Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 mutations, is characterized by recurrent ischemic strokes and progressive cognitive decline. It remains unclear whether cerebral microbleeds (CMBs) can serve as a surrogate marker for disease progression in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. We aimed to investigate the CMB burdens in NOTCH3 mutation carriers at different disease stages and test their associations with cognitive performance. Methods and Results Forty-nine individuals carrying NOTCH3 cysteine-altering mutations received brain magnetic resonance imaging with T1-weighted and susceptibility-weighted images. Whole brain images were segmented into 14 regions using Statistical Parametric Mapping and FreeSurfer software, and semiautomatic methods were used to locate and quantify the number and volume of CMBs. In our study participants, the median of CMB counts was 13, with a wide individual variation (range, 0-286). CMBs were most frequently present in thalamus, followed by temporal lobe. In the whole brain, the CMB counts and CMB volume ratios (ie, CMB volume divided by the volume of corresponding brain region) gradually increased as the disease advanced. CMB counts in the thalamus and temporal and frontal lobes increased more rapidly than other brain regions as disease progressed. There were significant associations between Mini-Mental State Examination scores and CMB counts in the frontal lobe, temporal lobe, and pons. Conclusions CMBs may have an influential role in the clinical manifestations of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CMB burdens and their distribution in different brain regions may be capable to serve as a disease marker for monitoring the disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Keywords: CADASIL; Mini‐Mental State Examination; NOTCH3 gene; cerebral microbleeds.