Opsoclonus-myoclonus-ataxia syndrome due to Covid-19

Opsoclonus-myoclonus-ataxia syndrome due to Covid-19 | 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 Opsoclonus-myoclonus-ataxia syndrome due to Covid-19 Michael Adamaszek, Soenke Langner, Alexander Heinrich, Jan Mehrholz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3192635/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2023 Read the published version in The Cerebellum → Version 1 posted 7 You are reading this latest preprint version Abstract Opsoclonus myoclonus syndrome (OMS) is a rare neurological encephalopathic entity associated with non-specific infections or cancer processes that has been occasionally described in the setting of SARS-CoV-2 infection. We report a case of a 53-year-old man with SARS-CoV-2 infection, who developed clinical features of opsoclonus-myoclonus syndrome. Of particular note, cerebrospinal fluid analysis (CSF) analysis revealed the production of myelin oligodendrocyte glycoprotein (MOG) antibodies, suggesting an underlying neuroimmunological mechanism associated with infection with the novel SARS-CoV-2 virus. Full Text In addition to the primary medical and epidemiological challenges, the SARS-CoV-2 pandemic has triggered a vivid research activity on the organic dysfunctions associated with the virus known as Covid-19 and numerous investigations have been undertaken aiming to capture and refine the pathogenetic features of this virus (Ritchie et al., 2021 ). In addition to cardiorespiratory and haemastaseological organ manifestations, the effects of the virus on neuronal tissues of the peripheral and central nervous systems have increasingly been observed and discussed (Ellul et al., 2020 ; Helms et al., 2020 ; Balcom et al., 2021 ) including direct pathogenic activities of SARS-CoV-2 predominantly in the brain, and immunologically mediated mechanisms (Jha et al., 2021 ). The peripheral nervous system is frequently involved in the form of Guillian-Barré syndrome-like acute polyneuritis, and the central nervous system may be affected in form of a multifocal encephalitis as well as myelitis (Ellul et al., 2020 ; Balcom et al., 2021 ; Jha et al., 2021 ). According to a recent review, most cases of CNS syndromes in relation to SARS-CoV-2 are immunologically mediated disorders (Sriwastava et al., 2021 ). In analogy to other established parainfectious neurological diseases, detailed functional-analytical, i.e. neurophysiological, radiological and laboratory chemical investigations are necessary to establish a presumed causal relationship between a neurological manifestation and SARS-CoV-2 infection, if not to prove it. Over the past two and a half years, in addition to numerous systematic studies, a large number of individual cases of neurological disease as a result of SARS-CoV-2 infection have been reported. However, opsoclonus-myoclonus syndrome (OMS) has been only very rarely reported in association with SARS-CoV-2 infection (Foucard et al., 2021 ; Emamikkah et al., 2021 ; Saha et al., 2021 ; Chacko and Maramattom, 2022 ). Here we present an additional case of acute central nervous movement disorder secondary to acute SARS-CoV-2 infection. A 54-year-old man with a negative neurological history was admitted to hospital with respiratory symptoms. A few days earlier, he had tested positive for SARS-CoV-2 antigen. The patient's general condition deteriorated with fever, progressive respiratory insufficiency, opsoclonus and generalised myoclonic jerks. Covid-19 pneumonia was then diagnosed by computed tomography and the patient was transferred to the intensive care unit, where full heparinisation and treatment with dexamethasone were initiated. Symptomatic treatment of myoclonus with levetiracetam and clonazepam was initiated and later supplemented with valproic acid due to inadequate symptom control. Additional pharmacological treatment with clonidine and nepresol was given to control arterial blood pressure. In addition to a gradual stabilisation of respiratory function, a moderate improvement of myoclonus and opsoclonus was initially achieved. However, the patient developed a delirious state with agitation, oral automatisms and pronounced grimacing. After the patient's general condition became increasingly stable, he was transferred to a neurorehabilitative treatment, where myoclonia and orofacial dyskinesia were still occasionally present. Further reduction of symptoms, particularly myoclonus, was achieved by increasing the dose of valproic acid and clonazepam. Due to unsatisfactory clinical control of the intermittent oromandibular myoclonia with significant speech and swallowing impairment, trihexphenidyl was added. With this triple therapy, extensive symptom control of the oromandibular myoclonia was achieved, allowing a gradual dose reduction without recurrence of symptoms. Neuroradiological examination showed calcifications within the basal ganglia, wide perivascular spaces and morphological features of cerebral microangiopathy, but no evidence of inflammatory changes on MRI. EEG showed no hypersynchronous activity but intermittent focal rhythm slowing in the theta spectrum frontoparietally bilaterally. CSF analysis was positive for MOG Ig-G antibodies (1:80), although there was no pleocytosis, and oligoclonal bands were negative. Clinical neurorehabilitation focused mainly on ataxia, but also on hypertonic dysarthria, aphasia and fluctuating cognitive impairment, mainly in the attentional domain, resulting in marked improvements in both motor and neurocognitive skills. The patient was discharged home with a walker as a temporary mobility aid. The present case illustrates an opsoclonus-myoclonus syndrome (OMS) in connection with a SARS-CoV-2 infection, which has been rarely reported before by other authors in the course of the Covid-19 pandemic. A causal relationship between OMS and the SARS-CoV-2 infection or the clinically definable Covid-19 in the present case can be assumed, not only because of the temporal relationship (Mirmosayyeb et al., 2023 ), but also with regard to the CSF-analytical proof of antibody production against neural myelin protein (myelin oligodendrocyte glycoprotein; MOG). The striking cognitive impairment in this case are in line with numerous clinical observations of a parainfectious encephalopathy with an OMS following viral infection (Foucard et al., 2021 ). OMS is characterised by a variable combination of opsoclonus, i.e. irregular, involuntary and arrhythmic eye movements in horizontal, vertical and diagonal directions, and myoclonus, characterised by sudden and brief spasms of multiple muscles resulting in jerky movements (Gorman, 2010 ). In addition, cerebellar ataxia is one of the clinical features of this entity, and cognitive impairments such as aphasia or attention problems have been reported on several occasions (Goth et al., 2020). OMS is a rare disease with a predominantly paraneoplastic or parainfectious aetiology associated with a wide range of viral infections (Verma and Brozman, 2002 ; Glatz et al, 2003 ; Khosla et al, 2005 ; Zaganas et al, 2007 ; Ertekin and Tan, 2010 ; Kanjanasut et al, 2010 ; Oh et al, 2019 ). Associations with anti-Ri or anti-ANNA-2 antibodies have been reported in paraneoplastic cases of extracranial solid tumours (Klaas et al., 2012 ; Armangué et al., 2016 ; Sriwastava et al., 2021 ). However, as a reliable diagnostic immunological marker has not yet been found, a significant number of patients cannot be definitively diagnosed and are often diagnosed as having idiopathic OMS. Nevertheless, OMS was rarely reported as a case of central nervous system (CNS) involvement with SARS-CoV-2 during the Covid-19 pandemic. Of note, the causal mechanisms of CNS involvement after SARS-CoV-2 infection are still under discussion, including direct virus-mediated tissue damage, a secondary pathway due to systemic effects such as hypoxia or cerebrovascular injury, but also tissue damage due to autoimmune mechanisms (Ellul et al., 2020 ; Jha et al., 2021 ) seem to play a crucial role. The finding of MOG-specific antibody production identified in the present case is interesting, as MOG-specific antibodies have been repeatedly reported in cases of encephalitis following SARS-CoV-2 infection (Durovic et al., 2021 ; Peters et al., 2021 ; Mirmosayyeb et al., 2023 ), but with different clinical and radiological features, including cognitive impairment, paresis and sensory disturbances, and diffuse cerebral hyperintensities and leptomeningeal enhancement on MRI. Observations in the patient reported here and in another paediatric case of MOG antibody-positive OMS following SARS-CoV-2 infection (Adhikari et al., 2021 ) suggest that OMS may be a rare manifestation of MOG antibody-associated encephalitis. MOG antibodies have been found in CNS inflammatory diseases following a variety of systemic infections, suggesting that SARS-CoV-2 infection with Covid-19 may have been an immunological trigger for MOG antibody production in our case (Sato et al., 2020 ; Sriwastava et al., 2021 ). The normal CSF laboratory parameters observed in the present case are consistent with the majority of reports of SARS-CoV-2 infection with neurological disorders (Balcom et al., 2021 ; Sriwastava et al., 2021 ). In addition, normal brain MRI findings in patients with neurological disorders including OMS associated with SARS-CoV-2 infections have been described in several reports (e.g. overview of Sriwastava et al., 2021 , and also Mirmosayyeb et al., 2023 ). Considering the diversity of autoantigens reported in OMS in the absence of a disease-specific antibody marker (Bataller et al., 2005), OMS is thought to be caused by cerebellar degeneration following neuroimmunological processes against various surface targets (Blaes et al., 2005 ). Notable, MOG-specific antibodies have been shown to have a high affinity to cerebellar surface antigens (Banks et al., 2020 ), supporting the notion of a causal role for MOG-antibodies in the present case. MOG-antibody production has been observed in several cases of acute neurological diseases such as acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), or transverse myelitis (MY) associated with SARS-CoV-2 infection (Sriwastava et al., 2021 ), even at low MOG antibody titres (1:160) and normal cell counts in CFS (Sawalha et al., 2020 ). Immunosuppressive treatments with steroids, intravenous immunglobulins or monoclonal antibodies such as rituximab have been successfully administered in such cases (Oh et al., 2019 ; Foucard et al., 2021 ; Mirmosayyeb et al., 2023 ) and were considered in our case of OMS. However, the clinical course in our patient was favourable and the combined symptomatic treatment of myoclonus with levetiracetam, valproic acid, clonazepam and finally trihexphenidyl ultimately proved effective, as in similar cases (Levy and Chen, 2016 ), thus avoiding the need for prolonged immunosuppressive treatment after the initial administration of steroids. In addition to pharmacological treatment, neurorehabilitative approaches focusing on oromandibular and speech coordination, but also on posture and gait in the face of ataxia, appear equally relevant for a favourable functional outcome. Declarations Acknowledgement : The authors would like to thank the patient for his participation and permission to publish his medical data about his neurological disorder.. Author contribution: Data recording and production of manuscript: Michael Adamaszek. All authors read and approved the final manuscript. Ethical compliance statement: The authors confirm that the approval of an institutional review board was not required for this work. A written informed consent of the patient was obtained for the publication of his data. The authors have read the Journal´s position on issues involved in ethical publication and affords that this work is consistent with those guidelines. Competing interests: The authors declare no competing interests. CONFLICT OF INTEREST The authors declare that they have no conflict of interest. References Adhikari S, Thuringer A, Maali L, Jassam Y (2021) Opsoclonus myoclonus syndrome in a postpartum period. Mult Scler Relat Disord 50:102862 Armangué T, Sabater L, Torres-Vega E, Martínez-Hernández E, et al (2016) Clinical and Immunological Features of Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies. JAMA Neurol 73(4):417-24 Balcom EF, Nath A, Power C (2021) Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease. Brain 144: 3576-3588 Banks SA, Morris PP, Chen JJ, Pittock SJ, et al. (2020) Brainstem and cerebellar involvement in MOG-IgG-associated disorder cersus aquaporin-4-IgG and MS. J Neurol Neurosurg Psychiatry. doi.10.1136/jnnp-2020-325121 Bataller L, Rosenfeld MR, Graus F, Vilchez JJ, Cheung NKV, Dalmau J (2003) Autoantigen diversity in the opsoclonus–myoclonus syndrome. Ann Neurol 53:347–353 Blaes F, Fuehlhuber V, Korfei M, et al. (2005) Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome. Ann Neurol 58(2):313-317 Chacko J, Maramattom BV (2022) Parainfectious Opsoclonus Myoclonus Syndrome with COVID-19. Ann Indian Acad Neurol 25(3): 546-548 Durovic E, Bien C, Bien CG, Isenmann S (2021) MOG antibodyassociated encephalitis secondary to Covid-19: a case report. BMC Neurol 21:414 Ellul MA, Benjamin L, Singh B, Lant S, et al (2020) Neurological associations of COVID-19. Lancet Neuro 19(9): 767-783 Emamikkah M, Babadi M, Mehrabani M, Jalili M, et al. (2021) Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of the literature. J Neurovirol 27(1): 26-34 Ertekin V, Tan H (2010) Opsoclonus–myoclonus syndrome attributable to Hepatitis C infection. Pediatr Neurol 42:441–442 Foucard C, San-Galli A, Tarrano C, Chaumont H, et al. (2021) Acute cerebellar ataxia and myoclonus with or without opsoclonus: a para-infectious syndrome associated with COVID-19. Eur J Neurol 28(10): 3533-3536 Glatz K, Meinck HM, Wildemann B (2003) Parainfectious opsoclonus myoclnus syndrome: high dose intravenous immunoglobulins are effective. J Neurol Neurosurg Psychiat 74: 279-80 Goh EL, Scarff K, Satariano S, Lim M, Anand G (2020) Evolving cognitive dysfunction in children with neurologically stable opsoclonus-myclonus syndrome. Children 7(9): 104. Gorman MP (2010) Update on diagnosis, treatment, and prognosis in opsoclonus-myoclonus-ataxia syndrome. Curr Opin Pediatr 22: 745-50 Helms J, Kremer S, Merdji H, et al. (2020) Neurological features in severe SARS-CoV-2 infection. N Eng J Med 382(23):2268-2270 Jha NK, Ohja S, Jha SK, Dureja H, et al. (2021) Evidence of Coronavirus (CoV) pathogenesis and emerging pathogen SARS-CoV-2 in the nervous system: a review on neurological impairments and manifestations. J Mol Neurosci 71:2192-2209 Kanjanasut N, Phanthumchinda K, Bhidayasiri R (2010) HIV-related opsoclonus–myoclonus-ataxia syndrome: report on two cases. Clin Neurol Neurosurg 112:572–574 Khosla JS, Edelman MJ, Kennedy N, Reich SG (2005) West Nile virus presenting as opsoclonus–myoclonus cerebellar ataxia. Neurology 64:1095–1095 Klaas JP, Ahlskog JE, Pittock SJ, Matsumoto JY, et al. (2012) Adult-onset opsoclonus-myoclonus syndrome. Arch Neurol 69(12): 1598-1607 Levy A, Chen R (2016) Myoclonus: pathophysiology and treatment options. Curr Treat Options Neurol 18(5):21 Mirmosayyeb O, Ghaffary EM, Dehghan MS, Ghoshouni H, et al. (2023) Myelin Oligodenrocyte Glycoprotein antibody-associated disease and Covid-19: a systematic review. J Cent Nerv Sys Dis 15:1-15 Oh SY, Kim JA, Dieterich M (2019) Update on opsoclonus-myoclonus syndrome in adults. J Neurol 266(6): 1541-48 Peters J, Alhasan S, Vogels CBF, Grubaugh ND, et al. (2021) MOG-associated encephalitis following SARS-CoV-2 infection. Mult Scle Rel Dis 50: 102857 Ritchie H, Ortiz-Ospina E, Beltekian D, Mathieu E, et al. (2021) Coronavirus-Pandemic (COVID-19). Saha B, Saha S, Chong WH (2021) 78-year-old woman with opsoclonus myoclonus ataxia syndrome secondary to COVID-19. BMJ Case Rep 14, e243165 Sawalha K, Adeodokun S, Kamoga GR (2020) Covid-19-induced acute bilateral optic neuritis. J Investig Med High Impact Case Rep 8:2324709620976018 Sato R, Okanari K, Maeda T, Kaneko K, et al. (2020) Postinfectious acute disseminated encephalomyelitis associated with antmyelin oligodendrocyte glycoprotein antibody. Child Neurol Open 7: 1-5 Sriwastava S, Tandon M, Podury S, Prasad A, et al. (2021) COVID-19 and neuroinflammation: a literature review of relevant neuroimaging and CFS markers in central nervous system inflammatory disorders from Sars-CoV2. J Neurol 268(12): 4448-78 Trigo LJ, Martinez PE, Carrancho GA, Pedraza HMI (2021) Opsoclonus-myoclonus syndrome secondary to duloxetine poisoning (Sindrome de opsoclono-mioclono secundario a intoxicación por dulocetina. Neurologio (Engl Ed) 36(3): 250-52 Verma A, Brozman B (2002) Opsoclonus–myoclonus syn-drome following Epstein-Barr virus infection. Neurology 58:1131–1132 Zaganas I, Prinianakis G, Xirouchaki N, Mavridis M (2007) Opsoclonus–myoclonus syndrome associated with cytomegalo-virus encephalitis. Neurology 68:1636 56. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2023 Read the published version in The Cerebellum → Version 1 posted Editorial decision: Major revision 16 Aug, 2023 Reviews received at journal 04 Aug, 2023 Reviewers agreed at journal 25 Jul, 2023 Reviewers invited by journal 25 Jul, 2023 Submission checks completed at journal 24 Jul, 2023 Editor assigned by journal 24 Jul, 2023 First submitted to journal 21 Jul, 2023 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-3192635","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":221333132,"identity":"bff2c23b-d46b-41a7-91ad-c50d3898c74b","order_by":0,"name":"Michael Adamaszek","email":"data:image/png;base64,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","orcid":"","institution":"Klinik Bavaria","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Adamaszek","suffix":""},{"id":221333133,"identity":"45046933-2ae6-4252-abd9-e0dfbe2282c7","order_by":1,"name":"Soenke Langner","email":"","orcid":"","institution":"Rostock University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Soenke","middleName":"","lastName":"Langner","suffix":""},{"id":221333134,"identity":"bf20e8b3-d95d-44e4-bebd-9f60e4b4b7a2","order_by":2,"name":"Alexander Heinrich","email":"","orcid":"","institution":"Joint Practice Neurology and Psychiatry Geislingen","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Heinrich","suffix":""},{"id":221333135,"identity":"f37d5aec-4151-4cdd-ac56-410dd6d649aa","order_by":3,"name":"Jan Mehrholz","email":"","orcid":"","institution":"Technical University Dresden","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jan","middleName":"","lastName":"Mehrholz","suffix":""}],"badges":[],"createdAt":"2023-07-21 16:29:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3192635/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3192635/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12311-023-01610-9","type":"published","date":"2023-10-09T15:00:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":44699709,"identity":"c97e8d8c-c790-447e-9f75-8a8d9fde53c6","added_by":"auto","created_at":"2023-10-16 15:04:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":160444,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3192635/v1/faa3596e-c469-48d4-8384-3b43d01d2454.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Opsoclonus-myoclonus-ataxia syndrome due to Covid-19","fulltext":[{"header":"Full Text","content":"\u003cp\u003eIn addition to the primary medical and epidemiological challenges, the SARS-CoV-2 pandemic has triggered a vivid research activity on the organic dysfunctions associated with the virus known as Covid-19 and numerous investigations have been undertaken aiming to capture and refine the pathogenetic features of this virus (Ritchie et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In addition to cardiorespiratory and haemastaseological organ manifestations, the effects of the virus on neuronal tissues of the peripheral and central nervous systems have increasingly been observed and discussed (Ellul et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Helms et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Balcom et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) including direct pathogenic activities of SARS-CoV-2 predominantly in the brain, and immunologically mediated mechanisms (Jha et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The peripheral nervous system is frequently involved in the form of Guillian-Barr\u0026eacute; syndrome-like acute polyneuritis, and the central nervous system may be affected in form of a multifocal encephalitis as well as myelitis (Ellul et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Balcom et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Jha et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). According to a recent review, most cases of CNS syndromes in relation to SARS-CoV-2 are immunologically mediated disorders (Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In analogy to other established parainfectious neurological diseases, detailed functional-analytical, i.e. neurophysiological, radiological and laboratory chemical investigations are necessary to establish a presumed causal relationship between a neurological manifestation and SARS-CoV-2 infection, if not to prove it. Over the past two and a half years, in addition to numerous systematic studies, a large number of individual cases of neurological disease as a result of SARS-CoV-2 infection have been reported. However, opsoclonus-myoclonus syndrome (OMS) has been only very rarely reported in association with SARS-CoV-2 infection (Foucard et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Emamikkah et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Saha et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Chacko and Maramattom, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Here we present an additional case of acute central nervous movement disorder secondary to acute SARS-CoV-2 infection.\u003c/p\u003e \u003cp\u003eA 54-year-old man with a negative neurological history was admitted to hospital with respiratory symptoms. A few days earlier, he had tested positive for SARS-CoV-2 antigen. The patient's general condition deteriorated with fever, progressive respiratory insufficiency, opsoclonus and generalised myoclonic jerks. Covid-19 pneumonia was then diagnosed by computed tomography and the patient was transferred to the intensive care unit, where full heparinisation and treatment with dexamethasone were initiated. Symptomatic treatment of myoclonus with levetiracetam and clonazepam was initiated and later supplemented with valproic acid due to inadequate symptom control. Additional pharmacological treatment with clonidine and nepresol was given to control arterial blood pressure. In addition to a gradual stabilisation of respiratory function, a moderate improvement of myoclonus and opsoclonus was initially achieved. However, the patient developed a delirious state with agitation, oral automatisms and pronounced grimacing. After the patient's general condition became increasingly stable, he was transferred to a neurorehabilitative treatment, where myoclonia and orofacial dyskinesia were still occasionally present. Further reduction of symptoms, particularly myoclonus, was achieved by increasing the dose of valproic acid and clonazepam. Due to unsatisfactory clinical control of the intermittent oromandibular myoclonia with significant speech and swallowing impairment, trihexphenidyl was added. With this triple therapy, extensive symptom control of the oromandibular myoclonia was achieved, allowing a gradual dose reduction without recurrence of symptoms. Neuroradiological examination showed calcifications within the basal ganglia, wide perivascular spaces and morphological features of cerebral microangiopathy, but no evidence of inflammatory changes on MRI. EEG showed no hypersynchronous activity but intermittent focal rhythm slowing in the theta spectrum frontoparietally bilaterally. CSF analysis was positive for MOG Ig-G antibodies (1:80), although there was no pleocytosis, and oligoclonal bands were negative. Clinical neurorehabilitation focused mainly on ataxia, but also on hypertonic dysarthria, aphasia and fluctuating cognitive impairment, mainly in the attentional domain, resulting in marked improvements in both motor and neurocognitive skills. The patient was discharged home with a walker as a temporary mobility aid.\u003c/p\u003e \u003cp\u003eThe present case illustrates an opsoclonus-myoclonus syndrome (OMS) in connection with a SARS-CoV-2 infection, which has been rarely reported before by other authors in the course of the Covid-19 pandemic. A causal relationship between OMS and the SARS-CoV-2 infection or the clinically definable Covid-19 in the present case can be assumed, not only because of the temporal relationship (Mirmosayyeb et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), but also with regard to the CSF-analytical proof of antibody production against neural myelin protein (myelin oligodendrocyte glycoprotein; MOG). The striking cognitive impairment in this case are in line with numerous clinical observations of a parainfectious encephalopathy with an OMS following viral infection (Foucard et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). OMS is characterised by a variable combination of opsoclonus, i.e. irregular, involuntary and arrhythmic eye movements in horizontal, vertical and diagonal directions, and myoclonus, characterised by sudden and brief spasms of multiple muscles resulting in jerky movements (Gorman, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). In addition, cerebellar ataxia is one of the clinical features of this entity, and cognitive impairments such as aphasia or attention problems have been reported on several occasions (Goth et al., 2020). OMS is a rare disease with a predominantly paraneoplastic or parainfectious aetiology associated with a wide range of viral infections (Verma and Brozman, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Glatz et al, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Khosla et al, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; Zaganas et al, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Ertekin and Tan, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Kanjanasut et al, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2010\u003c/span\u003e; Oh et al, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Associations with anti-Ri or anti-ANNA-2 antibodies have been reported in paraneoplastic cases of extracranial solid tumours (Klaas et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Armangu\u0026eacute; et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, as a reliable diagnostic immunological marker has not yet been found, a significant number of patients cannot be definitively diagnosed and are often diagnosed as having idiopathic OMS. Nevertheless, OMS was rarely reported as a case of central nervous system (CNS) involvement with SARS-CoV-2 during the Covid-19 pandemic. Of note, the causal mechanisms of CNS involvement after SARS-CoV-2 infection are still under discussion, including direct virus-mediated tissue damage, a secondary pathway due to systemic effects such as hypoxia or cerebrovascular injury, but also tissue damage due to autoimmune mechanisms (Ellul et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Jha et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) seem to play a crucial role. The finding of MOG-specific antibody production identified in the present case is interesting, as MOG-specific antibodies have been repeatedly reported in cases of encephalitis following SARS-CoV-2 infection (Durovic et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Peters et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Mirmosayyeb et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), but with different clinical and radiological features, including cognitive impairment, paresis and sensory disturbances, and diffuse cerebral hyperintensities and leptomeningeal enhancement on MRI. Observations in the patient reported here and in another paediatric case of MOG antibody-positive OMS following SARS-CoV-2 infection (Adhikari et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) suggest that OMS may be a rare manifestation of MOG antibody-associated encephalitis. MOG antibodies have been found in CNS inflammatory diseases following a variety of systemic infections, suggesting that SARS-CoV-2 infection with Covid-19 may have been an immunological trigger for MOG antibody production in our case (Sato et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The normal CSF laboratory parameters observed in the present case are consistent with the majority of reports of SARS-CoV-2 infection with neurological disorders (Balcom et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In addition, normal brain MRI findings in patients with neurological disorders including OMS associated with SARS-CoV-2 infections have been described in several reports (e.g. overview of Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e, and also Mirmosayyeb et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsidering the diversity of autoantigens reported in OMS in the absence of a disease-specific antibody marker (Bataller et al., 2005), OMS is thought to be caused by cerebellar degeneration following neuroimmunological processes against various surface targets (Blaes et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Notable, MOG-specific antibodies have been shown to have a high affinity to cerebellar surface antigens (Banks et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), supporting the notion of a causal role for MOG-antibodies in the present case. MOG-antibody production has been observed in several cases of acute neurological diseases such as acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), or transverse myelitis (MY) associated with SARS-CoV-2 infection (Sriwastava et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), even at low MOG antibody titres (1:160) and normal cell counts in CFS (Sawalha et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Immunosuppressive treatments with steroids, intravenous immunglobulins or monoclonal antibodies such as rituximab have been successfully administered in such cases (Oh et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Foucard et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Mirmosayyeb et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) and were considered in our case of OMS. However, the clinical course in our patient was favourable and the combined symptomatic treatment of myoclonus with levetiracetam, valproic acid, clonazepam and finally trihexphenidyl ultimately proved effective, as in similar cases (Levy and Chen, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), thus avoiding the need for prolonged immunosuppressive treatment after the initial administration of steroids. In addition to pharmacological treatment, neurorehabilitative approaches focusing on oromandibular and speech coordination, but also on posture and gait in the face of ataxia, appear equally relevant for a favourable functional outcome.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the patient for his participation and permission to publish his medical data about his neurological disorder..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData recording and production of manuscript: Michael Adamaszek. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical compliance statement: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the approval of an institutional review board was not required for this work. A written informed consent of the patient was obtained for the publication of his data. The authors have read the Journal\u0026acute;s position on issues involved in ethical publication and affords that this work is consistent with those guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAdhikari S, Thuringer A, Maali L, Jassam Y (2021) Opsoclonus myoclonus syndrome in a postpartum period. 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BMJ Case Rep 14, e243165\u003c/li\u003e\n\u003cli\u003eSawalha K, Adeodokun S, Kamoga GR (2020) Covid-19-induced acute bilateral optic neuritis. J Investig Med High Impact Case Rep 8:2324709620976018\u003c/li\u003e\n\u003cli\u003eSato R, Okanari K, Maeda T, Kaneko K, et al. (2020) Postinfectious acute disseminated encephalomyelitis associated with antmyelin oligodendrocyte glycoprotein antibody. Child Neurol Open 7: 1-5\u003c/li\u003e\n\u003cli\u003eSriwastava S, Tandon M, Podury S, Prasad A, et al. (2021) COVID-19 and neuroinflammation: a literature review of relevant neuroimaging and CFS markers in central nervous system inflammatory disorders from Sars-CoV2. J Neurol 268(12): 4448-78 \u003c/li\u003e\n\u003cli\u003eTrigo LJ, Martinez PE, Carrancho GA, Pedraza HMI (2021) Opsoclonus-myoclonus syndrome secondary to duloxetine poisoning (Sindrome de opsoclono-mioclono secundario a intoxicaci\u0026oacute;n por dulocetina. Neurologio (Engl Ed) 36(3): 250-52\u003c/li\u003e\n\u003cli\u003eVerma A, Brozman B (2002) Opsoclonus\u0026ndash;myoclonus syn-drome following Epstein-Barr virus infection. Neurology 58:1131\u0026ndash;1132 \u003c/li\u003e\n\u003cli\u003eZaganas I, Prinianakis G, Xirouchaki N, Mavridis M (2007) Opsoclonus\u0026ndash;myoclonus syndrome associated with cytomegalo-virus encephalitis. Neurology 68:1636 56. \u003c/li\u003e\n\u003c/ol\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":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3192635/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3192635/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Opsoclonus myoclonus syndrome (OMS) is a rare neurological encephalopathic entity associated with non-specific infections or cancer processes that has been occasionally described in the setting of SARS-CoV-2 infection. We report a case of a 53-year-old man with SARS-CoV-2 infection, who developed clinical features of opsoclonus-myoclonus syndrome. Of particular note, cerebrospinal fluid analysis (CSF) analysis revealed the production of myelin oligodendrocyte glycoprotein (MOG) antibodies, suggesting an underlying neuroimmunological mechanism associated with infection with the novel SARS-CoV-2 virus.","manuscriptTitle":"Opsoclonus-myoclonus-ataxia syndrome due to Covid-19","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-07-28 10:42:56","doi":"10.21203/rs.3.rs-3192635/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-08-16T16:02:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-08-04T09:39:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"921fd67b-7e7e-447d-8aeb-0c89fcfb4c84","date":"2023-07-25T16:07:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-07-25T06:58:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-24T06:55:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-07-24T06:55:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Cerebellum","date":"2023-07-21T16:16:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ebe62a39-f58b-47f3-99f4-fce1094ce50a","owner":[],"postedDate":"July 28th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T15:03:20+00:00","versionOfRecord":{"articleIdentity":"rs-3192635","link":"https://doi.org/10.1007/s12311-023-01610-9","journal":{"identity":"the-cerebellum","isVorOnly":false,"title":"The Cerebellum"},"publishedOn":"2023-10-09 15:00:34","publishedOnDateReadable":"October 9th, 2023"},"versionCreatedAt":"2023-07-28 10:42:56","video":"","vorDoi":"10.1007/s12311-023-01610-9","vorDoiUrl":"https://doi.org/10.1007/s12311-023-01610-9","workflowStages":[]},"version":"v1","identity":"rs-3192635","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3192635","identity":"rs-3192635","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}