自身免疫性脑炎研究热点追踪与思考

自抗N-甲基-D-天冬氨酸受体脑炎被发现以来,翻开了针对自身免疫性脑炎(autoimmune encephalitis,AE)研究的新篇章,有关AE的研究成为临床研究的热点和重点.经过10多年的不断努力,在探索AE病因、机制和治疗方面均取得长足的进步.虽然现阶段对AE的认识仍有许多未知,但不断更新的研究结果将为今后攻克...     

自身免疫性脑炎临床鉴别诊断及治疗研究

目的分析自身免疫性脑炎的鉴别诊断及治疗措施。方法选取2015-01—2016-02我院治疗的病毒性脑炎患者为病毒性脑炎组,自身免疫性脑炎患者为自身免疫性脑炎组,每组50例,进行相关鉴别诊断;同时将自身免疫性脑炎患者按随机数字表法分为观察组(25例)与对照组(25例),观察组给予免疫球蛋白、激素治疗,对照组仅给予激素治疗。观察并比较自身免疫性脑炎的鉴别诊断及效果。结果自身免疫性脑炎组脑脊液蛋白质含量正常率(74.00%)、亚急性发作率(52.00%)、脑脊液与血清中抗NMDA抗体(54.00%)均高于病毒性脑炎组,影像学累及颞叶率(12.00%)低于病毒性脑炎组;观察组总有效率(84.00%)优于对照组(56.00%),差异具有统计学意义(P0.05)。结论自身免疫性脑炎大多亚急性发作,其脑脊液蛋白质含量基本正常,自身免疫性脑炎患者在脑脊液与血清中均存在不同程度的自身免疫性抗体,同时免疫球蛋白联合激素有更好的治疗效果。     

1例自身免疫性脑炎及与精神障碍的鉴别

正1病例患者女性,16岁,因"发作性反应迟钝,言语断续,肢体不自主运动20天",门诊考虑"癔症",于2015年9月29日收治入院。入院前情况不详,急性起病,曾在基层医院就诊,考虑为癔症。入院后表现为精神运动性抑制、缄默状态,不与外界交流,约30~90 min左右有所缓解,缓解时应答切题,但言语稍含混,自诉头昏,全身乏力,右下肢无力,活动不灵活,查体时无异常,住院第二天,患者右下肢无力较     

自身免疫性脑炎患者并发抑郁综合征的研究进展

自身免疫性脑炎泛指一类免疫反应介导的脑炎，由特殊抗体介导的为新型自身免疫性脑炎。精神障碍作为自身免疫性脑炎患者的主要表现之一，受到了广泛的关注，而抑郁综合征作为精神障碍的一种表现，临床中并不少见，但与其相关的诊断、治疗及预后等研究却较少。为丰富临床医师对自身免疫性脑炎患者抑郁综合征的认识，本文从抑郁综合征在自身免疫性脑炎中的患病率、发病机制、诊断、治疗及其预后方面进行综述。     

抗谷氨酸脱羧酶抗体阳性自身免疫性脑炎三例临床特征分析

目的探讨抗谷氨酸脱羧酶(glutamic acid decarboxylase,GAD)抗体阳性自身免疫性脑炎的临床症状及相关辅助检查特点,为临床正确诊疗抗GAD相关脑炎提供依据。方法对作者医院自2016年1月至2018年8月期间明确诊断的3例抗GAD抗体阳性自身免疫性脑炎患者进行回顾性研究,分析其一般人口学、临床症状学、脑脊液细胞学、影像学、脑电图、治疗及预后等特征。结果3例患者均为女性,发病年龄分别为44岁、26岁、27岁,其中2例患者以难治性癫痫状态起病,1例以头痛起病,病程中均出现一定程度意识障碍及显著认知功能下降,其中1例患者病情恢复期出现类似吉兰-巴雷综合征样周围神经损害;头颅MRI均表现为双侧海马、颞叶等边缘叶系统核异常信号,且进行性加重。3例均检测到GAD65抗体,其中1例发病初期即检测到该抗体,2例患者发病初期神经元抗体检测为阴性,分别于发病43 d、79 d脑脊液检测到;3例患者发病初期脑电图表现中-重度广泛性、多灶样异常,中-高波幅3~5 Hz慢波阵发,杂有稍多量尖棘波发放。1例患者发病初期脑脊液白细胞计数增高(淋巴细胞97%),10 d后复查恢复正常,余2例患者脑脊液常规生化免疫及细胞学未见明显异常。三例患者经甲泼尼龙及大剂量免疫球蛋白治疗后认知功能较症状高峰期基本恢复,未再有癫痫发作。结论此3例抗GAD抗体阳性自身免疫性脑炎患者均为女性,中青年发病,初期表现难治性癫痫持续状态或者耐药性癫痫,恢复期出现认知功能减退,病程中均无显著精神症状;影像学以双侧额颞叶、海马受累较为明显;病程中脑脊液抗GAD 65抗体均阳性,且脑脊液中该抗体发病初期可为阴性。     

晚发型自身免疫性脑炎:一项单中心回顾性队列研究

目的 研究晚发型自身免疫性脑炎(A E)患者临床特征、治疗及预后情况.方法 收集2014年6月至2019年10月作者医院收治的A E患者67例,根据首发年龄将患者分为晚发型A E(首发年龄≥45岁)25例和早发型AE(首发年龄<45岁)42例.比较两组患者临床表现、实验室检查、影像学特征、治疗及预后等情况.结果(1)晚...     

重叠抗体自身免疫性脑炎的研究进展

近年来对于重叠抗体自身免疫性脑炎的报道越来越多,其重叠抗体形式多种多样.常见重叠形式为自身免疫性脑炎叠加神经胶质抗体、自身免疫性脑炎与其他全身性自身免疫性疾病并存、自身免疫性脑炎相关重叠抗体,但各类型的临床意义尚未明确.文中收集国内外对重叠抗体自身免疫性脑炎的研究现状,对该类脑炎可能的发病机制、重叠类型、临床表现特点及...     

自身免疫性脑炎与睡眠障碍

自身免疫性脑炎与睡眠障碍关系密切。抗Ma2抗体介导的神经系统副肿瘤综合征可以导致发作性睡病和快速眼动睡眠期行为障碍。边缘性脑炎和Morvan综合征可以导致严重失眠及其他睡眠障碍,常伴抗电压门控性钾离子通道抗体(包括抗富亮氨酸胶质瘤失活基因1抗体和抗接触蛋白相关蛋白-2抗体)阳性。中枢性低通气常见于抗N-甲基-D-天冬氨酸受体脑炎患者。阻塞性睡眠呼吸暂停、喘鸣和异态睡眠是抗IgLON家族蛋白5抗体相关脑病的常见表现。由此可见,睡眠障碍是自身免疫性脑炎的重要表现,免疫治疗有可能改善临床症状和预后。     

合并多种抗体阳性自身免疫性脑炎临床分析

目的总结自身免疫性脑炎合并多种抗神经元抗体阳性患者的临床特点及意义。方法回顾性分析郑州大学第一附属医院2015-01-2019-05确诊的7例合并多种抗神经元抗体阳性自身免疫性脑炎患者的临床表现、实验影像学检查及治疗效果,并进行相关文献复习。结果255例自身免疫性脑炎患者仅出现7例合并多抗体阳性患者,其中4例抗NMDAR抗体阳性患者分别合并抗LGI1抗体、抗-Ma2、抗-Yo抗体阳性,2例抗GABABR脑炎分别合并抗Hu、抗amphiphsin阳性,1例抗LGI1脑炎合并抗Hu阳性。6例免疫治疗有效好转,1例对症治疗后好转,其中2例患者病情严重并于治疗后半年死亡,余5例均明显好转。结论多种抗神经元抗体阳性的自身免疫性脑炎并不多见,临床表现更复杂多样,极易引起误诊或漏诊。潜在肿瘤风险更大,合并的肿瘤类型可能更广泛,加重病情、增加复发率及病死率,需引起高度重视,全面的实验室检查及定期复查是必要的。     

自身免疫性脑炎临床特点及治疗分析

目的 总结自身免疫性脑炎的临床特点及治疗转归。方法 收集2017-10—2022-03在聊城市人民医院住院治疗的18例自身免疫性脑炎患者的临床资料,回顾性分析其临床表现、实验室检查、影像学检查、脑电图和治疗转归。结果 18例患者中男12例,女6例,平均发病年龄41.8岁（15～68岁）。临床表现：16例患者有癫痫发作史,13例患者认知功能下降,15例患者精神行为异常。脑脊液检查：3例患者脑脊液压力超过300 mmH2O,8例患者白细胞计数升高,均低于100×106个/L,以淋巴细胞和单核细胞为主,部分可见激活单核细胞和转化淋巴细胞,8例脑脊液蛋白轻度升高,脑脊液相关抗体检测均为阳性。影像学检查：8例抗NMDAR脑炎患者发现异常,1例抗GABABR抗体相关脑炎及2例抗LGI1抗体相关脑炎患者可见颞叶及海马异常信号。脑电图检查：10例患者存在异常,重度异常者2例,中度异常者2例。治疗转归：所有患者均予以糖皮质激素联合免疫球蛋白的一线治疗,12例患者出院时改良Rankin评分0～2分。结论 自身免疫性脑炎特征性临床表现较少,仍以癫痫发作、认知障碍、精神异常等表现为主,对于临床上有此表现的患者...     

副肿瘤性边缘叶脑炎的临床和影像学特征

目的 探讨副肿瘤性边缘叶脑炎(PLE)的临床和影像学特征。方法 报告2例PLE患者(分别合并侵袭性胸腺瘤及肺癌)的临床、实验室及影像学资料。结果 2例均有癫痫发作、记忆及定向降碍、明显精神异常。头颅MRI均表现为颞叶海马长T1、长T2信号。1例在急性期胸部正电子发射扫描(PET)表现为病灶部位放射性浓集。结论 临床表现及影像学检查是诊断PLE的重要手段。     

Validity and prognostic utility of clinical assessment scale for autoimmune encephalitis (CASE) score in children with autoimmune encephalitis

IntroductionThe clinical assessment scale for autoimmune encephalitis (CASE) is a recently developed and validated scale to rate the severity of autoimmune encephalitis (AE) in adults. But it is yet to be validated in pediatric AE cases.MethodsIn a prospective observational study, we determined the validity and prognostic utility of CASE in the pediatric population with a diagnosis of probable or definite AE. We also determined clinical, neuroimaging, or laboratory-based prognostic factors for favorable clinical outcomes at 3 months after presentation. We used weighted kappa statistics and the intra-class correlation coefficient of individual item scores and total scores for determining inter-observer and intra-observer reliability respectively.ResultsWe enrolled a total of 54 patients (28 girls, probable [45%] or definite [55%] AE). Functional status score (FSS), CASE score, and other scores showed significant improvement at the time of discharge and 3-months, as compared to baseline (p < 0.0001). The intra-observer and interobserver reliability of the total scores was excellent (k = 0.94 and 0.95 respectively). CASE was also found to have good internal consistency (Cronbach-α = 0.83). The corrected item-total correlations of all items were >0.40. The correlation between the total CASE score and FSS score at admission, at discharge, and at 3 months was strong (r = 0.90, 0.92, and 0.94, p < 0.001). In multivariate analysis, only seropositivity or definite AE and CASE score at baseline was found to be significant predictive factors for functional status at 3 months (p = 0.03, 0.01).ConclusionCASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up.     

Characterisation of a syndrome of autoimmune adult onset focal epilepsy and encephalitis

We report a series of patients with a clinical syndrome characterised by the explosive onset in adulthood of recurrent focal seizures of frontotemporal onset and features suggestive of autoimmune encephalitis. We propose that this presentation of “autoimmune adult onset focal epilepsy and encephalitis” is a recognisable clinical syndrome, and provide evidence it may be associated with heterogeneous immunological targets. Between 2008 and 2011 we encountered six patients with new-onset epilepsy in whom we suspected an autoimmune aetiology. We first characterised the clinical, electroencephalographic, cerebrospinal fluid (CSF), imaging, and pathological findings of this syndrome. We subsequently tested them for antibodies against both intracellular and neuronal cell surface antigens. All patients presented with recurrent seizures with focal frontotemporal onset, refractory to multiple anticonvulsants. Four had focal T2-weighted hyperintensities on MRI. CSF mononuclear cells were variably elevated with positive oligoclonal bands in four. Brain biopsy in one patient demonstrated perivascular lymphocytic infiltration. Two were treated with immunosuppression and went on to achieve complete seizure control and return to baseline cognition. Three of four patients who received only pulsed steroids or no treatment had ongoing frequent seizures, with two dying of sudden unexpected death in epilepsy. Subsequently, three had antibodies identified against neuronal cell surface antigens including N-methyl-d-aspartate receptor and leucine-rich glioma inactivated 1. We suggest that patients with such a presentation should be carefully evaluated for a suspected autoimmune aetiology targeting cell surface antigens and have a therapeutic trial of immunosuppression as this may improve their long-term outcome.     

伴有精神症状的自身免疫性脑炎的临床特点分析

目的 分析不同抗体类型自身免疫性脑炎患者精神症状的特点.方法 回顾性研究了自身免疫性脑炎患者的临床特点.对自免脑患者的精神症状进行分析.对象:2019年9月到2020年12月就诊于中国医科大学附属第一医院神经内科确诊为自身免疫性脑炎的患者.结果 抗体阳性为20例,临床表现中最常见的依次是抽搐发作、精神症状、意识障碍、记...     

N-methyl D-aspartate receptor encephalitis: A new addition to the spectrum of autoimmune encephalitis

A large proportion of “encephalitis” is caused by unknown agents. Of late, a new category of disorders, “autoimmune encephalitis,” has been described, which present with features similar to viral encephalitides. A well-delineated and common entity among this group is the recently described anti-NMDAR encephalitis (NMDARE). Although this entity was initially described in young women harboring ovarian teratomas, it is now characterised as well in children and men. Approximately 60% of the patients have an underlying tumor, usually an ovarian teratoma. In 40% of the patients, no cause can be found (idiopathic NMDARE). NMDARE typically presents with psychiatric features followed by altered level of consciousness, severe dysautonomia, hyperkinetic movement disorders, seizures and central hypoventilation. Orofacial dyskinesias resulting in lip and tongue mutilation are quite common. Seizures, are common and may be difficult to treat. The disease can be confirmed by serum and cerebrospinal fluid anti-NMDAR antibodies. Titers of these antibodies can also guide response to treatment. Tumor removal is necessary if identified, followed by immunological treatment. Intravenous methylprednisolone and immunoglobulins aim to suppress/modulate immune response while plasma exchange attempts to remove antibodies and other inflammatory cytokines. Rituximab and cyclophosphamide aim to suppress antibody production. Recovery is slow and often with neurological deficits if treatment is delayed. With many distinctive clinical features, a specific antibody that aids diagnosis, and early effective treatment with commonly available drugs leading to good outcomes, NMDARE is a diagnosis that should be considered early in any case of “unexplained encephalitis.”     

Clinical analysis of psychiatric symptoms of Japanese encephalitis during the convalescent Period: A single center study in Chongqing,China

BackgroundThis study aimed to analyze clinical and imaging features of children with severe Japanese encephalitis (JE), and to analyze causes and solutions for psychiatric symptoms of JE during the convalescent period.MethodsWe analyzed clinical information for 78 children with severe JE at the Department of Neurology, Department of Infection, and Department of Rehabilitation in our hospital during 2014–2016. Seventy-eight cases of severe JE were divided into patients with psychiatric symptoms and no psychiatric symptoms groups. We focused on analysis of the patients with psychiatric symptoms group.ResultsThe incidence of psychiatric symptoms during the convalescent period was 46.15% (36/78). Antipsychotic drugs can effectively control psychiatric symptoms and shorten duration of symptoms. Seventy-one patients underwent reexamination with a head MRI. Of these, 8 cases (8/36 = 22.22%) in patients with psychiatric symptoms group showed new lesions in the basal ganglia, insula, and hippocampus. During the 12-month follow-up, two cases showed reappearance of psychiatric symptoms that had been relieved previously.ConclusionThis study found that severe JE cases revealed a considerable proportion with psychiatric symptoms during the convalescent period.     

抗NMDA受体脑炎45例特点和临床转归分析

目的探讨本组抗NMDA受体脑炎患者的临床特点。方法收集北京丰台右安门医院和北京宣武医院神经内科2012年10月至2015年4月收治的45例抗NMDA受体脑炎患者的临床资料,分析病例特点,随访病情转归。结果本组的45例患者年龄为14~61岁,平均年龄32.2±13.24岁;男性27例,其中3例(11%)合并肿瘤。女性18例,其中5例(28%)合并卵巢畸胎瘤。23例(51%)出现前驱症状。本组45例临床症状表现为精神症状(91%)、癫痫发作(76%)、不自主运动(42%)、中枢性低通气(24%)、意识水平下降(47%)及自主神经功能障碍(40%)。脑脊液(CSF)常规、生化检查阳性率为89%,所有患者CSF抗NMDA受体抗体阳性。脑电图(EEG)多表现为双额、颞、中央导联为主的轻度(21%)至中度(59%)慢波。53%患者头颅CT平扫或MRI检查有异常表现,多见于额颞叶T2-Flair异常信号。所有患者均给予激素和丙种球蛋白治疗,6例患者接受环磷酰胺或吗替麦考酚治疗。除1例失访,44例患者预后良好(MRS评分0-2分)者占86%。结论抗NMDAR脑炎发病男性并不少见,肿瘤合并率低。以精神行为异常、癫痫发作、CSF抗NMDA受体抗体阳性为其主要临床特点。绝大部分患者EEG异常,并与病情严重程度相关。79%患者一线免疫治疗效果良好。8例合并肿瘤患者病情严重且预后不良,畸胎瘤摘除术不能完全预防该病发生,但能减轻病情严重程度。     

Autoimmune encephalitis: Recent updates and emerging challenges

The knowledge of immune dysregulation and autoimmunity in neurological disorders has expanded considerably in recent times. Recognition of clinical syndromes, reliable methods of diagnosis, and early targeted immunotherapy can lead to a favourable outcome in acute and subacute neurological disorders that may be associated with significant morbidity and mortality if left untreated. This review focuses on the rapidly expanding field of autoimmune encephalitis. We describe the differences between limbic encephalitis associated with antibodies targeting intracellular antigens, and neuronal surface antibody syndromes (NSAS) where the antigens are primarily receptors or synaptic proteins located on the neuronal cell surface. We chronologically highlight important developments in NSAS by focusing on voltage gated potassium channel complex-associated antibody mediated encephalitis, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, and anti-dopamine 2 receptor antibody-associated basal ganglia encephalitis. Contentious issues such as the complexities of using serum antibodies as biomarkers, the initiation of central nervous system autoimmunity, and possible pathogenic mechanisms of these antibodies will be reviewed. The therapeutic challenges that clinicians face such as the timing of therapy and the role of second-line therapy will be discussed, with crucial concepts highlighted in the form of clinical vignettes. Future directions will involve the identification of novel antigens and methods to establish their pathogenicity, as well as evaluation of the most efficacious therapeutic strategies in patients with established NSAS.