Neuropathy, Peripheral


A disease of the peripheral nervous system (PNS) that has multiple etiologies including diabetes, neurotoxic agents, alcohol use, nutrition deficiencies, immune-mediated causes, nerve compression, nerve injury, genetic mutations, and idiopathic (1)


  • A functional or structural disorder of the PNS, affecting any combination of motor, sensory, or autonomic nerves
  • Peripheral motor involvement causes muscle atrophy, weakness, cramps, and fasciculations.
  • Disorders of sensory nerves produce negative phenomena (loss of sensibility, lack of balance) or heightened phenomena (tingling or pain). Large sensory fiber dysfunction impairs touch and vibration sensation, whereas small fiber sensory neuropathy (SFSN) affects pin and thermal sensation and causes neuropathic pain.
  • The autonomic nervous system (ANS) dysfunction causes cardiovascular, gastrointestinal, and sudomotor symptoms.
  • Peripheral neuropathy (PN) can be subdivided as mononeuropathies, multifocal neuropathies, and polyneuropathies.


  • Diabetic PN is the most common cause of neuropathy globally (2).
  • Approximately 50% of Diabetics will develop PN (3).
  • Chemotherapy-induced PN (CIPN) is a frequent side effect of chemotherapeutic agents with an estimated 30% of patients experiencing CIPN at 6 months after chemotherapy (1).

Etiology and Pathophysiology

  • The most common cause of acquired PN is diabetes mellitus, which manifests most commonly at approximately 75% in the pattern of a distal sensory polyneuropathy (DSP).
  • Other causes include:
    • Vascular: ischemia, vasculitis
    • Infectious: HIV, hepatitis C, cryoglobulinemia, Lyme disease, varicella zoster
    • Traumatic: compression, crush, stretch, or transection (e.g., due to broken or dislocated bones, slipped disks between vertebrae, arthritis)
    • Autoimmune: rheumatoid arthritis, Sjögren syndrome, lupus
    • Metabolic: renal failure, hypothyroidism, vitamin B12 deficiency, celiac disease, porphyria
    • Iatrogenic/toxic: chemotherapy, platinum, taxanes, metronidazole, colchicine, infliximab, lead, alcoholism
    • Neoplastic/paraneoplastic: paraproteinemia, Waldenström macroglobulinemia, multiple myeloma, amyloidosis, neurofibromatosis

Approximately 50% of undiagnosed PN is hereditary.

Risk Factors

Diabetes and alcoholism

General Prevention

Management of underlying preventable causes of PN such as glycemic control, nutritional deficiencies, and avoiding neurotoxic agents

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