Intracerebral distribution of mitochondrial abnormalities in 21 cases of infantile spongy dystrophy.

Using a monoclonal antibody to an inner mitochondrial membrane antigen and light microscopic immunohistochemistry, we investigated the distribution of increased immunostaining (mitochondrial anomalies, MA) on paraffin sections from 21 brains with infantile spongy dystrophy (Leigh's disease, 8; Canavan's disease, 4; Alpers' syndrome, 2; mixed spongy dystrophy, 7). Compared with an age-matched control group, MA were present in all cases of Leigh's disease (leptomeningeal and intracerebral endothelial and vascular smooth muscle cells, choroid plexus epithelia, ependymal cells, astrocytes or some neurons), in 2 cases of Canavan's disease and the Alpers' syndrome cases (astrocytes and occasionally some neurons). The MA were restricted to spongy areas in Canavan's disease and Alpers' syndrome, whereas they were distributed throughout the brain in Leigh's disease. In mixed spongy dystrophies the Leigh histology was associated with MA, but not the Canavan histology. Brains with Wernicke's encephalopathy (3 cases), adult infarction (3), and multicystic encephalopathy (5) showed no MA, but one with methylmalonaciduria did. Our results substantiate the classification of Leigh's disease as primary mitochondrial encephalopathy.