Last updated: November 20, 2023

Summarytoggle arrow icon

Polyneuropathy is a disorder that involves damage to multiple peripheral nerve fibers. Causes include diabetes mellitus, alcohol use disorder, hereditary diseases, toxins, infection, or other inflammatory conditions. The classic presentation is a symmetrical distal burning sensation or loss of sensation. Further clinical features depend on whether an axonal or demyelinating nerve injury has occurred. Diagnosis is usually clinical, supported by laboratory studies to rule out common causes such as diabetes. Further diagnostic tests such as electrodiagnostic studies are reserved for patients with 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).

See also “Diabetic neuropathy.”

Etiologytoggle arrow icon

Diabetes mellitus and alcohol use disorder account for most cases in developed countries.


Clinical featurestoggle arrow icon


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
Associated conditions


Subtypes and variantstoggle arrow icon

See also “Diabetic neuropathy.”

Alcoholic polyneuropathy [12][13][14]

Hereditary motor sensory neuropathy (HMSN) [15][16][17]

Overview [17]

HMSN type I

Other types of HMSN [17][20][21]

HMSN is a heterogeneous group of diseases with variable symptom onset and severity. Generally, progression of symptoms is slow and life expectancy is unaffected. [15]

Refsum disease [23][24]

Chronic inflammatory demyelinating polyneuropathy (CIDP) [25]

Diagnosticstoggle arrow icon

Approach [6][30][31]

  • All patients
    • Obtain initial laboratory workup to evaluate for common causes.
    • Consider further laboratory studies based on clinical features.
  • Atypical clinical presentation or nondiagnostic initial workup: Refer to neurology for further studies.

In many cases of polyneuropathy, the underlying cause remains unknown despite thorough clinical evaluation, laboratory testing, and electrodiagnostic studies. [6]

Laboratory studies [6][32]

Electrodiagnostic studies [6]

  • Indications
    • Acute onset or rapid progression of symptoms
    • Asymmetrical symptoms
    • Primarily motor or autonomic dysfunction
    • Diffuse reflex loss [35]
    • Nondiagnostic initial workup
  • Modalities [35]

Electrodiagnostic studies can help identify and localize nerve dysfunction, but often do not reveal the underlying cause of neuropathy. [35]

Additional testing [6][33]

Only request imaging of the brain or spine if there are clinical features of CNS lesions or radiculopathy. [6]

Differential diagnosestoggle arrow icon

Mononeuritis multiplex

Differential diagnosis of impaired sensation and sensory ataxia

Polyneuropathy Multiple sclerosis Subacute combined degeneration Tabes dorsalis Compressive myelopathy


Impairment of sensation
  • 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.

Treatmenttoggle arrow icon

Approach [6][30][38]

Management of polyneuropathy is based on treating the underlying cause and providing symptom control.

Nonpharmacological methods [6]

Pharmacological therapy [6][38]

Pharmacological treatment of peripheral neuropathy [38]
Drug class Drugs Clinical considerations
Tricyclic antidepressants
  • Reduce the dose in patients with renal dysfunction.


  • Reduce the dose in patients with renal dysfunction.
Topical analgesics
  • Lidocaine patches
  • Capsaicin patches [42]
  • Capsaicin cream [43]
  • Capsaicin patches should only be applied under close physician supervision. [42]
Opioid agonists

Avoid combining antidepressant classes or antidepressants with tramadol because of the risk of serotonin syndrome. [38]

Treatment efficacy can only be assessed after 3–8 weeks of therapy. Since complete pain relief is often not possible, a tolerable level of pain may be an acceptable treatment goal. [38]

Referencestoggle arrow icon

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