Adult-onset MELAS - Evidence for involvement of neurons as well as cerebral vasculature in strokelike episodes

Background We report a 46-year-old woman with implications regarding pathogenesis of strokelike episodes in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). She had a 10-month history of episodic seizures, strokes, cognitive decline, vomiting, and ileus. She also had sensorineural hearing loss, insulin-dependent diabetes mellitus of several years' duration, and persistent lactic acidosis. Family history was pertinent for a similar syndrome in her deceased mother (onset in her sixties), for hearing loss and diabetes mellitus in two brothers, and for hearing loss in her only child, a son. Case Description Serial MRIs of the brain revealed severe but evanescent cerebral cortical abnormalities. A left temporal brain biopsy was performed to exclude encephalitis. Light microscopy revealed a diffuse fibrillary gliosis with abundant reactive gemistocytes, focal evidence of ischemic neuronal injury, and edema. Electron microscopy revealed bizarre enlarged mitochondria and changes consistent with cellular edema. Succinate dehydrogenase staining was strongly reactive within cerebral blood vessels and within neurons. A point mutation was subsequently found at nt 3243 of the mitochondrial tRNA(Leu(UUR)) gene in peripheral leukocytes and in brain, confirming the clinical diagnosis of MELAS. Quantitation revealed that 82% of brain mitochondria carried the disease mutation, indicating that most, if not all, tissues were affected. Conclusions Our findings suggest that strokelike episodes in MELAS result from defects in neuronal metabolism, as well as in cerebral vasculature.