The proposed studies will extend and enrich ongoing research into the nature and extent of myopathy and neuropathy associated with excessive alcohol use among selected clinical alcoholic subpopulations (race, gender, and age interactions). Our approach will be multidisciplinary in nature, employing measures of intact muscle performance (exercise physiology), skeletal muscle tissue pathology (histology), and an evaluation of the integrity of the motoneurones (via EMG) that innervate the muscle and of the spinal proprioceptive reflexes that influence motor control (neurology and neurophysiology). Taken together, these measures will provide a unique, comprehensive and much-needed profile of neuromotor dysfunction in chronic alcoholism. This research will continue to stress the importance of intact muscle function (strength and endurance of contractions of muscles in the arms and legs) as central to the definition of myopathy. At the same time, probes into the neurophysiological bases of alcohol myopathy and neuropathy will be expanded to include important measures in addition to electromyographic and nerve (motor, somato-sensory) conduction velocity measures now being employed. The integrity of spinal reflexes and the alpha and gamma motor pathways that regulate motor coordination will be assessed, as well as facilitatory and inhibitory mechanisms. The application of standard spectral analysis procedures to the EMG, coupled with deconvolution analysis of the distribution of conduction velocities of peripheral nerves will allow for an assessment of the relative decrements in slow-vs-fast twitch fibers accompanying alcohol abuse. All of these measures of neuromotor function outlined above, as well as muscle tissue biopsies, will reveal relationships between functional impairment and underlying tissue changes resulting from excessive alcohol consumption. In addition to the above observations on healthy, screened alcoholics, a description of the muscle performance deficits in a cross-section of unscreened alcoholics will be prepared for comparison. A separate substudy will monitor the recovery of function in selected subjects with chronic alcohol myopathy for a one-year period following cessation of alcohol use. In these studies, the recovery of function will be related to the underlying biological changes revealed by the neurophysiological procedures described.
