Nighoghossian Norbert, Berthezène Yves, Mechtouff Laura, Derex Laurent, Cho Tae Hee, Ritzenthaler Thomas, Rheims Sylvain, Chauveau Fabien, Béjot Yannick, Jacquin Agnès, Giroud Maurice, Ricolfi Frédéric, Philippeau Frédéric, Lamy Catherine, Turc Guillaume, Bodiguel Eric, Domigo Valérie, Guiraud Vincent, Mas Jean-Louis, Oppenheim Catherine, Amarenco Pierre, Cakmak Serkan, Sevin-Allouet Mathieu, Guillon Benoit, Desal Hubert, Hosseini Hassan, Sibon Igor, Mahagne Marie-Hélène, Ong Elodie, Mewton Nathan, Ovize Michel
From the Departments of Neurology (N.N., L.M., L.D., T.H.C., T.R., S.R., E.O.) and Neuroradiology (Y. Berthezène, F.C.), Hôpital Neurologique Pierre Wertheimer, Creatis CNRS UMR 5220, INSERM U1044, Université Lyon 1, INSA Lyon; Dijon Stroke Registry (Y. Béjot, A.J., M.G., F.R.) (EA 4184, Inserm, Invs), University Hospital of Dijon, Regional Council and University of Burgondy, CHU le Bocage, Dijon; Department of Neurology (F.P.), Centre Hospitalier de Fleyriat, Bourg en Bresse; Departments of Neurology (C.L., G.T., E.B., V.D., V.G., J.-L.M.) and Neuroradiology (C.O.), CH Sainte-Anne, University Paris-Descartes, INSERM U894, DHU NeuroVasc Sorbonne Paris Cité; Department of Neurology (P.A.), Hôpital Bichat-Claude Bernard, Paris; Department of Neurology (S.C.), Hôpital Nord-Ouest, Plateau d'Ouilly, Villefranche sur Saône; Department of Neurology (M.S.-A., B.G., H.D.), Hôpital Nord-Laënnec, Saint-Herblain; Department of Neurology (H.H.), Hôpital Henri Mondor, Créteil; Department of Neurology (I.S.), Groupe Hospitalier Pellegrin, Place Amélie Raba-Léon, Bordeaux; Unité Neurosciences (M.-H.M.), Hôpital Saint Roch, Nice; Hôpital Louis Pradel (N.M., M.O.), Service d'Explorations Fonctionelles Cardiovasculaires, Centre d'Investigation Clinique & UMR1060 (CarMeN), Université Claude Bernard Lyon 1, France.
Neurology. 2015 Jun 2;84(22):2216-23. doi: 10.1212/WNL.0000000000001639. Epub 2015 May 6.
We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size.
Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis.
From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009).
Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization.
This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.
我们研究了静脉注射环孢素联合溶栓治疗是否能减小脑梗死体积。
年龄在18至85岁、出现前循环卒中且符合溶栓治疗条件的患者被纳入这项多中心、单盲、对照试验。随机分组15分钟后，患者接受静脉推注2.0mg/kg环孢素（山德士，诺华公司）或安慰剂。主要终点是30天时MRI上的梗死体积。次要终点包括根据动脉闭塞部位（近端/远端）划分的梗死体积以及溶栓后的再通情况。
2009年10月至2013年7月，共纳入127例患者。127例患者中的110例评估了主要终点。与对照组相比，环孢素组梗死体积的减小总体上不显著（分别为21.8mL[四分位间距，IQR 5.1，69.2mL]和28.8mL[IQR 7.7，95.0mL]；p = 0.18）。然而，在近端闭塞且再通有效的患者中，与对照组相比，环孢素组的梗死体积显著减小（分别为14.9mL[IQR 1.3，23.2mL]和48.3mL[IQR 34.5，118.2mL]；p = 0.009）。
环孢素一般对减小梗死体积无效。然而，在大脑中动脉近端闭塞且再通有效的患者中观察到梗死体积较小。
本研究提供了I级证据，即在急性前循环卒中患者中，与单纯溶栓相比，溶栓加静脉注射环孢素不会显著降低30天MRI梗死体积。
