Last updated: January 27, 2022

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Polyneuropathy is a disorder that involves damage to multiple peripheral nerve fibers. The condition can be caused by diabetes mellitus, alcoholism, hereditary diseases, toxins, infection, or other inflammatory conditions. The classic presentation is a symmetric distal burning or loss of sensation. Further clinical features depend on whether an axonal or demyelinating nerve injury has occurred. Diagnostic tests such as electrodiagnostic studies are indicated in the case of atypical clinical features, unknown etiology, and/or severe or rapidly progressive symptoms. Management involves treatment of the underlying disorder and symptomatic therapy (e.g., control of neuropathic pain).



Axonal vs. demyelinating

Overview of axonal and demyelinating neuropathies
Features Axonal Demyelinating
Chronic Acute Chronic Acute


  • Slow decline over years
  • Months to years of slow, yet incomplete recovery
  • Variable (periods of recovery, stabilization, exacerbations, or slow decline)
  • Variable
  • Affects longer axons first (begins in lower extremities → sternum (intercostal nerves) → head)
  • Early disease: sensory symptoms > motor symptoms
  • Similar, but symptoms more severe
  • Significant pain
  • Early disease: motor symptoms = sensory symptoms
  • Early disease: motor symptoms > sensory symptoms
  • Distal muscle wasting: feet, lower legs, hands (severe cases)
  • Distal sensory loss (pain, temperature, proprioception, vibration)
  • Reduced or absent distal reflexes (usually begins in the ankles)
Associated conditions


Diabetic polyneuropathy

Alcoholic polyneuropathy

Hereditary motor sensory neuropathies (HMSN)

HMSN type I (Charcot-Marie-Tooth disease)

  • Etiology: most commonly caused by duplication of the gene PMP22 in chromosome 17
  • Clinical features
    • Distal symmetric sensorimotor polyneuropathy
      • Foot drop
      • Atrophy of the calf muscles (“stork legs”)
      • Pes cavus deformity
      • Hammer toe
      • Intrinsic hand musculature may become involved after several years.
      • Sensory loss (occurs late)
    • May be associated with sleep apnea
  • Diagnostics

HMSN type IV (Refsum disease)

HMSN type V

Other types of hereditary motor sensory neuropathies


Further tests are usually indicated in patients with atypical clinical features, an unknown etiology, and/or severe or rapidly progressive symptoms.


Mononeuritis multiplex

Differential diagnosis of impaired sensation and sensory ataxia

Polyneuropathy Multiple sclerosis Subacute combined degeneration Tabes dorsalis Compressive myelopathy


Impairment of sensation
  • Symmetrical distal loss of all the types of sensation (stocking-and-glove distribution)
  • Loss of all types of sensation is possible (distribution depends on the lesion).
Motor neuron signs
  • None
Other features

Other considerations

The differential diagnoses listed here are not exhaustive.

Treatment efficacy can only be assessed after 2–4 weeks of therapy. Since complete pain relief is often not possible, a tolerable level of pain may be an acceptable treatment goal.


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