Leprosy is a frequent infective cause in endemic regions

Classification

  • Axonal neuropathy shows reduced amplitudes on nerve conduction studies
  • Demyelinating neuropathy shows slowed conduction velocity and prolonged distal latency
  • CMT1 is demyelinating and CMT2 is axonal

Clinical Features

  • Stocking and glove sensory loss, starting in the toes
  • Early loss of ankle reflexes and vibration sense
  • Intrinsic wasting, claw toes and cavovarus feet in hereditary types
  • Neuropathic ulcers under the metatarsal heads of insensate feet
  • Charcot neuroarthropathy of the midfoot and ankle, see Charcot arthropathy
  • Positive Romberg test with large fibre loss
  • Failure to feel the 10 g Semmes-Weinstein monofilament predicts ulceration

Investigations

  • Glucose, HbA1c, B12, thyroid and renal function, and serum protein electrophoresis
  • Nerve conduction studies separate axonal from demyelinating disease, see electrophysiological studies
  • PMP22 duplication testing in suspected CMT1A
  • Foot radiographs for Charcot change and osteomyelitis

Differential Diagnosis

Management

  • Glycaemic control. Slows progression of diabetic neuropathy
  • Foot care. Daily inspection, protective footwear and podiatry prevent ulcers
  • Ankle foot orthosis. Foot drop
  • Total contact cast. Offloads neuropathic plantar ulcers
  • Surgery. Tendon transfer and osteotomy for flexible or rigid cavovarus deformity
  • Neuropathic pain agents. Duloxetine, pregabalin or amitriptyline for painful neuropathy

Complications

  • Ulceration, infection and amputation in diabetic feet
  • Charcot collapse after an unrecognised fracture or surgery

References

  1. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW, Viswanathan V. Diabetic neuropathy. Nat Rev Dis Primers. 2019, 5(1), 41. PubMed
  2. Pareyson D, Marchesi C. Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Lancet Neurol. 2009, 8(7), 654-67. PubMed

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.