Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Addenbrookes Hospital, Neurology Unit, Box 83, Cambridge CB2 2QQ, UK.
Brain. 2011 Jun;134(Pt 6):1765-76. doi: 10.1093/brain/awr100.
There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established positive impact of penumbral salvage. In order to test this hypothesis, non-core-non-penumbral tissue was identified in two independent prospectively recruited cohorts, using computed tomography perfusion, and magnetic resonance perfusion- and diffusion-weighted imaging, respectively. Follow-up structural magnetic resonance imaging was obtained about 1 month later in all patients to map the final infarct. The volumes of both the acutely silent but eventually infarcted tissue, and the eventually non-infarcted penumbra, were determined by performing voxel-wise analysis of the acute and follow-up image sets, using previously validated perfusion thresholds. Early neurological course was expressed as change in National Institutes of Health Stroke Scale scores between the acute and 1-month assessments, relative to the acute score. The relationship between the acutely silent but eventually infarcted tissue volume and early neurological course was tested using a multivariate regression model that included the volume of non-infarcted penumbra. Thirty-four and 58 patients were recruited in the computed tomography perfusion and magnetic resonance perfusion cohorts, respectively (mean onset-to-imaging time: 136 and 156 min; 27 and 42 patients received intravenous thrombolysis, respectively). Infarction of acutely silent tissue was identified in most patients in both cohorts. Although its volume (median 0.2 and 2 ml, respectively) was much smaller than that of salvaged penumbra (59.3 and 93 ml, respectively), it was substantial in ∼10% of patients. As expected, salvaged penumbra strongly positively influenced early neurological course. Even after correcting for the latter effect in the multivariate model, infarction of acutely silent tissue independently negatively influenced early neurological course in both cohorts (P=0.018 and 0.031, respectively). This is the first systematic study to document infarction of acutely silent tissue after anterior circulation stroke, and to show that it affects a sizeable fraction of patients and has the predicted negative impact on clinical course. These findings were replicated in two independent cohorts, regardless of the perfusion imaging modality used. Preventing infarction of the tissue not initially at risk should have direct clinical benefit.
在前循环中风后，早期神经功能的变化存在较大的个体间差异，但这种差异的病理生理学机制尚不完全清楚。在这里，我们假设，尽管目前的病理生理学模型没有预测到，但“非核心-非半暗带”（即临床无症状）脑组织的梗死可能仍然会发生，并对临床病程产生负面影响，超过半暗带挽救所产生的积极影响。为了验证这一假设，我们分别使用计算机断层灌注和磁共振灌注及弥散加权成像，在两个独立的前瞻性入组队列中识别非核心-非半暗带组织。在所有患者中，大约 1 个月后进行随访结构磁共振成像，以绘制最终梗死图。通过对急性和随访图像集进行体素分析，使用先前验证的灌注阈值，确定急性无症状但最终梗死的组织和最终未梗死的半暗带的体积。早期神经功能变化通过 NIHSS 评分在急性和 1 个月评估之间的变化来表示，相对于急性评分。使用包括未梗死半暗带体积的多变量回归模型，测试急性无症状但最终梗死的组织体积与早期神经功能变化之间的关系。计算机断层灌注和磁共振灌注队列分别纳入 34 例和 58 例患者（发病至影像学时间中位数：136 分钟和 156 分钟；分别有 27 例和 42 例患者接受静脉溶栓治疗）。在两个队列的大多数患者中都发现了急性无症状组织的梗死。尽管其体积（中位数分别为 0.2 和 2ml）远小于挽救的半暗带体积（分别为 59.3 和 93ml），但在约 10%的患者中，梗死体积较大。正如预期的那样，挽救的半暗带对早期神经功能变化有强烈的积极影响。即使在多变量模型中校正了后者的影响，急性无症状组织的梗死在两个队列中仍然独立地对早期神经功能变化产生负面影响（分别为 P=0.018 和 0.031）。这是第一项系统研究，记录了前循环中风后急性无症状组织的梗死，并表明它影响了相当一部分患者，对临床病程有预测性的负面影响。这些发现在前循环中风后，在两个独立的队列中得到了复制，与使用的灌注成像方式无关。预防最初无风险组织的梗死应该具有直接的临床获益。
