From the Centre for Clinical Brain Sciences (A.C.C.J., C.A., F.C., T.R., F.D., S.M.M., J.M.W.), UK Dementia Research Institute (A.C.C.J., C.A., F.C., T.R., F.D., S.M.M., J.M.W.), and Centre for Discovery Brain Sciences (M.H.), University of Edinburgh, United Kingdom.
Neurology. 2022 Nov 29;99(22):e2454-e2463. doi: 10.1212/WNL.0000000000201205. Epub 2022 Sep 19.
White matter hyperintensities (WMHs) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal intraindividual WMH volume changes in sporadic SVD.
We searched EMBASE and MEDLINE for articles up to 28 January 2022 on WMH volume changes using MRI on ≥2 time points in adults with sporadic SVD. We classified populations (healthy/community-dwelling, stroke, cognitive, other vascular risk factors, and depression) based on study characteristics. We performed random-effects meta-analyses with Knapp-Hartung adjustment to determine mean WMH volume change (change in milliliters, percentage of intracranial volume [%ICV], or milliliters per year), 95% CI, and prediction intervals (PIs, limits of increase and decrease) using unadjusted data. Risk of bias assessment tool for nonrandomized studies was used to assess risk of bias. We followed Preferred Reporting in Systematic Review and Meta-Analysis guidelines.
Forty-one articles, 12,284 participants, met the inclusion criteria. Thirteen articles had low risk of bias across all domains. Mean WMH volume increased over time by 1.74 mL (95% CI 1.23-2.26; PI -1.24 to 4.73 mL; 27 articles, N = 7,411, mean time interval 2.7 years, SD = 1.65); 0.25 %ICV (95% CI 0.14-0.36; PI -0.06 to 0.56; 6 articles, N = 1,071, mean time interval 3.5 years, SD = 1.54); or 0.58 mL/y (95% CI 0.35-0.81; PI -0.26 to 1.41; 8 articles, N = 3,802). In addition, 13 articles specifically mentioned and/or provided data on WMH regression, which occurred in asymptomatic, stroke, and cognitive disorders related to SVD.
Net mean WMH volume increases over time mask wide-ranging change (e.g., mean increase of 1.75 mL ranging from 1.25 mL decrease to 4.75 mL increase), with regression documented explicitly in up to one-third of participants. More knowledge on underlying mechanisms, associated factors, and clinical correlates is needed, as WMH regression could be an important intervention target.
脑白质高信号（WMH）是小血管疾病（SVD）的常见影像学特征，与不良临床结局相关。WMH 随时间的进展已有充分描述，但最近也有报道其出现消退，尽管其频率和相关因素尚不清楚。本系统评价和荟萃分析旨在评估散发性 SVD 中个体的 WMH 体积随时间的纵向变化。
我们检索了 EMBASE 和 MEDLINE 数据库，以获取截至 2022 年 1 月 28 日的文章，这些文章使用 MRI 对≥2 个时间点的散发性 SVD 患者的 WMH 体积变化进行了研究。我们根据研究特征将人群（健康/社区居住者、卒中、认知障碍、其他血管危险因素和抑郁）进行分类。我们使用未调整数据进行随机效应荟萃分析，采用 Knapp-Hartung 调整来确定 WMH 体积变化的平均值（以毫升、颅内体积百分比[%ICV]或毫升/年表示）、95%置信区间和预测区间（PI，增加和减少的上限）。非随机研究的偏倚风险评估工具用于评估偏倚风险。我们遵循了系统评价和荟萃分析的首选报告规范。
41 篇文章、12284 名参与者符合纳入标准。13 篇文章在所有领域的偏倚风险均较低。WMH 体积随时间呈增加趋势，平均增加 1.74 毫升（95%置信区间 1.23-2.26；PI -1.24 至 4.73 毫升；27 篇文章，N=7411，平均时间间隔 2.7 年，SD=1.65）；0.25%ICV（95%置信区间 0.14-0.36；PI -0.06 至 0.56；6 篇文章，N=1071，平均时间间隔 3.5 年，SD=1.54）；或 0.58 毫升/年（95%置信区间 0.35-0.81；PI -0.26 至 1.41；8 篇文章，N=3802）。此外，13 篇文章专门提到并/或提供了与 SVD 相关的无症状、卒中和认知障碍相关的 WMH 消退的数据。
随时间的净平均 WMH 体积增加掩盖了广泛的变化（例如，1.75 毫升的平均增加，范围从 1.25 毫升减少到 4.75 毫升增加），多达三分之一的参与者明确记录了消退。需要更多关于潜在机制、相关因素和临床相关性的知识，因为 WMH 消退可能是一个重要的干预靶点。
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