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自身免疫性脑炎是一组可能由某些自身抗体、活性细胞或者相关因子与中枢神经系统神经元表面的蛋白等相互作用而导致的疾病。该组疾病中各个疾病典型的临床表现分别与目前已知的某个特异性抗体相对应,病情通常与抗体水平相关,少数病例可能与某些潜在的肿瘤有关。目前已知的自身免疫性脑炎常见的有边缘叶脑炎(lim-bic encephalitis,LE)、莫万综合征(movan’s syndrome,MOS)、桥本脑病(Hashimoto’s encephalitis)以及抗NMDA受体脑炎等,广义的讲还包括免疫相关疾病的脑炎表现。疾病分类复杂,诊断主要依靠临床表现和有关特异性检查(免疫标记物、影像)等做出,本文将对目前这一组疾病的诊断和鉴别做一总结。     

抗N-甲基-D-天冬氨酸受体抗体脑炎的研究进展

自身免疫性脑炎指机体自身免疫系统针对中枢神经系统抗原产生的抗原抗体反应,从而引起中枢神经系统损伤的一类疾病。其病因可能是由于某些自身抗体、活性细胞或相关因子与中枢神经系统神经元表面的蛋白等相互作用。主要分为特异性抗原抗体相关性脑炎和非特异性抗原抗体相关性脑炎两类,其中非特异抗原抗体相关性脑炎（如急性播散性脑脊髓炎）临床较多见。     

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脑炎是神经内科常见急症之一。早期诊断并给予适当的治疗至关重要。自身免疫性脑炎(AE)泛指一大类由于免疫系统针对中枢神经系统抗原产生反应而导致的疾病,并且逐渐被认为是非感染因素所致可逆转性脑炎的重要原因。根据病因学及治疗方法,AE可大致分为特异性抗原(抗体)相关性AE以及非特异性抗原(或抗体)相关性AE。了解有关AE的知识,对发现新疾病及加深对现有中枢神经系统疾病免疫病理机制的理解有重要意义。     

副肿瘤性边缘叶脑炎

报道４例肺小细胞癌导致的副肿瘤性边缘叶脑炎，其中单纯型和复合型各２例。全组均有记忆障碍。ＷＡＩＳ测定，智商４８～７７。癫痫３例，抑郁状态及定向障碍２例。合并感觉性神经元病及感觉运动性神经元神经病各１例。免疫组化显示４例患者血清、脑脊液及尿液中存在特异性神经元抗核抗体（Ｈｕ抗体）。结合文献对副肿瘤性边缘叶脑炎的临床分类、病理特点、病因和发病机制进行了讨论。     

抗γ-氨基丁酸B型受体脑炎老年患者临床特点分析

目的回顾分析抗γ-氨基丁酸B型受体(GABABR)脑炎老年患者的病例资料,提高对该病的认识。方法回顾2014年12月至2015年12月在该院就诊的7例60岁以上抗GABABR脑炎患者的病例资料,总结临床特点、影像、电生理、实验室检查、治疗及预后。结果 7例抗GABABR脑炎患者多以抽搐起病,病程中可出现精神行为异常、记忆力下降等临床表现。6例脑脊液检查异常,白细胞或蛋白轻度升高。6例患者血清和脑脊液GABABR抗体均为阳性,1例患者仅血清GABABR抗体阳性。头部MRI多表现为海马、颞叶、丘脑异常信号,脑电图常提示部分性发作。1例患者合并肺癌。免疫治疗后多数患者预后好。结论当临床怀疑边缘叶脑炎时,需完善血和脑脊液相关免疫抗体检测、脑脊液常规检查、头部MRI、脑电图以明确诊断。以加强对抗GABABR脑炎的关注,尽早诊断及治疗有利于改善患者的预后。     

新疆阿勒泰山地蜱传脑炎疫源地调查北大核心CSCD

目的调查新疆阿勒泰山地蜱传脑炎疫源地特征,分离鉴定蜱传脑炎病毒。方法通过家畜体表捡法采集寄生蜱;利用间接免疫荧光法检测当地健康人群血清中蜱传脑炎病毒IgG抗体;通过将蜱研磨液接种实验小鼠进行病原动物分离;通过接种BHK-21细胞对蜱传脑炎病毒进行分离培养;利用RT-PCR方法对病毒E蛋白基因片段进行扩增和测序,通过序列分析明确病毒系统进化特征。结果新疆阿勒泰山地白哈巴地区分布有2种蜱,森林革蜱为优势种(55.6%),其次为边缘革蜱(44.4%);当地人群蜱传脑炎IgG抗体阳性率5.31%(6/113);通过动物试验和细胞分离培养,从森林革蜱中分离出一株森林脑炎病毒;对病毒E蛋白基因序列的系统进化分析表明,蜱传脑炎病毒阿勒泰分离株属于远东亚型。结论首次从病原学上证实新疆阿勒泰山地存在蜱传脑炎疫源地,媒介为森林革蜱,病毒流行株为远东亚型。     

新疆阿勒泰山地蜱传脑炎疫源地调查

目的 调查新疆阿勒泰山地蜱传脑炎疫源地特征,分离鉴定蜱传脑炎病毒。方法 通过家畜体表捡法采集寄生蜱;利用间接免疫荧光法检测当地健康人群血清中蜱传脑炎病毒IgG抗体;通过将蜱研磨液接种实验小鼠进行病原动物分离;通过接种BHK-21细胞对蜱传脑炎病毒进行分离培养;利用RT-PCR方法对病毒E蛋白基因片段进行扩增和测序,通过序列分析明确病毒系统进化特征。结果 新疆阿勒泰山地白哈巴地区分布有2种蜱,森林革蜱为优势种(55.6%),其次为边缘革蜱(44.4%);当地人群蜱传脑炎IgG抗体阳性率5.31%(6/113);通过动物试验和细胞分离培养,从森林革蜱中分离出一株森林脑炎病毒;对病毒E蛋白基因序列的系统进化分析表明,蜱传脑炎病毒阿勒泰分离株属于远东亚型。结论 首次从病原学上证实新疆阿勒泰山地存在蜱传脑炎疫源地,媒介为森林革蜱,病毒流行株为远东亚型。     

以非惊厥性癫痫持续状态为主要表现的抗Amphiphysin抗体相关自身免疫性脑炎一例报道并文献复习

自身免疫性脑炎类型较多,但抗Amphiphysin抗体相关自身免疫性脑炎在临床上少见。抗Amphiphysin抗体相关自身免疫性脑炎患者主要表现为癫痫发作、认知功能下降、精神异常等,但以非惊厥性癫痫持续状态为主要表现的患者较少。本文报道陕西省人民医院收治的1例以非惊厥性癫痫持续状态为主要表现的抗Amphiphysin抗体相关自身免疫性脑炎患者的诊疗经过,并进行相关文献复习,以加强临床医生对该病的认识。     

抗谷氨酸脱羧酶65抗体脑炎及相关自身免疫性多内分泌腺病综合征

抗谷氨酸脱羧酶65(GAD65)抗体脑炎是自身免疫性脑炎的一种亚型，常表现为僵人综合征、小脑性共济失调、颞叶癫痫等神经综合征，早期识别诊断并给予免疫治疗对于患者的预后有极大改善。目前对于抗GAD65抗体脑炎的诊断主要依赖于血清中检测出高滴度的GAD65抗体或脑脊液中GAD65抗体阳性，然而GAD65抗体与广泛的自身免疫性疾病相关，在非神经系统中可引起自身免疫疾病包括1型糖尿病和甲状腺炎等。因此，诊治抗GAD65抗体脑炎的过程中需要筛查潜在的内分泌腺体的变化，在多内分泌免疫环境下出现神经症状也需要考虑合并抗GAD65抗体脑炎的可能。     

乙型脑炎病毒抗体捕获ELISA检测方法的初步建立

目的 建立检测乙型脑炎病毒抗体的抗体捕获ELISA方法.方法 以乙型脑炎病毒E蛋白抗原表位E39特异的单克隆抗体包被ELISA板,吸附乙型脑炎减毒活疫苗株SA14-14-2病毒粒子,再以吸附的病毒粒子捕获乙型脑炎病毒抗体,建立抗体捕获ELISA方法:同时与以乙型脑炎病毒细胞培养上清包被的间接ELISA方法进行对比,并检测临床血清样品105份.结果 间接ELISA方法背景无法消除,1:10、1:100、1:1000各稀释度的阳性血清与阴性血清吸光度(A)值相近,A阳性血清/阴性血清分别为1.02、0.99、1.13,均<2.1.而抗体捕获ELISA方法1:10、1:100稀释度的A阳性血清/阴性血清分别为3.57、2.94,均>2.1;1:1000稀释度的A阳性血清/阴性血清为1.42,<2.1,表明血清稀释度为1:100时可以显著区别乙型脑炎病毒感染的阳性血清与阴性血清,明显消除间接ELISA方法中背景过高的问题.抗体捕获ELISA方法检测105份临床血清样品,A阳性血清/阴性血清为0.257～0.321(0.262±0.050),均<2.1,为乙型脑炎病毒抗体阴性血清.结论 初步建立了乙型脑炎病毒抗体捕获ELISA方法,该方法特异性较高,对于建立乙型脑炎病毒群的快速鉴别诊断方法具有重要意义.     

Limbic encephalitis. A misdiagnosed syndrome

Patients with limbic encephalitis (LE) display various disorders including anterograde amnesia, mood disturbances (irritability, agitation or pseudo-depressive symptoms) and epilepsy, often partial but sometimes generalized, and rapidely progressive course. On account of the variability of the initial symptoms, limbic encephalitis is clearly under-diagnosed and often misdiagnosed as viral encephalitis. From a pathophysiological point of view, two types of LE can be identified. First, LE associated with antibodies directed against an intracellular neuronal antigen. They correspond to the traditional paraneoplastic LE, and are characterized by a weak response to treatment even when the causal tumor is treated. Second, LE associated with antibodies directed against antigens present on cellular membranes. These LE can be paraneoplastic or idiopathic, and present a better response to immunological treatments.     

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由于人们对细胞表面抗原抗体相关脑炎的认识不足,延误诊治,对其预后造成不良影响。细胞表面抗原抗体相关脑炎的靶抗原,在突触传递、重塑和神经兴奋方面起着重要作用,包括N-甲基-D天冬氨酸(NMDA)受体、α-氨基-3-羟基-5-甲基-4-异恶唑基丙酸(AMPA)受体、γ-氨基丁酸B(GABAB)受体和其他自身抗原,如LGI1和Caspr2等。该类疾病主要涉及儿童和年轻人,病情较重,病程较长,可伴或不伴发肿瘤,早期治疗后预后较好,但存在复发趋势。文章旨在阐述该类疾病临床特征,诊断和治疗的新进展,以引起临床医生的关注。     

Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies

We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance/decreased viral dissemination, reduced disease progression, and less CNS damage.     

Anti-LGI1 Encephalitis Developing Immunoglobulin Responsive Orthostatic Hypotension after Remission

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody is associated with limbic encephalitis. We herein report a patient with anti-LGI1 encephalitis who developed severe orthostatic hypotension (OH) responsive to immunoglobulin therapy five years after developing symptoms of encephalitis. A 71-year-old man presented with amnesia caused by limbic encephalitis. The symptoms of encephalitis improved partially without any immunotherapy. Five years later, he developed severe OH, and anti-LGI1 antibody was positive. The catecholamine dynamics indicated that the central autonomic nervous system was the lesion of his OH. Intravenous immunoglobulin therapy improved the OH. This case suggests that anti-LGI1 antibody can be associated with severe OH.     

Paraneoplastic limbic encephalitis and lung cancer

Paraneoplastic limbic encephalitis (PLE) is a disorder characterized by severe cognitive dysfunction and seizures. It is usually associated with small cell lung carcinoma. Diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer. Serological detection of antineuronal antibodies can be useful. We describe a patient with symptoms of limbic encephalitis, negative for paraneoplastic antibodies, in whom lung cancer was detected.     

Paraneoplastic limbic encephalitis--case report and review of literature

We report a 77-year old man who presented with a sub-acute dementia associated with aggressive behaviour, ataxia, rapid progression and death. No cause for his illness could be detected in his lifetime, but at post mortem he was found to have paraneoplastic limbic encephalitis and a bronchogenic tumour. A diagnosis of paraneoplastic limbic encephalitis should be considered in the differential diagnosis of unexplained dementias and appropriate investigations performed to diagnose the condition.     

Anti-Ma2 antibody encephalitis associated with Sjogren's syndrome

IntroductionOnconeuronal antibodies directed against intracellular antigens are strongly associated with paraneoplastic syndromes and their detection in the absence of cancer is unusual. We herein report a case of anti-Ma2 encephalitis associated with Sjogren's syndrome (SS).Case reportAn 81-year-old woman followed for a cutaneous lupus with vasculitis associated with SS presented a flare of her disease with neurological worsening including walking difficulty, hypersialorrhea and dysphagia. A paraneoplastic origin of the symptoms was suspected and anti-Ma2 antibodies were positive in serum. The search for an underlying neoplasia was negative. The diagnosis of anti-Ma2 encephalitis secondary to a SS was made. In the literature, the association of anti-Ma2 encephalitis and SS has been previously reported twice. Cases of patients with other onconeuronal antibodies associated with SS have been also reported. Anti-Ma2 encephalitis is a rare condition with a wide spectrum of symptoms associated with a cancer in more than 90% of the cases. Anti-Ma2 encephalitis has also been described after the use of immune check points inhibitors underscoring the role of autoimmunity in its pathogenesis.ConclusionAnti-Ma2 encephalitis is essentially associated with neoplasia but can occur in Sjogren's syndrome.     

Paraneoplastic neurological syndromes

Paraneoplastic neurological syndromes (PNS) are uncommon and defined by an acute or subacute neurological syndrome associated with a cancer. These syndromes often antedate the diagnostis of the underlying neoplasia that is usually not clinically evident. An early diagnosis is the main condition for a better neurological and carcinologic outcome. Subacute cerebellar ataxia, subacute sensitive neuropathy, limbic encephalomyelitis, Lambert-Eaton myasthenic syndrome, opsoclonus myoclonus, dermatopolymyositis and intestinal pseudo-obstruction belong to the well-characterized PNS and their presence must lead to onconeuronal antibodies (ONA) detection. Treatment of the underlying neoplasia is the mainstay of treatment to obtain a better outcome. However, recent findings lead to consider immunological specific treatment according to the subtype of associated ONA. PNS associated with ONA targeting membrane antigens are thus usually responsive to immunomodulator therapies. Conversely, PNS associated with ONA targeting intracellular antigens are of poor outcome despite mild improvement under immunosuppressive therapies in some patients.