Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy

Andria L. Ford, Victoria W. Chin, Slim Fellah, Michael M. Binkley, Allie M. Bodin, Vamshi Balasetti, Yewande Taiwo, Peter Kang, Doris Lin, Joanna C. Jen, M. Gilbert Grand, Madonna Bogacki, M. Kathryn Liszewski, Dennis Hourcade, Yasheng Chen, Jason Hassenstab, Jin Moo Lee, Hongyu An, Jonathan J. Miner, John P. Atkinson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


ObjectiveTo characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI.MethodsWe 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.ResultsTwenty 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).ConclusionRVCL-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.

Original languageEnglish (US)
Pages (from-to)E1918-E1931
Issue number14
StatePublished - Oct 6 2020

ASJC Scopus subject areas

  • Clinical Neurology


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