A new familial adult-onset leukodystrophy manifesting as cerebellar ataxiaand dementia

Background: Among hereditary leukodystrophies, a considerable number remain unclassified. Patient and results: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy wi th possible dominant inheritance. A 44-year-old man presented with cerebell ar ataxia as the initial symptom, and later, dementia and hyperreflexia wit h ankle clonus developed. T-2-weighted brain MRI showed brain atrophy and d iffuse high signal intensity of the cerebral white matter and the brain ste m. The patient's mother and older brother also had cerebellar ataxia and de mentia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurologi cal symptoms of adult-onset. Our patient died of pneumonia 5 years after th e onset of disease. The histopathological findings consisted mainly of patc hily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regi ons, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. Co nclusions: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophi es. (C) 2001 Elsevier Science B.V. All rights reserved.