Search Results (166)

Background/Objectives: Gut dysbiosis has been implicated in multiple sclerosis (MS), but microbial signatures remain inconsistent across studies. Machine learning (ML) algorithms based on global microbiome data integration can reveal key disease-associated microbial biomarkers and new insights into MS pathogenesis. This study aimed to investigate gut microbial signatures associated with MS and to evaluate the potential of ML for diagnostic applications. Methods: Fecal samples from 29 relapsing–remitting MS patients during exacerbation and 27 healthy controls were analyzed using 16S rRNA gene sequencing. Differential abundance analysis was performed, and data were integrated with 29 published studies. Four ML models were developed to distinguish MS-associated microbiome profiles. Results: MS patients exhibited reduced levels of Eubacteriales (p = 0.037), Lachnospirales (p = 0.021), Oscillospiraceae (p = 0.013), Lachnospiraceae (p = 0.012), Parasutterella (p = 0.018), Faecalibacterium (p = 0.004), and higher abundance of Lachnospiraceae UCG-008 (p = 0.045) compared to healthy controls. The Light Gradient Boosting Machine classifier demonstrated the highest performance (accuracy: 0.88, AUC-ROC: 0.95) in distinguishing MS microbiome profiles from healthy controls. Conclusions: This study highlights specific microbiome dysbiosis in MS patients and supports the potential of ML for diagnostic applications. Further research is needed to elucidate the mechanistic role of these microbial alterations in MS progression and their therapeutic utility. Full article

Multiple sclerosis (MS) is a chronic progressive neurodegenerative disease that leads to disabilities such as difficulty moving and slowed cognitive processing. It is the leading non-traumatic cause of disability worldwide. MS also has a high potential to become a model for neurodegenerative diseases with a progression like Alzheimer’s or Parkinson’s. Cardiovascular diseases (CVDs) remain the leading cause of global deaths and have a considerable economic impact. The higher incidence of cardiovascular comorbidities in patients with MS compared to healthy individuals of the same age worsens the prognosis of neurological pathology, leading to a higher level of disability, poorer physical outcomes, higher depression scores, cognitive aging, and diminished quality of life. Classical observational studies often have questionable elements that can represent a source of error, making it difficult to establish a causal relationship between MS and CVD. Genetic studies, including genome-wide evaluation, may resolve this issue and may represent a topic for future research. We report the case of a 31-year-old male patient with a history of multiple sclerosis (MS) diagnosed seven years prior, who presented with acute chest pain upon returning from vacation. Despite the previous recommendation for disease-modifying therapy, the patient had discontinued treatment by personal choice. Electrocardiography (ECG) revealed ST-segment elevation in inferior leads, and emergent coronary angiography identified severe multi-vessel coronary artery disease (CAD), requiring immediate revascularization. This case highlights the potential cardiovascular risks in young patients with MS and the importance of continuous medical supervision. Full article

Cognitive impairment is common but often overlooked in patients with inflammatory demyelinating diseases such as multiple sclerosis and neuromyelitis optica spectrum disorder. The conventional assessments may fail to detect subtle deficits and require substantial time and expertise. We collected neuropsychological scores and real-time handwriting data across nine drawing tasks and tasks from the Symbol Digit Modalities Test in 93 patients. Temporal, pressure, and kinematic features were extracted, and machine learning classifiers were trained using five-fold cross-validation with bootstrap confidence intervals. The response timing and pen pressure metrics correlated significantly with global cognitive scores (|r| = 0.30–0.37, p < 0.01). A support vector machine using eight selected features achieved an area under the receiver-operating characteristic curve (AUC) of 0.910, and a streamlined five-feature variant maintained an equivalent performance (AUC = 0.921) while reducing the assessment time by 35%. These results indicate that digital handwriting metrics can complement the standard screening by capturing fine motor and temporal characteristics overlooked in conventional testing. Validation in larger, disease-balanced, and longitudinal cohorts is needed to confirm their clinical utility. Full article

Background: Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly understood more than four decades after exposure. Methods: In this case-control study, 50 individuals with clinically confirmed TOS were compared to 50 healthy controls matched for age, sex, and education. All participants completed a comprehensive neuropsychological assessment, along with questionnaires evaluating fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models were adjusted for demographic and vascular risk factors, as well as for mood symptoms, fatigue, and use of central nervous system-acting medications. Structural equation modeling was used to explore the potential mediating effects of affective and fatigue symptoms on cognitive performance. Results: TOS survivors showed significantly poorer performance than controls in attention, executive function, processing speed, and global cognition after adjusting for demographic and vascular risk factors. However, these differences were no longer statistically significant after additional adjustment for fatigue, depression, anxiety, and central nervous system-acting medications. Structural equation modeling analyses revealed that affective symptoms—particularly fatigue—substantially mediated the relationship between TOS and cognitive performance. Conclusions: The cognitive profile observed mirrors that of disorders characterized by subcortical dysfunction and impaired neural connectivity, such as multiple sclerosis and vascular cognitive impairment. Although early postmortem studies in TOS did not demonstrate overt white matter lesions, our findings raise the possibility of long-lasting alterations involving both white and gray matter networks. These results emphasize the need to consider mood and fatigue symptoms when evaluating cognition in TOS survivors and point to the potential for widespread, enduring neurobiological effects stemming from the original toxic exposure. Full article

Neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors—oligodendrocyte progenitor cells (OPCs)—in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity—manifesting as demyelination, hypomyelination, or dysmyelination—have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances. Full article

Background: Recent studies indicate that in progressive multiple sclerosis (MS)—an inflammatory and degenerative disease of the central nervous system—the biological pathways associated with these effects remain poorly understood. Changes in body weight, whether presenting as overweight or underweight, as well as alterations in adipose and muscle tissue, together with chronic inflammation, may contribute to the disease and influence its course. Objective: This case–control study aimed to measure inflammatory markers and myokine levels (myostatin and irisin), brain-derived neurotrophic factor (BDNF), and IL-6 in the serum of patients with multiple sclerosis and healthy control and assess whether the myokines and cytokines are associated with nutritional status. Methods: The study included 92 MS patients and 75 healthy volunteers. Nutritional status was assessed using the NRS (Nutritional Risk Screening) 2002 and GLIM (Global Leadership Initiative on Malnutrition) criteria. The risks of malnutrition or malnutrition were diagnosed based on ESPEN recommendations. Body composition analysis was performed using the BIA method with the InBody 120 analyzer. Routine laboratory parameters (albumin, lipidogram) were measured. Myostatin, irisin, BDNF, IL-6, and hsCRP were measured using ELISA methods. Statistical analysis was conducted using Statistica 13.0 software. Comparisons between the two groups were conducted using Student’s t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables; the differences between groups were calculated using either ANOVA or the Kruskal–Wallis test. Post hoc analysis by the Bonferroni method was applied. Results: In the MS group, high risks of malnutrition (69.0%) and malnutrition (14.0%) were observed. A statistically significant correlation was found between malnutrition (GLIM) and s-albumin (R = 0.2; p < 0.05) and hsCRP (R = 0.23; p < 0.05). The MS patient group displayed significantly lower levels of irisin, higher levels of hsCRP, and lower s-albumin compared to healthy volunteers. Malnourished patients with MS exhibited significantly lower irisin levels, as well as higher hsCRP in comparison to MS patients who were at risk or well nourished. The levels of myostatin, BDNF, and IL6 did not differ depending on nutritional status. Irisin correlated with hsCRP (R Spearman = −0.5; p = 0.01). Conclusions: Our findings highlight the interplay between chronic inflammation, nutritional status, and myokines level in multiple sclerosis. Full article

Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), atherosclerosis, and inflammatory bowel disease (IBD), pose major global health concerns. These disorders are marked by persistent inflammation, immune system dysfunction, tissue injury, and fibrosis, ultimately leading to severe organ dysfunction and diminished quality of life. Osteopontin (OPN), a multifunctional extracellular matrix protein, plays a crucial role in immune regulation, inflammation, and tissue remodeling. It promotes immune cell recruitment, stimulates pro-inflammatory cytokine production, and contributes to fibrosis through interactions with integrins and CD44 receptors. Additionally, OPN activates key inflammatory pathways, including NF-κB, MAPK, and PI3K/Akt, further aggravating tissue damage in chronic inflammatory conditions. Our review highlights the role of OPN in chronic inflammation, its potential as a biomarker, and its therapeutic implications. We explore promising preclinical approaches, such as monoclonal antibodies, small molecule inhibitors, and natural compounds like curcumin, which have demonstrated potential in mitigating OPN-driven inflammation. However, challenges persist in selectively targeting OPN while maintaining its essential physiological roles, including bone remodeling and wound healing. Our review offers insights into therapeutic strategies and future research directions. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune condition that impacts the central nervous system and has a rising incidence globally, especially in Saudi Arabia. Materials and Methods: This study examines environmental, lifestyle, and familial risk factors associated with MS in the Aljouf Region by a cross-sectional analysis of 155 clinically diagnosed MS patients. Data were gathered using structured questionnaires and medical record examinations to evaluate sociodemographic characteristics, sun exposure, smoking, obesity, eating habits, and childhood infections. Results: Logistic regression research found insufficient daily sun exposure (<15 min/day), smoking, obesity, and childhood measles infection as significant risk factors, but substantial weekend sun exposure (>4 h/day), exclusive breastfeeding, and regular fish consumption were deemed protective. While familial history of MS was statistically significant (5.5%, p = 0.04), parental consanguinity (38.7%) did not show a significant association with MS risk (p = 0.07). Conclusions: The findings underscore the complex nature of MS and the pressing necessity for preventive efforts, such as advocating for vitamin D supplementation, smoking cessation, obesity prevention, and dietary adjustments. Mitigating these controllable risk factors may alleviate the prevalence of MS in Saudi Arabia. Full article

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), represent a significant challenge to global health due to their progressive nature and the absence of curative treatments. These disorders are characterized by oxidative stress, protein misfolding, and neuroinflammation, which collectively contribute to neuronal damage and death. Recent advancements in nanotechnology have introduced nanozymes—engineered nanomaterials that mimic enzyme-like activities—as promising therapeutic agents. This review explores the multifaceted roles of nanozymes in combating oxidative stress and inflammation in neurodegenerative conditions. By harnessing their potent antioxidant properties, nanozymes can effectively scavenge reactive oxygen species (ROS) and restore redox balance, thereby protecting neuronal function. Their ability to modify surface properties enhances targeted delivery and biocompatibility, making them suitable for various biomedical applications. In this review, we highlight recent findings on the design, functionality, and therapeutic potential of nanozymes, emphasizing their dual role in addressing oxidative stress and pathological features such as protein aggregation. This synthesis of current research underscores the innovative potential of nanozymes as a proactive therapeutic strategy to halt disease progression and improve patient outcomes in neurodegenerative disorders. Full article

Background: Malnutrition in amyotrophic lateral sclerosis (ALS) is associated with disease severity, and epigenetic regulation may be involved. The aim of this study was to assess the methylation levels of specific DNA sequences from the nuclear and mitochondrial genomes in a population with ALS to elucidate their relationship with nutritional status and the evolution of the disease. Methods: Patients with ALS were evaluated between 2013 and 2021 (n = 66). They were categorized according to their nutritional status, using the Global Leadership Initiative on Malnutrition (GLIM) criteria, and disease progression, using the ALS Functional Rating (ALSFRS-R) Scale. DNA samples were extracted from leukocytes at the time of diagnosis for analysis of DNA methylation levels of markers of oxidative stress, mitochondrial function and global methylation (D-loop, GSTP1, and LINE-1). Results: According to the GLIM criteria, 29 (43.9%) patients had malnutrition (22.7%—moderate; 21.2%—severe), which was positively correlated with ALS disease progression (r = 0.414; p < 0.01) and death (r = 0.687; p < 0.01). Mortality occurred in 43.9% of the patients (median time to death, 18.7 (1.7–82.7) months). A significant association was observed between DNA methylation levels of the D-loop, GSTP1, and the CpG1 site of LINE-1 and malnutrition, disease progression at diagnosis, and death. The D-loop was the best predictor of malnutrition (AUC, 0.79; p < 0.01), disease progression (AUC, 0.70; p < 0.01), and mortality (AUC, 0.71; p < 0.01). Conclusions: This study revealed, for the first time, the early detection of D-loop methylation levels as a potential biomarker of nutritional status in patients with ALS, which may be useful for personalized nutritional management aimed at counteracting disease progression. Full article

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology—including tau accumulation, amyloid dysregulation, and microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain’s role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification. Full article

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and prion disease, represent a group of age-related disorders that pose a growing and formidable challenge to global health. Despite decades of extensive research that has uncovered key genetic factors and biochemical pathways, the precise molecular mechanisms underlying these diseases and effective therapeutic strategies remain elusive. Caenorhabditis elegans (C. elegans) has emerged as a powerful model organism for studying NDDs due to its unique biological features such as genetic tractability, conserved molecular pathways, and ease of high-throughput screening. This model provides an exceptional platform for identifying molecular targets associated with NDDs and developing novel therapeutic interventions. This review highlights the critical role of C. elegans in elucidating the complex molecular mechanisms of human NDDs, with a particular focus on recent advancements and its indispensable contributions to the discovery of molecular targets and therapeutic strategies for these NDDs. Full article

Background/Objectives: The COVID-19 pandemic disrupted healthcare systems globally, altering the management of chronic conditions like multiple sclerosis (MS) and interrupting the regular monitoring and support that people with MS (pwMS) typically need. The aim of this study was to examine changes in the utilization of MS healthcare resources over various periods during the COVID-19 pandemic in 2020 and 2021, and to assess how these changes affected the perceptions of pwMSregarding their care. Methods: A longitudinal survey study was conducted at the MS Center at the University Hospital Dresden, Germany, involving four survey periods from April 2020 to December 2021. The study assessed the use of healthcare resources, including consultations with specialists, the use of rehabilitative therapy facilities, and unmet healthcare needs, across various phases of the pandemic, encompassing both lockdown and less restrictive periods. Results: At the onset of the pandemic in April 2020, during the first lockdown, 750 questionnaires were evaluated. While most pwMS reported consistent medical care compared with pre-pandemic levels, 19.2% had fewer general practitioner visits, and 10.6% fewer neurologist visits. During the follow-up survey periods, the use of medical care generally remained stable, although there were notable reductions reported by a subset of participants. Conclusions: The findings suggest that medical and therapeutic care for pwMS in Germany remained largely accessible during the COVID-19 pandemic in 2020 and 2021. However, the study also reveals certain gaps in care that may be addressed by incorporating digital technologies into medical care and rehabilitation, potentially enhancing the management of healthcare during future pandemics or similar situations. Full article

Diet is considered a possible cofactor, which affects the immune system and potentially causes dysregulation of intestinal homeostasis and inflammation. This study aimed to review the quality of evidence on the effects of specific diet composition on symptoms of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis (RA), spondyloarthritis, multiple sclerosis (MS), inflammatory bowel disease (IBD) [remission maintenance of Crohn’s disease and ulcerative colitis], psoriasis and psoriatic arthritis in adult patients. We conducted a review of meta-analyses and Cochrane systematic reviews using PubMed and EMBASE, from inception to September 2024, and Google Scholar. The methodological quality of the meta-analyses was assessed using the AMSTAR 2 rating system. Three Cochrane systematic reviews and eight meta-analyses were evaluated. Some specific composition diets have been shown to reduce the symptoms of RA, IBD, and MS and improve activity parameters in IBD and RA, with critically low or low levels of evidence. The reduction in inflammatory biomarker levels is unclear. This review summarizes the global evidence for specific dietary interventions, mostly with anti-inflammatory properties due to their components, to improve IMID symptoms, clarifying the weaknesses of clinical trials and dietary meta-analyses with critically low or low levels of evidence; and shows the need to use indices such as the Dietary Inflammatory Index, which allows diets to be classified by their pro-inflammatory or anti-inflammatory food content, to better compare diet groups in clinical trials. The difficulty of obtaining high-level evidence from dietary studies is apparent and may delay the application of the results. Clinicians should be aware of the role of diets with anti-inflammatory properties as a complement to pharmacological treatments in IMIDs. Full article