Autosomal dominant leukodystrophy with axonal spheroids and pigmented glia: clinical and neuropathological characteristics.

We report two autopsy cases of siblings with adult-onset autosomal dominant leukodystrophy characterized by destruction of cerebral white matter, large numbers of axonal spheroids and pigmented glia in the fronto-temporal lobes. Both patients presented with motor and cognitive symptoms and aphasia, 2-3 years before death. At autopsy, the brain showed brown coloration and decreased volume of white matter in the frontal and temporal lobes as well as corpus callosum. Microscopically, marked loss of myelin and axons and abundant axonal spheroids without apparent neuronal loss were observed in the frontal and temporal lobes, which was consistent with hereditary diffuse leukodystrophy with spheroids (HDLS). In addition, glial cells, most consistent with macrophages and containing pigments that were stained by Sudan III and PAS, were found in the white matter lesions. The present cases showed overlapping features with HDLS and pigmentary type of orthochromatic leukodystrophy, suggesting that the pathomechanisms of these two diseases are closely related.