White matter dementia in CADASIL

Cerebral white matter disorders may be associated with profound neurobehavi oral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dement ia. 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 l earning with intact recognition, and perseveration. Magnetic resonance imag ing of the brain-revealed extensive leukoencephalopathy. Right frontal brai n biopsy showed ill-defined white matter pallor with hyaline narrowing of w hite matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginin e for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosoma l dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL). This case illustrates that CADASIL can manifest as an isolated ne urobehavioral disorder over an extended time period. The dementia associate d with CADASIL closely resembles that which may occur with other white matt er disorders, and represents an example of white matter dementia. (C) 1999 Elsevier Science BN. All rights reserved.