双重滤过血浆置换治疗重症抗N-甲基-D-天冬氨酸受体脑炎9例疗效分析

Efficacy of double filtration plasmapheresis on nine patients with severe anti-N-methyl-D-aspartate receptor encephalitis

目的探讨双重滤过血浆置换(DFPP)对重症抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的治疗效果及临床意义。方法回顾性分析2014年1月至2018年3月海军军医大学(第二军医大学)长海医院确诊的、经甲泼尼龙冲击治疗无效的9例重症抗NMDAR脑炎患者的病例资料。收集患者在DFPP治疗前后的临床表现及实验室、脑电图、影像学检查资料,并分析DFPP的治疗效果。结果9例抗NMDAR脑炎患者(男4例、女5例)均入住神经内科重症监护病房治疗,年龄为15~69岁,中位发病年龄为37岁,平均住院时间为(33.2±7.6)d。主要临床症状有精神行为异常(9例)、自主神经功能障碍(9例)、癫发作(7例)、中枢性低通气(5例)、意识障碍(5例)。1例合并卵巢畸胎瘤。9例患者脑脊液抗NMDAR均呈阳性,7例血清抗NMDAR阳性。9例患者均行脑电图检查,7例显示异常,以弥漫性改变、异常慢波为主要表现。头颅磁共振成像检查示:4例患者额叶、顶叶、颞叶、海马等脑区可见异常信号,余5例未见异常。9例患者经甲泼尼龙冲击治疗均无效,行DFPP治疗后5例完全恢复,4例临床症状显著改善、遗留部分症状。结论对于糖皮质激素治疗无反应的重症抗NMDAR脑炎患者,DFPP作为一种可选择的替代血浆置换的治疗手段可取得较好的临床疗效,且不受异体血浆资源的限制。

Objective To investigate the therapeutic effect of double filtration plasmapheresis(DFPP)on severe anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis and its clinical significance.Methods We retrospectively analyzed the clinical data from 9 patients with severe anti-NMDAR encephalitis confirmed by Changhai Hospital of Naval Medical University(Second Military Medical University)from Jan.2014 to Mar.2018.The 9 patients did not respond to methylprednisolone shock therapy.We collected the clinical manifestations,and examination results of laboratory,electroencephalogram and imaging,and analyzed the therapeutic effect of DFPP.Results Nine anti-NMDAR encephalitis patients,including 5 females and 4 males,were admitted to neurology intensive care unit.Their ages were ranged from 15 to 69 years old,median age of onset was 37 years old,and average hospital stay was(33.2±7.6)d.The main clinical symptoms were mental behavioral abnormalities(9 cases),autonomic dysfunction(9 cases),seizures(7 cases),central hypopnea(5 cases),and consciousness disorders(5 cases).One patient was complicated with ovarian teratoma.Nine patients were positive for anti-NMDAR antibodies in cerebrospinal fluid,and 7 patients were positive for anti-NMDAR antibodies in serum.All the 9 patients were examined by electroencephalogram,and 7 of them had abnormal findings,mainly with diffuse changes and abnormal slow waves.Brain magnetic resonance imaging showed that abnormal signals could be seen in the frontal lobe,parietal lobe,temporal lobe,hippocampus and other brain regions of 4 patients,and no abnormal signals were found in the other 5 patients.Nine patients were treated with DFPP after ineffective treatment with methylprednisolone,5 of them recovered completely,and the other 4 cases had significantly improved residual symptoms.Conclusion DFPP can be used as an alternative for patients with severe anti-NMDAR encephalitis who are not sensitive to glucocorticoid therapy.It has better clinical efficacy and it is not restricted by allogeneic plasma resources.