Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course. METHODS: Prospectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease. RESULTS: We identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097). CONCLUSION: Sex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.

Short-chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset.

OBJECTIVE: The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric-onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. METHODS: A multicenter case-control study in which 35 pediatric-onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self-reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co-occurrence networks and for predicting functional abundances based on marker gene sequences. RESULTS: Two microbial co-occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short-chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family-level findings from an independent Canadian-US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. INTERPRETATION: Our results suggest that short-chain fatty acid producers may be important contributors to multiple sclerosis onset.

Smoking and multiple sclerosis risk in black people: A nested case-control study.

BACKGROUND: Smoking is a well-established risk factor for MS; however, it is not known whether its effect on disease risk varies by race/ethnicity. METHODS: We conducted a nested case-control study among US military personnel who have serum samples stored at the Department of Defense Serum Repository. We measured serum cotinine levels, a marker of tobacco smoke exposure, in 157 Black and 23 White individuals who developed MS during follow-up. Controls were randomly selected and matched to each case by age, sex, race/ethnicity, dates of sample collection, and branch of military service. RESULTS: Smoking was not associated with an increased risk of MS in Black people (RR: 1.08, 95 % CI: 0.63-1.85). The results remained similar in analyses restricted to smoking status at baseline, to samples collected 5 years before symptom onset, and using different cut-off levels in cotinine to define smoking status. Smoking was not statistically significantly associated with MS risk in White people, but the point estimate was similar to what has previously been reported in other studies (RR: 1.85, 95 % CI: 0.56-6.16). CONCLUSIONS: Smoking was not associated with MS risk in Black people. Given the consistent association between smoking and MS risk in predominantly White populations, this may suggest that the association between smoking and MS varies by race/ethnicity.

Expanded disability status scale by phone BR: Brazilian Portuguese validation.

BACKGROUND: The Expanded Disability Status Scale (EDSS) is widely used and accepted by regulatory agencies for the assessment of neurological disability secondary to Multiple Sclerosis. The "Expanded Disability Status Scale (EDSS) by phone" was developed to be a patient-reported telephone-based alternative for the assessment of EDSS functional system scores when a physical examination is not possible. The scale has been validated in multiple languages; however, its reliability has not been assessed in Brazilian Portuguese. METHODS: After cross-cultural translation and adaptation, 57 people with MS with a recent in-person visit (±6 months) were invited to answer the EDSS by phone scale on two occasions, 15 days apart. The agreement between scales (in-person and telephone-based) and between telephone-based assessments was evaluated using intraclass correlation coefficients (ICC) for absolute agreement and weighted Kappa coefficients. RESULTS: An excellent reliability was obtained for the agreement between the in-person and telephone assessments (ICC: 0.95, 95 %CI 0.92-0.97, Kappa: 0.83, 95 %CI 0.78-0.89) and between telephone-based assessments (ICC: 0.99, 95 %CI 0.98-0.99, Kappa: 0.93, 95 %CI 0.88-0.97). After stratification by disability level, the agreement between scales was less pronounced for subjects with an EDSS ≤ 4.0. CONCLUSION: this study offers evidence that supports the validity of the EDSS by phone questionnaire translated into Brazilian Portuguese, particularly for patients with higher EDSS scores.

Gene-environment interactions and risk of pediatric-onset multiple sclerosis associated with time spent outdoors.

BACKGROUND: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk. METHODS: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02). RESULTS: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56-0.78, p < 0.001; OR 0.78, 95 % CI 0.62-0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors. CONCLUSIONS: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.

Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD. METHODS: T2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach. RESULTS: The %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, p < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1-10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%). CONCLUSION: The %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset.

Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination.

Importance: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. Objective: To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. Design, Setting, and Participants: This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. Main Outcomes and Measures: Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. Results: After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). Conclusion and Relevance: In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.

Several serum lipid metabolites are associated with relapse risk in pediatric-onset multiple sclerosis.

BACKGROUND: The circulating metabolome is altered in multiple sclerosis (MS), but its prognostic capabilities have not been extensively explored. Lipid metabolites might be of particular interest due to their multiple roles in the brain, as they can serve as structural components, energy sources, and bioactive molecules. Gaining a deeper understanding of the disease may be possible by examining the lipid metabolism in the periphery, which serves as the primary source of lipids for the brain. OBJECTIVE: To determine if altered serum lipid metabolites are associated with the risk of relapse and disability in children with MS. METHODS: We collected serum samples from 61 participants with pediatric-onset MS within 4 years of disease onset. Prospective longitudinal relapse data and cross-sectional disability measures (Expanded Disability Status Scale [EDSS]) were collected. Serum metabolomics was performed using untargeted liquid chromatography and mass spectrometry. Individual lipid metabolites were clustered into pre-defined pathways. The associations between clusters of metabolites and relapse rate and EDSS score were estimated utilizing negative binomial and linear regression models, respectively. RESULTS: We found that serum acylcarnitines (relapse rate: normalized enrichment score [NES] = 2.1, q = 1.03E-04; EDSS: NES = 1.7, q = 0.02) and poly-unsaturated fatty acids (relapse rate: NES = 1.6, q = 0.047; EDSS: NES = 1.9, q = 0.005) were associated with higher relapse rates and EDSS, while serum phosphatidylethanolamines (relapse rate: NES = -2.3, q = 0.002; EDSS: NES = -2.1, q = 0.004), plasmalogens (relapse rate: NES = -2.5, q = 5.81E-04; EDSS: NES = -2.1, q = 0.004), and primary bile acid metabolites (relapse rate: NES = -2.0, q = 0.02; EDSS: NES = -1.9, q = 0.02) were associated with lower relapse rates and lower EDSS. CONCLUSION: This study supports the role of some lipid metabolites in pediatric MS relapses and disability.

Sexual dysfunction in Brazilian patients with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (PwMS) show an increased risk of sexual dysfunction (SD), both in women and men. OBJECTIVE: The aim of the present study was to apply the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and evaluate our results by comparing them with those in in the literature, as well as to assess the ease of applying the scale and the engagement of the patients in discussing the topic of sexuality. METHODS: We developed and applied a web-based Google form questionnaire that the respondents completed online, which included the MSISQ-19, for the assessment of sexual function. Baseline characteristics were reported as proportions and mean ± standard deviation (SD) or median ± interquartile range (IQR) as appropriate according to data distribution. Categorical variables were stratified by sex and compared with chi-squared tests. Statistical analyses were performed using STATA v. 16 (StataCorp., College Station, TX, USA). RESULTS: Of the 621 respondents, 541 were included in the analysis. Among the patients with MS, a total of 347 (64.14%) exhibited SD. When stratified by gender, the frequencies of SD were not significantly different. CONCLUSION: There is a high incidence of sexual dysfunction among PwMS and we need to identify the reasons for this and implement strategies to treat and counsel our patients. The MSISQ-19 can be used to help clinicians to assess sexual functioning in a quick and easy way and give patients the possibility to address this topic and receive appropriate help and support.

ANTECEDENTES: Pacientes com esclerose múltipla apresentam altas taxas de disfunção sexual em diversos estudos. OBJETIVO: Avaliar a aplicação e resultados da ferramenta para avaliação de disfunção sexual em pacientes com Esclerose Multipla, Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), bem como comparar os resultados encontrados com a literatura já existente e ter a percepção do engajamento dos pacientes sobre o tema. MéTODOS: Realizado através de questionário on-line na plataforma Google Forms, composto por questões sobre perfil demográfico e relacionadas à doença e o questionário MSISQ-19. Os dados demográficos e sobre a doença foram descritos como proporções e média ± desvio padrão (DP) ou mediana ± intervalo interquartil (IIQ). As variáveis categóricas foram estratificadas por sexo e comparadas com testes de qui-quadrado. As análises estatísticas foram realizadas no programa STATA v. 16 (StataCorp., College Station, TX, EUA). RESULTADOS: Um total de 621 pacientes responderam ao questionário, sendo inclusos na análise 541 respostas, após a aplicação dos critérios de elegibilidade. Um total de 347 (64,14%) pacientes apresentaram disfunção sexual, sem diferença entre os gêneros. CONCLUSãO: Disfunção sexual apresenta alta prevalência no grupo estudado, sendo necessário identificar as causas e implementar estratégias de tratamento. O MSISQ-19 é uma ferramenta fácil e rápida de ser aplicada, podendo ser utilizada para facilitar a comunicação com os pacientes sobre o tema, possibilitando assim o tratamento das disfunções sexuais nessa população.

Sexual dysfunction in Brazilian patients with multiple sclerosis / Disfunção sexual em pacientes brasileiros com esclerose múltipla

Abstract Background People with multiple sclerosis (PwMS) show an increased risk of sexual dysfunction (SD), both in women and men. Objective The aim of the present study was to apply the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and evaluate our results by comparing them with those in in the literature, as well as to assess the ease of applying the scale and the engagement of the patients in discussing the topic of sexuality. Methods We developed and applied a web-based Google form questionnaire that the respondents completed online, which included the MSISQ-19, for the assessment of sexual function. Baseline characteristics were reported as proportions and mean ± standard deviation (SD) or median ± interquartile range (IQR) as appropriate according to data distribution. Categorical variables were stratified by sex and compared with chisquared tests. Statistical analyses were performed using STATA v. 16 (StataCorp., College Station, TX, USA). Results Of the 621 respondents, 541 were included in the analysis. Among the patients with MS, a total of 347 (64.14%) exhibited SD. When stratified by gender, the frequencies of SD were not significantly different. Conclusion There is a high incidence of sexual dysfunction among PwMS and we need to identify the reasons for this and implement strategies to treat and counsel our patients. The MSISQ-19 can be used to help clinicians to assess sexual functioning in a quick and easy way and give patients the possibility to address this topic and receive appropriate help and support.

Resumo Antecedentes Pacientes com esclerose múltipla apresentam altas taxas de disfunção sexual em diversos estudos. Objetivo Avaliar a aplicação e resultados da ferramenta para avaliação de disfunção sexual em pacientes com Esclerose Multipla, Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), bem como comparar os resultados encontrados com a literatura já existente e ter a percepção do engajamento dos pacientes sobre o tema. Métodos Realizado através de questionário on-line na plataforma Google Forms, composto por questões sobre perfil demográfico e relacionadas à doença e o questionário MSISQ-19. Os dados demográficos e sobre a doença foram descritos como proporções e média ± desvio padrão (DP) ou mediana ± intervalo interquartil (IIQ). As variáveis categóricas foram estratificadas por sexo e comparadas com testes de qui-quadrado. As análises estatísticas foram realizadas no programa STATA v. 16 (StataCorp., College Station, TX, EUA). Resultados Um total de 621 pacientes responderam ao questionário, sendo inclusos na análise 541 respostas, após a aplicação dos critérios de elegibilidade. Um total de 347 (64,14%) pacientes apresentaram disfunção sexual, sem diferença entre os gêneros. Conclusão Disfunção sexual apresenta alta prevalência no grupo estudado, sendo necessário identificar as causas e implementar estratégias de tratamento. O MSISQ-19 é uma ferramenta fácil e rápida de ser aplicada, podendo ser utilizada para facilitar a comunicação com os pacientes sobre o tema, possibilitando assim o tratamento das disfunções sexuais nessa população.

Gene-environment interactions increase the risk of paediatric-onset multiple sclerosis associated with household chemical exposures.

BACKGROUND: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. METHODS: Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090). RESULTS: 490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes. CONCLUSIONS: The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.

Stroke Outcomes and Hyperacute Treatment Utilization in Multiple Sclerosis.

BACKGROUND: People with MS (pwMS) have higher prevalence of comorbidities at disease onset and face increased risk of developing cardiovascular disorders. Stroke is of particular concern for this population with previous neurological disability. However, data on stroke outcomes and resource utilization in those pwMS remains scarce. OBJECTIVE: To assess the risk of adverse stroke outcomes and hyperacute treatment utilization for pwMS in a U.S. population-based sample of hospitalized patients. METHODS: This study identified patients discharged with a diagnosis of ischemic stroke in the 2018 National Inpatient Sample. We compared the discharge outcomes and hyperacute stroke treatment utilization in MS (n = 2,795) versus non-MS patients (n = 682.730). Regression models adjusted for cardiovascular risk factors and hospital characteristics were used to account for the complex sampling design. RESULTS: The odds of a good discharge were 32% less likely to occur in pwMS (adj.OR 0.68 [95%CI 0.58-0.81], p<0.001). However, this was not associated with an increased risk of mortality. PwMS had a 57% reduction in the risk of receiving endovascular thrombectomy (EVT) (adj.OR 0.43 [95%CI 0.22-0.83], p = 0.01) but no difference in rates of thrombolysis. CONCLUSION: Patients with MS have lower rates of good discharge outcomes and EVT with ischemic stroke, despite similar rates of thrombolysis.

N-Acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis (NACPMS) trial: Study protocol for a randomized, double-blind, placebo-controlled add-on phase 2 trial.

INTRODUCTION: Patients with progressive multiple sclerosis (PMS) experience relentless disability worsening. Current approved therapies have very modest effects on disability progression and purely focus on immunomodulation. While some inflammatory processes exist in non-active PMS, other biological processes such as neuronal injury from oxidative stress are likely more critical. N-acetyl cysteine (NAC) directly scavenges free radicals and restores neuronal glutathione, a major endogenous antioxidant. Our group has recently evaluated the safety of high dose NAC in a pilot trial in PMS with no tolerability concerns. We aim now to assess the safety, tolerability, and effect of NAC on progression of several MRI, clinical and biological markers in PMS patients. METHODS: The NACPMS trial is a multi-site, randomized, double-blind, parallel-group, placebo-controlled add-on phase 2 trial. Ninety-eight PMS patients with EDSS 3.0-7.0 and aged 40-70 years will be randomized to NAC 1200 mg TID or matching placebo (1:1) as an add-on to the standard of care stratified by site and disease type during a 15-month intervention period. It is hypothesized that a reduction in oxidative stress injury will lessen brain atrophy estimated by MRI. The primary outcome analysis will compare the percent change over 12 months (Month 15 vs Month 3) between treatment and control arms using multivariable linear regression adjusted by age, sex, and disease duration. ETHICS: This study was approved by the Institutional Review Board at the University of California, San Francisco (IRB21-34143), and an Investigational New Drug approval was obtained from the FDA (IND127184). TRIAL REGISTRATION: NCT05122559.

Paracentral acute middle maculopathy in Susac syndrome after dual exposure to SARS-CoV-2 antigen.

We report a case of Susac syndrome after SARS-CoV-2 infection and subsequent vaccination that presented with meningitis and retinal microembolisation in the form of paracentral acute middle maculopathy (PAMM). After presenting with headache, fever and myalgia followed by scotomata, a woman in her 50s was hospitalised for meningitis; she had had mild COVID-19 infection 2 months prior to admission, having received the first vaccine dose 1 month prior to the neurological manifestation. Eye fundus examination and optical coherence tomography were suggestive of PAMM. D-dimer levels and erythrocyte sedimentation rate were elevated. Before infectious investigation results were available, she was started on empirical antibiotic and antiviral treatment. Having ruled out infectious causes, she was started on high-dose prednisolone. After 1 month, there was partial resolution of retinal lesions. This case highlights that exposure to SARS-CoV-2 antigen may be related to this rare syndrome; treatment with steroids may improve central and retinal impairment.

Drug-related demyelinating syndromes: understanding risk factors, pathophysiological mechanisms and magnetic resonance imaging findings.

Some drugs and medications can precipitate immune system deregulations, which might be confused with recurrent demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO), exacerbations of an existing disease, neoplastic lesions or other conditions. In this narrative review we describe some of the most relevant drugs and medications associated with iatrogenic demyelination. The anthelminthic agent levamisole is a frequent cocaine adulterant and can precipitate an exacerbated immune response attacking the central nervous system (CNS). High-efficacy multiple sclerosis (MS) drugs might induce a selective CNS immunosuppression, making it susceptible for opportunistic infections that course with demyelination, such as progressive multifocal leukoencephalopathy. Sometimes, the interruption of a high-efficacy drug to treat MS can induce a rapid CNS reentry of lymphocytes, exacerbating demyelinating processes and triggering rebound syndromes. Furthermore, selective cytokines inhibition, such as anti-TNFα agents, might induce an imbalance between cell death and proliferation inducing a paradoxical increase of CNS tumor necrosis factor (TNF), affecting the activity of lymphocytes, microglia and macrophages, triggering aberrant inflammation and demyelination. Immune checkpoint inhibitors are a new class of antineoplastic drugs that enhance the immune response against tumor cells by an upregulation of T-cell activity. However, this hyperactivation of the immune system might be associated with induction of unwanted autoimmune responses. In this paper we review the risk factors, the possible pathological mechanisms and the magnetic resonance imaging (MRI) findings of these drug-related demyelinating syndromes.

Popular knowledge of stroke in São Paulo: a cross-sectional study within the World Stroke Campaign

ABSTRACT BACKGROUND: Stroke is the second leading cause of death in Brazil and the main cause of disability. Inability to identify alarm signals causes delays in seeking emergency services, thereby leading to a worse prognosis. OBJECTIVES: To assess the population's knowledge of how to recognize and prevent stroke. DESIGN AND SETTING: Prospective cross-sectional study on data derived from a questionnaire that was administered during the 2016 World Stroke Campaign, launched in the city of São Paulo, Brazil. METHODS: Data on 806 interviewees were evaluated using descriptive statistics and univariate and multivariate analyses. RESULTS: Among all the interviewees, 52.1% knew how to conceptualize stroke; 70.07% knew someone who had suffered a stroke; and 29.03% listed three or more risk factors. Only 27.5% mentioned controlling high blood pressure as a preventive measure. In the event of witnessing a stroke, 57.8% would call the emergency service and 2.9% would check the timing. Less educated individuals were 5.6 times more likely (95% confidence interval, CI 3.45-9.02) to have poor knowledge of stroke, compared with the more educated group. Knowing someone who had had a stroke reduced the chances of not knowing the terms relating to the disease (odds ratio, OR = 0.56; 95% CI 0.4-0.78). CONCLUSIONS: Despite the severity and prevalence of stroke, the population still has little information on this disease. In this context, the importance of mounting campaigns to improve prevention and treatment and to contribute to healthcare policies becomes evident.

Popular knowledge of stroke in São Paulo: a cross-sectional study within the World Stroke Campaign.

BACKGROUND: Stroke is the second leading cause of death in Brazil and the main cause of disability. Inability to identify alarm signals causes delays in seeking emergency services, thereby leading to a worse prognosis. OBJECTIVES: To assess the population's knowledge of how to recognize and prevent stroke. DESIGN AND SETTING: Prospective cross-sectional study on data derived from a questionnaire that was administered during the 2016 World Stroke Campaign, launched in the city of São Paulo, Brazil. METHODS: Data on 806 interviewees were evaluated using descriptive statistics and univariate and multivariate analyses. RESULTS: Among all the interviewees, 52.1% knew how to conceptualize stroke; 70.07% knew someone who had suffered a stroke; and 29.03% listed three or more risk factors. Only 27.5% mentioned controlling high blood pressure as a preventive measure. In the event of witnessing a stroke, 57.8% would call the emergency service and 2.9% would check the timing. Less educated individuals were 5.6 times more likely (95% confidence interval, CI 3.45-9.02) to have poor knowledge of stroke, compared with the more educated group. Knowing someone who had had a stroke reduced the chances of not knowing the terms relating to the disease (odds ratio, OR = 0.56; 95% CI 0.4-0.78). CONCLUSIONS: Despite the severity and prevalence of stroke, the population still has little information on this disease. In this context, the importance of mounting campaigns to improve prevention and treatment and to contribute to healthcare policies becomes evident.

Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. OBJECTIVE: To discuss strategies to manage those patients. METHODS: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. CONCLUSIONS: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach / Manejo de doenças desmielinizantes do sistema nervoso central na pandemia de doença do coronavírus 2019: uma abordagem prática

ABSTRACT Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

RESUMO Introdução: A mais recente pandemia causada pelo coronavírus SARS-CoV-2 (COVID-19, do inglês coronavirus disease 2019) representa uma ameaça potencial para pacientes com doenças autoimunes, incluindo esclerose múltipla (EM) e transtorno do espectro de neuromielite óptica (NMOSD, do inglês neuromyelitis optica spectrum disorders). Esses pacientes são geralmente tratados com medicamentos imunomoduladores ou imunossupressores que podem alterar a resposta normal do organismo a infecções. Até o momento, não há consenso sobre como o manejo dos pacientes com EM e NMOSD deve ser realizado durante a pandemia. Objetivo: Discutir estratégias para manejar esses pacientes. Métodos: Focamos em como 1) reduzir o risco de infecção por COVID-19, como distanciamento social, telemedicina e exames laboratoriais e de imagem em intervalos mais amplos; 2) manejo de surtos, incluindo evitar tratamento de surto leve e uso de corticoide oral; 3) gerenciar terapias modificadoras de doença, como a preferência por medicamentos associados a menor risco de infecção (interferons, glatirâmer, teriflunomida e natalizumabe) e infusão em intervalo estendido de natalizumabe, quando seguro; 4) individualizar a escolha da terapia de indução para EM (anticorpos monoclonais anti-CD20, alentuzumabe e cladribina); 5) manejar terapias preventivas de NMOSD, incluindo seleção inicial de terapia e manutenção do tratamento atual; 6) manejar pacientes com EM/NMOSD que foram infectados por COVID-19. Conclusão: No futuro, séries de casos de pacientes com MS/NMOSD infectados com COVID-19 nos ajudará a definir as melhores estratégias de manejo. Por enquanto, contamos com a experiência e orientação especializadas.