New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan.

Purpose Definite diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy (CADASIL) is mostly done by identification of NOTCH3 mutations. We aimed to develop criteria for selecting patients suspected for CADASIL to undergo genetic testing. Subjects and methods All subjects were Japanese. We recruited CADASIL patients genetically diagnosed up until 2011 (n = 37, Group 1) or after 2011 (n = 65, Group 2), 67 young stroke patients (≤ 55 years old), and 53 NOTCH3 -negative CADASIL-like patients. The members of Japanese research committee for hereditary cerebral small vessel disease discussed and generated the new criteria to maximize positive rate in Group 1 CADASIL patients, followed by validation of sensitivity and specificity. Results In Group 1 CADASIL patients, the ages at onset excluding migraine were distributed widely (37–74 years old) and bimodal (< 55 and > 55 years old). Frequencies of an autosomal dominant family history and vascular risk factor(s) were 73 and 65%, respectively. From these findings, the panel considered appropriate cut-off values and weighting for each item. In CADASIL Group 1 versus young stroke controls, the sensitivity and specificity of the new criteria were 97.3% and 80.6%, respectively. However, in CADASIL Group 2 versus NOTCH3 -negative controls, the sensitivity and specificity were 96.9% and 7.5%, respectively. Forty mutations of NOTCH3 distributed in exons 2–8, 11, 14, 18, 19, and 21 were identified in this study. Ten mutations were unreported ones. Conclusion We propose the new criteria of high sensitivity, which will help physicians to assess the need for genetic testing. [ABSTRACT FROM AUTHOR]