Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study.
Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study.
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DOI：
10.1016/s1474-4422(12)70310-1
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发表时间：
2013-02
期刊：
影响因子：
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通讯作者：
Dalmau J
中科院分区：
文献类型：
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作者：
Titulaer MJ;McCracken L;Gabilondo I;Armangué T;Glaser C;Iizuka T;Honig LS;Benseler SM;Kawachi I;Martinez-Hernandez E;Aguilar E;Gresa-Arribas N;Ryan-Florance N;Torrents A;Saiz A;Rosenfeld MR;Balice-Gordon R;Graus F;Dalmau J
抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是一种自身免疫性疾病，其免疫治疗的使用和长期结果尚未确定。在这项多机构观察性研究(2007-2012)中，所有GluN1抗体患者在症状出现时以及4、8、12、18和24个月时使用改进的Rankin量表(MRS)进行评估。治疗包括一线免疫治疗(类固醇、静脉注射免疫球蛋白、血浆置换)、二线免疫治疗(利妥昔单抗、环磷酰胺)和肿瘤切除。宾夕法尼亚大学和巴塞罗那大学使用具有二元分布的广义线性混合模型确定了结果的预测因素。577例患者(1~85岁，中位数21岁)，其中212例为儿童(18岁)。治疗效果和结果在501个月(平均随访24个月)中可评估：472例(94%)接受了一线免疫治疗或肿瘤切除，251例(53%)在四周内有所改善。在221例一线治疗失败的患者中，125例(57%)接受了二线免疫治疗，其预后优于未接受一线治疗的患者(OR 2·69，CI 1·24-5·80，P=0.012)。在前24个月，394/501达到良好结果(MRS 0-2；中位数6个月)，30例死亡。术后24个月随访，204/252例(81%)效果良好。在症状出现后长达18个月的时间里，结果继续改善。早期治疗(OR 0.62，CI 0.50~0.76，P<；0.0001)和未入院ICU(OR 0.12，CI 0.06~0.22，P<；0.0001)是预后良好的预测因素。45例患者有一次或多次复发(两年内的风险为12%)；46/69(67%)的复发比以前的发作要轻(p<；0.0001)。在177名儿童中，二线免疫治疗的良好结果和疗效大小的预测因子与整个队列的预测因子相当。抗NMDAR脑炎患者对免疫治疗有反应。当一线治疗失败时，二线免疫治疗通常有效。恢复可能需要18个月以上的时间。
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. In this multi-institutional observational study (2007-2012), all patients with GluN1 antibodies were assessed at symptom onset and 4, 8, 12, 18, and 24 months using the modified Rankin Scale (mRS). Treatment included first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumor removal. Predictors of outcome were determined at the Universities of Pennsylvania and Barcelona using generalized linear mixed models with binary distribution. 577 patients (1-85 years, median 21) were studied, 212 were children (<18 years). Treatment effects and outcome were assessable in 501 (median follow-up 24 months): 472 (94%) underwent first-line immunotherapy or tumor removal, resulting in improvement within four weeks in 251 (53%). Of 221 patients who failed first-line therapy, 125 (57%) received second-line immunotherapy resulting in better outcome than those who did not (OR 2·69, CI 1·24-5·80, p=0·012). During the first 24 months, 394/501 reached good outcome (mRS 0-2; median 6 months), and 30 died. At 24 month follow-up 204/252 (81%) had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment (OR 0·62, CI 0·50-0·76, p<0·0001) and lack of ICU admission (OR 0.12, CI 0·06-0·22,p<0·0001). 45 patients had one or multiple relapses (representing a 12% risk within 2 years); 46/69 (67%) relapses were milder than previous episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were comparable to those of the entire cohort. Patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line therapies fail. Recovery can take more than 18 months.