Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, the Netherlands.
Institute for Stroke and Dementia Research (ISD), University Hospital LMU Munich, Munich, Germany.
JAMA Neurol. 2020 May 1;77(5):643-647. doi: 10.1001/jamaneurol.2019.5106.
Neuropathology studies show a high prevalence of cortical microinfarcts (CMIs) in aging individuals, especially in patients with cerebrovascular disease and dementia. However, most, are invisible on T1- and T2-weighted magnetic resonance imaging (MRI), raising the question of how to explain this mismatch. Studies on small acute infarcts, detected on diffusion-weighted imaging (DWI), suggest that infarcts are largest in their acute phase and reduce in size thereafter. Therefore, we hypothesized that a subset of the CMI that are invisible on MRI can be detected on MRI in their acute phase. However, to our knowledge, a serial imaging study investigating the temporal dynamics of acute CMI (A-CMI) is lacking.
To determine the prevalence of chronic CMI (C-CMI) and the cumulative incidence and temporal dynamics of A-CMI in individuals with cerebral small vessel disease (SVD).
DESIGN, SETTING, PARTICIPANTS AND EXPOSURES: The RUN DMC-Intense study is a single-center hospital-based prospective cohort study on SVD performed between March 2016 and November 2017 and comprising 10 monthly 3-T MRI scans, including high-resolution DWI, 3-dimensional T1, 3-dimensional fluid-attenuated inversion recovery, and T2. One hundred six individuals from the previous longitudinal RUN DMC study were recruited based on the presence of progression of white matter hyperintensities on MRI between 2006 and 2015 and exclusion of causes of cerebral ischemia other than SVD. Fifty-four individuals (50.9%) participated. The median total follow-up duration was 39.5 weeks (interquartile range, 37.8-40.3). Statistical data analysis was performed between May and October 2019.
We determined the prevalence of C-CMI using the baseline T1, fluid-attenuated inversion recovery, and T2 scans. Monthly high-resolution DWI scans (n = 472) were screened to determine the cumulative incidence of A-CMI. The temporal dynamics of A-CMI were determined based on the MRI scans collected during the first follow-up visit after A-CMI onset and the last available follow-up visit.
The median age of the cohort at baseline MRI was 69 years (interquartile range, 66-74 years) and 34 participants (63%) were men. The prevalence of C-CMI was 35% (95% CI, 0.24-0.49). Monthly DWI detected 21 A-CMI in 7 of 54 participants, resulting in a cumulative incidence of 13% (95% CI, 0.06-0.24). All A-CMI disappeared on follow-up MRI.
Acute CMI never evolved into chronically MRI-detectable lesions. We suggest that these A-CMI underlie part of the submillimeter C-CMI encountered on neuropathological examination and thereby provide a source for the high CMI burden on neuropathology.
神经病理学研究表明,皮质微梗死(CMI)在衰老个体中非常普遍,尤其是在患有脑血管病和痴呆的患者中。然而,大多数 CMI 在 T1-和 T2 加权磁共振成像(MRI)上不可见,这就提出了一个问题,即如何解释这种不匹配。关于在弥散加权成像(DWI)上检测到的小急性梗死的研究表明,梗死在其急性期最大,并在此后减小。因此,我们假设在 MRI 的急性期可以检测到一部分在 MRI 上不可见的 CMI。然而,据我们所知,缺乏关于急性 CMI(A-CMI)时间动态的连续成像研究。
确定脑小血管病(SVD)患者中慢性 CMI(C-CMI)的患病率以及 A-CMI 的累积发病率和时间动态。
设计、地点、参与者和暴露情况:RUN DMC-Intense 研究是一项于 2016 年 3 月至 2017 年 11 月在医院进行的针对 SVD 的单中心前瞻性队列研究,包括 10 次每月的 3-T MRI 扫描,包括高分辨率 DWI、3 维 T1、3 维液体衰减反转恢复和 T2。根据 2006 年至 2015 年 MRI 上白质高信号的进展,从之前的 RUN DMC 纵向研究中招募了 106 名参与者,并排除了除 SVD 以外的其他引起脑缺血的原因。有 54 名参与者(50.9%)参加。中位总随访时间为 39.5 周(四分位距,37.8-40.3)。统计数据分析于 2019 年 5 月至 10 月进行。
我们使用基线 T1、液体衰减反转恢复和 T2 扫描来确定 C-CMI 的患病率。每月筛选高分辨率 DWI 扫描(n=472),以确定 A-CMI 的累积发病率。根据 A-CMI 发病后第一次随访和最后一次可获得的随访期间收集的 MRI 扫描,确定 A-CMI 的时间动态。
基线 MRI 时队列的中位年龄为 69 岁(四分位距,66-74 岁),34 名参与者(63%)为男性。C-CMI 的患病率为 35%(95%CI,0.24-0.49)。每月的 DWI 在 7 名 54 名参与者中检测到 21 例 A-CMI,累积发病率为 13%(95%CI,0.06-0.24)。所有 A-CMI 在随访 MRI 上均消失。
急性 CMI 从未发展为慢性 MRI 可检测到的病变。我们认为,这些 A-CMI 构成了神经病理学检查中遇到的亚毫米 C-CMI 的一部分,从而为 CMI 在神经病理学上的高负担提供了来源。