Comparison of Clinical Course and Sequential Electrophysiological Tests in Diabetics with Symptomatic Polyneuropathy and its Implications for Clinical Trials

Abstract

The use of electrophysiological (EP) tests as the primary basis for determining outcome in clinical trials of therapy for symptomatic diabetic polyneuropathy, and the frequently short duration of such trials, is based on assumptions at variance with the pathology and natural history of this disorder and with the evidence that the commonly employed EP tests predominantly reflect the status of the large myelinated nerve fibers. The course of painful, distal symmetrical, primarily sensory polyneuropathy was studied in nine chronic diabetics, aged 21-59 yr, selected for the absence of other forms of diabetic neuropathy, other causes of neuropathy, and other significant illness. All were treated with modifications of diet, insulin, and a daily multivitamin tablet, and, on a randomized basis, also received either placebo or myo-inositol tablets. Initially, and after 2, 4, and 6 mo, a standardized questionnaire was used to assess symptoms, and a standardized neurological examination and battery of EP tests were performed. A minimum of 6 mo was found necessary to assess the clinical course of this syndrome. Clinical improvement occurred in both legs and arms in four patients, as judged by improvement both in symptoms and in the extent of deficits in pinprick and temperature perception; abnormalities in sensory modalities mediated by large myelinated fibers, however, were generally unaltered after 6 mo. A nonuniform distribution of abnormal EP tests of sensory components of the commonly studied nerves of the leg and arm was demonstrated in the study group at the outset, and clinical improvement was not accompanied by evidence of any consistent pattern of improvement in the initially abnormal EP tests. A significant fraction of chronic diabetics with painful, distal symmetrical, primarily sensory polyneuropathy selected by standard criteria appear to have potential for clinical improvement over 6 mo, but primarily in sensory modalities that make it inappropriate to use the common EP tests as the primary basis of judging outcome.