Evaluation of polyneuropathy

Polyneuropathy is a generalized disease of the peripheral nerves due to damage to the axon and/or myelin sheath. Estimates on the prevalence in the general population range from 1% to 7%.[1]Italian General Practitioner Study Group (IGPSG). Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample. Neurology. 1995;45:1832-1836. http://www.ncbi.nlm.nih.gov/pubmed/7477977?tool=bestpractice.com [2]Bharucha NE, Bharucha AE, Bharucha EP. Prevalence of peripheral neuropathy in the Parsi community of Bombay. Neurology. 1991;41:1315-1317. http://www.ncbi.nlm.nih.gov/pubmed/1650932?tool=bestpractice.com [3]Savettieri G, Rocca WA, Salemi G, Meneghini F, et al. Prevalence of diabetic neuropathy with somatic symptoms: a door-to-door survey in two Sicilian municipalities. Sicilian Neuro-Epidemiologic Study (SNES) Group. Neurology. 1993;43:1115-1120. http://www.ncbi.nlm.nih.gov/pubmed/8170554?tool=bestpractice.com [4]Hanewinckel R, van Oijen M, Ikram MA, et al. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016 Jan;31(1):5-20. https://link.springer.com/article/10.1007/s10654-015-0094-6 http://www.ncbi.nlm.nih.gov/pubmed/26700499?tool=bestpractice.com

Polyneuropathies are frequent neurological manifestations of systemic illnesses. For example, approximately 50% of diabetic patients and patients with advanced HIV infection develop a neuropathy.[5]Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr;43(4):817-24. http://www.ncbi.nlm.nih.gov/pubmed/8469345?tool=bestpractice.com [6]Simpson DM, Kitch D, Evans SR et al. HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology. 2006;66:1679-1687. http://www.ncbi.nlm.nih.gov/pubmed/16769940?tool=bestpractice.com ​ Most neuropathies caused by toxins and metabolic factors are axonal. The etiologies of demyelinating polyneuropathy (e.g., Guillain-Barre syndrome [GBS], chronic inflammatory demyelinating polyradiculoneuropathy, monoclonal gammopathies, certain hereditary neuropathies) are limited.

Clinical presentation

Polyneuropathy most commonly presents as symmetric numbness, paresthesias, and dysesthesias in the feet and distal lower extremities (distal symmetrical sensorimotor polyneuropathy). In severe cases, sensory symptoms and signs progress proximally to fit a stocking-glove distribution. Balance and gait may be impaired. Early motor signs include atrophy of the intrinsic foot muscles and ankle weakness. The autonomic nervous system may be involved, resulting in symptoms such as early satiety, diarrhea or constipation, erectile dysfunction, sweating disturbances, and orthostatic lightheadedness. Other clinical phenotypes may be present, including purely sensory or purely motor symptoms, and polyneuropathies with an acute presentation (e.g., GBS).

Small-fiber neuropathies do not affect the large nerve fibers measured by nerve conduction studies, but do show changes in nerve fiber density on skin biopsy and abnormalities on quantitative sensory testing.[7]Shy ME, Frohman EM, So YT, et al. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003 Mar 25;60(6):898-904. https://www.doi.org/10.1212/01.wnl.0000058546.16985.11 http://www.ncbi.nlm.nih.gov/pubmed/12654951?tool=bestpractice.com [8]Devigili G, Cazzato D, Lauria G. Clinical diagnosis and management of small fiber neuropathy: an update on best practice. Expert Rev Neurother. 2020 Sep;20(9):967-80. http://www.ncbi.nlm.nih.gov/pubmed/32654574?tool=bestpractice.com Small-fiber neuropathies may present with painful pure sensory syndromes, and may be idiopathic, or secondary to a variety of systemic causes.[9]Oaklander AL, Nolano M. Scientific advances in and clinical spproaches to small-fiber polyneuropathy: A review. JAMA Neurol. 2019;76(10):1240–51 http://www.ncbi.nlm.nih.gov/pubmed/31498378?tool=bestpractice.com [10]Devigili G, Rinaldo S, Lombardi R, et al. Diagnostic criteria for small fibre neuropathy in clinical practice and research. Brain. 2019 Dec 1;142(12):3728-36. https://academic.oup.com/brain/article/142/12/3728/5610119 http://www.ncbi.nlm.nih.gov/pubmed/31665231?tool=bestpractice.com [11]Gondim FAA, Barreira AA, Claudino R, et al. Definition and diagnosis of small fiber neuropathy: consensus from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology. Arq Neuropsiquiatr. 2018 Mar;76(3):200-8. https://www.scielo.br/j/anp/a/8zryR4hQ8HtXqTxhBd9Jn9s/?lang=en http://www.ncbi.nlm.nih.gov/pubmed/29809227?tool=bestpractice.com [12]de Greef BTA, Hoeijmakers JGJ, Gorissen-Brouwers CML, et al. Associated conditions in small fiber neuropathy - a large cohort study and review of the literature. Eur J Neurol. 2018 Feb;25(2):348-55. https://onlinelibrary.wiley.com/doi/10.1111/ene.13508 http://www.ncbi.nlm.nih.gov/pubmed/29112785?tool=bestpractice.com

Asymmetric neuropathies or neuropathies presenting initially with upper extremity signs or symptoms should alert the practitioner to alternate neuropathy diagnoses, including entrapment neuropathies (focal neuropathies) or vasculitic neuropathies (multifocal neuropathies). The differential diagnosis of focal and multifocal neuropathies overlaps but is distinct from that of polyneuropathies.

Hyperreflexia or other upper motor neuron findings should prompt the examiner to consider lesions of the central nervous system. Multiple lumbosacral radiculopathies may also mimic a polyneuropathy presentation.