Assessing changes on large cerebral arteries in CADASIL: Preliminary insights from a case-control analysis

Abstract

Introduction: Parent large brain arteries are intimately related to their offspring's small arteries. Whether the CADASIL phenotype is confined to small vessels is unclear, and the involvement of large arteries in CADASIL has not been systematically studied.

Methods: We conducted a retrospective observational study with patients with CADASIL and randomly selected controls with acute lacunar stroke from the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry. We measured the diameters of both groups' basilar artery (BA) and intracranial internal carotid artery (ICA) on T2-weighted images. Z-scores of the arteries were calculated to derive a Brain Arterial Remodeling (BAR) score. We rated cervical ICA tortuosity as 0=no tortuosity, 1 = 45-90° deviation, and 2= >90°. Generalized linear models compared large artery characteristics, adjusting for demographics and clinical variables.

Results: We matched 37 patients with CADASIL with 104 controls. Patients with CADASIL were less likely to be Hispanic/Latino (p < 0.001), hypertensive (p < 0.001), or current smokers (p = 0.02) but more likely to have a prior stroke (p < 0.001) than controls. In adjusted models, patients with CADASIL had larger BA diameters than controls (p = 0.002), but there were no differences in the right and left ICA diameters (p = 0.73, p = 0.88). There was a statistical trend for higher cervical ICA tortuosity in patients with CADASIL compared to controls (p = 0.08).

Conclusions: Traditionally considered a small-vessel disease, patients with CADASIL have larger BA diameters and possibly higher cervical ICA tortuosity than controls. Whether these changes are part of the NOTCH-3 mutation phenotype or influence the clinical course is uncertain but should be further investigated.

Keywords: Arterial dilatation; Dementia; NOTCH3; Small-vessel-disease; Stroke.

Fig. 1.. Arterial diameter and tortuosity measurements

Fig. 1: a) In the T2-weighted MRI sequences, the diameter of the internal carotid artery was measured in the cavernous portion using two orthogonal planes. b) For the basilar artery, T2-weighted MRI sequences were utilized, and the diameter was measured in two orthogonal planes. c) In the sagittal plane of the Time-of-Flight neck MRA, cervical ICA tortuosity was measured by tracing an imaginary line along the carotid path at each coiled or curved section. The angle of divergence was 65°, corresponding to a tortuosity score of 1. d) Similarly, in the sagittal plane of the Time-of-Flight neck MRA, the internal carotid artery’s angle of divergence was 110°, corresponding to a tortuosity score of 2.