SKELETAL-MUSCLE MITOCHONDRIAL DYSFUNCTION IN ALTERNATING HEMIPLEGIA OF CHILDHOOD

Alternating hemiplegia of childhood is an uncommon disease characteriz ed by repeated, transient attacks of hemiplegia. Its pathophysiology i s uncertain, but attention recently has focused on possible mitochondr ial abnormalities. Using P-31 magnetic resonance spectroscopy, we stud ied gastrocnemius muscle in 5 patients with alternating hemiplegia, ag ed 8 to 30 (mean, 18) years, at rest and during incremental aerobic ex ercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) ye ars. Exercise performance was grossly impaired in the patients, the me an duration being 30% of normal. The total change in pH during exercis e was somewhat less than in control subjects, while the changes in pho sphocreatine concentration and intracellular ADP were similar. Thus th e average overall rate of fall of phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, th e initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both th e initial rate of phosphocreatine resynthesis and the calculated mitoc hondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.