Guadagno J V, Jones P S, Aigbirhio F I, Wang D, Fryer T D, Day D J, Antoun N, Nimmo-Smith I, Warburton E A, Baron J C
Department of Clinical Neurosciences, Neurology Unit, Addenbrooke's Hospital, Cambridge, UK.
Brain. 2008 Oct;131(Pt 10):2666-78. doi: 10.1093/brain/awn175. Epub 2008 Aug 4.
Selective neuronal loss (SNL) in the rescued penumbra could account for suboptimal clinical recovery despite effective early reperfusion. Previous studies of SNL used single-photon emission tomography (SPECT), did not account for potential volume loss secondary to collapse of the infarct cavity, and failed to show a relationship with initial hypoperfusion. Here, we obtained acute-stage computerized tomography (CT) perfusion and follow-up quantitative (11)C-flumazenil (FMZ)-PET to map SNL in the non-infarcted tissue and assess its relationship with acute-stage hypoperfusion. We prospectively recruited seven patients with evidence of (i) acute (<6 h) extensive middle cerebral artery territory ischaemia based on clinical deficit (National Institutes of Health stroke scale, NIHSS score range: 8-23) and CT Perfusion (CTp) findings and (ii) early recanalization (spontaneous or following thrombolysis) based on spectacular clinical recovery (DeltaNIHSS > or =6 at 24 h), good clinical outcome (NIHSS < or =5) and small final infarct (6/7 subcortical) on late-stage MRI. Ten age-matched controls were also studied. FMZ image analysis took into account potential post-stroke volume loss. Across patients, clusters of significantly reduced FMZ binding were more prevalent and extensive in the non-infarcted middle cerebral artery cortical areas than in the non-affected hemisphere (P = 0.028, Wilcoxon sign rank test). Voxel-based between-group comparisons revealed several large clusters of significantly reduced FMZ binding in the affected peri-insular, superior temporal and prefrontal cortices (FDR P < 0.05), as compared with no cluster on the unaffected side. Finally, comparing CTp and PET data revealed a significant negative correlation between FMZ binding and initial hypoperfusion. Applying correction for volume loss did not substantially alter the significance of these results. Although based on a small patient sample sometimes studied late after the index stroke, and as such preliminary, our results establish the presence and distribution of FMZ binding loss in ultimately non-infarcted brain areas after stroke. In addition, the data suggest that this binding loss is proportional to initial hypoperfusion, in keeping with the hypothesis that the rescued penumbra is affected by SNL. Although its clinical counterparts remain uncertain, it is tempting to speculate that peri-infarct SNL could represent a new therapeutic target.
尽管早期再灌注有效，但获救半暗带中的选择性神经元丢失（SNL）可能是导致临床恢复欠佳的原因。以往关于SNL的研究采用单光子发射断层扫描（SPECT），未考虑梗死腔塌陷继发的潜在体积丢失，也未能显示出与初始低灌注的关系。在此，我们获取了急性期计算机断层扫描（CT）灌注图像以及随访定量（11）C-氟马西尼（FMZ）-正电子发射断层扫描（PET）图像，以描绘非梗死组织中的SNL情况，并评估其与急性期低灌注的关系。我们前瞻性招募了7例患者，这些患者有以下证据：（i）基于临床缺损（美国国立卫生研究院卒中量表，NIHSS评分范围：8 - 23）和CT灌注（CTp）结果，存在急性（<6小时）大脑中动脉广泛区域缺血；（ii）基于显著的临床恢复（24小时时DeltaNIHSS≥6）、良好的临床结局（NIHSS≤5）以及晚期磁共振成像（MRI）显示的最终梗死灶较小（7例中有6例为皮质下梗死），存在早期再通（自发或溶栓后）。还研究了10例年龄匹配的对照者。FMZ图像分析考虑了卒中后的潜在体积丢失。在患者中，FMZ结合显著降低的簇在非梗死的大脑中动脉皮质区域比在未受影响的半球更普遍且范围更广（P = 0.028，Wilcoxon符号秩检验）。基于体素的组间比较显示，与未受影响侧无簇相比，在受影响的岛周、颞上和前额叶皮质中有几个大的FMZ结合显著降低的簇（FDR P < 0.05）。最后，比较CTp和PET数据发现FMZ结合与初始低灌注之间存在显著负相关。应用体积丢失校正并未实质性改变这些结果的显著性。尽管基于有时在索引卒中后较晚进行研究的小样本患者，因此具有初步性，但我们的结果证实了卒中后最终非梗死脑区中FMZ结合丢失的存在及其分布。此外，数据表明这种结合丢失与初始低灌注成正比，这与获救半暗带受SNL影响的假设一致。尽管其临床对应情况仍不确定，但推测梗死周围SNL可能代表一个新的治疗靶点很诱人。
