抗NMDAR脑炎的临床特点分析

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点及治疗预后。方法收集2018年12月至2020年6月于北京朝阳中西医结合急诊抢救中心神经内二科诊治的12例抗NMDAR脑炎患者的临床资料,回顾性分析其一般资料、脑脊液检测、抗NMDAR抗体检测、影像学表现、脑电图表现及治疗预后。结果 12例患者中男性3例,女性9例;年龄15～59(33.14±5.47)岁。起病形式多呈急性或亚急性,临床表现为有前驱感染症状4例,精神行为异常12例,认知障碍9例,癫痫发作6例,意识障碍4例,言语障碍3例,自主神经功能障碍3例。脑脊液检测:压力升高8例,白细胞数升高10例,蛋白升高8例。抗NMDAR抗体检测:脑脊液抗NMDAR抗体阳性12例,血清抗NMDAR抗体阳性4例。影像学检查:头颅MRI增强扫描结果异常8例,其中颞叶内侧6例、岛叶4例、额叶3例(有的患者异常部位多处)。胸部及全腹CT检查发现异常1例,提示卵巢畸胎瘤。脑电图检查:轻度异常5例,中度异常2例,重度异常1例,主要表现为局灶性或弥漫性慢波节律。治疗预后:多数患者使用糖皮质激素、免疫球蛋白等免疫治疗,其中1例转外院行畸胎瘤切除术。...     

抗NMDA受体脑炎误诊分析并文献复习

目的探讨抗N-甲基-D-天冬氨酸(N-methyl-D-asparate,NMDA)受体脑炎的临床特点,提高该病诊治水平。方法对我院诊治的抗NMDA受体脑炎1例误诊资料进行回顾性分析,并复习相关文献。结果患者为青年女性,因发作性意识丧失伴肢体抽动6 d入院。外院按癫痫发作处理效果不佳,转我院后视频脑电图检查示间隙期双额颞区慢波,头颅MRI检查未见明显异常,初步诊断癫痫?予左乙拉西坦口服。病程中出现发热、精神行为异常、性格改变,伴幻觉及口面部不自主运动。盆腔影像学检查提示卵巢畸胎瘤,高度怀疑抗NMDA受体脑炎,行血液及脑脊液抗NMDA受体抗体检测阳性,明确诊断抗NMDA受体脑炎。在免疫治疗的基础上行手术切除畸胎瘤后,患者神经精神症状消失,痊愈出院。结论当年轻卵巢畸胎瘤患者出现不明原因的精神症状伴意识和运动障碍时,应高度怀疑抗NMDA受体脑炎,行血液及脑脊液抗NMDA受体抗体检测可确诊。     

抗N-甲基-D-天冬氨酸受体脑炎八例分析

目的：探讨抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎患者的临床表现、辅助检查特点、治疗和预后。 方法：回顾性分析我院8例确诊为抗NMDAR脑炎患者的临床资料。结果：5例患者出现前驱症状;所有患者 临床症状均出现快速进展的精神行为异常、认知障碍,4例为首发症状,此外表现有言语障碍、癫痫发作、运 动障碍、意识水平下降及自主神经功能障碍等;8例患者脑脊液抗NMDAR抗体阳性,3例头MRI检查显示异 常病灶,位于大脑皮质、丘脑、海马、脑干等部位。6例患者脑电图异常,为弥漫性慢波或局灶性痫样放电。 所有患者均接受一线免疫治疗,延误诊治的1例患者对治疗反应差并出现复发。结论：抗NMDAR脑炎临床 表现复杂多样,但具有其特点,对于出现不明原因的精神行为异常或认知障碍的青年患者,及时行抗NMDAR抗体筛查十分必要,早期治疗预后良好。     

儿童抗N-甲基-D-天冬氨酸受体脑炎诊治新进展

抗N-甲基-D-天冬氨酸(NMDAR)受体脑炎是一种与NMDAR受体GluN1亚基IgG抗体相关的疾病。儿童及青年好发,临床表现主要以行为异常、癫痫发作等神经症状为主,目前临床诊断标准尚未统一,脑脊液抗体阳性是本病确诊的可靠依据。免疫治疗效果较好,但脑脊液培养耗时较长,首次发病、难治性或复发抗NMDAR受体脑炎患者治疗尚无标准化方案,而及早诊断、治疗是本病预后良好的重要因素。     

自身免疫性脑炎临床特征初探

目的:探讨自身免疫性脑炎(AE)的临床特征、治疗及预后。方法:对7例AE患者的临床表现、实验室检查、治疗及预后等临床资料进行回顾性分析。结果:7例AE患者中,4例为抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎,其中2例伴畸胎瘤;2例为抗富含亮氨酸胶质瘤失活蛋白1(LGI1)脑炎;1例为抗γ-氨基丁酸B型受体(GABABR)脑炎。以精神行为异常(5/7)、癫痫发作(4/7)、意识清晰度下降(4/7)、面-臂肌张力障碍发作(FBDs)(1/7)、近事记忆力下降(2/7)为主要临床表现。2例颅脑MRI检查异常。2例脑脊液(CSF)抗NMDAR抗体阳性,2例CSF抗LGI1抗体阳性,1例CSF抗GABABR抗体阳性。2例血清抗NMDAR抗体阳性,1例血清抗GABABR抗体阳性。7例经治疗后4例基本恢复,2例遗留癫痫发作(1例伴精神行为异常),复发1例。结论:以急性发作的精神行为异常、癫痫发作及FBDs为主要临床表现的患者要警惕AE可能。AE临床治疗以激素、免疫球蛋白及手术(伴有畸胎瘤患者)治疗为主,早期诊疗多数预后良好。     

抗NMDAR脑炎二例临床误诊分析

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,减少误诊误治。方法对我院近期收治的抗NMDAR脑炎2例的临床资料进行回顾性分析并复习相关文献。结果本组2例因精神行为异常、意识障碍、癫痫发作就诊,例1曾按病毒性脑炎予抗病毒治疗;例2曾按分离性精神障碍予抗精神药物治疗。入我科后经综合分析,考虑自身免疫相关脑炎可能,行腰椎穿刺脑脊液及血液检查示NMDAR抗体均强阳性,确诊为抗NMDAR脑炎。予糖皮质激素、免疫球蛋白等治疗,例1合并畸胎瘤行手术切除后予利妥昔单抗、环磷酰胺及抗癫痫等对症治疗,后2例症状均明显改善出院。随访3个月~1年,例1畸胎瘤复发;例2病情出现反复,再次入院予对症治疗后好转出院。结论抗NMDAR脑炎临床表现无特异性,易误诊。及时行相关抗体检测、伴有肿瘤者及时切除肿瘤并早期予免疫抑制剂是避免误诊误治的关键。     

单中心卵巢畸胎瘤患者中合并抗N-甲基-D-天冬氨酸受体脑炎的比例调查及临床特征分析

目的探究卵巢畸胎瘤患者中发生抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的比例,并将合并抗NMDAR脑炎的卵巢畸胎瘤患者与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的临床特征进行总结对比。方法收集卵巢畸胎瘤患者的临床资料,将其分为合并抗NMDAR脑炎组与未合并抗NMDAR脑炎组,对其临床特征进行对比分析。结果共收集到168例卵巢畸胎瘤患者,其中14例(8.3%)合并抗NMDAR脑炎;合并抗NMDAR脑炎的卵巢畸胎瘤患者年龄低于未合并抗NMDAR脑炎的卵巢畸胎瘤患者[(23.8±5.5)岁vs.(29.8±9.1)岁,P=0.016]。合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以癌抗原125及血清铁蛋白升高为主,而未合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以糖类抗原199升高为主。合并抗NMDAR脑炎与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的肿瘤组织均可含有神经组织。结论卵巢畸胎瘤患者中发生抗NDMAR脑炎的比例不低,对于无明显症状的卵巢畸胎瘤患者,可考虑积极行手术治疗,以降低发生抗NMDAR脑炎的风险。     

抗N-甲基-D-天冬氨酸受体脑炎研究进展

抗N-甲基-D-天冬氨酸受体脑炎(抗NMDA受体脑炎)是一种自身免疫介导性脑炎,病程呈多阶段进展,临床表现为急性或亚急性起病,以近记忆缺损、自主神经功能障碍、精神行为异常及癫痫发作为特点。抗NMDA受体脑炎病因不明确,大多有不典型的临床症状,漏诊误诊率高,诊断上需要检测血清和脑脊液抗NMDAR抗体,治疗上以尽早免疫治疗、合并肿瘤手术切除、支持治疗,ICU监护等,预后大多数良好,疾病可能复发,需要长期随访。     

抗NMDA受体脑炎纠误挽治回顾分析

目的总结抗N-甲基-D-天冬氨酸(N-methyl-D-asparate,NMDA)受体脑炎早期诊断要点,减少误诊。方法回顾性分析1例抗NMDA受体脑炎临床资料。结果患者为青年女性,因反复发热20余日,伴精神异常进行性加重9 d就诊,外院诊断为呼吸道感染、精神分裂症,予相应治疗效果不佳,入我院。入院后怀疑脑炎,行血清炎性指标、脑脊液常规及生化检查无异常,脉搏氧饱和度降低,考虑有中枢性通气不足,病程中出现唾液分泌明显增多,口面部不自主运动,动态脑电图提示弥漫性慢波,盆腔影像学提示畸胎瘤,高度怀疑抗NMDA受体脑炎,行血液及脑脊液抗NMDA受体抗体检测阳性,明确诊断。在免疫治疗的基础上行手术切除畸胎瘤后,患者康复出院。结论对年轻患者临床出现不明原因的精神症状伴意识和运动障碍,特别是伴卵巢畸胎瘤者,应高度怀疑抗NMDA受体脑炎,积极行脑脊液和(或)血液抗NMDA受体抗体检测,以明确诊断。     

儿童抗N-甲基-D-天冬氨酸受体脑炎3例用药护理

正近年来,关于自身免疫性脑炎的报道越来越多,抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎也备受关注。2005年Vitaliani等[1]首次报道了4例年轻女性患者的临床症状,主要表现为伴有卵巢畸胎瘤、流感样前驱症状、失忆健忘、意识障碍、精神行为异常、痫性发作、运动功能异常及幻听、幻视等,患者血清及脑脊液的实验室检查中NMDAR抗体阳性。本病进展较快,精神症状较重,具有潜在致死性,诊断不明确,尤其     

儿童抗MOG抗体合并抗NMDAR抗体双阳性自身免疫性脑炎2例并文献复习

目的 探讨儿童抗髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoprotein, MOG)抗体合并抗N-甲基-D-门冬氨酸受体(N-methyl-D-aspartate receptor, NMDAR)抗体双阳性自身免疫性脑炎的临床特点。方法 回顾性分析邯郸市中心医院收治的2例抗MOG抗体合并抗NMDAR抗体双阳性自身免疫性脑炎患儿的病例资料,并复习相关文献。结果 2例脑脊液白细胞数目均增多,1例颅脑磁共振成像(magnetic resonance imaging, MRI)同时存在幕上及幕下病变,1例仅有幕上病变且其视频脑电图结果与抗NMDAR脑炎典型脑电图相似。经甲泼尼龙冲击、人免疫球蛋白治疗后,2例症状均得到改善,3个月后随访,均无复发。结论 该病多发于青少年,既有抗MOG抗体相关疾病的脑病表现,也有抗NMDAR脑炎的表现,且以抗NMDAR脑炎的表现更易被识别。颅脑MRI及视频脑电图等无创检查对此病诊断有一定提示意义,但确诊仍需神经抗体检查,诊疗方面一线治疗为激素、免疫球蛋白、血浆置换,多数患儿对此治疗反应良好,但发病机制仍需进一步研究。     

Adjunct therapeutic plasma exchange for anti-N-methyl-D-aspartate receptor antibody encephalitis: a case report and review of literature

Encephalitis associated with autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR) is usually a paraneoplastic syndrome that presents in young females with ovarian teratomas. We report a case of a previously healthy 14-year-old girl with sudden-onset paranoia, hallucinations, hyperactivity, increased speech, decreased sleep, seizures, and violent behavior deteriorating to catatonia. Her cerebrospinal fluid tested positive for anti-NMDAR antibodies. She was treated with five sessions of therapeutic plasma exchange (TPE) after having failed therapy with antibiotics, intravenous steroids, intravenous immunoglobulin (IVIG), one dose of rituximab, and seven sessions of electroconvulsive therapy (ECT). The American Society for Apheresis assigns a Category III (Grade 2C) recommendation for TPE in paraneoplastic neurologic syndromes; however, apheresis specifically for anti-NMDAR encephalitis has not been well studied. Literature review revealed two case reports describing outstanding improvement in patients with anti-NMDAR encephalitis following TPE. We report no improvement in our patient's symptoms after plasma exchange and discuss possible reasons for why it failed along with review of the literature.     

Acute non-herpetic encephalitides

"Acute non-herpetic encephalitis" was consisted of several non-herpetic encephalitides including "acute juvenile female non-herpetic encephalitis (AJFNHE)" and "non-herpetic limbic encephalitis(NHLE)". In 1997, we first reported five young adult female patients with acute non-herpetic encephalitis who presented with severe prolonged coma and status epilepticus, but achieved a good recovery. Following this report, the results of a clinical analysis on 89 serial patients with encephalitides indicated that such patients presented specific and different clinical features, including the frequent detection of anti-glutamate receptor (GluR) antibody as compared with other etiologies of encephalitis. Since all of their 11 patients were young adult women, we designated these patients as "acute juvenile female non-herpetic encephalitis (AJFNHE)". In 2007, Dalmau et al. reported anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis associated with ovarian teratoma. We recently reported the results of a nationwide survey on AJFNHE in Japan. This result was indicated that AJFNHE and anti-NMDAR encephalitis were inferred to be almost identical condition. AJFNHE thus represented a clinical concept based on the specific clinical features, and anti-NMDAR encephalitis represented a clinical entity based on the neuro-oncological findings including the NMDAR NR1 and NR2 heteromer antibody.     

1H-MR波谱分析急性期抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎额叶代谢物变化

目的 采用¹H-MR波谱（¹H-MRS）观察急性期抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎双侧额叶代谢物变化及其与认知障碍的关系,评估其应用价值。方法 采集20例急性期抗NMDAR脑炎患者（脑炎组）和20名健康成年人（对照组）双侧额叶¹H-MRS,获得相应MRS及各代谢物N-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌醇（mI）、谷氨酸盐复合物（Glx）和肌酸（Cr）的峰下面积,计算NAA/Cr、Cho/Cr、mI/Cr及Glx/Cr比值。记录脑炎组脑脊液抗NMDAR抗体滴度检测结果,以简易精神状态检查量表（MMSE）和蒙特利尔认知评估（MoCA）量表评估2组认知功能,比较组间¹H-MRS参数差异,并分析其与抗NMDAR脑炎患者MMSE评分、MoCA评分及与脑脊液抗NMDAR抗体的相关性。结果 脑炎组双侧额叶NAA/Cr、Cho/Cr、mI/Cr、Glx/Cr差异均无统计学意义（t=1.03、2.29、－0.73、0.15,P均>0.05）。与对照组相比,脑炎组双侧额叶NAA/Cr下降、Glx/Cr升高（P均<0.05）,而双侧额叶Cho／Cr、mI/Cr差异均无统计学意义（P均>0.05）。脑炎组双侧额叶NAA/Cr、Cho/Cr、mI/Cr及Glx/Cr与MMSE评分、MoCA总分和脑脊液抗NMDAR抗体均无明显相关性（P均>0.05）。结论 ¹H-MRS有助于诊断急性期抗NMDAR脑炎及监测病情;抗NMDAR脑炎急性期双侧额叶NAA/Cr降低、Glx/Cr升高,但与认知障碍无明显相关。     

N-methyl-D-aspartate receptor encephalitis: laboratory diagnostics and comparative clinical features in adults and children

Introduction: N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis due to autoantibodies against neuronal surface antigens, can affect both children and adults, leading to neurological and neuropsychological sequelae. However, it is potentially treatable and the prompt start of immunotherapy associates with better prognosis. Conversely, misdiagnosis can be harmful. The detection of NMDAR antibodies in serum and cerebrospinal fluid plays a pivotal role in the diagnostic work-up. Reliable methods for NMDAR antibody detection are thus fundamental to assure accurate diagnosis and allow early treatments.

Areas covered: This review recapitulates the pathogenic mechanisms of NMDAR encephalitis as a model of antibody mediated synaptopathy, and gives insights into the related state-of-the-art laboratory testing. The differences in clinical presentations, tumor associations and responses to treatments between adults and children are also described.

Expert commentary: The relevance of NMDAR encephalitis has placed neuroimmunology laboratories in a crucial position, but methods for NMDAR antibody detection are awaiting thorough and consensus-based standardizations. In the next few years, this process, along with novel insights into the pathogenic mechanisms, could improve the disease management and clarify the still pending role of NMDAR antibodies in healthy people and in other more common neuropsychiatric disorders.     

电压门控钾离子通道复合物相关抗体脑炎7例分析

目的:探讨电压门控钾离子通道复合物(VGKC)相关抗体脑炎的临床特点及诊治。方法:回顾性分析VGKC相关抗体脑炎7例的临床资料。结果:患者发病前无前驱症状;出现癫痫发作6例,精神症状3例,认知障碍2例;伴睡眠障碍者4例,心慌、多汗1例,低钠血症者3例,面-肩臂肌张力障碍者1例。脑脊液富亮氨酸胶质瘤失活蛋白1(LGI-1)抗体阳性4例(其中2例同时血清LGI-1抗体阳性),血清LGI-1抗体阳性1例,脑脊液和血清接触蛋白相关蛋白2(Caspr2)抗体阳性1例,血清Caspr2抗体阳性1例。头MRI平扫表现为主要累及颞叶内侧、海马区伴或不伴基底节区T2和FLAIR序列高信号;视频脑电图监测异常3例。均未发现肿瘤。应用丙种球蛋白、甲泼尼龙冲击或二者联合治疗,随访3个月,好转6例,复发、放弃治疗1例。结论:VGKC相关抗体脑炎首发症状多为癫痫,LGI-1脑炎多伴有低钠血症、睡眠障碍,Caspr2脑炎多伴有自主神经功能障碍。头颅MRI不能鉴别脑炎的类型,脑电图无特征性的改变,脑脊液和血清自免脑抗体检测有助于确定诊断。多数病例早期免疫治疗有效,少数病例可复发。