Distal symmetrical polyneuropathy: A definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation


      England JD, Gronseth GS, Franklin G, Miller RG, Asbury AK, Carter GT, Cohen JA, Fisher MA, Howard JF, Kinsella LJ, Latov N, Lewis RA, Low PA, Sumner AJ. Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.
      The objective of this report was to develop a case definition of “distal symmetrical polyneuropathy” to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

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        • Jones J.
        • Hunter D.
        Consensus methods for medical and health services research.
        BMJ. 1995; 311: 376-380
        • Rempel D.
        • Evanoff B.
        • Amadio P.C.
        • et al.
        Consensus criteria for the classification of carpal tunnel syndrome in epidemiologic studies.
        Am J Public Health. 1998; 88: 1447-1451
        • Dyck P.J.
        • Bushek W.
        • Spring E.M.
        • et al.
        Vibratory and cooling detection thresholds compared with other tests in diagnosing and staging diabetic neuropathy.
        Diabetes Care. 1987; 10 (Class II): 432-440
        • Dyck P.J.
        • Davies J.L.
        • Litchy W.J.
        • O’Brien P.C.
        Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort.
        Neurology. 1997; 49 (Class III): 229-239
        • Feldman E.L.
        • Stevens M.J.
        • Thomas P.K.
        • Brown M.B.
        • Canal N.
        • Greene D.A.
        A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy.
        Diabetes Care. 1994; 17 (Class III): 1281-1289
        • Franklin G.M.
        • Kahn L.B.
        • Baxter J.
        • Marshall J.A.
        • Hamman R.F.
        Sensory neuropathy in non-insulin-dependent diabetes mellitus.
        Am J Epidemiol. 1990; 131 (Class I): 633-643
        • Franse L.V.
        • Valk G.D.
        • Dekker J.H.
        • Heine R.J.
        • van Eijk J.T.
        “Numbness of the feet” is a poor indicator for polyneuropathy in type 2 diabetic patients.
        Diabet Med. 2000; 17 (Class I): 105-110
        • Gentile S.
        • Turco S.
        • Corigliano G.
        • Marmo R.
        • S.I.M.S.D.N. Group
        Simplified diagnostic criteria for diabetic distal polyneuropathy.
        Acta Diabetol. 1995; 32 (Class II): 7-12
        • Maser R.E.
        • Becker D.J.
        • Drash A.L.
        • et al.
        Pittsburgh Epidemiology of Diabetes Complications Study.
        Diabetes Care. 1992; 15 (Class II): 525-527
        • Meijer J.W.
        • van Sonderen E.
        • Blaauwwiekel E.E.
        • et al.
        Diabetic neuropathy examination.
        Diabetes Care. 2000; 23 (Class III): 750-753
        • Monticelli M.L.
        • Beghi E.
        Chronic symmetric polyneuropathy in the elderly: a field screening investigation in two regions of Italy: background and methods of assessment: The Italian General Practitioner Study Group (IGPSG).
        Neuroepidemiology. 1993; 12 (Class II): 96-105
        • Teunissen L.L.
        • Notermans N.C.
        • Franssen H.
        • et al.
        Differences between hereditary motor and sensory neuropathy type 2 and chronic idiopathic axonal neuropathy.
        Brain. 1997; 120 (Class III): 955-962
        • Valk G.D.
        • Nauta J.J.
        • Strijers R.L.
        • Bertelsmann F.W.
        Clinical examination versus neurophysiological examination in the diagnosis of diabetic polyneuropathy.
        Diabet Med. 1992; 9 (Class II): 716-721
        • Van Dijk G.W.
        • Wokke J.H.
        • Notermans N.C.
        • van Gijn J.
        • Franssen H.
        Diagnostic value of myotatic reflexes in axonal and demyelinating polyneuropathy.
        Neurology. 1999; 53 (Class III): 1573-1576
        • Dyck P.J.
        • Sherman W.R.
        • Hallcher L.M.
        • et al.
        Human diabetic endoneurial sorbital, fructose and myo-inositol related to sural nerve morphometry.
        Ann Neurol. 1980; 8: 590-596
        • Dyck P.J.
        • Karnes J.L.
        • Daube J.
        • O’Brien P.
        • Service F.J.
        Clinical and neuropathological criteria for the diagnosis and staging of diabetic polyneuropathy.
        Brain. 1985; 108: 861-880
        • Dyck P.J.
        • Karnes J.L.
        • O’Brien P.C.
        • Litchy W.J.
        • Low P.A.
        • Melton L.J.
        The Rochester Diabetic Neuropathy Study.
        Neurology. 1992; 42: 1164-1170
      1. Quantitative sensory testing. a consensus report from the Peripheral Neuropathy Association.
        Neurology. 1993; 43: 1050-1052
        • Shy M.E.
        • Frohman E.M.
        • So Y.T.
        • et al.
        • Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology
        Quantitative sensory testing.
        Neurology. 2003; 60: 898-904
        • Peripheral Nerve Society
        Diabetic polyneuropathy in controlled clinical trials.
        Ann Neurol. 1995; 38: 478-482
      2. Proceedings of a consensus development conference on standardized measures in diabetic neuropathy.
        Neurology. 1992; 42: 1823-1839
        • American Association of Electrodiagnostic Medicine
        Guidelines in electrodiagnostic medicine.
        Muscle Nerve. 1999; 22: S3-S300
        • Holland N.R.
        • Stocks A.
        • Hauer P.
        • Cornblath D.R.
        • Griffin J.W.
        • McArthur J.C.
        Intraepidermal nerve fiber density in patients with painful sensory neuropathy.
        Ann Neurol. 1997; 48: 708-711
        • Kennedy W.R.
        • Wendelschafer-Crabb G.
        The innervation of human epidermis.
        J Neurol Sci. 1993; 115: 184-190
        • McArthur J.C.
        • Stocks A.E.
        • Hauer P.
        • Cornblath D.R.
        • Griffin J.W.
        Epidermal nerve fiber density.
        Arch Neurol. 1998; 55: 1513-1520
        • Lauria G.
        • Sghirlanzoni A.
        • Lombardi R.
        • Pareyson D.
        Epidermal nerve fiber density in sensory ganglionopathies.
        Muscle Nerve. 2001; 24: 1034-1039