The natural history of CADASIL - A pooled analysis of previously publishedcases

Background and Purpose-Although numerous families with cerebral autosomal d ominant arteriopathy with subcortical infarcts and leukoencephalopathy (CAD ASIL) have been reported, our understanding of the disease remains incomple te. Thus, we performed this study to investigate the phenotypic range and n atural history of CADASIL. Methods-We performed a pooled analysis of previously published cases. Results-We identified 105 symptomatic patients in 33 families. Vascular ris k factors were uncommon, with hypertension reported in only 8 patients. The mean age of symptom onset was 36.7+/-12.9 years, Stroke or transient ische mic attack was an initial symptom in 45 patients, with a mean age of onset of 41.2+/-9.2 years. Migraine was also a common initial symptom, reported b y 42 patients at a younger mean age of 28.3+/-11.7 years, Other initial sym ptoms included depression in 9 patients, cognitive impairment in 6 patients , and seizures in 3 patients. Regarding clinical course, 71 patients experi enced a stroke or transient ischemic attack, and 52 of those patients had 1 or more recurrent ischemic events. Dementia was reported in 44 patients. O nly 3 additional patients experienced migraine at a later time, while 13 ad ditional patients developed depression. Six patients had seizures. Twenty-m io of the 105 patients had died, with a mean age of death of 54.8+/-10.6 ye ars. Nineteen of those 22 patients had experienced a stroke or transient is chemic attack and 19 patients were demented. Conclusions-CADASIL typically becomes evident in early or middle adulthood with migraine or an ischemic event, later manifests itself through recurren t subcortical ischemic strokes leading to a stepwise decline and dementia, and results in reduced survival.