Systemic sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease characterized by immune activation, vasculopathy and progressive fibrosis of the skin and internal organs. Immunosuppressive treatment is commonly used in early inflammatory disease and in SSc-associated interstitial lung disease (SSc-ILD), yet the optimal first-line agent depends on the dominant clinical phenotype. Methotrexate (MTX) and mycophenolate mofetil (MMF) are two widely used conventional immunomodulatory options. This review summarizes the clinical trial evidence from the last four decades and places it into the context of contemporary guideline recommendations and real-world comparative effectiveness data. Two randomized placebo-controlled trials support a modest role for MTX in early diffuse cutaneous SSc, particularly for skin and musculoskeletal manifestations, but evidence for lung benefit is limited. MMF has stronger evidence for SSc-ILD, principally from the Scleroderma Lung Study II, a randomized double-blind trial showing comparable efficacy to oral cyclophosphamide with better tolerability, and from subsequent pilot, open-label, and real-world studies. Overall, the current evidence supports a phenotype-driven approach: MTX may be considered when skin or joint disease predominates without clinically relevant ILD, whereas MMF is generally preferred for SSc-ILD and systemic inflammatory disease. Direct head-to-head MTX versus MMF trials are lacking and remain an important research priority.
Background/Objectives: Optic neuritis is associated with demyelinating diseases such as multiple sclerosis (MS), but atypical presentations, particularly bilateral optic nerve involvement or coexisting systemic symptoms, necessitate broader diagnostic consideration. Case presentation: This case report describes a 50-year-old male with untreated, active hepatitis C virus (HCV) infection who presented with bilateral optic neuritis. Cerebrospinal fluid (CSF) analysis revealed elevated myelin basic protein, positive oligoclonal bands, an elevated immunoglobulin G index, and an HCV viral load of 9.3 million international units/milliliter (IU/mL). Magnetic resonance imaging (MRI) of the orbits showed bilateral optic neuritis with perineuritis. The patient had no history of interferon therapy and lacked markers of cryoglobulinemia, making this a rare case of optic neuritis possibly associated with chronic hepatitis C viral infection. The patient was treated with intravenous immunoglobulin (IVIG) without corticosteroids, with some improvement in vision. Conclusions: This case adds to the expanding spectrum of multiple sclerosis (MS) mimics and underscores diagnostic challenges associated with atypical optic neuritis presentations, particularly in the setting of coexisting systemic viral infections.
Background: Spasticity is one of the most disabling manifestations of multiple sclerosis (MS), contributing to limitations in walking and transfers, pain, progressive functional limitation, and reduced quality of life. Despite advances in rehabilitation, pharmacological therapies, botulinum toxin injections, and intrathecal baclofen, many patients continue to experience refractory focal or multifocal spasticity requiring alternative therapeutic approaches. Percutaneous cryoneurolysis has recently emerged as a minimally invasive peripheral neuromodulation technique capable of selectively reducing pathological muscle overactivity through reversible axonotmesis while preserving the structural framework necessary for nerve regeneration. Growing clinical experience has expanded its application across several neurological disorders; however, its role in MS has not yet been comprehensively defined. Methods: A structured narrative review was conducted through comprehensive searches of PubMed/MEDLINE, Scopus, and Web of Science. Original clinical studies evaluating percutaneous cryoneurolysis for neurological spasticity were identified and critically synthesized. Because disease-specific evidence in MS remains limited, studies involving other upper motor neuron disorders, including stroke, cerebral palsy, traumatic brain injury, and spinal cord injury, were also considered to provide a broader overview of current clinical applications, procedural techniques, safety, and functional outcomes. Results: The available evidence includes case reports, case series, and prospective and retrospective observational studies, together with recent evidence syntheses. Across different neurological conditions, ultrasound-guided cryoneurolysis has consistently demonstrated technical feasibility and a favorable safety profile, with reported reductions in spasticity, improvements in passive range of motion, pain reduction, facilitation of positioning and nursing care, and, in selected studies, improved functional performance. Recent observational cohorts and prospective studies have expanded the evidence base by providing larger patient populations and longer follow-up, while systematic evidence syntheses have confirmed the growing clinical interest in this technique. Nevertheless, substantial heterogeneity persists regarding patient selection, target nerves, procedural protocols, outcome measures, and duration of follow-up. Evidence specifically addressing patients with MS remains limited and is currently derived primarily from individual case reports and small clinical series. Conclusions: Current evidence suggests that percutaneous cryoneurolysis represents a promising minimally invasive adjunctive treatment for selected patients with focal or multifocal neurological spasticity, including those with multiple sclerosis. However, the available evidence remains predominantly observational, and randomized controlled trials comparing cryoneurolysis with established therapies are still lacking. Future multicenter prospective studies, standardized treatment protocols, and disease-specific investigations are required to better define patient selection, long-term efficacy, safety, and the role of cryoneurolysis within contemporary multidisciplinary spasticity management.
Background/Objectives: Amyotrophic Lateral Sclerosis (ALS) is a rare, neurodegenerative disease with complex genetic and environmental determinants. The MTHFR C677T (rs1801133) variant, known for reducing enzymatic activity in the folate cycle, has been implicated in ALS risk, though findings remain inconsistent across diverse populations. Methods: A population-based case–control study was conducted in 248 age-matched individuals to investigate the MTHFR C677T (rs1801133) and ALS susceptibility. Molecular analysis was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Genetic associations were evaluated under multiple inheritance models, while survival analysis utilized the Kaplan–Meier method to assess the relationship between MTHFR genotypes and patient prognosis. Results: The C677T variant showed a significant association under the codominant and recessive models, suggesting involvement in ALS risk (OR = 4.63; p = 0.01 and OR = 3.92; p = 0.02), respectively. However, stratification by sex demonstrated an association predominantly in women (OR = 7.10, p = 0.02; OR = 5.87, p = 0.04). Additionally, Kaplan–Meier analysis revealed a numerically shorter mean survival time for the mutant genotype compared with wild-type and heterozygous carriers, without statistical significance. Conclusions: Notably, we identified a significant association between the MTHFR C677T (rs1801133) variant and ALS risk, particularly among women. These findings suggest that the mutant (T/T) genotype showed a stronger association, potentially reflecting postmenopausal hormonal influences on one-carbon metabolism and related susceptibility pathways.
Background/Objectives: Digital, remote, and ecological tools may complement clinic-based assessment in multiple sclerosis (MS), but the distribution of evidence across fatigue/fatigability, mobility, and real-world functional activity remains unclear. This scoping review mapped tools, metrics, constructs, contexts of use, and reported clinical utility in adults with MS, with attention given to whether the evidence was balanced across domains. Methods: Following Joanna Briggs Institute guidance and PRISMA-ScR/PRISMA-S reporting standards, five databases were searched on 14 March 2026. After deduplication, title/abstract screening, full-text assessment, and manual extraction and verification, the findings were synthesized descriptively without formal critical appraisal. Results: Of 3100 records identified, 1433 unique records were screened and 125 sources were included. Gait was the most frequently assessed domain (105/125), followed by fatigue/fatigability (33/125), physical activity (29/125), and sleep (2/125). The most frequent technologies were wearable devices (60/125), accelerometry (54/125), remote/home-based/telemonitoring modalities (52/125), and inertial measurement units (42/125). Conclusions: The evidence is predominantly gait- and mobility-focused, while fatigue/fatigability and broader real-world functional activity are less consistently represented. Reported clinical utility was usually framed around functional assessment, longitudinal/remote monitoring, rehabilitation planning, patient stratification, and decision support, but these characteristics were extracted as reported and were not independently appraised.
Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by immune dysregulation, microvascular damage, and progressive fibrosis affecting multiple organs. While cardiopulmonary, renal, and gastrointestinal manifestations have been extensively investigated, involvement of the vestibular system remains insufficiently explored and is likely underrecognized in clinical practice. Vestibular symptoms such as dizziness, vertigo, imbalance, and postural instability may significantly affect quality of life and functional independence in patients with SSc. The pathophysiology of vestibular involvement in SSc is presumed to be multifactorial, involving microangiopathy of the inner ear, immune-mediated damage to vestibular end organs, fibrotic changes affecting inner ear homeostasis, and, in some cases, central nervous system involvement. This narrative review provides a comprehensive and critical synthesis of the current literature on vestibular alterations in systemic sclerosis. We discuss underlying mechanisms, clinical manifestations, diagnostic strategies, associations with common vestibular disorders, and the role of vestibular rehabilitation. By consolidating existing evidence and identifying knowledge gaps, this review aims to promote a more systematic and multidisciplinary approach to the evaluation and management of vestibular dysfunction in SSc.
Nailfold capillaroscopy has earned its place as a cornerstone of clinical assessment in systemic sclerosis (SSc). Its ability to detect early microvascular changes, distinguish primary from secondary Raynaud’s phenomenon, and contribute to disease classification has fundamentally reshaped the clinical approach to early diagnosis and disease stratification. The recognition of distinct capillaroscopic patterns offers a structured framework for tracking disease evolution and identifying patients who warrant closer surveillance or proactive therapeutic intervention. The inclusion of capillaroscopic abnormalities in the ACR/EULAR 2013 classification criteria validates its diagnostic importance and facilitates identification of patients with early or limited cutaneous disease. Beyond diagnosis, emerging evidence supports prognostic applications, particularly for predicting digital ulcers, though the predictive value for other organ complications requires further validation. As a non-invasive, safe, and reproducible technique, capillaroscopy is particularly well-suited to long-term disease monitoring. Quantitative scoring systems allow for rigorous, objective tracking of microangiopathic progression and hold considerable promise as outcome measures in clinical trials targeting vasculopathy. Ongoing technological advances, particularly in automated image analysis and integration with functional assessment tools, promise to enhance the clinical utility of capillaroscopy while reducing operator dependency. Standardization efforts and validation of capillaroscopic parameters as clinical trial endpoints will be crucial for realizing the full potential of this technique.
Background: The diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) relies on sensitive serological detection of MOG-IgG. Fixed cell-based assays (CBAs) may yield low-positive or borderline results that complicate early clinical decision-making, whereas live CBAs—recommended as the reference method—preserve native antigen conformation and offer higher analytical sensitivity. Importantly, low-positive titres should not be confused with true seronegativity, as they may nevertheless be clinically meaningful. Case Presentation: A 14-year-old previously healthy male presented with left optic neuritis and perineuritis following an upper respiratory infection. Initial MOG-IgG testing on a fixed CBA was low-positive (1:10). He partially responded to intravenous methylprednisolone and required intravenous immunoglobulin (IVIG) for complete resolution. Over three years, he experienced sequential, steroid-dependent bilateral optic neuritis with perineuritis, relapsing on every steroid taper. Rituximab and subsequently mycophenolate mofetil failed to induce remission. Repeat testing with a live CBA at a reference laboratory yielded a high-positive MOG-IgG titre of 1:1000, confirming MOGAD. Tocilizumab (8 mg/kg every 4 weeks) was initiated and allowed complete corticosteroid withdrawal. At age 18, the patient remained asymptomatic, with an Expanded Disability Status Scale score of 0, best-corrected visual acuity of 20/20 in both eyes, and stable peripapillary retinal nerve fibre layer thickness on spectral-domain optical coherence tomography. Conclusions: In paediatric patients with recurrent optic neuritis with perineural involvement and borderline fixed-CBA results, confirmatory testing with a live CBA at a reference laboratory should be considered to avoid diagnostic delay and therapeutic misdirection. In refractory, steroid-dependent cases, IL-6 receptor blockade may represent a reasonable therapeutic option, in line with emerging evidence.
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by immune dysregulation, microvascular injury, and progressive cutaneous and internal organ fibrosis. Despite advances in the understanding of SSc pathogenesis, effective disease-modifying therapies remain limited, and there is ongoing interest in targeted approaches that may modulate early inflammatory-vascular mechanisms linked to subsequent fibrotic remodeling. The IL-23/Th17 axis contributes to SSc biology, providing a rationale for IL-23p19 blockade as a potential therapeutic strategy. This focused narrative review summarizes currently available clinical signals of IL-23p19 inhibition in SSc, centered on guselkumab, and interprets reported outcomes using a domain-based framework. Published evidence remains confined to uncontrolled reports totaling 4 patients (one case report of early limited cutaneous SSc and a three-patient case series of early diffuse cutaneous SSc with comorbid psoriasis). Across these reports, investigators described improvements most consistently in the cutaneous domain (modified Rodnan skin score [mRSS], modified Rodnan total skin score [mRTSS], and the American College of Rheumatology Combined Response Index in Systemic Sclerosis [CRISS]) and in microvascular manifestations, including Raynaud’s phenomenon and nailfold microangiopathy, whereas pulmonary and gastrointestinal findings remain preliminary. We discuss key limitations of the current literature, including publication and reporting bias, the heterogeneity of phenotypes and endpoints, and confounding by comorbid psoriatic disease and natural disease fluctuation. Overall, IL-23p19 inhibition offers a pathway-specific approach in SSc, but establishing efficacy and defining responsive phenotypes requires adequately powered controlled evidence. Findings pertain specifically to guselkumab and cannot be generalized to IL-23 inhibition as a class.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in patients with systemic sclerosis. High-resolution computed tomography (HRCT) provides anatomical detail but cannot directly assess disease activity, inflammation, or fibroblast activation. Molecular positron emission tomography/computed tomography (PET/CT) offers functional imaging that may complement structural assessment. This narrative review examines the role of molecular PET/CT in SSc-ILD, including fluorodeoxyglucose (FDG) PET/CT for metabolic activity assessment, fibroblast activation protein inhibitor (FAPI) tracers for fibrosis imaging, and other molecular probes targeting inflammation and tissue remodelling. We synthesize evidence on the diagnostic feasibility, prognostic value, and clinical applications of molecular PET/CT in SSc-ILD and related fibrotic interstitial lung diseases. Quantitative PET metrics, radiomics approaches, and artificial intelligence integration are also discussed. Although molecular PET/CT shows potential for phenotyping disease activity and predicting outcomes, current evidence is limited by small sample sizes and heterogeneous study designs. Standardization of imaging protocols, validation in multicenter cohorts, and integration with clinical and molecular biomarkers are needed before the clinical utility of molecular PET/CT in SSc-ILD can be established.
Multiple sclerosis is an immune-driven neurological disease that affects myelinated axons in the central nervous system. However, the trigger of the (dysregulated) immune reactions is not known. According to Wilkin’s primary lesion theory, myelin-reactive T cells present in the immune repertoire hyper-react to myelin antigens that are released from idiopathic lesions within the central nervous system. However, neither the cause of the primary lesion nor the cause of the immune hyper-reactivity is known. We investigated whether these unknown activation signals may be relayed by common herpesviruses. In this concept paper, we propose the novel paradigm that the trigger of autoimmunity in MS comprises a conspiracy of three common herpesviruses: human herpesvirus-6A as a potential trigger of primary lesions due to its proven capacity to cause oligodendrogliopathy, cytomegalovirus as a trigger for the formation of effector memory cytotoxic T cells with proven capacity to induce multiple sclerosis pathology in a non-human primate MS model and Epstein-Barr Virus due to its capacity to render B cells capable to effectively present a critical myelin antigen to these effector memory cytotoxic T cells.
Background/Objectives: Multiple sclerosis (MS) significantly impairs quality of life (QoL) beyond physical disability, affecting psychosocial well-being. Although nurses play a central role in holistic, person-centered care, region-specific evidence from Western Greece remains limited. This study aimed to evaluate QoL and its biopsychosocial determinants among adults with MS in Western Greece and synthesize evidence on modifiable factors to guide nursing interventions. Methods: A cross-sectional study was conducted among 128 adults with MS (82% response rate from a pool of 156). QoL was measured with the MSQOL-54, depression with the Beck Depression Inventory-II, and social support with the Multidimensional Scale of Perceived Social Support. Data were analyzed using descriptive statistics, correlations, and multiple regression. Results: Participants reported moderate QoL impairment (Physical Composite Score = 53.6; Mental Composite Score = 57.4). Unemployment (52% of sample) was significantly associated with poorer physical QoL (p < 0.001). Fatigue, pain, and depressive symptoms showed strong negative correlations with QoL (p < 0.001). Higher perceived social support was a significant predictor of better mental health (β = 0.42, p < 0.01). The systematic review confirmed these predictors and reinforced social support as a key protective factor. Conclusions: Nurses should prioritize psychosocial aspects of MS care. Routine assessment and strengthening of social support networks, along with addressing employment barriers, are essential. Integrating targeted psychosocial strategies into standard nursing practice can effectively improve holistic well-being and mitigate QoL deterioration in individuals with MS.
Background/Objectives: Evidence suggests that modifiable lifestyle interventions improve disability in relapsing multiple sclerosis (MS); however, interactions between different factors may impact outcomes. Thus, the objective of this secondary analysis was to investigate diet-induced effects on the impact of MS and effect modification by other modifiable lifestyle factors. Methods: The physical and psychological impact of MS was assessed with the MS Impact Scale-29 (MSIS) at run-in, baseline, 12 weeks, and 24 weeks. Participants were randomized at baseline to the Swank low-saturated fat or Wahls modified Paleolithic elimination diets and instructed to maintain usual physical activity, objectively measured with an accelerometer, throughout the trial. Baseline information on sleep, physical activity, alcohol, and smoking was explored as effect modifiers. Results: Among the Swank group, MSIS-Physical scores improved from 33.8 ± 3.8 at baseline to 28.7 ± 3.6 at 12 weeks (p = 0.04) and 25.3 ± 3.5 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 35.7 ± 3.3 at baseline to 25.6 ± 2.6 at 12 weeks (p = 0.001) and 22.8 ± 2.4 at 24 weeks (p < 0.001). Among the Wahls group, MSIS-Physical scores improved from 33.8 ± 3.1 at baseline to 21.7 ± 3.0 at 12 weeks (p < 0.001) and 19.0 ± 3.1 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 38.4 ± 3.8 at baseline to 25.5 ± 3.8 at 12 weeks (p < 0.001) and 20.6 ± 3.6 at 24 weeks (p < 0.001). Improvements in MSIS-Physical were greater among participants who were physically inactive or drank little alcohol at baseline. Conclusions: Both diets led to favorable within-group improvements in the perceived impact of MS. People with MS who are physically inactive or drink little alcohol may benefit the most from dietary interventions.
Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease with important disability accumulation. Early-onset NMOSD, defined as disease onset before age 50, exhibits distinct clinical characteristics compared to late-onset disease. We present a case series of patients with first symptom onset before age 30. Methods: A retrospective review of 10 patients diagnosed with NMOSD at our center in San Luis Potosí, Mexico, with disease onset before age 30. Clinical presentation, imaging findings, AQP4 antibody status, treatment response, and disability outcomes were analyzed. Results: The mean age at onset was 18.6 years (range 6–30). Area postrema syndrome was the most common presentation (40%), followed by acute myelitis and optic neuritis (30% each). All tested patients were AQP4-positive. The mean EDSS at follow-up was 6.6, indicating severe disability. Most patients received rituximab with variable response rates. Conclusions: Our cohort showed higher disability than reported in other early-onset series, emphasizing the need for prompt diagnosis and aggressive treatment in this population.
Background/Objectives: Gait impairment is a common finding in multiple sclerosis (MS). Clinicians have used both treadmill and overground walking for its evaluation and treatment. However, there is little evidence that these two types of walking are equivalent. Methods: An incidental finding from another study revealed differences between treadmill and overground walking speed in 24 persons with MS. We compared this to walking speed in healthy controls walking in the same two conditions. Results: Walking speed was significantly reduced on the treadmill relative to overground walking in persons with MS, while there was no difference between the two conditions for controls. Conclusions: Clinicians should consider that treadmill walking may not generalize to overground walking in this population.
Background: Amyotrophic lateral sclerosis (ALS) progressively impairs motor function, compromising speech and limiting communication. Augmentative and alternative communication (AAC) is essential to maintain autonomy, social participation, and quality of life for people with ALS (PALS). This review maps technological developments in AAC, from low-tech tools to advanced brain–computer interface (BCI) systems. Methods: We conducted a scoping review following the PRISMA extension for scoping reviews. PubMed, Web of Science, SciELO, MEDLINE, and CINAHL were screened for studies published up to 31 August 2025. Peer-reviewed RCT, cohort, cross-sectional, and conference papers were included. Single-case studies of invasive BCI technology for ALS were also considered. Methodological quality was evaluated using JBI Critical Appraisal Tools. Results: Thirty-seven studies met inclusion criteria. High-tech AAC—particularly eye-tracking systems and non-invasive BCIs—were most frequently studied. Eye tracking showed high usability but was limited by fatigue, calibration demands, and ocular impairments. EMG- and EOG-based systems demonstrated promising accuracy and resilience to environmental factors, though evidence remains limited. Invasive BCIs showed the highest performance in late-stage ALS and locked-in syndrome, but with small samples and uncertain long-term feasibility. No studies focused exclusively on low-tech AAC interventions. Conclusions: AAC technologies, especially BCIs, EMG and eye-tracking systems, show promise in supporting autonomy in PALS. Implementation gaps persist, including limited attention to caregiver burden, healthcare provider training, and the real-world use of low-tech and hybrid AAC. Further research is needed to ensure that communication solutions are timely, accessible, and effective, and that they are tailored to functional status, daily needs, social participation, and interaction with the environment.
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system, traditionally considered distinct from neuromuscular diseases, which primarily affect the peripheral nervous system, neuromuscular junction, or skeletal muscle. Growing clinical and experimental evidence, however, indicates that certain neuromuscular disorders may coexist with MS or shared overlapping pathophysiological, immunological, and metabolic mechanisms. This narrative review summarizes reported associations between MS and neuromuscular diseases, with particular focus on well-characterized overlaps such as Leber hereditary optic neuropathy (LHON)-associated MS (Harding’s disease), combined central and peripheral demyelination (CCPD), and myasthenia gravis (MG) co-occurring with MS. Additional associations with Charcot–Marie–Tooth disease, mitochondrial disorders with MS-like phenotypes, inherited and autoimmune myopathies, and rare syndromes such as Guillain–Barré syndrome are also discussed. This review highlights proposed mechanisms potentially linking these conditions, including immune dysregulation, T- and B-cell-mediated autoimmunity, antibody-driven demyelination, mitochondrial dysfunction, impaired neuromuscular transmission, and molecular mimicry. Limitations of the current literature are acknowledged, particularly the predominance of case reports for rare associations and the frequent lack of systematic screening for coexisting disorders. By integrating evidence from case series, cohort studies, and mechanistic research, this review provides a comprehensive overview of the biological and clinical intersections between MS and neuromuscular diseases. Enhanced understanding of these overlaps may improve diagnostic accuracy, guide individualized management strategies, and inform future research on shared neuroimmunological and neurodegenerative pathways.
Multiple sclerosis (MS) is a heterogeneous autoimmune disease driven by peripheral immune dysregulation and compartmentalized central nervous system (CNS) inflammation. Despite more than 20 approved disease-modifying therapies, disability accrual remains common, particularly in patients with highly active relapsing disease and progressive phenotypes characterized by silent progression and smoldering neuroinflammation. Two emerging therapeutic strategies address these unmet needs: Bruton’s tyrosine kinase (BTK) inhibitors and autologous haematopoietic stem cell transplantation (HSCT). Although mechanistically distinct, both aim to overcome limitations of conventional immunosuppression by intervening more deeply in the autoimmune cascade. This narrative review synthesized mechanistic, clinical, and translational evidence identified through a comprehensive search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov from January 2010 to August 2025. BTK inhibitors are oral, CNS-penetrant therapies that selectively modulate B-cell signaling and CNS-resident myeloid cells without broad lymphocyte depletion, enabling continuous immunomodulation. Phase II–III trials of evobrutinib, tolebrutinib, and fenebrutinib show consistent MRI activity suppression but variable effects on relapses and disability, suggesting relevance in microglial-driven, relapse-independent disease. HSCT is a one-time immune reconstitution therapy that eradicates autoreactive immune clones and restores immune tolerance. Randomized and real-world studies demonstrate profound suppression of inflammatory activity, stabilization or improvement of disability, and durable treatment-free remission in selected patients with highly active relapsing–remitting MS, although procedure-related risks require strict eligibility criteria and experienced centers. Together with BTK inhibitors, HSCT represents a complementary strategy within an increasingly personalized MS treatment paradigm, emphasizing biomarker-guided patient selection and optimized therapeutic sequencing.
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.
