Zhu Zilong, Fu Ying, Tian Decai, Sun Na, Han Wei, Chang Guoqiang, Dong Yinhua, Xu Xiaolin, Liu Qiang, Huang Deren, Shi Fu-Dong
Departments of Neurology, Immunology, Radiology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Department of Neurology, Tianjin HuanHu Hospital, Tianjin, China.
Circulation. 2015 Sep 22;132(12):1104-1112. doi: 10.1161/CIRCULATIONAHA.115.016371. Epub 2015 Jul 22.
Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset.
In this multicenter trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone and 22 patients to receive alteplase plus oral fingolimod 0.5 mg daily for 3 consecutive days within 4.5 hours of the onset of ischemic stroke. Compared with patients who received alteplase alone, patients who received the combination of fingolimod with alteplase exhibited lower circulating lymphocytes, smaller lesion volumes (10.1 versus 34.3 mL; P=0.04), less hemorrhage (1.2 versus 4.4 mL; P=0.01), and attenuated neurological deficits in National Institute of Health Stroke Scales (4 versus 2; P=0.02) at day 1. Furthermore, restrained lesion growth from day 1 to 7 (-2.3 versus 12.1 mL; P<0.01) with a better recovery at day 90 (modified Rankin Scale score 0-1, 73% versus 32%; P<0.01) was evident in patients given fingolimod and alteplase. No serious adverse events were recorded in all patients.
In this pilot study, combination therapy of fingolimod and alteplase was well tolerated, attenuated reperfusion injury, and improved clinical outcomes in patients with acute ischemic stroke. These findings need to be tested in further clinical trials.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02002390.
脑缺血引发的炎症和免疫反应会使中风的临床结局恶化，并导致与静脉注射阿替普酶相关的出血转化、大量水肿和再灌注损伤。我们评估了免疫调节剂芬戈莫德与阿替普酶联合使用在减轻症状发作后4.5小时内接受治疗的急性缺血性中风患者再灌注损伤方面是否安全有效。
在这项多中心试验中，我们将25例符合条件的因大脑前动脉或大脑中动脉闭塞导致的半球缺血性中风患者随机分配为单独接受阿替普酶治疗，将22例患者在缺血性中风发作后4.5小时内随机分配为接受阿替普酶加口服芬戈莫德0.5毫克，连续3天。与单独接受阿替普酶治疗的患者相比，接受芬戈莫德与阿替普酶联合治疗的患者循环淋巴细胞水平较低，病变体积较小（10.1对34.3毫升；P=0.04），出血较少（1.2对4.4毫升；P=0.01），并且在第1天时美国国立卫生研究院卒中量表中的神经功能缺损减轻（4对2；P=0.02）。此外，在接受芬戈莫德和阿替普酶治疗的患者中，从第1天到第7天病变生长受到抑制（-2.3对12.1毫升；P<0.01），在第90天时恢复更好（改良Rankin量表评分0-1，73%对32%；P<0.01）。所有患者均未记录到严重不良事件。
在这项初步研究中，芬戈莫德与阿替普酶联合治疗耐受性良好，减轻了再灌注损伤，并改善了急性缺血性中风患者 的临床结局。这些发现需要在进一步的临床试验中进行验证。
