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

Neuromyelitis optica spectrum disorders (NMOSD) are rare but often devastating neuroinflammatory autoimmune diseases of the central nervous system. Acute treatment is critically important and it should be initiated early and aggressively, as relapses result in severe residual disability. Acute treatments are still based on clinical experience and observational studies. The most commonly used treatments are steroids and plasmapheresis. Several new treatments to improve management and recovery after relapses in NMOSD are currently under investigation.This review discusses current and the most recent advances in active development of phase II/III clinical trials for acute treatment options and therapeutic strategies that can help management improvement of NMOSD during a relapse. These treatments include bevacizumab, ublituximab and HBM9161.NMOSD relapses require prompt evaluation and timely treatment to restore function and mitigate disability. Timing is critical. Plasmapheresis showed better outcomes in terms of recovery when compared to high-dose intravenous methylprednisolone alone. Some groups suggest that plasmapheresis could be considered as an initial treatment approach in different clinical scenarios due to its higher effectiveness. Future research and/or real-world data will establish the advantages and disadvantages of these new treatments and define the appropriate patient profile.

Background: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). Methods: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Results: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. Conclusions: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.

The objective of the study was to describe the clinical and demographic aspects of patients with secondary progressive multiple sclerosis (SPMS) included in the Argentine MS Registry (RelevarEM, Clinical Trials registry number 03375177). RelevarEM is a longitudinal, strictly observational registry of patients with MS and neuromyelitis optica spectrum disorders. Clinical and demographic aspects were described in patients with SPMS and compared with relapsing remitting MS patients (RRMS). A total of 1723 patients with MS were included (1605, 93.2% RRMS and 118, 6.8%, SPMS). In SPMS, the median age was 53 (inter quartile range [IQR] 47-62) years, 67% were women, median disease duration of 19.5 (IQR 14-26) years, median EDSS (expanded disability status scale) 6.5 and 48.3% were under treatment for their MS. Only 23.7% of patients with SPMS were actively working and 86% had a disability certificate; 35.6% of patients with SPMS presented new lesions in MRI and 5% had clinical relapses during the past 12 months of the registry entry showing a significantly lower disease activity compared with RRMS (p < 0.01).

Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS.Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs.In comparison to other DMTs, we did not find evidence of protective effects of interferon-β on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-β. This study does not support the use of interferon-β as a treatment to reduce COVID-19 severity in MS.

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).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.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).No differences were observed between NMOSD (seropositive and seronegative) and MOGAD in survival curves.

Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed.Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab.Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95% CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2–8), 3% (95% CI 1–5), and 1% (95% CI 0–3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19.Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19. BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but severe neuroimmunological condition associated with a significant financial burden. NMOSD is also associated with increased health care utilization, including neurology outpatient visits, magnetic resonance imaging (MRI) use, long-term medication, among others. We aimed to evaluate real-world patient experiences in access to care and NMOSD burden in an Argentinean cohort.This cross-sectional study used a self-administered survey and was conducted in Argentina (2022). Patients with NMOSD were divided into three groups: private health insurance (PHI), social health insurance (SHI), and public health insurance (PHI, Ministry of Public Health). Differences in access and health care barriers were assessed.One hundred patients with NMOSD (74 women) with a mean age at diagnosis of 38.7 years were included. Their EDSS was 2.8 and they were followed for 5.2 years. Of them, 51%, 11%, and 13% were employed (full-time: 57.5%), currently unemployed and retired by NMOSD, respectively. 55% of them visited between 2-3 specialists before NMOSD diagnosis. Aquaporin-4-antibody and/or myelin oligodendrocyte glycoprotein-antibody testing was requested in 91% (health insurance covered this partially in 15.3% and 32.9% of the time the test was entirely paid by patient/family). Patients with NMOSD receiving private medical care reported greater access to MRI, outpatient visits, and fewer issues to obtain NMOSD medications compared to those treated at public institutions. A longer mean time to MRI and neurology visit was found in the PHI group when compared with the other two subgroups. Regression analysis showed that private insurance (OR=3.84, p=0.01) was the only independent factor associated with appropriate access to NMOSD medications in Argentina.These findings suggest that barriers to access and utilization of NMOSD care services in Argentina are common. NMOSD patients experienced problems to receive NMOSD medication properly, especially those from the public sector.

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).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.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).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.

Background: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). Methods: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Results: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. Conclusions: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration. We thank the sponsors of the MSDA and all the data custodians who completed and shared the questionnaire with the MSDA community. Special thanks to all the people involved in the data collection and management of the different data sources and registries. Funding/Support We thank our sponsors. The MSDA receives income from a range of corporate sponsors, recently including Biogen, Bristol Myers Squibb, Janssen Pharmaceuticals, Merck, Mylan, Novartis, QMENTA, and Roche

The objective of this study was to evaluate the association between glutamate (Glu) levels in cerebrospinal fluid (CSF) at disease onset and disease progression during follow up in a cohort of multiple sclerosis (MS) patients. Glu level was measured at disease onset (first relapse). MRI was obtained at baseline and follow-up (every 12 months) to determine the percent of brain volume change (PBVC), cortical thickness (CT), and T2 lesion volume (T2LV). The primary predictors of interest were baseline CSF Glu levels, PBVC and CT, as well as clinical disease progression [measured by Expanded Disability Status Scale (EDSS) and annualized relapse rate] during follow-up. A total of 26 MS patients were included. Mean concentration of Glu in CSF at diagnosis was 5.3 ± 0.4 uM/l. A significant association was observed between higher baseline levels of Glu and an increase in EDSS during follow up (b = 1.06, 95%CI 0.47-1.66, p = 0.003) as well as PBVC (b = -0.71 95%CI -0.56-1.38, p = 0.002) and CT (b = -0.15, 95%CI -0.06-0.33, p = 0.01). We did not observe an association between baseline Glu levels and relapse rate or T2LV during follow-up (b = 0.08, 95%CI -0.11-0.43, p = 0.11 and b = 195, 95%CI -39-330, p = 0.22, respectively). Higher Glu concentrations at disease onset were associated with an increase in PBVC and EDSS progression during follow-up in MS patients.El objetivo del trabajo fue evaluar la asociación entre el nivel de glutamato en el líquido cefalorraquídeo (LCR) al inicio de la enfermedad y la progresión de la enfermedad durante el seguimiento en una cohorte de pacientes con esclerosis múltiple (EM). Se determinaron niveles de glutamato (Glu) en LCR al inicio de la enfermedad. Se realizó una resonancia basal y durante el seguimiento cada 12 meses con el objeto de determinar el porcentaje de cambio de volumen cerebral (PCVC), grosor cortical (GC) y volumen lesional cerebral en secuencia T2 (VLT2). Los predictores primarios de interés fueron los niveles basales de Glu en LCR, PCVC Y GC, así como la progresión clínica de la enfermedad [medida por Expanded Disability Status Scale (EDSS) y tasa anual de recaídas]. Un total de 26 pacientes fueron incluidos. La concentración media de Glu fue de 5.3 ± 0.4 uM/l. Se encontró una asociación significativa entre concentraciones basales elevadas de Glu y la progresión del EDSS (b = 1.06, IC 95% 0.47-1.66, p = 0.003), así como también el PCVC (b = -0.71, IC 95% -0.56-1.38, p = 0.002) y CG (b = -0.15, IC 95% -0.06-0.33, p = 0.01). No se encontró asociación entre los niveles de Glu y la tasa anual de recaídas como tampoco el VLT2 (b = 0.08, IC 95% -0.11-0.43, p = 0.11 y b = 195, IC -39-330, p = 0.22, respectivamente). Los niveles aumentados de Glu se asociaron con un mayor cambio en el PCVC y progresión del EDSS durante el seguimiento.

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.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.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.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.

Several factors have been associated with poor adherence to disease-modifying drugs (DMD). The aim of this study is to evaluate the adherence to DMD in people with multiple sclerosis (PwMS) in Argentina and Ecuador.A cross-sectional study was performed. The study was carried out between June 2020 and October 2020, and 303 PwMS treated with DMD were included. Patients undergoing immune reconstitution treatments were excluded. Two definitions of DMD adherence were previously determined. Adherence to MS treatments was assessed using the multiple sclerosis treatment adherence questionnaire (MS-TAQ). The logistic regression model was used to evaluate factors related to adherence, and p 0.05 was considered significant.The mean age at study entry for patients was 40.7 ± 11.2 years, 207 (68.3%) were female, and the mean EDSS score was 2.2 ± 1.9. The overall adherence in our sample was 78.1% (79.7% in Argentina and 76% Ecuador, p = 0.23). Patients using infusion therapies significantly more often belonged to the adherent group (p = 0.042). Sharing decision-making (OR = 3.4, 95% CI: 1.7-6.9, p = 0.01), lower EDSS (OR = 0.8, 95% IC: 0.6-0.9, p = 0.004), and lower treatment duration (OR = 0.8, 95% IC: 0.6-0.9, p = 0.001) were independent predictors of adherence in our multivariate model.We found a prevalence of non-adherence similar to that previously reported. Furthermore, new factors associated with lower adherence were identified.

The objective of the study was to describe the clinical and demographic aspects of patients with secondary progressive multiple sclerosis (SPMS) included in the Argentine MS Registry (RelevarEM, Clinical Trials registry number 03375177). RelevarEM is a longitudinal, strictly observational registry of patients with MS and neuromyelitis optica spectrum disorders. Clinical and demographic aspects were described in patients with SPMS and compared with relapsing remitting MS patients (RRMS). A total of 1723 patients with MS were included (1605, 93.2% RRMS and 118, 6.8%, SPMS). In SPMS, the median age was 53 (inter quartile range [IQR] 47-62) years, 67% were women, median disease duration of 19.5 (IQR 14-26) years, median EDSS (expanded disability status scale) 6.5 and 48.3% were under treatment for their MS. Only 23.7% of patients with SPMS were actively working and 86% had a disability certificate; 35.6% of patients with SPMS presented new lesions in MRI and 5% had clinical relapses during the past 12 months of the registry entry showing a significantly lower disease activity compared with RRMS (p0.01).El objetivo del estudio fue evaluar los aspectos clínicos y demográficos de los pacientes con esclerosis múltiple (EM) secundaria progresiva (EMSP) en los pacientes incluidos en el Registro Argentino de EM (RelevarEM, número de registro de Clinical Trials 03375177). RelevarEM es un registro longitudinal, estrictamente observacional, de pacientes con EM y trastornos del espectro de neuromielitis óptica. Los aspectos clínicos y demográficos fueron descriptos en pacientes con EMSP respecto a aquellos con EM recaída en remisión (EMRR). Se incluyeron 1723 pacientes con EM (1605, 93.2% EMRR y 118, 6.8%, EMSP). En el grupo con EMSP la mediana de edad fue de 53 (intervalo inter-cuartil [IIQ] 47-62) años, 67% eran mujeres, mediana de tiempo de evolución de enfermedad 19.5 (IIQ 14-26) años, EDSS (expanded disability status scale), 6.5 y 48.3% estaban en tratamiento para su EM. Solo el 23.7% con EMSP estaban trabajando activamente y el 86% tenía certificado de discapacidad. Un 35.6% con EMSP presentaron nuevas lesiones en resonancia magnética y 5% tuvo recaídas clínicas en los 12 meses previos al análisis, mostrando una actividad de la enfermedad significativamente menor respecto a la forma EMRR (p0.01).

During recent years, the development of measures to assess the accumulation of disability and inflammatory activity in the progressive forms of multiple sclerosis (MS) has been a central point of research in various groups. Several instruments have been developed and implemented in order to accurately and early identify the activity and progression in this MS phenotype. Many of these tools, with greater or lesser sensitivity, have been used in clinical trials, although their use in healthcare practice is not entirely familiar to professionals involved in the care of patients with MS. The objective of this review is to describe the clinical and imaging evaluation measures implemented during the last years to identify the activity and the evolution of the disease in its progressive forms.

Myelin-associated glycoprotein (MAG) is a key molecule involved in the nurturing effect of myelin on ensheathed axons. MAG also inhibits axon outgrowth after injury. In preclinical stroke models, administration of a function-blocking anti-MAG monoclonal antibody (mAb) aimed to improve axon regeneration demonstrated reduced lesion volumes and a rapid clinical improvement, suggesting a mechanism of immediate neuroprotection rather than enhanced axon regeneration. In addition, it has been reported that antibody-mediated crosslinking of MAG can protect oligodendrocytes (OLs) against glutamate (Glu) overload by unknown mechanisms.To unravel the molecular mechanisms underlying the protective effect of anti-MAG therapy with a focus on neuroprotection against Glu toxicity.MAG activation (via antibody crosslinking) triggered the clearance of extracellular Glu by its uptake into OLs via high affinity excitatory amino acid transporters. This resulted not only in protection of OLs but also nearby neurons. MAG activation led to a PKC-dependent activation of factor Nrf2 (nuclear-erythroid related factor-2) leading to antioxidant responses including increased mRNA expression of metabolic enzymes from the glutathione biosynthetic pathway and the regulatory chain of cystine/Glu antiporter system xcMAG activation triggers Glu uptake into OLs under conditions of Glu overload and induces a robust protective antioxidant response.

We aimed to describe the health-related quality of life (HRQoL) in patients with neuromyelitis optica spectrum disorders (NMOSD), to compare HRQoL between NMOSD patients, multiple sclerosis (MS), and healthy controls (HC) and to study the associations between HRQoL and the clinical variables of the disease.A cross-sectional study was carried out. Patients with NMOSD seropositive, MS, and HC were enrolled and age-matched. The HRQoL was studied using the Argentinean validation of the SF-36 health questionnaire. Demographic and clinical characteristics were analyzed, as well as the EDSS and the total scores and subscales of the SF-36.243 individuals were included (NMOSD= 53, MS =100, and HC =90). The mean EDSS was 3.06 ± 2.01 in NMOSD and 2.67 ± 1.83 in MS with a mean of disease duration of 6.2 ± 4.4 and 6.3 ± 5.3 years, respectively. Significant statistical differences were observed in the total SF-36 score between both NMOSD and MS vs. HC (p0.01), but no differences were found when the total SF-36 score was compared between NMOSD vs. MS. Overall, NMOSD patients scored significantly lower in the total SF-36 and subscale scores compared to HC (p0.05). NMOSD patients also showed significant differences in bodily pain (58.8 ± 29.8 vs 75.1 ± 25.1, p0.01) and general health (44.4 ± 20.9 vs.31.9 ± 23.1, p0.01) when compared with MS, but no differences were found after comparing the rest of the subscales. We found that higher EDSS scores (β -1.28 p = 0.03) and disease duration (β 0.8, p = 0.02) were significantly associated to lower (worse) general health (dependent variable) score in NMOSD patients after having applied multiple linear regression analysis. Additionally, we observed that higher EDSS scores (β -10.2 p = 0.008) and the presence of relapses in the previous year (β -28.9, p = 0.02) were significantly associated to lower (worse) physical functioning (dependent variable) score.Pain seems to be a significant undertreated symptom in NMOSD patients that strongly impact on HRQoL. Patient-reported HRQoL scales scores provide comprehensive additional prognostic information beyond physical disability score.

En los pacientes de edad avanzada, el perfil de factores de riesgo vascular y el subtipo de accidente cerebrovascular (ACV) es diferente en comparación con pacientes más jóvenes. El objetivo del presente trabajo fue describir el perfil de factores de riesgo y subtipo de ACV isquémico en nuestra población de pacientes ancianos. Incluimos a pacientes mayores de 80 años con diagnóstico de ACV isquémico y ataque isquémico transitorio (AIT) entre junio de 2003 y junio de 2006. De 535 pacientes con eventos cerebrovasculares isquémicos, en 366 casos el diagnóstico fue de ACV y 169 de AIT. El 33.5% (179 pacientes) fueron mayores de 80 años. La edad media fue de 84.4 ± 4.4 años. Los factores de riesgo más frecuentes fueron: hipertensión arterial 82.7%, dislipemia 40.2% y fibrilación auricular 24.6%. El subtipo de ACV que se presentó con mayor frecuencia fue la enfermedad de pequeñas arterias en un 41.7%, seguido por el evento cardioembólico en el 19.7%, enfermedad de gran arteria 6%, otras causas en el 0.8%. De los factores de riesgo vasculares tradicionales, los más significativos fueron hipertensión e hipercolesterolemia. Estos datos son coincidentes con estudios epidemiológicos previos y explican la mayor incidencia de infartos lacunares.Young and old age stroke groups have different vascular risk profiles for cerebral ischemic events. The objective of the study was to describe the risk factor profile and stroke subtype in this population of very elderly people. We included patients over 80 years old with diagnosis of ischemic stroke and transient ischemic attack registered between June 2003 and June 2006. We described the demographic data and subtype of ischemic stroke. Of 535 patients with cerebrovascular ischemic events, the final diagnosis was stroke in 366 cases and transient ischemic attack in 169. Of these patients 33.5% were over 80 years old (179). The mean age was 84.4 ± 4.4 years. The most frequent risk factors were: hypertension 82.7%, dyslipemia 40.2% and atrial fibrillation 24.6%. Stroke subtype was: large artery disease 6%, cardioembolic stroke 19.7%, small artery disease 41.7%, and other causes 0.8%. Among traditional risk factors for stroke in our very elderly patients, the most significant were hypertension and dyslipemia. This agrees with previous epidemiological studies. The high incidence of small artery disease in our patients may be explained by the risk factor profile.

Las ataxias espino cerebelosas (AEC), constituyen un grupo de trastornos hereditarios neurodegenerativos de herencia autosómica dominante. Se caracterizan principalmente por la presencia clínica de ataxia cerebelosa asociada a oftalmoplejía, disartria, signos piramidales o extrapiramidales y pérdida de la sensibilidad profunda. La AEC 7 pertenece al grupo de las ataxias espinocerebelosas en la cual el trastorno es consecuencia de la expansión del triplete CAG localizado en el cromosoma 3 p12-p21. La característica clínica de dicha ataxia es la pérdida de la agudeza visual y posterior ceguera. Presentamos tres individuos de una familia con ataxia cerebelosa, pérdida de la agudeza visual y otros signos neurológicos. El diagnóstico fue confirmado por medio del análisis genético en el cual se observó la anormalidad característica de la AEC 7. Este es el primer caso de AEC 7 en Argentina confirmado por estudio genético. En la revisión de la literatura (hasta enero 2006) se hallaron sólo dos familias notificadas en América Latina. El objetivo del trabajo es el de enfocar la atención en el diagnóstico de esta enfermedad degenerativa en pacientes que se presentan con ataxia cerebelosa progresiva asociada con disminución de la agudeza visual e historia familiar positiva.Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.

El conocimiento de los factores de riesgo y los aspectos epidemiológicos del accidente cerebrovascular (ACV) provienen fundamentalmente de estudios de EE.UU. y Europa, con escasa información procedente de los países en desarrollo. Las características clínicas y epidemiológicas del ACV son variables en relación a factores regionales, por lo cual es necesario conocer cuál es la situación en nuestro continente. El objetivo del trabajo es describir los subtipos clínicos y los factores de riesgo de los pacientes con ACV isquémico. Se analizaron consecutivamente los pacientes ingresados desde el 01/06/2003 al 01/06/2005 con diagnostico de ACV isquémico. Sobre un total de 395 pacientes, la edad media fue de 71.36 años (± 13.82), el 55% fueron varones. Los subtipos de ACV fueron los siguientes: infarto lacunar (40%), enfermedad de gran arteria (20%), cardioembolia (10%) y otras causas (5%). La hipertensión arterial (76%), la dislipidemia (50%) y el antecedente de ACV previo (34%) fueron los factores de riesgo más frecuentes. Los pacientes con síntomas corticales presentaron más frecuentemente estenosis carotídea > del 70% en el doppler de vasos de cuello, siendo esto estadísticamente significativo. La información sobre el ACV en los países en desarrollo es difícil de obtener. Esta puede ser la razón del escaso número de registros provenientes de Sudamérica. La hipertensión fue el factor de riesgo más prevalente en nuestra serie. El subtipo de ACV difiere de lo informado en otras regiones del mundo predominando la enfermedad de pequeña arteria.Current knowledge of stroke risk factors and epidemiology is based mostly on USA or European studies; scarce data have been published from developing countries. Because epidemiological and clinical characteristics in stroke vary according to regional factors, we need to know the peculiarities of stroke on this subcontinent. The purpose is to describe the clinical subtypes and risk factors in patients with ischemic stroke. We analyzed all consecutive ischemic stroke in patients admitted at Hospital Italiano of Buenos Aires, between June 1, 2003 and June 1, 2005. Among 395 ischemic stroke patients, the mean age was 71.36 years (± 13.82) and 55% were male. Ischemic stroke subtypes were as follows: 40% patients had lacunar, 20% atherosclerotic stroke, 10% cardioembolic infarction, and 5% other causes of stroke. Hypertension (76%), hyperlipemia (50%) and prior stroke (34%) were the most frequent risk factors. Most patients with cortical symptoms had significant large-artery atherosclerosis (> 70%). Stroke informations in developing countries is difficult to obtain. This could be the reason for the very few stroke registries in South America. Hypertension was the most frequent risk factor in our registry. The pattern of stroke subtypes seems to be different from that reported in other regions of the world, with a higher frequency of small-vessel disease.

The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimer's disease. We performed a retrospective study including patients with mild stage of Alzheimer's disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimer's disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11% of the patients (n = 23) remained in the mild stage of the disease, 54% (n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35% (n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimer's disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimer's disease.

Young and old age stroke groups have different vascular risk profiles for cerebral ischemic events. The objective of the study was to describe the risk factor profile and stroke subtype in this population of very elderly people. We included patients over 80 years old with diagnosis of ischemic stroke and transient ischemic attack registered between June 2003 and June 2006. We described the demographic data and subtype of ischemic stroke. Of 535 patients with cerebrovascular ischemic events, the final diagnosis was stroke in 366 cases and transient ischemic attack in 169. Of these patients 33.5% were over 80 years old (179). The mean age was 84.4 +/- 4.4 years. The most frequent risk factors were: hypertension 82.7%, dyslipemia 40.2% and atrial fibrillation 24.6%. Stroke subtype was: large artery disease 6%, cardioembolic stroke 19.7%, small artery disease 41.7%, and other causes 0.8%. Among traditional risk factors for stroke in our very elderly patients, the most significant were hypertension and dyslipemia. This agrees with previous epidemiological studies. The high incidence of small artery disease in our patients may be explained by the risk factor profile.

Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.

Current knowledge of stroke risk factors and epidemiology is based mostly on USA or European studies; scarce data have been published from developing countries. Because epidemiological and clinical characteristics in stroke vary according to regional factors, we need to know the peculiarities of stroke on this subcontinent. The purpose is to describe the clinical subtypes and risk factors in patients with ischemic stroke. We analyzed all consecutive ischemic stroke in patients admitted at Hospital Italiano of Buenos Aires, between June 1, 2003 and June 1, 2005. Among 395 ischemic stroke patients, the mean age was 71.36 years (+/- 13.82) and 55% were male. Ischemic stroke subtypes were as follows: 40% patients had lacunar, 20% atherosclerotic stroke, 10% cardioembolic infarction, and 5% other causes of stroke. Hypertension (76%), hyperlipemia (50%) and prior stroke (34%) were the most frequent risk factors. Most patients with cortical symptoms had significant large-artery atherosclerosis (70%). Stroke informations in developing countries is difficult to obtain. This could be the reason for the very few stroke registries in South America. Hypertension was the most frequent risk factor in our registry. The pattern of stroke subtypes seems to be different from that reported in other regions of the world, with a higher frequency of small-vessel disease.