Bilateral Pulmonary Embolism in Anti-NMDA Receptor Encephalitis Presenting as Acute Psychosis | 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 Research Article Bilateral Pulmonary Embolism in Anti-NMDA Receptor Encephalitis Presenting as Acute Psychosis Natali Sorajja, Priyansh Shah, Luca Biavati, Sudhamsh Desai, Adir Alper This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9298747/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 Background: Anti–N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder that frequently presents with prominent psychiatric manifestations, often leading to misdiagnosis as a primary psychiatric illness. Early recognition is critical, as timely immunotherapy significantly improves outcomes. Case Presentation: We report a 26-year-old previously healthy male who presented with acute psychosis, hallucinations, and altered mental status. Notable precipitating events included recent stress regarding his mother's health and first-time use of marijuana 3 days prior. He was initially diagnosed with brief psychotic disorder and treated with antipsychotics. During hospitalization, he developed a fever, prompting cerebrospinal fluid (CSF) analysis, which revealed anti–NMDA receptor antibodies in both serum and CSF. His hospital course was complicated by bilateral pulmonary emboli—likely provoked by prolonged immobilization and systemic inflammation—and drug-induced liver injury secondary to polypharmacy. He was treated with intravenous immunoglobulin (IVIG) and high-dose corticosteroids, resulting in marked clinical improvement. Malignancy work-up was negative. Conclusion: This case underscores the importance of considering autoimmune encephalitis in young patients presenting with new-onset psychosis. It further highlights venous thromboembolism and hepatotoxicity as underrecognized complications that warrant prophylactic measures and routine monitoring in this population. anti-NMDA receptor encephalitis autoimmune encephalitis pulmonary embolism drug-induced liver injury Figures Figure 1 Figure 2 Dear Editor We present a case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis in a young adult male, initially misdiagnosed as brief psychotic disorder, complicated by bilateral pulmonary emboli and drug-induced liver injury. This case highlights diagnostic challenges, underrecognized systemic complications, and the importance of early cerebrospinal fluid (CSF) evaluation in patients with new-onset psychosis. A 26-year-old previously healthy male presented to the emergency department with one week of progressive hallucinations, paranoia, and behavioral changes. Precipitating factors included emotional distress regarding his mother’s health and first-time marijuana use three days prior to symptom onset. The family initially sought religious and spiritual interventions before seeking medical care. On arrival, the patient was agitated and uncooperative, requiring chemical and physical restraints. Urine toxicology and routine laboratories were unremarkable. Psychiatry diagnosed brief psychotic disorder and initiated haloperidol. Despite treatment, the patient exhibited fluctuating responsiveness, poor oral intake, and features suggestive of catatonia. Valproate was added for seizure precaution. A transient fever prompted further evaluation. Consent for lumbar puncture was delayed two days due to family concerns. CSF analysis revealed anti-NMDA receptor IgG antibodies (CSF titer 1:20; serum titer 1:320). Electroencephalography demonstrated diffuse slowing with a delta brush pattern. Brain MRI was unremarkable (Figure 1). The patient received a seven-day course of intravenous immunoglobulin (IVIG) followed by high-dose methylprednisolone with an oral prednisone taper. During hospitalization, computed tomography revealed bilateral pulmonary emboli. Transthoracic echocardiography showed normal biventricular function. Hematology attributed the emboli to immobilization and systemic inflammation. Apixaban was initiated. Additionally, elevated transaminases developed (Figure 2), attributed to drug-induced liver injury from the combination of antipsychotics, valproate, benzodiazepines, IVIG, and corticosteroids. Malignancy screening was negative. Following immunotherapy, the patient demonstrated marked clinical improvement and was discharged 36 days after admission, oriented and cooperative, with mild residual cognitive impairment. This case illustrates several important points. Anti-NMDA receptor encephalitis frequently mimics primary psychiatric disorders, and cases without distinguishing clinical features from other psychoses have been reported [1, 2]. A high index of suspicion, particularly in young patients with rapidly progressive psychosis or poor antipsychotic response, is essential to prompt timely CSF evaluation. Potential triggers in this case included marijuana use and emotional stress. Marijuana has been implicated in anti-NMDA receptor encephalitis through proposed mechanisms including molecular mimicry between cannabinoid and NMDA receptors [3]. These triggers merit consideration especially in cases without paraneoplastic etiology. Venous thromboembolism is an underrecognized complication in severe autoimmune encephalitis. Our patient’s prolonged catatonia and agitation-related immobility, combined with IVIG therapy—which has a known association with thromboembolic events [4]—likely contributed. Prophylactic anticoagulation should be considered in patients with prolonged catatonia [5]. Finally, drug-induced liver injury warrants routine monitoring given the polypharmacy typical of anti-NMDA receptor encephalitis management. Declarations Competing Interests: The authors declare that they have no conflict of interest. Funding: No funding was received for conducting this study. Ethics Approval: Not applicable. Consent to Publish: Written, signed informed consent was obtained from the patient for the publication of their clinical history. Author Contributions: All authors contributed to the study conception and design. Material preparation and data collection were performed by Natali Sorajja and Adir Alper. The first draft of the manuscript was written by Natali Sorajja and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments: The authors would like to thank the patient and his family for granting permission to share this case for educational purposes. References Pădureanu V, Dop D, Pădureanu R, Pîrșcoveanu DFV, Olaru G, Streata I, et al (2025) Anti-NMDA Receptor Encephalitis: A Narrative Review. Brain Sci 15(5):518. https://doi.org/10.3390/brainsci15050518 Zandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, et al (2011) Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 258(4):686–688. https://doi.org/10.1007/s00415-010-5788-9 Hau L, Csabi G, Rozsai B, Stankovics J, Tenyi T, Hollody K (2016) Anti-N-methyl-D-aspartate receptor encephalitis and drug abuse – the probable role of molecular mimicry or the overstimulation of CB receptors in a 17-year-old adolescent – case report. Neuropsychopharmacol Hung 18(3):162–164 Nguyen L, Wang C (2023) Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies. IJGM 16:7–21. https://doi.org/10.2147/IJGM.S397429 Ishida T, Shimada M, Mizuno M, Suzuki T, Uchida H (2025) Risk factors for venous thromboembolism among psychiatric inpatients: a case control study. J Psychiatr Res 190:6–10. https://doi.org/10.1016/j.jpsychires.2025.07.001 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. 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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-9298747","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":620570705,"identity":"187819bb-731d-47a2-b049-b6d04b634c49","order_by":0,"name":"Natali Sorajja","email":"","orcid":"","institution":"Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Natali","middleName":"","lastName":"Sorajja","suffix":""},{"id":620570707,"identity":"b5d78446-c927-42f0-be54-fea2d6377909","order_by":1,"name":"Priyansh Shah","email":"","orcid":"","institution":"Jacobi Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Priyansh","middleName":"","lastName":"Shah","suffix":""},{"id":620570708,"identity":"efab174b-d8fe-4133-aefb-fe7152eeeeb8","order_by":2,"name":"Luca Biavati","email":"","orcid":"","institution":"Jacobi Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Luca","middleName":"","lastName":"Biavati","suffix":""},{"id":620570709,"identity":"ebdc8f32-7588-4191-a827-0f2614acc11a","order_by":3,"name":"Sudhamsh Desai","email":"","orcid":"","institution":"Jacobi Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sudhamsh","middleName":"","lastName":"Desai","suffix":""},{"id":620570714,"identity":"7c0316d3-2252-4749-b630-061790f33c7c","order_by":4,"name":"Adir Alper","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYDACdjBpA8Q8bERqYQaTaaRrOUyCFv5m3oOPK2rO5xkcP3vswQ8Gm3x5BwJaJA7zJRueOXa72OBMXrphD0Oa5cYDhKw5zGMm2cB2O3HDDR4zaSDXwLCBgA75wzzmPxv+nSNBiwHQFsbGtgMILfKE3GUI9ItkY19y4swzOWaSPQZpBgaEtMgd7z34seGbXWLf8TNmEj8qbAzkCTkMGB0QSuEA2J1AdIBYLXDDibBlFIyCUTAKRhgAAKhIPgLyEsgSAAAAAElFTkSuQmCC","orcid":"","institution":"Jacobi Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Adir","middleName":"","lastName":"Alper","suffix":""}],"badges":[],"createdAt":"2026-04-02 06:10:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9298747/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9298747/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107255702,"identity":"27a5cf6c-a7d3-4eff-bb01-cf3541d1fbd7","added_by":"auto","created_at":"2026-04-19 12:11:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":228366,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline of symptom onset, diagnostic evaluation, and treatment course.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9298747/v1/b1d099443f6a4e81029fb7ac.png"},{"id":107484976,"identity":"9282e0a1-3cb4-4d70-9054-7e210de7b44d","added_by":"auto","created_at":"2026-04-22 02:33:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75245,"visible":true,"origin":"","legend":"\u003cp\u003eTrends in liver transaminases during hospitalization.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9298747/v1/b4f102cae6354db4d615e4a3.png"},{"id":107487316,"identity":"2bd3d64c-a1a7-46a9-8c9c-94a2607f76fe","added_by":"auto","created_at":"2026-04-22 02:40:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":371417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9298747/v1/538ca35f-6c7e-434d-aab6-be826d0fc044.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bilateral Pulmonary Embolism in Anti-NMDA Receptor Encephalitis Presenting as Acute Psychosis","fulltext":[{"header":"Dear Editor","content":"\u003cp\u003eWe present a case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis in a young adult male, initially misdiagnosed as brief psychotic disorder, complicated by bilateral pulmonary emboli and drug-induced liver injury. This case highlights diagnostic challenges, underrecognized systemic complications, and the importance of early cerebrospinal fluid (CSF) evaluation in patients with new-onset psychosis.\u003c/p\u003e\n\u003cp\u003eA 26-year-old previously healthy male presented to the emergency department with one week of progressive hallucinations, paranoia, and behavioral changes. Precipitating factors included emotional distress regarding his mother\u0026rsquo;s health and first-time marijuana use three days prior to symptom onset. The family initially sought religious and spiritual interventions before seeking medical care. On arrival, the patient was agitated and uncooperative, requiring chemical and physical restraints. Urine toxicology and routine laboratories were unremarkable. Psychiatry diagnosed brief psychotic disorder and initiated haloperidol. Despite treatment, the patient exhibited fluctuating responsiveness, poor oral intake, and features suggestive of catatonia. Valproate was added for seizure precaution.\u003c/p\u003e\n\u003cp\u003eA transient fever prompted further evaluation. Consent for lumbar puncture was delayed two days due to family concerns. CSF analysis revealed anti-NMDA receptor IgG antibodies (CSF titer 1:20; serum titer 1:320). Electroencephalography demonstrated diffuse slowing with a delta brush pattern. Brain MRI was unremarkable (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe patient received a seven-day course of intravenous immunoglobulin (IVIG) followed by high-dose methylprednisolone with an oral prednisone taper. During hospitalization, computed tomography revealed bilateral pulmonary emboli. Transthoracic echocardiography showed normal biventricular function. Hematology attributed the emboli to immobilization and systemic inflammation. Apixaban was initiated. Additionally, elevated transaminases developed (Figure 2), attributed to drug-induced liver injury from the combination of antipsychotics, valproate, benzodiazepines, IVIG, and corticosteroids. Malignancy screening was negative. Following immunotherapy, the patient demonstrated marked clinical improvement and was discharged 36 days after admission, oriented and cooperative, with mild residual cognitive impairment.\u003c/p\u003e\n\u003cp\u003eThis case illustrates several important points. Anti-NMDA receptor encephalitis frequently mimics primary psychiatric disorders, and cases without distinguishing clinical features from other psychoses have been reported [1, 2]. A high index of suspicion, particularly in young patients with rapidly progressive psychosis or poor antipsychotic response, is essential to prompt timely CSF evaluation.\u003c/p\u003e\n\u003cp\u003ePotential triggers in this case included marijuana use and emotional stress. Marijuana has been implicated in anti-NMDA receptor encephalitis through proposed mechanisms including molecular mimicry between cannabinoid and NMDA receptors [3]. These triggers merit consideration especially in cases without paraneoplastic etiology.\u003c/p\u003e\n\u003cp\u003eVenous thromboembolism is an underrecognized complication in severe autoimmune encephalitis. Our patient\u0026rsquo;s prolonged catatonia and agitation-related immobility, combined with IVIG therapy\u0026mdash;which has a known association with thromboembolic events [4]\u0026mdash;likely contributed. Prophylactic anticoagulation should be considered in patients with prolonged catatonia [5]. Finally, drug-induced liver injury warrants routine monitoring given the polypharmacy typical of anti-NMDA receptor encephalitis management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish:\u0026nbsp;\u003c/strong\u003eWritten, signed informed consent was obtained from the patient for the publication of their clinical history.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. Material preparation and data collection were performed by Natali Sorajja and Adir Alper. The first draft of the manuscript was written by Natali Sorajja and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThe authors would like to thank the patient and his family for granting permission to share this case for educational purposes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePădureanu V, Dop D, Pădureanu R, P\u0026icirc;rșcoveanu DFV, Olaru G, Streata I, et al (2025) Anti-NMDA Receptor Encephalitis: A Narrative Review. Brain Sci 15(5):518. https://doi.org/10.3390/brainsci15050518\u003c/li\u003e\n\u003cli\u003eZandi MS, Irani SR, Lang B, Waters P, Jones PB, McKenna P, et al (2011) Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 258(4):686\u0026ndash;688. https://doi.org/10.1007/s00415-010-5788-9\u003c/li\u003e\n\u003cli\u003eHau L, Csabi G, Rozsai B, Stankovics J, Tenyi T, Hollody K (2016) Anti-N-methyl-D-aspartate receptor encephalitis and drug abuse \u0026ndash; the probable role of molecular mimicry or the overstimulation of CB receptors in a 17-year-old adolescent \u0026ndash; case report. Neuropsychopharmacol Hung 18(3):162\u0026ndash;164\u003c/li\u003e\n\u003cli\u003eNguyen L, Wang C (2023) Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies. IJGM 16:7\u0026ndash;21. https://doi.org/10.2147/IJGM.S397429\u003c/li\u003e\n\u003cli\u003eIshida T, Shimada M, Mizuno M, Suzuki T, Uchida H (2025) Risk factors for venous thromboembolism among psychiatric inpatients: a case control study. J Psychiatr Res 190:6\u0026ndash;10. https://doi.org/10.1016/j.jpsychires.2025.07.001\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":"anti-NMDA receptor encephalitis, autoimmune encephalitis, pulmonary embolism, drug-induced liver injury","lastPublishedDoi":"10.21203/rs.3.rs-9298747/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9298747/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAnti–N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder that frequently presents with prominent psychiatric manifestations, often leading to misdiagnosis as a primary psychiatric illness. Early recognition is critical, as timely immunotherapy significantly improves outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation:\u003c/strong\u003e We report a 26-year-old previously healthy male who presented with acute psychosis, hallucinations, and altered mental status. Notable precipitating events included recent stress regarding his mother's health and first-time use of marijuana 3 days prior. He was initially diagnosed with brief psychotic disorder and treated with antipsychotics. During hospitalization, he developed a fever, prompting cerebrospinal fluid (CSF) analysis, which revealed anti–NMDA receptor antibodies in both serum and CSF. His hospital course was complicated by bilateral pulmonary emboli—likely provoked by prolonged immobilization and systemic inflammation—and drug-induced liver injury secondary to polypharmacy. He was treated with intravenous immunoglobulin (IVIG) and high-dose corticosteroids, resulting in marked clinical improvement. Malignancy work-up was negative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This case underscores the importance of considering autoimmune encephalitis in young patients presenting with new-onset psychosis. It further highlights venous thromboembolism and hepatotoxicity as underrecognized complications that warrant prophylactic measures and routine monitoring in this population.\u003c/p\u003e","manuscriptTitle":"Bilateral Pulmonary Embolism in Anti-NMDA Receptor Encephalitis Presenting as Acute Psychosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 12:11:02","doi":"10.21203/rs.3.rs-9298747/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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