Simple MRI Lesion Levels Improve Two-Year Prognostic Accuracy Beyond Clinical History in CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small-vessel disease. The CADASIL MRI Inventory Tool summarizes individual MRI findings as simple, type-specific lesion levels. We assessed the predictive value of these levels beyond clinical information. METHODS: At baseline, CADASIL MRI Inventory Tool levels were assigned for periventricular, deep, and superficial white matter hyperintensities, lacunes, cerebral microbleeds, perivascular spaces in the centrum semiovale and basal ganglia, superficial and deep atrophy, large infarcts, and macrobleeds. Outcomes included stroke, migraine with aura (MA), moderate or severe cognitive impairment, and disability, which were assessed at baseline and during 2-year follow-up. Multivariable logistic regression was performed, with adjustment for age, sex, vascular risk factors, mutation location, and education level. RESULTS: We analyzed 743 patients from France, Germany, and Taiwan (mean age, 53±12; 55% with prior stroke; 35% with MA; 15% with disability; 18% with cognitive impairment). At baseline, higher deep white matter hyperintensities and lacune levels were associated with stroke, whereas cerebral microbleeds and superficial atrophy were inversely associated with MA. Superficial atrophy and periventricular white matter hyperintensities were higher, and superficial white matter hyperintensities were lower, among those with cognitive impairment, whereas deep atrophy and lacunes were linked to disability. Over 2 years (n=547), 11.7% experienced ischemic stroke events, 22.2% MA attacks, 6.5% developed disability, and 6.9% moderate or severe cognitive impairment. After adjustment, lacune levels independently predicted ischemic stroke events (odds ratio, 6.10 [95% CI, 2.09-26.02] for all levels combined). Superficial atrophy and higher superficial white matter hyperintensities predicted a lower risk of MA (odds ratio, 0.29 and 0.21 [95% CI, 0.12-0.68] and [0.06-0.77]). Lacunes and deep atrophy predicted disability, and lacunes with superficial atrophy predicted cognitive impairment. CONCLUSIONS: CADASIL MRI Inventory Tool lesion levels are differentially associated with CADASIL manifestations and provide independent 2-year prognostic information beyond clinical covariates. These simple measures may supplement clinical evaluation to improve short-term risk stratification and support patient selection in clinical trials.