Supranuclear ophthalmoparesis and vacuolar degeneration of the cerebral white matter in amyotrophic lateral sclerosis: a clinicopathological study.

Possible clinicopathological relationship between vacuolar degeneration of cerebral white matter and clinical manifestation, especially of supranuclear ophthalmoparesis, both infrequent in amyotrophic lateral sclerosis (ALS) patients, was tested. Of 104 ALS sequential series, cases with vacuolar degeneration of the cerebral white matter were selected to yield 14 cases pathologically surveyed in this study. Clinical features were retrospectively assessed in their clinical records. Microscopic examination clarified vacuolar changes with fibrous gliosis, infiltration of macrophages, axonal degeneration with segmental dilatation and partial loss of myelin on electron microscopy. This histological change was extended into the cerebral white matter just under the cortices but sometimes accentuated as restricted areas along the pyramidal tract and precentral regions. In a patient with the most extensive focal lesion, these white matter vacuolar changes were detected with magnetic resonance imaging. The clinical manifestations linked to this focal vacuolar degeneration were disturbance of vertical ocular movements and shorter duration of the illness, compared with patients without vacuolar degeneration. In conclusion, histological demonstration of characteristic vacuolar degeneration in the white matter of ALS and its focal accentuation along precentral-pyramidal tracts are mutually related and possibly linked to clinical manifestations such as supranuclear ophthalmoparesis, an exceptional but possible manifestation of ALS.