title: White matter dementia in CADASIL.
abstract: Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.
authors.affiliation: Department of Neurology, UCHSC, and Denver Veterans Affairs Medical Center, CO 80262, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Filley
authors.forename: L L
authors.initials: LL
authors.lastname: Thompson
authors.forename: C I
authors.initials: CI
authors.lastname: Sze
authors.forename: J A
authors.initials: JA
authors.lastname: Simon
authors.forename: J F
authors.initials: JF
authors.lastname: Paskavitz
authors.forename: B K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
mesh_terms: D001921:Brain / Q000473:pathology; D002539:Cerebral Arterial Diseases / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D002544:Cerebral Infarction / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003072:Cognition Disorders; D015161:Dementia, Multi-Infarct / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D004815:Epidermal Growth Factor / Q000235:genetics; D006801:Humans; D007859:Learning Disabilities; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012867:Skin / Q000473:pathology
chemical_list: D004815:Epidermal Growth Factor