Sclerosis, Volume 3, Issue 2 (June 2025) – 8 articles

Background: Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and fatal neurodegenerative disease that affects the muscles and results in paralysis. The onset and development of ALS involve complex interactions among metabolic signaling, genetic pathways, and external factors (epigenetics). New biomarkers and alternative therapeutic targets have been suggested; nonetheless, the results have been unsatisfactory. Mutations in SOD1, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43) have been identified in sporadic amyotrophic lateral sclerosis and approximately 12–20% of familial amyotrophic lateral sclerosis (fALS). Aim: This review analyzes dysregulated microRNA signaling pathways and their interactions with metabolic pathways in the context of ALS progression. Significance: Despite this, biomarkers remain unreliable, and the current medications prolong life without providing a cure. Some proposed approaches to control ALS progression include balancing autophagy and apoptosis, eliminating aggregated proteins, addressing mitochondrial dysfunction, and reducing inflammation. There is a need for studies on new biomarkers, medications, and therapeutic targets. In this context, deregulated circulating microRNAs are attracting attention for new studies on ALS at various phases of the disease. Despite the extensive literature on microRNAs as potential biomarkers for ALS, the proposition for translational clinical use remains limited. Studies have indicated a significant downregulation or upregulation of microRNAs in the motor neurons of ALS patients compared with those with other neurodegenerative disorders and healthy controls. The microRNA biogenesis highlights the importance of this study. MicroRNAs regulate protein synthesis (translation); all human cells express many microRNAs. The complementary structures of microRNA sequences and their mRNA targets allow them to significantly alter cellular and physiological processes. Studies have examined these microRNAs as potential biomarkers for several physiological states and diseases. Comments: The success of these studies may lead to simple, low-cost, and efficient solutions for controlling the progression of ALS and other degenerative diseases. As a result, it is challenging to identify a specific biomarker with total reliability, as a specific microRNA that is increased in one disease phase can decrease in another. These points require careful consideration. They exhibit several complexities and varied interactions, focusing on mRNA targets. The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Conclusions: The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Full article

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting over 2.8 million people around the world. Artificial intelligence (AI) is becoming increasingly utilised in many areas, including patient care for MS. AI is revolutionising the diagnosis and treatment of MS by enhancing the accuracy and efficiency of both processes. AI algorithms, particularly those based on machine learning, are being used to analyse medical imaging data, such as MRI scans, to detect early signs of MS, monitor disease progression and assess patient treatment response with greater precision. AI can help identify subtle changes in the brain and spinal cord that may be missed by human clinicians, leading to earlier diagnosis and more personalised treatment plans. Additionally, AI is being employed to predict disease outcomes, which could allow clinicians to tailor therapies for individual patients based on their unique disease characteristics. In drug development, AI is accelerating the identification of potential therapeutic targets and the optimisation of clinical trial designs, potentially leading to faster development of new treatments for MS. AI is also playing a critical role in MS fundamental research by promoting efficient analysis of vast amounts of single-cell data. Through these advancements, AI could improve the overall management of MS, offering more timely interventions and better patient outcomes. In this review, we discuss these topics and whether the influence of AI on diagnosis, treatment and research of MS can change the future of this field. Full article

Introduction: Cognitive impairment (CI) is recognized as a very frequent feature of persons with multiple sclerosis (pwMSs). Multiple studies have demonstrated the effectiveness of cognitive rehabilitation (CR) in improving CI linked to cerebral functional connectivity facilitation and increased strategies to cope with daily living activities. Nevertheless, there is considerable heterogeneity in the methodologies and protocols proposed to pwMSs. Aim: This study aimed to establish a current state of CR for pwMSs, among different types of healthcare providers (HCPs) in France. Methods: A Web-based survey was conducted between March and September 2024 among HCPs involved in the care of pwMSs. Results: One hundred and one HCPs involved in the care of pwMSs participated in this survey. CR was considered efficient by 97% of HCPs, especially when multimodal. Based on the responses, CR is proposed mainly following cognitive complaints, for moderate or severe cognitive disorders, and at the onset of the disease (45%). HCPs mentioned several obstacles to the implementation of CR, notably the cost of remediation (37%), and the lack of availability of both professionals (58%) and patients (51%). Conclusions: This rehabilitation requires specific tools combined with psychoeducative advice provided by multidisciplinary HCPs. Full article

Multiple sclerosis (MS) is a chronic and incurable neurological disease of the central nervous system. Three main forms of the disease have been distinguished: relapsing–remitting form (RRMS), secondary progressive form (SPMS), and primary progressive form (PPMS). Currently, in patients with MS, in addition to pharmacotherapy, neurorehabilitation is indicated to improve the motor function of the body and action in the most physiological movement patterns possible. In this therapy, work on lost or incorrect functions is used to provide the patient with self-sufficiency in everyday life. Kinesiotherapy is used as part of neurorehabilitation. This therapy for MS includes coordination exercises aimed at facilitating movement, strengthening exercises and resistance training, balance exercises, improving stability during everyday activities stretching and relaxation exercises, improving tissue elasticity, reducing tension, and breathing exercises. In this article, we present various possibilities for using kinesiotherapy in patients with MS at various stages of disease development. Moreover, we would like to draw attention to the benefits of physical activity leading to a significant improvement in the quality of life in MS patients. We believe that a regular exercise program should be part of the neurorehabilitation program in these patients in the future. Full article

Behavioral activation therapy (BAT) was initially developed to treat depression and was subsequently extended as a transdiagnostic therapy for other psychiatric and neurocognitive disorders. However, research on its impact in people with multiple sclerosis (MS) is lacking. We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living—key components of MS-related quality of life. Our proposed adaptation of the traditional therapy includes a focus on increasing engagement in cognitive, physical, or social activities (activity demand characteristics) to improve cognition and daily life function. In addition, these activities should be individually perceived as energizing, relaxing, or meaningful (subjective activity characteristics) to benefit neuropsychiatric symptoms and social connectedness. Finally, we propose that BAT in MS should specifically focus on reducing stressful activities (i.e., unenjoyable, high-arousal activities) and increasing relaxing activities (i.e., enjoyable, low-arousal activities), as this dimension might tackle the neuroinflammatory etiology of MS. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy, immune dysregulation, and progressive fibrosis affecting the skin and internal organs. Pulmonary complications, including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are major contributors to morbidity and mortality, while skin fibrosis remains a hallmark of disease heterogeneity. Despite advances in understanding SSc pathogenesis, early diagnosis and timely therapeutic intervention remain challenging due to the rapid progression of inflammation and the narrow window before irreversible fibrosis occurs. The identification of reliable biomarkers is crucial for improving diagnosis, monitoring disease activity, and guiding treatment decisions in SSc. While autoantibodies are well-established diagnostic tools, this review focused on non-autoantibody biomarkers, including soluble proteins, cytokines, chemokines, epigenetic modifiers, and oxidative stress indicators. These biomarkers reflect diverse pathogenic mechanisms such as endothelial injury, fibroblast activation, immune signaling, and extracellular matrix remodeling. By examining the available evidence across both clinical and preclinical studies, this review provides an updated overview of molecular markers involved in inflammation and fibrosis in SSc. Understanding their biological significance and therapeutic potential may improve risk stratification, guide targeted interventions, and ultimately contribute to the development of precision medicine strategies in systemic sclerosis. Full article

Introduction: Approximately 80% of individuals with multiple sclerosis (MS) have a positive response to autologous hematopoietic stem cell transplantation (aHSCT). Markers that may predict the transplant outcome are necessary. The objective of this work is to identify markers that may refine the selection of patients with multiple sclerosis who could benefit from aHSCT. Methods: We evaluated the levels of six biomarkers in the peripheral blood of patients with MS before aHSCT. The design of this study is cross-sectional; patients were divided into two transplant-responses-at-12-months groups, responders (ΔEDSS < 0) and non-responders (ΔEDSS > 0). Pre-transplant samples were used to assess the different markers. Results: Thirty-four patients were enrolled: fourteen were non-responders and twenty were responders to aHSCT. Among the evaluated biomarkers, a significant difference was only detected in miR-146a levels, with increased values in the non-responder group. Conclusions: The biomarker miR146a could be useful to evaluate the response to aHSCT in patients with MS. Full article

Background/Objectives: Health locus of control (LOC) refers to one’s perceptions of who or what controls one’s health. Recent evidence has found that chance LOC (CLOC) is associated with improved quality of life (QoL) in multiple sclerosis (MS). The purpose of the current study was to identify mediators and moderators of the LOC-QoL relationship in MS. Methods: For this study, 5266 participants with MS completed a questionnaire pack that included the Multidimensional Health Locus of Control Scale, the Unidimensional Self-Efficacy Scale for MS (USE-MS), and the World Health Organization Quality of Life Scale—BREF (WHOQoL-BREF). The relationship between LOC and QoL was examined within a structural equation model (SEM). Results: In the total sample, self-efficacy was found to fully mediate the relationship between LOC and QoL for both internal (ILOC) and CLOC orientations. Powerful others LOC (PLOC) had no association with QoL. The same results were found for the relationship of LOC to functioning. In the secondary progressive MS subgroup, the relationship between CLOC and QoL was only partially mediated by self-efficacy. Conclusions: LOC influences QoL through its impact on self-efficacy, one of several potentially mediating factors between LOC and QoL in MS. Disability did not moderate the associations of LOC, but moderation of the CLOC-QoL relationship by disease subtype was found. Psychological training to improve self-efficacy in MS may be particularly useful in those subgroups where LOC-QoL is largely mediated by self-efficacy. Full article