Mitochondrial encephalomyopathy, lactic acidosis, stroke‐like episodes (MELAS): Clinical, radiological, pathological, and genetic observations

We reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke‐like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged‐red fibers. In patients with earlier onset of symptoms (<2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine‐like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged‐red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes.