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Key Features

Essentials of Diagnosis

  • Weakness, sensory disturbances, or both in the extremities

  • Pain is common

  • Depressed or absent tendon reflexes

  • May have family history of neuropathy

  • May have history of systemic illness or toxic exposure

General Considerations

  • Categorized as axonal or demyelinating based on neurophysiologic findings

  • The cause is suggested by the history, mode of onset, and predominant clinical manifestations


  • Charcot-Marie-Tooth disease

  • Dejerine-Sottas disease (HMSN type III)

  • Friedreich ataxia

  • Refsum disease (HMSN type IV)

  • Porphyria (axonal)

    • Motor symptoms usually occur first, and weakness is often most marked proximally and in the upper limbs

    • Sensory symptoms and signs may be proximal or distal in distribution

    • Autonomic involvement is sometimes pronounced


  • Diabetes mellitus

    • Symmetric sensory or mixed polyneuropathy

    • Asymmetric motor radiculoneuropathy or plexopathy (diabetic amyotrophy)

    • Thoracoabdominal radiculopathy

    • Autonomic neuropathy

    • Isolated lesions of individual nerves may occur singly or in any combination

  • Uremia

    • Symmetric sensorimotor polyneuropathy

    • Tends to affect the lower limbs more than the upper limbs

    • More marked distally than proximally

  • Alcoholism and nutritional deficiency (thiamine and B12)

    • Axonal distal sensorimotor polyneuropathy

    • Frequently accompanied by painful cramps, muscle tenderness, and painful paresthesias

    • Often more marked in legs than arms

    • Symptoms of autonomic dysfunction may be conspicuous

    • A similar distal sensorimotor polyneuropathy is a well-recognized feature of beriberi (thiamine deficiency)

    • In vitamin B12 deficiency, distal sensory polyneuropathy may develop but is usually overshadowed by CNS manifestations

  • Paraproteinemias, especially plasma cell myeloma (formerly multiple myeloma), but also with macroglobulinemia and cryoglobulinemia

    • A gradual onset, progressive, symmetric sensorimotor neuropathy

    • Often accompanied by pain and dysesthesias in the limbs

    • Carpal tunnel syndrome may be seen in generalized amyloidosis


  • Leprosy

    • Sensory disturbances from involvement of intracutaneous nerves

    • Motor deficits from involvement of superficial nerves where their temperature is lowest, eg, the ulnar nerve in the region proximal to the olecranon groove

  • AIDS

    • Chronic symmetric sensorimotor axonal polyneuropathy with normal cerebrospinal fluid (CSF) findings

    • Progressive polyradiculopathy or radiculomyelopathy that leads to leg weakness and urinary retention (CSF may show mononuclear pleocytosis and increased protein and low glucose concentrations); cytomegalovirus is responsible in at least some cases

    • An inflammatory demyelinating polyradiculoneuropathy with weakness more obvious distally than proximally and depressed or absent tendon reflexes (CSF shows an increased cell count and protein concentration)

  • Lyme borreliosis

  • Sarcoidosis

  • Polyarteritis

  • Rheumatoid arthritis


  • Initial manifestation may be difficulty in weaning from a mechanical ventilator

  • In more advanced cases, there is wasting and weakness of the extremities and loss of tendon reflexes

  • Sensory abnormalities are relatively inconspicuous

  • Good prognosis if patients recover from the underlying critical illness


  • Toxic neuropathies

  • Neuropathies associated with malignant diseases (see ...

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