Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review

Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short report Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review Yi Xie, Jia Wen, Zhihua Zhao, Hongbo Liu, Nanchang Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-34130/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A 60-year-old man presented with slow response and psychosis. Apart from hyponatremia, serum test also showed positive anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1) and anti-γ-aminobutyric acid-beta-receptor (anti-GABA B R), and electroencephalogram exhibited moderate diffusion abnormality. The patient responded well to steroid treatment. Here we report the first autoimmune encephalitis(AE) characterized by positive anti-LGI1 and anti-GABA B R, as well as summarizing AE with multiple auto-antibodies reported so far, hopefully to provide experience for clinical practice. Neurobiology of Disease multiple auto-antibody autoimmune encephalitis anti-LGI1 anti-GABABR Figures Figure 1 Background There are basically two kinds of auto-antibodies related to autoimmune encephalitis(AE). One is against neuron surface receptor, among which anti- N-methyl-D-aspartic acid receptor (anti-NMDAR) is the most common, others also including anti-γ-aminobutyric acid-beta-receptor (anti-GABA B R), anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (anti-AMPAR), anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1), etc. The other kind is against neuronal intracellular antigen, mainly referring to classic paraneoplastic neurosis antibody, such as anti-Hu, etc [1-2] . Different types of auto-antibodies correspond to specific neurological syndrome, which has strong specificity or directivity for etiological diagnosis. The majority of AE patients have only one of the above auto-antibodies, and very few with multiple auto-antibodies. Herein we report a patient with positive anti-LGI1 and anti-GABA B R who improved greatly by steroid therapy. Case Presentation A 60-year-old Chinese male presented with one-month of slow response and abnormal behavior. He had typhia 40 years ago and left no sequel. Neurological exam revealed poor mental state, slow response and damaged memory, attention, calculation and orientation. Mini mental state examination score was 15. Cerebrospinal fluid (CSF) electrophoresis IgG index was 0.71 (reference 0.3~0.7). Intracranial pressure was 150mmH 2 O. CSF routine biochemistry for protein content and glucose were normal and infectious test for virus, tuberculosis and Cryptococcus were negative. CSF cytology and cytometry were negative for malignant cells. Brain MRI scan with contrast enhancement was normal. Chest enhanced CT scan revealed inflammation in left lower lobe. Serum procalcitonin was 0.048ng/mL (reference<0.046ng/mL), C reaction protein was 8.05mg/L (reference<5mg/L). Serum AE antibody spectrum demonstrated positive anti-LGI1 IgG and anti-GABA B R IgG, while CSF auto-antibody test was negative. Blood studies revealed sodium was 119mmol/L (reference 135~153mmol/mL) and chlorine was 81mmol/L (reference 90~110mmol/L) at first admission. Electroencephalogram (EEG) indicated moderate diffusion abnormality (Figure 1A and 1B). For treatment of AE with multiple co-existing antibody, he received 1g and 0.5g intravenous methylprednisolone separately, 3 days for each dosage, and then remained on an oral steroid taper for half year. After intravenous and oral sodium supplement, blood sodium and chlorine gradually increased to normal(Table 1). His mental state improved greatly and EEG recovered to normal. Table 1. Blood test for sodium and chlorine Date/time Blood sodium(mmol/L) Blood chlorine(mmol/L) 2020-04-21 11:00 119.0 81.0 2020-04-21 20:00 121.9 82.0 2020-04-22 124.0 85.0 2020-04-23 129.0 92.0 2020-04-24 135.0 93.0 2020-04-26 138.0 92.0 2020-04-29 134.0 91.0 2020-04-30 135.0 91.0 Discussion Co-existence of serum anti-LGI1 and anti-GABA B R in AE patient has not been previously reported. The 60-year-old patient, with subacute onset, mainly manifested cognitive decline, behavioral abnormality and hyponatremia. The serum anti-LGI1 and anti-GABA B R were double positive, and EEG indicated moderate diffusion abnormality. According to the patients' symptoms, AE auto-antibody spectrum test and EEG results, the patient was diagnosed as AE with double auto-antibody positive, ie, anti-LGI1 and anti-GABA B R. The patient responded well to glucocorticoid treatment, and we will continue to follow up the prognosis. Anti-LGI1 encephalitis, which is mostly found in elderly men with subacute onset, is related to hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion. Most patients demonstrated cognitive impairment, and about 90% of them have behavioral and/or personality changes. Frequent seizures, especially focal seizure, are seen in the majority of patients, while generalized tonic clonic seizures are not very common. Most patients have no related tumors, only about 10% had thymoma, while other tumors were rare. Up to 75% of cases have normal CSF routine analysis. EEG can show mild diffuse slow wave, and about half may have swelled medial temporal lobe with high T2/flair signal. The good news is the relatively low recurrence rate [3-4] . Anti-GABA B R encephalitis mostly presents limbic encephalitis symptoms, with temporal lobe epilepsy as the core symptomatology, and most of them are accompanied by cognitive function decline, personality change and mental behavior abnormality. About 50% of patients have small cell lung cancer or neuroendocrine tumor. It is suggested that anti-GABA B R encephalitis should further take chest CT or PET examination [5] . The overlying of neuronal auto-antibodies may cause the superposition of clinical syndrome, but not a simple complete superposition, which needs to be analyzed according to the specific antibody type and clinical manifestation. According to Professor Guan Hongzhi's newly published review, it is necessary to distinguish whether the antibodies in patients belong to pathogenic markers or concomitant antibodies [6] . The main manifestations of this case are psychobehavioral abnormality and hyponatremia, more similar to clinical manifestations of anti-LGI1 AE. The co-existence of multiple auto-antibody is rare(summarized in Table 2). Ren Haitao reported 531 cases of AE with auto-antibodies, and only 10 cases detected multiple anti-neuronal antibodies, among whom 5 cases were anti-GABA B R/anti-Hu(+), 1 anti-NMDAR/APQ-4(+), 1 anti-LGI1/anti-CASPR2(+), 1 anti-LGI1/anti-Yo(+), 1 anti-AMPAR/anti-CV2(+) and 1 anti-AMPAR/anti-Hu(+) [6] . In the 20 anti-GABA B R AE cases reported by Hoftberger, 7 detected multiple auto-antibodies, among whom 3 cases with anti-Sox1, 1 with anti-Ri, 1 with anti-amphiphysin, 1 with anti-GAD65 and 1 with anti-NMDAR [7] . Liu XY recently reported one case characterized by double positive of anti-LGI1 and anti-NMDAR [8] . Boronat reported a case of anti-GABA B R combined with anti-GAD65, menifestating cerebellar ataxia and thymoid carcinoid [9] . Qi Hengchang reported two cases of AE with multiple auto-antibodies against neuron (one was anti-NMDAR(+), anti-GABA B R(+), and the other anti-LGI1(+), anti CASPR2(+). Both patients were adult women with acute onset. Their first symptom was epilepsy, and the treatment effect was good [10] . The clinical significance of multiple auto-antibody has already raised attention of many neurologists and needs to be interpreted in combination with clinical practice. For example, anti-GABA B R can be combined with anti-Hu. When anti-GABA B R is positive, it is recommended to screen anti-Hu and carry out tumor screening at the same time, such as chest CT, tumor markers, etc., excluding the possibility of tumor as much as possible. In this case chest enhanced CT scan didn’t find tumor, but the patient was advised to take regular examination during follow-up. At present, many reports of anti-NMDAR combined with anti-MOG suggest that it is necessary to consider the clinical syndrome superposition caused by the antibody superposition, pay attention to the clinical process, and inquire in detail the history and imaging data whether there is a basis for demyelination [11] . Table 2 clinical data of AE cases with multiple auto-antibodies N. Sex, age AE auto-Abs Other Abs Clinical menifestation Brain MRI tumor prognosis serum CSF serum CSF 1 M,62 GABA B R GABA B R Hu - Memory loss, somnolence, conculsion, cough, hoarseness Normal Lung cancer Improve 2 M,61 GABA B R GABA B R Hu - Epilepsy, somnolence, memory loss Normal Lung cancer Improve 3 M,59 GABA B R GABA B R Hu Hu Epilepsy, psychosis Lesions of bilateral hippocampus Lung cancer Improve 4 M,58 GABA B R GABA B R Hu Hu Psychosis, memory loss, numbness of limbs Lesions of bilateral hippocampus Lung cancer Improve 5 M,61 GABA B R GABA B R NMDAR Hu - Epilepsy, memory loss, coma ND Lung cancer Improve 6 F,19 - NMDAR AQP4 AQP4 Psychosis, memory loss, blepharoptosis Lesions of bilateral basal ganglia, brainstem No Improve 7 F,40 LGI1 CASPR2 LGI1 - - Myalgia, fasciculation, epilepsy, insomnia Normal No Improve 8 F,56 LGI1 LGI1 Yo Yo Memory loss, conculsion, somnolence, polyphagia Normal No Improve 9 F,50 AMPAR AMPAR CV2 CV2 Memory loss, psychosis Normal Thymoma Improve 10 F,51 AMPAR AMPAR Hu - Psychosis, dysphagia, dysdipsia Lesions of bilateral cortex Mediastinal occupying Dead 11 M,44 ND GABA B R NMDAR - - Limbic encephalitis Not mentioned No Complete improve 12 F,63 - GABA B R GAD65 * Status epilepticus Not mentioned No Dead 13 M,60 GABA B R GABA B R SOX1 * Limbic encephalitis Not mentioned SCLC Partial recovery 14 M,62 GABA B R GABA B R Ri * Limbic encephalitis Not mentioned SCLC - 15 F,68 GABA B R GABA B R SOX1 * Limbic encephalitis Not mentioned SCLC Partial recovery 16 M,74 GABA B R ND SOX1 ND Limbic encephalitis Not mentioned SCLC Dead 17 M,77 GABA B R GABA B R Amphiphysin * Limbic encephalitis Not mentioned SCLC Unresponsive 18 F,57 LGI1 NMDAR - - - Faciobrachial dystonic seizure, hyponatremia, mental disorder - No Improve 19 M,66 GABA B R * GAD * Seizures, confusion Normal SCLC Not available 20 M,47 GABA B R * SOX1 * VGKC Seizures, behavior change, memory impairment Bilateral temporal lesions SCLC Partial recovery 21 M,70 GABA B R * GAD * SOX1 Seizures, memory impairment, confusion Normal SCLC Unresponsive, dead 22 M,58 GABA B R * Hu * Seizures, memory impairment Bilateral temporal lesions SCLC Unresponsive, dead 23 M,61 GABA B R * BRSK2 * Memory impairment Bilateral temporal lesions SCLC Unresponsive 24 F,57 GABA B R * GAD * Subacute cerebellar ataxia Normal Carcinoid of thymus Complete recovery 25 F,30 NMDAR GABA B R NMDAR - - Epilepsy, psychosis, insomnia Normal No Improve 26 F,43 LGI1 CASPR2 CASPR2 - - Seizures, weight loss, calculation/ memory/speech disorder Bilateral hippocampus/ occipital/parietal lesions No Improve Declarations 1. Ethics approval and consent to participate Protocols were established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics committee of first hospital of Zhengzhou University. Written informed consent was obtained from individual participant. 2. Consent for publication Written informed consent was obtained from the patient for publication of this case report and companying images. 3. Availability of data and materials All data generated or analyzed during this study are included in this published article. 4. Competing Interests The authors declare that they have no competing interests. 5. Funding This study was funded by the the Joint Construction Project of Henan Province (No. 2018020114 and No. 2018020083) and National Natural Science Foundation of China(81971214). 7. Acknowledgements Not applicable. Conclusions Here we first report a case of AE with co-existing auto-antibodies anti-LGI1 and anti-GABA B R. The clinical characteristics of this case are more inclined to anti-LGI1 encephalitis, showing abnormal mental behavior, hyponatremia, and sensitive to corticosteroid impulse therapy. With the discovery of more multiple auto-antibody positive cases of AE, it will provide evidence for further revealing the clinical characteristics, treatment and prognosis. Abbreviations anti-Leucinie-rich Glioma Inactivated 1 anti-LGI1 anti-γ-aminobutyric acid-beta-receptor anti-GABA B R anti- N-methyl-D-aspartic acid receptor anti-NMDAR anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor anti-AMPAR Cerebrospinal fluid CSF autoimmune encephalitis AE Declarations Ethics approval and consent to participate Protocols were established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics committee of first hospital of Zhengzhou University. Written informed consent was obtained from individual participant. Consent for publication Written informed consent was obtained from the patient for publication of this case report and companying images. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing Interests The authors declare that they have no competing interests. Funding This study was funded by the the Joint Construction Project of Henan Province (No. 2018020114 and No. 2018020083) and National Natural Science Foundation of China(81971214). Authors’ contributions Yi Xie and Jia Wen together collected disease history and radiological data and drafted this manuscript. Zhihua Zhao and Hongbo Liu contributed to the collection and interpretation of the data. Nanchang Xie participated in the design of the article. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology, 2011, 77(2): 179-189. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, Honnorat J, Smitt PS, Vedeler Ch, Verschuuren JJ, Vincent A, Voltz R. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J. Neurol. Neurosurg. Psychiatry, 2004, 75(8): 1135-114. Griffith SP, Malpas CB, Alpitsis R, O'Brien TJ, Monif M. The neuropsychological spectrum of anti-LGI1 antibody mediated autoimmune encephalitis. J. Neuroimmunol. 2020, 345: 577271. Yang X, Li AN, Zhao XH, Liu XW, Wang SJ. Clinical Features of Patients With Anti-Leucine-Rich Glioma inactivated-1 Protein Associated Encephalitis: A Chinese Case Series. Int. J. Neurosci., 2019, 129(8): 754-761. Maureille A, Fenouil T, Joubert B, Picard G, Rogemond V, Pinto AL, Thomas L, Ducray F, Quadrio I, Psimaras D, Berzero G, Antoine JC, Desestret V, Honnorat J. Isolated seizures are a common early feature of paraneoplastic anti-GABA receptor encephalitis. J Neurol, 2019, 266(1): 195-206. Ren HT, Yang XZ, Guan HZ, Gao XY, Peng B, Zhu YC, Cui LY. Clinical analysis of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies. Chin J Neurol, 2016, 49(1): 21-25. Höftberger R, Titulaer MJ, Sabater L, Dome B, Rózsás A, Hegedus B, Hoda MA, Laszlo V, Ankersmit HJ, Harms L, Boyero S, de Felipe A, Saiz A, Dalmau J, Graus F. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology, 2013, 81(17): 1500-1506. Liu XY, Chen Z, Wu GL, Peng T. A case of anti-LGI1 and anti-NMDAR autoimmune encephalitis. Natl Med J China, 2020, 100(11): 871-872. Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology, 2011, 76(9); 795-800. Qi HC. Multi-anti-neuronal antibody-positive autoimmune encephalitis: 2 case reports and review of literature[D]. Guangxi: Guangxi Medical University, 2018. Wegener-Panzer A, Cleaveland R, Wendel EM, Baumann M, Bertolini A, Häusler M, Knierim E, Reiter-Fink E, Breu M, Sönmez Ö, Della Marina A, Peters R, Lechner C, Piepkorn M, Roll C, Höftberger R, Leypoldt F, Reindl M, Rostásy K. Clinical and imaging features of children with autoimmune encephalitis and MOG antibodies. Neurol Neuroimmunol Neuroinflamm, 2020, 7(4): e731. Supplementary Files serumantibody.jpg csfantibody.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-34130","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short report","associatedPublications":[],"authors":[{"id":671057,"identity":"871aca8c-e2b8-4295-bb25-f6065cfdd4e0","order_by":0,"name":"Yi Xie","email":"","orcid":"https://orcid.org/0000-0003-0030-1498","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Xie","suffix":""},{"id":671058,"identity":"925a9f6d-c2df-4f9c-8718-2b18bb70d48e","order_by":1,"name":"Jia Wen","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Wen","suffix":""},{"id":671059,"identity":"4b20b802-5850-40b3-90f8-7096c60bb57d","order_by":2,"name":"Zhihua Zhao","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhihua","middleName":"","lastName":"Zhao","suffix":""},{"id":671060,"identity":"1025cebf-1009-41f0-aa64-cc7ef691d8ad","order_by":3,"name":"Hongbo Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongbo","middleName":"","lastName":"Liu","suffix":""},{"id":671061,"identity":"db7aa783-2447-410b-9527-4a4ebdb60643","order_by":4,"name":"Nanchang Xie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYDACZgiVAMSMDxIMJOTY2NsPEK2F2eBDhYUxH8+ZBKIsA6lik5xxpiJxnoSDAV6lBseZjz34ucMuj392+wVp3jaJ9DYJoP4fFdtwapFsZks37D2TXCxx50yBMVBLbpt04wHGnjO3cWrhZ+Yxk+BtO5DYcCMnIRmsReZAAjNjG24tbMz83yT/ArXMB2o5DHIYm0SCAV4tQFvYpEG2bLiRfrBxxhmJBIJagH4xk5ZtS07ceCOHmeFDhYRhGzCQD+Lzi8H5w88k37bZJc67kf78R4JBnbx8e/vBBz8qcGtBAjyI6DhAjHogYH9ApMJRMApGwSgYaQAA5OxYla81fBsAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nanchang","middleName":"","lastName":"Xie","suffix":""}],"badges":[],"createdAt":"2020-06-08 21:32:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-34130/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-34130/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":1345581,"identity":"b8967115-5d8f-454a-82d7-09523239a9cc","added_by":"auto","created_at":"2020-06-16 19:23:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":546935,"visible":true,"origin":"","legend":"1A. EEG of the patient before treatment(2020-04-21):moderate diffusion abnormality, Wide range of slow waves occur in medium-high waves. 1B. EEG of the patient after treatment(2020-04-29):normal.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34130/v1/1.jpg"},{"id":13541969,"identity":"3ed15b74-3034-4c69-a1c5-b267765182b3","added_by":"auto","created_at":"2021-09-17 01:52:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":347794,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-34130/v1/6872eea1-e0bf-4e31-85de-18f7e2be2676.pdf"},{"id":1345582,"identity":"c1a19538-2e5b-41f5-861b-09f03a794c48","added_by":"auto","created_at":"2020-06-16 19:23:23","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":475361,"visible":true,"origin":"","legend":"","description":"","filename":"serumantibody.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34130/v1/serumantibody.jpg"},{"id":1345583,"identity":"bc151cfd-b3d5-4109-9bd3-dbfe2afc137d","added_by":"auto","created_at":"2020-06-16 19:23:23","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":313560,"visible":true,"origin":"","legend":"","description":"","filename":"csfantibody.jpg","url":"https://assets-eu.researchsquare.com/files/rs-34130/v1/csfantibody.jpg"}],"financialInterests":"","formattedTitle":"Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review","fulltext":[{"header":"Background","content":"\u003cp\u003eThere are basically two kinds of auto-antibodies related to autoimmune encephalitis(AE). One is against neuron surface receptor, among which anti- N-methyl-D-aspartic acid receptor (anti-NMDAR) is the most common, others also including anti-\u0026gamma;-aminobutyric acid-beta-receptor (anti-GABA\u003csub\u003eB\u003c/sub\u003eR), anti-\u0026alpha;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (anti-AMPAR), anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1), etc. The other kind is against neuronal intracellular antigen, mainly referring to classic paraneoplastic neurosis antibody, such as anti-Hu, etc\u003csup\u003e[1-2]\u003c/sup\u003e. Different types of auto-antibodies correspond to specific neurological syndrome, which has strong specificity or directivity for etiological diagnosis. The majority of AE patients have only one of the above auto-antibodies, and very few with multiple auto-antibodies. Herein we report a patient with positive anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR who improved greatly by steroid therapy.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 60-year-old Chinese male presented with one-month of slow response and abnormal behavior. He had typhia 40 years ago and left no sequel. Neurological exam revealed poor mental state, slow response and damaged memory, attention, calculation and orientation.\u003c/p\u003e\n\u003cp\u003eMini mental state examination score was 15. Cerebrospinal fluid (CSF) electrophoresis IgG index was 0.71 (reference 0.3~0.7). Intracranial pressure was 150mmH\u003csub\u003e2\u003c/sub\u003eO. CSF routine biochemistry for protein content and glucose were normal and infectious test for virus, tuberculosis and Cryptococcus were negative. CSF cytology and cytometry were negative for malignant cells. Brain MRI scan with contrast enhancement was normal. Chest enhanced CT scan revealed inflammation in left lower lobe. Serum procalcitonin was 0.048ng/mL (reference\u0026lt;0.046ng/mL), C reaction protein was 8.05mg/L (reference\u0026lt;5mg/L). Serum AE antibody spectrum demonstrated positive anti-LGI1 IgG and anti-GABA\u003csub\u003eB\u003c/sub\u003eR IgG, while CSF auto-antibody test was negative. Blood studies revealed sodium was 119mmol/L (reference 135~153mmol/mL) and chlorine was 81mmol/L (reference 90~110mmol/L) at first admission. Electroencephalogram (EEG) indicated moderate diffusion abnormality (Figure 1A and 1B).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor treatment of AE with multiple co-existing antibody, he received 1g and 0.5g intravenous methylprednisolone separately, 3 days for each dosage, and then remained on an oral steroid taper for half year. After intravenous and oral sodium supplement, blood sodium and chlorine gradually increased to normal(Table 1). His mental state improved greatly and EEG recovered to normal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Blood test for sodium and chlorine\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003eDate/time\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003eBlood sodium(mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003eBlood chlorine(mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-21 11:00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e119.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e81.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-21 20:00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e121.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e82.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e124.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e85.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e129.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e92.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e135.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e93.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e138.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e92.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e134.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e91.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e2020-04-30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e135.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"184\"\u003e\n\u003cp\u003e91.0\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eCo-existence of serum anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR in AE patient has not been previously reported. The 60-year-old patient, with subacute onset, mainly manifested cognitive decline, behavioral abnormality and hyponatremia. The serum anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR were double positive, and EEG indicated moderate diffusion abnormality. According to the patients' symptoms, AE auto-antibody spectrum test and EEG results, the patient was diagnosed as AE with double auto-antibody positive, ie, anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR. The patient responded well to glucocorticoid treatment, and we will continue to follow up the prognosis.\u003c/p\u003e\n\u003cp\u003eAnti-LGI1 encephalitis, which is mostly found in elderly men with subacute onset, is related to hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion. Most patients demonstrated cognitive impairment, and about 90% of them have behavioral and/or personality changes. Frequent seizures, especially focal seizure, are seen in the majority of patients, while generalized tonic clonic seizures are not very common. Most patients have no related tumors, only about 10% had thymoma, while other tumors were rare. Up to 75% of cases have normal CSF routine analysis. EEG can show mild diffuse slow wave, and about half may have swelled medial temporal lobe with high T2/flair signal. The good news is the relatively low recurrence rate\u003csup\u003e[3-4]\u003c/sup\u003e. Anti-GABA\u003csub\u003eB\u003c/sub\u003eR encephalitis mostly presents limbic encephalitis symptoms, with temporal lobe epilepsy as the core symptomatology, and most of them are accompanied by cognitive function decline, personality change and mental behavior abnormality. About 50% of patients have small cell lung cancer or neuroendocrine tumor. It is suggested that anti-GABA\u003csub\u003eB\u003c/sub\u003eR encephalitis should further take chest CT or PET examination\u003csup\u003e[5]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe overlying of neuronal auto-antibodies may cause the superposition of clinical syndrome, but not a simple complete superposition, which needs to be analyzed according to the specific antibody type and clinical manifestation. According to Professor Guan Hongzhi's newly published review, it is necessary to distinguish whether the antibodies in patients belong to pathogenic markers or concomitant antibodies\u003csup\u003e[6]\u003c/sup\u003e. The main manifestations of this case are psychobehavioral abnormality and hyponatremia, more similar to clinical manifestations of anti-LGI1 AE.\u003c/p\u003e\n\u003cp\u003eThe co-existence of multiple auto-antibody is rare(summarized in Table 2). Ren Haitao reported 531 cases of AE with auto-antibodies, and only 10 cases detected multiple anti-neuronal antibodies, among whom 5 cases were anti-GABA\u003csub\u003eB\u003c/sub\u003eR/anti-Hu(+), 1 anti-NMDAR/APQ-4(+), 1 anti-LGI1/anti-CASPR2(+), 1 anti-LGI1/anti-Yo(+), 1 anti-AMPAR/anti-CV2(+) and 1 anti-AMPAR/anti-Hu(+)\u003csup\u003e[6]\u003c/sup\u003e. In the 20 anti-GABA\u003csub\u003eB\u003c/sub\u003eR AE cases reported by Hoftberger, 7 detected multiple auto-antibodies, among whom 3 cases with anti-Sox1, 1 with anti-Ri, 1 with anti-amphiphysin, 1 with anti-GAD65 and 1 with anti-NMDAR\u003csup\u003e[7]\u003c/sup\u003e. Liu XY recently reported one case characterized by double positive of anti-LGI1 and anti-NMDAR\u003csup\u003e[8]\u003c/sup\u003e. Boronat reported a case of anti-GABA\u003csub\u003eB\u003c/sub\u003eR combined with anti-GAD65, menifestating cerebellar ataxia and thymoid carcinoid\u003csup\u003e[9]\u003c/sup\u003e. Qi Hengchang reported two cases of AE with multiple auto-antibodies against neuron (one was anti-NMDAR(+), anti-GABA\u003csub\u003eB\u003c/sub\u003eR(+), and the other anti-LGI1(+), anti CASPR2(+). Both patients were adult women with acute onset. Their first symptom was epilepsy, and the treatment effect was good\u003csup\u003e[10]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe clinical significance of multiple auto-antibody has already raised attention of many neurologists and needs to be interpreted in combination with clinical practice. For example, anti-GABA\u003csub\u003eB\u003c/sub\u003eR can be combined with anti-Hu. When anti-GABA\u003csub\u003eB\u003c/sub\u003eR is positive, it is recommended to screen anti-Hu and carry out tumor screening at the same time, such as chest CT, tumor markers, etc., excluding the possibility of tumor as much as possible. In this case chest enhanced CT scan didn\u0026rsquo;t find tumor, but the patient was advised to take regular examination during follow-up. At present, many reports of anti-NMDAR combined with anti-MOG suggest that it is necessary to consider the clinical syndrome superposition caused by the antibody superposition, pay attention to the clinical process, and inquire in detail the history and imaging data whether there is a basis for demyelination\u003csup\u003e[11]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 clinical data of AE cases with multiple auto-antibodies\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"28\"\u003e\n\u003cp\u003eN.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"38\"\u003e\n\u003cp\u003eSex,\u003c/p\u003e\n\u003cp\u003eage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"113\"\u003e\n\u003cp\u003eAE auto-Abs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"94\"\u003e\n\u003cp\u003eOther Abs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"151\"\u003e\n\u003cp\u003eClinical menifestation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"113\"\u003e\n\u003cp\u003eBrain MRI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"95\"\u003e\n\u003cp\u003etumor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"94\"\u003e\n\u003cp\u003eprognosis\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eserum\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eCSF\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eserum\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eCSF\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMemory loss, somnolence, conculsion, cough, hoarseness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eLung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,61\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eEpilepsy, somnolence, memory loss\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eLung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eEpilepsy, psychosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eLesions of bilateral hippocampus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eLung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003ePsychosis, memory loss, numbness of limbs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eLesions of bilateral hippocampus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eLung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,61\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR NMDAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eEpilepsy, memory loss, coma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eND\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eLung cancer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eNMDAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eAQP4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eAQP4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003ePsychosis, memory loss, blepharoptosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eLesions of bilateral basal ganglia, brainstem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1\u003c/p\u003e\n\u003cp\u003eCASPR2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMyalgia, fasciculation, epilepsy, insomnia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eYo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eYo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMemory loss, conculsion, somnolence, polyphagia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eAMPAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eAMPAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eCV2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eCV2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMemory loss, psychosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eThymoma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,51\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eAMPAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eAMPAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003ePsychosis, dysphagia, dysdipsia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eLesions of bilateral cortex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eMediastinal occupying\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eDead\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eND\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003cp\u003eNMDAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eComplete improve\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eGAD65\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eStatus epilepticus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eDead\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eSOX1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003ePartial recovery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eRi\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eSOX1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003ePartial recovery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eND\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eSOX1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eND\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eDead\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eAmphiphysin\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eLimbic encephalitis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNot mentioned\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eUnresponsive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1\u003c/p\u003e\n\u003cp\u003eNMDAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eFaciobrachial dystonic seizure, hyponatremia, mental disorder\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eGAD\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSeizures, confusion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eNot available\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eSOX1\u003csup\u003e*\u003c/sup\u003eVGKC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSeizures, behavior change, memory impairment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eBilateral temporal lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003ePartial recovery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eGAD\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eSOX1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSeizures, memory impairment, confusion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eUnresponsive, dead\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eHu\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSeizures, memory impairment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eBilateral temporal lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eUnresponsive, dead\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eM,61\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eBRSK2\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eMemory impairment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eBilateral temporal lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eSCLC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eUnresponsive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eGABA\u003csub\u003eB\u003c/sub\u003eR\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003eGAD\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSubacute cerebellar ataxia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eCarcinoid of thymus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eComplete recovery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eNMDAR GABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eNMDAR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eEpilepsy, psychosis, insomnia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"28\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"38\"\u003e\n\u003cp\u003eF,43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eLGI1 CASPR2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003eCASPR2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"47\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003eSeizures, weight loss, calculation/ memory/speech disorder\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eBilateral hippocampus/ occipital/parietal lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eImprove\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003ch2\u003e1. Ethics approval and consent to participate\u003c/h2\u003e \u003cp\u003eProtocols were established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics committee of first hospital of Zhengzhou University. Written informed consent was obtained from individual participant.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e2. Consent for publication\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and companying images.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e3. Availability of data and materials\u003c/strong\u003e \u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e4. Competing Interests\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e \u003ch2\u003e5. Funding\u003c/h2\u003e \u003cp\u003eThis study was funded by the the Joint Construction Project of Henan Province (No. 2018020114 and No. 2018020083) and National Natural Science Foundation of China(81971214).\u003c/p\u003e \u003ch2\u003e7. Acknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e "},{"header":"Conclusions","content":"\u003cp\u003eHere we first report a case of AE with co-existing auto-antibodies anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR. The clinical characteristics of this case are more inclined to anti-LGI1 encephalitis, showing abnormal mental behavior, hyponatremia, and sensitive to corticosteroid impulse therapy. With the discovery of more multiple auto-antibody positive cases of AE, it will provide evidence for further revealing the clinical characteristics, treatment and prognosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eanti-Leucinie-rich Glioma Inactivated 1 anti-LGI1\u003c/p\u003e\n\u003cp\u003eanti-\u0026gamma;-aminobutyric acid-beta-receptor anti-GABA\u003csub\u003eB\u003c/sub\u003eR\u003c/p\u003e\n\u003cp\u003eanti- N-methyl-D-aspartic acid receptor anti-NMDAR\u003c/p\u003e\n\u003cp\u003eanti-\u0026alpha;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor anti-AMPAR\u003c/p\u003e\n\u003cp\u003eCerebrospinal fluid CSF\u003c/p\u003e\n\u003cp\u003eautoimmune encephalitis AE\u003c/p\u003e"},{"header":"Declarations","content":"\u003col\u003e\n\u003cli\u003eEthics approval and consent to participate\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eProtocols were established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics committee of first hospital of Zhengzhou University. Written informed consent was obtained from individual participant.\u003c/p\u003e\n\u003col start=\"2\"\u003e\n\u003cli\u003eConsent for publication\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and companying images.\u003c/p\u003e\n\u003col start=\"3\"\u003e\n\u003cli\u003eAvailability of data and materials\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003col start=\"4\"\u003e\n\u003cli\u003eCompeting Interests\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003col start=\"5\"\u003e\n\u003cli\u003eFunding\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThis study was funded by the the Joint Construction Project of Henan Province (No. 2018020114 and No. 2018020083) and National Natural Science Foundation of China(81971214).\u003c/p\u003e\n\u003col start=\"6\"\u003e\n\u003cli\u003eAuthors\u0026rsquo; contributions\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eYi Xie and Jia Wen together collected disease history and radiological data and drafted this manuscript. Zhihua Zhao and Hongbo Liu contributed to the collection and interpretation of the data. Nanchang Xie participated in the design of the article. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003col start=\"7\"\u003e\n\u003cli\u003eAcknowledgements\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology, 2011, 77(2): 179-189.\u003c/li\u003e\n\u003cli\u003eGraus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, Honnorat J, Smitt PS, Vedeler Ch, Verschuuren JJ, Vincent A, Voltz R. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J. Neurol. Neurosurg. Psychiatry, 2004, 75(8): 1135-114.\u003c/li\u003e\n\u003cli\u003eGriffith SP, Malpas CB, Alpitsis R, O'Brien TJ, Monif M. The neuropsychological spectrum of anti-LGI1 antibody mediated autoimmune encephalitis. J. Neuroimmunol. 2020, 345: 577271.\u003c/li\u003e\n\u003cli\u003eYang X, Li AN, Zhao XH, Liu XW, Wang SJ. Clinical Features of Patients With Anti-Leucine-Rich Glioma inactivated-1 Protein Associated Encephalitis: A Chinese Case Series. Int. J. Neurosci., 2019, 129(8): 754-761.\u003c/li\u003e\n\u003cli\u003eMaureille A, Fenouil T, Joubert B, Picard G, Rogemond V, Pinto AL, Thomas L, Ducray F, Quadrio I, Psimaras D, Berzero G, Antoine JC, Desestret V, Honnorat J. Isolated seizures are a common early feature of paraneoplastic anti-GABA receptor encephalitis. J Neurol, 2019, 266(1): 195-206.\u003c/li\u003e\n\u003cli\u003eRen HT, Yang XZ, Guan HZ, Gao XY, Peng B, Zhu YC, Cui LY. Clinical analysis of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies. Chin J Neurol, 2016, 49(1): 21-25.\u003c/li\u003e\n\u003cli\u003eH\u0026ouml;ftberger R, Titulaer MJ, Sabater L, Dome B, R\u0026oacute;zs\u0026aacute;s A, Hegedus B, Hoda MA, Laszlo V, Ankersmit HJ, Harms L, Boyero S, de Felipe A, Saiz A, Dalmau J, Graus F. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology, 2013, 81(17): 1500-1506.\u003c/li\u003e\n\u003cli\u003eLiu XY, Chen Z, Wu GL, Peng T. A case of anti-LGI1 and anti-NMDAR autoimmune encephalitis. Natl Med J China, 2020, 100(11): 871-872.\u003c/li\u003e\n\u003cli\u003eBoronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology, 2011, 76(9); 795-800.\u003c/li\u003e\n\u003cli\u003eQi HC. Multi-anti-neuronal antibody-positive autoimmune encephalitis: 2 case reports and review of literature[D]. Guangxi: Guangxi Medical University, 2018.\u003c/li\u003e\n\u003cli\u003eWegener-Panzer A, Cleaveland R, Wendel EM, Baumann M, Bertolini A, H\u0026auml;usler M, Knierim E, Reiter-Fink E, Breu M, S\u0026ouml;nmez \u0026Ouml;, Della Marina A, Peters R, Lechner C, Piepkorn M, Roll C, H\u0026ouml;ftberger R, Leypoldt F, Reindl M, Rost\u0026aacute;sy K. Clinical and imaging features of children with autoimmune encephalitis and MOG antibodies. Neurol Neuroimmunol Neuroinflamm, 2020, 7(4): e731.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"multiple auto-antibody, autoimmune encephalitis, anti-LGI1, anti-GABABR","lastPublishedDoi":"10.21203/rs.3.rs-34130/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-34130/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA 60-year-old man presented with slow response and psychosis. Apart from hyponatremia, serum test also showed positive anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1) and anti-γ-aminobutyric acid-beta-receptor (anti-GABA\u003csub\u003eB\u003c/sub\u003eR), and electroencephalogram exhibited moderate diffusion abnormality. The patient responded well to steroid treatment. Here we report the first autoimmune encephalitis(AE) characterized by positive anti-LGI1 and anti-GABA\u003csub\u003eB\u003c/sub\u003eR, as well as summarizing AE with multiple auto-antibodies reported so far, hopefully to provide experience for clinical practice.\u003c/p\u003e","manuscriptTitle":"Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-06-16 19:23:22","doi":"10.21203/rs.3.rs-34130/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"23342699-a72d-4f1e-a5a4-85867f3fa52b","owner":[],"postedDate":"June 16th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":121503,"name":"Neurobiology of Disease"}],"tags":[],"updatedAt":"2020-06-21T11:45:17+00:00","versionOfRecord":[],"versionCreatedAt":"2020-06-16 19:23:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-34130","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-34130","identity":"rs-34130","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}