Polyneuropathy

Last updated: July 18, 2022

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).

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

References:[1][2][3][4][5][6]

General

Axonal vs. demyelinating

Overview of axonal and demyelinating neuropathies
Features Axonal Demyelinating
Chronic Acute Chronic Acute

Progression

  • Slow decline over years
  • Months to years of slow, yet incomplete recovery
  • Variable (periods of recovery, stabilization, exacerbations, or slow decline)
  • Variable
Characteristics
  • 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

References:[8][9][10][11]

Diabetic neuropathies

Diabetic neuropathies are the development of progressive nerve injury (e.g., peripheral, autonomic) due to chronic hyperglycemia.

Distal symmetric polyneuropathy in diabetes [12][13][14]

Patients with diabetic peripheral neuropathy are often asymptomatic. Regular examinations are recommended to identify sensory deficits early and initiate measures to prevent injury. [12]

Other forms of diabetic neuropathy [12]

Alcoholic polyneuropathy [15][16][17]

Hereditary motor sensory neuropathy (HMSN) [18][19][20]

Overview [20]

HMSN type I

Other types of HMSN [20][23][24]

HMSN is a heterogeneous group of diseases with variable symptom onset and severity. Generally, progression of symptoms is slow and life expectancy is unaffected. [18]

Refsum disease [26][27]

Chronic inflammatory demyelinating polyneuropathy (CIDP) [28]

Approach [6][33][34]

  • 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][35]

Electrodiagnostic studies [6]

  • Indications
    • Acute onset or rapid progression of symptoms
    • Asymmetrical symptoms
    • Primarily motor or autonomic dysfunction
    • Diffuse reflex loss [38]
    • Nondiagnostic initial workup
  • Modalities [38]

Electrodiagnostic studies can help identify and localize nerve dysfunction, but often do not reveal the underlying cause of neuropathy. [38]

Additional testing [6][36]

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

Mononeuritis multiplex

Differential diagnosis of impaired sensation and sensory ataxia

Polyneuropathy Multiple sclerosis Subacute combined degeneration Tabes dorsalis Compressive myelopathy

Pathogenesis

Impairment of sensation
  • Symmetrical distal loss of all the types of sensation (stocking-and-glove distribution)
  • 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.

Approach [6][33][41]

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

Nonpharmacological methods [6]

Pharmacological therapy [6][41]

Pharmacological treatment of peripheral neuropathy [41]
Drug class Drugs Clinical considerations
Tricyclic antidepressants
SNRIs
  • Reduce the dose in patients with renal dysfunction.

Gabapentinoids

  • Reduce the dose in patients with renal dysfunction.
Topical analgesics
  • Lidocaine patches
  • Capsaicin patches [45]
  • Capsaicin cream [46]
  • Capsaicin patches should only be applied under close physician supervision. [45]
Opioid agonists

Avoid combining antidepressant classes or antidepressants with tramadol because of the risk of serotonin syndrome. [41]

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. [41]

  1. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2016; 40 (1): p.136-154. doi: 10.2337/dc16-2042 . | Open in Read by QxMD
  2. Snyder MJ, Gibbs LM, Lindsay TJ. Treating Painful Diabetic Peripheral Neuropathy: An Update.. Am Fam Physician. 2016; 94 (3): p.227-34.
  3. Vinik AI. Diabetic Sensory and Motor Neuropathy. N Engl J Med. 2016; 374 (15): p.1455-1464. doi: 10.1056/nejmcp1503948 . | Open in Read by QxMD
  4. Julian T, Glascow N, Syeed R, Zis P. Alcohol-related peripheral neuropathy: a systematic review and meta-analysis. J Neurol. 2018; 266 (12): p.2907-2919. doi: 10.1007/s00415-018-9123-1 . | Open in Read by QxMD
  5. Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006; 19 (5): p.481-486. doi: 10.1097/01.wco.0000245371.89941.eb . | Open in Read by QxMD
  6. Vittadini G. Alcoholic polyneuropathy: a clinical and epidemiological study. Alcohol Alcohol. 2001; 36 (5): p.393-400. doi: 10.1093/alcalc/36.5.393 . | Open in Read by QxMD
  7. Castelli G, Desai KM, Cantone RE. Peripheral Neuropathy: Evaluation and Differential Diagnosis.. Am Fam Physician. 2020; 102 (12): p.732-739.
  8. Laurá M, Pipis M, Rossor AM, Reilly MM. Charcot–Marie–Tooth disease and related disorders: an evolving landscape. Curr Opin Neurol. 2019; 32 (5): p.641-650. doi: 10.1097/wco.0000000000000735 . | Open in Read by QxMD
  9. Szigeti K, Lupski JR. Charcot–Marie–Tooth disease. Eur J Hum Genet. 2009; 17 (6): p.703-710. doi: 10.1038/ejhg.2009.31 . | Open in Read by QxMD
  10. Bertorini TE. Neuromuscular Disorders E-Book. Elsevier Health Sciences ; 2021
  11. Stevens F, Weerkamp NJ, Cals JWL. Foot drop. BMJ. 2015; 350 (apr27 6): p.h1736-h1736. doi: 10.1136/bmj.h1736 . | Open in Read by QxMD
  12. Tracy JA, Dyck PJ, Klein CJ, Engelstad JK, Meyer JE, Dyck PJB. Onion‐bulb patterns predict acquired or inherited demyelinating polyneuropathy. Muscle Nerve. 2019; 59 (6): p.665-670. doi: 10.1002/mus.26452 . | Open in Read by QxMD
  13. Reilly MM. Classification of the hereditary motor and sensory neuropathies. Curr Opin Neurol. 2000; 13 (5): p.561-564. doi: 10.1097/00019052-200010000-00009 . | Open in Read by QxMD
  14. Barisic N, Claeys KG, Sirotković-Skerlev M, et al. Charcot-Marie-Tooth Disease: A Clinico-genetic Confrontation. Ann Hum Genet. 2008; 72 (3): p.416-441. doi: 10.1111/j.1469-1809.2007.00412.x . | Open in Read by QxMD
  15. Schwartzman RJ. Differential Diagnosis in Neurology. IOS Press ; 2019
  16. Wanders RJA, Jansen GA, Skjeldal OH. Refsum Disease, Peroxisomes and Phytanic Acid Oxidation: A Review. J Neuropathol Exp Neurol. 2001; 60 (11): p.1021-1031. doi: 10.1093/jnen/60.11.1021 . | Open in Read by QxMD
  17. A.J. Wills. Refsum's disease. QJM. 2001; 94 (8): p.403-406. doi: 10.1093/qjmed/94.8.403 . | Open in Read by QxMD
  18. Van den Bergh PYK, Doorn PA, Hadden RDM, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force—Second revision. Journal of the Peripheral Nervous System. 2021; 26 (3): p.242-268. doi: 10.1111/jns.12455 . | Open in Read by QxMD
  19. Lehmann HC, Burke D, Kuwabara S. Chronic inflammatory demyelinating polyneuropathy: update on diagnosis, immunopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2019; 90 (9): p.981-987. doi: 10.1136/jnnp-2019-320314 . | Open in Read by QxMD
  20. Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Incidence and Prevalence of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2019; 52 (3-4): p.161-172. doi: 10.1159/000494291 . | Open in Read by QxMD
  21. Dyck PJB, Tracy JA. History, Diagnosis, and Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy. Mayo Clin Proc. 2018; 93 (6): p.777-793. doi: 10.1016/j.mayocp.2018.03.026 . | Open in Read by QxMD
  22. Mathey EK, Park SB, Hughes RAC, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry. 2015; 86 (9): p.973-985. doi: 10.1136/jnnp-2014-309697 . | Open in Read by QxMD
  23. Hughes R. Investigation of peripheral neuropathy. The BMJ. 2010; 341 (6100). doi: 10.1136/bmj.c6100 . | Open in Read by QxMD
  24. Massey EW, Stolp KA. Peripheral neuropathy in pregnancy. Phys Med Rehabil Clin N Am. 2008; 19 (1): p.149-162. doi: 10.1016/j.pmr.2007.10.004 . | Open in Read by QxMD
  25. Cojocaru IM, Cojocaru M, Silosi I, Vrabie CD. Peripheral nervous system manifestations in systemic autoimmune diseases. Maedica (Buchar). 2014; 9 (3): p.289-294.
  26. Delanian S, Lefaix J-L, Pradat P-F. Radiation-induced neuropathy in cancer survivors. Radiother Oncol.. 2012; 105 (3): p.273–282. doi: 10.1016/j.radonc.2012.10.012 . | Open in Read by QxMD
  27. Brizzi KT, Lyons JL. Peripheral nervous system manifestations of infectious diseases. Neurohospitalist. 2014; 4 (4): p.230–240. doi: 10.1177/1941874414535215 . | Open in Read by QxMD
  28. Said G. Uremic neuropathy. Elsevier ; 2013 : p. 607-612
  29. Disorders of the Nervous System - Chapter 9 - Sensory System Evaluation. https://www.dartmouth.edu/~dons/part_1/chapter_9.html. Updated: January 1, 2008. Accessed: June 13, 2017.
  30. Smith SJM, Ali Z, Fowler CJ. Cutaneous thermal thresholds in patients with painful burning feet. J Neurol Neurosurg Psychiatry. 1991; 54 (10): p.877-881.
  31. Cruse RP, Nordli DR, Firth HV, Shefner JM, Dashe JF. Hereditary Primary Motor Sensory Neuropathies, Including Charcot-Marie-Tooth Disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hereditary-primary-motor-sensory-neuropathies-including-charcot-marie-tooth-disease.Last updated: April 13, 2016. Accessed: June 15, 2017.
  32. Rutkove SB, Shefner JM, Dashe JF. Overview of Polyneuropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-polyneuropathy.Last updated: December 1, 2015. Accessed: June 16, 2017.
  33. Callaghan BC, Price RS, Feldman EL. Distal Symmetric Polyneuropathy. JAMA. 2015; 314 (20): p.2172. doi: 10.1001/jama.2015.13611 . | Open in Read by QxMD
  34. Barohn RJ, Amato AA. Pattern-Recognition Approach to Neuropathy and Neuronopathy. Neurol Clin. 2013; 31 (2): p.343-361. doi: 10.1016/j.ncl.2013.02.001 . | Open in Read by QxMD
  35. England JD, Gronseth GS, Franklin G, et al. Practice Parameter: Evaluation of distal symmetric polyneuropathy: Role of laboratory and genetic testing (an evidence-based review). Neurology. 2008; 72 (2): p.185-192. doi: 10.1212/01.wnl.0000336370.51010.a1 . | Open in Read by QxMD
  36. Tavee JO. Office approach to small fiber neuropathy. Cleve Clin J Med. 2018; 85 (10): p.801-812. doi: 10.3949/ccjm.85a.17124 . | Open in Read by QxMD
  37. Albers JW, Fink JK. Porphyric neuropathy. Muscle Nerve. 2004; 30 (4): p.410-422. doi: 10.1002/mus.20137 . | Open in Read by QxMD
  38. Ginsberg MR, Morren JA, Levin K. Using and interpreting electrodiagnostic tests. Cleve Clin J Med. 2020; 87 (11): p.671-682. doi: 10.3949/ccjm.87a.19154 . | Open in Read by QxMD
  39. Kincaid JC. Neurophysiologic Studies in the Evaluation of Polyneuropathy. Continuum (Minneap Minn). 2017; 23 (5): p.1263-1275. doi: 10.1212/con.0000000000000521 . | Open in Read by QxMD
  40. Kollmer J, Bendszus M. Magnetic Resonance Neurography: Improved Diagnosis of Peripheral Neuropathies. Neurotherapeutics. 2021; 18 (4): p.2368-2383. doi: 10.1007/s13311-021-01166-8 . | Open in Read by QxMD
  41. Bates D, Schultheis BC, Hanes MC, et al. A Comprehensive Algorithm for Management of Neuropathic Pain. Pain Medicine. 2019; 20 (Supplement_1): p.S2-S12. doi: 10.1093/pm/pnz075 . | Open in Read by QxMD
  42. Staff NP, Windebank AJ. Peripheral neuropathy due to vitamin deficiency, toxins, and medications. Continuum (Minneap Minn). 2014; 20 (5 Peripheral Nervous System Disorders): p.1293-306. doi: 10.1212/01.CON.0000455880.06675.5a . | Open in Read by QxMD
  43. Kuwabara S, Misawa S, Mori M, Tamura N, Kubota M, Hattori T. Long term prognosis of chronic inflammatory demyelinating polyneuropathy: a five year follow up of 38 cases. J Neurol Neurosurg Psychiatry. 2006; 77 (1): p.66-70. doi: 10.1136/jnnp.2005.065441 . | Open in Read by QxMD
  44. Callaghan BC, Reynolds E, Banerjee M, Chant E, Villegas-Umana E, Feldman EL. Central Obesity is Associated With Neuropathy in the Severely Obese. Mayo Clin Proc. 2020; 95 (7): p.1342-1353. doi: 10.1016/j.mayocp.2020.03.025 . | Open in Read by QxMD
  45. Derry S, Rice AS, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017; 2021 (7). doi: 10.1002/14651858.cd007393.pub4 . | Open in Read by QxMD
  46. Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2009 . doi: 10.1002/14651858.cd007393.pub2 . | Open in Read by QxMD
  47. Umesawa M, Uchiyama K, Taneichi H, Kobashi G. Risk Factors for Ossification of Posterior Longitudinal Ligament. Springer Singapore ; 2018 : p. 15-31

3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer