Traditional first-line treatment failure rates in neuromyelitis optica spectrum disorder patients included in the Argentinean registry (RelevarEM).

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.

Clinical effectiveness of dimethyl fumarate in multiple sclerosis patients from Argentina.

BACKGROUND: We assessed the effectiveness, safety and patient-reported outcomes (PROs) of dimethyl fumarate (DMF) in real-world clinical practice in patients with multiple sclerosis (PwMS) from Argentina. METHODS: We conducted a multicenter ambispective cohort study in Argentina between September 2020 and March 2023. Changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, magnetic resonance imaging (MRI), no evidence of disease activity (NEDA), PROs (depression, anxiety, fatigue, burden of treatment and quality of life), and safety data were collected at clinical visits performed every 6 months for at least 24 months. RESULTS: We included 161 PwMS (64% female). DMF treatment was associated with a significant reduction in ARR from baseline after 24 months of treatment (from 0.87 to 0.23, p < 0.001). Disability progression was observed in 27.9% vs. 9.3% pre- and post-DMF, and disability improvement was found in 13% of patients from baseline to month 24. MRI activity was significantly reduced compared with baseline. Fatigue, depression, and quality of life scores were significantly improved from baseline to 24 months. Flushing was the most frequent adverse event reported in 19.2%. No significant reduction was observed in the hospitalization rate pre- and post-DMF (19.8% vs. 5.6%, p = 0.32). During follow-up, 135 (83%) patients were relapse-free, 110 (68.3%) were MRI free activity (Gad + lesion) and 108 (67%) reached NEDA. CONCLUSIONS: DMF significantly reduced disease activity in PwMS from Argentina with a good safety profile in real-world settings. A significant impact on the quality of life during follow-up was found.

Diagnostic MRI Score to Differentiate Susac Syndrome from Primary Angiitis of the Central Nervous System and Multiple Sclerosis.

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.

Real-World Effectiveness and Safety of Cladribine in Multiple Sclerosis: Longitudinal Data From the Nationwide Registry in Argentina.

OBJECTIVE: The aim was to evaluate patient profiles, effectiveness and safety of cladribine (CLAD) in patients with relapsing-remitting multiple sclerosis in Argentina. METHODS: This was a substudy included in RelevarEM (MS and neuromyelitis optica registry in Argentina, NCT03375177). Patients with MS who received CLAD tablets and were followed up for at least 24 months were included. Clinical evaluations every 3 months collect information about: a) clinical relapses; b) progression of physical disability, evaluated through Expanded Disability Status Scale, and c) new lesions found in the magnetic resonance imaging. Lymphopenia was evaluated during the follow-up and defined as grade 1: absolute lymphocyte count (ALC) 800-999/µL; grade 2: ALC 500-799/µL; grade 3: ALC 200-499/µL and grade 4: ALC <200/µL. RESULTS: A total of 240 patients were included from 19 centers from Argentina. The mean annualized relapse rate during the 12-month pre-CLAD initiation was 1.19 ± 0.56 versus 0.22 ± 0.18 at month 12 and 0.19 ± 0.15 at month 24 ( P < 0.001). A total of 142 (59.2%) fulfilled the criteria of disease activity during the 12 months before treatment initiation, whereas 27 (11.3%) fulfilled it at month 12 and 38 (15.8%) at month 24, P < 0.001. Regarding no evidence of disease activity (NEDA), 202 (84.2%) patients achieved NEDA status at month 12 and 185 (77%) at month 24. The most frequent incidence density of lymphopenia for course 2 observed was also for grade 1, 6.1 (95% confidence interval [CI] = 5.5-7.1). The overall incidence density of lymphopenia grade 4 was 0.1 (95% CI = 0.06-0.19). CONCLUSION: This information will help when choosing the best treatment option for Argentinean patients.

Treatment strategies and responses for attacks of neuromyelitis optica spectrum disorder: A real-world retrospective cohort study.

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.

Selection of disease modifying therapies in multiple sclerosis based on patient's age and disease activity: Data from a nationwide registry.

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.

Incidence of SARS-CoV-2 infection in patients with multiple sclerosis who received SARS-CoV-2 vaccines and are under treatment with high-efficacy therapies in Argentina.

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.

Mortality of neuromyelitis optica spectrum disorder patients in an Argentinean population: A study from the RelevarEM registry.

We aimed to evaluate mortality and causes of death among Argentinean neuromyelitis optica spectrum disorder (NMOSD) patients and identify predictors of death. Retrospective study included 158 NMOSD patients and 11 (7%) patients died after 11 years of follow-up for a total exposure time of 53,345 days with an overall incidence density of 2.06 × 10.000 patients/day (95% CI 1.75-2.68). Extensive cervical myelitis with respiratory failure (45%) was the most frequent cause of death. Older age (HR = 2.05, p = 0.002) and higher disability score (HR = 2.30, p < 0.001) at disease onset were independent predictors of death. We found an 11-year mortality rate of 7% in Argentinean NMOSD patients.

Evaluation of the use of high-efficacy treatments (HETs) in patients with relapsing-remitting multiple sclerosis in Argentina.

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.

Serological response to SARS-COV-2 vaccines in patients with multiple sclerosis in Argentina / Respuesta serológica a vacunas contra SARS-CoV-2 en pacientes con esclerosis múltiple en Argentina

Abstract Introduction : The objective was to assess the im munogenicity 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 im munogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evalua ted 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 mul tiple 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. Immu nological 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 anti bodies 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 diag nosed with COVID-19. Conclusion: We found that MS patients that recei ved Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Resumen Introducción : El objetivo fue evaluar la inmunogeni cidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT 03375177). Métodos : Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detec ción de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la defi nición del Ministerio de Salud. Resultados : Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remiten te-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pa cientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas he terólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p ≤ 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión : Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Frequency of new asymptomatic MRI lesions during attacks and follow-up of patients with NMOSD in a real-world setting.

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.

Serological response to SARS-CoV-2 vaccines in patients with multiple sclerosis in Argentina.

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.

Introducción: El objetivo fue evaluar la inmunogenicidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT03375177). Métodos: Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detección de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la definición del Ministerio de Salud. Resultados: Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remitente-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pacientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas heterólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p = 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión: Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Frequency of NMOSD misdiagnosis in a cohort from Latin America: Impact and evaluation of different contributors.

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.

Argentinean consensus recommendations for the use of telemedicine in clinical practice in adult people with multiple sclerosis.

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.

Disability outcomes in NMOSD and MOGAD patients: data from a nationwide registry in Argentina.

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.

Incidence of COVID-19 after vaccination in people with multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

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.

Rebound activity after fingolimod cessation: A case - control study.

BACKGROUND: There has been an increase in the number of reports of multiple sclerosis (MS) rebound activity (RA), which is usually defined as a severe disease reactivation after natalizumab or fingolimod withdrawal that exceeds pre-treatment baseline inflammatory activity. The frequency and risk factors that could predict RA remain unknown. Fingolimod is currently the most frequently prescribed disease modifying therapy for MS in Argentina, so that there is a need to determine possible predictors of RA. OBJECTIVES: To identify risk factors for developing RA after fingolimod cessation; to describe RA characteristics, management and evolution. METHODS: The study was a multicenter, retrospective, case-control study of patients with MS who had discontinued fingolimod and were followed up to nine months after discontinuation. Demographic, clinical and paraclinical data was extracted, including age, gender, MS phenotype, reason for discontinuation, number of relapses during the year prior to suspension, time treated with fingolimod, EDSS before, during and after rebound, MRI findings. RESULTS: 26 cases of RA were matched 1:1 with patients without RA. The median time elapsed to RA was 50 days. 68% showed worsening of the EDSS in the evaluation at 3 months of RA. When compared with the control group, no difference was found in terms of age, gender, phenotype, EDSS at the moment of suspension, reason for discontinuation, number of relapses in the previous year, and time on therapy. CONCLUSION: In this case-controlled study, no risk factors could be identified to predict RA after fingolimod cessation. Further controlled, prospective, better powered studies are needed to confirm these findings.

Clinical and demographic characteristics of male MS patients included in the national registry-RelevarEM. Does sex or phenotype make the difference in the association with poor prognosis?

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.