高血糖、胰岛素治疗与急性卒中预后的关键半暗带区域：INSULINFARCT试验的进一步见解
Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.
作者信息
Rosso Charlotte, Pires Christine, Corvol Jean-Christophe, Baronnet Flore, Crozier Sophie, Leger Anne, Deltour Sandrine, Valabregue Romain, Amor-Sahli Mélika, Lehéricy Stéphane, Dormont Didier, Samson Yves
机构信息
Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; CONAM, UPMC Paris 6, Inserm, U1127, CNRS, UMR 7225, Paris, France; APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle épinière, Centre de Neuro-Imagerie de Recherche (CENIR), Paris, France.
APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
出版信息
PLoS One. 2015 Mar 20;10(3):e0120230. doi: 10.1371/journal.pone.0120230. eCollection 2015.
BACKGROUND
Recently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.
METHODS
We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.
FINDINGS
Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.
CONCLUSION
These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00472381.
背景
最近，“临床相关半暗带”的概念被定义为通过动脉再通得以挽救的区域，且与卒中预后相关。这一临床相关半暗带位于皮质下结构，尤其是脑室周围白质。我们的目的是证实这一假说，研究入院时高血糖及胰岛素治疗对该区域缺血性损伤严重程度的影响，并探讨梗死体积和临床相关半暗带的缺血性损伤严重程度对3个月预后的各自作用。
方法
我们纳入了胰岛素梗死试验中的99例患者。对第1天获得的表观扩散系数（ADC）图进行基于体素的分析，以定位在以下两类患者中损伤更严重的区域：i）3个月时临床预后较差的患者；ii）未实现动脉再通的患者。我们确定检测区域的交集，其代表临床相关半暗带，并研究高血糖状态和胰岛素治疗方案是否会影响该区域缺血性损伤的严重程度。我们进行逻辑回归分析，以检验该关键区域的梗死体积或早期ADC降低对3个月预后的作用。
研究结果
预后较差的患者（p<0.0001）及未实现动脉再通的患者（p<0.0001），其放射冠的ADC值较低。追踪分析显示，该区域的病变中断了许多重要通路。高血糖患者该区域的ADC值低于血糖正常的患者（平均降低41.6±20.8×10⁻⁶mm²/s），且不受胰岛素治疗方案的影响（p：0.10）。临床相关半暗带的ADC值而非梗死体积是3个月预后的显著预测指标。
结论
这些结果证实深部半球白质是临床相关半暗带的一部分，并表明高血糖会在24小时内加剧该区域不可逆缺血性损伤的出现。然而，早期强化胰岛素治疗未能保护该区域免于梗死。
试验注册
ClinicalTrials.gov NCT00472381
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