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Polyneuropathy

Last updated: September 29, 2021

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Polyneuropathy is a disorder that involves damage to multiple peripheral nerve fibers. The condition can be caused by diabetes mellitus, alcoholism, hereditary diseases, toxins, infection, or other inflammatory conditions. The classic presentation is a symmetric distal burning or loss of sensation. Further clinical features depend on whether an axonal or demyelinating nerve injury has occurred. Diagnostic tests such as electrodiagnostic studies are indicated in the case of 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).

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
  • Distal muscle wasting: feet, lower legs, hands (severe cases)
  • Distal sensory loss (pain, temperature, proprioception, vibration)
  • Reduced or absent distal reflexes (usually begins in the ankles)
Associated conditions

References:[6][8][9][10]

Diabetic polyneuropathy

Alcoholic polyneuropathy

Hereditary motor sensory neuropathies (HMSN)

HMSN type I (Charcot-Marie-Tooth disease)

  • Etiology: most commonly caused by duplication of the gene PMP22 in chromosome 17
  • Clinical features
    • Distal symmetric sensorimotor polyneuropathy
      • Foot drop
      • Atrophy of the calf muscles (“stork legs”)
      • Pes cavus deformity
      • Hammer toe
      • Intrinsic hand musculature may become involved after several years.
      • Sensory loss (occurs late)
    • May be associated with sleep apnea
  • Diagnostics

HMSN type IV (Refsum disease)

HMSN type V

Other types of hereditary motor sensory neuropathies

References:[10][11][12][13][14][15][16][17][18][19][20][21]

Further tests are usually indicated in patients with atypical clinical features, an unknown etiology, and/or severe or rapidly progressive symptoms.

References:[6][22][23][24]

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.

Treatment efficacy can only be assessed after 2–4 weeks of therapy. Since complete pain relief is often not possible, a tolerable level of pain may be an acceptable treatment goal.

References:[6][25][26][27]

  1. Charness ME, Aminoff MJ, Wilterd JL. Overview of the Chronic Neurologic Complications of Alcohol. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-the-chronic-neurologic-complications-of-alcohol.Last updated: May 17, 2012. Accessed: April 3, 2017.
  2. 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.
  3. Feldman EL, Shefner JM, Dashe JF. Clinical Manifestations and Diagnosis of Diabetic Polyneuropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-diabetic-polyneuropathy.Last updated: December 15, 2016. Accessed: June 16, 2017.
  4. Tracy JA, Dyck JB. The spectrum of diabetic neuropathies. Phys Med Rehabil Clin N Am. 2008; 19 (1). doi: 10.1016/j.pmr.2007.10.010 . | Open in Read by QxMD
  5. Marchettini P, Lacerenza M, Mauri E, Marangoni C. Painful peripheral neuropathies. Curr Neuropharmacol.. 2006; 4 (3): p.175–181.
  6. Izenberg A, Perkins BA, Bril V. Diabetic neuropathies. Semin Neurol. 2015; 35 (4): p.424-430.
  7. Twydell PT, Shefner JM, Dashe JF. Diabetic Amyotrophy and Idiopathic Lumbosacral Radiculoplexus Neuropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diabetic-amyotrophy-and-idiopathic-lumbosacral-radiculoplexus-neuropathy.Last updated: December 28, 2016. Accessed: June 16, 2017.
  8. Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012; 73 (3): p.348–362. doi: 10.1111/j.1365-2125.2011.04111.x . | Open in Read by QxMD
  9. Aminoff MJ. Neurology and General Medicine. Elsevier Health Sciences ; 2008
  10. HEREDITARY MOTOR SENSORY NEUROPATHIES (HMSN; CMT). http://neuromuscular.wustl.edu/time/hmsn.html. . Accessed: June 16, 2017.
  11. Wanders RJA, Schiffmann R. Peroxisomal disorders. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/peroxisomal-disorders.Last updated: December 29, 2015. Accessed: June 16, 2017.
  12. Charcot-Marie-Tooth Neuropathy Type 2. https://www.ncbi.nlm.nih.gov/books/NBK1285/. Updated: April 14, 2016. Accessed: June 16, 2017.
  13. Hughes R. Investigation of peripheral neuropathy. The BMJ. 2010; 341 (6100). doi: 10.1136/bmj.c6100 . | Open in Read by QxMD
  14. 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
  15. Cojocaru IM, Cojocaru M, Silosi I, Vrabie CD. Peripheral nervous system manifestations in systemic autoimmune diseases. Maedica (Buchar). 2014; 9 (3): p.289-294.
  16. 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
  17. 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
  18. 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.
  19. Said G. Uremic neuropathy. Elsevier ; 2013 : p. 607-612
  20. 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.
  21. 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.
  22. Chung T, Prasad K, Lloyd TE. Peripheral neuropathy – clinical and electrophysiological considerations . Neuroimaging Clin N Am. 2013; 24 (1): p.49-65. doi: 10.1016/j.nic.2013.03.023 . | Open in Read by QxMD
  23. Avitzur O. EMG findings of axonal polyneuropathy. Medscape . 2005 .
  24. Laboratory Diagnosis of Peripheral Neuropathy. http://www.questdiagnostics.com/testcenter/testguide.action?dc=WP_LabDiagnosis_PeripheralNeurop. Updated: September 1, 2015. Accessed: June 16, 2017.
  25. Wright DV. Non-narcotic options for pain relief with chronic neuropathic conditions. Journal for Nurse Practitioners. 2008; 4 (4): p.263-270.
  26. Jefferies K. Treatment of neuropathic pain. Semin Neurol. 2010; 30 (4): p.425-432.
  27. Ziegler D. Current concepts in the management of diabetic polyneuropathy. Curr Diabetes Rev. 2011; 7 (3): p.208-220.
  28. Umesawa M, Uchiyama K, Taneichi H, Kobashi G. Risk Factors for Ossification of Posterior Longitudinal Ligament. Springer Singapore ; 2018 : p. 15-31