中国人群抗NMDA受体脑炎的病例分析及文献回顾

发布时间：2018-01-29 14:23

本文关键词： N-甲基-D-天冬氨酸受体(NMDA受体) 抗N-甲基-D-天冬氨酸受体脑炎(抗NMDA受体脑炎) 自身免疫性脑炎中国人群　出处：《浙江大学》2015年博士论文　论文类型：学位论文

【摘要】：目的：自2007年N-甲基-D-天冬氨酸受体(N-Methyl-D-Aspartate Receptor, NMDAR)抗体发现以来,欧美国家已展开了大规模的临床观察研究。但自从2010年我国第一例病例报道以来,国内尚无大规模的临床研究,中国人群抗NMDA受体脑炎的临床特征尚不清晰。本研究通过总结本院的抗NMDA受体脑炎患者的病例特征,并结合文献回顾中报道的病例,分析中国人群抗NMDA受体脑炎的患者一般情况、临床表现、辅助检查及治疗预后的临床特征及影响因素。方法：本研究纳入自2012年1月至2015年3月,就诊于浙江大学医学院附属第二医院的抗NMDA受体脑炎患者,收集性别、年龄、临床表现、辅助检查结果、治疗方案及预后相关资料。同时,搜索维普、万方、中国知网及pubmed、Cochrane、 Web of Science中报道中国患者的文献,提取相应临床资料。分别统计我院及文献回顾中的患者临床特征,并将二者合并后分析影响各临床特征的因素。结果：抗NMDA受体脑炎好发于青年女性。约49%患者在发病前有前驱症状。大部分人以精神症状起病。几乎所有的患者均有精神症状,约60%的患者有运动障碍和(或)痫样发作。约38%的患者会出现自主神经功能障碍。辅助检查结果缺乏特异性,大多数患者的脑脊液压力、有核细胞、蛋白、糖、氯化物正常或轻度升高。绝大多数(85%)患者脑电图存在异常,以慢波增多为主要表现。约50%患者有磁共振检查异常信号,FLAIR序列可能有更高的阳性率。大多数(79%)患者脑脊液和血液中抗体滴度基本相同,约20%的患者血液中抗体滴度偏低,脑脊液检查有异常表现者血液中抗体滴度偏低风险较高(p=0.021)。约20%的患者合并肿瘤,女性发生率高于男性(p=0.04)。女性好发畸胎瘤,而男性则为肺癌。研究中涉及的治疗方案有四种,即单纯丙种球蛋白、单纯激素、丙种球蛋白联合激素和手术联合免疫抑制治疗。其中,单纯使用丙种球蛋白的治疗效果弱于其他三种(p0.001),而是否发生中枢性低通气则是影响预后的重要因素(p=0.01)。结论：本研究通过回顾我院病例和中国人群的病例报告,总结了抗NMDA受体脑炎的临床特征及可能影响临床表现的因素,为临床实践提供了循证医学支持。
[Abstract]:Objective: Since the discovery of N-Methyl-D-Aspartate Receptor- (NMDAR) antibody against N-methyl-Daspartic acid receptor (NMDAR) in 2007. Large scale clinical observation studies have been carried out in Europe and America. However, since 2010, there has been no large-scale clinical study in China since the first case was reported in China. The clinical characteristics of anti NMDA receptor encephalitis in Chinese population are not clear. This study summarized the case characteristics of anti NMDA receptor encephalitis in our hospital and combined with the cases reported in literature review. To analyze the general situation, clinical manifestation, adjuvant examination and prognosis of patients with NMDA receptor encephalitis in Chinese population. Methods: From January 2012 to March 2015, this study included patients with anti NMDA receptor encephalitis who were admitted to the second affiliated Hospital of Zhejiang University School of Medicine to collect gender, age and clinical manifestations. Results of adjuvant examination, treatment plan and prognosis. Meanwhile, search for Weip, Wanfang, ChinaNet and pubmedan Cochrane. The Web of Science reports the Chinese patients' literature, extracts the corresponding clinical data, and counts the clinical characteristics of the patients in our hospital and literature review. The factors influencing the clinical characteristics were analyzed after combining the two methods. Results: Anti NMDA receptor encephalitis occurs in young women. About 49% patients have precursor symptoms before onset. Most of them start with mental symptoms. Almost all patients have mental symptoms. About 60% of the patients had dyskinesia and / or epileptiform seizures. About 38% of the patients had autonomic nervous dysfunction. The results of the adjuvant tests were unspecific and most patients had cerebrospinal fluid pressure and nucleated cells. Protein, sugar and chloride were normal or slightly elevated. Most of the patients had abnormal EEG, with the increase of slow wave as the main manifestation. About 50% patients had abnormal signal of magnetic resonance examination. FLAIR sequence may have higher positive rate. Most of the patients have the same titer of antibodies in cerebrospinal fluid and blood, and about 20% patients have lower titer of antibodies in blood. Patients with abnormal cerebrospinal fluid examination had a higher risk of low titer of antibodies in their blood. About 20% of the patients were complicated with tumor. The incidence of teratoma in women is higher than that in men. The incidence of teratoma in women is higher than that in men. Gamma globulin combined with hormone and surgery combined with immunosuppressive therapy. The effect of using gamma globulin alone was weaker than that of the other three groups (P 0.001). The occurrence of central hypopnea is an important factor affecting prognosis. Conclusion: In this study, the clinical characteristics of anti NMDA receptor encephalitis and the factors that may affect its clinical manifestation were summarized by reviewing the case reports of our hospital and Chinese population, which provided evidence based medicine support for clinical practice.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R747.9

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