The epidemiology and burden of neuromyelitis optica spectrum disorder, multiple sclerosis, and MOG antibody-associated disease in a province in Thailand: A population-based study.

BACKGROUND: Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown. OBJECTIVES: To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon. METHODS: Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated. RESULTS: Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well. CONCLUSION: CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases.

Optic neuromyelitis after vaccination against SARS-CoV-2.

Neuromyelitis optica is an autoimmune demyelinating astrocytopathy of the central nervous system that primarily affects the optic nerve and spinal cord. It is considered a multifactorial disease associated with antibodies against aquaporin 4, with complement cascade activation and lymphocytic infiltration leading to axonal loss and causing significant morbidity and disability. In addition, cases of inflammatory diseases of the central nervous system have been described after vaccination against SARS-CoV-2, mainly acute disseminated encephalomyelitis. Also, a few cases of neuromyelitis optica spectrum disorder, mostly aquaporin 4+, have been reported. We describe a patient who developed symptoms suggestive of acute disseminated encephalomyelitis the next day after vaccination against SARS-CoV-2. Three months later, a longitudinally extensive transverse myelitis compatible with aquaporin 4+ neuromyelitis optica was successfully treated with an interleukin 6 inhibitor. There is no proven association and research is needed to establish whether optic neuromyelitis is related to vaccination; this is a single case report from which no conclusion can be drawn.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Aquaporin-4 IgG neuromyelitis optica spectrum disorder onset after Covid-19 vaccination: Systematic review.

Neuromyelitis optica spectrum disorder (NMOSD) is rarely reported following Coronavirus disease 2019 (COVID-19) vaccination. We identified 16 cases of new onset NMOSD with positive aquaporin-4 IgG (AQP4-IgG) following COVID-19 vaccination. Transverse myelitis was the most common clinical presentation (75%). Most patients received high dose steroids for acute treatment and maintenance therapy was started in 12 patients (75%). Twelve patients (75%) had improvement of their symptoms at the time of discharge or follow-up. The included cases share similar epidemiology and natural course to non-vaccine related cases. Clinicians should be aware of possible post-vaccination NMOSD to help with earlier diagnosis and treatment.

Subtle vascular and astrocytic changes in the brain of coronavirus disease 2019 (COVID-19) patients.

BACKGROUND AND PURPOSE: In the central nervous system, a multitude of changes have been described associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, such as microglial activation, perivascular lymphocyte cuffing, hypoxic-ischaemic changes, microthrombosis, infarcts or haemorrhages. It was sought here to assess the vascular basement membranes (vBMs) and surrounding perivascular astrocytes for any morphological changes in acute respiratory syndrome (coronavirus disease 2019, COVID-19) patients. METHODS: The light microscopy morphology of the vBMs and perivascular astrocytes from brains of 14 patients with confirmed SARS-CoV-2 infection was analysed and compared to four control patients utilizing fluorescent immunohistochemistry for collagen IV and astrocytes (GFAP), endothelia (CD31), tight junction 1 (TJ1) adhesion protein, as well as the aquaporin 4 (AQP4) water channel. On 2D and 3D deconvoluted images from the cortex and white matter, vessel densities, diameters, degree of gliosis, collagen IV/GFAP and GFAP/AQP4 colocalizations were calculated, as well as the fractal dimension of astrocytes and vBMs viewed in tangential planes. RESULTS: Fractal dimension analysis of the GFAP-stained astrocytes revealed lower branching complexities and decreased GFAP/collagen IV colocalization for COVID-19 patients. Interestingly, vBMs showed significantly increased irregularities (fractal dimension values) compared to controls. Vessel diameters were increased in COVID-19 cases, especially for the white matter, TJ1 protein decreased its colocalization with the endothelia, and AQP4 reduced its co-expression in astrocytes. CONCLUSIONS: Our data on the irregularity of the basement membranes, loss of endothelial tight junction, reduction of the astrocyte end-feet and decrease of AQP4 suggest subtle morphological changes of the blood-brain barrier in COVID-19 brains that could be linked with indirect inflammatory signalling or hypoxia/hypercapnia.

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).

COVID-19 infection after two doses of SARS-CoV-2 mRNA vaccine in multiple sclerosis, AQP4-antibody NMOSD and MOGAD.

BACKGROUND: In pre-vaccinated people with multiple sclerosis (MS), certain disease-modifying therapies (DMTs), particularly the anti-CD20 treatments, appear to be associated with an increased risk of COVID-19 infection and indeed with severe infection. It is still not known if such observations extend to vaccinated individuals and there have been considerably fewer studies in aquaporin-4-antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) patients. In this study, we investigated the rates of symptomatic COVID-19 infection in adult patients with MS, AQP4-NMOSD and MOGAD who had received 2 doses of SARS-CoV-2 mRNA vaccine. METHODS: This was a prospective observational study conducted at the 2 main neuroimmunology referral centres in Singapore. Only patients on active follow-up were recruited to ensure robust data collection. Data on demographics, disease history, DMTs and SARS-CoV-2 mRNA vaccinations were recorded, and for those infected with COVID-19, data on COVID-19 infection was collected. RESULTS: Nineteen (13 MS, 5 AQP4-NMOSD, 1 MOGAD) out of 365 (231 MS, 106 AQP4-NMOSD, 28 MOGAD) patients had COVID-19 infection despite 2 doses of SARS-CoV-2 mRNA vaccine. Amongst the infected patients, 11 patients were on DMTs (3 rituximab, 2 interferons, 1 azathioprine, 1 mycophenolate, 1 prednisolone, 1 cladribine, 1 alemtuzumab, 1 fingolimod), while 8 patients were untreated. The crude infection rate was calculated using time-at-risk analysis, revealing that rituximab had the highest infection rate amongst all the DMTs. A lower crude infection rate was observed in patients who received a third vaccination. The majority of infections were mild and no patients required oxygen supplementation. CONCLUSION: Our findings suggest that patients on rituximab are still at risk of COVID-19 infection after 2 vaccinations and the receipt of a third vaccination may help to prevent infection. Future large scale studies will be required to better delineate the infection risk of different DMTs after the second and subsequent vaccinations.

Aquaporin-4 protein antibody-associated optic neuritis related to neuroendocrine tumor after receiving an inactive COVID-19 vaccine.

Neuromyelitis optica (NMO), also known as Devic's disease, is a rare, autoimmune, and recurrent demyelinating disorder that primarily affects the spinal cord and optic nerve. We report a case with recurrent optic neuritis caused by the paraneoplastic NMO spectrum disorder in the setting of a gastric neuroendocrine tumor 2 weeks after receiving an inactive COVID-19 vaccine.

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.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Impact of COVID-19 public health measures on myelin oligodendrocyte glycoprotein IgG-associated disorders in children.

BACKGROUND: Despite better characterization of the spectrum of MOG-IgG-associated disorders (MOGAD) in children, the role of infection in its pathophysiology remains unclear. The goal of this study was to evaluate if public health measures put in place to prevent the spread of SARS-CoV-2 in March 2020 in Ontario (Canada) have been associated with a change in the incidence of MOGAD and other neuroinflammatory disorders in children. METHODOLOGY: We reviewed a single-centre cohort of children referred for a suspicion of neuroinflammatory disorder between January 2015 and March 2021. Age, date, sex, diagnosis, MOG-IgG antibodies status and detected pathogens at presentation were identified. Comparative statistical analysis was performed based on diagnosis between years and seasons using Pearson's Chi-squared test or Fisher's exact test for categorical variables and using ANOVA or Kruskal-Wallis test for continuous variables, as appropriate. We compared the post-lockdown period (March 17th, 2020, to March 31st, 2021) to previous calendar years (2015 to 2019) alone and to previous calendar years and the pre-lockdown 2020 period (January 1st, 2020, to March 16th, 2020). A p-value of < 0.05 was considered significant. Post-hoc pairwise comparisons between the post-lockdown period and previous years were performed on significant results. A false discovery rate adjustment with an adjusted p-value (q-value) < 0.05 was computed. We hypothesized that the number of new MOGAD would be significantly lower in the post-lockdown period compared to previous years due to decreased regional pathogen transmission. RESULTS: Among 491 referred cases, we identified 415 new cases of neuroinflammatory disorder between January 2015 and March 2021. The number of new neuroinflammatory disorder diagnoses did not change between years. We noted significantly fewer new MOGAD diagnoses in 2020 compared to previous years, with no MOGAD patients presenting in 2020 after the spring lockdown (q=0.0009). In addition, there were significantly fewer parainfectious neuroinflammatory cases (q=0.04) and pathogen detected (q=0.04) in the post-lockdown period. The number of new multiple sclerosis (MS) and aquaporin-4 neuromyelitis optica spectrum disorders (AQP4-NMOSD) cases remained stable despite the lockdown (q=0.185 and 0.693 respectively). INTERPRETATION: Enhanced population-based infection control strategies may have a role in modulating the incidence of MOGAD and parainfectious neuroinflammatory disorders, but not MS or AQP4-NMOSD.

Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases.

BACKGROUND: The COVID-19 vaccines are currently recommended for people with rare neuroimmunological diseases such as neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody disease (MOGAD), and transverse myelitis. However, the safety profile of the vaccines in this population is uncertain. OBJECTIVE: To report real-world safety data of the COVID-19 vaccines in persons with rare neuroimmunological diseases. METHODS: An anonymous survey was distributed to patients recruited on social media. Participants answered general demographic and disease-related questions, and specific questions about their experiences with the COVID-19 vaccines. RESULTS: 438 participants completed the questionnaire. The median age was 51 (range 18-82 years); 366 were female (83.6%); 102 (23.3%) had associated comorbidities, and 354 (80.1%) were treated with immunotherapies. 242 participants (55.3%) reported a diagnosis of NMOSD; 99 (22.6%) had MOGAD; 79 (18%) had transverse myelitis. 239 participants (66.2%) were younger than 55 years of age. 138 participants (31.5%) reported earlyadverse events. Of these, 93 (67.4%) were < 55 years old, and 45 (32.6%) were > 55 years old (p=0.0086). The most common adverse events were local reactions, including pain, redness, and swelling at the injection site, reported by 155 participants (35.4%). 73 participants (16.7%) reported new or worsening neurological symptoms following the vaccination. Most symptoms occurred within the first week after vaccination and resolved within three days. CONCLUSIONS: This survey indicates an overall favorable safety and tolerability profile of the COVID-19 vaccines among persons with rare neuroimmunological diseases. Longer-term studies are warranted to confirm these data.