Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases: A case report

lNTRODUCTlON

In several individuals, anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe) may occur with myelin oligodendrocyte glycoprotein (MOG) antibody disease sequentially or simultaneously[1-3].However, there have been few reports of recurrent anti-NMDARe with MOG antibody disease overlap syndrome worldwide. We present a case of a young man initially admitted with headache, fever,behavioral abnormalities and intellectual decline, followed by hoarseness, blurred vision, disturbance of consciousness as well as seizures. Magnetic resonance imaging (MRI) involved multiple regions (,the parietal lobe, frontal lobe, midbrain, thalamus, cerebellum and medulla oblongata). From this case,we recommend the simultaneous detection of viruses, autoimmune encephalitis-associated antibodies and central nervous system demyelination-associated antibodies for patients suspected of having central nervous system demyelinating disease or anti-NMDARe. The aim is to increase the understanding of autoimmune encephalitis overlap syndrome as their clinical and prognostic features may differ from those of single-antibody disease.

CASE PRESENTATlON

Chief complaints

A 29-year-old man presented to the Neurology Department of our hospital complaining of headache,fever, intermittent abnormal behavior, decreased intelligence, limb twitching and loss of consciousness.During his presentation, he experienced aggravated symptoms.

The patient was admitted to the hospital for the second time for abnormal mental behavior and increased limb movements.

The patient was admitted for hoarseness and double vision for the third time. During his presentation, the patient’s visual acuity further decreased.

History of present illness

The patient began to experience symptoms of headache, fever, nausea and vomiting 7 d before admission. He experienced limb weakness, intermittent behavioral abnormalities and decreased intelligence 4 d before admission. He experienced limb twitching and loss of consciousness 2 d before admission.

History of past illness

The daughter of the uncle in the family suffered from lupus erythematosus.

Personal and family history

The patient had a history of previous surgery for otitis media.

Physical examination

First admission: Clear consciousness, poor orientation to time, place and personality, poor numeracy and unremarkable physical examination.

Second admission: Intermittent clear consciousness, uncooperative rest of nervous system.

Third admission: Horizontal movement of the eyeball was limited, nystagmus to the left in left vision,nystagmus to the right in right vision, vertical nystagmus in upper and lower visions, decreased lateral acupuncture sensation in bilateral face, weak closure of left eyelid, less sensitive corneal reflex, left central facial paralysis, less powerful elevation of right soft palate, left deviation of uvula, left muscle strength grade 4, less stable finger and nose, decreased tendon reflexes in four extremities and positive Babinski sign on the left side were identified.

这条道路的坚持彰显了卓越的世界意义。社会主义革命的胜利和社会主义建设，无疑是通过民族国家的形式得以实现，但社会主义事业的实现或者完成，则需要“全人类”的共同参与。如果不能超越资本主义发展道路的世界性、文明性，仅仅偏安于一隅之地，那么，所谓的社会主义也仅仅徒有虚名而已。因此，“道路自信”作为中国特色社会主义“文明自信”的实践写照，承担着学习世界一切优秀成果、面向世界、走向世界、引领世界，并将自身“成为世界”的文明使命和文明担当意义。

使用SPSS17.0软件处理数据资料,计数数据对比采用x2检验,计量数据对比采用t检验,P<0.05有统计学意义。

Laboratory examinations

First admission: Mycobacterium tuberculosis antibody detection reported no abnormality.Cerebrospinal fluid examination revealed: white blood cells 40 × 10/L; total protein 0.4 g/L; glucose 3.12 mol/L; and chloride 126.9 mmol/L. External examination of cerebrospinal fluid and serum results revealed: serum NMDAR antibody (Ab) (-); cerebrospinal fluid NMDAR-Ab (+) 1:10; cerebrospinal fluid herpes simplex virus antibody (HSVI, II IgG, IgM) (-); rubella virus antibody (RVIgG, IgM) (-); cytomegalovirus (CMVIgG, IgM) (-); Epstein-Barr virus (EBV) early antigen antibody IgG, IgM, IgA (-); EBV virus capsid antigen antibody IgM, IgA (-); and EBV virus capsid antigen antibody IgG (+).

Second admission: The results of autoimmune encephalitis antibody were serum NMDAR-Ab weakly positive and cerebrospinal fluid NMDAR-Ab positive.

Third admission: Serum anti-MOG (+) 1:10 and NMDAR antibody (+) 1:10 were examined.

Imaging examinations

First admission: Head MRI, chest X-ray and electroencephalography were normal. Re-examination of cranial MRI showed punctate abnormal signals in the left parietal lobe (Figure 1A).

Second admission: Examination of electroencephalography and cranial MRI showed no abnormality(Figure 1B).

Third admission: Examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe (Figure 1C), and synoptophore examination indicated concomitant esotropia. In such a period, the re-examination of cranial MRI + enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata, left pons arm, left cerebellum and right midbrain(Figure 1D-F).

例如“衣二三”，只需月付499元，就可以随心换穿全球数百万件时装，而且包邮。“我太喜欢租赁这个想法了，因为我不认为中国的再利用系统已经十分发达，使用租赁软件的用户至少会使用租来的东西。”紧跟租赁潮流的北京年轻女孩微微（音）对埃菲社记者说。她认为，这款应用不仅可以让人每天换穿新衣，而且是“可持续”的方式，不仅环保，也让中产阶级节省了资金。“以前人们用这个应用来试穿买不起的名牌衣服，但现在各种时装都被包括在内，人们寻求的是用最低的成本穿出多样性，”微微补充说，“去购买一年只穿一两次的衣服没有意义。”

MULTlDlSClPLlNARY EXPERT CONSULTATlON

盖尔达耶的居民在对沙漠中的光与热进行顽强抗争的过程中，通过一代代人的思维的积淀，不断地完善聚落的规划理念和民居的建造特色，通过低技策略，将民居打造为适应极端气候的可持续建筑，并影响了很多知名建筑师的思想。聚落和民居特征的形成过程是居民为躲避极端恶劣气候的伤害自发性选择的结果，也是一种意识形态的显化表达，一种文化的积淀和传承。

祝国寺现在与社区的和谐、融入，甚至扩展到整个东川城区。素祥法师说，每年大年三十晚上，都有一两万人聚集到祝国寺，这已经成了当地的一种新的民俗。

FlNAL DlAGNOSlS

The final diagnosis of the presented case was MOG antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome.

TREATMENT

The patient underwent medical treatment with methylprednisolone and gamma globulin pulse therapy and olanzapine to improve sleep after the first admission. The patient was assessed to be tumor-free at the second admission and given standard gamma globulin and steroid pulse therapy with a steroid dose reduced to 75 mg, 1 tablet every 2 wk. At the same time, according to the consensus, immunosuppressive agents (mofetil) 1-2 mg/d, orally for at least 1 year and antiepileptic treatment with sodium valproate and olanzapine increased to 2 mg/time to control psychiatric symptoms was prescribed. At the last admission, the patient was successfully treated with methylprednisolone, gamma globulin pulse therapy and rituximab treatment.

中频逆变电阻焊机在诸如汽车制造中不可或缺。基于MCGS的上位机监控系统和焊机控制器密切配合，组成了一套完整的控制系统，实现了焊接过程中数据的可视化与实时化。因此该监控系统对于焊机工业的应用，起到了不小程度上的提升。

坚持问题导向，聚焦区级馆服务能力不强、区域内公共文化资源缺乏整合、城乡公共文化服务发展不均衡等突出问题，坚持政府主导、改革创新、强化基层、实事求是的原则，大力推进公共图书馆总分馆制建设，为更好地满足广大群众基本文化需求创造良好条件，提供有力保障。

OUTCOME AND FOLLOW-UP

Yin XJ, Bao LH and Li BX, were the patient’s physician, reviewed the literature and contributed to manuscript drafting; Feng ZC and Zhang J performed and analyzed the magnetic resonance imaging; Zhang LF and Chen JH were responsible for the revision of the manuscript for important intellectual content; All authors issued final approval for the version to be submitted.

DlSCUSSlON

The concept of anti-NMDARe was first introduced in 2007 by Dalmau[4]. MOG antibodies are related to demyelinating diseases of the central nervous system. Therefore, the concept of MOG antibody-related demyelinating diseases of the central nervous system (MOG antibody disease) was proposed[6,7]. Some patients suffering anti-NMDARe have positive serum MOG antibody, and some patients suffering MOG antibody have positive cerebrospinal fluid anti-NMDAR antibody, which is called MOG antibody disease with anti-NMDARe overlap syndrome (MNOS)[1,8,9]. In several individuals, anti-NMDARe may occur with MOG antibody disease sequentially or simultaneously[1-3].However, there have been rare reports of recurrent anti-NMDARe with MOG antibody disease overlap syndrome worldwide.

Lin Wang, MD, Chief Physician, Department of Neurology, Beijing Xuanwu Hospital. The patient confirmed the diagnosis of anti-NMDARe for first admission. The patient should undergo medical treatment with methylprednisolone and gamma globulin pulse therapy and olanzapine to improve sleep. In addition, this patient required regular re-examination of electroencephalography.

Encephalitis is a neurological disorder caused by diffuse or multiple inflammatory lesions of the brain parenchyma. Among them, autoimmune encephalitis generally refers to a type of encephalitis mediated by autoimmune mechanisms[10]. At present, the proportion of autoimmune encephalitis accounts for 10%-20% of encephalitis cases, of which anti-NMDARe is the most common, accounting for about 80%[11,12]. Autoimmune encephalitis should be differentiated from central nervous system infections caused by herpes simplex encephalitis, epidemic encephalitis B, neurosyphilis, bacteria, fungi, parasites,Creutzfeldt-Jakob disease and the presence or absence of opportunistic infectious diseases associated with immunosuppressive or anti-tumor agents[13,14].

We thank the patient for consenting to our reporting of this case.

Five months after improvement of treatment, the patient once again developed psychiatric symptoms and increased limb movements, and the cerebrospinal fluid NMDAR antibody (+) was 1:10. Given the definition of recurrent anti-NMDARe,new symptoms not able to be explained by other reasons or aggravation of original symptoms were identified 2 mo after the improvement of NMDARe treatment[2,10], the diagnosis of recurrent anti-NMDARe could be confirmed. Subsequently, the patient developed hoarseness and double vision, and the re-examination of cranial MRI + enhancement indicated new lesions. On the whole, anti-NMDARe was not related to optic nerve damage and sensory disturbance in clinical practice, and patients suffering demyelinating diseases of the central nervous system are considered to be combined with MRI and clinical manifestations. The detection of serum MOG antibody indicated MOG (+) 1:10, by complying with the diagnostic criteria of MOG antibody disease[18]. Then diagnosis of anti-NMDARe with MOG antibody disease overlap syndrome was confirmed.

Hongzhi Guan, MD, Professor and Chief, Department of Central Nervous System Infection, Beijing Xiehe Hospital. The patient confirmed the diagnosis of recurrent anti-NMDARe for second admission.The patient had psychiatric symptoms, language disorder, autonomic dysfunction and other symptoms in this attack, which were considered to be comprehensive recurrent type. First, the presence of tumors in the patient’s body was assessed, gamma globulin and hormone pulse therapy were standardized in those without tumors, and the hormone dose was reduced to 75 mg, 1 tablet every 2 wk. At the same time, according to the consensus, immunosuppressant (mofetil) 1-2 mg/d, orally for at least 1 year,antiepileptic treatment with sodium valproate and olanzapine increased to 2 mg/time to control psychiatric symptoms.

Characteristics of this case include: (1) Etiology: it has been reported in the literature that anti-NMDARe is related to tumors, but the incidence of tumors detected in patients suffering MNOS is small, and the prognosis is good[2,10,19]. The present patient agreed with previous literature reports in which no tumor was detected during a 2-year course; (2) Affected population: MOG antibody disease and anti-NMDARe are usually more common in women, and the incidence of MNOS in children is higher than that in adults[1,5,9]. However, the patient in this case was an adult male, it was relatively rare; (3) Clinical manifestations: the clinical symptoms of recurrent anti-NMDARe are mild, overall manifested as a single symptom, which is mild when recurrent[10,20]. Nevertheless, this patient was inconsistent with existing literature reports, showing psychiatric symptoms, language impairment and autonomic dysfunction. At the time of recurrence, he displayed considerable clinical symptoms,comprehensive recurrent anti-NMDARe; (4) MRI findings: the cranial MRI of patients suffering anti-NMDARe may be unremarkable, or there may be only scattered cortical and subcortical dot-like abnormalities[4,20]. The first two episodes in this patient were consistent with the findings in previous reports. All patients suffering MNOS will have supratentorial lesions and less infratentorial lesions[1],but both supratentorial and infratentorial cranial MRI were involved in this patient; (5) Prognosis: the optic nerve injury and encephalitis of this patient recovered completely, thereby not complying with the findings of Titulaer[2], who found that patients suffering MNOS had a delayed recovery from demyelinating disease and a more pronounced residual deficit; and (6) Concomitant disease: At present,anti-NMDARe secondary to EBV-related viral encephalitis has not been reported worldwide, and psoriasis was reported by dermatoscopy during the 6-mo follow-up of the patient. Psoriasis[21] is an immune-mediated polygenic genodermatosis, which may be the result of a combination of genetic,environmental and immunological factors. To the best of the authors’ knowledge, there have been no reported related cases worldwide.

CONCLUSlON

In clinical practice, simultaneous detection of viruses, autoimmune encephalitis-related antibodies and central nervous system demyelination-related antibodies is recommended for patients suffering from suspected central nervous system demyelinating disease or anti-NMDARe. First, when the patient has a typical course of “bimodal symptoms,”the first peak has “fever, psycho-behavioral abnormalities,epilepsy” as the symptoms and the second peak has “psycho-behavioral abnormalities, memory loss,dyskinesia, autonomic dysfunction” as the primary symptoms to consider autoimmune encephalitis secondary to viral encephalitis. Second, when anti-NMDARe patients are identified to develop symptoms involving the optic nerve and spinal cord (, decreased visual acuity, limb motor or sensory impairment), the coexistence of MOG antibody disease should be considered. Third, when patients suffering MOG antibody disease develop encephalitis symptoms (, psycho-behavioral abnormalities or cognitive impairment) and novel lesions are seen on cranial MRI, anti-NMDARe coexistence should be considered.

路灯心跳的主要目的是保活应用层连接，属于非必须功能，尤其考虑通信按连接收取资费，客户可能会减少甚至取消心跳；因此路灯心跳时间Tm参数设计为可配变量，当前IoT平台设定的应用层老化时间一般为30min，建议设置为25min。如果心跳过于频繁，会对网络资源、用户资费造成浪费。

ACKNOWLEDGEMENTS

Cerebrospinal fluid antibodies were negative in the acute phase of the above infectious diseases[15].In this case, relevant examinations such as cerebrospinal fluid cytology, culture, virus, antibody, cranial MRI, electroencephalogram, tumor screening [tumor markers, chest computed tomography, scrotum,both kidneys, hepatobiliary b-ultrasound] and positron emission tomography-computed tomography were perfected for differential significance[9,16]. We report a young man who initially presented with headache, fever and epilepsy as the first symptoms, followed by behavioral abnormalities, intellectual decline, dyskinesia and decreased autonomic function in accordance with the course of “bimodal encephalitis” reported in the literature[17]. Combined with cerebrospinal fluid NMDAR antibody (+)1:10, EBV viral capsid antigen antibody IgG (+), negative tumor screening program and other examinations, it was considered to be anti-NMDARe secondary to non-tumor viral encephalitis. The disadvantage of this case is that metagenomic next-generation sequencing was not further refined to identify the presence of other bacterial or viral infections.

FOOTNOTES

The patient had an uneventful clinical course, whilst dexamethasone was decreased progressively until its cessation. At the follow-up visit 1 year after hospital discharge, the patient was asymptomatic. An MRI scan showed complete removal of the lesion. However, we observed scattered red rashes on both upper limbs and trunk. Since dermoscopy showed scattered red spots and plaque changes on the glans penis and ventral surface of the extremities and a few scales, the diagnosis of psoriasis was considered.Halometasone ointment was applied externally.

Health Commission of Shanxi Province Issued "Four Approval" Scientific and Technological Innovation Projects in 2020, No. 2020XM38.

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

依据《中华人民共和国监察法》等有关规定，经研究，决定将郝建华涉嫌犯罪问题移送人民检察院依法审查、提起公诉。

一是县世行项目办结合项目措施安排，聘请农业、林业、水利、水保部门的技术专家，在小流域内有针对性地对镇项目办人员、村干部和农户进行培训，让农户掌握相应技术，特别重视面向经果林示范农户的培训工作。二是通过县与项目镇签订责任状，将坡改梯工程的维护，经果林的除草、施肥、苗木管护责任落实到每个村组或个人。三是工程完工后，树立以治理措施名称、面积、管护者等信息为内容的管护责任标志牌，制定封山育林公约和经果林管护公约。四是转让治理成果，让有资金、管理经验的公司（大户）经营。

Xue-Jing Yin 0000-0002-4365-3699; Li-Fang Zhang 0000-0002-7925-2686; Li-Hua Bao 0000-0001-9509-3171; Zhi-Chao Feng 0000-0002-5547-3388; Jin-Hua Chen 0000-0002-0231-3786; Bing-Xia Li 0000-0001-6554-0284; Juan Zhang 0000-0002-3925-1507.

Liu JH

Filipodia

sprintf(pageName, "%s%d%s","/ata0a/rPage",fileNumber,".jpg");

Liu JH