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

Chun-Min Liang; Wei Lee; Chien-Chih Chou; Hsin Tung; Hung-Chieh Chen; Hsian-Min Chen; Wei-Ju Lee; Yi-Ming Chen

doi:10.1016/j.jns.2024.123109

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

J Neurol Sci. 2024 Jul 15:462:123109. doi: 10.1016/j.jns.2024.123109. Epub 2024 Jun 23.

Authors

Chun-Min Liang¹, Wei Lee¹, Chien-Chih Chou², Hsin Tung³, Hung-Chieh Chen⁴, Hsian-Min Chen⁵, Wei-Ju Lee⁶, Yi-Ming Chen⁷

Affiliations

¹ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
² Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Center of Faculty Development, Taichung Veterans General Hospital, Taichung, Taiwan; Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Neuroradiology, Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Center for Quantitative Imaging in Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan; Dementia Center, Taichung Veterans General Hospital, Taichung, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁷ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan. Electronic address: [email protected].

PMID: 38941707
DOI: 10.1016/j.jns.2024.123109

Abstract

Background: 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.

Methods: 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.

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).

Conclusion: 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.

Keywords: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); Cerebral small vessel disease; NOTCH3 mutations; Nailfold capillaroscopy; White matter hyperintensities.

MeSH terms

Adult
Aged
Brain / diagnostic imaging
Brain / pathology
CADASIL* / diagnostic imaging
CADASIL* / genetics
Capillaries* / diagnostic imaging
Capillaries* / pathology
Female
Humans
Magnetic Resonance Imaging
Male
Microscopic Angioscopy* / methods
Middle Aged
Mutation*
Nails / blood supply
Nails / diagnostic imaging
Receptor, Notch3* / genetics
White Matter / diagnostic imaging
White Matter / pathology

Substances

Receptor, Notch3
NOTCH3 protein, human