Distal symmetric polyneuropathy: A definition for clinical research

The objective of this report was to develop a case definition of distal symmetric 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 symmetric 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 symmetric 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. NEUROLOGY 2005;64:199–207 Mission statement. The American Academy of Neurology (AAN) in conjunction with the American Association of Electrodiagnostic Medicine (AAEM) and the American Academy of Physical Medicine and Rehabilitation (AAPM&R) determined that there was a need for a formal case definition of polyneuropathy. Because of inconsistency in the literature, no consistent case definition exists. The use of a formal case definition across future research studies would ensure greater consistency of patient selection. This review describes the development of such a case definition for distal symmetric polyneuropathy. Justification. Polyneuropathy is a common neurologic disorder of diverse etiologies. Although experienced clinicians can usually diagnose polyneuropathy in patients presenting with the characteristic history and classic neurologic examination findings, the exact criteria for the diagnosis are not formalized. In particular, accurate criteria for the diagnosis of distal symmetric polyneuropathy are debated. The principal purpose of this project was to develop a definition of distal symmetric polyneuropathy with a reasonably high sensitivity and specificity that would serve as a basis for future research studies. Clinicians Approved by the QSS on July 25, 2003; by the Practice Committee on April 28, 2004; and by the AAN Board of Directors on October 16, 2004. From the American Academy of Neurology, St. Paul, MN; the American Association of Electrodiagnostic Medicine, Rochester, MN; and the American Academy of Physical Medicine and Rehabilitation, Chicago, IL. P.A.L. has acted as a consultant on Q SWEAT devices for W.R. Medical Co. Received August 27, 2003. Accepted in final form September 3, 2004. Address correspondence and reprint requests to American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116. Copyright © 2005 by AAN Enterprises, Inc. 199 may find the criteria useful for routine clinical diagnosis. To achieve greater focus, other neuropathy phenotypes including polyradiculopathy, mononeuropathy multiplex, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and related conditions were excluded from the final case definition. Although small-fiber polyneuropathy is an important subset of distal symmetric polyneuropathy, the evidence-based medical literature is insufficient to provide an adequate case definition for isolated or pure small-fiber polyneuropathy at this time. The case definition of distal symmetric polyneuropathy described herein is based upon a systematic analysis of peer-reviewed literature supplemented by consensus from an expert panel. Process. Formation of expert panel. The Polyneuropathy Task Force included 14 physicians with representatives from AAN, AAEM, and AAPM&R. All of the task force members had extensive experience and expertise in the area of polyneuropathy. Additionally, three physicians with expertise in evidence-based methodology and practice parameter development participated in the project. Finding the best evidence. The literature search included OVID MEDLINE (1970 to April 2004), OVID Excerpta Medica (EMBASE; 1980 to April 2004), and OVID Current