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Background: Immunosuppressive therapies as azathioprine (AZA), mycophenolate mofetil (MMF) and rituximab (RTX) are widely prescribed as first-line treatment to prevent relapses in NMOSD. However, the rate of response to these traditional therapies is unknown in Argentina. We aimed to describe and compare treatment failure rates in NMOSD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177)., Methods: A retrospective cohort study was conducted in NMOSD patients included in RelevarEM (a nationwide, longitudinal, observational, non-mandatory registry of MS and NMOSD in Argentina). NMOSD patients were defined based on validate diagnostic criteria. Only NMOSD patients who received AZA or MMF for at least 6 months or RTX for at least 1 month were included. Patients who were receiving AZA, MMF, or RTX and then switched to another 1 of these 3 therapies were included if the above-mentioned criteria for each drug were fulfilled. Data on patient demographics, clinical, neuroradiological findings, and treatments administered were collected. Treatment failure was defined as any new attack/relapse that occurred despite immunosuppressive treatment., Results: We included 139 NMOSD patients who were receiving AZA (n = 105), MMF (n = 5) or RTX (n = 29) with a mean follow-up time of 41.3 ± 11.4 months and median of EDSS at treatment initiation of 3. We observed a reduction in the annualized relapse rate from pre-treatment to post-treatment of 51.1 %, 48.4 %, and 79.1 % respectively with a Hazard Risk relative to RTX (95 % CI) of 1.67 (1.34-3.54, p = 0.01) for AZA and 2.01 (1.86-4.43, p = 0.008) for MMF. AZA, MMF and RTX failure was observed in 45/105 (42.8 %), 2/5 (40 %) and 3/29 (10.3 %) patients, respectively., Conclusions: Treatment failure rates were higher for AZA and MMF than RTX in Argentinean NMOSD patients in a real-world setting. High-efficacy treatment increases the opportunity to prevent attacks of NMOSD., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cladribine was approved for Multiple Sclerosis (MS) in our country in 2018. A previous study by our group showed that its use among high efficacy therapies options has been increasing along the years., Objective: to analyze the cladribine use trend across time since its approval., Method: A retrospective cohort study was performed. People with MS (pwMS) treated with cladribine were included. Two periods were defined: P1 = 2018 - 2020 and P2 = 2021 - 2023. A comparative analysis was carry out between P1 and P2 to assess the trend of use, clinical/demographic characteristics, and effectiveness., Results: One hundred ninety- seven people with MS (pwMS) were included, mean EDSS: 2.2 ± 3.08, 72.6% female, mean age: 35.2 ± 9 years, mean disease duration: 6.6 ± 5.6 years, mean time lapse under cladribine: 26.1 ± 12.4 months. Regarding patient profile, we found significant differences between P1 and P2 in the MS evolution (p = 0.001) and EDSS ( p = 0.018) prior to initiation of cladribine. In the individualized analysis by year, we found a decrease in relapse number in the year prior to starting cladribine (p = 0.02). A higher proportion of No Evidence of Disease Activity (NEDA) was found in patients treated at P2 compared to those treated at P1 (p < 0.001)., Conclusion: An earlier use of cladribine achieved a significant increase in reaching NEDA. This learning curve in the use of cladribine allows a better identification of the candidate patient and influences the treatment effectiveness., Competing Interests: Declarations Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the institutions involved. Competing interests None of the authors present conflicts of interest in relation to this research., (© 2024. Fondazione Società Italiana di Neurologia.)

We aimed to assess the treatment strategies utilized in patients with neuromyelitis optica spectrum disorder (NMOSD) experiencing relapses, including their frequency, types, and response after 6 months based on the Expanded Disability Status Scale (EDSS) score., Methods: We conducted a retrospective study involving NMOSD patients from the Argentinean MS and NMOSD registry (RelevarEM, NCT03375177). Treatment response at 6 months was categorized as "good" if the EDSS score decreased by ≥1 point after a nadir EDSS score ≤ 3, or by ≥2 points after a nadir EDSS score > 3, "poor" if the EDSS score decrease was slighter, and as "absent" if the EDSS score remained unchanged or worsened., Results: We included 120 NMOSD patients (seropositive N = 75), who experienced 250 NMOSD-related relapses and received 248 treatments. At 6 months, complete recovery was achieved in 70/98 (71.4%) and 15/19 (79%) patients, respectively. Predictors of a "good" response in our regression model were a younger age at disease onset (OR:3.54, CI95% 2.45-5.01, p < 0.0001) and a short delay from onset of relapse to treatment initiation (OR:1.56, CI95% 1.22-2.13, p = 0.004)., Conclusions: Approximately two-thirds of patients experienced complete recovery, and younger age and a short delay to start treatment were independent predictors of a "good" response., Competing Interests: Declaration of Competing Interest The authors declared no potential conflict of interest with respect to this research, authorship, and/or publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting., Methods: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET)., Results: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01)., Conclusion: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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: We aimed to assess the frequency of new asymptomatic lesions on brain and spinal imaging (magnetic resonance imaging (MRI)) and their association with subsequent relapses in a large cohort of neuromyelitis optica spectrum disorder (NMOSD) patients in Argentina., Methods: We retrospectively reviewed 675 MRI (225 performed during an attack and 450 during the relapse-free period (performed at least 3 months from the last attack)) of NMOSD patients who had at least 2 years of clinical and MRI follow-up since disease onset. Kaplan-Meier (KM) curves were used for depicting time from remission MRI to subsequent relapse., Results: We included 135 NMOSD patients (64.4% were aquaporin-4-immunoglobulin G (AQP4-IgG)-positive). We found that 26 (19.26%) and 66 (48.88%) of patients experienced at least one new asymptomatic MRI lesion during both the relapse-free period and attacks, respectively. The most frequent asymptomatic MRI lesions were optic nerves followed by short-segment myelitis during the relapse-free period and attacks. KM curves did not show differences in the time taken to develop a new relapse., Conclusion: Our findings showed that new asymptomatic lesions are relatively frequent. However, the presence of new asymptomatic MRI lesions during the relapse-free period and at relapses was not associated with a shorter time to developing subsequent relapses.

The objective was to evaluate time to reach an EDSS of 4, 6, and 7 in NMOSD and MOGAD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03,375,177)., Methods: NMOSD patients diagnosed according to 2015 criteria and with MOGAD were identified. Patients with at least 3 years of follow-up and periodic clinical evaluations with EDSS outcomes were included. AQP4-antibody and MOG-antibody status was recorded, and patients were stratified as seropositive and seronegative for AQP4-antibody. EDSS of 4, 6, and 7 were defined as dependent variables. Log rank test was used to identify differences between groups., Results: Registry data was provided for a total of 137 patients. Of these, seventy-five presented AQP4-ab-positive NMOSD, 45 AQP4-ab-negative NMOSD, and 11 MOGAD. AQP4-ab status was determined by cell-based assay (CBA) in 72% of NMOSD patients. MOG-ab status was tested by CBA in all cases. Mean time to EDSS of 4 was 53.6 ± 24.5 vs. 63.1 ± 32.2 vs. 44.7 ± 32 months in seropositive, seronegative NMOSD, and MOGAD, respectively (p = 0.76). Mean time to EDSS of 6 was 79.2 ± 44.3 vs. 75.7 ± 48.6 vs. 54.7 ± 50 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.23), while mean time to EDSS of 7 was 86.8 ± 54 vs. 80.4 ± 51 vs. 58.5 ± 47 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.39)., Conclusion: No differences were observed between NMOSD (seropositive and seronegative) and MOGAD in survival curves., (© 2022. Fondazione Società Italiana di Neurologia.)

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.)

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: 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.)

We aimed to examine treatment interventions implemented in patients experiencing neuromyelitis optica spectrum disorders (NMOSD) attacks (frequency, types, and response)., Methods: Retrospective study. Data on patient demographic, clinical and radiological findings, and administered treatments were collected. Remission status (complete [CR], partial [PR], no remission [NR]), based on changes in the EDSS score was evaluated before treatment, during attack, and at 6 months. CR was analyzed with a generalized estimating equations (GEEs) model., Results: A total of 131 patients (120 NMOSD and 11 myelin oligodendrocyte glycoprotein-antibody-associated diseases [MOGAD]), experiencing 262 NMOSD-related attacks and receiving 270 treatments were included. High-dose steroids (81.4%) was the most frequent treatment followed by plasmapheresis (15.5%). CR from attacks was observed in 47% (105/223) of all treated patients. During the first attack, we observed CR:71.2%, PR:16.3% and NR:12.5% after the first course of treatment. For second, third, fourth, and fifth attacks, CR was observed in 31.1%, 10.7%, 27.3%, and 33.3%, respectively. Remission rates were higher for optic neuritis vs. myelitis (p < 0.001). Predictor of CR in multivariate GEE analysis was age in both NMOSD (OR = 2.27, p = 0.002) and MOGAD (OR = 1.53, p = 0.03)., Conclusions: This study suggests individualization of treatment according to age and attack manifestation. The outcome of attacks was generally poor., (© The Author(s) 2021.)

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 purpose of this study was to assess family planning (FP) among women with multiple sclerosis (WwMS)., Methods: We invited 604 WwMS to answer a survey focused on FP: a) Temporal relationship between pregnancy and the diagnosis of multiple sclerosis; b) History of FP; c) Childbearing desire; d) Information on family planning. Comparisons between pregnancy and not pregnancy after MS, as well as, planned and unplanned pregnancy were analyzed. Multivariate and univariate analyses were used to assess the impact of independent variables and FP., Result: 428 (71.7%) WwMS completed the survey. A 19.1% got pregnant after MS diagnosis and we evaluated FP in the last pregnancy, 56.1% patients had a planned pregnancy. Professional addressing FP (OR = 0.27, 95%-CI 0.08-0.92, p = 0.03) and non-injection drug treatment before pregnancy (OR = 2.88, 95%-CI 1.01-8.21, p = 0.047) were independent predictors of unplanned pregnancy in our multivariate model. Among WwMS ≤ 40 years, 48.7% had future childbearing desire. Young age (p < 0.001), PDDS <3 (p = 0.018), disease duration <5 years (p = 0.02), not childbearing before MS diagnosis (p < 0.001) and neurologist addressing family planning (p = 0.01) were significantly associated with childbearing desire., Conclusions: This research highlights that pregnancy remains an important concern among WwMS., (© The Author(s) 2021.)

Background: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America., Objective: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19., Methods: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission., Results: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU., Conclusion: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD., Competing Interests: Disclosure of conflicts of interest Edgardo Cristiano 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. Juan Ignacio Rojas 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, Novartis Argentina. Liliana Patrucco has received honoraria for scientific and research grants from Teva Tuteur, Merck Serono, Biogen Idec, and Bayer Schering. Ricardo Alonso and Berenice Silva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Novartis, Sanofi -Genzyme and Roche. Orlando Garcea has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Novartis, Sanofi -Genzyme and Roche. Liesbet M. Peeters has no personal pecuniary interests to disclose, other than being the chair of The MS Data Alliance (MSDA), which receives income from a range of corporate sponsors, recently including: Biogen, BristolMyersSquibb (formerly Celgene), Canopy Growth Corporation, Genzyme, Icometrix, Merck, Mylan, Novartis, QMENTA, Quanterix, Roche. The rest of authors declares no conflict of interest with the study project., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.)

Introduction: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina., Aim: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care., Development: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients., Conclusion: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.

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: 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.

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: 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.)

The objective of this study was to describe and compare the baseline epidemiological data of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients included in RelevarEM (Clinical Trials registry number NCT03375177)., Methods: RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort., Results: A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7 years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6 years. In NMOSD, the mean age was 40 ± 7 years, female sex 78.7%, mean disease duration 5 ± 3.5 years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p < 0.001 between groups). In NMOSD, the CCI was 0 in 64% while ≥ 1 was in 36%. The MS/NMOSD ratio found was 21/1., Conclusions: This is the first analysis of the longitudinal Argentinean registry of MS and NMOSD describing and comparing conditions that contributes to provide reliable real-world data in the country.

Introduction: During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients., Methods: A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process., Conclusions: The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina., Competing Interests: Declaration of competing interest RA, AAP, EAB, MEB, MB, EC, MCC, ND, MIG, OG, DG, MJH, JPH, MJ, EK, RL, JM, PGN, RP, MLS, VS, DS, AT, SAV, AV, CV has nothing to disclose. EC has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme, Merck, Novartis. AGB has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme, Novartis, Teva, Gador, Raffo, Biosidus, Synthon – Bagó and Roche. SB has received reimbursement for research grants and travel stipends from Merck, Biogen and Genzyme. FC received fees for consultancy and Advisory Board membership and fees for travel, academic conferences and research projects from Novartis, Merck-Serono, Teva, Genzyme and Biogen Idec. ECC has received reimbursement for developing educational presentations, educational and research grants, consultation fees and travel stipends from Biogen, Genzyme. NFL has received consulting fees from Biogen, Novartis and Genzyme as a lecturer from Merck Serono, Novartis and Biogen, and collaboration for attendance to national and international congresses from Biogen, Novartis, Merck Serono, Bayer and Gador. GGL has received reimbursement for developing educational presentations, consultations fees, clinical trials fees and travel stipends from Biogen, Genzyme, Merck, Novartis, Teva, Tuteur. ADM has received reimbursement for research grants, and travel stipends from Bagó, Raffo and Biosidus. LP has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. JIR has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis. RRE has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Schering Argentina, Bayer Schering Pharma, Bayer, Serono Argentina and Merck. VS has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Biosidus, Gador and Raffo. MCY has received reimbursement for developing educational presentations and travel/accommodations stipends from Merck-Serono Argentina, Biogen-Idec Argentina, Genzyme Argentina, Bayer Inc., Novartis Argentina and TEVA-Tuteur Argentina. JC has received reimbursement for developing educational presentations, educational and research grants, consultations fees and travel stipends from Biogen, Genzyme, Merck, Novartis, and Roche., (Copyright © 2019. Published by Elsevier B.V.)

Background: Multiple sclerosis (MS) has a low prevalence in Argentina. However, MS has a high burden of disease, which implies frequent neurological visits, magnetic resonance images (MRI) use and chronic MS medication during follow-up, with a high impact on the healthcare system. Therefore, MS care is essential to optimize disease management and improve patients' outcome. We aimed to evaluate the access and barriers to MS care and identified differences in treatment and management of MS patients over a period of 12 months in an Argentinean cohort., Methods: A cross-sectional study based on a self-administered survey was carried out from August to December 2017 in 13 provinces from Argentina. MS patients (n = 219) were divided into three groups as follows: prepaid health insurance (PHI), social health insurance (SHI) and state-run health insurance (SRHI, Public Health Ministry) and they were assessed in order to detect differences in employment, access and barriers to MS care (neurological visit, MRI use and MS medication)., Results: A total of 185 (84.5%) MS patients were employed (full-time: 59%), 34 (15.5%) were currently unemployed and 15 (6.8%) retired by MS. In addition, 132 had SHI, 45 PHI and 40 SRHI. No statistical differences were found in disease severity, frequency of neurological visit, waiting time for neurological visit as well as frequency and waiting time for MRI use. MS patients with SRHI experienced a longer waiting time (first prescription and during follow-up) and inappropriate delivery of MS medication during follow-up compared to MS patients with PHI and SHI. A total of 8/45 (17.7%) in PHI, 17/40 (42.5%) in SRHI and 25/132 (18.9%) in SHI did not receive the MS medication as properly as prescribed for their neurologists. PHI was independently associated with appropriate delivery of MS medication (OR = 0.81, p = 0.01)., Conclusion: This study showed that MS patients had access barriers to receive MS medication properly, especially those with SRHI (public sector)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite that different registries already exist in various countries in Europe and North America, no ongoing nationwide registry exists in Latin America (LATAM), a region where the disease behaves differently than in other regions. The objective of this document is to describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. METHODS: In this article, we described the creation, implementation and data management of the nationwide MS registry in Argentina. The registry contains information on the structure, ethical aspects, implementation and variables of the registry (Clinical Trials registry number NCT NCT03375177). CONCLUSION: RelevarEM is the first MS nationwide registry in Argentina, as well as in LATAM, with the objective of providing reliable real-world data of MS in the country., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Restless legs syndrome (RLS) frequency, and its association with depression, anxiety, sleep disorders, and fatigue, has not been previously studied in Latin American patients with multiple sclerosis (MS). We aimed to assess RLS frequency in patients with MS living in Argentina and to examine potential associations with depression, anxiety, and sleep disorders., Methods: A cross-sectional study (n = 427) was conducted using a self-administered questionnaire, including International RLS Study Group criteria, to compare RLS frequency in patients with MS versus controls. The Hospital Anxiety and Depression Scale and the Fatigue Severity Scale were administered to all participants. Insomnia, excessive daytime somnolence, and other risk factors in patients with MS with RLS were analyzed using logistic regression., Results: We included 189 patients with definite MS and 238 controls. The RLS frequency was 29.1% in patients with MS versus 13.0% in controls (odds ratio [OR] = 2.74, P = .00005). Moreover, clinically significant RLS (csRLS; ie, symptoms present ≥2 days per week) frequency was 19.4% in patients with MS versus 4.2% in controls (OR = 5.37, P < .00001). Longer MS duration and presence of anxiety, depression, insomnia, and smoking cigarettes were all significantly associated with RLS. Multivariate analysis showed that anxiety and fatigue were significantly associated with MS with RLS and MS with csRLS., Conclusions: Both RLS and csRLS showed strong association with MS, supporting the need to screen for anxiety/depression, sleep quality, and fatigue in this patient population. We believe that identifying the presence and severity of these conditions would contribute to better MS management and treatment., Competing Interests: The authors declare no conflicts of interest.

One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina., Methods: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used., Results: Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients., Conclusions: The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina., (Copyright © 2018 Elsevier B.V. All rights reserved.)