Relapsing Seronegative Limbic Encephalitis During Pregnancy: A Rare Case with Bilateral Hippocampal Atrophy and Favorable Maternal-Fetal Outcome

Relapsing Seronegative Limbic Encephalitis During Pregnancy: A Rare Case with Bilateral Hippocampal Atrophy and Favorable Maternal-Fetal Outcome | 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 Case Report Relapsing Seronegative Limbic Encephalitis During Pregnancy: A Rare Case with Bilateral Hippocampal Atrophy and Favorable Maternal-Fetal Outcome Yunus Emre Aktas¹ This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6892381/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 We report a rare case of a 24-year-old primigravida who developed relapsing seronegative autoimmune limbic encephalitis (LE) during pregnancy. The initial episode occurred at 24 weeks of gestation, presenting with altered consciousness and a generalized tonic-clonic seizure, following a herpes labialis outbreak. Brain MRI revealed bilateral mesial temporal hyperintensities. Extensive workup, including cerebrospinal fluid analysis, HSV PCR, and autoimmune antibody panel (anti-NMDAR, LGI1, GABA-B, AMPAR, GAD65), was negative. The patient responded well to intravenous immunoglobulin (IVIG). However, she experienced a relapse near term, requiring emergency cesarean section. Postpartum MRI showed bilateral hippocampal atrophy. Despite seizure control, persistent cognitive symptoms remained. This case underscores the diagnostic complexity of seronegative LE in pregnancy and highlights that IVIG can be a safe and effective treatment option, even in the absence of confirmatory biomarkers. Our case also adds to the scarce literature on cognitive sequelae and long-term management in such scenarios. Limbic encephalitis pregnancy hippocampal atrophy autoimmune encephalitis IVIG Figures Figure 1 Figure 2 Introduction Autoimmune limbic encephalitis (LE) is a rare inflammatory brain disease involving the mesial temporal lobes, commonly associated with autoantibodies such as anti-NMDA, anti-LGI1, and anti-GAD65. Seronegative forms represent a diagnostic challenge due to the lack of definitive biomarkers. LE during pregnancy is exceedingly rare and further complicates management due to limitations in diagnostic procedures and therapeutic options [ 1 , 2 ]. Previous literature emphasizes the need for high clinical suspicion in atypical cases [ 3 , 4 ]. Case Presentation A 24-year-old woman, gravida 1 para 0, presented at 24 weeks of gestation with fever, altered mental status, and a generalized tonic-clonic seizure. She had a history of herpes labialis one week prior. On admission, the patient was disoriented with a Glasgow Coma Scale of 11. Brain MRI demonstrated bilateral hyperintensities in the mesial temporal lobes on FLAIR sequences. EEG revealed diffuse delta slowing. Lumbar puncture yielded normal opening pressure, clear CSF, no pleocytosis, normal protein and glucose, and negative oligoclonal bands. HSV PCR was negative. Given the clinical-radiological dissociation and negative infectious workup, autoimmune LE was suspected. An autoimmune encephalitis panel including anti-NMDA, LGI1, GABA-B, AMPAR, and GAD65 was negative. The patient received 0.4 g/kg/day IVIG for 5 days, resulting in gradual improvement and discharge without further seizures. At 36 weeks of gestation, she experienced a relapse characterized by a new seizure. Repeat MRI showed persistent mesial temporal changes. EEG findings were similar. Emergency cesarean section was performed, and a healthy neonate was delivered. She received another 5-day course of IVIG. CSF remained normal. In the postpartum period, the patient remained seizure-free with maintenance IVIG for 12 months. Control MRI revealed bilateral hippocampal atrophy. Cognitive complaints including forgetfulness and irritability persisted. She was maintained on levetiracetam and fluoxetine. Discussion Diagnosing autoimmune LE during pregnancy presents unique challenges due to overlapping infectious and metabolic differentials, limited use of certain imaging modalities, and contraindicated immunotherapies such as high-dose steroids or second-line agents like rituximab. While autoimmune LE is a well-defined clinical entity, seronegative variants remain diagnostically elusive, accounting for up to 20–30% of cases in some cohorts [ 5 , 6 ]. In pregnancy, LE is particularly rare, with only a few cases reported in the literature [ 7 – 9 ]. To our knowledge, this is the first reported case of relapsing seronegative LE in a pregnant patient with long-term cognitive impairment and bilateral hippocampal atrophy, managed exclusively with IVIG. Our patient had an initial episode in the second trimester and relapsed near term, which may suggest an immune reactivation influenced by gestational immune modulation [ 1 , 2 ]. The decision to use IVIG, which is considered relatively safe during pregnancy, was driven by the need to avoid corticosteroids and immunosuppressants due to potential fetal risks [ 5 ]. IVIG resulted in rapid clinical improvement in both episodes and maintained seizure control postpartum. The presence of bilateral hippocampal atrophy, observed on follow-up imaging, suggests irreversible structural damage, which correlates with her ongoing cognitive symptoms [ 6 ]. Previous imaging studies further support the association between hippocampal involvement and long-term memory deficits in autoimmune encephalitis [ 10 , 11 ]. This case contributes valuable insights to the scarce literature on autoimmune LE in pregnancy and emphasizes the need for long-term neurological and neuropsychological monitoring of affected patients [ 12 ]. Conclusion Relapsing seronegative autoimmune LE in pregnancy is exceedingly rare. Our case emphasizes the importance of clinical vigilance when antibody testing is negative and infectious causes are ruled out. IVIG appears to be a viable treatment option with favorable maternal and fetal outcomes. However, long-term cognitive follow-up is essential, especially when hippocampal involvement is observed. Declarations Conflicts of Interest Disclosure The author declares that there are no conflicts of interest related to this study. Ethical Considerations Written informed consent was obtained from the patient for publication of this case report and accompanying images. According to institutional policy, ethics committee approval is not required for single case reports. A formal exemption was obtained from Erzurum City Hospital. Author Contribution YEA: The author was solely responsible for the conception, clinical evaluation, data collection, literature review, manuscript writing, figure preparation, and final approval of the submitted version. References Vinet, É., Pineau, C. A., Clarke, A. E., & Bernatsky, S. (2017). Pregnancy outcomes in women with systemic autoimmune diseases. Current Opinion in Rheumatology , 29(3), 241–247. https://doi.org/10.1097/BOR.0000000000000387 Lee, W. J., Lee, S. T., Moon, J., et al. (2016). Autoimmune encephalitis associated with pregnancy. Epilepsy & Behavior , 64(Pt A), 213–216. https://doi.org/10.1016/j.yebeh.2016.10.002 Graus, F., & Dalmau, J. (2012). Paraneoplastic and autoimmune encephalitides. Current Opinion in Neurology , 25(3), 795–801. https://doi.org/10.1097/WCO.0b013e3283545df5 Budhram, A., Leung, A., Nicolle, M. W., & Burneo, J. G. (2019). Diagnosing autoimmune limbic encephalitis. Canadian Medical Association Journal , 191(34), E960–E964. https://doi.org/10.1503/cmaj.190262 Levy, R. A., & Tavares, M. (2015). IVIG in pregnancy: Evidence and practical issues. Rheumatic Disease Clinics , 41(1), 145–156. https://doi.org/10.1016/j.rdc.2014.09.004 Finke, C., Kopp, U. A., Prüss, H., et al. (2012). Cognitive deficits following anti-NMDA receptor encephalitis. Journal of Neurology, Neurosurgery & Psychiatry , 83(2), 195–198. https://doi.org/10.1136/jnnp-2011-300411 Gultekin, S. H., Rosenfeld, M. R., Voltz, R., et al. (2000). Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. Brain , 123(7), 1481–1494. https://doi.org/10.1093/brain/123.7.1481 Vitaliani, R., Mason, W., Ances, B., et al. (2005). Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Annals of Neurology , 58(4), 594–604. https://doi.org/10.1002/ana.20614 Tüzün, E., & Dalmau, J. (2007). Limbic encephalitis and variants: Classification, diagnosis and treatment. The Neurologist , 13(5), 261–271. https://doi.org/10.1097/NRL.0b013e31812dc6b8 Heine, J., Prüss, H., Bartsch, T., et al. (2021). Imaging of autoimmune encephalitis – relevance for clinical practice and translational research. Frontiers in Neurology , 12, 661017. https://doi.org/10.3389/fneur.2021.661017 Heine, J., Prüss, H., Bartsch, T., Ploner, C. J., Paul, F., & Finke, C. (2015). Imaging of autoimmune encephalitis–Relevance for clinical practice and hippocampal function. Neuroscience , 309 , 68-83. Armangue, T., Leypoldt, F., & Dalmau, J. (2014). Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Current Opinion in Neurology , 27(3), 361–368. https://doi.org/10.1097/WCO.0000000000000107 Additional Declarations No competing interests reported. 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-6892381","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":488387309,"identity":"210baa87-f369-42f2-95e6-9662a0e77e90","order_by":0,"name":"Yunus Emre Aktas¹","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYFACNoYDjA0MDPwgdkIBKVokG0BaDIjUwgDSYnAAxCFGC397W+KBnztsEjefX5344YEBgzy/2AH8WiTOHDtwsPdMWuK2G283SwAdZjhzdgJ+LQYS6Q2HGdsOA7Wc3QDSkmBwm5AW+ecgLf8TN884u/kHcVok2A4AtRxI3MDfu404WyTOpCUA/ZJsPOMG7zaLBAMJwn7hbz9m/OHnDjvZ/v6zm2/+qLCR55cmoAUGHBskwColiFMOAvYM/AeIVz0KRsEoGAUjCwAATCRMsDk5bXUAAAAASUVORK5CYII=","orcid":"","institution":"Erzurum City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yunus","middleName":"Emre","lastName":"Aktas¹","suffix":""}],"badges":[],"createdAt":"2025-06-14 07:08:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6892381/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6892381/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87382915,"identity":"6dfda3d7-b2e0-40f9-807b-6232e7df4620","added_by":"auto","created_at":"2025-07-23 08:40:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":354543,"visible":true,"origin":"","legend":"\u003cp\u003ea. Initial brain MRI (FLAIR) during the first episode showing bilateral mesial temporal hyperintensities (axial view).\u003c/p\u003e\n\u003cp\u003eb. Initial brain MRI (coronal section) supporting mesial temporal involvement.\u003c/p\u003e\n\u003cp\u003ec. Further axial FLAIR section confirming bilateral limbic signal alterations.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6892381/v1/5f81e40416918c1f88454e02.png"},{"id":87379964,"identity":"e43bf469-8a24-4f06-9da4-f3ef1cc87842","added_by":"auto","created_at":"2025-07-23 08:32:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":320094,"visible":true,"origin":"","legend":"\u003cp\u003ea. Follow-up brain MRI (FLAIR axial) approximately one year postpartum showing bilateral hippocampal atrophy.\u003c/p\u003e\n\u003cp\u003eb. Follow-up brain MRI (coronal section) confirming hippocampal volume loss.\u003c/p\u003e\n\u003cp\u003ec. Additional axial view highlighting bilateral hippocampal atrophy.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6892381/v1/ede2910fc2ffef5e4a89d521.png"},{"id":88031026,"identity":"0845b746-41e8-4386-8868-610d153cce84","added_by":"auto","created_at":"2025-07-31 15:32:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":958697,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6892381/v1/823822c7-31ce-4723-8643-1f4675ac2661.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRelapsing Seronegative Limbic Encephalitis During Pregnancy: A Rare Case with Bilateral Hippocampal Atrophy and Favorable Maternal-Fetal Outcome\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAutoimmune limbic encephalitis (LE) is a rare inflammatory brain disease involving the mesial temporal lobes, commonly associated with autoantibodies such as anti-NMDA, anti-LGI1, and anti-GAD65. Seronegative forms represent a diagnostic challenge due to the lack of definitive biomarkers. LE during pregnancy is exceedingly rare and further complicates management due to limitations in diagnostic procedures and therapeutic options [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Previous literature emphasizes the need for high clinical suspicion in atypical cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 24-year-old woman, gravida 1 para 0, presented at 24 weeks of gestation with fever, altered mental status, and a generalized tonic-clonic seizure. She had a history of herpes labialis one week prior. On admission, the patient was disoriented with a Glasgow Coma Scale of 11. Brain MRI demonstrated bilateral hyperintensities in the mesial temporal lobes on FLAIR sequences. EEG revealed diffuse delta slowing. Lumbar puncture yielded normal opening pressure, clear CSF, no pleocytosis, normal protein and glucose, and negative oligoclonal bands. HSV PCR was negative. Given the clinical-radiological dissociation and negative infectious workup, autoimmune LE was suspected. An autoimmune encephalitis panel including anti-NMDA, LGI1, GABA-B, AMPAR, and GAD65 was negative. The patient received 0.4 g/kg/day IVIG for 5 days, resulting in gradual improvement and discharge without further seizures. At 36 weeks of gestation, she experienced a relapse characterized by a new seizure. Repeat MRI showed persistent mesial temporal changes. EEG findings were similar. Emergency cesarean section was performed, and a healthy neonate was delivered. She received another 5-day course of IVIG. CSF remained normal. In the postpartum period, the patient remained seizure-free with maintenance IVIG for 12 months. Control MRI revealed bilateral hippocampal atrophy. Cognitive complaints including forgetfulness and irritability persisted. She was maintained on levetiracetam and fluoxetine.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiagnosing autoimmune LE during pregnancy presents unique challenges due to overlapping infectious and metabolic differentials, limited use of certain imaging modalities, and contraindicated immunotherapies such as high-dose steroids or second-line agents like rituximab. While autoimmune LE is a well-defined clinical entity, seronegative variants remain diagnostically elusive, accounting for up to 20\u0026ndash;30% of cases in some cohorts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In pregnancy, LE is particularly rare, with only a few cases reported in the literature [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. To our knowledge, this is the first reported case of relapsing seronegative LE in a pregnant patient with long-term cognitive impairment and bilateral hippocampal atrophy, managed exclusively with IVIG.\u003c/p\u003e\u003cp\u003eOur patient had an initial episode in the second trimester and relapsed near term, which may suggest an immune reactivation influenced by gestational immune modulation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The decision to use IVIG, which is considered relatively safe during pregnancy, was driven by the need to avoid corticosteroids and immunosuppressants due to potential fetal risks [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. IVIG resulted in rapid clinical improvement in both episodes and maintained seizure control postpartum.\u003c/p\u003e\u003cp\u003eThe presence of bilateral hippocampal atrophy, observed on follow-up imaging, suggests irreversible structural damage, which correlates with her ongoing cognitive symptoms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Previous imaging studies further support the association between hippocampal involvement and long-term memory deficits in autoimmune encephalitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis case contributes valuable insights to the scarce literature on autoimmune LE in pregnancy and emphasizes the need for long-term neurological and neuropsychological monitoring of affected patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRelapsing seronegative autoimmune LE in pregnancy is exceedingly rare. Our case emphasizes the importance of clinical vigilance when antibody testing is negative and infectious causes are ruled out. IVIG appears to be a viable treatment option with favorable maternal and fetal outcomes. However, long-term cognitive follow-up is essential, especially when hippocampal involvement is observed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflicts of Interest Disclosure\u003c/h2\u003e\u003cp\u003eThe author declares that there are no conflicts of interest related to this study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthical Considerations\u003c/h2\u003e\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and accompanying images. According to institutional policy, ethics committee approval is not required for single case reports. A formal exemption was obtained from Erzurum City Hospital.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYEA: The author was solely responsible for the conception, clinical evaluation, data collection, literature review, manuscript writing, figure preparation, and final approval of the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eVinet, \u0026Eacute;., Pineau, C. A., Clarke, A. E., \u0026amp; Bernatsky, S. (2017). Pregnancy outcomes in women with systemic autoimmune diseases. \u003cem\u003eCurrent Opinion in Rheumatology\u003c/em\u003e, 29(3), 241\u0026ndash;247. https://doi.org/10.1097/BOR.0000000000000387\u003c/li\u003e\n\u003cli\u003eLee, W. J., Lee, S. T., Moon, J., et al. (2016). Autoimmune encephalitis associated with pregnancy. \u003cem\u003eEpilepsy \u0026amp; Behavior\u003c/em\u003e, 64(Pt A), 213\u0026ndash;216. https://doi.org/10.1016/j.yebeh.2016.10.002\u003c/li\u003e\n\u003cli\u003eGraus, F., \u0026amp; Dalmau, J. (2012). Paraneoplastic and autoimmune encephalitides. \u003cem\u003eCurrent Opinion in Neurology\u003c/em\u003e, 25(3), 795\u0026ndash;801. https://doi.org/10.1097/WCO.0b013e3283545df5\u003c/li\u003e\n\u003cli\u003eBudhram, A., Leung, A., Nicolle, M. W., \u0026amp; Burneo, J. G. (2019). Diagnosing autoimmune limbic encephalitis. \u003cem\u003eCanadian Medical Association Journal\u003c/em\u003e, 191(34), E960\u0026ndash;E964. https://doi.org/10.1503/cmaj.190262\u003c/li\u003e\n\u003cli\u003eLevy, R. A., \u0026amp; Tavares, M. (2015). IVIG in pregnancy: Evidence and practical issues. \u003cem\u003eRheumatic Disease Clinics\u003c/em\u003e, 41(1), 145\u0026ndash;156. https://doi.org/10.1016/j.rdc.2014.09.004\u003c/li\u003e\n\u003cli\u003eFinke, C., Kopp, U. A., Pr\u0026uuml;ss, H., et al. (2012). Cognitive deficits following anti-NMDA receptor encephalitis. \u003cem\u003eJournal of Neurology, Neurosurgery \u0026amp; Psychiatry\u003c/em\u003e, 83(2), 195\u0026ndash;198. https://doi.org/10.1136/jnnp-2011-300411\u003c/li\u003e\n\u003cli\u003eGultekin, S. H., Rosenfeld, M. R., Voltz, R., et al. (2000). Paraneoplastic limbic encephalitis: Neurological symptoms, immunological findings and tumour association in 50 patients. \u003cem\u003eBrain\u003c/em\u003e, 123(7), 1481\u0026ndash;1494. https://doi.org/10.1093/brain/123.7.1481\u003c/li\u003e\n\u003cli\u003eVitaliani, R., Mason, W., Ances, B., et al. (2005). Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. \u003cem\u003eAnnals of Neurology\u003c/em\u003e, 58(4), 594\u0026ndash;604. https://doi.org/10.1002/ana.20614\u003c/li\u003e\n\u003cli\u003eT\u0026uuml;z\u0026uuml;n, E., \u0026amp; Dalmau, J. (2007). Limbic encephalitis and variants: Classification, diagnosis and treatment. \u003cem\u003eThe Neurologist\u003c/em\u003e, 13(5), 261\u0026ndash;271. https://doi.org/10.1097/NRL.0b013e31812dc6b8\u003c/li\u003e\n\u003cli\u003eHeine, J., Pr\u0026uuml;ss, H., Bartsch, T., et al. (2021). Imaging of autoimmune encephalitis \u0026ndash; relevance for clinical practice and translational research. \u003cem\u003eFrontiers in Neurology\u003c/em\u003e, 12, 661017. https://doi.org/10.3389/fneur.2021.661017\u003c/li\u003e\n\u003cli\u003eHeine, J., Pr\u0026uuml;ss, H., Bartsch, T., Ploner, C. J., Paul, F., \u0026amp; Finke, C. (2015). Imaging of autoimmune encephalitis\u0026ndash;Relevance for clinical practice and hippocampal function. \u003cem\u003eNeuroscience\u003c/em\u003e, \u003cem\u003e309\u003c/em\u003e, 68-83.\u003c/li\u003e\n\u003cli\u003eArmangue, T., Leypoldt, F., \u0026amp; Dalmau, J. (2014). Autoimmune encephalitis as differential diagnosis of infectious encephalitis. \u003cem\u003eCurrent Opinion in Neurology\u003c/em\u003e, 27(3), 361\u0026ndash;368. https://doi.org/10.1097/WCO.0000000000000107\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":"Limbic encephalitis, pregnancy, hippocampal atrophy, autoimmune encephalitis, IVIG","lastPublishedDoi":"10.21203/rs.3.rs-6892381/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6892381/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe report a rare case of a 24-year-old primigravida who developed relapsing seronegative autoimmune limbic encephalitis (LE) during pregnancy. The initial episode occurred at 24 weeks of gestation, presenting with altered consciousness and a generalized tonic-clonic seizure, following a herpes labialis outbreak. Brain MRI revealed bilateral mesial temporal hyperintensities. Extensive workup, including cerebrospinal fluid analysis, HSV PCR, and autoimmune antibody panel (anti-NMDAR, LGI1, GABA-B, AMPAR, GAD65), was negative. The patient responded well to intravenous immunoglobulin (IVIG). However, she experienced a relapse near term, requiring emergency cesarean section. Postpartum MRI showed bilateral hippocampal atrophy. Despite seizure control, persistent cognitive symptoms remained. This case underscores the diagnostic complexity of seronegative LE in pregnancy and highlights that IVIG can be a safe and effective treatment option, even in the absence of confirmatory biomarkers. Our case also adds to the scarce literature on cognitive sequelae and long-term management in such scenarios.\u003c/p\u003e","manuscriptTitle":"Relapsing Seronegative Limbic Encephalitis During Pregnancy: A Rare Case with Bilateral Hippocampal Atrophy and Favorable Maternal-Fetal Outcome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 08:32:02","doi":"10.21203/rs.3.rs-6892381/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":"47158f0b-f463-41f0-a25e-aa913b28c452","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-31T15:24:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-23 08:32:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6892381","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6892381","identity":"rs-6892381","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}