Gray matter lesions in Nasu-Hakola disease: a report on three autopsy cases

Abstract

Nasu-Hakola disease is an autosomal recessively inherited disease characterized by lipomembranous polycystic osteodysplasia and sclerosing leukoencephalopathy. While white matter lesions prominent in the brain have been reported in the literature, gray matter lesions have not received particular attention. In this study, we examined three autopsy cases of Nasu-Hakola disease in order to focus specifically on gray matter lesions. The ages at onset of the three cases were 20, 23 and 29 years, and the disease durations were 29, 19 and 8 years, respectively. In addition to characteristic degeneration in the cerebral white matter, such as demyelination with conspicuous fibrillary gliosis and axonal changes, all three cases showed overt pathology in the gray matter. Neuronal loss with gliosis in the thalamus (particularly in the dorsomedial nucleus and anterior nucleus), caudate nucleus, putamen and substantia nigra was prominent in all cases, and the severity corresponded to the disease duration. The cerebral cortices were relatively preserved in all cases. One case showed neuronal loss and gliosis in the gray matter of the hippocampus, possibly due to repeated episodes of epileptic convulsions. These gray matter pathologies are considered to be responsible for some of the clinical manifestations of the disease, including extrapyramidal symptoms.