Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy.
Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy.
复制标题
DOI：
10.1212/wnl.0000000000010659
复制
发表时间：
2020-10-06
期刊：
影响因子：
9.9
通讯作者：
Atkinson JP
中科院分区：
文献类型：
--
作者：
Ford AL;Chin VW;Fellah S;Binkley MM;Bodin AM;Balasetti V;Taiwo Y;Kang P;Lin D;Jen JC;Grand MG;Bogacki M;Liszewski MK;Hourcade D;Chen Y;Hassenstab J;Lee JM;An H;Miner JJ;Atkinson JP
使用多模式MRI表征视网膜血管病变伴脑白质脑病和全身表现（RVCL-S）的病变演变和神经变性。我们前瞻性地对RVCL-S和健康对照队列进行了MRI和认知测试。量化灰色和白色物质体积以及白色物质微观结构的破坏。不对称自旋回波采集允许逐体素氧提取分数（OEF）计算作为微血管缺血的体内标志物。RVCL-S队列被纳入病变亚型的纵向分析中，其中液体衰减反转恢复（FLAIR）、T1-后钆和弥散加权成像上的高信号病变被描绘和定量。招募了20名RVCL-S患者和26名对照。与对照组相比，RVCL-S患者的白色物质体积和显微结构下降更快。RVCL-S的白色萎缩呈高度线性（ρ =-0.908，p < 0.0001）。RVCL-S的标准化OEF升高，并随病程延长而增加。多个认知领域，特别是那些测量工作记忆和处理速度，在RVCL-S受损。无论何种亚型，病变体积随着年龄的变化而进展/消退，变异性很高，而FLAIR病变负荷在临近死亡时增加（p < 0.001）。RVCL-S是一种单基因微血管病，主要影响白色物质，涉及萎缩和认知障碍。RVCL-S中的白色物质体积呈线性下降，提供了一个潜在的指标，用于测试未来疗法的疗效。进行性升高的白色物质OEF表明微血管缺血可能是RVCL-S神经变性的基础。
To characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI. 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. 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). 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.