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-天冬氨酸受体抗体脑炎复发的临床特征

目的总结复发性抗N-甲基-D-天冬氨酸受体(NMDAR)抗体脑炎的临床特点、诊断及治疗。方法回顾性分析2013年5月至2017年2月郑州大学人民医院诊治的57例抗NMDAR抗体脑炎中10例复发者的临床症状、实验室检查、影像学特点和免疫治疗。结果 10例(19%)复发中男5例,女5例,平均年龄27.5岁,10例共复发14次,其中2例复发2~3次,平均复发间隔时间7.1个月(1~19月)。复发时最常见症状为癫痫(8/14)和精神行为异常(8/14),其中1例次复发仅表现为不典型症状,如眩晕、行走不稳和复视。复发时13例次行抗NMDAR抗体检测,脑脊液抗体阳性率100%(13/13),血清抗体阳性率69%(9/13)。13例次复发再次给予免疫治疗仍有效,1例次拒绝治疗,出院后平均随访18.9月,3例完全恢复正常,4例遗留轻微后遗症,3例遗留较明显后遗症,影响日常生活。结论抗NMDAR脑炎复发时可表现为典型或不典型症状,脑脊液抗NMDAR抗体检测有助诊断,积极免疫治疗仍有效。     

抗N-甲基-D-天冬氨酸受体脑炎1例报告

目的提高临床医生对抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的认识。方法收集1例18岁女性抗NMDAR脑炎患者的临床资料,对抗NMDAR脑炎的治疗及肿瘤搜索结合文献进行探讨。结果患者因头痛发热9 d,言语行为异常5 d入院,入院后频繁癫发作。肿瘤标记物、免疫、TORCH检查和影像学肿瘤搜索2次检查结果均为阴性,但抗NMDAR抗体阳性,诊断抗NMDAR脑炎、癫持续状态。经呼吸机辅助呼吸、抗癫药和免疫治疗后症状好转。病程约5个月后发现卵巢肿瘤,接受腹腔镜肿瘤切除,病理检查提示畸胎瘤。术后患者高级神经功能迅速恢复。结论抗NMDAR脑炎严重影响患者生活质量,尤其对于年轻女性应积极进行肿瘤搜索,切除肿瘤后患者恢复更快。     

重症抗N-甲基-D-天冬氨酸受体脑炎的临床特点及预后分析

目的探讨重症抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点及预后。方法回顾性分析9例重症抗NMDAR脑炎患者的临床资料。结果 9例患者(女7例,男2例)均入住ICU治疗;平均发病年龄27.7岁;平均病程22.4 d,ICU平均住院时间50.9 d。主要临床表现有发热(7例)、精神行为异常(9例)、癫痫发作(9例)、意识障碍(8例)、运动功能异常(7例)、自主神经功能障碍(9例)及低通气(6例)。3例合并畸胎瘤。所有患者CSF抗NMDAR抗体均阳性,6例血清抗NMDAR抗体阳性,7例CSF-Ig A升高。3例患者头颅MRI示颞叶或海马异常信号。5例患者EEG示异常慢波。9例患者接受糖皮质激素、丙种球蛋白或血浆置换等免疫调节治疗。5例患者完全恢复,4例患者症状改善伴残留症状。结论重症抗NMDAR脑炎常表现为进展迅速的精神行为改变、癫痫等症状,还有意识障碍、运动障碍、自主神经功能障碍,合并肿瘤并不多见。多数重症抗NMDAR脑炎患者积极免疫治疗预后较好。     

EB病毒脑炎继发抗N-甲基-D-天冬氨酸受体脑炎的临床特点（附2例报告）

目的 探讨EB病毒(EBV)脑炎继发抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点。方法 回顾性分析2例诊断为EBV脑炎继发抗NMDAR脑炎患儿的临床资料,并通过文献检索总结分析其临床特点。结果 2例患儿均为女性,年龄分别为2岁8个月及8岁,均以发热、惊厥起病。2例患儿CSF提示有核细胞数增高,且以单个核细胞比例为主。1例血液变异淋巴细胞10%,同时伴血清抗EBV-衣壳抗原-IgM及CSF中EBV-DNA阳性;1例CSF病原高通量基因检测到EBV,同时CSF中EBV-DNA阳性。2例患儿分别在病程第12 d、第4 d出现精神行为异常、不自主运动、言语障碍及认知障碍,完善CSF抗NMDAR抗体分别为1∶10及1∶100,CT检查均未发现肿瘤。2例患儿通过抗癫痫药物、阿昔洛韦、人免疫球蛋白及甲泼尼龙冲击治疗后症状均好转,但1例患儿在3个月后出现复发,使用4次利妥昔单抗治疗后恢复。结论 EBV脑炎临床症状非特异,其诊断还需结合EBV特异性抗体及EBV-DNA等结果。EBV脑炎可继发抗NMDAR脑炎,当EBV脑炎患儿在病程中出现精神行为异常、不自主运动及认知障碍等症状时,需警惕继发抗...     

抗N-甲基-D-天冬氨酸受体脑炎:三例报告并文献复习

目的回顾分析抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者临床表现,总结其发病特点。方法与结果共3例经临床、实验室和影像学检查明确诊断为抗NMDAR脑炎患者,男性2例、女性1例,年龄33~34岁,平均33.30岁。临床主要表现为头痛(2例),精神异常(3例),言语障碍(3例),运动异常(1例)或幻觉(1例);MRI显示脑回肿胀、颞叶异常信号或脱髓鞘改变;脑电图呈局灶性或弥漫性慢波;脑脊液白细胞计数(3例)和蛋白定量(2例)升高。均经甲泼尼龙和免疫球蛋白治疗痊愈。结论抗NMDAR脑炎是一种严重但可治性疾病,是临床上可以鉴别且可用血清学方法诊断的疾病。早期诊断和及时治疗有助于改善抗NMDAR脑炎患者预后。     

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     

抗NMDA受体脑炎的临床分型和调查

目的 了解抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎分型、疗效和预后。方法 2013年1月～2015年8月在武汉同济医院和襄阳市中心医院收集抗NMDAR脑炎确诊患者。抗体检测方法均采用转染细胞免疫荧光法(CBA),将抗NMDAR脑炎分为三种亚型,急性期治疗方案首选采用甲强龙冲击治疗、丙种球蛋白(0.4 g·kg^-1·d^-1,5 d)、血浆置换治疗,二线治疗方案为环磷酰胺,随访方法为12个月改良Rankin量表。结果 32例患者完成研究,所有患者均没有发现畸胎瘤等肿瘤。32例患者采用甲强龙冲击治疗方案; 对疗效不佳的23例患者又采用丙种球蛋白治疗; 没有患者行血浆转换; 9例患者采用免疫抑制剂治疗方案。12个月时改良Rankin量表(0～2分)转归为24例。结论 采用国外学者提出的诊断标准、临床分型和治疗方案后大部分抗NMDAR脑炎患者取得较好疗效。     

抗NMDAR脑炎临床特点及影像表现分析

目的探讨抗NMDAR脑炎的临床特点、影像表现及意义。方法回顾性分析陕西省人医院2014-01-2020-08确诊的11例抗NMDAR脑炎患者的临床及影像资料。结果11例患者为急性或亚急性起病,首发症状表现为精神症状2例,认知功能损害2例,痫性发作4例,非特异性症状3例。11例患者的脑脊液抗NMDAR抗体均为阳性,其中2例脑脊液HSV抗体阳性,1例脑脊液麻疹病毒抗体阳性。头颅MRI 7例表现为侧脑室旁、岛叶、颞叶、额叶及海马等部位高T2 FLAIR信号,4例未见明显病灶。MRI首次阳性者,病灶范围会随病情好转而缩小或加重而增大。MRI首次阴性者,复查可出现阳性或仍为阴性。结论抗NMDAR脑炎临床表现复杂多样,MRI阳性者结合临床特点可提示诊断,动态观察MRI表现可反映疾病进展、演变。     

首发为精神症状的抗N-甲基-D-天冬氨酸受体脑炎误诊分析

目的:探讨首发为精神症状的抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点及误诊分析.方法:回顾性分析22例误诊为精神疾病的抗NMDAR脑炎患者的临床资料.结果:22例患者为少年到中年人;均以急性或亚急性起病,首发症状为精神及行为紊乱;均误诊为"精神障碍"收住精神科,并接受相应的精神科药物或电休克治疗,但无效....     

Suppression of synaptic plasticity by cerebrospinal fluid from anti-NMDA receptor encephalitis patients

The functional effects of cerebrospinal fluid (CSF) from patients with anti-NMDA receptor (NMDAR) encephalitis on the NMDAR-mediated synaptic plasticity were evaluated by using mouse hippocampus slices. Anti-NMDAR antibody detection system was established by immunostaining recombinant NMDAR heteromers expressed in HEK cell culture as well as native NMDARs in cultured hippocampal neurons. Under a complete blind manner for the clinical information, CSF and sera collected from 36 pre-diagnosed patients were tested for anti-NMDAR antibodies. With this test, thirteen patients were diagnosed as anti-NMDAR encephalitis. CSF positive for anti-NMDAR antibodies suppressed induction of long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in mouse hippocampal slices. LTP induction was not suppressed by CSF collected from herpes simplex virus (HSV) encephalitis or non-encephalitis control patients. Antibody absorption with NMDAR-expressing HEK cell culture reversed the suppression of LTP by anti-NMDAR encephalitis patients' CSF, confirming that anti-NMDAR antibodies suppressed LTP. The present experiments firmly support the proposal that the anti-NMDAR encephalitis autoantibody is responsible for cognitive disorders like amnesia accompanying this disease.     

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.     

20例抗N-甲基-D-天冬氨酸受体脑炎患者临床特点分析

目的回顾性分析总结20例抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者的临床特点,增强对抗NMDAR脑炎的认识。方法对90例临床疑似脑炎患者的血清和脑脊液进行抗NMDAR-IgG检测,分析确诊为抗NMDAR脑炎的20例患者的临床表现、实验室检查、治疗及预后。结果抗NMDAR脑炎患者男女比例为6:14,中位年龄24岁,首发症状及主要精神症状多有不同。20例抗NMDAR脑炎患者中有12例患者血清和脑脊液中抗NMDAR-IgG抗体均阳性,其他8例仅在血清或脑脊液中检测到抗NMDAR-IgG抗体。5例盆腔检查异常,其中1例病理确诊为成熟囊性畸胎瘤。6例患者脑电图异常,7例头颅MRI异常。除1例患者未接受免疫治疗死亡外,其余患者接受免疫治疗后症状均有不同程度的缓解,其中3例未伴畸胎瘤的患者用二线免疫治疗后复检血清和脑脊液中抗NMDAR-IgG抗体水平下降。结论抗NMDAR脑炎患者中年轻女性发病率较高。二线免疫治疗可能对不伴有畸胎瘤患者的疗效更好。CSF中的抗NMDAR-IgG抗体的阳性率高于血清,同时检测血清和脑脊液中抗NMDAR抗体可以提高疾病的诊断效率。     

晚发型抗N-甲基-D-天冬氨酸受体脑炎临床特征分析

目的分析晚发型抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特征。方法收集2010-01-01—2019-05-01于郑州大学第一附属医院住院确诊为抗NMDAR脑炎的患者临床资料,分析晚发型(≥50岁)患者数据,并与早发型(18~49岁)患者进行对比。结果18例晚发型患者中,男11例(61%),发病年龄50~84岁。晚发型患者中,9例(50%)患者出现前驱症状,精神行为异常是最常见的首发症状(44%)和临床表现(78%);头颅磁共振提示脑实质炎性病变9例(9/17,53%);脑脊液检验结果异常17例(94%);合并肿瘤4例(22%),均非畸胎瘤。相比于早发组患者,晚发组患者有更高的自主神经功能障碍比例(72%vs 45%,P=0.032),更高的岛叶病变比例(67%vs 27%,P=0.047),更高的脑脊液蛋白升高比例(56%vs 28%,P=0.023),以及更高的脑脊液鞘内IgG合成率升高比例(73%vs 44%,P=0.041)。晚发组合并肿瘤均非畸胎瘤,早发组合并肿瘤均为畸胎瘤(P=0.001)。结论相比早发型抗NMDAR脑炎患者,晚发型患者更易出现岛叶病变,更易出现脑脊液炎症反应,其发病机制可能与畸胎瘤不相关。     

儿童抗MOG抗体及抗NMDAR抗体双阳性中枢神经系统脱髓鞘1例报道并文献复习

目的 探讨缺血性脑卒中(Cerebral ischemic stroke,CIS)患者发生睡眠呼吸紊乱(Sleep-disordered breathing,SDB)的影响因素。方法 纳入2018年2月-2019年4月本院神经内科收治的288例首次发病的CIS患者,于发病后的第7 d左右采用Apnea Link^TM睡眠测试装置整夜连续进行呼吸睡眠检测,发生SDB的患者[呼吸暂停-低通气指数(Apnoea-hypopnoea index,AHI)≥10]纳入研究组,未发生SDB的患者纳入对照组,考察CIS患者中SDB的发生率,采用单因素分析的方法比较发生SDB的可疑危险因素,对于单因素分析有意义的自变量,采用Logistic回归逐步向前法进一步识别SDB的独立影响因素。结果 CIS患者中SDB的发病率为63.1%。多因素Logistic回归分析显示,年龄≥65岁[OR(95%CI)=2.078(1.317～3.28),P=0.002]、脑干病变[OR(95%CI)=2.306(1.418～3.75),P=0.001]、NIHSS得分[OR(95%CI)=2.368(1.34～4.185),P=0.003]、mRS得分[OR(95%CI)=2.033(1.146～3.606),P=0.015]和发生吞咽困难[OR(95%CI)=2.392(1.031～5.545),P=0.042]是脑卒中患者发生SDB的独立危险因素。结论 脑干损伤是脑卒中患者发生SDB的主要危险因素,而SDB加重了急性期缺血性脑卒中患者的神经系统症状,老年缺血性脑卒中患者是SDB的易感人群。对脑干损伤的老年患者,要重视早期监测呼吸睡眠功能,发生SDB迹象时要及时采取干预措施。     

Japanese encephalitis-induced anti-N-methyl-d-aspartate receptor encephalitis: A hospital-based prospective study

ObjectivesA hospital-based prospective study was performed to determine: 1) whether Japanese encephalitis (JE) normally triggers anti-N-methyl-d-aspartate receptor (NMDAR) immunoglobulin G (IgG) synthesis, especially in monophasic JE patients; and 2) the incidence of JE-induced anti-NMDAR encephalitis in pediatric patients with JE.MethodsWe detected the level of anti-NMDAR IgG in the serum and cerebral spinal fluid (CSF) of JE patients within one week of onset. If patients relapsed during the convalescence phase, we detected JE virus RNA in the CSF and anti-NMDAR IgG in both the serum and CSF. For patients who did not relapse during the convalescence phase, serum was collected and anti-NMDAR IgG was detected during the 30–60-day course of the disease.ResultsWe enrolled 65 JE patients, who were negative for anti-NMDAR IgG in the serum and CSF during the acute phase, of which 63 patients were successfully followed up. Five patients relapsed during the convalescence phase, for whom JE virus RNA in the CSF was negative and excluded latent JE reactivation. The distinctive symptoms of four younger patients were choreoathetosis, whereas the psychiatric and behavioral manifestations were the distinctive symptoms experienced by the teenager. Anti-NMDAR IgG in the CSF of three patients was positive and they were diagnosed with anti-NMDAR encephalitis. The other two patients were negative for anti-NMDAR IgG in both the serum and CSF. For the 58 patients who did not relapse during the convalescence phase, anti-NMDAR IgG was negative in the serum of all patients at 30–60 days during the course of the disease.ConclusionsJE does not typically trigger anti-NMDAR IgG synthesis. Besides anti-NMDAR IgG, other unknown autoantibodies can also cause autoimmune encephalitis in the convalescence phase of JE. The incidence of JE-induced autoimmune encephalitis in pediatric patients with JE was 7.9%, and the incidence of JE-induced anti-NMDAR encephalitis was 4.7%.     

Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and experience in Hong Kong

Aim

The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl-d-aspartate receptor encephalitis in children from Hong Kong.