Dreier Jens P, Woitzik Johannes, Fabricius Martin, Bhatia Robin, Major Sebastian, Drenckhahn Chistoph, Lehmann Thomas-Nicolas, Sarrafzadeh Asita, Willumsen Lisette, Hartings Jed A, Sakowitz Oliver W, Seemann Jörg H, Thieme Anja, Lauritzen Martin, Strong Anthony J
Department of Experimental Neurology and Neurology, Charité University Medicine, Berlin, Germany.
Brain. 2006 Dec;129(Pt 12):3224-37. doi: 10.1093/brain/awl297. Epub 2006 Oct 25.
Progressive ischaemic damage in animals is associated with spreading mass depolarizations of neurons and astrocytes, detected as spreading negative slow voltage variations. Speculation on whether spreading depolarizations occur in human ischaemic stroke has continued for the past 60 years. Therefore, we performed a prospective multicentre study assessing incidence and timing of spreading depolarizations and delayed ischaemic neurological deficit (DIND) in patients with major subarachnoid haemorrhage (SAH) requiring aneurysm surgery. Spreading depolarizations were recorded by electrocorticography with a subdural electrode strip placed on cerebral cortex for up to 10 days. A total of 2110 h recording time was analysed. The clinical state was monitored every 6 h. Delayed infarcts after SAH were verified by serial CT scans and/or MRI. Electrocorticography revealed 298 spreading depolarizations in 13 of the 18 patients (72%). A clinical DIND was observed in seven patients 7.8 days (7.3, 8.2) after SAH. DIND was time-locked to a sequence of recurrent spreading depolarizations in every single case (positive and negative predictive values: 86 and 100%, respectively). In four patients delayed infarcts developed in the recording area. As in the ischaemic penumbra of animals, delayed infarction was preceded by progressive prolongation of the electrocorticographic depression periods associated with spreading depolarizations to >60 min in each case. This study demonstrates that spreading depolarizations have a high incidence in major SAH and occur in ischaemic stroke. Repeated spreading depolarizations with prolonged depression periods are an early indicator of delayed ischaemic brain damage after SAH. In view of experimental evidence and the present clinical results, we suggest that spreading depolarizations with prolonged depressions are a promising target for treatment development in SAH and ischaemic stroke.
动物体内进行性缺血性损伤与神经元和星形胶质细胞的扩展性去极化有关，可检测为扩展性负向慢电压变化。在过去60年里，关于扩展性去极化是否发生在人类缺血性卒中一直存在猜测。因此，我们进行了一项前瞻性多中心研究，评估需要进行动脉瘤手术的重大蛛网膜下腔出血（SAH）患者中扩展性去极化的发生率和时间，以及延迟性缺血性神经功能缺损（DIND）。通过将硬膜下电极条放置在大脑皮层上进行皮质脑电图记录扩展性去极化，记录时间长达10天。共分析了2110小时的记录时间。每6小时监测一次临床状态。SAH后的延迟性梗死通过系列CT扫描和/或MRI进行验证。皮质脑电图显示18例患者中有13例（72%）出现298次扩展性去极化。7例患者在SAH后7.8天（7.3，8.2）出现临床DIND。在每一个病例中，DIND都与一系列反复出现的扩展性去极化时间相关（阳性和阴性预测值分别为86%和100%）。4例患者在记录区域出现延迟性梗死。与动物缺血半暗带一样，在每一个病例中，延迟性梗死之前都有与扩展性去极化相关的皮质脑电图抑制期逐渐延长至>60分钟。这项研究表明，扩展性去极化在重大SAH中发生率很高，且发生在缺血性卒中中。反复出现的扩展性去极化且抑制期延长是SAH后延迟性缺血性脑损伤的早期指标。鉴于实验证据和目前的临床结果，我们认为抑制期延长的扩展性去极化是SAH和缺血性卒中治疗开发的一个有前景的靶点。
