抗N-甲基-D-天冬氨酸受体脑炎:一种新型自身免疫性脑炎

抗-N-甲基-D天冬氨酸受体(NMDAR)脑炎是目前较受关注的自身免疫性脑炎,可伴或不伴卵巢畸胎瘤。临床表现包括显著前驱高热、精神症状、癫发作、意识障碍、口手运动障碍及自主神经功能障碍等;脑脊液和血清抗NMDAR抗体检测呈阳性反应,脑电图呈特异性"δ刷"表现。早期施行肿瘤切除和免疫抑制剂治疗有效。本文拟就抗NMDAR脑炎发病机制、临床表现、辅助检查等研究进展进行概述。     

抗 N-甲基- D-天冬氨酸受体脑炎运动障碍的研究进展

抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是由NMDAR抗体介导的中枢神经系统自身免疫性疾病。运动障碍是抗NMDAR脑炎的临床特征之一, 包括口面部不自主运动、肢体刻板运动等多种形式, 对疾病的诊断具有指示作用, 但目前临床上对此症状的认识及重视仍不足, 且缺乏针对运动障碍的具体治疗策略。本文现围绕抗NMDAR脑炎运动障碍的临床特点及治疗措施等方面的研究进展进行综述, 以期提高临床医生对此症状的识别能力及治疗水平。     

抗N-甲基-D-门冬氨酸受体脑炎

抗N-甲基-D-门冬氨酸受体脑炎(anti-N-methyl-D-aspartate-receptor encephalitis),即抗NMDAR脑炎,是一种抗体介导的脑炎,其发病机制与NMDAR抗体有关,常伴有卵巢畸胎瘤的发生,临床症状十分复杂,病情严重,甚至可危及生命,但是通过积极的治疗,大部分患者可以治愈[1-4].抗NMDAR脑炎最早发现于卵巢畸胎瘤相关性边缘性脑炎(ovarian teratoma-associated limbic encephalitis,OTLE)患者.早在1992年,Sebire等首先报道了该病的临床特征,1997年日本报道了2例OTLE,对其临床表现进行了详细描述,但是对该病的发病机制尚不明确.2005年Dalmau和他的研究团队首次在OTLE患者脑组织中发现了一种新的神经元细胞膜抗原抗体,2年后,他们又鉴定了NMDAR的NR1/NR2B异聚体,揭示了OTLE的发生与NMDAR抗体有关[5-7].     

卵巢畸胎瘤合并抗N-甲基-D-天冬氨酸受体脑炎的临床特点分析

目的探讨卵巢畸胎瘤合并抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者的临床特点、治疗及预后。方法回顾性分析2013年2月至2018年2月诊断为抗NMDAR脑炎且合并或无合并卵巢畸胎瘤的35例女性患者的临床资料。随访其预后,通过改良Rankin量表(mRS)评估患者不同阶段的神经功能情况。结果合并畸胎瘤的抗NMDAR脑炎患者病毒感染样前驱症状及脑脊液淋巴细胞反应比例较低,脑脊液抗NMDAR抗体强阳性比例较高(3+～4+)。伴有畸胎瘤患者中复杂部分性癫发作常见,1例出现非惊厥性癫持续状态。所有患者均接受免疫治疗。其中伴有卵巢畸胎瘤的抗NMDAR脑炎患者入院时的平均mRS评分、需要一线及二线免疫治疗联合控制的比例、首次出院后第1和18个月以及末次随访的mRS评分均低于无合并畸胎瘤的抗NMDAR脑炎患者,且术后抗NMDAR脑炎的复发率更低。结论是否合并畸胎瘤对脑脊液抗NMDAR滴度及细胞学检测结果有所影响,提示可能存在不同的发病机制;合并卵巢畸胎瘤的抗NMDAR脑炎患者多数症状较轻,及时手术切除畸胎瘤有助于改善预后并防止复发。     

抗NMDAR脑炎并发隐球菌性脑膜炎一例

抗N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎是由NMDAR抗体介导的自身免疫性脑炎,常以发热、头痛为前驱症状,主要表现为精神行为异常、癫痫发作、意识水平下降或昏迷。隐球菌性脑膜炎是中枢神经系统常见的真菌感染,其在免疫功能低下时易发病,常以发热、头痛、呕吐为首发症状。抗NMDAR脑炎并发隐球菌性脑膜炎目前尚未见相关报道,本文对作者医院收治的1例抗NMDAR脑炎并发隐球菌性脑膜炎病例进行报道。1病例报告患者女,60岁,因“头痛6个月,头痛加重伴有精神行为异常1个月”于2018-08-08入作者医院。     

抗谷氨酸脱羧酶(GAD65)抗体相关脑炎1例报告并文献复习

<正>自身免疫性脑炎(autoimmune encephalitis,AE)~([1])泛指一大类由于免疫系统对中枢神经系统抗原产生抗原抗体反应而导致的疾病,以急性或亚急性发病的认知障碍、精神症状及癫痫发作等为主要临床特点。自2007年抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎被发现以来~([2]),陆续发现了抗神经元细胞表面或突触蛋白的自身抗体,目前以抗NMDAR脑炎最常见,约占AE的80%,其次为抗富含亮氨酸胶质瘤失     

抗N-甲基-D-天冬氨酸受体脑炎临床分析及血清抗体动态观察

目的研究抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点及其血清抗NMDAR抗体动态变化情况。方法分析2013年1月至2017年3月期间我院收治的54例抗NMDAR脑炎患者的临床表现[以改良Rankin量表(mRS)评估病情严重程度]、脑脊液及血清的抗NMDAR抗体滴度,头颅影像学特点,治疗方案及复发情况。并于患者出院后随访观察血清抗NMDAR抗体滴度变化情况,随访时间为出院半年、1年、2年,如复发则立即检测抗体滴度,随访截至2017年12月底。结果本组抗NMDAR脑炎患者女性平均发病年龄低于男性[(21.5±17.4)岁比(34.6±18.4)岁,P=0.01],且疾病严重程度女性重于男性[中位mRS评分分别为女性4(1,5)分,男性2.5(1,5)分,P=0.002)]。患者疾病严重程度与血清及脑脊液中抗体滴度呈显著正相关(血清:r=0.458,P=0.004;脑脊液:r=0.387,P=0.020)。抗NMDAR脑炎复发患者12例(22.2%),复发症状大多轻于首次发病[mRS 3.5(1,5)分比1(1,3)分,P=0.002]。54例患者中31例患者成功进行了血清抗NMDAR抗体随访,复发组抗体滴度上升患者比例大于未复发组(66.67%比10.53%,P=0.002)。结论本组抗NMDAR脑炎患者女性与男性比较,发病年龄偏低,疾病严重程度偏重;抗NMDAR脑炎存在复发表现,复发症状大多症状较轻。血清抗NMDAR抗体滴度在复发组中更容易出现上升表现。     

复发性抗N-甲基-D-天冬氨酸受体脑炎研究进展

复发性抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是近年来报道越来越多的一种自身免疫性脑炎,其影像学表现和临床表现多种多样,并伴脑脊液中抗NMDAR抗体再次升高,伴或不伴有抗NMDAR脑炎特征性的影像学表现。研究表明,不适当的治疗可导致复发性抗NMDAR脑炎的再次发生或多次复发,免疫抑制剂的应用可降低该病的复发率。本文对复发性抗NMDAR脑炎的病因、临床表现、实验室检查、治疗等研究进展做一综述。     

抗N-甲基-D-天冬氨酸受体脑炎合并卵巢畸胎瘤3例分析

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎合并卵巢畸胎瘤的流行病学、发病机制、临床表现、辅助检查、治疗及预后,以提高对该类型脑炎合并畸胎瘤患者的认识。方法回顾性分析郑州大学人民医院收治的3例抗NMDAR脑炎合并卵巢畸胎瘤患者的临床特点。结果 3例患者均有前驱症状,且临床过程中均出现精神行为异常、癫痫发作、低通气、不自主运动及自主神经系统功能异常。2例出现记忆力下降,另外1例正常。3例均接受畸胎瘤切除手术,术后病理均提示成熟型畸胎瘤。3例血清及脑脊液抗NMDAR抗体均呈阳性,随访3~12个月,1例遗留记忆力减退及反应迟钝,2例完全恢复正常,3例均未出现症状及肿瘤复发。结论合并畸胎瘤的抗NMDAR脑炎患者,早期给予畸胎瘤切除术并联合免疫治疗,预后良好。     

抗N-甲基-D-天冬氨酸受体脑炎精神症状特点

目的分析抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎精神症状特点,以帮助早期识别该疾病。方法回顾11例抗NMDAR脑炎患者临床资料,采用神经精神症状问卷(neuropsychiatric inventory,NPI)及精神检查评估患者精神症状出现时间及特点。结果 11例抗NMDAR脑炎患者精神症状NPI评分症状呈现多样性,得分中位数(下四分位数,上四分位数)为63(41, 66)分。精神症状主要表现为激越冲动、情感异常、幻觉妄想、紧张症及感觉异常、现实解体、失眠等。在发病后的第1周,感觉异常、失眠等最常见(10例),其次是情感异常(8例),以及幻觉妄想(4例),激越冲动在第2～3周最多见(8例),紧张症第2周出现最多(3例),所有精神症状均可在第1～3周出现。所有患者在发病第1周即伴随言语异常、谵妄、抽搐、自主神经功能异常等多种神经症状。结论抗NMDA受体脑炎的精神症状出现时间早、症状表现丰富,早期即伴随神经症状。     

"Neuro-sweet disease": benign recurrent encephalitis with neutrophilic dermatosis.

OBJECTIVE: To describe benign recurrent encephalitis in a case of Sweet syndrome that also showed clinical features of Beh?et disease. CASE REPORT: A 37-year-old Japanese man developed relapsing and remitting encephalitis and mucocutaneous symptoms mimicking Beh?et disease. Magnetic resonance images showed at least 5 episodes of transient abnormal signal intensity in various cerebral regions over a period of 5 years. A skin biopsy specimen of the cutaneous edematous erythematous plaques revealed neutrophilic dermatitis compatible with Sweet syndrome. HLA typing showed B54, which is frequent in Sweet syndrome but rare in Beh?et disease. Oral prednisolone therapy (10-60 mg/d) was remarkably effective for the encephalitis as well as for the mucocutaneous symptoms. CONCLUSION: We propose that there is an entity that is like Sweet disease, but with recurrent encephalitis characterized by an association with HLA-B54 and a high responsiveness to corticosteroid therapy, which we have tentatively named neuro-Sweet disease, that is distinct from the classic central nervous system involvement of Beh?et disease.     

感染后脑炎(附26例报告)

目的根据最新版国际疾病分类神经学分册(ICD-NA),感染后脑炎是一个独立的疾病,本文报告26例.方法采用美国国家和地区流行病学家委员会(CSTE)和疾病控制和预防中心(CDC)制定的统一标准,对我院近5年收治的符合CSTE和CDC诊断标准的感染后脑炎进行分析.结果该组感染后脑炎病例均有前驱感染史,以精神异常、意识障碍为主要临床表现,激素治疗有效.结论根据本文资料,感染后脑炎在我国作为独立疾病存在,约占脑炎病人的10%.     

Bilateral Rasmussen encephalitis: postmortem documentation in a five-year-old

A case of Rasmussen encephalitis with bilateral involvement and onset at age 2 years is reviewed. Rasmussen encephalitis is a rare progressive disease that causes intractable seizures, cognitive decline, and inflammatory changes in the brain. The neurologic involvement is characteristically unilateral. Bilateral involvement in this case was suspected within 5 months of presentation and was confirmed by bilateral frontal lobe biopsies. The severity and progression of the disease in this case was remarkable and resulted in the patient's death by age 5 years, despite numerous attempted therapeutic interventions. Autopsy findings confirmed the diagnosis of Rasmussen encephalitis with bilateral involvement.     

Morphological demonstration of the virus of tick-borne encephalitis in the human brain

Summary A case is presented in which the fourfold increase of the HI titer during the progression of the disease, and an increase in IgM content found at the beginning of the second week of the disease confirmed the diagnosis of tick-borne encephalitis. The light microscopic changes corresponded to the findings accepted as characteristic to tick-borne encephalitis.Viruses, morphologically belonging to the Havivirus genus, were found by electron microscopy in the thalamus, substantia nigra, and cerebellum of the dissected brain. This paper presents the first demonstration of the virus in a case of human tick-borne encephalitis.     

Hashimoto''s encephalitis and sleep disorders

Hashimoto's encephalitis is a rare cause of encephalitis which is improved by corticosteroid treatment. We report the case of a 42-year-old woman who developed progressive dementia associated with episodes of recurrent discorders of consciousness which rapidly improved with corticosteroids. During these episodes, no sleep activity was recorded on the holter EEG. These discorders were reversible with treatment and a normal EEG sleep pattern reappeared. At physical examination, Hashimoto's encephalitis can mimic Creutzfeld-Jakob disease. Systematic sleep-EEG recordings can be helpful for diagnosis of sleep disorders related Hashimoto's encephalitis. This case illustrates the importance of searching for antithyroid antibodies in patients with unexplained encephalitis.     

Postinfectious encephalitis in two siblings

A 33-year-old man and his 32-year-old sister developed, with an interval of 2 years, an acute fatal encephalitis following an upper respiratory tract infection of unknown etiology. Autopsy documented postinfectious encephalitis in both.

This is the first report of postinfectious encephalitis occurring in first degree relatives, suggesting that specific genetic factors play a role in the pathogenesis of this disease.     

Autoimmune-mediated encephalitis and mimics: A neuroimaging review

Autoimmune encephalitis is a category of autoantibody-mediated neurological disorders that often presents a diagnostic challenge due to its variable clinical and imaging findings. The purpose of this image-based review is to provide an overview of the major subtypes of autoimmune encephalitis and their associated autoantibodies, discuss their characteristic clinical and imaging features, and highlight several disease processes that may mimic imaging findings of autoimmune encephalitis. A literature search on autoimmune encephalitis was performed and publications from neuroradiology, neurology, and nuclear medicine literature were included. Cases from our institutional database that best exemplify major imaging features were presented.     

Relapsing meningitis and confusion: limbic encephalitis revealing Hodgkin's disease

Introduction

An observation of limbic encephalitis associated with Hodgkin’s disease is compared with rare cases of the literature. The clinical presentation was relapsing episodes of febrile cognitive disorders with confusion and meningitis, curable after treatment of Hodgkin’s disease. Recent concepts on limbic encephalitis are discussed.

Case report

A seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin’s disease. The treatment of Hodgkin’s disease led to perfect recovery of cognitive function, so that the patient could drive his car.

Conclusion

Lymphoproliferative disease, such as Hodgkin’s disease, is a possible diagnosis in patients with limbic encephalitis. A dysimmune process underlying Hodgkin’s disease might be operating in this association.     

Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain

Aims: Microglia are involved in neurodegeneration, are prime targets for anti-inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti-TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO-positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti-inflammatory pharmacological target.     

Progressive supranuclear palsy: New disease or variant of postencephalitic parkinsonism?

We review the etiological importance of the epidemic encephalitis for progressive supranuclear palsy (PSP) and addresses the question of whether the explosion of PSP literature in the mid-20th century reflects the appearance of a new disease. We examined 2,000 studies on Parkinson's disease from 1861 to 1963 and found PSP-like cases in the past, before the epidemic encephalitis era. It can be assumed that PSP is neither a new disease nor a variant of postencephalitic parkinsonism.