Peripheral Neuropathy: Evaluation and Differential Diagnosis


Am Fam Physician. 2020 Dec 15;102(12):732-739.

Author disclosure: No relevant financial affiliations.

Peripheral neuropathy, a common neurologic problem encountered by family physicians, can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease. The prevalence of peripheral neuropathy in the general population ranges from 1% to 7%, with higher rates among those older than 50 years. Common identifiable causes include diabetes mellitus, nerve compression or injury, alcohol use, toxin exposure, hereditary diseases, and nutritional deficiencies. Peripheral neuropathy is idiopathic in 25% to 46% of cases. Diagnosis requires a comprehensive history, physical examination, and judicious laboratory testing. Early peripheral neuropathy may present as sensory alterations that are often progressive, including sensory loss, numbness, pain, or burning sensations in a “stocking and glove” distribution of the extremities. Later stages may involve proximal numbness, distal weakness, or atrophy. Physical examination should include a comprehensive neurologic and musculoskeletal evaluation. If the peripheral nervous system is identified as the likely source of the patient's symptoms, evaluation for potential underlying etiologies should initially focus on treatable causes. Initial laboratory evaluation includes a complete blood count; a comprehensive metabolic profile; fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; and serum protein electrophoresis with immunofixation. If the initial evaluation is inconclusive, referral to a neurologist for additional testing (e.g., electrodiagnostic studies, specific antibody assays, nerve biopsy) should be considered. Treatment of peripheral neuropathy focuses on managing the underlying etiology. Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain.

Peripheral neuropathy is one of the most common neurologic problems encountered by family physicians.1,2 Peripheral neuropathy can be classified clinically by the anatomic pattern of presenting symptoms and, if indicated, by results of electrodiagnostic studies for axonal and demyelinating disease.2,3 Peripheral nerves consist of motor, sensory, and autonomic nerve fibers. It is important to differentiate peripheral neuropathy from other disorders with similar presentations and to identify and address potential causes.

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Clinical recommendationEvidence ratingComments

Initial evaluation of a patient with suspected peripheral neuropathy should include a complete blood count; comprehensive metabolic profile; fasting blood glucose, thyroid-stimulating hormone, and vitamin B12 levels; and serum protein electrophoresis with immunofixation.1,20,21


Expert opinion and consensus guideline in the absence of clinical trials

Patients with peripheral neuropathy should be referred for electrodiagnostic studies if symptoms are worrisome (e.g., acute onset, asymmetrical, predominant motor or autonomic symptoms, rapidly progressive clinical course) or if initial workup is normal and symptoms persist.1,20,22


Expert opinion and consensus guideline in the absence of clinical trials

Imaging should not be routinely ordered to aid in the diagnosis of peripheral neuropathy. In cases of polyradiculopathy, plexopathy, or radiculoplexus neuropathy, magnetic resonance imaging may help in localizing an atypical neuropathy.23,25


Expert opinion and consensus guideline in the absence of clinical trials

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to

The Authors

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GREGORY CASTELLI, PharmD, BCPS, BC-ADM, is a clinical pharmacist and the program director of the Pharmacy Residency Program at the University of Pittsburgh (Pa.) Medical Center St. Margaret....

KRISHNA M. DESAI, MD, is an assistant professor at the Center for Family and Community Medicine at Columbia University Medical Center, New York, N.Y.

REBECCA E. CANTONE, MD, is the director of student education and an assistant professor in the Department of Family Medicine at Oregon Health and Science University, Portland.

Address correspondence to Gregory Castelli, PharmD, BCPS, BC-ADM, UPMC Saint Margaret, 815 Freeport Rd., Pittsburgh, PA 15215 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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