Download PDF
Semin Neurol 2019; 39(05): 519-530
DOI: 10.1055/s-0039-1694747
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Clinician's Approach to Peripheral Neuropathy

Peter Siao
1   Department of Neurology, Boston University School of Medicine, Neuromuscular Unit and Electromyography Laboratory, Boston Medical Center, Boston, Massachusetts
,
Michelle Kaku
1   Department of Neurology, Boston University School of Medicine, Neuromuscular Unit and Electromyography Laboratory, Boston Medical Center, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
22 October 2019 (online)

    Permissions and Reprints

Abstract

Peripheral neuropathies are a group of disorders that affect the peripheral nervous system, for which hundreds of etiologies have been identified. This article presents a stepwise approach to the evaluation and workup of peripheral neuropathy, which starts with a detailed history of symptoms, family and occupational history, and a neurological as well as general physical exam. Pattern recognition of various neuropathies can help to build a differential diagnosis based on the presentation. Such patterns include acute versus chronic, primary demyelinating versus axonal, hereditary versus acquired, asymmetric versus symmetric, presence of facial palsies, sensory or motor predominant, and presence of prominent autonomic symptoms. Early categorization of the type of neuropathy can help focus the workup for peripheral neuropathy. Nerve conduction studies and electromyography (NCS/EMG) is the primary diagnostic tool in the evaluation of patients with large-fiber polyneuropathy. One of the most important roles of NCS/EMG is to help categorize polyneuropathy as primary axonal versus primary demyelinating. The finding of a primary demyelinating polyneuropathy narrows the differential diagnosis of polyneuropathy dramatically and increases the chances of finding a treatable etiology. Laboratory workup includes serum studies and potentially cerebrospinal fluid, genetic studies, immunological markers, and fat pad biopsy for select patients. Skin biopsy may be used to assess intraepidermal nerve fiber density if small-fiber neuropathy is suspected, and nerve biopsy may be useful in select cases. In recent years, magnetic resonance imaging and neuromuscular ultrasound have also shown promise in the evaluation of peripheral neuropathy. Identification of the etiology of neuropathy is crucial and often time-sensitive, as an increasing number of causes are now reversible or treatable.

Keywords

peripheral neuropathy - polyneuropathy - diagnosis - clinical - neurophysiologic
 

  • References

  • 1 Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry 1997; 62 (04) 310-318
    CrossrefPubMedGoogle Scholar
  • 2 Osterberg A, Boivie J, Thuomas KA. Central pain in multiple sclerosis--prevalence and clinical characteristics. Eur J Pain 2005; 9 (05) 531-542
    CrossrefPubMedGoogle Scholar
  • 3 Li Y. Axonal sensorimotor polyneuropathies. Continuum. Continuum (Minneap Minn) 2017; 23 (5, Peripheral Nerve and Motor Neuron Disorders): 1378-1393
    PubMedGoogle Scholar
  • 4 Dyck PJ, Oviatt KF, Lambert EH. Intensive evaluation of referred unclassified neuropathies yields improved diagnosis. Ann Neurol 1981; 10 (03) 222-226
    CrossrefPubMedGoogle Scholar
  • 5 Lauria G, Hsieh ST, Johansson O. , et al; European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2010; 17 (07) 903-912 , e44–e49
    CrossrefPubMedGoogle Scholar
  • 6 Devata S, Hari P, Markelova N, Li R, Komorowski R, Shidham VB. Detection of amyloid in abdominal fat pad aspirates in early amyloidosis: role of electron microscopy and Congo red stained cell block sections. Cytojournal 2011; 8: 11
    CrossrefPubMedGoogle Scholar
  • 7 Buchmann SJ, Penzlin AI, Kubasch ML, Illigens BM, Siepmann T. Assessment of sudomotor function. Clin Auton Res 2019; 29 (01) 41-53
    CrossrefPubMedGoogle Scholar
  • 8 Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am 2003; 14 (02) 261-286
    CrossrefPubMedGoogle Scholar
  • 9 Ishikawa T, Asakura K, Mizutani Y. , et al. MR neurography for the evaluation of CIDP. Muscle Nerve 2017; 55 (04) 483-489
    CrossrefPubMedGoogle Scholar
  • 10 Mah JK, van Alfen N. Neuromuscular ultrasound: clinical applications and diagnostic values. Can J Neurol Sci 2018; 45 (06) 605-619
    CrossrefPubMedGoogle Scholar
  • 11 England JD, Gronseth GS, Franklin G. , et al; American Academy of Neurology. Practice parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 2009; 72 (02) 177-184
    CrossrefPubMedGoogle Scholar
  • 12 Malandrini A, Villanova M, Dotti MT, Federico A. Acute inflammatory neuropathy in Charcot-Marie-Tooth disease. Neurology 1999; 52 (04) 859-861
    CrossrefPubMedGoogle Scholar
  • 13 Marques Jr W, Funayama CAR, Secchin JB. , et al. Coexistence of two chronic neuropathies in a young child: Charcot-Marie-Tooth disease type 1A and chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2010; 42 (04) 598-600
    CrossrefPubMedGoogle Scholar
  • 14 Panosyan FB, Kirk CA, Marking D. , et al. Carpal tunnel syndrome in inherited neuropathies: a retrospective survey. Muscle Nerve 2018; 57 (03) 388-394
    CrossrefPubMedGoogle Scholar
  • 15 Morgan G, Wilbourn AJ. Cervical radiculopathy and coexisting distal entrapment neuropathies: double-crush syndromes?. Neurology 1998; 50 (01) 78-83
    CrossrefPubMedGoogle Scholar
  • 16 Rubens O, Logina I, Kravale I, Eglite M, Donaghy M. Peripheral neuropathy in chronic occupational inorganic lead exposure: a clinical and electrophysiological study. J Neurol Neurosurg Psychiatry 2001; 71 (02) 200-204
    CrossrefPubMedGoogle Scholar
  • 17 Nordentoft T, Andersen EB, Mogensen PH. Initial sensorimotor and delayed autonomic neuropathy in acute thallium poisoning. Neurotoxicology 1998; 19 (03) 421-426
    PubMedGoogle Scholar
  • 18 Staff NP, Windebank AJ. Peripheral neuropathy due to vitamin deficiency, toxins, and medications. Continuum (Minneap Minn) 2014; 20 (5 Peripheral Nervous System Disorders): 1293-1306
    PubMedGoogle Scholar
  • 19 Yiannikas C, Pollard JD, McLeod JG. Nitrofurantoin neuropathy. Aust N Z J Med 1981; 11 (04) 400-405
    CrossrefPubMedGoogle Scholar
  • 20 Johnston SR, Burn D, Brooks DJ. Peripheral neuropathy associated with lithium toxicity. J Neurol Neurosurg Psychiatry 1991; 54 (11) 1019-1020
    CrossrefPubMedGoogle Scholar
  • 21 Shorvon SD, Reynolds EH. Anticonvulsant peripheral neuropathy: a clinical and electrophysiological study of patients on single drug treatment with phenytoin, carbamazepine or barbiturates. J Neurol Neurosurg Psychiatry 1982; 45 (07) 620-626
    CrossrefPubMedGoogle Scholar
  • 22 Ropper AH, Gorson KC. Neuropathies associated with paraproteinemia. N Engl J Med 1998; 338 (22) 1601-1607
    CrossrefPubMedGoogle Scholar
  • 23 Gosselin S, Kyle RA, Dyck PJ. Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol 1991; 30 (01) 54-61
    CrossrefPubMedGoogle Scholar
  • 24 Olney RK. Neuropathies associated with connective tissue disease. Semin Neurol 1998; 18 (01) 63-72
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Logigian EL, Steere AC. Clinical and electrophysiologic findings in chronic neuropathy of Lyme disease. Neurology 1992; 42 (02) 303-311
    CrossrefPubMedGoogle Scholar
  • 26 Kaku M, Simpson DM. HIV neuropathy. Curr Opin HIV AIDS 2014; 9 (06) 521-526
    CrossrefPubMedGoogle Scholar
  • 27 Sabin TD, Swift TR. Neurologic complications of leprosy. In: Aminoff MJ, Josephson SA. , eds. Aminoff's Neurology and General Medicine. 5th ed. New York, NY: Elsevier; 2014: 845-856
    Google Scholar
  • 28 Kutlu G, Ertem GT, Coskun O. , et al. Brucella: a cause of peripheral neuropathy. Eur Neurol 2009; 61 (01) 33-38
    CrossrefPubMedGoogle Scholar
  • 29 Gainsborough N, Hall SM, Hughes RA, Leibowitz S. Sarcoid neuropathy. J Neurol 1991; 238 (03) 177-180
    CrossrefPubMedGoogle Scholar
  • 30 Bedlack RS, Vu T, Hammans S. , et al. MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2004; 29 (03) 364-368
    CrossrefPubMedGoogle Scholar
  • 31 Finsterer J. Inherited mitochondrial neuropathies. J Neurol Sci 2011; 304 (1–2): 9-16
    CrossrefPubMedGoogle Scholar
  • 32 Collins MP, Periquet MI. Non-systemic vasculitic neuropathy. Curr Opin Neurol 2004; 17 (05) 587-598
    CrossrefPubMedGoogle Scholar
  • 33 Iannella G, Greco A, Granata G. , et al. Granulomatosis with polyangiitis and facial palsy: literature review and insight in the autoimmune pathogenesis. Autoimmun Rev 2016; 15 (07) 621-631
    CrossrefPubMedGoogle Scholar
  • 34 Pehlivanoglu F, Yasar KK, Sengoz G. Tuberculous meningitis in adults: a review of 160 cases. ScientificWorldJournal 2012; 2012: 169028
    PubMedGoogle Scholar
  • 35 Sathirapanya P, Fujitnirun C, Setthawatcharawanich S. , et al. Peripheral facial paralysis associated with HIV infection: a case series and literature review. Clin Neurol Neurosurg 2018; 172: 124-129
    CrossrefPubMedGoogle Scholar
  • 36 Gilden DH. Clinical practice. Bell's palsy. N Engl J Med 2004; 351 (13) 1323-1331
    CrossrefPubMedGoogle Scholar
  • 37 Hadithi M, Stam F, Donker AJ, Dijkmans BA. Sjögren's syndrome: an unusual cause of Bell's palsy. Ann Rheum Dis 2001; 60 (07) 724-725
    CrossrefPubMedGoogle Scholar
  • 38 Chweya CM, Anzalone CL, Driscoll CLW, Lane JI, Carlson ML. For whom the Bell's toll: recurrent facial nerve paralysis, a retrospective study and systematic review of the literature. Otol Neurotol 2019; 40 (04) 517-528
    CrossrefPubMedGoogle Scholar
  • 39 Wong K, Sequeira S, Bechtel K. Pediatric bilateral facial paralysis: an unusual presentation of lyme disease. Pediatr Emerg Care 2018 (e-pub ahead of print). Doi: 10.1097/PEC.0000000000001648
    PubMedGoogle Scholar
  • 40 George MK, Pahor AL. Sarcoidosis: a cause for bilateral facial palsy. Ear Nose Throat J 1991; 70 (08) 492-493
    PubMedGoogle Scholar
  • 41 Kumar P, Charaniya R, Bahl A, Ghosh A, Dixit J. Facial diplegia with paresthesia: an uncommon variant of Guillain-Barre syndrome. J Clin Diagn Res 2016; 10 (07) OD01-OD02
    PubMedGoogle Scholar
  • 42 Gaudin RA, Jowett N, Banks CA, Knox CJ, Hadlock TA. Bilateral facial paralysis: a 13-year experience. Plast Reconstr Surg 2016; 138 (04) 879-887
    CrossrefPubMedGoogle Scholar
  • 43 Wechsler AF, Ho DD. Bilateral Bell's palsy at the time of HIV seroconversion. Neurology 1989; 39 (05) 747-748
    CrossrefPubMedGoogle Scholar
  • 44 Keane JR. Bilateral seventh nerve palsy: analysis of 43 cases and review of the literature. Neurology 1994; 44 (07) 1198-1202
    CrossrefPubMedGoogle Scholar
  • 45 Cai Z, Li H, Wang X. , et al. Prognostic factors of Bell's palsy and Ramsay Hunt syndrome. Medicine (Baltimore) 2017; 96 (02) e5898
    PubMedGoogle Scholar
  • 46 Denny MC, Fotino AD. The Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis. Proc (Bayl Univ Med Cent) 2013; 26 (04) 390-392
    PubMedGoogle Scholar
  • 47 Eviston TJ, Croxson GR, Kennedy PG, Hadlock T, Krishnan AV. Bell's palsy: aetiology, clinical features and multidisciplinary care. J Neurol Neurosurg Psychiatry 2015; 86 (12) 1356-1361
    CrossrefPubMedGoogle Scholar
  • 48 Kiuru S. Gelsolin-related familial amyloidosis, Finnish type (FAF), and its variants found worldwide. Amyloid 1998; 5 (01) 55-66
    CrossrefPubMedGoogle Scholar
  • 49 Sasaki Md, Leite PG, Leite AG, de Almeida SM. Bilateral peripheral facial palsy secondary to lymphoma in a patient with HIV/AIDS: a case report and literature review. Braz J Infect Dis 2002; 6 (01) 50-54
    PubMedGoogle Scholar
  • 50 Lopate G, Pestronk A, Al-Lozi M. , et al. Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndrome. Muscle Nerve 2006; 33 (05) 672-676
    CrossrefPubMedGoogle Scholar
  • 51 Siao P. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1996. A 36-year-old woman with bilateral facial and hand weakness and impaired truncal sensation. N Engl J Med 1996; 334 (21) 1389-1394
    CrossrefPubMedGoogle Scholar
  • 52 Nagappa M, Taly AB, Mahadevan A. , et al. Tangier's disease: an uncommon cause of facial weakness and non-length dependent demyelinating neuropathy. Ann Indian Acad Neurol 2016; 19 (01) 137-139
    CrossrefPubMedGoogle Scholar
  • 53 Albers JW, Fink JK. Porphyric neuropathy. Muscle Nerve 2004; 30 (04) 410-422
    CrossrefPubMedGoogle Scholar
  • 54 Vucic S, Tian D, Chong PST, Cudkowicz ME, Hedley-Whyte ET, Cros D. Facial onset sensory and motor neuronopathy (FOSMN syndrome): a novel syndrome in neurology. Brain 2006; 129 (Pt 12): 3384-3390
    CrossrefPubMedGoogle Scholar
  • 55 Van Schaik INLJ, Nobile-Orazio E. , et al; Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. J Peripher Nerv Syst 2010; 15 (04) 295-301
    CrossrefPubMedGoogle Scholar
  • 56 Delmont E, Benaïm C, Launay M, Sacconi S, Soriani M-H, Desnuelle C. Do patients having a decrease in SNAP amplitude during the course of MMN present with a different condition?. J Neurol 2009; 256 (11) 1876-1880
    CrossrefPubMedGoogle Scholar
  • 57 Larner AJ. A Dictionary of Neurological Signs. 4th ed. Cham: Springer; 2016
    Google Scholar
  • 58 Willison HJ, O'Leary CP, Veitch J. , et al. The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies. Brain 2001; 124 (Pt 10): 1968-1977
    CrossrefPubMedGoogle Scholar
  • 59 Camdessanché JP, Antoine JC, Honnorat J. , et al. Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients. Brain 2002; 125 (Pt 1): 166-175
    CrossrefPubMedGoogle Scholar
  • 60 Rosenfeld CS, Broder LE. Cisplatin-induced autonomic neuropathy. Cancer Treat Rep 1984; 68 (04) 659-660
    PubMedGoogle Scholar
  • 61 Nobile-Orazio E. Chronic inflammatory demyelinating polyradiculoneuropathy and variants: where we are and where we should go. J Peripher Nerv Syst 2014; 19 (01) 2-13
    CrossrefPubMedGoogle Scholar
  • 62 Albers JW, Robertson Jr WC, Daube JR. Electrodiagnostic findings in acute porphyric neuropathy. Muscle Nerve 1978; 1 (04) 292-296
    CrossrefPubMedGoogle Scholar
  • 63 Pearn J. Neurology of ciguatera. J Neurol Neurosurg Psychiatry 2001; 70 (01) 4-8
    CrossrefPubMedGoogle Scholar
  • 64 Auld RB, Bedwell SF. Peripheral neuropathy with sympathetic overactivity from industrial contact with acrylamide. Can Med Assoc J 1967; 96 (11) 652-654
    PubMedGoogle Scholar
  • 65 Nazir HF, AlFutaisi A, Zacharia M. , et al. Vincristine‐induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement. Pediatr Blood Cancer 2017; 64: e26677
    CrossrefPubMedGoogle Scholar
  • 66 Dermitzakis EV, Kimiskidis VK, Lazaridis G. , et al. The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer. BMC Neurol 2016; 16 (01) 190
    CrossrefPubMedGoogle Scholar
  • 67 Manolis AS, Tordjman T, Mack KD, Estes III NA. Atypical pulmonary and neurologic complications of amiodarone in the same patient. Report of a case and review of the literature. Arch Intern Med 1987; 147 (10) 1805-1809
    CrossrefPubMedGoogle Scholar
  • 68 Hoyle C, Ewing DJ, Parker AC. Acute autonomic neuropathy in association with systemic lupus erythematosus. Ann Rheum Dis 1985; 44 (06) 420-424
    CrossrefPubMedGoogle Scholar
  • 69 Edmonds ME, Jones TC, Saunders WA, Sturrock RD. Autonomic neuropathy in rheumatoid arthritis. BMJ 1979; 2 (6183): 173-175
    CrossrefPubMedGoogle Scholar
  • 70 Edelman J, Gubbay SS, Zilko PJ. Acute pandysautonomia due to mixed connective tissue disease. Aust N Z J Med 1981; 11 (01) 68-70
    CrossrefPubMedGoogle Scholar
  • 71 Kim DH, Zeldenrust SR, Low PA, Dyck PJ. Quantitative sensation and autonomic test abnormalities in transthyretin amyloidosis polyneuropathy. Muscle Nerve 2009; 40 (03) 363-370
    CrossrefPubMedGoogle Scholar
  • 72 Cable WJ, Kolodny EH, Adams RD. Fabry disease: impaired autonomic function. Neurology 1982; 32 (05) 498-502
    CrossrefPubMedGoogle Scholar
  • 73 Vallet A-E, Verschueren A, Petiot P. , et al. Neurological features in adult Triple-A (Allgrove) syndrome. J Neurol 2012; 259 (01) 39-46
    CrossrefPubMedGoogle Scholar
  • 74 Singleton R, Helgerson SD, Snyder RD. , et al. Neuropathy in Navajo children: clinical and epidemiologic features. Neurology 1990; 40 (02) 363-367
    CrossrefPubMedGoogle Scholar
  • 75 Thomas PK. Autonomic involvement in inherited neuropathies. Clin Auton Res 1992; 2 (01) 51-56
    CrossrefPubMedGoogle Scholar
  • 76 Fernandez A, Hontebeyrie M, Said G. Autonomic neuropathy and immunological abnormalities in Chagas' disease. Clin Auton Res 1992; 2 (06) 409-412
    CrossrefPubMedGoogle Scholar
  • 77 Piradov MA, Pirogov VN, Popova LM, Avdunina IA. Diphtheritic polyneuropathy: clinical analysis of severe forms. Arch Neurol 2001; 58 (09) 1438-1442
    CrossrefPubMedGoogle Scholar
  • 78 Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu--associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 1992; 71 (02) 59-72
    CrossrefPubMedGoogle Scholar
  • 79 Koike H, Tanaka F, Sobue G. Paraneoplastic neuropathy: wide-ranging clinicopathological manifestations. Curr Opin Neurol 2011; 24 (05) 504-510
    CrossrefPubMedGoogle Scholar
  • 80 Chai J, Herrmann DN, Stanton M, Barbano RL, Logigian EL. Painful small-fiber neuropathy in Sjogren syndrome. Neurology 2005; 65 (06) 925-927
    CrossrefPubMedGoogle Scholar
  • 81 Gwathmey KG. Sensory neuronopathies. Muscle Nerve 2016; 53 (01) 8-19
    CrossrefPubMedGoogle Scholar
  • 82 Pandolfo M. Friedreich ataxia: the clinical picture. J Neurol 2009; 256 (Suppl. 01) 3-8
    PubMedGoogle Scholar
  • 83 Kuntzer T, Antoine JC, Steck AJ. Clinical features and pathophysiological basis of sensory neuronopathies (ganglionopathies). Muscle Nerve 2004; 30 (03) 255-268
    CrossrefPubMedGoogle Scholar
  • 84 Szmulewicz DJ, McLean CA, Rodriguez ML. , et al. Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS. Neurology 2014; 82 (16) 1410-1415
    CrossrefPubMedGoogle Scholar
  • 85 Duggins AJ, McLeod JG, Pollard JD. , et al. Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy. Brain 1999; 122 (Pt 7): 1383-1390
    CrossrefPubMedGoogle Scholar
  • 86 Preston DC, Shapiro BE. Needle electromyography. Fundamentals, normal and abnormal patterns. Neurol Clin 2002; 20 (02) 361-396 , vi
    CrossrefPubMedGoogle Scholar
  • 87 Vucic S, Cairns KD, Black KR, Chong PST, Cros D. Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy. Clin Neurophysiol 2004; 115 (10) 2329-2335
    CrossrefPubMedGoogle Scholar
  • 88 Sander HW, Latov N. Research criteria for defining patients with CIDP. Neurology 2003; 60 (08) (Suppl. 03) S8-S15
    CrossrefPubMedGoogle Scholar
  • 89 Van den Bergh PY, Hadden RD, Bouche P. , et al; Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—first revision. J Peripher Nerv Syst 2010; 15 (01) 1-9
    PubMedGoogle Scholar