Skip to main content

Advertisement

Log in

Peripheral Neuropathy

  • Neurology of Aging (KS Marder, Section Editor)
  • Published:
Current Geriatrics Reports Aims and scope Submit manuscript

Abstract

Peripheral neuropathy is thought to affect approximately 24 % of the population over age 70 [3]. It is associated with significant disability and sometimes pain, and its management is often challenging for practitioners. Proper identification and diagnosis is essential as several of its etiologies are treatable, and treatment may not only slow progression but also lead to improvement in nerve function. This review will address the appropriate initial evaluation of these patients, including suitable initial testing and novel diagnostic considerations. Common treatment strategies are discussed, with a focus on neuropathic pain and mobility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular importance, published recently, have been highlighted as: ••Of major importance

  1. Bharucha NE, Bharucha AE, Bharucha EP. Prevalence of peripheral neuropathy in the Parsi community of Bombay. Neurology. 1991;41(8):1315–7.

    Article  PubMed  CAS  Google Scholar 

  2. Gregg EW, Gu Q, Williams D, de Rekeneire N, Cheng YJ, Geiss L, et al. Prevalence of lower extremity diseases associated with normal glucose levels, impaired fasting glucose, and diabetes among U.S. adults aged 40 or older. Diabetes Res Clin Pract. 2007;77(3):485–8.

    Article  PubMed  CAS  Google Scholar 

  3. Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA. Mechanisms of association between obesity and chronic pain in the elderly. Pain. 2011;152(1):53–9.

    Article  PubMed Central  PubMed  Google Scholar 

  4. van Hecke, O., Austin, S. K., Khan, R. A., Smith, B. H., & Torrance, N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain. 2013;155(4):654–662. doi:10.1016/j.pain.2013.11.013.

    Google Scholar 

  5. Peters MJ, Bakkers M, Merkies IS, Hoeijmakers JG, van Raak EP, Faber CG. Incidence and prevalence of small-fiber neuropathy: a survey in the Netherlands. Neurology. 2013;81(15):1356–60.

    Article  PubMed  Google Scholar 

  6. Verghese J, Bieri PL, Gellido C, Schaumburg HH, Herskovitz S. Peripheral neuropathy in young-old and old-old patients. Muscle Nerve. 2001;24(11):1476–81.

    Article  PubMed  CAS  Google Scholar 

  7. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73(4):638–52. doi:10.1016/j.neuron.2012.02.008.

    Article  Google Scholar 

  8. Alport AR, Sander HW. Clinical approach to peripheral neuropathy: anatomic localization and diagnostic testing. Continuum (Minneap Minn). 2012;18(1):13–38.

    Google Scholar 

  9. Boruchow SA, Gibbons CH. Utility of skin biopsy in management of small fiber neuropathy. Muscle Nerve. 2013;48(6):877–82. This is a retrospective chart review of 69 patients who underwent skin biopsy for evaluation of small fiber neuropathy. The study found that that based on results of the biopsy, management or diagnosis was changed in 52 % of patients (meaning either a change in treatment, establishment of a new diagnosis or disproval of a previously made diagnosis).

    Article  PubMed  Google Scholar 

  10. Saperstein DS, Levine TD, Levine M, Hank N. Usefulness of skin biopsies in the evaluation and management of patients with suspected small fiber neuropathy. Int J Neurosci. 2013;123(1):38–41. This retrospective chart review demonstrated the utility of skin biopsy in the diagnosis and management of patients with small fiber neuropathy. Of 145 patients with normal nerve conduction studies and sensory symptoms, 59 % were found to have abnormal skin biopsies. Those with pathologically confirmed small fiber neuropathy were found to be more than twice as likely to respond to neuropathic pain medication.

    Article  PubMed  Google Scholar 

  11. England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice parameter: the evaluation of distal symmetric polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Pm R. 2009;1(1):14–22.

    Article  PubMed  CAS  Google Scholar 

  12. Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013;36(11):3646–51. This study looked at 47 controls and 111 patients with type 1 and 2 diabetes, who were stratified according to severity of neuropathy. Corneal confocal microscopy (CCM) was performed on all patients, and quantified values were found to worsen with worsening severity of neuropathy, and were markedly different between diabetic patients and controls. This demonstrated CCM to be an effective non-invasive method to detect corneal nerve loss and related it to the severity of neuropathy.

    Article  PubMed  Google Scholar 

  13. Tavakoli M, Marshall A, Pitceathly R, Fadavi H, Gow D, Roberts ME, et al. Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy. Exp Neurol. 2010;223(1):245–50.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Tavakoli M, Petropoulos IN, Malik RA. Corneal confocal microscopy to assess diabetic neuropathy: an eye on the foot. J Diabetes Sci Technol. 2013;7(5):1179–89. This comprehensive review paper discusses the novel technique of corneal confocal microscopy (CCM), and the ways in which it can be used to help diagnose neuropathy early (particularly in diabetic patients), assess its severity, and perhaps serve as an outcome measure to assess the benefit of interventions.

    PubMed  Google Scholar 

  15. Tavakoli M, Quattrini C, Abbott C, Kallinikos P, Marshall A, Finnigan J, et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010;33(8):1792–7.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Singleton JR, Smith AG, Bromberg MB. Painful sensory polyneuropathy associated with impaired glucose tolerance. Muscle Nerve. 2001;24(9):1225–8.

    Article  PubMed  CAS  Google Scholar 

  17. Ziegler, D., Rathmann, W., Dickhaus, T., Meisinger, C., Mielck, A., & Group, K. S. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009;10(2):393–400. doi:10.1111/j.1526-4637.2008.00555.x.

    Article  Google Scholar 

  18. Dyck PJ, Clark VM, Overland CJ, Davies JL, Pach JM, Dyck PJ, et al. Impaired glycemia and diabetic polyneuropathy: the OC IG Survey. Diabetes Care. 2012;35(3):584–91. doi:10.2337/dc11-1421. Looking at a population of subjects in Minnesota, this study noted that the prevalence of diabetic neuropathy was significantly increased only in those subjects with a true diagnosis of diabetes, and not in those with impaired glycemia or impaired glucose tolerance. This highlighted the importance of evaluating for alternative etiologies of neuropathy in patients found to have glucose intolerance.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Hughes RA, Umapathi T, Gray IA, Gregson NA, Noori M, Pannala AS, et al. A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy. Brain. 2004;127(Pt 8):1723–30.

    Article  PubMed  CAS  Google Scholar 

  20. Callaghan B, Feldman E. The metabolic syndrome and neuropathy: therapeutic challenges and opportunities. Ann Neurol. 2013;74(3):397–403. This review discusses the emerging association between the metabolic syndrome and neuropathy and the possible mechanisms and pathophysiology. It discusses clinical trials that have looked at the effects of glucose control and incidence of both type 1 and 2 diabetes.

    PubMed  CAS  Google Scholar 

  21. Zhou L, Li J, Ontaneda D, Sperling J. Metabolic syndrome in small fiber sensory neuropathy. J Clin Neuromuscul Dis. 2011;12(4):235–43.

    Article  PubMed  Google Scholar 

  22. Hinder LM, Vincent AM, Hayes JM, McLean LL, Feldman EL. Apolipoprotein E knockout as the basis for mouse models of dyslipidemia-induced neuropathy. Exp Neurol. 2013;239:102–10.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Wiggin TD, Sullivan KA, Pop-Busui R, Amato A, Sima AA, Feldman EL. Elevated triglycerides correlate with progression of diabetic neuropathy. Diabetes. 2009;58(7):1634–40.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Smith AG, Singleton JR. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. J Diabet Complicat. 2013;27(5):436–42. The Utah Diabetic Neuropathy Study (UDNS) looked at 218 patients with type 2 diabetes and looked at associated risk factors for peripheral neuropathy (the patients were asymptomatic at the onset). Several studies including serum studies, NCS, and skin biopsy were done on all patients. They assessed several risk factors including glycemic control, lipid levels, blood pressure, and obesity. An increased risk of developing neuropathy was demonstrated to be associated with obesity and hypertriglyceridemia independent of glycemic control. Elevated HgA1c was found to be associated with loss of large fiber loss, whereas obesity and hypertriglyceridemia was associated with loss of small unmyelinated fibers.

    Article  Google Scholar 

  25. Hou R, Goldberg AC, Tobin GS. A case of severe neuropathy associated with hypertriglyceridemia. Endocr Pract. 2008;14(8):1020–2.

    Article  PubMed  Google Scholar 

  26. Barohn RJ. Approach to peripheral neuropathy and neuronopathy. Semin Neurol. 1998;18(1):7–18.

    Article  PubMed  CAS  Google Scholar 

  27. Kelly Jr JJ, Kyle RA, O'Brien PC, Dyck PJ. Prevalence of monoclonal protein in peripheral neuropathy. Neurology. 1981;31(11):1480–3.

    Article  PubMed  Google Scholar 

  28. Rajabally YA. Neuropathy and paraproteins: review of a complex association. [Review]. Eur J Neurol. 2011;18(11):1291–8. doi:10.1111/j.1468-1331.2011.03380.x.

    Article  PubMed  CAS  Google Scholar 

  29. Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the peripheral nerves. Curr Opin Neurol. 2005;18(5):598–603.

    Article  PubMed  Google Scholar 

  30. Shen TC, Lebwohl B, Verma H, Kumta N, Tennyson C, Lewis S, et al. Peripheral neuropathic symptoms in celiac disease and inflammatory bowel disease. J Clin Neuromuscul Dis. 2012;13(3):137–45.

    Article  PubMed  Google Scholar 

  31. Chin RL, Sander HW, Brannagan TH, Green PH, Hays AP, Alaedini A, et al. Celiac neuropathy. Neurology. 2003;60(10):1581–5.

    Article  PubMed  CAS  Google Scholar 

  32. Brannagan 3rd TH, Hays AP, Chin SS, Sander HW, Chin RL, Magda P, et al. Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings. Arch Neurol. 2005;62(10):1574–8.

    Article  PubMed  Google Scholar 

  33. Saporta AS, Sottile SL, Miller LJ, Feely SM, Siskind CE, Shy ME. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. [Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't]. Ann Neurol. 2011;69(1):22–33. doi:10.1002/ana.22166.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Shy ME, Jani A, Krajewski K, Grandis M, Lewis RA, Li J, et al. Phenotypic clustering in MPZ mutations. [Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review]. Brain. 2004;127(Pt 2):371–84. doi:10.1093/brain/awh048.

    Article  PubMed  Google Scholar 

  35. England JD, Asbury AK. Peripheral neuropathy. Lancet. 2004;363(9427):2151–61. doi:10.1016/S0140-6736(04)16508-2.

    Article  PubMed  Google Scholar 

  36. Chia L, Fernandez A, Lacroix C, Adams D, Plante V, Said G. Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly. A retrospective review of 100 consecutive patients. Brain. 1996;119(Pt 4):1091–8.

    PubMed  Google Scholar 

  37. Dyck PJ, Oviatt KF, Lambert EH. Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol. 1981;10(3):222–6.

    Article  PubMed  CAS  Google Scholar 

  38. Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care. 2006;29(6):1294–9.

    Article  PubMed  Google Scholar 

  39. Singleton JR, Smith AG. The diabetic neuropathies: practical and rational therapy. Semin Neurol. 2012;32(3):196–203.

    Article  PubMed  Google Scholar 

  40. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343–50.

    Article  PubMed  CAS  Google Scholar 

  41. Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, et al. Intravenous immune globulin (10 % caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7(2):136–44. doi:10.1016/S1474-4422(07)70329-0.

    Article  PubMed  CAS  Google Scholar 

  42. Dyck PJ, Litchy WJ, Kratz KM, Suarez GA, Low PA, Pineda AA, et al. A plasma exchange versus immune globulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 1994;36(6):838–45. doi:10.1002/ana.410360607.

    Article  PubMed  CAS  Google Scholar 

  43. Hughes R, Bensa S, Willison H, Van den Bergh P, Comi G, Illa I, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50(2):195–201.

    Article  PubMed  CAS  Google Scholar 

  44. Brannagan 3rd TH. Current treatments of chronic immune-mediated demyelinating polyneuropathies. [Review]. Muscle Nerve. 2009;39(5):563–78. doi:10.1002/mus.21277.

    Article  PubMed  CAS  Google Scholar 

  45. Attal N. Neuropathic pain: mechanisms, therapeutic approach, and interpretation of clinical trials. Continuum (Minneap Minn). 2012;18(1):161–75.

    Google Scholar 

  46. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Pm R. 2011;3(4):345–52. 352 e341-321.

    Article  PubMed  Google Scholar 

  47. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1–2):109–18.

    Article  PubMed  CAS  Google Scholar 

  48. Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. Oxcarbazepine for neuropathic pain. Cochrane Database Syst Rev. 2013;3:CD007963. doi:10.1002/14651858.CD007963.pub2. This Cochrane Review discusses four double blind placebo controlled trials of oxcarbazepine in the treatment of painful diabetic neuropathy (three trials) and pain due to radiculopathy (one trial). One trial looking at pain in diabetic neuropathy demonstrated that oxcarbazepine is moderately effective at reducing pain in these patients compared to controls, but there is no clear evidence that it is effective in treating pain related to radiculopathy.

    PubMed  Google Scholar 

  49. Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol. 2006;63(4):513–8.

    Article  PubMed  Google Scholar 

  50. Richardson, J. K., Demott, T., Allet, L., Kim, H., & Ashton-Miller, J. A. (2013). Hip strength:Ankle proprioceptive threshold ratio predicts falls and injury in diabetic neuropathy. Muscle Nerve.

  51. Allet L, Kim H, Ashton-Miller JA, Richardson JK. Which lower lumb fontralplane sensory and motor functions predict gait speed and efficiency on uneven surfaces in older persons with diabetic neuropathy? Phyis Med Rehabilit. 2012;4(10):726–33.

    Google Scholar 

  52. Manor B, Lipsitz LA, Wayne PM, Peng CK, Li L. Complexity-based measures inform Tai Chi's impact on standing postural control in older adults with peripheral neuropathy. BMC Complement Altern Med. 2013;13:87.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Comana M. Cioroiu declares that she has no conflict of interest.

Thomas H. Brannagan III has received compensation from Grifols and Baxter for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas H. Brannagan III.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cioroiu, C.M., Brannagan, T.H. Peripheral Neuropathy. Curr Geri Rep 3, 83–90 (2014). https://doi.org/10.1007/s13670-014-0079-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13670-014-0079-4

Keywords

Navigation