Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS Registry (RelevarEM).

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.

Neuro rehabilitation effectiveness based on virtual reality and tele rehabilitation in people with multiple sclerosis in Argentina: Reavitelem study.

Virtual Reality (VR) has emerged as a new treatment approach in neurorehabilitation (NR). REAVITELEM Study is a specific NR intervention program based on VR at center (VRC) and tele-rehabilitation (TR) in Argentina. Methods First national multicenter study with a 12-week program intervention of VRC and TR. Participants were assessed at baseline, at 6th and 12th week. Phase I: recruitment and gather of 5 NR Centers from Argentina by the coordinator center (INEBA) to unify evaluation and intervention criteria. Phase II, all centers completed VRC an TR programs. Intervention was 30-minute session, twice a week for 12 weeks. Outcome measures: Expanded Disability Status Scale (EDSS), Fist and Key Pinch Dynamometry, Beck Depression Inventory-Fast Screen, Fatigue Severity Scale, Functional Independence Measure (FIM), International Questionnaire investigating Quality of life in MS (MusiQol) and a Visual Analogue Scale (VAS) of satisfaction after treatment. Results A total of 54 PWMS (23 males) were recruited for VRC. Afterwards, 14 completed TR. The mean age for VRC was 44.72 (SD ± 13.74) and 41.71 (SD ± 10.5) for TR. The median EDSS was 4, 75 for VR. At VRC, 42 have RRMS, 8 have SPMS and 4 PPMS. At TR, 13 have RRMS and 1 have SPMS. The VAS reported an excellent level of satisfaction after treatment with an average of 9, 02 (SD±1.35) in VRC and 9.42 (SD±0.66) in TR. There were significant differences for MusiQol, which improved from baseline to the post-intervention assessment at VRC (p=<0.001) and at TR (p = 0.004) as well as FIM post-intervention assessment at VCR (p = 0.02) and TR (p = 0.04). Conclusion this study suggest that the NR treatment based on VR in MS in Argentina, is an additional effective tool, which favors improvements in the level of functioning in activities of daily living, quality of life, mood, and satisfaction with the treatment.

Accumulative risk of clinical event in high-risk radiologically isolated syndrome in Argentina: data from the nationwide registry RelevarEM.

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

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.

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.

What percentage of AQP4-ab-negative NMOSD patients are MOG-ab positive? A study from the Argentinean multiple sclerosis registry (RelevarEM).

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.

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

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.

Absence of latitudinal gradient in oligoclonal bands prevalence in Argentina.

BACKGROUND: Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient. METHODS: For each province, an average latitude was calculated, and OCB frequency was investigated. Multivariate logistical regression analysis and linear correlation were performed. Statistical analysis was repeated after excluding patients from centers using isoelectric focusing (IEF) in less than 95% of patients (CwIEF<95). RESULTS: We included 2866 patients. OCB where positive in 73.9% of patients. No association or correlation were found between OCB and latitude of residence, even after excluding patients from (CwIEF<95). CONCLUSION: OCB positivity does not follow a latitudinal gradient in Argentina. Also, OCB positivity is lower than described in other world regions.

The Argentinean multiple sclerosis registry (RelevarEM): Methodological aspects and directions.

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.