Sclerosis

Systemic sclerosis (SSc) is a rare, multifactorial autoimmune disease characterized by widespread vascular damage and fibrosis. Pulmonary involvement is a significant manifestation of SSc, contributing to considerable morbidity and mortality. Therefore, identifying reliable biomarkers is of the utmost importance. This review explores emerging biomarkers to enhance diagnostic accuracy, prognostic assessment, and disease monitoring in SSc lung involvement. We discuss recent findings in immunological biomarkers, inflammatory indicators, and other parameters that can function as potential diagnostic and prognostic tools. A comprehensive understanding of these biomarkers could result in earlier and more accurate detection of pulmonary complications in SSc, aiding in timely intervention. Furthermore, we explore the advances in disease monitoring through innovative biomarkers, focusing on their roles in disease activity and treatment response. Integrating these novel biomarkers into current clinical practice and therapeutic protocols through clinical trials can revolutionize the management of SSc-related lung disease, ultimately improving patient outcomes and quality of life. Full article

Multiple sclerosis (MS) is associated with a high prevalence of emotional disorders affecting the health-related quality of life of patients and their families. Pseudobulbar affect (PBA), also referred to as pathological laughing and crying, is an under-recognized and under-treated co-morbidity. We conducted a systematic literature review of 16 studies to determine the prevalence and clinical characteristics of PBA in patients with MS of all ages. Based on conservative figures available from 8/16 studies, the prevalence of PBA in the context of MS was found to range between 2% and 10% (median 10%), with higher percentages in the female population. Possible reasons for the observed variability in the prevalence data include heterogeneity of the diagnostic methodologies and common presence of confounding factors, such as co-morbid affective disorders. The clinical presentation was found to be comparable to that of PBA in the context of other neurological disorders, as it reflected the location of underlying lesions (especially in the brainstem) rather than the associated pathology. Clinicians should be prompted to consider PBA in the differential diagnosis of emotional disorders in the context of MS by using both clinical criteria and psychometric instruments. Further studies should be conducted to develop standardized diagnostic protocols and to optimize therapeutic approaches for the clinical management of this patient population. Full article

Background: This systematic review searched to identify a potential biomarker in serum/plasma or cerebrospinal fluid (CSF) to differentiate between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). There is currently no definitive method for determining whether a patient is in the RRMS course or has converted to the SPMS course. A biomarker could therefore aid the clinician to make this diagnosis. The aim of this study is to assess if there are biomarkers or combinations of biomarkers in serum/plasma or CSF that can detect secondary progression in multiple sclerosis at an early stage. Methods: The PubMed and EMBASE databases were searched to identify relevant studies. Both MeSH terms and text words in the title/abstract were used in both search strategies. The method included forward and backward citation searches. A risk of bias tool was used to assess all the studies that were included. Results: A total of 7581 articles were identified from the initial search. Additionally, 3386 articles were added after the citation search. Of these, 39 articles fulfilled the inclusion criteria and none of the exclusion criteria. The review investigated 28 different biomarkers in CSF and serum/plasma. Discussion: Of the 28 different biomarkers, six biomarkers appeared to be the most promising: neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Galectin-9, YKL-40/CHI3L1, osteopontin, and MCP-1. This review provides new insights into potential directions for future studies to investigate biomarkers as a diagnostic tool for SPMS. Full article

Emerging evidence links dietary interventions to favorable multiple sclerosis (MS) outcomes; however, evidence for the efficacy of dietary interventions on functional disability remains sparse. Data from two 12-week, randomized, controlled pilot trials were pooled to investigate the efficacy of a modified Paleolithic diet (Paleo) on functional disability, as assessed by the MS Functional Composite (MSFC), among people diagnosed with MS. Pooled baseline-referenced MSFC scores were calculated from the nine-hole peg test (NHPT), timed 25-foot walk (T25FW), and Paced Auditory Serial Addition Test (PASAT) Z-scores. There was no significant difference in the mean change in MSFC scores between groups (p = 0.07). In the Paleo group, a significant increase was observed in the MSFC scores (p = 0.03), NHPT (p < 0.001), and PASAT (p = 0.04) Z-scores at 12 weeks, indicating reduced functional disability compared to baseline values. No significant changes were observed within the Control group. Study-specific differences in the MSFC changes between groups were observed. Functional disability was reduced compared to the baseline in the Paleo group, possibly depending on MS type. These results provide preliminary observations on the efficacy of a modified Paleolithic diet for reducing or maintaining functional disability in MS. Full article

Background: Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness and paralysis. Understanding the molecular basis of ALS is crucial for the development of effective therapies. Objective: This study aims to explore the genetic and epigenetic underpinnings of ALS, focusing on the interplay between gene mutations, protein interactions, and epigenetic factors. Methods: We conducted an extensive analysis of key ALS-associated genes including TARDBP, SOD1, ANG, VAPB, and CHMP2B. We used computational tools to assess the functional consequences of identified mutations on neuronal health and explored DNA methylation patterns in gene promoters to investigate epigenetic regulation. Results: Our findings reveal that mutations in ALS-associated genes disrupt critical processes such as amyloid fibril formation and autophagy. We also identified altered DNA methylation patterns, suggesting a mechanism for changes in gene expression linked to ALS. Molecular docking studies highlighted Humulene and Buddledin C as compounds with high binding affinities to the SOD1 enzyme, suggesting their potential to mitigate hallmark features of ALS pathology such as SOD1 aggregation and oxidative stress. Conclusions: Our comprehensive analysis underscores the complexity of ALS pathogenesis, combining genetic, epigenetic, and proteomic approaches. The insights gained not only enhance our understanding of ALS but also pave the way for novel therapeutic strategies, highlighting the importance of integrated approaches in tackling this challenging neurodegenerative disease. Full article

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS). In MS, oligodendrocytes and myelin that surround axons to facilitate transmission of neuronal signals are destroyed by adaptive and innate immune cells, resulting in the formation of demyelinating plaques. For many years, research into MS pathophysiology has identified immune cell populations in lesions such as T cells, B cells, and myeloid and innate lymphoid cells. In this review, we discuss the involvement of these immune cells in MS pathophysiology and demonstrate how findings from histopathology studies and single-cell analyses in animal and human models have identified which immune cell subsets contribute to disease. This knowledge has facilitated the introduction of numerous immune-targeted therapeutics towards CD20, CD52, interferon-beta, sphingosine-1-phosphate receptor, Bruton’s tyrosine kinase, and many more. These treatments have shown effective reduction in new lesion formation and management of symptoms in MS patients. Furthermore, as MS is a chronic disease, these therapeutics slow disease progression, reduce cognitive disabilities, and prevent relapses. Further research is required to develop a cure for MS with limited side effects. The ongoing research that utilises innovative methods to identify and assess MS pathophysiology could transform the treatment landscape for patients in the future. Full article

Cognitive reserve (CR) seems to be an ability to adapt cognitive processes in response to brain disease and may influence rehabilitation outcomes. This is a secondary analysis of the “Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressive MultiplE sclerosis patients” (RAGTIME) trial to investigate the influence of CR on the outcomes after gait rehabilitation in people with multiple sclerosis (PwMS). We included 53 PwMS and severe gait disability (EDSS 6–7). The participants were randomized into two groups to receive either robot-assisted gait training or overground walking (three times/week over four weeks). CR was evaluated by the Cognitive Reserve Index questionnaire (CRIq), which encompasses three sections (CRI Education, CRI Working Activity, and CRI Leisure Time). We stratified the patients using the 115 cut-off CRIq total score of at least a medium-high CR. The outcome measures were Timed 25-Foot Walk, 6 min walking test, Berg Balance Scale, Multiple Sclerosis Impact Scale—29, Multiple Sclerosis Walking Scale—12, Patient Health Questionnaire—9, and Fatigue Severity Scale (FSS). After gait rehabilitation, the FSS was significantly improved in those patients with higher CR compared with the others (F = 4.757, p = 0.015). In our study, CR did not affect the gait, balance, disability perception, and depression. Conversely, it positively influenced the fatigue after gait rehabilitation. Full article

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, this review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS. Full article

Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or problem-solving. While the precise mechanisms involved in the onset and evolution of cognitive decline remain unknown, several risk factors have been associated with intellectual disability. With increasing data on this topic in recent years, the main aim of this review is to summarize the most relevant risk factors correlated with cognitive impairment in multiple sclerosis patients. Firstly, the authors demonstrate the importance of mental disability based on epidemiological data from multiple sclerosis patient cohorts. Subsequently, the intensely debated major risk factors for cognitive decline are discussed, with brief insights into the pathophysiology and possible underlying mechanisms. Finally, the authors describe the impact of medication on cognitive impairment in multiple sclerosis patients, highlighting the main research directions for future studies. Full article

Background: People with Multiple Sclerosis (PwMS) have reported a higher unemployment rate compared to the general population. The complexity of environmental-contextual factors, such as structural and functional social support, may influence employment status (ES). Objectives: to study the relationship between perceived social support and ES, assess the effects of potential mediators, and analyze how these predictors influence components of ES, including absenteeism, work harassment, negative work events, and the use of accommodations. Material and Method: 90 PwMS were recruited. A single-visit assessment included: the Medical Outcomes Study Social Support Survey (MOS-SSS), the Buffalo Vocational Monitoring Survey, the Symbol Digit Modalities Test (SDMT), patient-reported outcomes measuring depression (Beck Depression Inventory-II (BDI-II) and fatigue (Fatigue Severity Scale), and the EDSS. Results: Sixty-three (70%) of PwMS were employed. Mediation analysis revealed the involvement of BDI-II and SDMT in the relationship between social support and ES. The functional social support of friends had a significant effect on absenteeism and NWEs. Total functional support was related to harassment, while family support had a significant effect on accommodations. Conclusion: These results show that structural and functional social support, in relation to the clinical variables of the disease, increase the probability of employment and a better quality of work. Full article

Fatigue is a common symptom in Multiple Sclerosis (MS), and its assessment depends entirely on patient reports. Importantly, managing MS symptoms is increasingly supported by Digital Health Technology (DHT), which includes Mobile Health Technology (mHT). Considering the growing interest, we aimed to synthesise evidence about smartphone applications for the assessment and management of fatigue in MS, as well as to investigate their usability, feasibility, and reliability. We performed a literature search in PubMed, Science Direct, and Embase using a scoping review approach. We included 16 articles and, although many lacked crucial methodological details, DHT was evaluated in all MS clinical subtypes and with disease durations up to more than 20 years. Despite the marked heterogeneity in terms of the employed methods, all documented a high degree of usability, assessed both as feedback from participants and completed tasks. Moreover, the feasibility assessment also showed good results, as apps were able to discriminate between patients with and without fatigue. Importantly, most also showed excellent results in terms of reliability, and some patients reported a reduction in fatigue thanks to mHT. Despite limitations, mHT has been positively evaluated by patients, suggesting a promising role of DHT in the self-management of MS. Full article

Multiple sclerosis is an autoimmune disease that affects the central nervous system. In Brazil, there are currently several therapeutic options for the treatment of this condition, with some being distributed free of charge, while others are not included in the list of free medications. The objective of this article is to provide a pharmacoepidemiological analysis of the available medications in the country, covering their mechanisms of action, the historical context of approval and free distribution within the healthcare system, and their geographical distribution of application. Additionally, we discuss the impact of the inclusion of these medications on hospitalization and mortality rates in the country. We hope that this work serves as a resource for healthcare professionals to better understand pharmacoepidemiology and for health policymakers seeking data for the planning of public policies aimed at the treatment of multiple sclerosis. Full article

This case report describes a 38-year-old female patient with a 3-year history of multiple sclerosis who developed rituximab-induced pancolitis, possibly representing a new onset of inflammatory bowel disease. The patient presented with bloody diarrhea, epigastric pain, fever, and general malaise. Laboratory testing revealed elevated acute inflammation markers, and endoscopy showed deep ulcerations and severe perianal disease. The patient was treated effectively with corticosteroids. Monthly doses of ustekinumab have been administered during follow-up due to perianal disease that has remitted. Rituximab was discontinued and ozanimod was initiated with clinical and analytical stability to date. Full article

While previous studies have described the time course of the dissipation of motor sleep inertia (around 70 min after wake-up time) and motor wake inertia (around 20 min after bedtime) in healthy controls (HCs), the corresponding knowledge for persons with early relapsing–remitting multiple sclerosis (RRMS) is lacking. To fill in this knowledge gap, we carried out a secondary analysis of previously collected data in 35 persons (24 females; mean age = 31.51 ± 7.74 years) with early relapsing–remitting multiple sclerosis (RRMS) and 35 (24 females; mean age = 31.29 ± 8.02) healthy controls (HCs). Each participant wore an actigraphic Micro Motionlogger Watch (Ambulatory Monitoring, Ardlsey, NY, USA) for seven consecutive days. The Functional Linear Modeling statistical framework was adopted to compare the dissipation of motor sleep inertia as well as motor wake inertia between RRMS and HC. As regards motor sleep inertia, no significant differences in motor activity were observed in the first 70 min after the wake-up time; however, with reference to motor wake inertia, the motor activity of RRMS persons was significantly higher than HCs in approximately the first 30 min after bedtime. Despite the small sample size, this pattern of results suggests that the dissipation of motor wake inertia is only slower in persons with RRMS as opposed to HCs. Full article

The aim of this study was to investigate signal patterns and parameters of digital biomarkers in the assessment of mobility in individuals with multiple sclerosis, captured through motion sensors. This is an integrative literature review based on the PRISMA recommendations, which included studies that used wearable technology, such as accelerometers, wearable sensors or inertial sensors, and analyzed mobility/gait-related parameters, such as speed, step count, rhythm, balance, duration and intensity of activity. A total of 1602 studies were identified, of which only 21 were included in the final qualitative synthesis. The main digital biomarkers identified presented signal patterns and parameters captured through different wearable devices, including triaxial accelerometers, inertial sensors, smartphones or smartwatches. The studies employed different objective biomarker reference measures, such as walking speed and step count, and subjective biomarker reference measures, such as fatigue and quality of life assessment scales, for a comprehensive assessment of the participants’ health and mobility. It was found that digital biomarkers play a fundamental role in any individual’s health assessment and protocols. However, it is essential to understand these signals and standardize the choice of the best method to capture signals of high quantity and quality, especially for individuals affected by some neurological pathology. Full article

Lower urinary tract dysfunction is frequently observed in individuals with multiple sclerosis (MS), significantly impacting their quality of life and increasing the risk of upper urinary tract (UUT) damage. Magnetic resonance imaging (MRI) serves as the gold standard imaging technique for identifying demyelinating lesions and aiding in the clinical diagnosis of MS. However, despite its diagnostic utility, the precise relationship between MRI lesions and bladder dysfunction remains poorly established. We aimed to examine the correlation between MRI lesion localizations and both urodynamic parameters and risk factors for UUT damage. In this retrospective study, we conducted a comprehensive review of 201 patients diagnosed with MS who were referred for primary neurourological evaluation, including a videourodynamic study (VUDS). To explore potential significant relationships between the independent variable of MRI lesion localization and the dependent outcome variables, we conducted a multivariate analysis of variance (MANOVA) regression. A significant correlation was observed between the presence of a brainstem lesion and specific urodynamic parameters, including lower maximum cystometric bladder capacity and higher bladder compliance. Similarly, an increased number of diverse MRI lesion localizations demonstrated a significant correlation with these urodynamic parameters. In conclusion, MRI findings did not exhibit a significant association with urodynamic risk factors for UUT damage, thereby limiting their utility in stratifying MS patients for subsequent neurourological assessment and treatment. Full article

Multiple sclerosis (MS) is an autoimmune, neurological, and demyelinating disease of unknown etiology. Neuroinflammation caused by the disease has been associated with air pollution as well as bioclimatic conditions. The aim of this study was to investigate the impacts of air pollution and human thermal discomfort on hospitalizations for multiple sclerosis in Sao Paulo, Brazil, from 2008 to 2015. Generalized Additive Model for Location Scale and Shape (GAMLSS) with Zero Inflated Poisson was used to relate multiple sclerosis hospitalizations in three age groups (less than 30 years old, between 30 and 50 years old, and more than 50 years old) and gender (female and male) with atmospheric pollutants PM₁₀, SO₂, NO₂, NO, and NO_x and thermal discomfort. The results showed that the exposure to an increase of 1 µg/m³ in SO₂ concentration is highly associated with a 10% increase of the risk of MS hospitalization (95% CI: 2–21%) in female patients and a 7.5% (95% CI: 1.5–16%) increase in male patients. PM₁₀ and NO were associated with increased MS risk only for female patients, mainly aged between 30 and 50 years old (2% and 1% increase in hospitalizations, respectively). The cold discomfort was also associated with MS hospitalization, mainly in males (2% increase in hospitalizations; 95% IC: 1–3%). These results are important, since there are few studies that relate air pollution and thermal discomfort with hospitalizations for multiple sclerosis in Brazil. Full article

Extracellular vesicles (EVs) are involved in the regulation of immune system functioning and central nervous system (CNS) homeostasis, suggesting a possible role in multiple sclerosis (MS). Indeed, by carrying several types of mediators, such as cytokines, enzymes, and RNAs, EVs can display both anti- and pro-inflammatory roles on the innate and adaptive immune system, and are involved in several CNS functions, including neuronal plasticity, trophic support, disposal of cellular components, axonal maintenance and neuroprotection. In this review, we provide an overview of the studies carried out to understand the role of EVs in the compromised immune system and CNS functioning typical of MS. Moreover, we also highlight the potential of EVs for the diagnosis of this disorder, thanks to their ability to cross the blood-brain barrier (BBB). In addition, we describe the advances in the use of EVs as therapeutic agents by describing their therapeutic potential. Full article

Multiple sclerosis (MS) is a chronic neurological disease with a global prevalence that has risen over the past decade. The literature suggests that in comparison with a healthy control (HC) group, people with MS experience lower levels of quality of life (QoL). The purpose of this study was (1) to investigate the differences in QoL and a set of psychosocial variables between MS patients and an HC group; (2) to examine the correlations between QoL and psychosocial, sociodemographic, and clinical variables; and (3) to assess the predictive value of a set of psychosocial, sociodemographic, and clinical variables for the QoL of patients with MS. Participants in the clinical group (n = 135) and the HC group (n = 170) filled in a sociodemographic questionnaire and self-report assessments measuring QoL, body appreciation, body acceptance by others, functionality appreciation, body responsiveness, meaning in life, and difficulties in emotion regulation. The results show that the MS group had lower general, physical, psychological, and social QoL than the HC group and that body appreciation, body acceptance by others, body functionality, meaning in life, and difficulties in emotion regulation are important predictors of QoL. Full article