Steiner T, Jüttler E, Ringleb P
Neurologische Klinik, Universitätsklinikum, Heidelberg.
Nervenarzt. 2007 Oct;78(10):1147-54. doi: 10.1007/s00115-007-2352-7.
This article covers three major topics of acute stroke therapy: extension of the time window for thrombolysis with desmoteplase, decompressive surgery after malignant middle cerebral artery infarction, and the effect of hemostatic therapy with recombinant activated factor VII (rFVIIa) in patients with spontaneous primary intracerebral hemorrhage. Thrombolytic therapy with recombinant tissue or tissue-type plasminogen activator is still the only approved acute stroke therapy within a 3-h time window. Imaging-based patient selection seems to help extending this time window. After promising results of two phase II trials with the thrombolytic agent desmoteplase in an extended time window after acute ischemic stroke, the DIAS-II study was reconducted in Europe, North America, and Australia as a phase III trial. First results of the included 186 patients are shown. Surprisingly, patients treated with desmoteplase had no better outcome than placebo-treated patients, and there was increased mortality in the high-dose group. Among all stroke subtypes, space-occupying malignant middle cerebral artery is one with the poorest prognosis. Most patients die within a few days due to the development of massive brain edema, despite maximum intensive care. Decompressive hemicraniectomy represents a much more effective therapy for the treatment of local brain swelling. However, until recently this method was highly controversial. Here we present the results of the randomized trials published in 2007 and discuss their relevance for acute therapy. Hematoma growth occurs within 4 h in one third of patients who suffer from intracerebral hemorrhage. Prospective, placebo-controlled, multicenter trials have shown that intravenous application of rFVIIa reduces volume increase. We present preliminary results of the latest phase III trial (FAST: recombinant factor VIIa in acute hemorrhagic stroke), which tried to find whether the hemostatic effect will translate into clinical effect.
使用去氨普酶延长溶栓时间窗、恶性大脑中动脉梗死术后减压手术,以及重组活化因子 VII(rFVIIa)止血治疗对自发性原发性脑出血患者的疗效。重组组织型纤溶酶原激活剂溶栓治疗仍是 3 小时时间窗内唯一获批的急性中风治疗方法。基于影像学的患者选择似乎有助于延长这一时间窗。在急性缺血性中风后延长时间窗内使用溶栓剂去氨普酶的两项 II 期试验取得有前景的结果后,DIAS-II 研究在欧洲、北美和澳大利亚重新开展为一项 III 期试验。展示了纳入的 186 例患者的初步结果。令人惊讶的是,接受去氨普酶治疗的患者预后并不比接受安慰剂治疗的患者更好,且高剂量组死亡率增加。在所有中风亚型中,占位性恶性大脑中动脉梗死是预后最差的一种。尽管进行了最大程度的重症监护,大多数患者仍会因大量脑水肿的发展在数天内死亡。减压性颅骨切除术是治疗局部脑肿胀更有效的方法。然而,直到最近这种方法仍存在很大争议。在此我们展示 2007 年发表的随机试验结果并讨论它们与急性治疗的相关性。三分之一的脑出血患者在 4 小时内会出现血肿扩大。前瞻性、安慰剂对照、多中心试验表明,静脉应用 rFVIIa 可减少血肿体积增加。我们展示了最新 III 期试验(FAST:急性出血性中风中的重组因子 VIIa)的初步结果,该试验试图探寻止血效果是否会转化为临床效果。