Bilateral longitudinally extensive optic perineuritis post-COVID-19 presenting as "idiopathic" intracranial hypertension: A case report

Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) has been associated with several neuro-ophthalmic manifestations. We report a case of bilateral longitudinally extensive optic perineuritis suspected due to SARSCoV2. Case Presentation: A 32-year-old woman developed headaches, photophobia, pulsatile tinnitus, and blurred vision 8 d after having a positive SARS-CoV-2 qualitative polymerase chain reaction (PCR) testing for coronavirus disease 2019 (COVID-19). She was diagnosed with and treated for idiopathic intracranial hypertension (IIH) elsewhere. Repeat evaluation at our institution showed a poor visual acuity in both eyes with Frisen grade II papilledema and cotton wool spots on fundoscopic examination. Orbital magnetic resonance imaging (MRI) showed bilateral longitudinally extensive optic nerve sheath enhancement. Repeat lumbar puncture revealed an elevated cerebrospinal fluid (CSF) opening pressure and protein, a finding that is incompatible with the diagnosis of IIH. Myelin oligodendrocyte glycoprotein, aquaporin-4 (AQP4)-IgG antibodies, and other serological tests for optic neuritis were unremarkable. Her visual acuity partially improved after corticosteroids. With the growing association of demyelinating disorders and COVID-19, unremarkable serological workup, and temporal relation of the patient's symptoms to the infection, we believe that her diagnosis is SARS-CoV-2 associated bilateral optic neuritis. Conclusion(s): There is a growing association between demyelinating disorders and COVID-19 and COVID-19 vaccination, and it is essential to recognize CSF abnormalities that are incompatible with a diagnosis of IIH, such as increased protein in our case, and may lead to an incorrect diagnosis.Copyright © 2023 The Authors. Clinical and Experimental Neuroimmunology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society for Neuroimmunology.

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.

An unusually fulminant case of encephalomyelitis in an 80 year old

Background: There have been reports of demyelinating syndromes in association with COVID-19 and to a much lesser extent COVID 19 vaccines. The association between demyelination and vaccines, in general, remains controversial. We review a presentation of fulminant demyelination, and discuss antecedent COVID-19 vaccination, the formulation of a broader differential diagnosis and ultimately the pathologic diagnosis. Case presentation: An 80-year-old woman presented with seizure, encephalopathy, quadriparesis and ultimately expired. She received a SARS-CoV-2 vaccine one day prior. Imaging revealed contrast enhancing cerebral lesions, longitudinally extensive transverse myelitis. CSF was markedly inflammatory. Pathologic examination of the CNS lesions revealed demyelination and inflammation beyond white matter, not restricted to a perivenular distribution. Conclusion(s): This case depicts a seemingly fulminant course of a diffuse demyelinating syndrome characterized clinicopathologically as Marburg's variant of multiple sclerosis. There are several unique aspects of this case including the extremely rapid course, the unusual evolution of CSF abnormalities, with hypoglycorrhachia and markedly elevated protein. The proximity to vaccination is a pertinent association to document, though we cannot unequivocally prove causation.Copyright © 2022 The Authors

Immunotherapy-responsive recurrent extensive white matter disease without neuronal or glial surface antibodies: A case report

Background: Acute disseminated encephalomyelitis (ADEM) is classically considered as a monophasic immune-mediated demyelinating disorder. A relapse can occur in children but extremely rare in adults. Case-report: A 57-year-old man presented with fulminant ADEM-like episode without proceeding viral illness. Neurological deficits rapidly developed associated with extensive demyelinating brain lesions with vasogenic edema. After the initiation of aggressive immunotherapy, his symptoms resolved, but he relapsed twice during 26-month observation period;one was a mild episode characterized by rapidly evolving MRI lesions without development of symptoms, and the other was a fulminant ADEM-like episode similar to the first one. The second fulminant episode occurred only 2 days after getting a flu shot despite no clinical or radiological relapse when he received COVID-19 vaccinations. The patient's symptoms and extensive brain MRI lesions improved after the initiation of aggressive immunotherapy at the early stage. No autoantibodies against neuronal surface (such as GABA A receptor) or glial surface antigens (aquaporin 4, or myelin oligodendrocyte glycoprotein) were identified in either serum or CSF. Conclusion(s): Extensive white matter lesions can occur without neuronal or glial surface antibodies, recurrent fulminant ADEM-like episode can develop even in an adult patient, and flu shot may provoke fulminant ADEM-like episode.Copyright © 2022

Neurological complications of SARS-CoV-2 infection.

SARS-CoV-2 virus was first identified in 2019 in Wuhan (China) and is responsible for the ongoing COVID-19 pandemic. Although the virus causes mild, transient symptoms of an upper respiratory tract infection in most cases, it can also lead to severe pneumonia, respiratory failure and/or death. Approximately 85% of patients experience central and peripheral neurological symptoms. In the acute phase of the disease, ischaemic strokes, intracranial haemorrhages, meningitis and encephalitis, acute demyelinating diseases and acute inflammatory polyneuropathies may occur. However, mild neurological symptoms that can persist for months and significantly affect daily functioning are much more common. These include headache and dizziness, olfactory and gustatory dysfunction, mild cognitive disturbances, as well as depressive, anxiety, and sleep disorders. Some of them are encompassed by popular terms "post-covid syndrome" and "brain fog." The pathogenesis of neurological complications of SARS-CoV-2 infection is still not fully understood;overproduction of cytokines induced by viral infection may be of great importance. There is no causal treatment, while symptomatic treatment is of limited effectiveness. Primary prevention in the form of SARS-CoV-2 vaccinations is of great importance. In the following review, we would like to present the current knowledge on epidemiology, pathology, pathogenesis and treatment of neurological complications after SARS-CoV-2 infection. Further multi-centre, large-scale clinical studies are necessary to identify the exact pathogenetic mechanismsCopyright © 2022 Sawicka et al.

Encephalitis as a post-COVID-19 complication: causation or association?

Case Report: Although the coronavirus disease 2019 (COVID-19) affects the respiratory system, neurological complications in children have been reported. Neurological manifestations in children with acute COVID-19 infection are rare and range from headaches, transverse myelitis, strokes, and encephalitis which presents as a part of Multisystem Inflammatory Syndrome in Children (MIS-C). However, encephalitis presenting post-COVID-19 in the absence of MIS-C in children has not been described. Case presentation: A 9-year-old Hispanic female with no past medical history presented with altered mental status and seizures. Associated symptoms prior to seizures included worsening headaches and vomiting. Initial labs were significant for an elevated erythrocyte sedimentation rate of 32 mm/hr, C-reactive protein of 2 mg/dL, and white blood cell (WBC) count of 28 000 cells/mcl with neutrophilia. Comprehensive metabolic panel was normal. Computed tomography of the head and urine drug screen were normal. Magnetic resonance imaging of the brain demonstrated diffusion restriction in the left frontal lobe as well as mild leptomeningeal enhancement concerning for meningoencephalitis. Lumbar puncture (LP) showed pleocytosis (WBC 169 cells/mcl, 76% neutrophils), elevated glucose 77 mg/dl, normal protein 56 mg/dl, and elevated myelin basic protein indicative of a demyelinating disease. Infectious workup was significant for a positive COVID-19 immunoglobulin (Ig) G (19.66), positive Mycoplasma pneumoniae (M. pneumoniae) IgM (0.87 units/L), with an equivocal IgG (0.11 units/L). Autoimmune workup was negative. She received dexamethasone 0.15 mg/kg/dose for 1 day, followed by methylprednisolone (10 mg/kg/dose) for 3 days and oral prednisone for 5 days resulting in significant improvement. Although CSF cultures returned negative, she received a 7-day course of doxycycline for a possible coexisting M. pneumoniae infection. Repeat LP showed improving pleocytosis, and lymphocytic predominance. Discussion: In this case report, rapid neurological recovery after administration of corticosteroids in the presence of positive COVID-19 IgG and demyelinating disease was suggestive of encephalitis presenting post- COVID-19 infection. Although M. pneumoniae can present with neurological symptoms (e.g., encephalitis), repeat titers at follow-up after recovery did not show the expected 4-fold increase in IgG, making it less likely the cause of this presentation. The proposed pathophysiology of COVID-19-mediated encephalitis includes direct invasion of the nervous system, immune-mediated cytokine response, and molecular mimicry between coronaviruses and neuronal proteins causing demyelination. The mainstay treatment includes immunomodulators such as corticosteroids, Intravenous Immunoglobulin, monoclonal antibodies (eg., rituximab), or plasma exchange. Conclusion: COVID-19 infection should be considered when evaluating a patient with meningoencephalitis or post-infectious encephalitis.

Clinico-Radiological Features in Demyelinating Lesion Post COVID 19 Disease

Background: One of the reported neurological complications of severe COVID-19 is the demolition of the myelin sheath. Indeed, the complex immunological dysfunction provides a substrate for the development of demyelination. Nevertheless, few published reports in the literature describe demyelination in patients with COVID-19. Material(s) and Method(s): We describe a case of a 9-year-old girl who developed weakness of her right arm distal more than proximal. The patient has a history of COVID 19 two months before (in July 2022). The patient has a history of COVID 19 in May 2021. The patient showed improvement in power after starting steroid medicine. Result(s): MRI brain was done as part of the investigation and showed single peripherally enhancing lesion in the left posterior limb of internal capsule suggestive of demyelinating process. Conclusion(s): The case needs to be published to show the association between the demyelinating disease and COVID-19 in paediatrics.

Acute flaccid myelitis diagnosed after IVIG: a diagnostic dilemma

Case Report: A 4-year-old African American male presented to an outside emergency department (ED) following sudden inability to move left upper extremity. Past medical history was unremarkable and routine vaccinations were up to date. Radiograph of affected extremity ruled out fractures and patient was discharged to follow up with primary care physician. Two days later mother brought him to our ED due to persistent left upper extremity paralysis, poor appetite, and subjective fever. On exam his left arm was warm and tender to dull and sharp touch;he had definite loss of active movement, hypotonia and absence of deep tendon reflexes. The patient had winging of left scapula and could not shrug left shoulder. MRI of cervical and thoracic spine showed enlargement of spinal cord from C2-C6 level with gray matter hyperintensity, slightly asymmetric to the left. Laboratory studies showed leukocytosis (14 000/mcL) and CSF studies showed pleocytosis of 89 WBC/mcL (93.3% mononuclear cells and 6.7% polymorphonuclear cells), 0 RBCs, normal glucose and protein, and a negative CSF meningoencephalitis multiplex PCR panel. Due to high suspicion of demyelinating or autoimmune condition he was treated with high dose steroids and IVIG. Subsequently neuromyelitis optica was ruled out as aquaporin-4 receptor antibodies (AB) and myelin oligodendrocyte glycoprotein AB were normal. CSF myelin basic protein and oligoclonal bands were absent ruling out demyelinating disorders. CSF arboviruses IgM and West Nile IgM were negative. He showed minimal improvement in left upper extremity movement but repeat spinal cord MRI one week later showed improved cord thickness with less hyperintensity. Respiratory multiplex PCR was negative including enteroviruses. Repeat CSF studies after IVIG showed increased IgG index and IgG synthesis suggestive of recent spinal cord infection, consistent with acute flaccid myelitis (AFM). Pre-IVIG blood PCR was invalid for enteroviruses due to PCR inhibitors found in the sample. Blood post-IVIG was negative for mycoplasma IgM, West Nile IgM, and arboviruses IgM. Enterovirus panel titers (post-IVIG) were positive for coxsackie A (1:32), coxsackie B type 4 (1:80) and 5 (1:320), echovirus type 11 (1:160) and 30 (1:80) as well as positive for poliovirus type 1 and 3. These titers could not distinguish acute infection from patient's immunity or false-positives as a result of IVIG. He was discharged with outpatient follow-up visits with neurology, infectious disease, occupational and physical therapy, showing only mild improvement after discharge. Discussion(s):With the anticipated resurgence of AFM after the peak of COVID-19 pandemic, our case illustrates the need to consider this diagnostic possibility in patients with flaccid paralysis. It is important to remember CSF IgG synthesis is not affected by IVIG. In addition when treatment plans include IVIG, appropriate samples should be collected before IVIG to facilitate accurate work-up for infectious diseases. Copyright © 2023 Southern Society for Clinical Investigation.

Epidemiology and Burden of NMOSD, MS, and MOGAD in Thailand: a Population-Based Study

Objective To determine cumulative incidence and point prevalence of neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in Thailand using population-based data of Chumphon province. Background CNS inflammatory demyelinating diseases (CNSIDDs) have a great interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a Mainland Southeast Asian country, is unknown. Design/Methods Searching for CNSIDD patients at a public secondary care hospital in Chumphon from January 2016 to December 2021 was performed using relevant ICD-10-CM codes. All neurology patients were systematically referred to this hospital as it was the only hospital in the province with a neurologist. Diagnoses were individually ascertained by retrospective chart review. Cumulative incidence over 2016-2021, point prevalence on December 31st, 2021, attack rate, mortality rate, and disabilityadjusted life years (DALYs) were calculated. Population data were obtained from the National Statistical Office of Thailand. As of December 31st, 2021, the population census of Chumphon was 509,479. Results NMOSD was the most prevalent CNSIDD in adult Thai population at 3.33 per 100,000 persons (crude prevalence 2.55). The age-adjusted prevalence of aquaporin-4 antibody-positive NMOSD alone was 3.08 per 100,000 persons. Age-adjusted incidence rate of NMOSD was 1.65 per 100,000 persons/year (crude incidence rate 0.20). Age-adjusted prevalence of MS followed at 0.77 and MOGAD at 0.51 per 100,000 persons (crude prevalence 0.59 and 0.39, respectively). Although most had a fair recovery, disability was worst amongNMOSD with a DALY of 3.47 years per 100,000 persons. Mortality and attack rates were highest in NMOSD as well. No increase in incidence or attack rate were observed during the COVID-19 pandemic. Conclusions CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian countries. NMOSD caused the highest DALYs among CNSIDDs.

Neurological Immune-Related Adverse Events After COVID- 19 Vaccination: A Systematic Review

Objective The goal of this study is to compile published data reporting neurological immune-related adverse events following COVID-19 vaccination, not including those relating to hematologic abnormalities such as thrombosis or hemorrhage. Background COVID-19 vaccination has been repeatedly shown to reduce the incidence and severity of COVID-19 infection. The expedited timeline of these vaccines has given rise to many discussions pertaining to their safety. Many neurological and non-neurological adverse events have been linked to COVID-19 vaccination including acute MI, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, transverse myelitis, and many others. Design/Methods The following databases were searched in April 2021 using different keywords: PubMed, Medline, Embase, Scopus, Web of Science, Science, Direct, MedRxiv, and Lens.org. Studies were included if they reported any adverse immune-related neurological events secondary to COVID-19 vaccination. Studies were excluded if they were not in English, included self-reported events only, or did not report primary data. Screening and extraction were conducted by 2 different reviewers using Covidence. Results The search strategy yielded 18 studies which reported a total of 61 patients who had received a COVID-19 vaccination and experienced = 1 neurological adverse events. Most reported adverse events were facial nerve palsy (52.5%), reactivation of herpes zoster (11.5%), Guillian-Barre syndrome (6.6%), demyelinating disease (6.6%), and neuropathy (11.5%). Other reported adverse effects were delirium, periauricular vesicular rash, bilateral sensorineural hearing loss, visual disturbance, gait disturbance, serotonin syndrome, and vestibular ataxia (16.4%). Conclusions The symptoms were time-limited and self-resolving in nature. In addition, the incidence of the reported events following COVID-19 vaccination compared to the general population is similar. Hence, there is little to no evidence suggesting a causal relationship between COVID-19 vaccination and neurological adverse events.

Acute Central Nervous System Demyelination Following COVID-19 Vaccination

Objective To describe features of central nervous system (CNS) demyelinating events following vaccination against coronavirus disease 19 (COVID- 19). Background Several reports suggest a potential association between COVID-19 vaccines and acute CNS inflammation. Design/Methods A case series was performed at the BARLO MS Centre in Toronto, Ontario, Canada. Clinicians reported patients who experienced an acute CNS demyelinating event within 60 days after receiving at least one COVID-19 vaccination from March 2021 to January 2022. Clinical characteristics were evaluated. Results Twenty patients were identified (median age 39 years (range 25-82);13 (65.0%) female). Two had pre-existing multiple sclerosis (MS). Individuals received the Pfizer (n = 14), Moderna (n = 5) or Astrazeneca (n = 1) COVID-19 vaccines. Within 1-53 days (median 12) of the first (n = 8) or second (n = 12) vaccine dose, patients developed transverse myelitis (TM) (n = 15), optic neuritis (n = 4) or brain demyelination (n = 4). Diagnoses at last follow up (median 114 days (range 39-255)) were relapsing remitting MS (n = 8), post-vaccine TM (n = 5), clinically isolated syndrome (n = 3), myelin oligodendrocyte glycoprotein antibody disease (n = 2), MS relapse (n = 1) and neuromyelitis optica spectrum disorder (n = 1). Thirteen patients received pulse corticosteroids, and of these, 4 received plasma exchange. Seven did not receive acute treatment. 20.0% returned to baseline (n = 4), 75.0% partially recovered (n = 15) and 5.0% worsened (n = 1). At last follow up, 11 were on disease modifying therapy and 9 were not. Nine patients received a subsequent COVID-19 vaccine. Of these, one experienced symptom recrudescence without radiologic evidence of a new demyelinating attack. Conclusions To our knowledge, this is the largest series to date describing acute CNS demyelination after vaccination against COVID-19. The rate of vaccination in the eligible general population was high during the time of the cases and we could not determine whether the number of demyelinating events was higher than expected. Repeat vaccination was not associated with recurrent adverse events in this small observational series.

Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar.

BACKGROUND: This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods. RESULTS: In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1-7.0) in SAkuraSky and 4.0 years (range 0.1-6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies. CONCLUSION: The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).

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.

Exploring Feature Genes for Ischemic Stroke Based on Bioinformatics and Machine Learning

Background and Aims: This study aims to screen the feature genes of ischemic stroke (IS) by bioinformatics and machine learning (ML) and explore the possible pathophysiological mechanism of the genes in IS. Method(s): Two RNA sequencing datasets were downloaded from NCBI Gene Expression Omnibus (GEO) database. The GSE122709 dataset with a larger sample size was used as the training set and analyzed for differentially expressed genes (DEGs), while the GSE140275 dataset was used as the test set. The DEGs were further analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analyses. Then, feature genes selection was performed by two ML algorithms. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the ML algorithms. Result(s): A total of 378 DEGs (Fold Change>=2 and p value<=0.05) were identified. The GO and KEGG analyses demonstrated that the majority of DEGs were associated with inflammatory response, immune regulation and COVID-19. The DO analysis revealed that the DEGs were mainly linked to demyelinating disease and cancer. The TVP23C and B3GAT1 were identified as feature genes by ML algorithms, and the AUCs of them were closer to 1 both in the training and test set. It is found that B3GAT1 may be involved in brain injury of IS by regulating AMRA glutamate receptors. Conclusion(s): The integrated approach of bioinformatics and ML could be a novel approaches for screening feature genes, and the B3GAT1 gene may be a possible therapeutic target in IS.

Tocilizumab treatment of MOGAD encephalitis nonresponder to Anti CD-20 therapy: efficacy and safety during SARS-COV-2 infection

Introduction: Myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD) is an autoimmune disorder of the central nervous system distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder. Common clinical presentations include a recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis (ADEM) or ADEM-like syndromes, and brainstem encephalitis. Objectives/Aims: To report a case of patient affected by MOGAD encephalitis who experienced SARS-CoV-2 infection during the treatment with Tocilizumab. Methods and Results: We report a case of a 57-year-old Caucasian woman with a 5-year history of a demyelinating disease characterized by bilateral and symmetric fronto-temporoparietal demyelinating lesions and previously diagnosed as MS. The patient had been treated with severaltherapies, including interferon beta-1a, Natalizumab, anti-CD-20 monoclonal antibodies, with no benefits.Her symptoms and brain magnetic resonance imaging (MRI) lesionsload had progressively worsened, resulting in a significantmotor and cognitiveimpairment.In April 2020, the diagnosis was reviewed and classified as MOGAD+ encephalitis.Thepatient started anti-CD-20 monoclonal antibody therapy, stopped due to lack of efficacycharacterized by increasing MRI lesion load and worsening of cognitive impairment. In February 2022, Tocilizumab, an IL-6 receptor inhibitor, was initiated at the dosage of 8 mg/kg via intravenous route. Further administrations were repeated every four weeksin March and April 2022. The treatment was well tolerated and the patient did not report any adverse event. IL-6 levels decreased and the caregiver reported an improvement in patient's cognitive performances. Furtherneurological examinations showed a mild improvement in motor performances, walking ability, and brainstem and cognitive functions. On April25th, the patient, previously vaccinated with three doses of Pfizer-BioNTech vaccine, tested positive to SARS-CoV-2which resulted in symptoms characterized by.fever, cough, joint pain, and shortness of breath. Two days after the symptoms onset, she started therapy with nirmatrelvir/ ritonavirobtaining a dramatic regression of all the symptoms in about24 hourswithout any adverse events. Conclusion(s): In light of the lack of literature on the co-occurrence of COVID-19 in Tocilizumab-treated MOGAD patients, the present report highlights the safety and benefit of the use of antiviral therapy in these patients.

Impact of COVID-19 infection and COVID vaccinations on the management of MS and related disorders in a low middle income country-real world experience from a demyelinating disease registry

Background and objective: The impact of COVID-19 infection and the effect of vaccinations on patients with demyelinating central nervous system disease in low middle income countries (LMIC's) have not been reported in detail earlier. We sought to identify risk factors associated with COVID-19 infection and the role of vaccinations in patients with MS and related disorders in order to develop management guidelines relevant to our patients. Method(s): A total of 621 patients (297 MS and 324 non MS disorders) from our registry were contacted. COVID-19 infection and vaccination status were queried. Patients who had infection were compared with noninfected patients to identify factors associated with susceptibility for COVID-19 infection. Univariate and multivariate analysis of potential risk factors included demographic and clinical features, body mass index (BMI), presence of comorbidities, absolute lymphocyte count, treatment types and vaccination status. Result(s): Sixty seven patients with MS and 27 with non MS disorders developed COVID-19 infection. Among them 13 patients were hospitalized, all of whom recovered. Vaccination status was known in 582 patients among whom 69.8% had completed or taken one dose of vaccine at the time of inquiry. Majority of treated patients (61.3%) were on nonspecific immunosuppressants. Multivariate analysis of all patients with MS and related disorders showed that higher mean body mass index(BMI [p - 0.002, OR- 0.86,95% CI - 0.78-0.94]), presence of >= 1 comorbidity ( p-0.005, OR- 3.57,95% CI- 1.46- 8.7) and concurrent treatment with disease modifying therapy(p- 0.004, OR- 2.80, 95% CI- 1.39- 5.6)were significantly associated with risk of COVID-19 infection. Vaccination against COVID-19 infection was strongly protective (p- 0.0001, OR- 0.10, 95% CI- 0.05- 0.20). In the unvaccinated group, patients on treatment ( 61% were on nonspecific immunosuppressants) were significantly at risk of Covid-19 infection (p- 0.001, OR- 10.1, 95% CI- 4.59- 22.22) when compared to untreated patients. Conclusion(s): Frequency and severity of COVID-19 infection was low among our patient cohort.Higher rate of infection in the treated group was significant among unvaccinated patients. Our preliminary results suggests that in LMIC's, where off label therapies with inexpensive immunosuppressives are the main disease modifying drugs, mRNA vaccinations appear safe and protective against severe COVID-19 infection.

COVID-19 and the risk of CNS demyelinating diseases: a systematic review

Background: Viral infections are thought proposed as a possible cause of central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past two years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear. Objective(s): To investigate the relationship between CNS demyelinating disease development with antecedent and/or concurrent COVID-19 infection. Method(s): A systematic literature review of all publications describing either a new disease onset or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach. Result(s): Fifty articles were meet inclusion criteria for the study. Most of the reported cases ofNMOSD (n=10., 66.7% of reported cases)and MOGAD (n=12, 92% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases (n=11, 13% of reported cases), relapses (n=48, 56.5%) and pseudo-relapses (n=26, 30.5%). Median duration between COVID-19 infection and demyelinating event onset was 9 days (range 0-30 days) in NMOSD, 4 days (range-7-+21 days) in MOGAD, and 13.5 days (range-21-+180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome. Conclusion(s): Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low given the prevalence of infection. The clinical outcome of new-onset or relapsing MS, NMOSD or MOGAD associated with antecedent or concurrent infection is mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.

Prevalence and factors associated with COVID-19 vaccination in people with multiple sclerosis compared to the general population in Croatia

Background: The aim of this study was to determine the pooled prevalence of COVID-19 vaccination among people with multiple sclerosis (pwMS) compared to the general population in Croatia. Method(s): Data from all pwMS entered in the MS Base register until24.03.2022 were extracted including age, sex, MS phenotype, disease-modifying therapy (DMT), COVID-19 vaccine, and date of vaccination (1st, 2ndand/or 3rddose). Data on the general population of Croatia were obtained from the vaccination register of the Croatian Institute of Public Health. Result(s): 464 pwMS (317 females, with a median age of 38.1 years, disease duration of 6.1 years, EDSS 1.5) were included in the analysis. 386 (83.2%) pwMS had relapsing-remitting, 26 (5.6%) primary progressive, 19 (4.1%) secondary progressive phenotypes, and 16 (3.4%) clinically isolated syndrome. Fifty-six (12.1%) pwMS were treatment naive, 21 (4.5%) were not on DMT at the moment of the last visit, 134 (28.9%) were on injectable DMTs, 84 (18.1%) on 1stline oral DMTs, and 169 (36.4%) were on high efficacy DMTs. 295 (63.6%) pwMS were fully COVID-19 vaccinated compared to 59.7% of the general population (p=0.089). However, in the age groups, 20-24 and 35-39 significantly more pwMS received 2 doses compared to the general population (p=0.001 and p=0.03, respectively). Vaccinated pwMS were older (40.5 vs 37.6 years, p=0.01), had higher EDSS (2.0 vs 1.0, p=0.025), and longer disease duration (6.39 vs 5.35 years, p=0.02), were more likely to have progressive disease course (p=0.049) and on high efficacy DMTs (p=0.045) compared to unvaccinated pwMS.In a multivariable logistic regression model, there were no predictors for COVID-19 vaccination in pwMS. Conclusion(s): There was a similar prevalence of vaccinated individuals in pwMS and the general population. However, in younger age groups significantly more pwMS were vaccinated when compared to the general population.

More Than Meets the Eye: A Closer Look at Demyelinating Diseases in Zambia

Background: The number of people with multiple sclerosis (MS) globally has increased from 2.3 million in 2013 to 2.8 million in 2020. However, MS and other demyelinating diseases are reported to be very rare in sub-Saharan Africa. Objective(s): We aimed to describe demographic and clinical characteristics of the first cohort of patients with MS and neuromyelitis optica (NMO) from Zambia and one of the first such cohorts from the sub-Saharan African region. Method(s): Adults diagnosed with either MS, NMO, NMO spectrum disorder (NMOSD), or clinically isolated syndrome (CIS) at the neurology outpatient clinic at the University Teaching Hospital in Lusaka, Zambia, the only neurology clinic in the country, were eligible to participate. Participants were enrolled from October 2019 through February 2022 with significant interruptions due to Covid- 19. An MS-trained nurse administered structured questionnaires regarding sociodemographic characteristics, and each participant also underwent a comprehensive neurological history and examination by a neurologist. Finally, plasma 25-hydroxyvitamin D levels were obtained. For analysis, the cohort was dichotimized into a MS/CIS disease group and NMO/NMOSD disease group. Descriptive statistics of the cohort are presented and compared between both groups. Result(s): Amongst the 34 participants, mean age was 36 + 9 years, 65% (n=22) were female, 90% were Black-African, 10% were of Southeast Asian decent, 50% had MS/CIS, and 50% had NMO/NMOSD. The average age was 34 + 11 years in the MS/CIS group and 37 + 7 years in the NMO/NMOSD group (p=0.28). Females constituted 65% (n=11) of both disease groups. Median time to diagnosis was 242 days (interquartile range IQR: 91-974) and did not differ significantly between the groups. The majority (82%) of the NMO/NMOSD group presented with bilateral optic neuritis. Among the MS/CIS group, median EDSS was 4 (IQR: 2.25-4.25), median Disease Steps were 2 (IQR: 1-2), and 59% (n=10) had an abnormal gait at enrollment. Median 25-hydroxyvitamin D level was 29 (IQR: 24-46) ng/mL in the overall cohort but did not differ by disease group or supplementation status. Conclusion(s): In this sub-Saharan African cohort of adults with demyelinating diseases, MS and NMO were equally prevalent. Furthermore, delays in diagnosis resulted in high levels of disability in both groups. This demonstrates the need for more research and funding towards demyelinating diseases in sub-Saharan Africa.