Distal Symmetric Polyneuropathy: A Review

JAMA. 2015 Nov 24;314(20):2172-81. doi: 10.1001/jama.2015.13611.


Importance: Peripheral neuropathy is a highly prevalent and morbid condition affecting 2% to 7% of the population. Patients frequently experience pain and are at risk of falls, ulcerations, and amputations. We aimed to review recent diagnostic and therapeutic advances in distal symmetric polyneuropathy, the most common subtype of peripheral neuropathy.

Observations: Current evidence supports limited routine laboratory testing in patients with distal symmetric polyneuropathy. Patients without a known cause should undergo a complete blood cell count, comprehensive metabolic panel, vitamin B12 measurement, serum protein electrophoresis with immunofixation, fasting glucose measurement, and glucose tolerance test. The presence of atypical features such as asymmetry, non-length dependence, motor predominance, acute or subacute onset, and prominent autonomic involvement should prompt a consultation with a neurologist or neuromuscular specialist. Electrodiagnostic tests and magnetic resonance imaging of the neuroaxis contribute substantial cost to the diagnostic evaluation, but evidence supporting their use is lacking. Strong evidence supports the use of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, and voltage-gated calcium channel ligands in the treatment of neuropathic pain. More intensive glucose control substantially reduces the incidence of distal symmetric polyneuropathy in patients with type 1 diabetes but not in those with type 2 diabetes.

Conclusions and relevance: The opportunity exists to improve guideline-concordant testing in patients with distal symmetric polyneuropathy. Moreover, the role of electrodiagnostic tests needs to be further defined, and interventions to reduce magnetic resonance imaging use in this population are needed. Even though several efficacious medications exist for neuropathic pain treatment, pain is still underrecognized and undertreated. New disease-modifying medications are needed to prevent and treat peripheral neuropathy, particularly in type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Calcium Channel Blockers / therapeutic use
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / complications
  • Electrodiagnosis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Magnetic Resonance Imaging
  • Polyneuropathies / diagnosis*
  • Polyneuropathies / etiology*
  • Polyneuropathies / therapy*
  • Practice Guidelines as Topic
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use


  • Antidepressive Agents
  • Calcium Channel Blockers
  • Hypoglycemic Agents
  • Serotonin and Noradrenaline Reuptake Inhibitors