Adult-onset leukodystrophy with axonal spheroids

We report two cases of adult-onset leukodystrophy with axonal spheroids in a brother and sister, one with an autopsy, the other with a cerebral biopsy. Symptoms developed at 24 and 33years. The sister died within four years, her brother in 2 and a half. Her brain showed a large lesion in the frontal centrum semiovale extending through the corpus callosum and shading off into the normal appearing U-fibers. With routine stains axonal spheroids were most easily detected in the mildly affected regions, although stains for neurofilaments showed that they were actually more numerous, though more irregular in shape, where the lesions were more severe. Axons and myelin appeared equally affected. Pigmented cells were absent. Electron microscopy on the cerebral biopsy showed that the spheroids contained neurofilaments and neurotubules, mitochondria and degenerate mitochondria, with a suggestion of polarity such that neurofilaments were more common in the proximal part of spheroids. Many other axons were found whose size was only slightly increased although they were filled with sacs of abnormal granular material which were probably derived from mitochondria. The anterior commissure and the corticospinal tracts in the spinal cord of the sister showed fiber loss and large vacuoles within which occasional intact axons could be identified. This was considered to represent intramyelin edema. In the cerebral biopsy one vacuole arising from myelin splitting was found in confirmation of this hypothesis. We conclude that both myelin and axons are damaged, although the lesions of myelin are conditioned by axonal abnormalies in this genetic disease.