Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: A Case Report.

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Stephanie Kuntz, Georges Saab, Raphael Schneider This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1350279/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: We report a case of de novo aquaporin-4 positive neuromyelitis optica spectrum disorder following BNT162b SARS-CoV-2 vaccination. Case Presentation: An 80-year-old South Asian man presented two days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3-T4 to T9-T10. Serum antibody testing revealed positive aquaporin-4 (AQP4) antibodies. He was diagnosed with de novo AQP4 positive neuromyelitis optica spectrum disorder (NMOSD) and was treated with high dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean. Conclusions: Evidence suggests vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further. NMOSD Aquaporin-4 COVID-19 Vaccination Case Report Figures Figure 1 Background Our case of a man with no previous history of neurological or inflammatory disease presenting with longitudinally extensive transverse myelitis (LETM), is, to our knowledge, the first case of de novo AQP4 positive NMOSD following BNT162b SARS-CoV-2 vaccination. Although we cannot prove causality, it is plausible that vaccination may have triggered disease activity in an individual with underlying susceptibility. While seronegative post-vaccination myelitis is often monophasic, a positive aquaporin-4-antibody test suggests NMOSD and an increased risk of future relapses. Case presentation A South Asian man in his early 80s with no prior history of neurological symptoms presented to our hospital with falls within days of receiving his second COVID-19 vaccine. He was previously independent with no baseline disability. He received the first dose of the COVID-19 mRNA BNT162b2 vaccine in the spring of 2021 without any complications and then received the second dose in the early summer of 2021. Within two days of receiving his second dose, he started falling and noticed gait instability, difficulty voiding urine, progressive left-sided leg weakness and numbness. He presented to our hospital after the weakness and numbness worsened, leading to multiple falls. On examination, he was afebrile and vitally stable. The cranial nerve exam was normal. Tone was normal in all four limbs. Upper extremity power was full. There was bilateral leg weakness in a pyramidal distribution, worse on the left (4-/5) than the right (4/5). His reflexes were 2+ and symmetric. Plantar responses were extensor bilaterally. Sensation to pinprick, light touch, and temperature was reduced in the left leg with a sensory level at T10 on the same side. Vibration sensation was reduced to the knee on the right and to the hip on the left. He was found to be in urinary retention requiring catheterization. An MRI of the spine demonstrated a peripherally enhancing longitudinally extensive intramedullary lesion extending from T3-T4 down to T9-T10. Smaller, more chronic-appearing non-enhancing dorsal cord lesions were noted at C4-C5 and T1 (FIGURE 1). An MRI of the brain did not show any evidence of intracranial demyelination. Serum aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies were both positive. C-reactive protein was mildly elevated at 10.9 mg/L. Serological screening for rheumatological and infectious diseases was unremarkable. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 39 with 93% lymphocytes. Protein, glucose, cytology and infectious studies were unremarkable. The oligoclonal band assay was negative for CSF-specific bands. Computer tomography (CT) of the chest, abdomen and pelvis did not demonstrate any evidence of an underlying malignancy or infection. In light of the above investigations, he was diagnosed with seropositive neuromyelitis optica spectrum disorder (NMOSD) and was treated accordingly with a three-day course of high-dose (1g) intravenous methylprednisolone. He experienced mild improvement in his urinary dysfunction and left leg weakness. He then underwent five sessions of plasma exchange (PLEX). His lower extremity power improved to 5/5 on the right and 4+/5 on the left following PLEX. He was maintained on Prednisone 40 mg daily and started on Mycophenolate Mofetil with a slow steroid wean. Repeat antibody testing after two weeks and prior to PLEX revealed that AQP4 antibodies remained positive, but MOG antibodies were negative. In retrospect, the initial positive MOG antibodies were felt to be falsely positive. On the 3-month follow-up visit, he denied any new symptoms and reported further improvement. Discussion and Conclusions This case illustrates AQP4 antibody-positive NMOSD after a second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine. NMOSD is an antibody-mediated disease of the central nervous system [1]. Typical presentations of NMOSD include attacks of severe unilateral, bilateral, or rapidly sequential optic neuritis and transverse myelitis, which generally involve three or more vertebral segments on MRI (termed longitudinally extensive transverse myelitis or LETM). In addition, other areas of the central nervous system (CNS) can also be affected, resulting in area postrema, other brainstem, diencephalic, or cerebral presentations in some patients [2]. Factors responsible for triggering CNS inflammatory diseases, including NMOSD, are not well understood, but evidence suggests immunizations may be implicated in some cases. In a study by Karussis & Petrou, vaccinations were estimated to carry an overall risk of 0.1% in triggering central nervous system (CNS) inflammatory diseases. The most common post-vaccination CNS syndromes in this study were acute optic neuritis and transverse myelitis. NMOSD, acute disseminated encephalomyelitis (ADEM), and encephalitis with white matter involvement were also reported [3]. Vaccinations that have been associated with NMOSD onset and/or relapses include influenza, tetanus and diphtheria (Td), tetanus, diphtheria, and pertussis (Tdap), human papillomavirus, pneumococcal, hepatitis A, hepatitis B, typhoid, yellow fever, and Japanese encephalitis vaccines [4]. Interestingly, the risk of an NMOSD relapse after vaccination seems to be most clearly observed in patients who are not on preventative immunotherapy [5]. The pathophysiology of vaccine-triggered CNS disease remains incompletely understood, but some studies suggest post-vaccination demyelination is most likely triggering clinical disease expression in individuals who already have an underlying disease process [6]. Evidence suggests that AQP4 antibodies may be detected long before clinical NMOSD onset, suggesting AQP4 antibody carriers can be asymptomatic for extended periods of time [7] . Theoretically, these individuals may be particularly susceptible to developing clinical symptoms when faced with a possible trigger. In the era of the COVID-19 pandemic with increasing vaccination rates worldwide, vaccine safety remains at the forefront of discussion. Neurological symptoms which have been reported in the Centers for Disease Control Vaccine Adverse Event Reporting System include dizziness, headache, pain, muscle spasms, myalgia, and paresthesias as well as rare cases of tremor, diplopia, tinnitus, dysphonia, seizures, and reactivation of herpes zoster. There are also rare cases of stroke, Guillan Barre Syndrome, facial palsy, transverse myelitis, and acute disseminated encephalomyelitis [8] . With regards to NMOSD, there is very limited data linking COVID-19 vaccinations with disease onset. A case report from Fujikawa and colleagues describe a 46-year-old woman presenting with LETM involving C6-T2 without enhancement diagnosed 10 days following the SARS-CoV-2 mRNA-1273 (Moderna) vaccine [9]. In contrast to our case, serum AQP4 antibodies were negative. Another case report described a middle-aged woman who developed mild fever, diarrhea, and area postrema syndrome three days after her first dose of an “inactivated virus vaccine.” MRI brain demonstrated area postrema and bilateral hypothalamus lesions without gadolinium enhancement. Serum testing was positive for AQP4, antinuclear, SSA, SSB, Ro-52, and p-ANCA antibodies. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity [10]. Overall, the risk of CNS disease post-vaccination remains lower than rates following infections against which the vaccines are aimed to protect. Additionally, current epidemiological data suggests the benefits of vaccinations both at an individual and population level prevail over potential risks of CNS complications [3,8]. Our case of a man with no previous history of neurological or inflammatory disease presenting with LETM, is, to our knowledge, the first case of de novo AQP4 positive NMOSD following BNT162b SARS-CoV-2 vaccination. Although we cannot prove causality, it is plausible that vaccination may have triggered disease activity in an individual with underlying susceptibility. Thus, we believe that people with presumed post-vaccine myelitis should be tested for AQP4 antibodies and, if the diagnostic criteria are met [2], managed like other patients with NMOSD. Abbreviations AQP4 - aquaporin-4 CNS -central nervous system CSF - cerebrospinal fluid CT - Computer tomography LETM - longitudinally extensive transverse myelitis MOG - myelin oligodendrocyte glycoprotein NMOSD - Neuromyelitis Optica Spectrum Disorder PLEX - plasma exchange Declarations Ethics approval and consent to participate: The need for approval was waived for a single case report. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of data and materials: Not applicable. Competing interests : The authors declare they have no competing interests. Funding : None. Authors' contributions SK drafted the manuscript GS and RS revised the manuscript. All authors read and approved the final manuscript Acknowledgements : None. References 1 Akaishi T, Takahashi T, Fujihara K, et al. Risk factors of attacks in neuromyelitis optica spectrum disorders. J Neuroimmunol 2020;343:577236. doi:10.1016/j.jneuroim.2020.577236 2 Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177–89. doi:10.1212/wnl.0000000000001729 3 Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev 2014;13:215–24. doi:10.1016/j.autrev.2013.10.003 4 Aimen V, Dean W. Systematic Review Investigating Relationship Between Neuromyelitis Optica Spectrum Disorder (NMOSD) and Vaccination (P1.2-003). ;92:P1.2- 003.http://n.neurology.org/content/92/15_Supplement/P1.2-003.abstract 5 Mealy MA, Cook LJ, Pache F, et al. Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder. Mult Scler Relat Dis 2018;23:78–82. doi:10.1016/j.msard.2018.05.003 6 DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and Risk of Central Nervous System Demyelinating Diseases in Adults. Arch Neurol-chicago 2003;60:504–9. doi:10.1001/archneur.60.4.504 7 Nishiyama S, Ito T, Misu T, et al. A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. Neurology 2009;72:1960–1. doi:10.1212/wnl.0b013e3181a82621 8 Goss AL, Samudralwar RD, Das RR, et al. ANA Investigates: Neurological Complications of COVID‐19 Vaccines. Ann Neurol 2021;89:856–7. doi:10.1002/ana.26065 9 Fujikawa P, Shah FA, Braford M, et al. Neuromyelitis Optica in a Healthy Female After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccine. Cureus 2021;13:e17961. doi:10.7759/cureus.17961 10 Chen S, Fan X-R, He S, et al. Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19. Neurol Sci 2021;42:3537–9. doi:10.1007/s10072-021-05427-4 Supplementary Files CAREChecklistComplete.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Mar, 2022 Reviewers invited by journal 14 Mar, 2022 Editor assigned by journal 15 Feb, 2022 First submitted to journal 11 Feb, 2022 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-1350279","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":90552329,"identity":"b46137d6-dd74-4e60-af6f-6885c17d40f7","order_by":0,"name":"Stephanie Kuntz","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Kuntz","suffix":""},{"id":90552330,"identity":"008ed2c9-f960-47e3-82a3-d5688c26ff35","order_by":1,"name":"Georges Saab","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Georges","middleName":"","lastName":"Saab","suffix":""},{"id":90552331,"identity":"0cc7fcf0-165b-4b5b-8cb1-0788960c6b0d","order_by":2,"name":"Raphael Schneider","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-1776-2418","institution":"University of Toronto","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Raphael","middleName":"","lastName":"Schneider","suffix":""}],"badges":[],"createdAt":"2022-02-11 13:30:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1350279/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1350279/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":19246747,"identity":"30b08faa-a079-4a6d-9df8-7198fe67a8bd","added_by":"auto","created_at":"2022-03-15 15:12:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":542137,"visible":true,"origin":"","legend":"\u003cp\u003eMRI of longitudinal spinal cord lesions: T2 weighted sagittal view of the cervical and upper thoracic cord showing a longitudinally extensive cord signal abnormality (A, red arrows), predominantly involving the central aspect (B, red arrowhead) of the cord from T3-T4 down to T9-T10. T1 weighted sagittal view with gadolinium showing a peripheral enhancement pattern (C, green arrows).\u003c/p\u003e","description":"","filename":"FIG1.png","url":"https://assets-eu.researchsquare.com/files/rs-1350279/v1/2eeddad9e7fe23ae01a7aa3c.png"},{"id":19246750,"identity":"762c7754-822f-4220-b680-4714ac838aed","added_by":"auto","created_at":"2022-03-15 15:12:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":222058,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1350279/v1/8a2bc690-1838-4ce6-9a6c-5f80f7a423d3.pdf"},{"id":19246748,"identity":"0b3d11a3-70af-48ea-95f8-f5b6cedf88f5","added_by":"auto","created_at":"2022-03-15 15:12:08","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":1434109,"visible":true,"origin":"","legend":"","description":"","filename":"CAREChecklistComplete.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1350279/v1/bced2c29a6e07e0d2e54948c.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAntibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: A Case Report.\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOur case of a man with no previous history of neurological or inflammatory disease presenting with longitudinally extensive transverse myelitis (LETM), is, to our knowledge, the first case of de novo AQP4 positive NMOSD following BNT162b SARS-CoV-2 vaccination. Although we cannot prove causality, it is plausible that vaccination may have triggered disease activity in an individual with underlying susceptibility. While seronegative post-vaccination myelitis is often monophasic, a positive aquaporin-4-antibody test suggests NMOSD and an increased risk of future relapses.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA South Asian man in his early 80s with no prior history of neurological symptoms presented to our hospital with falls within days of receiving his second COVID-19 vaccine. He was previously independent with no baseline disability. \u0026nbsp; He received the first dose of the COVID-19 mRNA BNT162b2 vaccine in the spring of 2021 without any complications and then received the second dose in the early summer of 2021. Within two days of receiving his second dose, he started falling and noticed gait instability, difficulty voiding urine, progressive left-sided leg weakness and numbness. He presented to our hospital after the weakness and numbness worsened, leading to multiple falls. On examination, he was afebrile and vitally stable. The cranial nerve exam was normal. Tone was normal in all four limbs. Upper extremity power was full. There was bilateral leg weakness in a pyramidal distribution, worse on the left (4-/5) than the right (4/5). His reflexes were 2+ and symmetric. Plantar responses were extensor bilaterally. Sensation to pinprick, light touch, and temperature was reduced in the left leg with a sensory level at T10 on the same side. Vibration sensation was reduced to the knee on the right and to the hip on the left. He was found to be in urinary retention requiring catheterization.\u003c/p\u003e\n\u003cp\u003eAn MRI of the spine demonstrated a peripherally enhancing longitudinally extensive intramedullary lesion extending from T3-T4 down to T9-T10. Smaller, more chronic-appearing non-enhancing dorsal cord lesions were noted at C4-C5 and T1 (FIGURE 1). An MRI of the brain did not show any evidence of intracranial demyelination. Serum aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies were both positive. C-reactive protein was mildly elevated at 10.9 mg/L. Serological screening for rheumatological and infectious diseases was unremarkable. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 39 with 93% lymphocytes. Protein, glucose, cytology and infectious studies were unremarkable. The oligoclonal band assay was negative for CSF-specific bands. Computer tomography (CT) of the chest, abdomen and pelvis did not demonstrate any evidence of an underlying malignancy or infection.\u003c/p\u003e\n\u003cp\u003eIn light of the above investigations, he was diagnosed with seropositive neuromyelitis optica spectrum disorder (NMOSD) and was treated \u0026nbsp;accordingly with a three-day course of high-dose (1g) intravenous methylprednisolone. He experienced mild improvement in his urinary dysfunction and left leg weakness. He then underwent five sessions of plasma exchange (PLEX). His lower extremity power improved to 5/5 on the right and 4+/5 on the left following PLEX. He was maintained on Prednisone 40 mg daily and started on Mycophenolate Mofetil with a slow steroid wean.\u003c/p\u003e\n\u003cp\u003eRepeat antibody testing after two weeks and prior to PLEX revealed that AQP4 antibodies remained positive, but MOG antibodies were negative. In retrospect, the initial positive MOG antibodies were felt to be falsely positive. On the 3-month follow-up visit, he denied any new symptoms and reported further improvement.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThis case illustrates AQP4 antibody-positive NMOSD after a second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine. \u0026nbsp;NMOSD is an antibody-mediated disease of the central nervous system [1]. Typical presentations of NMOSD include attacks of severe unilateral, bilateral, or rapidly sequential optic neuritis and transverse myelitis, which generally involve three or more vertebral segments on MRI (termed longitudinally extensive transverse myelitis or LETM). In addition, other areas of the central nervous system (CNS) can also be affected, resulting in area postrema, other brainstem, diencephalic, or cerebral presentations in some patients [2].\u003c/p\u003e\n\u003cp\u003eFactors responsible for triggering CNS inflammatory diseases, including NMOSD, are not well understood, but evidence suggests immunizations may be implicated in some cases. In a study by Karussis \u0026amp; Petrou, vaccinations were estimated to carry an overall risk of 0.1% in triggering central nervous system (CNS) inflammatory diseases. The most common post-vaccination CNS syndromes in this study were acute optic neuritis and transverse myelitis. NMOSD, acute disseminated encephalomyelitis (ADEM), and encephalitis with white matter involvement were also reported [3]. Vaccinations that have been associated with NMOSD onset and/or relapses include influenza, tetanus and diphtheria (Td), tetanus, diphtheria, and pertussis (Tdap), human papillomavirus, pneumococcal, hepatitis A, hepatitis B, typhoid, yellow fever, and Japanese encephalitis vaccines [4]. Interestingly, the risk of an NMOSD relapse after vaccination seems to be most clearly observed in patients who are not on preventative immunotherapy [5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe pathophysiology of vaccine-triggered CNS disease remains incompletely understood, but some studies suggest post-vaccination demyelination is most likely triggering clinical disease expression in individuals who already have an underlying disease process [6]. Evidence suggests that AQP4 antibodies may be detected long before clinical NMOSD onset, suggesting AQP4 antibody carriers can be asymptomatic for extended periods of time\u003csup\u003e\u0026nbsp;[7]\u003c/sup\u003e. Theoretically, these individuals may be particularly susceptible to developing clinical symptoms when faced with a possible trigger. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the era of the COVID-19 pandemic with increasing vaccination rates worldwide, vaccine safety remains at the forefront of discussion. \u0026nbsp; Neurological symptoms which have been reported in the Centers for Disease Control Vaccine Adverse Event Reporting System include dizziness, headache, pain, muscle spasms, myalgia, and paresthesias as well as rare cases of tremor, diplopia, tinnitus, dysphonia, seizures, and reactivation of herpes zoster. There are also rare cases of stroke, Guillan Barre Syndrome, facial palsy, transverse myelitis, and\u0026nbsp;acute disseminated encephalomyelitis\u003csup\u003e[8]\u003c/sup\u003e. With regards to NMOSD, there is very limited data linking COVID-19 vaccinations with disease onset. A case report from Fujikawa and colleagues describe a 46-year-old woman presenting with LETM involving C6-T2 without enhancement diagnosed 10 days following the SARS-CoV-2 mRNA-1273 (Moderna) vaccine [9]. In contrast to our case, serum AQP4 antibodies were negative. Another case report described a middle-aged woman who developed mild fever, diarrhea, and area postrema syndrome three days after her first dose of an \u0026ldquo;inactivated virus vaccine.\u0026rdquo; MRI brain demonstrated area postrema and bilateral hypothalamus lesions without gadolinium enhancement. Serum testing was positive for AQP4, antinuclear, SSA, SSB, Ro-52, and p-ANCA antibodies. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity [10].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, the risk of CNS disease post-vaccination remains lower than rates following infections against which the vaccines are aimed to protect. Additionally, current epidemiological data suggests the benefits of vaccinations both at an individual and population level prevail over potential risks of CNS complications [3,8]. Our case of a man with no previous history of neurological or inflammatory disease presenting with LETM, is, to our knowledge, the first case of de novo AQP4 positive NMOSD following BNT162b SARS-CoV-2 vaccination. Although we cannot prove causality, it is plausible that vaccination may have triggered disease activity in an individual with underlying susceptibility. Thus, we believe that people with presumed post-vaccine myelitis should be tested for AQP4 antibodies and, if the diagnostic criteria are met [2], managed like other patients with NMOSD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAQP4 - aquaporin-4\u003c/p\u003e\n\u003cp\u003eCNS -central nervous system\u003c/p\u003e\n\u003cp\u003eCSF - cerebrospinal fluid\u003c/p\u003e\n\u003cp\u003eCT -\u0026nbsp;Computer tomography\u003c/p\u003e\n\u003cp\u003eLETM - longitudinally extensive transverse myelitis\u003c/p\u003e\n\u003cp\u003eMOG - myelin oligodendrocyte glycoprotein\u003c/p\u003e\n\u003cp\u003eNMOSD - Neuromyelitis Optica Spectrum Disorder\u003c/p\u003e\n\u003cp\u003ePLEX - plasma exchange\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The need for approval was waived for a single case report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e Not applicable. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eSK drafted the manuscript\u003c/li\u003e\n \u003cli\u003eGS and RS revised the manuscript.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAll authors read and approved the final manuscript\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: None.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1 Akaishi T, Takahashi T, Fujihara K, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eRisk factors of attacks in neuromyelitis optica spectrum disorders. \u003cem\u003eJ Neuroimmunol\u0026nbsp;\u003c/em\u003e2020;343:577236. doi:10.1016/j.jneuroim.2020.577236\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2 Wingerchuk DM, Banwell B, Bennett JL, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eInternational consensus diagnostic criteria for neuromyelitis optica spectrum disorders. \u003cem\u003eNeurology\u0026nbsp;\u003c/em\u003e2015;85:177\u0026ndash;89. doi:10.1212/wnl.0000000000001729\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3 Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. \u003cem\u003eAutoimmun Rev\u0026nbsp;\u003c/em\u003e2014;13:215\u0026ndash;24. doi:10.1016/j.autrev.2013.10.003\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4 Aimen V, Dean W. Systematic Review Investigating Relationship Between Neuromyelitis Optica Spectrum Disorder (NMOSD) and Vaccination (P1.2-003). ;92:P1.2- 003.http://n.neurology.org/content/92/15_Supplement/P1.2-003.abstract\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5 Mealy MA, Cook LJ, Pache F, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eVaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder. \u003cem\u003eMult Scler Relat Dis\u0026nbsp;\u003c/em\u003e2018;23:78\u0026ndash;82. doi:10.1016/j.msard.2018.05.003\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6 DeStefano F, Verstraeten T, Jackson LA, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eVaccinations and Risk of Central Nervous System Demyelinating Diseases in Adults. \u003cem\u003eArch Neurol-chicago\u0026nbsp;\u003c/em\u003e2003;60:504\u0026ndash;9. doi:10.1001/archneur.60.4.504\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7 Nishiyama S, Ito T, Misu T, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eA case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. \u003cem\u003eNeurology\u0026nbsp;\u003c/em\u003e2009;72:1960\u0026ndash;1. doi:10.1212/wnl.0b013e3181a82621\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8 Goss AL, Samudralwar RD, Das RR, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eANA Investigates: Neurological Complications of COVID‐19 Vaccines. \u003cem\u003eAnn Neurol\u0026nbsp;\u003c/em\u003e2021;89:856\u0026ndash;7. doi:10.1002/ana.26065\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9 Fujikawa P, Shah FA, Braford M, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eNeuromyelitis Optica in a Healthy Female After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccine. \u003cem\u003eCureus\u0026nbsp;\u003c/em\u003e2021;13:e17961. doi:10.7759/cureus.17961\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e10 Chen S, Fan X-R, He S, \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003eWatch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19. \u003cem\u003eNeurol Sci\u0026nbsp;\u003c/em\u003e2021;42:3537\u0026ndash;9. doi:10.1007/s10072-021-05427-4\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"NMOSD, Aquaporin-4, COVID-19, Vaccination, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-1350279/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1350279/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eWe report a case of de novo aquaporin-4 positive neuromyelitis optica spectrum disorder following BNT162b SARS-CoV-2 vaccination.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase Presentation: \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAn 80-year-old South Asian man presented two days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3-T4 to T9-T10. Serum antibody testing revealed positive aquaporin-4\u0026nbsp;(AQP4) antibodies. He was diagnosed with de novo AQP4 positive neuromyelitis optica spectrum disorder (NMOSD) and was treated with high dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Evidence suggests vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.\u003c/p\u003e","manuscriptTitle":"Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: A Case Report.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-03-15 15:12:06","doi":"10.21203/rs.3.rs-1350279/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2022-03-17T07:29:43+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-03-14T08:37:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-02-16T03:22:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2022-02-11T08:30:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7f7ebc3a-cfb4-434f-ac15-961072ae9582","owner":[],"postedDate":"March 15th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-06-14T11:08:51+00:00","versionOfRecord":[],"versionCreatedAt":"2022-03-15 15:12:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1350279","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1350279","identity":"rs-1350279","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}