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Objective: Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool., Methods: This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic-net model determined key variables., Results: The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes-like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium-enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%., Interpretation: When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024;96:846-854., (© 2024 American Neurological Association.)

Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2., Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2 nd dose (Sputnik V or AZD1222) and 3 nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed., Results: Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r 2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population., Discussion: Findings regarding humoral and cellular response are consistent with previous reports., Competing Interests: The authors declare that this study received funding from Novartis and donations from Merck Argentina and Synthon Bagó. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Author Berenice Anabel Silva, as principal investigator, received a 2-year research grant from the Research Council of the Ministry of Health of the Government of the City of Buenos Aires, Argentina., (Copyright © 2024 Silva, Miglietta, Casabona, Wenker, Eizaguirre, Alonso, Casas, Lázaro, Man, Portuondo, Lopez Bisso, Zavala, Casales, Imhoff, Steinberg, López, Carnero Contentti, Deri, Sinay, Hryb, Chiganer, Leguizamon, Tkachuk, Bauer, Ferrandina, Giachello, Henestroza, Garcea, Pascuale, Heitrich, Podhajcer, Vinzón, D’Alotto-Moreno, Benatar, Rabinovich, Pitossi and Ferrari.)

Introduction: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region., Material and Methods: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables., Results: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region., Conclusion: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

Clinical trials of disease-modifying therapies (DMTs) for people with multiple sclerosis (pMS) are conducted in selected populations, excluding patients with comorbidities or concomitant medications. However, a large percentage of pMS have some additional disease, which could affect the response and choice of the DMT. The objective of this review is to assess how concurrent pathologies can impact the choice of DMTs. Relevant articles were selected through a systematic search in PubMed. Comorbidities were grouped for better classification into autoimmune, chronic infections, cardiovascular and metabolic, oncological and neuropsychiatric. In autoimmune pathologies, it is key to take into account the effects of TME on them and the possibility of interaction with their specific treatments. Immunomodulatory therapies are safe for people with chronic infections. Immunosuppressive treatments are generally contraindicated in people with active infections. In cardiovascular and metabolic comorbidities, infusion reactions associated with monoclonal antibodies, and the phenomena of starting treatment with S1P modulators, must be taken into account. DMTs with an immunosuppressive effect are contraindicated in people with active malignancies. Although psychiatric pathology per se does not preclude the use of DMTs, caution should be exercised when new psychiatric symptoms appear. For these reasons, among the multiple factors that must be considered when starting or changing a DMT in pMS, comorbidities constitute a decisive element.

Background and Objectives: Primary-progressive multiple sclerosis (PPMS) is characterized by gradual neurological deterioration without relapses. This study aimed to investigate the clinical impact of gender and age at disease onset on disease progression and disability accumulation in patients with this disease phenotype., Methods: Secondary data from the RelevarEM registry, a longitudinal database in Argentina, were analyzed. The cohort comprised patients with PPMS who met inclusion criteria. Statistical analysis with multilevel Bayesian robust regression modeling was conducted to assess the associations between gender, age at onset, and Expanded Disability Status Scale (EDSS) score trajectories., Results: We identified 125 patients with a confirmed diagnosis of PPMS encompassing a total of 464 observations. We found no significant differences in EDSS scores after 10 years of disease progression between genders (-0.08; credible interval (CI): -0.60, 0.42). A 20-year difference in age at onset did not show significant differences in EDSS score after 10 years of disease progression (0.281; CI: -0.251, 0.814). Finally, we also did not find any clinically relevant difference between gender EDSS score with a difference of 20 years in age at onset (-0.021; CI: -0.371, 0.319)., Conclusion: Biological plausibility of gender and age effects does not correlate with clinical impact measured by EDSS score., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We aimed to evaluate the incidence of SARS-CoV-2 breakthrough infection of SARS-CoV-2 vaccines in people with MS (PwMS) on high-efficacy disease-modifying therapies (HET) included in the national MS registry in Argentina (RelevarEM)., Methods: Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI)., Results: Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period., Conclusions: We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) can be classified according to the efficacy in which they prevent inflammatory activity. To date, there are limited data regarding the use of high-efficacy treatments (HETs) in Latin America (LATAM). We aimed to analyze the use of HETs in Argentina, focusing on the clinical and sociodemographic characteristics of the patients who use these treatments and the changes in the trend of use over the years., Methods: A retrospective cohort study was done using the Argentina MS patient registry, RelevarEM. Patients diagnosed with relapsing-remitting MS (RRMS) according to validated diagnostic criteria and under treatment with natalizumab, alemtuzumab, cladribine, rituximab or ocrelizumab were included., Results: Out of 2450 RRMS patients under a DMT, 462 (19%) were on HETs. One third of those patients (35%) received HETs as the first treatment. The most frequent reason for switching to HETs was treatment failure to previous DMT (77%). The time from MS diagnosis to the first HET in treatment-naive patients was less than one year (IQR: 0-1 year) and in treatment-experienced patients it was 5 years (IQR: 3-9 years). Between 2015 and 2017 (P1), 729 patients included in RelevarEM started a new treatment, of which 85 (11.65%) were HETs. Between 2018 and 2020 (P2), 961 patients included in RelevarEM started a new treatment, of which 284 (29.55%) were HETs. When comparing P2 with P1, a significant increase in the use of HETs was observed (p < 0.01). The most frequently used HETs were alemtuzumab (50.59%) in P1, and cladribine (45.20%) in P2., Conclusion: The demographic and clinical characteristics of patients under HET in Argentina were identified. Based on a real-world setting, we found a significant trend towards and a rapid increase in the use of HETs in clinical practice in patients with RRMS., Competing Interests: Declaration of Competing Interest Irrestrictive research grants from Biogen Argentina, Genzyme Argentina, Merck Argentina, Novartis Argentina, and Roche Argentina allowed the development and implementation of the RELEVAREM Registry. Those grants did not interfere in the development plan, variables, PI selection, patient information nor other aspects of the Registry. Authors declare no conflict of interest with the research done., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: The emergence of several therapeutic options in multiple sclerosis (MS), which significantly modify the immune system functioning, has led to the need for the consideration of additional factors, such as risk of infections, in the decision-making process. The aim of these consensus recommendations was to discuss and perform a practical guide to Latin American neurologists on the risk of infections at diagnosis, follow-up and prior to initiation of DMDs., Methods: A panel of Latin American neurologists, experts in demyelinating diseases and dedicated to management and care of MS patients, gathered during 2021 and 2022 to make consensus recommendations on the risk of infections in PwMS treated with DMDs in Latin America. The RAND/UCLA methodology was developed to synthesize the scientific evidence and expert opinions on health care topics and was used for reaching a formal agreement., Results: Recommendations were established based on relevant published evidence and expert opinion, focusing on: 1- baseline infection disease and vaccination status; 2- opportunistic infections; 3- progressive multifocal leukoencephalopathy; 4- genitourinary system infections; 5- respiratory tract infections; 6- digestive system infections, 7-others local infections and 8- COVID-19., Conclusion: The recommendations of this consensus seek to optimize the care, management and treatment of PwMS in Latin America. The standardized evidence-based care of pwMS infections will allow better outcomes., Competing Interests: Declaration of Competing Interest BAS has received personal compensation for consulting, congresses, serving on a scientific advisory board, speaking, or other research activities with Biogen-Idec, Genzyme, Merck-Serono, Novartis, Teva, Roche, Bristol Myers Squibb, LACTRIMS, International Society For Neurochemistry, International Brain and Research Organization. ECC has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen-Idec, Genzyme, Merck-Serono, Novartis, Teva, Roche, LACTRIMS and the Guthy-Jackson Charitable Foundation. RA has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen-Idec, Genzyme, Merck-Serono, Novartis, Bristol Myers Squibb, Janssen, Roche and LACTRIMS. PAL has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen-Idec, Genzyme, Merck-Serono, Novartis, Bristol Myers Squibb, Raffo, Roche, Teva, and LACTRIMS. MFF has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen-Idec, Merck-Serono, Novartis, Teva. MFF is CEO and co-founder of Entelai LLC. OG has received personal compensation for consulting, congresses, serving on a scientific advisory board, speaking, or other research activities with Biogen-Idec, Merck-Serono, Novartis, Roche, Bristol Myers Squibb, LACTRIMS, Synthon Bago, Raffo. Rest of the authors had nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Differentiating multiple sclerosis (MS) from other relapsing inflammatory autoimmune diseases of the central nervous system such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is crucial in clinical practice. The differential diagnosis may be challenging but making the correct ultimate diagnosis is critical, since prognosis and treatments differ, and inappropriate therapy may promote disability. In the last two decades, significant advances have been made in MS, NMOSD, and MOGAD including new diagnostic criteria with better characterization of typical clinical symptoms and suggestive imaging (magnetic resonance imaging [MRI]) lesions. MRI is invaluable in making the ultimate diagnosis. An increasing amount of new evidence with respect to the specificity of observed lesions as well as the associated dynamic changes in the acute and follow-up phase in each condition has been reported in distinct studies recently published. Additionally, differences in brain (including the optic nerve) and spinal cord lesion patterns between MS, aquaporin4-antibody-positive NMOSD, and MOGAD have been described. We therefore present a narrative review on the most relevant findings in brain, spinal cord, and optic nerve lesions on conventional MRI for distinguishing adult patients with MS from NMOSD and MOGAD in clinical practice. In this context, cortical and central vein sign lesions, brain and spinal cord lesions characteristic of MS, NMOSD, and MOGAD, optic nerve involvement, role of MRI at follow-up, and new proposed diagnostic criteria to differentiate MS from NMOSD and MOGAD were discussed., (© 2023 American Society of Neuroimaging.)

Background: Information on performance of multiple sclerosis (MS) diagnostic criteria is scarce for populations from Latin America, Asia, or the Caribbean., Objective: To assess performance of revised 2017 McDonald criteria as well as evaluate genetic ancestry in a group of MS patients from Argentina experiencing a debut demyelinating event., Methods: Demographic and clinical characteristics, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) findings and new T2 lesions were recorded at baseline and during relapses. Diagnostic accuracy in predicting conversion to clinically defined MS (CDMS) based on initial imaging applying revised 2017 criteria was evaluated and genetic ancestry-informative markers analyzed., Results: Of 201 patients experiencing their first demyelinating event (median follow-up 60 months), CDMS was confirmed in 67. We found 2017 diagnostic criteria were more sensitive (84% vs 67%) and less specific (14% vs 33%) than 2010 criteria, especially in a group of patients revised separately, presenting positive oligoclonal bands (88% vs 8%). Genetic testing performed in 128 cases showed 72% of patients were of European ancestry and 27% presented genetic admixture., Conclusion: 2017 McDonald criteria showed higher sensitivity and lower specificity compared with 2010 criteria, shortening both time-to-diagnosis and time-to-treatment implementation.

Background: Neuromyelitis optica spectrum disorder (NMOSD) misdiagnosis (i.e. the incorrect diagnosis of patients who truly have NMOSD) remains an issue in clinical practice. We determined the frequency and factors associated with NMOSD misdiagnosis in patients evaluated in a cohort from Latin America., Methods: We retrospectively reviewed the medical records of patients with NMOSD, according to the 2015 diagnostic criteria, from referral clinics in six Latin American countries (Argentina, Chile, Paraguay, Colombia, Ecuador, and Venezuela). Diagnoses prior to NMOSD and ultimate diagnoses, demographic, clinical and paraclinical data, and treatment schemes were evaluated., Results: A total of 469 patients presented with an established diagnosis of NMOSD (73.2% seropositive) and after evaluation, we determined that 56 (12%) patients had been initially misdiagnosed with a disease other than NMOSD. The most frequent alternative diagnoses were multiple sclerosis (MS; 66.1%), clinically isolated syndrome (17.9%), and cerebrovascular disease (3.6%). NMOSD misdiagnosis was determined by MS/NMOSD specialists in 33.9% of cases. An atypical MS syndrome was found in 86% of misdiagnosed patients, 50% had NMOSD red flags in brain and/or spinal magnetic resonance imaging (MRI), and 71.5% were prescribed disease-modifying drugs., Conclusions: NMOSD misdiagnosis is relatively frequent in Latin America (12%). Misapplication and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis.

Background: The use of telemedicine has quickly increased during of the COVID-19 pandemic. Given that unmet needs and barriers to multiple sclerosis (MS) care have been reported, telemedicine has become an interesting option to the care of these patients. The objective of these consensus recommendations was to elaborate a guideline for the management of people with MS using telemedicine in order to contribute to an effective and high-quality healthcare., Methods: A panel of Argentinean neurologist's experts in neuroimmunological diseases and dedicated to the diagnosis, management,and care of MS patients gathered virtually during 2021 and 2022 to conduct a consensus recommendation on the use of telemedicine in clinical practice in adult people with MS. To reach consensus, the methodology of "formal consensus RAND/UCLA Appropriateness method" was used., Results: Recommendations were established based on relevant published evidence and expert opinion focusing on definitions, general characteristics and ethical standards, diagnosis of MS, follow-up (evaluation of disability and relapses of MS), identification and treatment of relapses, and finally disease-modifying treatments using telemedicine., Conclusion: The recommendations of this consensus would provide a useful guide for the proper use of telemedicine for the assessment, follow-up, management, and treatment of people with MS. We suggest the use of these guidelines to all the Argentine neurologists committed to the care of people with MS., (© 2022. Fondazione Società Italiana di Neurologia.)

Shared decision making is a way of incorporating patients' preferences and values into the decisions regarding the treatment and follow-up plan for the condition that affects them. It is currently applied mainly in the context of chronic disorders for which there is no cure available but nevertheless many therapeutic alternatives, such as multiple sclerosis (MS). Current views and opinions on shared decision making for the treatment of MS are discussed in this consensus based on a modified Delphi method that included a group of neurologists from Argentina. A set of statements was defined by the experts and seeks to serve as a guide to apply this concept in clinical practice., Competing Interests: Declaration of Competing Interest Medical writing support was provided by Biogen. S. Batagelj is an employee of Biogen. All other authors have no conflict of interests to report. The authors were not paid for their work developing the manuscript. Views and opinions expressed in this manuscript are solely those of the authors., (Copyright © 2022. Published by Elsevier B.V.)

Background: Multiple sclerosis (MS) is a neurological disease in which the myelin lining the central nervous system is damaged. The complex and unpredictable nature of MS disease makes the diagnosis process more difficult for the patient. The aim of this study was to review the lived experiences of patients with multiple sclerosis when receiving the diagnosis., Methods: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. A systematic search was performed using four databases including PubMed, Scopus, Web of Science, and psych info on April 2022., Results: We found 537 articles. After Applying relevant exclusion criteria removing duplicate and irrelevant articles, 13 studies were included in our systematic review after the abstract and full-text screening. Our findings collected data from 10 sub-themes in the following 3 themes to capture patients' experiences after receiving the diagnosis. These included: Emotional reactions to receiving the diagnosis; Communication with health professionals and knowledge about MS and Fear of being different., Conclusion: It is important to understand patients' experiences with the disease and identifying problems to help and support families, patients, and health care personnel's. Therefore, it is necessary to design or implement therapeutic interventions for patients at the time of receiving the diagnosis to reduce psychological problems., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The objective was to assess the immunogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry., Methods: A prospective cohort study between May and December 2021. The primary outcome was immunogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evaluated based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health., Results: 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting multiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immunological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed antibodies against spike antigen among those that were on ocrelizumab compared to other groups (p = 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diagnosed with COVID-19., Conclusion: We found that MS patients that received Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

The objective of the study was to evaluate the incidence of COVID-19 after complete vaccination in people with multiple sclerosis (PwMS) included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177)., Methods: cohort study conducted between May 2021 and December 2021. The primary outcome was the appearance of infection during the follow-up time (at least three months after complete vaccination (second dose)). Data was collected through the contact between the treating physician and the patient. Specific information was requested (date, symptoms, need for hospitalization, ventilatory assistance, treatment, and evolution). The contact was made every 30 days during the period of 3 months after the full dose vaccination. A positive COVID-19 case was defined according to the definition established by the Ministry of Health in Argentina. Cumulative incidence was reported by Kaplan Meier survival curves as well as incidence density., Results: A total of 576 PwMS were included, mean age 45.2 ± 13 years, 432 (75%) RRMS, 403 (70%) were female. The mean and median time of follow-up after the second dose was 91 ± 17 and 94 ± 21 days respectively. Most frequent first and second dose received was Astra-Zeneca vaccine, followed by Sputnik V vaccine. During follow-up a total of twenty COVID-19 cases were observed for a total exposure time of 39,557 days. The overall cumulative incidence for the observed period was 3.4% (SE 0.4%) with an overall incidence density of 5 × 10.000 patients/day (95%CI 0.7-12). We observed more cases in woman than men with an incidence density of 6 × 10.000 patients/day (95%CI 0.9-9) vs. 3 × 10.000 patients/day (95%CI 0.2-6) respectively, but not significantly different (IRR 1.7 95% CI 0.56-7.37 p = 0.15)., Conclusion: we found an incidence density of breakthrough COVID-19 infection of 5 × 10.000 patients/day (95%CI 0.7-12) after vaccination in Argentina., Competing Interests: Declaration of Competing Interest Authors declare no potential conflicts of interest regarding this research, authorship and/or publication of this article. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome, (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: the aim of this systematic review was to summarize the coping strategies utilized by people with multiple sclerosis (pwMS) and the association of these strategies with mood symptoms, quality of life, fatigue and disability in pwMS., Methods: search in the literature was performed across electronic databases of PubMed, Web of Science, and Scopus. No time constraint was applied for searching across the databases. Manual search was also performed on the list of references of the retrieved papers. Two authors independently evaluated the retrieved citations based on predetermined inclusion criteria in two screening stages. This systematic review followed Joanna Briggs Institute (JBI) guidelines for cross-sectional research. The findings related to the coping patterns against MS as well as the relationship between the patterns and MS symptoms were extracted and synthesized., Findings: A total of 2390 records were identified. After removing duplicates and based on screening, 39 papers met the eligibility criteria for qualitative synthesis, and they were evaluated in terms of quality of study. When comparing genders, women used more religious coping, social support seeking, and positive coping compared to men. Depression and anxiety were associated with maladaptive and emotion-oriented coping strategies. The patients who used positive and problem solving oriented coping strategies had a better score of quality of life. Disability and fatigue were associated with applying avoidance and maladaptive coping strategies., Conclusion: the findings of this review suggest that understanding the relationship between coping strategies and quality of life as well as the symptoms related to the disease is important to understand development of psychological interventions adopted by specialists to support these patients., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest relating to this study., (Copyright © 2022. Published by Elsevier B.V.)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system leading to demyelination and neurodegeneration. Basic and translational studies have shown that B cells and myeloid cells are critical players for the development and course of the disease. Bruton's tyrosine kinase (BTK) is essential for B cell receptor-mediated B cell activation and for normal B cell development and maturation. In addition to its role in B cells, BTK is also involved in several functions of myeloid cells. Although significant number of disease-modifying treatments (DMTs) have been approved for clinical use in MS patients, novel targeted therapies should be studied in refractory patients and patients with progressive forms of the disease. On the basis of its role in B cells and myeloid cells, BTK inhibitors can provide attractive therapeutic benefits for MS. In this article, we review the main effects of BTK inhibitors on different cell types involved in the pathogenesis of MS and summarise recent advances in the development of BTK inhibitors as novel therapeutic approaches in different MS clinical trials. Available data regarding the efficacy and safety of these drugs are described., Competing Interests: Edgar Carnero Contentti has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen, Bayer, Genzyme, Merck, Novartis, Roche, Raffo, and Teva. ECC has also received grants from LACTRIMS and Guthy Jackson Charitable Foundation. Jorge Correale is a board member of Merck Serono Argentina, Novartis Argentina, Genzyme LATAM, Genzyme global, Biogen-Idec LATAM and Merck-Serono LATAM. He is part of the Steering Committee for the clinical trials of Ofatumumab (Novartis Global). JC has received reimbursement for developing educational presentations for MerckSerono Argentina, Merck-Serono LATAM, Biogen-Idec Argentina, Genzyme Argentina, Novartis Argentina, Novartis LATAM, Novartis Global and Roche Argentina, as well as professional travel/accommodation stipends. The authors report no other conflicts of interest in this work., (© 2022 Carnero Contentti and Correale.)

Objectives: The objective of this study was to determine by a conjoint analysis the preferences for a range of disease-modifying treatment attributes in patients with multiple sclerosis (MS) and treating neurologists., Methods: This was a cross-sectional study throughout Argentina between August 2020 and February 2021. Participating patients were adults with relapsing-remitting MS, who had received a long-term specific disease-modifying treatment for at least the past 3 months and their treating neurologist. Patients and neurologist were sampled from the Argentinean MS patient registry (RelevarEM). We applied the methodology of conjoint analysis. Patient preferences for hypothetical treatment were collected from the overall sample and from stratified subgroups according to the expanded disability status scale (EDSS) score. An ordinary least squares regression model was used to estimate parameters., Results: A total of 275 patients from 25 centers (31 principal investigators) were included, mean age was 43.2 ± 10.9 years, 59.6% were female, and mean EDSS was 3.1 ± 2. For the entire sample, we observed that patients had higher preferences for treatments with lower side effect risks (28.7 relative preference [RP]), lower frequency of administration (21.4 RP), and higher impact on relapses (19.6 RP). Patients with a higher EDSS give significantly greater importance to a less frequent administration regime and the oral route than patients with a lower EDSS (23.5 RP vs 20.1 [P =.02] and 17.1 vs 15.3 [P =.03], respectively). For neurologists, the most important attribute was to prevent disease progression (RP 29.3)., Conclusion: Our study contributes to the understanding of treatment selection preferences from the perspectives of both patient and neurologists., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: The "1/3″ brain magnetic resonance imaging (MRI) criteria including 1) a lesion adjacent to the lateral ventricle and in the inferior temporal lobe, or 2) a juxtacortical lesion, or 3) a Dawson finger-type lesion were shown to distinguish multiple sclerosis (MS) from antibody-mediated conditions. In this large multicentre study, we aimed to assess how the criteria perform 1) in different onset phenotypes, 2) distinct ethnic groups, 3) when the absence of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD)-typical fluffy infratentorial (FIT) lesions and longitudinally extensive transverse myelitis (LETM) lesions are added as features ("2/4″ and 3/5″ criteria, respectively)., Methods: 577 patients with MS (n = 332), aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD) (n = 196) and MOGAD (n = 49) were recruited from 6 international centres (Buenos Aires, Sao Paolo, Maracaibo, Goyang, Oxford and Milan). Imaging scans were obtained at disease onset or relapse., Results: Adding the absence of FIT lesions increased the specificity of the "1/3″ criteria vs. AQP4-Ab NMOSD from 84.7% to 87.2% and vs. MOGAD from 85.7% to 93.9% without compromising their sensitivity (86%). In particular, for those presenting with brain/brainstem attacks "2/4″ had significantly higher specificity than "1/3″ (85% vs. 80% against AQP4-Ab NMOSD, 88.9% vs. 72.2% against MOGAD). Positive predictive values of the "1/3″ criteria for MS were lowest for Asian patients (84.8 vs. 99.1% for White) but were significantly increased by adding further criteria (94.1% for "3/5″)., Conclusion: The "1/3″ criteria perform well in discriminating MS from NMOSD and MOGAD regardless of ethnic background and clinical scenario. Adding the absence of FIT lesions increases the specificity in those presenting with brain/brainstem symptoms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Escalation (ES) and early high-efficacy (EHE) therapies have been the main treatment strategies adopted in multiple sclerosis (MS) in recent years. The aim of this study was to compare the effectiveness and safety of EHE versus ES strategies in MS patients from Argentina., Methods: This is a retrospective multicenter cohort study in Argentina. Eligible patients were categorized into 2 groups as follows: EHE if received natalizumab, ocrelizumab, rituximab, alemtuzumab, mitoxantrone, or cladribine; and ES if received interferon β, glatiramer acetate, teriflunomide, dimethyl fumarate, or fingolimod as initial therapy. The primary outcome was confirmed disability progression (Expanded Disability Status Scale [EDSS] increase). Additional outcomes included the proportion of patients and time to: EDSS 6; new relapses; new T2-magnetic resonance imaging (MRI) lesions; no evidence of disease activity; and specific adverse events. Propensity score-based nearest-neighbor matching (without replacement) was applied to homogenize the sample, and Cox regression model stratified by matched pairs was used for the analysis., Results: After propensity score matching, 193 and 112 patients were retained in the ES and EHE groups, respectively. The EHE significantly decreased the risk of EDSS progression (hazard ratio [HR], 0.62; 95% confidence interval [95% CI], 0.40-0.98; P = 0.04), relapses (HR, 0.66; 95% CI, 0.49-0.89; P = 0.006), and new MRI activity during follow-up (HR, 0.55; 95% CI, 0.40-0.75; P < 0.001). No significant differences were observed in specific adverse events between groups., Conclusions: Our study shows that EHE therapies prevent disease progression, relapses, and new MRI lesions and demonstrated no increased risk of specific adverse events when compared with ES therapy. These data should be considered when selecting a specific treatment for MS patients., Competing Interests: Conflicts of Interest and Source of Funding: E.C. has received fees for consultations as a scientific advisory board member and for travel to meetings, conferences, and clinical trials of the following companies: Avanir, Bayer, Biogen, Merck, Novartis, Roche, and Teva. J.I.R. has received honoraria from Novartis as a scientific advisor. He has received travel grants and attended courses and conferences on behalf of Merck Serono Argentina and Novartis Argentina. L.P. has received honoraria for scientific and research grants from Teva Tuteur, Merck Serono, Biogen Idec, and Bayer Schering. N.D. has received honoraria from Bayer, Genzyme, and Merck as a scientific advisor. She has received honoraria from Bayer, Merck, and Genzyme for scientific lectures and has participated as a principal investigator in studies from Bayer, Teva-Tuteur, Novartis, Genzyme, Biogen, Sanofi, Teva, Roche, and Merck. E.C.C., P.A.L. J.P.P., and A.C. have received personal compensation for consulting, serving on a scientific advisory board, speaking, and other activities with Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, Roche, and Bayer. R.A. and O.G. have received personal compensation for consulting, serving on a scientific advisory board, speaking, and other activities from Biogen, Merck Serono, Novartis, Sanofi-Genzyme, and Roche., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We aimed to analyze the accumulative risk of MRI and OB factors for evolution from RIS to MS in subjects included in the Argentinean MS registry (NCT03375177)., Methods: RIS subjects were identified according to RIS diagnosis criteria. Subjects were longitudinally followed with clinical and MRI at intervals of 6 months. Time from RIS identification to the first clinical event was estimated using Kaplan-Meier. Multivariable Cox regression models were created to assess the independent predictive value of demographic characteristics, as well as clinical, OB and MRI data on time to the first clinical event. The single and increased risk factor of evolution of RIS was quantified., Results: A total of 88 RIS subjects, mean follow-up time 42 ± 4 months were included. 39 (44.3%) and 23 (26.1%) had a new MRI lesion or a clinical event, respectively, during the follow-up. OB (HR 5.9, 95% CI 1.29-10.1, p = 0.004), infratentorial lesions (HR 3.7, 95% CI 1.09-7.5) and spinal cord lesions (HR 5.3, 95% CI 1.4-8.2, p = 0.01) at RIS identification were independent predictors associated with a subsequent clinical event. The accumulative risk showed that when two of the three factors (OB, infratentorial or spinal cord lesions) were present the HR was 10.4, 95% CI 4.4-22, p < 0.001, and when three factors were present, it was HR 15.6, 95% CI 5.7-28, p < 0.001 for a relapse., Conclusion: The presence of three factors significantly increased the risk of clinical event; high-risk subjects should probably be managed by a different approach than those used for individuals without high-risk factors., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We aimed to describe the health-related quality of life (HRQoL) in patients with neuromyelitis optica spectrum disorders (NMOSD), to compare HRQoL between NMOSD patients, multiple sclerosis (MS), and healthy controls (HC) and to study the associations between HRQoL and the clinical variables of the disease., Methods: A cross-sectional study was carried out. Patients with NMOSD seropositive, MS, and HC were enrolled and age-matched. The HRQoL was studied using the Argentinean validation of the SF-36 health questionnaire. Demographic and clinical characteristics were analyzed, as well as the EDSS and the total scores and subscales of the SF-36., Results: 243 individuals were included (NMOSD= 53, MS =100, and HC =90). The mean EDSS was 3.06 ± 2.01 in NMOSD and 2.67 ± 1.83 in MS with a mean of disease duration of 6.2 ± 4.4 and 6.3 ± 5.3 years, respectively. Significant statistical differences were observed in the total SF-36 score between both NMOSD and MS vs. HC (p < 0.01), but no differences were found when the total SF-36 score was compared between NMOSD vs. MS. Overall, NMOSD patients scored significantly lower in the total SF-36 and subscale scores compared to HC (p< 0.05). NMOSD patients also showed significant differences in bodily pain (58.8 ± 29.8 vs 75.1 ± 25.1, p < 0.01) and general health (44.4 ± 20.9 vs.31.9 ± 23.1, p < 0.01) when compared with MS, but no differences were found after comparing the rest of the subscales. We found that higher EDSS scores (β -1.28 p = 0.03) and disease duration (β 0.8, p = 0.02) were significantly associated to lower (worse) general health (dependent variable) score in NMOSD patients after having applied multiple linear regression analysis. Additionally, we observed that higher EDSS scores (β -10.2 p = 0.008) and the presence of relapses in the previous year (β -28.9, p = 0.02) were significantly associated to lower (worse) physical functioning (dependent variable) score., Conclusion: Pain seems to be a significant undertreated symptom in NMOSD patients that strongly impact on HRQoL. Patient-reported HRQoL scales scores provide comprehensive additional prognostic information beyond physical disability score., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: We aimed to assess platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte ratios (NLR) for differentiating multiple sclerosis (MS) from aquaporin-4-antibody-positive neuromyelitis optica spectrum disorders (NMOSD) at disease onset., Methods: We retrospectively enrolled and reviewed the medical records of patients with MS (N = 50) and NMOSD (N = 33) followed in specialized MS/NMOSD centers from Argentina. Demographical and clinical (manifestation and disability) data and neuroradiological features (new/enlarging or contrast-enhancing lesions) were assessed at baseline, 1 and 2 years. Serum samples were obtained during the first relapse without a previous acute or chronic treatment, at 1 and 2 years. Mixed-effects model was used to identify independent associations between the log-transformed NLR or PLR and MS/NMOSD outcomes., Results: PLR is increased in NMOSD when compared to MS (229.4 ± 86.74 vs. 186.6 ± 70.17, P = 0.01), but no significant differences were found for NLR (3.51 ± 1.29 vs. 3.30 ± 1.17, P = 0.43). PLR was the only independent predictor of poor physical disability score (EDSS ≥ 4) in NMOSD patients at 2 years (β=0.28, p = 0.02) after applying multivariate mixed-effects regression analysis. Additionally, multivariate logistic regression analysis showed that the PLR was the only independent predictor of EDSS ≥ 4 at 2 years (OR 28.8, p = 0.041) in the NMOSD group. The area under the receiver-operating characteristic curve was 0.841., Conclusion: PLR could be potentially useful as additional diagnostic tool in differentiating these two neuroinflammatory conditions at presentation. PLR can predict severity of neurological disability at 2 years in NMOSD patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders., Methods: A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients. Patients with complete relapse data (date, month and year) at onset and during follow-up were included. Attack counts were analyzed by month using a Poisson regression model with the median monthly attack count used as reference., Results: A total of 551 patients (431 MS and 120 NMOSD), experiencing 236 NMOSD-related attacks and 558 MS-related attacks were enrolled. The mean age at disease onset in NMOSD was 39.5 ± 5.8 vs. 31.2 ± 9.6 years in MS (p < 0.01). Mean follow-up time was 6.1 ± 3.0 vs. 7.4 ± 2.4 years (p < 0.01), respectively. Most of the included patients were female in both groups (79% vs. 60%, p < 0.01). We found a peak of number of attacks in June (NMOSD: 28 attacks (11.8%) vs MS: 33 attacks (5.9%), incidence rate ratio 1.82, 95%CI 1.15-2.12, p = 0.03), but no differences were found across the months in both disorders when evaluated separately. Strikingly, we observed a significant difference in the incidence rate ratio of attacks during the winter season when comparing NMOSD vs. MS (NMOSD: 75 attacks (31.7%) vs MS: 96 attacks (17.2%), incidence rate ratio 1.82, 95%CI 1.21-2.01, p = 0.02) after applying Poisson regression model. Similar results were observed when comparing the seropositive NMOSD (n = 75) subgroup vs. MS., Conclusions: Lack of seasonal variation in MS and NMOSD attacks was observed when evaluated separately. Future epidemiological studies about the effect of different environmental factors on MS and NMOSD attacks should be evaluated prospectively in Latin America population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In multiple sclerosis demographics there is a well-known female prevalence and male patients have been less specifically evaluated in clinical studies, though some clinical differences have been reported between sexes., Objective: The objective of this study was to assess clinical and demographic differences between male and female patients included in the national Argentine MS Registry-RelevarEM., Material and Methods: This study was observational, retrospective, and was based on the data of 3099 MS patients included as of 04 April 2021. The statistical analysis plan included bivariate analyses with the crude data and also after adjustment for the MS phenotype, further categorized as progressive-onset MS or relapsing-onset MS. In the adjusted analysis, the Mantel-Haenszel odds ratio was compared to the crude odds ratio, to account for the phenotype as a confounder., Results: The data from 1,074 (34.7%) men and 2,025 (65.3%) women with MS diagnosis were analysed. Males presented primary progressive disease two times more often than women (11% and 5%, respectively). In the crude analyses by sex, the presence of exclusively infratentorial lesions in the magnetic resonance imaging studies was more frequent in males than in females, but after adjustment by MS onset phenotype, such difference was only present in males with relapsing-onset MS (p = 0.00006). Similarly, worse Expanded Disability Status Scale scores were confirmed only in men with relapsing-onset disease after phenotype adjustment (p = 0.02)., Conclusion: We did not find any statistically significant clinical or demographic difference between sexes when the progressive MS phenotype was specifically considered. However, the differences we found between the clinical phenotypes are in line with the literature and highlight the importance of stratifying the analyses by sex and phenotype when designing MS studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background PPMS (primary progressive multiple sclerosis) patients represent less than 10% of MS patients in Argentina, men and women were similarly affected and most of them had a severe functional impairment. More rapid progression has been reported in males, but this is not the case in all datasets. The main objective of our study was to determine the time to EDSS (Expanded disability Status Scale) 4, 6 and 7 in PPMS patients. We also compared the times to reach these EDSS in men and women and aimed to identify factors associated with the disability progression. Method This cohort of patients with diagnosis of PPMS (n = 253) was selected from follow-up recorded in the RelevarEM registry database. Result The median times to EDSS 4, 6 and 7 were 24 (IQR 12-48), 72 (IQR 36-96) and 96 (IQR 60-120) months, respectively. Comparison of the survival curves to EDSS 4, 6 and 7 according to gender did not show significant differences (p = 0.33, p = 0.55 and p = 0.59). There is no evidence of an association between the clinical adjustment variables (sex, age >40 years at diagnosis, EDSS > 3 at onset and multifocal MS symptoms at disease onset) and the time of arrival at the EDSS 4, 6 and 7. Conclusion Severe disability was observed six years after the onset of symptoms. No association was found between the studied factors and the time to arrival to severe disability., (Copyright © 2022. Published by Elsevier B.V.)

Background: The objective of our study was to describe the availability of diagnostic tests and treatment for MS and NMOSD in Latin America (LATAM)., Methods: A survey instrument was used in a sample of physicians from LATAM countries. The goal of the survey was to understand availability of: 1) imaging tests for diagnosing MS and NMOSD and its barriers; 2) diagnostic laboratory tests for diagnosing MS and NMOSD and its barriers; and 3) treatments for MS and NMOSD in the acute and chronic phases of the disease., Results: Responses were received from 80 physicians. AQP4-ab test was available in 54% of the countries and MOG-ab test in 42%. All of countries had available use of high doses of intravenous methylprednisolone, oral steroids, plasmapheresis, and intravenous immunoglobulins for relapses. For NMOSD, 93% of the countries were able to use azathioprine and mycophenolate mofetil, and 87% rituximab. In MS, 93% of countries had available to them IFN beta, 69% glatiramer acetate, 75% teriflunomide, 93% fingolimod, 69% dimethyl-fumarate, 75% cladribine, 69% natalizumab, 93% ocrelizumab and 81% alemtuzumab. The most common challenge and barrier identified was the cost of medications., Conclusion: The present study allows an understanding of the delivery of care for MS and NMOSD in the region.

Multiple sclerosis (MS) is currently thought to arise by interactions between genetic susceptibility and environmental factors. Infections in general trigger autoimmune responses causing clinical manifestations of disease. However, as a result of regulatory T (Treg)- and regulatory B (Breg)-cell induction, helminth infections tend to dampen disease activity. IL-35, the newest member of the IL-12 family, is an inhibitory cytokine composed of an EBI3β chain subunit, and an IL-12p35 subunit. The aim of this study was to investigate the role of IL-35 during parasite infections occurring in individuals with MS. Numbers of IL-35-producing Breg cells are higher in CSF from helminth-infected than from uninfected MS subjects, a finding associated with decreased MRI disease activity. Interestingly, stimulation of CD19 + B cells with IL-35 promotes conversion of these cells to Breg cells producing both IL-35 and IL-10. Coculture of B cells from helminth-infected MS patients inhibits proliferation of Th1 and Th17 myelin peptide-specific T cells, as well as production of IFN-γ and IL-17. Following activation, CD4 + CD25 + Treg cells significantly upregulate expression of EBI3 and IL-12p35 mRNA. Furthermore, CD4 + CD25 - T cells activated in the presence of IL-35 induce a population of cells with regulatory function, known as iTR35. Finally, B cells from normal individuals cultured in vitro in the presence of the helminth antigen SEA increase expression of the transcription BATF, IRF4 and IRF8, acquiring a pattern similar to that of IL-35 Breg cells. These data highlight the important immunoregulatory effects of IL-35 on both Breg and Treg cells, observed in helminth-infected MS subjects., (© 2021 John Wiley & Sons Ltd.)

The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season and the reasons related to non-vaccination. Cross-sectional study between November and December 2020 in a large cohort of MS patients from LATAM. Patients responded about recommendation of receiving influenza vaccine and the use of it as well as reasons for not using the vaccine. Four hundred twelve MS patients were included in the analysis. 47.3% of patients were recommended to receive the vaccine from the treating physician. Nearly 54% of patients did not receive the influenza vaccine, and the most frequent cause was that it was neither recommended nor mentioned by the treating physician (27.4%). Female gender (OR = 2.3, 95%CI 1.4-3.8, p = 0.001) was associated with an increased risk of recommendation, while a progressive form of MS and higher EDSS decreased the risk (OR = 0.49, 95%CI 0.27-0.90, p = 0.023; OR = 0.65, 95%CI 0.55-0.97, p = 0.02, respectively). Despite the evidence to recommend the influenza vaccine in MS patients, a limited number of patients in clinical practice received such recommendation., (© 2021. Journal of NeuroVirology, Inc.)

As human and economic resources are limited, especially in Latin America (LATAM), it is important to identify research priorities to improve multiple sclerosis (MS) patients care in the region. The objective was to generate a multidisciplinary consensus on research priorities in MS for patients care in LATAM by involving healthcare professionals and MS patient associations. METHODS: consensus was reached through a four-step modified Delphi method designed to identify and rate research priorities in MS in LATAM. The process consisted of two qualitative assessments, a general ranking phase and a consensus meeting followed by a more detailed ranking phase RESULTS: a total of 62 participants (35 neurologists, 4 nurses, 12 kinesiologists, 7 neuropsychologists and 4 patient association members) developed the process. At the final ranking stage following the consensus meeting, each participant provided their final rankings, and the top priority research questions were outlined. 11 research priorities were identified focusing on healthcare access, costs of the disease, physical and cognitive evaluation and rehabilitation, quality of life, symptoms management, prognostic factors, the need of MS care units and patient's management in emergencies like COVID-19. CONCLUSION: this work establishes MS research priorities in LATAM from multiple perspectives. To pursue the actions suggested could launch the drive to obtain information that will help us to better understand the disease in our region and, especially, to better care for affected patients., (Copyright © 2021. Published by Elsevier B.V.)

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT03375177)., Methods: The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset., Results: A total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively)., Conclusion: 3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The use of cannabis to treat some symptoms of neurological diseases, including multiple sclerosis (MS), has increased worldwide. We aimed to assess the use of cannabis in patients with MS (PwMS) from Argentina, its reasons and patients' perceptions on the management of MS symptoms. Additionally, we assessed their association with socio-demographic and clinical aspects., Methods: A cross-sectional online survey that included 281 PwMS from Argentina was conducted. Screening instruments: Demographics and clinical data, health-related QoL (MS Impact Scale-29), Fatigue Severity Scale, The Hospital Anxiety and Depression Scale, sleep disorders, physical disability (self-administrated Expanded Disability Status Scale) and medical or recreational cannabis use were evaluated. A logistic regression model was carried out., Results: Current users (cannabis was used within the past year) was reported in 34.2% and former users (had tried cannabis but not used it within the past year) in 22.7%. Daily cannabis use was reported in 31.3% (current + former users) of the studied cohort, 41.9% started their use after MS diagnosis and 54.3% of them had never discussed about cannabis use with their neurologist. Recreational use was reported in 47.5%. Younger (age below 30 years) PwMS (OR = 2.39, p = 0.03), presence of chronic pain (OR = 2.42, p = 0.002) and current alcohol intake (OR = 3.33, p = 0.001) were predictors of current cannabis use in our multivariate model., Conclusion: A high prevalence of use of cannabis in PwMS from Argentina was observed. Demographic, symptoms and lifestyle factors predict cannabis use. Identifying the presence and severity of these conditions would contribute to a better MS management and treatment., Competing Interests: Declaration of Competing Interest None of the authors have any potential financial conflict of interest relating to this manuscript., (Copyright © 2021. Published by Elsevier B.V.)

Background: Technological advances and greater availability of magnetic resonance imaging have prompted an increment on incidental and unexpected findings within the central nervous system. The concept of radiologically isolated syndrome characterizes a group of subjects with images suggestive of demyelinating disease in the absence of a clinical episode compatible with multiple sclerosis. Since the description of this entity, many questions have arisen; some have received responses but others remain unanswered. A panel of experts met with the objective of performing a critical review of the currently available evidence. Definition, prevalence, biological bases, published evidence, and implications on patient management were reviewed. Thirty to 50% of subjects with radiologically isolated syndrome will progress to multiple sclerosis in 5 years. Male sex, age < 37 years old, and spinal lesions increase the risk. These subjects should be evaluated by a multiple sclerosis specialist, carefully excluding alternative diagnosis. An initial evaluation should include a brain and complete spine magnetic resonance, visual evoked potentials, and identification of oligoclonal bands in cerebrospinal fluid. Disease-modifying therapies could be considered when oligoclonal bands or radiological progression is present., Conclusion: At present time, radiologically isolated syndrome cannot be considered a part of the multiple sclerosis spectrum. However, a proportion of patients may evolve to multiple sclerosis, meaning it represents much more than just a radiological finding.

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been described in aquaporin-4-antibodies(AQP4-ab)-negative neuromyelitis optica spectrum disorder (NMOSD) patients. We aimed to evaluate the percentage of AQP4-ab-negative NMOSD patients who are positive for MOG-ab in a cohort of Argentinean patients included in RelevarEM (Clinical Trials registry number NCT03375177)., Methods: RelevarEM is a longitudinal, strictly observational multiple sclerosis (MS) and NMOSD registry in Argentina. Of 3031 consecutive patients (until March 2020), 165 patients with phenotype of suspected NMOSD, whose relevant data for the purpose of this study were available, were included. Data on demographic, clinical, paraclinical and treatment in AQP4-ab (positive, negative and unknown) and MOG-ab (positive and negative) patients were evaluated., Results: A total of 165 patients (79 AQP4-Ab positive, 67 AQP4-Ab negative and 19 unknown) were included. Of these, 155 patients fulfilled the 2015 NMOSD diagnostic criteria. Of 67 AQP4-Ab-negative patients, 36 (53.7%) were tested for MOG-Ab and 10 of them (27.7%) tested positive. Serum AQP4-ab levels were tested by means of cell-based assay (CBA) in 48 (35.2%), based on tissue-based indirect immunofluorescence assays in 58 (42.6%) and enzyme-linked immunosorbent assay in 4 (2.9%). All MOG-ab were tested by CBA. Optic neuritis (90%) was the most frequent symptom at presentation and optic nerve lesions the most frequent finding (80%) in neuroimaging of MOG-ab-associated disease. Of these, six (60%) patients were under immunosuppressant treatments at latest follow-up., Conclusion: We observed that 27.7% (10/36) of the AQP4-ab-negative patients tested for MOG-ab were positive for this antibody, in line with results from other world regions., (Copyright © 2021. Published by Elsevier B.V.)

Background: A period of diagnostic uncertainty often characterizes the clinical transition from relapsing to secondary progressive multiple sclerosis (SPMS)., Objective: The aim of this study was to describe the length of time required to reclassify relapsing-remitting MS (RRMS) patients who have clinically transitioned to SPMS (diagnosis uncertainty)., Methods: This is a retrospective multicenter cohort study conducted in Argentina, identifying in every center all patients with diagnosis of MS who transitioned from RRMS to SPMS during the follow-up. We identified the dates of the last definitive RRMS and first definitive SPMS diagnoses for diagnostic uncertainty. The time required to reclassify RRMS who transitioned to SPMS and the time from disease onset to reclassify SPMS were calculated using the Kaplan-Meier method., Results: A total of 170 patients were included, where the mean age at disease onset (first symptom) was 36 ± 6 years; the length of time required to reclassify RRMS patients who transitioned to SPMS was 3.3 ± 1.1 years (range = 1-7 years); and the time from disease onset to classify SPMS was 19.4 ± 8.5 years (range = 16-35 years)., Conclusion: A period of diagnostic uncertainty regarding the transition from RRMS to SPMS was present in many of our patients, with a mean time of 3.3 years.

Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles., Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America., Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging., Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days., Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.

The objective was to evaluate the interval from first symptom of multiple sclerosis (MS) to diagnosis with the introduction of MS diagnostic criteria in a Latin American (LATAM) population., Methods: Patients with relapsing-remitting MS (RRMS) completed a survey in 12 LATAM countries. Date of disease onset (first relapse) and date of diagnosis (confirmed disease) were required. Survival probabilities were evaluated for 5 diagnosis epoch groups: group 1: 1983-2000 Poser; group 2: 2001-2004 McDonald's first version; group 3: 2005-2009 revisions of 2005; group 4: 2010-2016 revisions of 2010; and group 5: 2017-2019 revisions of 2017., Results: 1188 (75.6% females) patients were included. Mean time from disease onset to diagnosis in group 1 was 21 ± 8 months; in group 2, 19 ± 7 months; in group 3, 16 ± 10 months; in group 4, 9.6 ± 8.5 months; and in group 5, 8.2 ± 10 months. Significant differences were observed between groups 1, 2, 3 vs. 4 and 5 (p<0.001), while no differences were observed between groups 4 and 5 (p=0.08)., Conclusion: We observed a significant shortening of time from MS onset to diagnosis with the adoption of new diagnostic criteria in LATAM., (Copyright © 2020. Published by Elsevier B.V.)

Background: Unemployment is common in people with multiple sclerosis (PwMS) and might be prevented if factors associated with work loss are identified., Objective: We aimed to assess the impact of multiple sclerosis (MS) on employment status in a cohort of PwMS from Argentina and to evaluate their association with anxiety, depression, fatigue and disability., Methods: A cross-sectional study was conducted to assess employment in PwMS using an anonymous, self-administered questionnaire, which also included the Hospital Anxiety and Depression Scale, Fatigue Severity Scale and Expanded Disability Status Scale. The data was compared between employed (full-time vs. part-time) vs. unemployed (looking for vs. not looking for work) PwMS. Univariate and multivariate models were designed to identify factors independently associated with unemployment., Results: Among the 167 PwMS, 120 (71.6%, full-time = 65%) were employed, and 47 (28.4%, looking for work = 27.6%) were currently unemployed. Age, gender, and duration of disease were similar in both groups. Univariate analysis showed that anxiety, depression, fatigue and disability were significantly associated with unemployed PwMS. However, only disability (OR = 1.36 (1.08-1.70), p = 0.007) was independently associated with unemployment after applying multivariate analysis (logistic regression)., Conclusion: Nearly one-third of PwMS from this sample in Argentina were unemployed. Neuropsychological factors and disability were associated with unemployment status.

Introduction: Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina., Methods: A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time., Result: The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p <0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p<0.01) were independently associated with choice of oDMTs., Conclusion: This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina., (Copyright © 2020. Published by Elsevier B.V.)

Background: Multiple sclerosis (MS), is an emergent disease in Latin America (LATAM), which raises substantial socioeconomic challenges to a region where most countries remain as economies in development., Objective: To assess barriers to access and utilization of MS care services in a regional cohort survey., Methods: We conducted a cross-sectional study based on a self-reported survey. Patients with MS (PwMS) completed this regional survey in 12 Latin American (LATAM) countries. PwMS were also divided into those with healthcare insurance (including certain local national social security programs) and those without healthcare insurance (treated at public institutions)., Results: We surveyed 1469 PwMS and identified significant regional differences in relation to access to complementary tests, rehabilitation services, and prescription of disease-modifying therapies (DMTs). Between 44.4% and 73.5% of PwMS were unemployed and nearly 50% had completed higher education. PwMS receiving care from the private sector reported greater access to imaging, DMTs, and fewer problems obtaining DMTs compared to those treated at public institutions. Multivariate analysis showed that lack of private insurance (OR = 2.21, p  < 0.001), longer MS duration (OR = 1.02, p  = 0.001), lower level of education (OR = 0.66, p  = 0.009), and unemployment (OR = 0.73, p  = 0.03) were independently associated with inappropriate delivery of DMTs., Conclusion: These findings suggest barriers to access and utilization of MS care services across LATAM are prevalent. We identified several factors predicting unmet healthcare needs in PwMS.

Background: Primary progressive multiple sclerosis (PPMS) is an infrequent clinical form of multiple sclerosis (MS). Scarce information is available about PPMS in Latin America. The aim of this work is to describe the clinical and demographic characteristics of PPMS patients in Argentina., Material and Methods: RelevarEM is a longitudinal, strictly observational registry in Argentina. Clinical and epidemiological data from PPMS patients were described., Results: There were 144 cases of PPMS. They represented 7% of MS patients. The mean age was 44.1 years. The female:male ratio was 1.08. The mean Expanded Disability Status Scale (EDSS) score was 5.5 and the mean disease evolution time was 10.6 years. Oligoclonal bands were found in 72.9%. At the time of diagnosis, magnetic resonance imaging showed spinal cord lesions in 82.6% and contrast-enhancing brain lesions in 18.1% of patients. Almost one third of patients were treated with a disease-modifying drug, and ocrelizumab was the most frequently used (55.8%)., Conclusions: PPMS is an infrequent subtype of MS and its recognition is of the highest importance as it has its own evolution, treatment, and prognosis. The importance of our research resides in providing local data and contributing to a better understanding of PPMS and its treatment in Latin America.

Background: The emergence of COVID-19 and its vertiginous spreading speed represents a unique challenge to neurologists managing multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The need for data on the impact of the virus on these patients grows rapidly. There is an urgent necessity of sharing information to enable evidence-based decision making on the clinical management. There are no data on what physicians are doing on clinical practice in Latin American countries., Aim: to investigate current management opinion of Latin American MS and/or NMOSD expert neurologists based on their experience and recommendations., Methods: we developed a voluntary web-based survey based on hypothetical situations that these patients may encounter, while taking into account the potential risk of developing severe COVID-19 infection., Results: 60% of the experts had the possibility of monitoring their patients by telemedicine. Most neurologists postpone magnetic resonance. Laboratory blood tests delay is associated with the type of treatment. Platform therapies, dimethyl-fumarate and natalizumab are considered safe options to initiate in naive patients., Conclusion: decision-making about MS and NMOSD patients has become even more complex in order to adapt to the COVID-19 pandemic. Risks and benefits should be taken into consideration throughout the patient follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is the most common chronic immune-mediated neurological disorder in young adults, more frequently found in women than in men. Therefore, pregnancy-related issues have become an object of concern for MS professionals and patients. The aim of this work was to review the existing data to develop the first Argentine consensus for family planning and pregnancy in MS patients., Methods: A panel of expert neurologists from Argentina engaged in the diagnosis and care of MS patients met both virtually and in person during 2019 to carry out a consensus recommendation for family planning and pregnancy in MS. To achieve consensus, the procedure of the "formal consensus-RAND/UCLA method" was used., Results: Recommendations were established based on published evidence and expert opinion focusing on pre-pregnancy counseling, pregnancy, and postpartum issues., Conclusion: The recommendations of these consensus guidelines are intended to optimize the management and treatment of MS patients during their reproductive age in Argentina., Competing Interests: Declaration of Competing Interest Nora Fernández Liguori has received consulting fees from Biogen Argentina, Novartis Argentina and Genzyme Argentina, as a lecturer from Merck Argentina, Novartis Argentina, Genzyme Argentina and Biogen Argentina, and collaboration for attendance to national and international congresses from Biogen Argentina, Novartis Argentina, Merck Argentina, Bayer Argentina, Gador and Roche Argentina. Ricardo Alonso has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities with Biogen Argentina, Genzyme Argentina, Merck Argentina, Novartis Argentina and Roche Argentina. María Eugenia Balbuena has received personal compensation for speaking from Roche, professional travel/accommodation stipends from Merck, Novartis and Teva and funding for research from Genzyme and Novartis. Andrés Barboza has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Sanofi, Merck, Roche, Novartis, Teva, Gador, Raffo, Biosidus and Synthon-Bagó. Santiago Bestoso has received personal compensation for speaking, professional travel/accommodation stipends or other activities from Merck, Biogen, Novartis, Gador and Genzyme. Marcos Burgos has received personal compensation for speaking from Merck, Novartis, Raffo, Sanofi Genzyme, Biogen, Roche and for research from Novartis and Biogen. Fernando Cáceres has received fees for being a member of advisory boards, for research, being a speaker and for traveling/accommodation for scientific medical meetings of the following companies: Novartis, Teva, Roche, Biogen, Sanofi Genzyme and Merck. Edgar Carnero Contentti has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities with Biogen Argentina, Genzyme Argentina, Merck Argentina, Novartis Argentina, Teva Argentina, Roche Argentina and Bayer Argentina. Adriana Carrá has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities with Bayer; Biogen; Biosidus; Genzyme; Merck; MS Synthon-Bago; Novartis; Roche; Teva, Tuteur. Edgardo Cristiano received consulting fees, funding for advisory boards and educational support from Biogen, Genzyme, Merck, Novartis and Roche. Norma Deri has received personal compensation for advisory boards for Bayer Argentina, Bayer Latinoamerica, Bayer Global, Merck Serono Argentina, Merck Serono Global, Genzyme Argentina, Genzyme Latinoamerica, Genzyme Global and Sanofi Global; for travel/ accommodation from Schering, Bayer, Serono, Merck Serono, Novartis, Biogen Idec, Teva-Tuteur, Teva and Roche; for research from Bayer Argentina, Biogen Idec Argentina,Genzyme Argentina, Novartis Argentina, Roche Argentina, Teva Argentina and Sanofi Argentina and for educational presentations from Bayer Argentina, Merck Serono Argentina and Genzyme Argentina. Marcela Fiol has received personal compensation for developing educational presentations, serving on a scientific advisory board from Merck-Serono Argentina, Sanofi Genzyme Argentina, TEVA-Tuteur Argentina and has received travel/accommodations stipends from Merck-Serono Argentina, Sanofi Genzyme Argentina, Biogen INC, Bayer Inc, Novartis, TEVA-Tuteur Argentina, ROCHE Argentina. María Inés Gaitán has received reimbursement for developing educational presentations, from Roche Argentina, Merck Argentina, Biogen Argentina, Sanofi-Genzyme Argentina, Bayer Inc Argentina and Novartis Argentina, and has received travel/accommodations stipends from Merck Argentina, Biogen Argentina, Roche Argentina, Novartis Argentina, and TEVA Argentina. Orlando Garcea has received personal compensation for consulting and speaking from Bayer, Merck, Biogen, Novartis and Genzyme. Mario Javier Halfon has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities from Biogen Argentina, Merck Argentina, Roche, Gador, Novartis, and Genzyme Argentina. Javier Hryb has received honoraria for the development of educational activities, and travel grants to congresses from Teva, Merck, Biogen, Roche, Tuteur, Synthon Bago and Novartis. Miguel Jacobo has received honoraria for the development of educational activities, research and travel grants to congresses from Biogen, Roche, Merck, Genzyme Novartis, Teva, Bayer, Raffo and Gador. Eduardo Knorre has received personal compensation for professional travel/accommodation stipends or other activities from Bagó, Tuteur and Roche. Pablo López has received personal compensation for consulting, serving on scientific advisory boards, speaking, professional travel/accommodation stipends or other activities with Biogen, Genzyme, Merck-Serono, Novartis, Teva, Roche and Bayer. Jimena Miguez has received personal compensation for professional travel/accommodation stipends or other activities from Merck, Novartis, Genzyme, Roche and for speaking from Merck, Novartis and Roche. Pedro Nofal has received honoraria for the development of educational activities, research and travel grants to congress from Novartis, Biogen, Merck Serono, Raffo, Genzyme, Gador and Bayer Schering. Raúl Piedrabuena has received personal compensation for the development of educational activities, serving on a scientific advisory board and research from Biogen, Merck, Novartis, Genzyme, Roche and Teva. Cecilia Pita has received honoraria for the development of educational activities, research and travel grants to congress from Biogen, Genzyme, Merck, Novartis and Roche. Juan Ignacio Rojas has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme, Merck, Novartis. Berenice Silva has received economic retribution for the development of educational, scientific activities and travel grants to congresses from Biogen, Novartis, Merck, Genzyme, TEVA, Bayer, Tuteur and Roche. Vladimiro Sinay has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities with Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Biosidus, Gador, Tuteur and Raffo/ Asofarma. Adriana Tarulla reports personal fees for speaking and support for travel to meetings from Bayer,Biogen Idec,Biosidus,Gador,Ivax-Teva,Merck Serono and Roche, out-side the submitted work. Darío Tavolini has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities Bayer, Biogen, Genzyme, Merck Serono, Novartis, Roche and Teva. Santiago Tizio has received professional travel accommodation stipends from Merck-Serono, Synthon Bago, Biogen-Idec, TEVA, Genzyme, Novartis and Roche; reimbursement for developing educational presentations from Biogen-Idec and Novartis and honoraria for advisory services from Merck-Serono, and Novartis. Verónica Tkachuk: has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities from Biogen, Roche, Merck, TEVA, Sanofi Genzyme, Novartis, Bayer y Raffo. Carlos Vrech has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities from Merck, Novartis, Biogen, Synthon Bago, Gador and Genzyme. Maria Célica Ysrraelit has received personal compensation for consulting, serving on a scientific advisory board, speaking, professional travel/accommodation stipends or other activities from Merck, Biogen, Novartis, Roche and Bayer Argentina. Liliana Patrucco has received speaker honoraria from Biogen, Genzyme, Merck-Serono, Novartis and Roche. Has received travel grants and attended courses and conferences on behalf of Merck-Serono, Genzyme and Roche. All the other authors have nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: There is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients., Methods: We retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included., Results: We included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p<0.001, CT = p<0.001, PBVL p = 0.01)., Conclusion: Different MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: We aimed to evaluate magnetic resonance imaging (MRI) previously used criteria (Matthews's criteria, MC) for differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD) in Caucasian and non-Caucasian populations (Argentina, Brazil and Venezuela) with positive (P-NMOSD), negative (N-NMOSD), and unknown (U-NMOSD) aquaporin-4 antibody serostatus at disease onset and to assess the added diagnostic value of spinal cord MRI in these populations., Methods: We reviewed medical records, and MRIs were assessed by two blinded evaluators and were scored using MC. Short-segment transverse myelitis (STM) was added as a new criterion. MC sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined., Results: We included 282 patients (MS = 188 and NMOSD = 94). MC applied to the entire cohort showed 97.8% sensitivity, 82.9% specificity, 92.0% PPV, and 95.1% NPV for differentiating MS from NMOSD. A subanalysis applied only to non-Caucasian (MS = 89 and NMOSD = 47) showed 100% sensitivity, 80.8% specificity, 90.8% PPV, and 100% NPV. Similar sensitivity, specificity, PPV, and NPV of MC for MS versus P-NMOSD ( n  = 55), N-NMOSD ( n  = 28), and U-NMOSD ( n  = 21) were observed., Conclusion: MC distinguished MS from NMOSD of all serostatus in a Latin American cohort that included non-Caucasian populations. Addition of STM to MC did not raise the accuracy significantly.