Sclerosis

Background/Objectives: People with MS continue to experience relapses despite the use of disease-modifying therapies. This has motivated growing interest in the potential of non-pharmacological factors to reduce relapse risk. However, previous studies have been heterogeneous, and current clinical guidelines lack clarity on which measures should be incorporated into routine care. We aim to conduct an umbrella review of systematic reviews with meta-analyses to determine the current evidence on non-pharmacological exposures associated with relapse risk in MS. Methods: We searched PubMed, Embase and Cochrane to identify systematic reviews with meta-analyses that evaluated the association between non-pharmacological exposures and relapse risk. We included observational studies that reported on relapses as an outcome. The effect sizes (relative risk [RR] or standardized mean difference [SMD]) and certainty of evidence were assessed using components of the GRADE framework. Results: We screened 3366 articles and identified 11 systematic reviews for inclusion. Protective factors were breastfeeding (RR 0.63, high certainty), pregnancy (SMD −0.52, moderate certainty), menopause (SMD −0.5, low certainty), autumn months (RR 0.97, moderate certainty) and increasing levels of vitamin D (RR 0.9, low certainty). Risk factors were early postpartum period (RR 1.87, moderate certainty) and stress (d = 0.53, moderate certainty). Influenza vaccination (low certainty), COVID-19 infection (low certainty), and vitamin D levels above 50 nmol/L (low certainty) were not statistically associated with relapse risk. Conclusions: Our umbrella review highlights the need for more robust studies to strengthen the certainty of evidence on non-pharmacological exposures and relapse risk in people with MS. Current findings support promoting breastfeeding, careful disease management throughout the pregnancy–postpartum period, and the implementation of stress mitigation strategies.

Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease.

Background/Objectives: Cognitive impairment is frequent in multiple sclerosis, yet routine screening is inconsistently implemented. We aimed to characterize cognitive impairment using CogEval in a Mexican cohort and to identify clinical and functional correlates. Methods: We conducted a cross-sectional study at UMAE No. 71 (Torreón, Mexico). Adults with MS (n = 81) underwent CogEval screening (classified as normal, mild, or severe). Disability, upper-limb dexterity (9-Hole Peg Test, mean of both hands), and gait speed (Timed 25-Foot Walk) were assessed. Bivariate tests and multivariable logistic regression examined associations with cognitive impairment. Results: Participants were 61.7% women; mean age was 35.7 ± 9.9 years. Median EDSS was 2.0 (IQR 1.0–4.0); 28.4% had EDSS ≥ 4. CogEval identified impairment in 49.4% (40/81), with 62.5% severe and 37.5% mild. In bivariate analyses, impairment was associated with higher EDSS (p < 0.001), slower 9-HPT (p < 0.001), and slower T25FW (p = 0.0058), but not with age, sex, or disease duration. In adjusted models, EDSS (OR 1.86, 95% CI 1.14–3.03; p = 0.012) and 9-HPT per second (OR 1.31, 95% CI 1.09–1.58; p = 0.005) independently predicted impairment, whereas T25FW and age were not significant. Discrimination was good (AUC = 0.863). Conclusions: About half of this Mexican MS cohort screened positive for cognitive impairment, particularly those with greater disability and reduced manual dexterity. CogEval appears feasible for routine screening and may help prioritize comprehensive neuropsychological assessment and rehabilitation.