ADULT-ONSET MELAS - EVIDENCE FOR INVOLVEMENT OF NEURONS AS WELL AS CEREBRAL VASCULATURE IN STROKE-LIKE EPISODES

Background We report a 46-year-old woman with implications regarding p athogenesis of strokelike episodes in MELAS (mitochondrial encephalomy opathy, lactic acidosis, and strokelike episodes). She had a 10-month history of episodic seizures, strokes, cognitive decline, vomiting, an d ileus. She also had sensorineural hearing loss, insulin-dependent di abetes mellitus of several years' duration, and persistent lactic acid osis. Family history was pertinent for a similar syndrome in her decea sed mother (onset in her sixties), for hearing loss and diabetes melli tus in two brothers, and for hearing loss in her only child, a son. Ca se Description Serial MRIs of the brain revealed severe but evanescent cerebral cortical abnormalities. A left temporal brain biopsy was per formed to exclude encephalitis. Light microscopy revealed a diffuse fi brillary gliosis with abundant reactive gemistocytes, focal evidence o f ischemic neuronal injury, and edema. Electron microscopy revealed bi zarre enlarged mitochondria and changes consistent with cellular edema . Succinate dehydrogenase staining was strongly reactive within cerebr al blood vessels and within neurons. A point mutation was subsequently found at nt 3243 of the mitochondrial tRNA(Leu(UUR)) gene in peripher al leukocytes and in brain, confirming the clinical diagnosis of MELAS . Quantitation revealed that 82% of brain mitochondria carried the dis ease mutation, indicating that most, if not all, tissues were affected . Conclusions Our findings suggest that strokelike episodes in MELAS r esult from defects in neuronal metabolism, as well as in cerebral vasc ulature.