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

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 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.