Lesion evolution and neurodegeneration in RVCL-S, a monogenic microvasculopathy
Creators
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Ford, Andria1
- Chin, Victoria1
- Fellah, Slim1
- Binkley, Michael M.1
- Bodin, Allie1
- Balasetti, Vamshi1
- Taiwo, Yewande1
- Kang, Peter1
- Lin, Doris2
- Jen, Joanna3
- Grand, Gilbert1
- Bogacki, Madonna1
- Liszewski, M. Kathryn1
- Hourcade, Dennis1
- Chen, Yasheng1
- Hassenstab, Jason1
- Lee, Jin-Moo1
- An, Hongyu1
- Miner, Jonathan1
- Atkinson, John P.1
- 1. Washington University in St. Louis School of Medicine
- 2. Johns Hopkins University School of Medicine
- 3. Icahn School of Medicine at Mount Sinai
Description
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 FLAIR, T1-post-gadolinium, 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 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 predominantly affecting 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 efficacy of future therapies. Progressive elevation of white matter OEF suggests microvascular ischemia may underlie neurodegeneration in RVCL-S.
Notes
This is supplemental data that did not fit into the manuscript.
Clayco Foundation, Energy 4 A Cure Foundation, Cure CRV Research, National Institutes of Health: National Heart, Lung, and Blood Institute (R01HL129241, A.L.F); Washington University St. Louis CTSA (UL1 TR000448, A.L.F.).
Funding provided by: Clayco Foundation
Crossref Funder Registry ID:
Award Number:
Funding provided by: Energy 4 A Cure Foundation
Crossref Funder Registry ID:
Award Number:
Funding provided by: Cure CRV Research
Crossref Funder Registry ID:
Award Number:
Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01HL129241
Funding provided by: Washington University St. Louis CTSA
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007268
Award Number: UL1 TR000448
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Related works
- Is cited by
- 10.1212/WNL.0000000000010659 (DOI)
- 10.1212/WNL.0000000000011323 (DOI)