Peripheral Neuropathy: Evaluation and Differential Diagnosis
Am Fam Physician. 2020 Dec 15;102(12):732-739.
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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.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
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 https://www.aafp.org/afpsort.
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Referencesshow all references
1. Doughty CT, Seyedsadjadi R. Approach to peripheral neuropathy for the primary care clinician. Am J Med. 2018;131(9):1010–1016....
2. Barrell K, Smith AG. Peripheral neuropathy. Med Clin North Am. 2019;103(2):383–397.
3. Mayans L, Mayans D. Causes of peripheral neuropathy: diabetes and beyond. J Fam Pract. 2015;64(12):774–783.
4. Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314(20):2172–2181.
5. Hanewinckel R, van Oijen M, Ikram MA, et al. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016;31(1):5–20.
6. Spallone V, Lacerenza M, Rossi A, et al. Painful diabetic polyneuropathy: approach to diagnosis and management. Clin J Pain. 2012;28(8):726–743.
7. Gwathmey KG, Pearson KT. Diagnosis and management of sensory polyneuropathy. BMJ. 2019;365:l1108.
8. Hanewinckel R, Ikram MA, Van Doorn PA. Peripheral neuropathies. Handb Clin Neurol. 2016;138:263–282.
9. Hanewinckel R, Drenthen J, van Oijen M, et al. Prevalence of polyneuropathy in the general middle-aged and elderly population. Neurology. 2016;87(18):1892–1898.
10. Arnold ML. Steering peripheral neuropathy workup. Phys Med Rehabil Clin N Am. 2018;29(4):761–776.
11. Azhary H, Farooq MU, Bhanushali M, et al. Peripheral neuropathy: differential diagnosis and management. Am Fam Physician. 2010;81(7):887–892. Accessed May 22, 2020. https://www.aafp.org/afp/2010/0401/p887.html
12. Alport AR, Sander HW. Clinical approach to peripheral neuropathy: anatomic localization and diagnostic testing. Continuum (Minneap Minn). 2012;18(1):13–38.
13. Poncelet AN. An algorithm for the evaluation of peripheral neuropathy. Am Fam Physician. 1998;57(4):755–764. Accessed July 13, 2020. https://www.aafp.org/afp/1998/0215/p755.html
14. Vinik AI. Clinical practice. Diabetic sensory and motor neuropathy [published corrections appear in N Engl J Med. 2016;374(18):1797, and N Engl J Med. 2016;375(14):1402]. N Engl J Med. 2016;374(15):1455–1464.
15. Karam C, Dyck PJB. Toxic neuropathies. Semin Neurol. 2015;35(4):448–457.
16. Rossor AM, Carr AS, Devine H, et al. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis. J Neurol Neurosurg Psychiatry. 2017;88(10):846–863.
17. Misra UK, Kalita J, Nair PP. Diagnostic approach to peripheral neuropathy. Ann Indian Acad Neurol. 2008;11(2):89–97.
18. Younger DS. Vasculitis of the nervous system. Curr Opin Neurol. 2004;17(3):317–336.
19. Watson JC, Dyck PJB. Peripheral neuropathy: a practical approach to diagnosis and symptom management. Mayo Clin Proc. 2015;90(7):940–951.
20. Willison HJ, Winer JB. Clinical evaluation and investigation of neuropathy. J Neurol Neurosurg Psychiatry. 2003;74(suppl 2):ii3–ii8.
21. England JD, Gronseth GS, Franklin G, et al.; American Academy of Neurology. Practice parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Neurology. 2009;72(2):185–192.
22. Bodofsky EB, Carter GT, England JD. Is electrodiagnostic testing for polyneuropathy overutilized? Muscle Nerve. 2017;55(3):301–304.
23. Callaghan BC, Kerber KA, Lisabeth LL, et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol. 2014;71(9):1143–1149.
24. Kwee RM, Chhabra A, Wang KC, et al. Accuracy of MRI in diagnosing peripheral nerve disease: a systematic review of the literature. AJR Am J Roentgenol. 2014;203(6):1303–1309.
25. Callaghan BC, Price RS, Chen KS, et al. The importance of rare subtypes in diagnosis and treatment of peripheral neuropathy: a review. JAMA Neurol. 2015;72(12):1510–1518.
26. Anish L, Nagappa M, Mahadevan A, et al. Neuropathy in elderly: lessons learnt from nerve biopsy. Age Ageing. 2015;44(2):312–317.
27. Gabriel CM, Howard R, Kinsella N, et al. Prospective study of the usefulness of sural nerve biopsy. J Neurol Neurosurg Psychiatry. 2000;69(4):442–446.
28. Hughes RAC. Peripheral neuropathy. BMJ. 2002;324(7335):466–469.
29. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173.
30. Attal N, Cruccu G, Baron R, et al.; European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113–1123.
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