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.

這條道路的堅持彰顯了卓越的世界意義。社會主義革命的勝利和社會主義建設，無疑是通過民族國家的形式得以實現，但社會主義事業的實現或者完成，則需要“全人類”的共同參與。如果不能超越資本主義發展道路的世界性、文明性，僅僅偏安于一隅之地，那么，所謂的社會主義也僅僅徒有虛名而已。因此，“道路自信”作為中國特色社會主義“文明自信”的實踐寫照，承擔著學習世界一切優秀成果、面向世界、走向世界、引領世界，并將自身“成為世界”的文明使命和文明擔當意義。

使用SPSS17.0軟件處理數據資料,計數數據對比采用x2檢驗,計量數據對比采用t檢驗,P<0.05有統計學意義。

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，就可以隨心換穿全球數百萬件時裝，而且包郵。“我太喜歡租賃這個想法了，因為我不認為中國的再利用系統已經十分發達，使用租賃軟件的用戶至少會使用租來的東西。”緊跟租賃潮流的北京年輕女孩微微（音）對埃菲社記者說。她認為，這款應用不僅可以讓人每天換穿新衣，而且是“可持續”的方式，不僅環保，也讓中產階級節省了資金。“以前人們用這個應用來試穿買不起的名牌衣服，但現在各種時裝都被包括在內，人們尋求的是用最低的成本穿出多樣性，”微微補充說，“去購買一年只穿一兩次的衣服沒有意義。”

MULTlDlSClPLlNARY EXPERT CONSULTATlON

蓋爾達耶的居民在對沙漠中的光與熱進行頑強抗爭的過程中，通過一代代人的思維的積淀，不斷地完善聚落的規劃理念和民居的建造特色，通過低技策略，將民居打造為適應極端氣候的可持續建筑，并影響了很多知名建筑師的思想。聚落和民居特征的形成過程是居民為躲避極端惡劣氣候的傷害自發性選擇的結果，也是一種意識形態的顯化表達，一種文化的積淀和傳承。

祝國寺現在與社區的和諧、融入，甚至擴展到整個東川城區。素祥法師說，每年大年三十晚上，都有一兩萬人聚集到祝國寺，這已經成了當地的一種新的民俗。

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.

中頻逆變電阻焊機在諸如汽車制造中不可或缺。基于MCGS的上位機監控系統和焊機控制器密切配合，組成了一套完整的控制系統，實現了焊接過程中數據的可視化與實時化。因此該監控系統對于焊機工業的應用，起到了不小程度上的提升。

堅持問題導向，聚焦區級館服務能力不強、區域內公共文化資源缺乏整合、城鄉公共文化服務發展不均衡等突出問題，堅持政府主導、改革創新、強化基層、實事求是的原則，大力推進公共圖書館總分館制建設，為更好地滿足廣大群眾基本文化需求創造良好條件，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.

路燈心跳的主要目的是保活應用層連接，屬于非必須功能，尤其考慮通信按連接收取資費，客戶可能會減少甚至取消心跳；因此路燈心跳時間Tm參數設計為可配變量，當前IoT平臺設定的應用層老化時間一般為30min，建議設置為25min。如果心跳過于頻繁，會對網絡資源、用戶資費造成浪費。

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

依據《中華人民共和國監察法》等有關規定，經研究，決定將郝建華涉嫌犯罪問題移送人民檢察院依法審查、提起公訴。

一是縣世行項目辦結合項目措施安排，聘請農業、林業、水利、水保部門的技術專家，在小流域內有針對性地對鎮項目辦人員、村干部和農戶進行培訓，讓農戶掌握相應技術，特別重視面向經果林示范農戶的培訓工作。二是通過縣與項目鎮簽訂責任狀，將坡改梯工程的維護，經果林的除草、施肥、苗木管護責任落實到每個村組或個人。三是工程完工后，樹立以治理措施名稱、面積、管護者等信息為內容的管護責任標志牌，制定封山育林公約和經果林管護公約。四是轉讓治理成果，讓有資金、管理經驗的公司（大戶）經營。

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

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