Loch Macdonald R
Division of Neurosurgery, St. Michael's Hospital, 30 Bond St., Toronto, ON, M5B 1W8, Canada,
Acta Neurochir Suppl. 2015;120:1-10. doi: 10.1007/978-3-319-04981-6_1.
Angiographic vasospasm as a complication of aneurysmal and other types of subarachnoid hemorrhage (SAH) was identified about 62 years ago. It is now hypothesized that angiographic vasospasm contributes to delayed cerebral ischemia (DCI) by multiple pathways, including reduced blood flow from angiographic vasospasm as well as microcirculatory constriction, microthrombosis, cortical spreading ischemia, and delayed effects of early brain injury. It is likely that other factors, such as systemic complications, effects of the subarachnoid blood, brain collateral and anastomotic blood flow, and the genetic and epigenetic makeup of the patient, contribute to the individual's response to SAH. Treatment of aneurysmal SAH and DCI includes neurocritical care management, early aneurysm repair, prophylactic administration of nimodipine, and rescue therapies (induced hypertension and balloon or pharmacologic angioplasty) if the patient develops DCI. Well-designed clinical trials of tirilazad, clasozentan, antiplatelet drugs, and magnesium have been conducted using more than a 1,000 patients each. Some of these drugs have almost purely vascular effects; other drugs are theoretically neuroprotective as well, but they share in common the ability to reduce angiographic vasospasm and, in many cases, DCI, but have no effect on clinical outcome. Experimental research in SAH continues to identify new targets for therapy. Challenges for the future will be to identify the most promising drugs to advance from preclinical studies and to understand why clinical trials have so frequently failed to show drug benefit on clinical outcome. Similar issues with treatment of ischemic stroke are being addressed by suggestions for improving the quality of experimental studies, collaborative preclinical trials, and multinational, multicenter clinical studies that can rapidly include many patients and be large enough to account for numerous factors that conspire to disrupt clinical trials.
血管造影性血管痉挛作为动脉瘤性和其他类型蛛网膜下腔出血（SAH）的一种并发症，大约在62年前被发现。现在有假说认为，血管造影性血管痉挛通过多种途径导致迟发性脑缺血（DCI），这些途径包括血管造影性血管痉挛导致的血流减少以及微循环收缩、微血栓形成、皮质扩散性缺血和早期脑损伤的延迟效应。其他因素，如全身并发症、蛛网膜下腔血液的影响、脑侧支和吻合支血流以及患者的基因和表观遗传组成，可能也会影响个体对SAH的反应。动脉瘤性SAH和DCI的治疗包括神经重症监护管理、早期动脉瘤修复、预防性使用尼莫地平，以及如果患者发生DCI则进行挽救治疗（诱导性高血压和球囊或药物血管成形术）。针对替拉扎特、克拉佐坦、抗血小板药物和镁进行了精心设计的临床试验，每项试验都纳入了1000多名患者。其中一些药物几乎只有纯粹的血管作用；其他药物理论上也具有神经保护作用，但它们都有减少血管造影性血管痉挛的能力，而且在许多情况下还能减少DCI，但对临床结局没有影响。SAH的实验研究仍在不断寻找新的治疗靶点。未来的挑战将是确定最有前景的药物，使其从临床前研究进入临床，以及理解为什么临床试验常常未能显示药物对临床结局有益处。改善实验研究质量的建议、合作性临床前试验以及跨国、多中心临床研究正在解决缺血性卒中治疗中类似的问题，这些研究能够迅速纳入大量患者，规模大到足以考虑众多可能干扰临床试验的因素。
