MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study

This report concerns an autopsy case of mitochondrial myopathy, encephalopa thy, lactic acidosis, and stroke-like episodes (MELAS) with unusual neuropa thological findings. The patient was a Japanese woman who was 21 years old at the time of death. Her mother is a patient with genetically confirmed ME LAS. Her clinical manifestations included convulsions and lactic acidosis i n the latter half of the first decade of life. followed by deafness, dement ia, muscle weakness in the lower extremities, slight ataxia in the upper an d lower extremities, and diabetes mellitus. Muscle biopsy revealed ragged-r ed fibers, and genetic study showed a point mutation at nucleotide pair 324 3 in mitochondrial DNA. She died of lactic acidosis. In the clinical course , she did not develop strokelike episodes. The neuropathological examinatio n revealed not only minute to small necrotic foci in the cerebral cortex, a mygdala, hippocampus, and cerebellum, but also prominent white matter glios is in the central nervous system and cerebellar cortical degeneration of gr anular cell type. Our neuropathological findings, including prominent white matter gliosis of the central nervous system and cerebellar cortical degen eration of granular cell type, may indicate morphologically widespread cell ular dysfunction, not restricted to either neuronal or vascular derangement , in the brain pathology of MELAS.