Cases with familial diffuse leukoencephalopathy

<p>We herein introduce two sisters with young-onset dementia and demonstrate their clinical course, radiographic findings, psychiatric abnormalities and neuropathological findings. They suffered from frontal lobe dementia with decreased motivation, impaired attention, amnestic syndrome and inappropriate affect. Visuospatial disorientation was developed two years later together with fecal and urinary incontinence two to three years later. They finally showed hypokinetic mutism and required nasal tube nutrition in the bed-ridden state five to six years later. Tonic-clonic seizures were observed three years later in the younger sister and ten years later in the elder sister after the onset of their illness. Laboratory tests were unremarkable. Computed tomography of the two cases demonstrated diffuse cerebral atrophy with ventricular enlargement and calcifications in bilateral basal ganglia. Brain magnetic resonance imaging revealed cerebral atrophy with diffuse changes in the white matter on T2-wighted sequences. Pathological bone fractures were not noted in either of their clinical courses. The genetic analysis was not performed because their family did not give a consent. Duration of clinical course of their illness was 22 years in the elder sister and 12 years in the younger sister, respectively.</p><p>Their autopsy revealed that the brain weight was 580g for the elderly sister and 935g for the younger sister as well as moderate to severe atrophy of the frontotemporal lobes and corpus callosum. A histological examination showed marked symmetrical damage of the cerebral white matter (myelin loss and axonal degeneration). Widespread presence of axonal changes such as fragmentation and spheroids in the white matter of the cerebral hemisphere, cerebellum, basal ganglia and brain stem were observed. Calcifications were apparent in both basal ganglia. The elder sister showed numerous senile plaques and a few neurofibrillary tangles in the cerebral cortices while other senility related changes were compatible with a diagnosis of Alzheimer's disease, who were regarded as having combined pathological features of both Alzheimer's disease and diffuse leukoencephalopathy.</p>