SPECT STUDY OF A GERMAN CADASIL FAMILY - A PHENOTYPE WITH MIGRAINE AND PROGRESSIVE DEMENTIA ONLY

Objective: We describe the clinical, molecular, genetic, MRI, and SPEC T features of a German family with autosomal dominant migraine and dem entia, mapping to the cerebral autosomal dominant arteriopathy with su bcortical infarcts and leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood flow, MRI, and cognitive function. Background: CADASIL is a small-vessel disease of the brain mapped to c hromosome 19p13.1. Mutations of the Notch3 gene cause this disorder. M ost phenotypes are characterized by transient ischemic attacks (TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A singl e photon emission computed tomographic (SPECT) study of this disorder has not yet been published. Methods: We studied 13 individuals clinica lly and performed neuroimaging studies with MRI and SPECT. Results: Ge netic analysis strongly supported linkage to the CADASIL locus, and th e disease haplotype was found in six individuals. Analysis by single-s trand confirmation polymorphism did not identify Notch3 mutations. All affected individuals had MRI white matter hyperintensities and four i ndividuals had additional basal ganglial signal abnormalities. Four af fected individuals had migraine, two of whom had slowly progressive de mentia. TIAs, stroke, and focal neurologic signs were absent. Cerebral blood flow reduction in SPECT studies of affected individuals matched with MRI signal abnormalities. Cognitive impairment was linked to sig nal abnormalities and hypoperfusion in the basal ganglia. Demented pat ients had a pattern of frontal, temporal, and basal ganglial hypoperfu sion. Conclusions: We describe a CADASIL phenotype that is characteriz ed by the absence of focal neurologic symptoms and present the first S PECT study of this disorder.