Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy. (6th October 2020)

• Record Type: Journal Article
• Authors: Ford, Andria L.; Chin, Victoria W.; Fellah, Slim; Binkley, Michael M.; Bodin, Allie M.; Balasetti, Vamshi; Taiwo, Yewande; Kang, Peter; Lin, Doris; Jen, Joanna C.; Grand, M. Gilbert; Bogacki, Madonna; Liszewski, M. Kathryn; Hourcade, Dennis; Chen, Yasheng; Hassenstab, Jason; Lee, Jin-Moo; An, Hongyu; Miner, Jonathan J.; Atkinson, John P.
• Is Part Of: Neurology. Volume 95:Number 14(2020)
• Publication Date: 2020-10-06
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000010659
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. Methods: We prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically. Results: Twenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL–S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = −0.908, p < 0.0001). Normalized OEF was elevated in RVCL-S and increased with disease duration. Multiple cognitive domains, specifically those measuring working memory and processing speed, were impaired in RVCL-S. Lesion volumes, regardless of subtype, progressed/regressed with high variability as a function of age, while FLAIR lesion burden increased near time to death ( p < 0.001). Conclusion: RVCL-S is a monogenic microvasculopathy affecting predominantly the white matter with regard to atrophy and cognitive impairment. White matter volumes in RVCL-S declined linearly, providing a potential metric against which to test the efficacy of future therapies. Progressive elevation of white matter OEF suggests that microvascular ischemia may underlie neurodegeneration in RVCL-S.