抗N-甲基-D-天冬氨酸受体脑炎

抗N-甲基-D-天冬氨酸(NMDA)受体脑炎是近几年发现的边缘叶脑炎,为抗NMDA受体抗体介导的一种自身免疫性疾病,常合并肿瘤表现为副肿瘤综合征。该病患者可出现边缘叶损害症状,颅脑MRI可见边缘叶异常信号,脑脊液及血清能检测到NMDA受体抗体。该疾病较其它副肿瘤综合征发病率高、易误诊且病情重,但及时治疗预后良好。本文就抗NMDA受体脑炎发病机制、临床特点、辅助检查、诊断治疗等研究现状进行综述,进而提高对该疾病的认识,指导临床治疗。     

抗N-甲基-D-天冬氨酸受体脑炎患者临床特点分析

目的 探讨抗N-甲基-D-天冬氨酸受体(N-methyl- D-aspartate receptor,NMDAR)脑炎的临床特征与抗NMDAR抗体在诊断该病中的意义.方法 选择62例各种病因的脑炎、脑病及其他中枢神经系统疾病患者,采用转染细胞间接免疫荧光法检测其血清及脑脊液抗NMDAR抗体,同时对该病的临床表现、实验室检查、治疗及预后进行分析.结果 28％(9/32)的临床诊断脑炎病例组患者血清或脑脊液抗NMDAR抗体为阳性.脑脊液抗体的阳性率高于血清,其中5例抗体滴度较高的患者伴有血脑屏障破坏.这些患者均未发现肿瘤,临床上以发热、精神异常、癫痫、肌张力障碍与自主神经功能障碍表现突出,并有头颅MRI与脑电图异常,早期免疫治疗有效.结论 脑脊液及血清中抗NMDAR抗体检测有助于自身免疫性抗NMDAR脑炎患者的早期诊断与治疗.     

抗N-甲基-D-天冬氨酸受体脑炎20例临床分析

目的分析抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者临床表现、头颅MRI、脑电图(EEG)、脑脊液(CSF)特点。方法收集20例抗NMDAR脑炎患者的临床、MRI、EEG和CSF资料。结果 20例抗NMDAR脑炎患者男性13例,女性7例。年龄3~61岁,平均年龄25±19岁。入院时头颅MRI异常率为60%(12/20),其中4例累及边缘系统,5例累及额顶颞枕叶、放射冠及半卵圆中心等结构。例4入院时头颅MRI检查未见异常,第24天复查见双顶枕叶、右侧胼胝体及扣带回区异常信号。16例患者行EEG检查,14例(88%)异常,异常的EEG主要为非特异性慢波,其中1例(例4)患者住院期间复查EEG出现大量δ波。90%(18/20)患者CSF结果异常;细胞学检查以淋巴细胞反应为主,例9有激活性单核细胞增多。11例(55%)患者血清和CSF NMDAR抗体阳性,7例(35%)患者仅CSF NMDAR抗体阳性,2例(例11、例14)患者仅血清NMDAR抗体阳性。结论本组以男性青少年多见。其主要临床表现为精神异常、癫痫、记忆力下降、行为异常、不自主运动等,严重者可出现中枢性低通气。头颅MRI病变不仅局限于边缘系统。重症患者EEG可出现δ波。早期诊断、治疗预后较好,部分患者可复发。     

抗N-甲基-D-天冬氨酸受体脑炎的抗体检测及临床意义

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的抗体检测意义及临床特征。方法选取本院收治的脑炎病人35例及对照组30例,分析临床资料,采用转染细胞间接免疫荧光法检测两组患者其血清及脑脊液抗NMDAR机体结果抗NMDAR抗体检测仅1例边缘叶脑炎患者结果阳性,该患者腑脊液细胞数增多、蛋白轻度升高、脑电图见双侧慢波、其余检查无异常。精神症状及意识水平障碍明显,免疫治疗有效。结论抗NMDAR脑炎发病率低,临床表现复杂多样,怀疑该病时需行抗NMDAR抗体检测。     

抗N-甲基-D-天冬氨酸受体脑炎患者脑脊液细胞学特点分析

目的 探讨抗N-甲基-D-天冬氨酸受体(anti-N-methyl-D-aspartate receptor,NMDAR)脑炎的脑脊液细胞学特点.方法 收集2015-01-01—2018-12-31河南省人民医院及北京协和医院收治的抗NMDAR脑炎患者的脑脊液细胞学、常规、生化、抗NMDAR抗体滴度、寡克隆区带等结果,...     

抗N-甲基-D-天冬氨酸受体脑炎的免疫学研究进展

抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是一种由抗体介导的中枢神经系统自身免疫性炎症,因抗体具有可检测性,为进一步认识中枢神经系统自身免疫性疾病提供了新机遇.该病突出的特点是严重的多阶段复杂的精神神经病学综合征,但部分可逆.若早期诊断与治疗,多数预后良好.现主要对抗NMDAR脑炎的免疫学相关进展进行综述,以期有利于对此病发病机制的深入理解和探讨.     

抗N-甲基-D-天冬氨酸受体脑炎患者细胞因子检测及其临床意义

目的 观察抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者脑脊液及血液细胞因子水平变化,并探讨其临床意义及与发病机制的联系.方法 收集北京协和医院2015年11月至2017年5月收治的抗NMDAR脑炎患者50例,同时收集中枢神经系统炎性脱髓鞘病与非炎性疾病患者的脑脊液与血清作为对照组.采用ELISA方法检测患者脑脊液...     

抗N-甲基-D-天冬氨酸受体脑炎研究现状

<正>2007年,美国宾夕法尼亚大学教授Dalmau等[1]提出了"抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎"的概念,系由机体针对NMDAR产生特异性IgG抗体导致的一种边缘性脑炎(LE)。此后,对该类型脑炎的研究如雨后春笋般成为临床最常见、最受重视的自身免疫性脑炎。抗NMDAR脑炎最早发现于合并卵巢畸胎瘤的女性患者,近年研究显示,抗NMDAR脑炎可见于任何年龄阶段的男性和女性患者,但儿童和男性患者较少合并肿瘤[2]。通常表现为一系列临床症状,包括前期的感染症状(如头痛、发热等),以及随后出     

视神经脊髓炎合并抗N-甲基-D-天冬氨酸受体脑炎1例

目的 探讨视神经脊髓炎合并抗N-甲基-D-天冬氨酸(NMDA)受体脑炎的临床特征。方法 报道本院收治的1例视神经脊髓炎合并抗N-甲基-D-天冬氨酸受体脑炎的临床特点及诊治经过,并结合文献分析该病的特征。结果 患者为21岁女性,表现为腹泻后急性起病的下肢麻木无力、昏睡、视物模糊; MRI示双侧基底节、海马、桥臂、齿状回、延髓背侧多发异常信号,同时伴有颈髓多发条片状长T₂异常信号。脑脊液NMDA受体抗体阳性,血清和脑脊液水通道蛋白4(AQP4)抗体阳性,合并心动过缓并发症,筛查未发现肿瘤; 经激素冲击、丙种球蛋白及免疫抑制剂治疗后症状逐渐好转至痊愈。结论 视神经脊髓炎合并抗N-甲基-D-天冬氨酸受体脑炎可以在感染后起病,症状和影像学主要表现为两种疾病的叠加,可出现心动过缓并发症,早期积极行免疫治疗效果较好。     

抗N-甲基-D-天冬氨酸受体脑炎一例

目的 探讨抗N-甲基-M-天冬氨酸(NMDA)受体脑炎的临床特点、诊断及治疗.方法报道1例伴卵巢畸胎瘤的抗NMDA受体脑炎患者的临床表现及诊治过程,并总结其临床特征.结果患者为青年女性,表现为精神行为异常及抽搐,意识障碍及通气不足.早期发现畸胎瘤,脑脊液中抗NMDA受体抗体阳性.行畸胎瘤手术切除,联合静脉用免疫球蛋白和激素冲击治疗,患者临床痊愈.结论 抗NMDA受体脑炎是一种自身免疫性的、能用血清学方法诊断的疾病.早期明确诊断和给予及时治疗,预后良好.     

脑脊液细胞学检查和病毒抗体检测对病毒性脑膜脑炎的诊断价值

目的:探讨脑脊液细胞学检测和病毒抗体检测对病毒性脑膜脑炎的诊断价值。方法:选择84例颅内感染患者分为:病毒性脑膜脑炎组32例,结核性脑膜脑炎组32例,化脓性脑膜脑炎组20例。结核性脑膜脑炎组和化脓性脑膜脑炎组作为对照。每例患者各取2次脑脊液,共168份脑脊液。分别行细胞学检测和ELISA法检测病毒系列抗体IgG、IgM。结果:病毒性脑膜脑炎的脑脊液细胞学超早期有明显的嗜中性粒细胞反应,随后出现激活的淋巴细胞反应;随着患者病情好转,激活的淋巴细胞逐渐减少;转而以淋巴细胞、单核细胞为主。病毒抗体IgG检测:病毒性脑膜脑炎组阳性率为86.7%,明显高于结核性脑膜脑炎组(48.3%)和化脓性脑膜脑炎组(15%);抗体IgM检测:病毒性脑膜脑炎组与结核性脑膜脑炎组和化脓性脑膜脑炎组比差异无统计学意义。结论:脑脊液细胞学检查快速、简便,是中枢神经系统病毒感染的重要指标之一;病毒特异性IgG抗体诊断病毒性脑膜脑炎的敏感度为54.7%,特异度为91.3%,是确诊病毒性脑膜脑炎病原的方法之一。     

Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Korea: Clinical Features,Treatment, and Outcome

Background and Purpose

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune synaptic encephalitis and it often responds to treatment. We analyzed the clinical characteristics of anti-NMDAR encephalitis in Korea.

Methods

Serum and/or cerebrospinal fluid (CSF) of adult patients (aged ≥18 years) with encephalitis of undetermined cause were screened for anti-NMDAR antibodies using a cell-based indirect immunofluorescence assay. The patients came from 41 university hospitals.

Results

Of the 721 patients screened, 40 were identified with anti-NMDAR antibodies and clinical details of 32 patients were obtained (median age, 41.5 years; 15 females). Twenty-two patients (68.8%) presented with psychiatric symptoms, 16 (50%) with seizures, 13 (40.6%) with movement disorders, 15 (46.9%) with dysautonomia, 11 (34.4%) with memory disturbance, and 11 (34.4%) with speech disturbance. Magnetic resonance imaging, electroencephalography, and CSF examinations yielded nonspecific findings. Tumor information was only available for 22 patients: 5 patients had tumors, and 2 of these patients had ovarian teratomas. Twenty-two patients received immunotherapy and/or surgery, and therapeutic responses were analyzed in 21 patients, of which 14 (66.7%) achieved favorable functional outcomes (score on the modified Rankin Scale of 0-2).

Conclusions

This study investigated the clinical characteristics of adult anti-NMDAR encephalitis in Korea. Currently, elderly patients who do not have tumors are commonly diagnosed with this condition. Understanding the detailed clinical characteristics of this disease will improve the early detection of anti-NMDAR encephalitis in patients both young and old.     

三种疱疹病毒性脑炎及一般脑炎的脑脊液细胞学表现

目的:比较三种常见疱疹病毒性脑炎的脑脊液细胞学表现,为临床鉴别诊断提供依据。方法:利用病毒抗体特异性指数对临床诊断的病毒性脑炎进行病原学诊断,获得三种较为常见的病毒性脑炎类型-单纯疱疹病毒性脑炎、EB病毒性脑炎、巨细胞病毒性脑炎;设立非病毒性脑炎组为对照组。对单纯疱疹病毒性脑炎、EB病毒性脑炎、巨细胞病毒性脑炎的脑脊液细胞学进行动态观察,分析比较脑脊液细胞学表现的差异;并且把脑炎组与对照组的脑脊液细胞学的异常类型进行比较。结果:单纯疱疹病毒性脑炎患者的脑脊液细胞学最为突出的特点是脑脊液中出现较多的红细胞,和红细胞吞噬细胞;EB病毒性脑炎和巨细胞病毒性脑炎患者脑脊液细胞学符合一般病毒性脑炎脑脊液细胞学特点:即典型脑脊液细胞学图象-淋巴样细胞反应。脑炎组与对照组脑脊液细胞学异常类型有明显差异。结论:单纯疱疹病毒性脑炎脑脊液中出现红细胞是一个特征性的现象;脑脊液细胞学在病毒性脑炎的鉴别诊断中有重要意义。     

单纯疱疹病毒性脑炎脑脊液三项检查的临床评价

为评价目前常用的单纯疱疹病毒性脑炎（ＨＳＥ）脑脊液（ＣＳＦ）３项检查方法的临床应用价值，作者按照平行试验的原则，对４３例ＨＳＥ患者同时进行了ＣＳＦ单纯疱疹病毒抗原（ＨＳＶ－Ａｇ）、抗体（ＨＳＶ－Ａｂ）和ＤＮＡ（ＨＳＶ－ＤＮＡ）检测。结果显示：ＨＳＶ－Ａｂ与ＨＳＶ－ＤＮＡ检测的阳性率高于ＨＳＶ－Ａｇ，分别为８６．０％、７６．７％和４８．８％；４３例患者中２项以上阳性者为３６例，占８３．７％。作者认为：对临床疑诊的所谓“散发性脑炎”患者均应同时进行ＣＳＦＨＳＶ３项检测，如２项或３项阳性者可确诊为ＨＳＥ，１项阳性者应高度怀疑为ＨＳＥ，并应早期使用无环鸟苷等有效药物治疗。     

Cerebrospinal fluid IgG profiles and oligoclonal bands in Chinese patients with multiple sclerosis

OBJECTIVES: To investigate the significance of oligoclonal bands (OCBs) and intrathecal IgG fractions (IgGIF) for the diagnosis of multiple sclerosis (MS) in northern China. MATERIALS AND METHODS: OCBs in cerebrospinal fluid from 30 patients with MS, 34 with other inflammatory neurological diseases (IND) and 22 with non-inflammatory neurological diseases (NIND) were detected using isoelectric focusing. IgGIF was calculated based on corresponding formula. RESULTS: There was no significant difference in the frequencies of positive OCBs and elevated IgGIF between the MS group and the IND group. Compared with NIND, the MS and IND groups had a significantly higher incidence of OCBs and elevated IgGIF. The sensitivity, specificity and positive result likelihood ratio of OCBs for the diagnosis of MS were 63.3%, 74.2% and 2.5 respectively; those of IgGIF were 36.7%, 84.5% and 2.4. CONCLUSIONS: The two parameters, OCBs and IgGIF are of less diagnostic value for MS in China.     

An Improved PCR Assay of Viral DNA in Cerebrospinal Fluid from Patients with Herpes Simplex Virus Type-1 Encephalitis

Abstract: Several investigators have attempted to establish a simple, sensitive and quantitative method for a PCR assay of viral DNA in the cerebrospinal fluid (CSF). However, the rate of a positive DNA test differs between laboratories using the same CSF samples from patients with herpes simplex virus type-1 (HSV-1) encephalitis because of differences in sensitivity of the detection. In the present study, we compared the sensitivity and quantity of nested PCR amplification from the pretreated CSF (nested PCR) with those of direct PCR that was performed by direct PCR amplification of the small amounts of CSF to the PCR "cocktail." We studied the advantages of the two different methods, "the direct and nested PCR," and established a two-step method as an improved PCR assay. HSV-1 DNA from the CSF samples obtained within 4 weeks after onset was detected in all seven cases.     

Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis

Antibody-mediated inflammation is believed to contribute to tissue injury in multiple sclerosis (MS). The majority of patients with MS have oligoclonal bands (OCB), corresponding to antibodies against a variety of antigens, in their cerebrospinal fluid (CSF). The relation of CSF OCB and disease progression in MS is uncertain. To investigate whether there is a relation between CSF OCB and a more aggressive disease course of MS, 143 patients with definite MS according to the Poser diagnostic criteria and CSF analysis at time of diagnosis were followed over a period of 5 years. There were no differences in presence or number of CSF OCB between patients with significant worsening of disability and stable patients. There were no differences in presence or number of CSF OCB between patients with stable relapsing-remitting MS and patients developing secondary progression during follow-up. The presence or number of CSF OCB does not seem to influence early disease progression in MS.     

PCR快速检测病毒性脑炎患者脑脊液中HSV、CXV和CMV

本文应用聚合酶链反应(PCR)和逆转录PCR(RT-PCR)技术检测了27例临床诊断为病毒性脑炎患者和25例其他神经疾病(OND)对照组患者脑脊液(CSF)中单纯疱疹病毒(HSV)、柯萨奇病毒(CXV)和巨细胞病毒(CMV)。27例患者组检出HSV13例、CXV2例、CMV1例，总阳性率为59．3％，而OND对照组皆为阴性。随着检测技术的完善及对更多种类病毒采用PCR早期快速诊断方法的建立，将有效地指导特异性抗病毒药物的选择应用，从而提高治愈率，降低病死率和改进预后。     

肌萎缩侧索硬化症患者脑脊液和血清中自介素-2水平与疾病进展率的相关性研究

目的 探讨肌萎缩侧索硬化症(ALS)患者脑脊液和血清白介素-2(IL-2)水平与ALS疾病进展率的相关性.方法 收集52例ALS患者(ALS组)和31例非ALS患者(对照组)为研究对象.采用酶联免疫吸附试验检测两组患者血清和脑脊液中IL-2水平.结果 ①ALS组血清和脑脊液IL-2水平与对照组比较均显著增加,差异均有统计学意义(P＜0.05);②ALS组血清和脑脊液IL-2水平未见相关性(r=0.041,P=0.84);③ALS组脑脊液IL-2水平与疾病进展率呈正相关,脑脊液IL-2水平与疾病进展率的相关系数分析有统计学意义(r=0.58,P=0.002);④ALS组血清IL-2水平与疾病进展率无相关性(r=0.086,P=0.545).结论 脑脊液IL-2水平与ALS疾病进展率具有正相关关系.     

颅内感染患儿脑脊液中可溶性白细胞介素2受体的测定

目的探讨脑脊液中可溶性白细胞介素2受体水平的变化对脑膜炎的鉴别诊断价值。方法用ELISA法对66例初诊为颅内感染患儿，其中化脓性脑膜炎（化脑）19例，结核性脑膜炎（结脑）20例，病毒性脑膜炎（病脑）27例．进行了脑脊液中可溶性白细胞介素2受体（sIL－2R）水平测定，并与对照组测定值进行比较。结果患儿组的测定位均明显高于对照组测定值．其中以结脑患儿组测定值最高，各患儿组之间的测定值均存在明显差别（P＜0．001）。结脑组和化脑组患儿sIL－2R的测定值存在部分重叠．与病脑组患儿的测定值无任何重叠。结论脑脊液中sIL－2R的测定可能有助于辅助病脑同结脑、化脑的鉴别。