Enfermedades Desmielinizantes.artículos

Childhood and Adolescent Environmental Risk Factors for Multiple Sclerosis: A Systematic Review With Meta-Analysis

2026-02-12T15:58:36Z

Childhood and Adolescent Environmental Risk Factors for Multiple Sclerosis: A Systematic Review With Meta-Analysis Vitturi, Bruno Kusznir; Cellerino, Maria; Boccia, Daniele; Leray, Emmanuelle; Correale, Jorge; Dobson, Ruth; van der Mei, Ingrid; Fujihara, Kazuo; Inglese, Matilde Background: We aimed to provide updated evidence from the current literature regarding pediatric environmental factors associated with the risk of developing multiple sclerosis (MS). Methods: Articles were searched in PubMed, SciVerse ScienceDirect, and Web of Science. We included all clinical studies assessing the occurrence of MS at any age in association with the exposure to any environmental risk factor during childhood or adolescence. The main outcome was the occurrence of MS. The quality assessment was performed with the critical appraisal checklist for case-control studies. Pooled unadjusted effect sizes (OR) were calculated and reported with a 95% CI from random-effects meta-analysis. Results: The review included 87 studies conducted across 20 countries. The studies analyzed diverse environmental risk factors, including infections, vaccinations, tobacco exposure, body mass index, and other pediatric exposures. EBV infection showed a significant positive association with MS risk (ES = 2.38, 95% CI = 1.80-3.15). Breastfeeding showed limited protective associations, and various adverse social experiences like bullying and sexual abuse were linked to increased MS risk. Active smoking during childhood/adolescence and obesity during these periods were associated with higher MS risk, while normal body mass index was protective. Antibiotic and chemical exposures, as well as vitamin D deficiency, were linked to higher MS risk. The review highlighted substantial heterogeneity and identified publication bias in studies on infections and vaccinations. Conclusions: Environmental risk factors for MS are important during childhood and adolescence. The first 20 years are a key window for prevention and should be seen as an opportunity.

Efficacy and safety of Cladribine as a therapeutic option in multiple sclerosis patients over 50 years of age: A real-world study

2026-02-03T17:58:00Z

Efficacy and safety of Cladribine as a therapeutic option in multiple sclerosis patients over 50 years of age: A real-world study Piedrabuena, María Agustina; Correale, Jorge; Silva, Berenice; Fiol, Marcela; Marrodán, Mariano; Zárate, María Agustina; Heriz, Alejandra; Ayerbe, Jeremías; Míguez, Jimena; Pita, Cecilia; Lázaro, Luciana; Casas, Magdalena; López, Pablo Adrián; Tkachuk, Verónica; Balbuena, María Eugenia; Nadur, Débora; Liwacki, Susana; Luetic, Geraldine; Burgos, Marcos; Ysrraelit, María Célica Background: Despite an aging multiple sclerosis (MS) population, clinical outcomes and long-termeffects of disease-modifying therapies in patients aged ≥50 years remain under-studied. Objective: To compare the efficacy and safety of cladribine in relapsing-remitting MS (RRMS) patients aged <50 versus ≥50 years. Methods: In this retrospective, observational multicenter study, 366 RRMS patients treated with cladribine (cumulative dose 3.5 mg/kg) were included. Patients were stratified by age at treatment initiation (<50 years, n = 317; ≥50 years, n = 49). Outcomes included annualized relapse rate (ARR), MRI activity, percentage of patients without EDSS progression, and no evidence of disease activity (NEDA-3) at 12 and 24 months. Safety endpoints encompassed lymphocyte nadirs, infection, and malignancy rates. Results: At baseline, the ≥50-year cohort had longer disease duration (9.8 ± 7.9 vs. 6.6 ± 5.3 years; p < 0.001) and higher EDSS (2.6 ± 1.6 vs. 1.7 ± 1.6; p = 0.001). Eighteen patients aged <50 years (5.7 %) discontinued cladribine before the second course due to breakthrough clinical or radiological activity; all patients ≥50 years completed both courses. After treatment, ARR was lower in the older cohort (0.02 vs. 0.11; p = 0.001). Percentage of patients free of EDSS progression was similar in both groups (97.3 ± 16.2 in <50 years versus 95.9 ± 20 in ≥50 years p = 0.6). NEDA-3 rates at 12 months were 73.2 % (<50 years) versus 77.6 % (≥50 years; p = 0.53) and at 24 months were 90.5 % versus 98.0 % (p = 0.31). Treatment failure occurred in 8.1 % of patients aged <50 years versus 3.0 % of those aged ≥50 years (p = 0.47). Lymphocyte nadirs were similar in both groups. Only one <50 year patient developed grade 4 lymphopenia. Infection (8.1 % vs. 2.3 %; p = 0.21) and malignancy rates (2.0 % vs. 0.6 %; p = 0.86) were similar between groups. Conclusions: Cladribine demonstrated sustained efficacy and a favorable safety profile in RRMS patients across age groups. The ≥50-year cohort showed a significantly lower ARR and no early treatment discontinuations due to clinical or radiological activity. These findings support its utility in the management of older patients with RRMS.

Therapeutic Plasma Exchange in Corticosteroid-Refractory Multiple Sclerosis Relapses: Mechanisms, Efficacy, and Integration into Clinical Practice

2026-02-03T16:04:54Z

Therapeutic Plasma Exchange in Corticosteroid-Refractory Multiple Sclerosis Relapses: Mechanisms, Efficacy, and Integration into Clinical Practice Marrodán, Mariano; Ysrraelit, María Célica; Correale, Jorge Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40-60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients' selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients.

Anti-NMDAR encephalitis across the lifespan: Clinical, electrophysiological, and prognostic insights from a Latin American cohort

2026-01-21T15:14:42Z

Anti-NMDAR encephalitis across the lifespan: Clinical, electrophysiological, and prognostic insights from a Latin American cohort Marrodán, Mariano; Perez Arana, Carolina I.; Kirchner, Ricardo J.; Varela, Francisco José; Orzuza, Gabriela I.; Schteinschnaider, Ángeles; Chaderevian, Miriam G.; Vita, Cristina; Farez, Mauricio Franco; Correale, Jorge Background and objectives: Anti-N-Methyl-d-aspartate receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis, primarily affecting young females. Its clinical heterogeneity, particularly in underrepresented populations, poses diagnostic and therapeutic challenges. Epidemiological data from Latin America remain limited. This study aimed to characterise the demographic, clinical, and neuroimaging features of NMDARE in Latin American tertiary centres, with a focus on age-related differences. Methods: A retrospective cohort study included NMDARE cases between January 2016 and December 2024. Inclusion criteria required anti-NMDAR antibody positivity in CSF and/or serum. Demographic, clinical, and paraclinical data were systematically collected. Comparisons between paediatric (<18 years) and adult (≥18 years) patients were conducted using appropriate statistical tests. Results: Of 1026 screened patients, 58 tested positive for anti-NMDAR antibodies, and 49 met inclusion criteria. Female predominance was higher among adults (61.5 % vs. 30.4 %; p = 0.03). Adults more frequently presented with confusion (57.7 % vs. 13 %; p = 0.003), mood disturbances (61.5 % vs. 26.1 %; p = 0.03), cognitive impairment (76.9 % vs. 36.1 %; p = 0.001), and dysautonomia (19.2 % vs. 0 %; p = 0.04). Speech disturbances (56.5 % vs. 34.6 %; p = 0.02), movement disorders (56.5 % vs 34.6 %, p = 0.06), and EEG abnormalities (69.6 % vs. 42.3 %; p = 0.01) were more frequent in paediatric patients. CSF pleocytosis was independently associated with ICU admission (OR = 11, p = 0.01). Relapse occurred in 10 % of cases. Discussion: In this Latin American cohort, NMDARE presents distinct age-dependent clinical profiles. While existing diagnostic criteria are broadly applicable, awareness of age-specific features-particularly psychiatric symptoms in adults and EEG abnormalities in children-may improve diagnostic accuracy and guide tailored management strategies. Larger cohort studies in other populations have reported different findings, underscoring the importance of regional studies and the need for additional research to validate and generalize these results.