Familial neuromyelitis optica spectrum disorders: Case series and systematic review.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. OBJECTIVES: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. METHODS: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. RESULTS: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. CONCLUSION: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

Safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of central nervous system: A single center experience.

Introduction: Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Materials and methods: Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Results: We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. Discussion: COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

Evaluation of the safety profile of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

INTRODUCTION: Vaccination against the coronavirus disease 2019 (COVID-19) is recommended for patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, vaccine safety in these patients taking immunotherapeutic agents is unclear as they were not included in the vaccine trials. OBJECTIVES: To evaluate the safety of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD. METHODS: We reviewed the medical records of MS, NMOSD, and MOGAD patients at the Keimyung University Dongsan Hospital. Information regarding vaccination schedules and adverse events was collected. RESULTS: A total of 56 patients (19, 22, and 15 patients with MS, NMOSD, and MOGAD, respectively) with a median age of 48.18 ± 15.72 years (range, 16-81 years) were included. Of them, 42 (75.0%) were female. In total, 76.8% (43/56) of all patients were vaccinated, and the vaccination rate was the highest for NMOSD patients (81.8%) and the lowest for MS patients (68.4%). All vaccinated patients were administered mRNA vaccines at least once in single or multiple vaccination doses. Only 3 of 43 (7.0%) vaccinated patients experienced clinical relapse following vaccination. Facial sensory changes with a brainstem lesion developed in an MS patient taking dimethyl fumarate, while myelitis occurred in a MOGAD patient receiving azathioprine maintenance therapy. The first episode of optic neuritis occurred in a patient who was later diagnosed with MOGAD. CONCLUSIONS: Our study demonstrated a favorable safety profile with no serious adverse events associated with COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccines: A systematic review.

BACKGROUND: The global COVID-19 pandemic began in March 2019, and given the number of casualties and adverse effects on the economy, society, and all aspects of the health system, efforts have been made to develop vaccines from the beginning of the pandemic. Numerous vaccines against COVID-19 infection have been developed in several technologies and have spread rapidly. There have been reported multiple complications of the COVID-19 vaccines as with other vaccines. A number of studies have reported multiple sclerosis (MS ) and neuromyelitis optica spectrum disorder (NMOSD) as complications of COVID-19 vaccines. METHODS: First, we found 954 studies from 4 databases (PubMed, Embase, Scopus, and Web of Science) from inception to March 1st, 2022. Next, duplicate articles were eliminated, and 476 studies remained. Then 412 studies were removed according to inclusion and exclusion criteria. After obtaining the full text of 64 articles, 12 studies were selected finally. RESULTS: The data were extracted from included studies in a table. Our data includes demographic data, comorbidities, vaccines information and side effects, NMOSD and MS symptoms, laboratory and cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) results, treatment, and outcome of all cases. CONCLUSION: MS and NMOSD are two neuroinflammatory disorders that arise in the CNS. Cases of MS and NMOSD have been reported following COVID-19 vaccination. Nevertheless, more studies with more subjects are needed to assess any possible relationship between the COVID-19 vaccine and central nervous system demyelination.

CNS inflammatory demyelinating events after COVID-19 vaccines: A case series and systematic review.

Background: Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms. Methods: Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed. Results: Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA (n = 46), adenoviral-vectored (n = 37), and inactivated vaccines (n = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones. Conclusion: Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology.

CNS demyelinating disease following inactivated or viral vector SARS-CoV-2 vaccines: A case series.

BACKGROUND: Several reports have been documented in possible association with the administration of different severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccines and central nervous system (CNS)demyelinating disorders, specifically post mRNA vaccines. We report twelve cases of developing Multiple sclerosis (MS) or Neuromyelitis Optica spectrum disorders (NMOSD) following neither the first nor second dose of inactivated or viral vector COVID-19 vaccine. METHODS: We retrospectively compiled twelve patients' medical information with a new onset of MS or NMOSD in their first six weeks following a COVID-19 vaccine. RESULTS: We report twelve cases of MS (n = 9), clinically isolated syndrome (CIS)(n = 1), and NMOSD (n = 2) following COVID-19 inactivated vaccines (n = 11) or viral vector vaccines (n = 1), within some days following either the first (n = 3), second dose (n = 8), or third dose (n = 1). Their median age was 33.3 years, ranging from 19 to 53 years. Ten were women (83 %). All patients fully (n = 5) or partially (n = 2) recovered after receiving 3 doses of Corticosteroids. Common medications were Natalizumab, Teriflunomide, Dimethyl fumarate, and Rituximab. Also, Interferon beta 1-a was administered to one patient with severe symptoms of numbness. CONCLUSION: Our case series identifies the Sinopharm BBIBP-CorV and the AstraZeneca AZD1222 vaccines as potential triggers for CNS demyelinating diseases. Vaccine administration routines are not affected by these rare and coincidental events. However, these manifestations are not deniable and require serious attention. Further investigations are needed to clarify the actual mechanisms and real associations.

Double seropositive neuromyelitis optica associated with COVID-19: A case report.

Neuromyelitis optica spectrum disorders are characterized by severe demyelination and axonal damage with autoimmune mechanisms, predominantly targeting the optic nerves and the spinal cord. Patients often test positive for anti-AQP4 antibodies, while some have anti-MOG antibodies. Double seropositivity has been described, with a variable prevalence (0 to 26%) dependent on the testing method. The clinical significance of double seropositivity remains unclear. We present the case of a 65-year-old patient, admitted to our clinic with optical neuritis, followed up approximately 10 days later by cervical myelitis, who tested positive for both anti-AQP4 and anti-MOG antibodies. The clinical onset coincided with a mild form of SARS-CoV-2 infection. The neurological symptoms were initially relatively subdued, which delayed the diagnosis. The patient was not vaccinated against SARS-CoV-2. The clinical picture was compatible with an anti-AQP4 phenotype. The patient was started on corticosteroid therapy, under which the clinical response was good. Our case reinforces the idea that SARS-CoV-2 can precipitate autoimmune demyelinating diseases since SARS-CoV-2 infection has already been demonstrated as a risk factor for NMOSD relapses. To the best of our knowledge, this is the first reported case of double seropositive neuromyelitis optica associated with COVID-19. We expect that in the near future, as the true burden of COVID becomes clearer, we shall encounter other cases which can trace their apparent clinical onset to a SARS-CoV-2 infection. Careful attention should be paid to the apparent minor neurological symptoms of COVID-19.

Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) associated with COVID-19: A case series and review.

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the case studies of MS, MOGAD, NMOSD, and ON associated with COVID-19 infection. CASE PRESENTATIONS: Case 1 (MS) was a 24-year-old female with paresthesia and bilateral weakness one week after COVID-19 symptom onset who showed demyelinating plaques and 12 isolated oligoclonal bands (OCBs). Case 2 (MOGAD) was a 41-year-old male with encephalomyelitis 16 days after COVID-19, who later developed MOG-antibody-associated optic neuritis. RESULTS: Out of 18 cases, NMOSD was the most common post-COVID manifestation (7, 39%), followed by MOGAD (5, 28%), MS (4, 22%), and isolated ON (2, 11%). The median duration between the onset of COVID-19 symptom onset and neurological symptoms was 14 days. 61% of these were male, with a mean age of 35 years. IVMP was the treatment of choice, and nearly all patients made a full recovery, with zero fatalities. CONCLUSIONS: Although these neurological sequelae are few, physicians must be cognizant of their underlying pathophysiology and associated clinical and neuro-diagnostic findings when treating COVID-19 patients with atypical presentations.

Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.

Watch out for neuromyelitis optica spectrum disorder onset or clinical relapse after COVID-19 vaccination: What neurologists need to know?

INTRODUCTION: The ongoing global COVID-19 pandemic has dramatically impacted our lives. We conducted this systematic review to investigate the safety of the COVID-19 vaccines in NMOSD patients. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase from the beginning of the COVID-19 vaccination to March 1, 2022. Except for the letters, posters, and reviews, we included all related articles to answer two main questions. Our first question examined the occurrence of NMOSD onset as an adverse effect of the COVID-19 vaccine. Our second question investigated the safety of the COVID-19 vaccines in NMOSD patients. RESULTS: Out of 262 records, nine studies, including five studies for the first question and four studies for the second question, met the inclusion criteria. Out of the six patients with NMOSD onset after COVID-19 vaccination, five (83.3%) were female. The median time to NMOSD onset was 6.5 days, and the frequency of the COVID-19 vaccine type was identical in all patients. The most common presentation was longitudinally extensive transverse myelitis, significantly improved by pulse methylprednisolone with or without plasma exchange. The maintenance therapy was described only in three patients: rituximab (n=2) and azathioprine (n=1). Regarding the second question, out of 67 patients, 77.61% were female, with a mean age of 54.75 years old, a mean EDSS of 2.83, and a mean disease duration of 9.5 years. 77% reported at least one preexisting comorbidity. 88.05% were under treatment, most of which were rituximab and azathioprine. 98.50% received two doses of the COVID-19 vaccine. mRNA vaccines were the most commonly used vaccine(86.56%), which were well tolerated. No significant adverse event was reported, and local pain was the most frequently reported. 4.67% of the patients experienced a clinical relapse after a mean interval of 49.75 days, which was mainly mild to moderate in severity. Unfortunately, the data on the COVID-19 vaccines were missing. CONCLUSION: The analysis suggests the safety profile of the COVID-19 vaccines. All NMOSD patients are strongly recommended to vaccinate for COVID-19. To maximize the effectiveness of the COVID-19 vaccines, further studies are needed to draw the best practice for vaccination.

Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: A need for reconsideration?

During the coronavirus disease 2019 (COVID-19) pandemic, mass vaccination was a beneficial strategy in many countries. Nevertheless, reports of serious complications such as postvaccination neuromyelitis optica spectrum disorder (NMOSD) raised concerns about the safety of vaccines. Anamnart and colleagues explained postvaccination NMOSD following different vaccines, including COVID-19. To emphasize the message of this article, in this letter, we present a unique case of postvaccination NMOSD with a fulminant and fatal course, which may show a plausible relationship between COVID-19 vaccination and triggering anti-aquaporin-4 antibody (AQP4-Ab).

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

In the era of the COVID-19 pandemic declared in March 2020, widespread vaccination protocols were initiated to mitigate the severity and spread of COVID-19. Although COVID-19 vaccines have been generally considered safe, adverse events post-vaccination have been reported, including the development of demyelinating disease. We report a rare case of de novo aquaporin-4-positive neuromyelitis optica spectrum disorder (NMOSD) in an 80-year-old man following BNT162b SARS-CoV-2 vaccination to raise the awareness of this possible severe adverse event in an older adult. An 80-year-old South Asian man presented 2 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 AQP4-positive 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. This case report adds to the existing literature and suggests that COVID-19 vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Although rare, our patient presented with new-onset NMOSD in his 80 s following COVID-19 vaccination. As such, it is relevant to consider AQP4 testing in those presenting with a post-vaccination myelitis, regardless of age. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.

Humoral response to SARS-CoV-2 infection and vaccines against COVID-19 in patients with neuromyelitis optica spectrum disorders: Impact of immunosuppressive treatment.

The aim of this study was to evaluate the humoral response to the SARS-CoV-2 infection and vaccination in the NMOSD patients, treated with various immunosuppresants (ISs). Serum IgG against the complete sequence of the receptor binding domain of the spike protein was measured using ELISA SARS-CoV-2 IgG, INEP, Belgrade. Seroconversion occurred in 8/10 patients with COVID-19, and in 5/9 after vaccination. One out of four patients treated with inebilizumab seroconverted (after COVID-19); antibodies were not detected in any of the remaining 3 patients who were vaccinated. Antibodies developed after COVID-19 in 4/5 patients treated with azathioprine and all treated with mycophenolate-mofetil, and after vaccination, in 5/6 patients treated with these ISs. Post-vaccination humoral response was impaired in our NMOSD patients treated with B-cell depleting therapies; seroconversion occurred in almost all patients treated with conventional synthetic disease modifying ISs.

Post COVID-19 infection neuromyelitis optica spectrum disorder (NMOSD): A case report-based systematic review.

BACKGROUND: One of the rare neuroinflammatory disorders is Neuromyelitis optica spectrum disorder (NMOSD) which involves the central nervous system (CNS), and develops by various etiologies. There is evident that viral infections could cause neurological disorders. In this regard, novel coronavirus (COVID-19) triggers NMOSD, based on reports. We performed this systematic review to evaluate NMOSD patients following COVID-19 infection. METHODS: We collected 345 studies from PubMed (Medline), Embase, Scopus, and Web of Science databases from inception to 20 October 2021, and our inclusion criteria were English case reports/case series. Other types of Coronaviridae virus studies, review articles, articles written in any language other than English were excluded as well. RESULTS: 11 case reports were selected from 345 studies and data was extracted according to inclusion criteria. In all cases, NMOSD was reported following COVID-19 infection, and various symptoms such as blurring or loss of vision, weakness, and numbness were common, and the COVID-19 infection was confirmed by different tests such as PCR test, immunoglobulin assay and chest imaging. CONCLUSION: Review regarding case reports showed that NMOSD is conceivable following COVID-19.

Immunology of COVID-19 and disease-modifying therapies: The good, the bad and the unknown.

OBJECTIVE: The outbreak of the SARS-CoV-2 pandemic, caused by a previously unknown infectious agent, posed unprecedented challenges to healthcare systems and unmasked their vulnerability and limitations worldwide. Patients with long-term immunomodulatory/suppressive therapies, as well as their physicians, were and are concerned about balancing the risk of infection and effects of disease-modifying therapy. Over the last few months, knowledge regarding SARS-CoV-2 has been growing tremendously, and the first experiences of infections in patients with multiple sclerosis (MS) have been reported. METHODS: This review summarizes the currently still limited knowledge about SARS-CoV-2 immunology and the commonly agreed modes of action of approved drugs in immune-mediated diseases of the central nervous system (MS and neuromyelitis optica spectrum disorder). Specifically, we discuss whether immunosuppressive/immunomodulatory drugs may increase the risk of SARS-CoV-2 infection and, conversely, may decrease the severity of a COVID-19 disease course. RESULTS: At present, it can be recommended in general that none of those therapies with a definite indication needs to be stopped per se. A possibly increased risk of infection for most medications is accompanied by the possibility to reduce the severity of COVID-19. CONCLUSIONS: Despite the knowledge gain over the last few months, current evidence remains limited, and, thus, further clinical vigilance and systematic documentation is essential.

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.

Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.

Post-vaccination disease relapses have been reported in patients with MOGAD and AQP4-IgG+NMOSD. In this retrospective multicenter Italian study we assessed the frequency of relapses after SARS-CoV-2 vaccination. We included 56 cases: MOGAD, 30; AQP4-IgG+NMOSD, 26. Vaccines received were BNT162b2-Pfizer-BioNTech in 42 patients and mRNA-1273-Moderna in 14 patients. Six patients had a history of SARS-CoV-2 infection; two of them experienced a post-infection disease relapse (MOGAD). The frequency of relapses within one month of SARS-CoV-2 vaccination was 4% (1/26) in the AQP4-IgG+NMOSD group and 0% in the MOGAD group. In these patients the potential benefits of vaccination overcome the risk of relapses.

Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: Case report and systematic review.

INTRODUCTION: The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports. METHOD: Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared. RESULT: Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status. DISCUSSION: The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports. CONCLUSION: Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals.

Bilateral Acute Optic Perineuritis Associated With COVID-19 in a Patient With Seronegative Myelin Oligodendrocyte Glycoprotein (MOG) Antibody.

Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) may cause various neuro-ophthalmologic manifestations including optic perineuritis. Optic perineuritis is a rare form of orbital inflammatory disease in which optic nerve sheath is inflamed and nonspecific fibrotic thickening with classic radiological finding is a perineural enhancement of optic nerve sheath. A 45-year-old gentleman with known diabetes mellitus, hypertension and dyslipidemia was admitted with a critically ill COVID-19 infection. During the recovery period, the patient developed sudden onset of painless loss of vision. MRI head and orbit with gadolinium was suggestive of optic perineuritis. Other secondary causes of autoimmune or vasculitis myelin oligodendrocyte glycoprotein (MOG) antibody disease and other common central nervous system (CNS) infection were excluded. The patient had dramatic response with steroids. This is the first rare case report of COVID-19-related optic perineuritis in critically ill COVID-19 patients with seronegative MOG antibody. Optic perineuritis is a rare orbital inflammatory disease and underlying mechanisms may arise from systemic response to COVID-19 infection as well as direct effects of the virus via angiotensin-converting enzyme 2 (ACE-2) receptors on ocular tissues. Optic perineuritis is a rare disease with inflammation restricted to the optic nerve sheath. Neuroimaging of the brain and orbit is the most important modality of choice for visualizing optic nerve sheath and optic nerve. Delay in the diagnosis of COVID-19-related optic perineuritis, may result in permanent optic nerve injury and irreversible vision loss.

COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Reports on outcomes of COVID-19 in patients with neuromyelitis optica spectrum disorder (NMOSD) are scarce, as well as those related to the safety profile of the vaccines in this population. The aim of this survey is to present demographic and clinical characteristics of patients with NMOSD who developed COVID-19 and safety data of the COVID-19 vaccines in these persons. METHODS: This study comprise all patients from the Hospital registry of NMOSD, of the Clinic of Neurology in Belgrade, who fulfilled the 2015 NMOSD diagnostic criteria, and who after invitation by phone call, from April 10 to May 10, 2021, accepted to participate and provide information regarding COVID-19 and vaccination against Sars-CoV-2 (n = 53). RESULTS: Sixteen out of 53 enrolled NMOSD patients were diagnosed with COVID-19. In three cases (18.8%), severity of COVID-19 clinical manifestations warranted hospitalization, and one of these patients, died due to COVID-19 (case fatality ratio = 6.25%), after invasive mechanical ventilation. The remaining two patients had grade II COVID -19 severity and were hospitalized because of pneumonia, not requiring supplemental oxygen. Median EDSS in patients requiring hospitalization was 4.5, and in the non-hospitalized group, it was 3.0. Nine out of 53 patients received two doses of vaccine against Sars-Cov-2 (8 Sinopharm and one Pfizer). Pain at the site of application was the only vaccine-related adverse effect. CONCLUSIONS: Our survey indicates overall favourable COVID-19 outcome and encouraging safety profile of the vaccines in persons with NMOSD, in our cohort. Prospective studies are warranted to confirm these data.