Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by NOTCH3 mutation. Nailfold capillaroscopy is a non-invasive technique typically used for rheumatic diseases. It has potential in other conditions linked to vascular pathology. However, capillaroscopy in CADASIL has not been explored. This study aims to investigate whether capillaroscopy measurements can correlate with brain vascular changes in preclinical CADASIL patients, specifically those with NOTCH3 mutation.

This study included 69 participants from the Taiwan Precision Medicine Initiative (TPMI) dataset who visited Taichung Veterans General Hospital from January to December 2022. All individuals underwent genetic studies, brain imaging and nailfold capillaroscopy. The Mann-Whitney U test was used to compare results of brain imaging between carriers and controls. It was also used to compare measurements in nailfold capillaroscopy within each group. Spearman Rank Correlation Analysis was used to explore the relationship between capillary measurements and brain MRI results.

White matter hyperintensities (WMH) expression was positively correlated with capillary dimension and negatively correlated with density. Our results presented that R544C carriers exhibited a diffuse increase in WMH (p < 0.001) and a global reduction in gray matter volume but preserved in specific areas. The white matter lesion scores in all brain regions were higher in the mutation carriers than the controls. (p < 0.001).

This research highlights the association of nailfold capillaroscopy findings with white matter lesions in preclinical CADASIL patients. Capillaroscopy guides an effective screening strategy in individuals with NOTCH3 mutations.