Enfermedades Desmielinizantes.artículos

Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?

2025-12-01T00:00:00Z

Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum? Piedrabuena, María Agustina; Marrodán, Mariano; Zárate, María Agustina; Fiol, Marcela; Ysrraelit, María Célica; Correale, Jorge Background: Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN). Objective: To characterize and compare the clinical, radiological, and therapeutic profiles of DN, AQP4-IgG+, and MOG-IgG+ patients. Methods: Retrospective analysis of patients meeting 2015 NMOSD criteria, grouped by serostatus (AQP4-IgG+, MOG-IgG+, and DN). Demographic, clinical, and imaging data were compared. Results: We analyzed 111 patients: 64 AQP4-IgG+, 31 DN, and 16 MOG-IgG+. At onset, AQP4-IgG+ patients were older than DN and MOG-IgG+ (49 ± 14 vs 41 ± 12 vs 35 ± 12 years, p < 0.0001). DN had more relapses in the first two years (p = 0.02) and higher EDSS (p < 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p < 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(p < 0.0001). Area postrema lesions were more frequent in DN (p = 0.02). Rituximab was mainly used in AQP4-IgG+ and DN (p < 0.001), with lower failure in DN (4.8 % vs 18 %). Conclusion: DN NMOSD shows distinct features but comparable disability to AQP4-IgG+ individuals. Conventional immunosuppressants seem effective, though further research is needed to clarify mechanisms and optimize treatment strategies.

The Neurochemical Landscape of Oligodendrocyte Physiology: From Myelination to Metabolic and Synaptic Modulation

2025-12-11T00:00:00Z

The Neurochemical Landscape of Oligodendrocyte Physiology: From Myelination to Metabolic and Synaptic Modulation Correale, Jorge Oligodendrocytes, traditionally recognized for their role in axonal myelination, are increasingly appreciated as metabolically dynamic and functionally diverse cells integral to central nervous system (CNS) homeostasis. This review delineates the evolving neurochemical landscape of oligodendrocyte physiology, emphasizing their roles beyond myelin production. We explore key processes including lipid metabolism, metabolic coupling with neurons, ion buffering, neurotransmitter signaling, and synaptic modulation. Oligodendrocytes preferentially utilize aerobic glycolysis and support axonal energy metabolism via the export of lactate and phosphocreatine, maintaining ATP levels even in the absence of mitochondria within the myelin sheath. Their capacity for regional and transcriptional heterogeneity allows adaptive responses to local microenvironments and neuronal activity. Lipid biosynthesis and storage mechanisms are intricately regulated through mTORC1, SREBPs, and lipophagy, enabling rapid membrane expansion, and structural integrity during myelination. Furthermore, oligodendrocytes modulate the periaxonal milieu via potassium buffering, pH regulation, and osmotic balance, primarily through Kir channels, carbonic anhydrases, and aquaporins. They also express a wide array of neurotransmitter receptors, enabling bidirectional communication with neurons and activity-dependent modulation of maturation and plasticity. Intracellular signaling pathways such as PI3K/Akt/mTOR, MAPK/ERK, and Wnt/β-catenin orchestrate the integration of metabolic and transcriptional programs. Collectively, these findings redefine oligodendrocytes as active participants in CNS physiology, contributing to neuronal health, circuit plasticity, and responses to injury or disease.

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

2025-10-28T00:00:00Z

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

2025-11-15T00:00:00Z

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.