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.

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.

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.

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.

Clinical outcomes and prognostic factors in patients with optic neuritis related to NMOSD and MOGAD in distinct ethnic groups from Latin America.

BACKGROUND: Optic neuritis (ON) can be an initial manifestation of neuromyelitis optica spectrum disorder (NMOSD) associated with aquaporin 4-antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD). Additionally, both diseases may have overlapping paraclinical and radiological features. These diseases may have different outcomes and prognoses. We aimed to compare clinical outcomes and prognostic features of patients with NMOSD and MOGAD presenting ON as first attack, from different ethnic groups in Latin America. METHODS: We conducted a retrospective observational multicenter study in patients from Argentina (n = 61), Chile (n = 18), Ecuador (n = 27), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 49) with MOGAD or NMOSD related ON. Predictors of disability outcomes at last follow-up, namely visual disability (Visual Functional System Score ≥4), motor disability (permanent inability to walk further than 100 m unaided) and wheelchair dependence based on EDSS score were evaluated. RESULTS: After a mean disease duration of 42.7 (±40.2) months in NMOSD and 19.7 (±23.6) in MOGAD, 55% and 22% (p>0.001) experienced permanent severe visual disability (visual acuity from 20/100 to 20/200), 22% and 6% (p = 0.01) permanent motor disability and 11% and 0% (p = 0.04) had become wheelchair dependent, respectively. Older age at disease onset was a predictor of severe visual disability (OR=1,03 CI95%1.01-1.05, p = 0.03); older age at disease onset (OR=1,04 CI95%1.01-1.07, p = 0.01), higher number of relapses (OR=1,32 CI95%1.02-1.71, p = 0.03) and rituximab treatment (OR=0,36 CI95%0.14-0.90, p = 0.02) were predictors of permanent motor disability, whereas ON associated with myelitis at disease onset was a predictor of wheelchair dependency (OR=4,16, CI95%1.23-14.08, p = 0,02) in NMOSD patients. No differences were found when evaluating distinct ethnic groups (Mixed vs. Caucasian vs. Afro-descendant) CONCLUSIONS: NMOSD was associated with poorer clinical outcomes than MOGAD. Ethnicity was not associated with prognostic factors. Distinct predictors of permanent visual and motor disability and wheelchair dependency in NMOSD patients were found.

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.

Therapeutic strategies in NMOSD and MOGAD patients: A multicenter cohort study in Latin America.

PURPOSE: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. METHODS: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. RESULTS: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60). CONCLUSION: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

Neuromyelitis optica spectrum disorders with and without associated autoimmune diseases.

OBJECTIVES: We aimed to determinate the frequency of this association and compare the features of neuromyelitis optica spectrum disorder (NMOSD) with and without associated autoimmune diseases (AD) in a Latin American (LATAM) population in clinical practice. METHODS: We retrospectively reviewed the medical records of patients with NMOSD according to the 2015 diagnostic criteria. Patients from Argentina (n=77), Brazil (n=46), and Venezuela (n=17) were enrolled and classified into two groups as follows: with AD or without AD. Clinical, paraclinical (including aquaporin-4 antibodies (AQP4-ab) status), magnetic resonance imaging (MRI), and prognosis data were analyzed and compared. Kaplan-Meier (KM) and the Nelson-Aalen estimator analyses were performed to estimate both time and the cumulative hazard risk of disability reaching an EDSS≥4; and time for the first recurrence. RESULTS: Out of 140 patients, 33 (23.5%) patients had associated an AD at presentation. The most frequent associated AD was Hashimoto disease (n=10) followed by lupus (n=7) and Sjogren's syndrome (n=6). However, rituximab use (42.4% vs. 21.5%, p=0.02), female gender (82.2% vs. 100%, p=0.006), corticospinal lesions on MRI (0% vs. 12.5%, p=0.01) at onset, and positivity for antinuclear antibodies (21.2% vs. 48.4%, p=0.03) were significantly associated with NMOSD patients with AD in comparison to NMOSD patients without AD. No differences were found in other clinical and paraclinical aspects between groups. KM and Nelson-Aalen estimator analyses did not show differences between groups. CONCLUSION: NMOSD patients associated with AD were observed in 23.5%. In addition, NMOSD patients with and without associated AD were similar in most evaluated features.

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.

Brain volume loss and physical and cognitive impairment in naive multiple sclerosis patients treated with fingolimod: prospective cohort study in Buenos Aires, Argentina.

BACKGROUND: The percentage of brain volume loss (PBVL) has been classically considered as a biomarker in multiple sclerosis (MS). OBJECTIVE: The objective of the present study was to analyze if the PBVL during the 1st year after the onset of the disease predicts physical and cognitive impairment (CI). METHODS: Prospective study that included naïve patients without cognitive impairment who initiated MS treatment with fingolimod. Patients were followed for 3 years and relapses, expanded disability status scale (EDSS) progression (defined as worsening of 1 point on the EDSS), the annual PBVL (evaluated by structural image evaluation using normalization of atrophy [SIENA]), and the presence of CI were evaluated. Cognitive impairment was defined in patients who scored at least 2 standard deviations (SDs) below controls on at least 2 domains. The PBVL after 1 year of treatment with fingolimod was used as an independent variable, while CI and EDSS progression at the 3rd year of follow-up as dependent variables. RESULTS: A total of 71 patients were included, with a mean age of 35.4 ± 3 years old. At the 3rd year, 14% of the patients were classified as CI and 6.2% had EDSS progression. In the CI group, the PBVL during the 1st year was - 0.52 (±0.07) versus -0.42 (±0.04) in the no CI group (p < 0.01; odds ratio [OR] = 2.24; 95% confidence interval [CI]: 1.72-2.44). In the group that showed EDSS progression, the PBVL during the 1st year was - 0.59 (±0.05) versus - 0.42 (±0.03) (p < 0.01; OR = 2.33; 95%CI: 1.60-2.55). CONCLUSIONS: A higher PBVL during the 1st year in naïve MS patients was independently associated with a significant risk of CI and EDSS progression.

ANTECEDENTES: A porcentagem de perda de volume cerebral (PPVC) é um biomarcador na esclerose múltipla (EM). OBJETIVO: Analisar se a PPVC durante o 1° ano após o início da doença prediz deterioração física (DF) e cognitiva (DC) em pacientes com EM. MéTODOS: Estudo de coorte prospectivo que incluiu pacientes recém-diagnosticados sem comprometimento cognitivo que iniciaram tratamento com fingolimode. Os pacientes foram acompanhados por 3 anos, sendo avaliados a presença de recidivas, progressão da Escala Expandida do Estado de Incapacidade (EDSS, na sigla em inglês) (definida como agravamento de 1 ponto na EDSS), o PPVC anual (avaliado pela avaliação de imagem estrutural de atrofia normalizada [SIENA, na sigla em inglês) e a presença de DC (avaliada no início do estudo e nos 2° e 3° anos). O PPVC no 1° ano de tratamento com fingolimode foi utilizado como variável independente. RESULTADOS: foram incluídos 71 pacientes com idade média de 35,4 ± 3 anos. No 3° ano, 14% dos pacientes tiveram DC e 6,2% tiveram progressão de EDSS. No grupo DC, o PPVC durante o 1o ano foi - 0,52 (±0,07) versus - 0,42 (±0,04) no grupo sem DC (p < 0,01; razão de probabilidades [OR, na sigla em inglês] = 2,24; intervalo de confiança [IC] de 95%: 1,72­2,44). No grupo que apresentou progressão da EDSS, o PPVC durante o 1° ano foi de - 0,59 (±0,05) versus - 0,42 (±0,03) (p < 0,01; OR = 2,33; IC95%: 1,60­2,55). CONCLUSõES: Um maior PPVC durante o 1° ano foi associado a um risco significativo de progressão de DC e EDSS durante o seguimento.

Brain volume loss and physical and cognitive impairment in naïve multiple sclerosis patients treated with fingolimod: prospective cohort study in Buenos Aires, Argentina / Perda de volume cerebral e comprometimento físico e cognitivo em pacientes recém-diagnosticados com esclerose múltipla tratados com fingolimode: estudo de coorte prospectivo em Buenos Aires, Argentina

Abstract Background The percentage of brain volume loss (PBVL) has been classically considered as a biomarker in multiple sclerosis (MS). Objective The objective of the present study was to analyze if the PBVL during the 1st year after the onset of the disease predicts physical and cognitive impairment (CI). Methods Prospective study that included naïve patients without cognitive impairment who initiated MS treatment with fingolimod. Patients were followed for 3 years and relapses, expanded disability status scale (EDSS) progression (defined as worsening of 1 point on the EDSS), the annual PBVL (evaluated by structural image evaluation using normalization of atrophy [SIENA]), and the presence of CI were evaluated. Cognitive impairment was defined in patients who scored at least 2 standard deviations (SDs) below controls on at least 2 domains. The PBVL after 1 year of treatment with fingolimod was used as an independent variable, while CI and EDSS progression at the 3rd year of follow-up as dependent variables. Results A total of 71 patients were included, with a mean age of 35.4 ± 3 years old. At the 3rd year, 14% of the patients were classified as CI and 6.2% had EDSS progression. In the CI group, the PBVL during the 1st year was-0.52 (± 0.07) versus-0.42 (± 0.04) in the no CI group (p < 0.01; odds ratio [OR] = 2.24; 95% confidence interval [CI]: 1.72-2.44). In the group that showed EDSS progression, the PBVL during the 1st year was - 0.59 (± 0.05) versus - 0.42 (± 0.03) (p < 0.01; OR = 2.33; 95%CI: 1.60-2.55). Conclusions A higher PBVL during the 1st year in naïve MS patients was independently associated with a significant risk of CI and EDSS progression.

Resumo Antecedentes A porcentagem de perda de volume cerebral (PPVC) é um biomarcador na esclerose múltipla (EM). Objetivo Analisar se a PPVC durante o 1° ano após o início da doença prediz deterioração física (DF) e cognitiva (DC) em pacientes com EM. Métodos Estudo de coorte prospectivo que incluiu pacientes recém-diagnosticados sem comprometimento cognitivo que iniciaram tratamento com fingolimode. Os pacientes foram acompanhados por 3 anos, sendo avaliados a presença de recidivas, progressão da Escala Expandida do Estado de Incapacidade (EDSS, na sigla em inglês) (definida como agravamento de 1 ponto na EDSS), o PPVC anual (avaliado pela avaliação de imagem estrutural de atrofia normalizada [SIENA, na sigla em inglês) e a presença de DC (avaliada no início do estudo e nos 2° e 3° anos). O PPVC no 1° ano de tratamento com fingolimode foi utilizado como variável independente. Resultados foram incluídos 71 pacientes com idade média de 35,4 ± 3 anos. No 3° ano, 14% dos pacientes tiveram DC e 6,2% tiveram progressão de EDSS. No grupo DC, o PPVC durante o 1o ano foi - 0,52 (± 0,07) versus - 0,42 (± 0,04) no grupo sem DC (p<0,01; razão de probabilidades [OR, na sigla em inglês] =2,24; intervalo de confiança [IC] de 95%: 1,72-2,44). No grupo que apresentou progressão da EDSS, o PPVC durante o 1° ano foi de - 0,59 (± 0,05) versus - 0,42 (± 0,03) (p < 0,01; OR = 2,33; IC95%: 1,60-2,55). Conclusões Um maior PPVC durante o 1° ano foi associado a um risco significativo de progressão de DC e EDSS durante o seguimento.

Effectiveness and Safety of Early High-Efficacy Versus Escalation Therapy in Relapsing-Remitting Multiple Sclerosis in Argentina.

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 ß, 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.

Towards imaging criteria that best differentiate MS from NMOSD and MOGAD: Large multi-ethnic population and different clinical scenarios.

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.

Evaluation of the times of disability progression and related factors in patients with primary progressive multiple sclerosis from Argentina.

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.

Platelet-to-lymphocyte ratio differs between MS and NMOSD at disease onset and predict disability.

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 (ß=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.

Chiasmatic lesions on conventional magnetic resonance imaging during the first event of optic neuritis in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease in a Latin American cohort.

BACKGROUND AND PURPOSE: Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS: We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS: A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group. CONCLUSIONS: Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.

Multiple sclerosis care units in Latin America: Consensus recommendations about its objectives and functioning implementation.

OBJECTIVE: Currently, there are several reasons to promote worldwide the concept of multiple sclerosis care units (MSCU) for a better management of affected patients. Ideally, the MSCU should have some human and technical resources that distinguish and improve the care of affected patients; however, local, and regional aspects should be considered when recommending how these units should operate. The objective of these consensus recommendations was to review how MSCU should work in Latin America to improve long-term outcomes in MS patients. METHODS: A panel of neurology experts from Latin America dedicated to the diagnosis and care of MS patients gathered virtually during 2019 and 2020 to carry out a consensus recommendation about objectives and functioning implementation of MSCU in Latin America. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations focused on the objectives, human and technical resources, and the general functioning that MSCU should have in Latin America. CONCLUSIONS: The recommendations of these consensus guidelines attempt to optimize the health care and management of MS patients by setting how MSCU should work in our region.