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Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, neurodegenerative disease of the central nervous system, significantly impacting patients’ quality of life. Understanding patient and healthcare professional (HCP) preferences for MS treatments is crucial for optimizing therapeutic strategies and improving adherence and outcomes. This Discrete-Choice Experiment (DCE) assesses preferences for various MS treatment attributes among Italian patients and HCPs. The sample included 1069 patients and 186 HCPs. Key attributes evaluated were treatment administration route, frequency, location, and Patient-Reported Outcome Measures (PROMs), such as cognitive impairment, fatigue, and mobility. Data were collected through questionnaires and responses were analyzed to determine the relative importance (RI) and utility of each attribute. Both patients and HCPs highly prioritized PROMs, with cognitive impairments and walking ability being the most critical factors. Patients showed a strong preference for oral administration and treatments administered biannually at home, whereas HCPs preferred hospital-based treatments. The “Time to Progression” attribute was more significant for HCPs than for patients, reflecting different priorities between the groups. The study highlighted the importance of treatment convenience, with patients favoring less-frequent administration schedules and home-based treatment options. This study underscores the necessity of incorporating both patient and HCP perspectives into MS treatment planning. Shared decision-making, which considers individual preferences, can enhance treatment adherence and outcomes. These insights into treatment preferences provide valuable guidance for personalized MS care, aiming to improve patient quality of life and optimize therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background: A strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment. Methods: In this retrospective cross-sectional study, 258 serum samples were included consisting of EBV-negative (n = 25) and EBV-positive (n = 36) controls, 192 MS samples including untreated relapsing-remitting MS (RRMS) with and without relapses, secondary progressive MS (SPMS) and primary progressive MS (PPMS) patients, and 106 patients on 8 different treatment regimens. IgG and IgM antibody titers against EBV docking/fusion proteins (gp350, gh/gp42, gh/gL/gp42), immediate early antigen (BZLF1), early antigens (EA p85, EA P138, EA P54), capsid antigens (VCA P18, VCA P23, VCA gp125) and late antigens (EBNA1) were measured. Specific EBNA1 and GlialCAM, CRYAB and ANO2 peptides were synthesized and also incorporated in our custom magnetic bead based multiplex assay. Results: We observed significantly elevated IgG antibody titers in EBV-positive controls, RRMS with and without relapse, SPMS and PPMS patients for all lifecycle antigens except for several early antigens when compared to EBV-negative controls. Significantly higher IgG antibody titers were observed in RRMS patients for fusion proteins and EBNA1 peptides when compared to EBV-positive controls. An MS specific response was observed for ANO2 but not for GlialCAM or CRYAB. No significant treatment effects or a specific IgM response were detectable. Conclusion: The MS-specific, differential antibody response to EBV antigens confirms an altered immunological response to EBV in MS patients. EBV reactivation does not appear to play an important role in MS pathogenesis and no differential antibody signatures were observed between MS disease phases. The MS-specific anti-ANO2 antibody response suggests a potential role for EBNA1 as an antigenic driver, although the exact role of anti-ANO2 antibodies needs to be determined. The precise pathophysiological role of EBV in MS remains uncertain and requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS causes many changes in the lives of its patients, forcing them to renegotiate their lives. Part of these changes are related to patients' self- and others- mental representations. Despite the importance of mental representations in changes caused by or adaptation to MS, limited research has been conducted to examine the mental representations of people with MS. Methods: This study examines the mental representations that Healthy Controls (HC) and people with MS (PWMS) have of themselves and others, including childhood and current self-images, as well as those of their mothers, love partners, and close friends. In both groups (HC (n = 82) and PWMS (n = 82)), participants completed demographic variables as well as a modified version of the comfortable interpersonal distance (CID) task in both passive (when protagonists approached them) and active modes (when participants approach protagonists). Participants estimated the point at which they felt discomforted. Results: The PWMS group preferred a significantly larger interpersonal distance than the HC group for both current self-image and love partner. There is no difference between the two groups in preferring interpersonal distance from their childhood self-image, mother, and friends. Conclusions: Based on the research results, it seems that PWMS experience a kind of alienation at the level of self-mental representations. This research can be helpful in modifying MS interventions and increasing the engagement of support systems. [ABSTRACT FROM AUTHOR]

The failure of endogenous repair mechanisms is a key characteristic of neurological diseases, leading to the inability to restore damaged nerves and resulting in functional impairments. Since the endogenously regenerative capacity of damaged nerves is limited, the enhancement of regenerative potential of quiescent neural stem cells (NSCs) presents as a therapeutic option for neural diseases. Our previous studies have shown exciting progress in treating sciatic nerve injury in mice and rats using NSCs in conjunction with neurotrophic factors such as fibroblast growth factor 1 (FGF1). Additionally, a recently discovered neurotrophic factor, IL12p80, has shown significant therapeutic effects in sciatic nerve injury repair via myelinating oligodendrocytes. IL12p80 induces oligodendrocyte differentiation from NSCs through phosphorylation of Stat3. Therefore, it might be possible to alleviate the myelination defects of oligodendrocytes in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and even schizophrenia through the administration of IL12p80. These applications could shed light on IL12p80 and FGF1, not only in damaged nerve repair, but also in rectifying the oligodendrocytes' defects in neurodegenerative diseases, such as ALS and MS. Finally, the synergistic effects of neurogenesis-induced FGF1 and myelination-induced IL12 might be able to supplant the need of NSCs for nerve repair and neuroregeneration. [ABSTRACT FROM AUTHOR]

This case highlights the importance of considering Neuro‐Behçet's disease (NBD) in the differential diagnosis of multiple sclerosis (MS), particularly in patients presenting with neurological manifestations, abnormal magnetic resonance imaging (MRI) findings, and systemic symptoms consistent with Behçet's disease (BD). [ABSTRACT FROM AUTHOR]

Background and Objectives: The main aim of this study was to evaluate the impact of cervical pain on the quality of life of patients with multiple sclerosis in comparison with a group of healthy people (without diseases of the Central Nervous System). Materials and Methods: Data were collected at the Specialist Hospital St. Łukasz in Końskie (Poland) in the period from November 2023 to August 2024. The inclusion criteria for this study were as follows: age (20–50 years), women and men, healthy people (without diseases of the Central Nervous System) and people suffering from multiple sclerosis. People from the study group were diagnosed according to the McDonald criteria and tested with the EDSS. The mobility of the cervical spine was measured, and neck pain was assessed using the following: Visual Analogue Scale (VAS), Laitinen Scale and the Neck Disability Index (NDI). All participants self-assessed their quality of life using EuroQol 5D-5L (EQ-5D-5L). Results: 80 people took part in this study, the vast majority of whom were women (71.3%). The most common form of multiple sclerosis was relapsing-remitting (75.0%), and the average EDSS score was higher in the male group (1.6 ± 1.8). Cervical spine pain was reported by 27 people from the study group (67.5%) and 16 people from the control group (40.0%). In both groups, the cervical spine mobility was lower in people with neck pain. The level of cervical spine pain was statistically significantly (p < 0.05) higher in women, people living in small towns and in people with multiple sclerosis, depending on the type of disease and its duration. Cervical spine pain in people with multiple sclerosis was higher in all three scales (VAS mean = 5.7, ES = 0.79; Laitinen Scale mean = 10.1, ES = 0.60; and NDI Scale mean = 21.1, ES = 0.89). The study group obtained significantly higher scores on the EQ-5D scale (mean = 15.3; ES = 0.79) and EQ-VAS (mean = 53.2; ES = 0.94). Conclusions: This study proved that cervical spine pain is more common among people with multiple sclerosis. In these people, this problem is rarely diagnosed and properly treated. [ABSTRACT FROM AUTHOR]

Background: While standard clinical assessments provide great value for people with multiple sclerosis (PwMS), they are limited in their ability to characterize patient perspectives and individual-level symptom heterogeneity. Objectives: To identify PwMS subgroups based on patient-reported outcomes (PROs) of physical, cognitive, and emotional symptoms. We also sought to connect PRO-based subgroups with demographic variables, functional impairment, hypertension and smoking status, traditional qualitative multiple sclerosis (MS) symptom groupings, and neuroperformance measurements. Methods: Using a cross-sectional design, we applied latent profile analysis (LPA) to a large database of PROs; analytic sample N = 6619). Results: We identified nine distinct MS subtypes based on PRO patterns. The subtypes were primarily categorized into low, moderate, and high mobility impairment clusters. Approximately 70% of participants were classified in a low mobility impairment group, 10% in a moderate mobility impairment group, and 20% in a high mobility impairment group. Within these subgroups, several unexpected patterns were observed, such as high mobility impairment clusters reporting low non-mobility impairment. Conclusions: The present study highlights an opportunity to advance precision medicine approaches in MS. Combining PROs with data-driven methodology allows for a cost-effective and personalized characterization of symptom presentations. that can inform clinical practice and future research designs. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS causes many changes in the lives of its patients, forcing them to renegotiate their lives. Part of these changes are related to patients’ self- and others- mental representations. Despite the importance of mental representations in changes caused by or adaptation to MS, limited research has been conducted to examine the mental representations of people with MS. Methods This study examines the mental representations that Healthy Controls (HC) and people with MS (PWMS) have of themselves and others, including childhood and current self-images, as well as those of their mothers, love partners, and close friends. In both groups (HC (n = 82) and PWMS (n = 82)), participants completed demographic variables as well as a modified version of the comfortable interpersonal distance (CID) task in both passive (when protagonists approached them) and active modes (when participants approach protagonists). Participants estimated the point at which they felt discomforted. Results The PWMS group preferred a significantly larger interpersonal distance than the HC group for both current self-image and love partner. There is no difference between the two groups in preferring interpersonal distance from their childhood self-image, mother, and friends. Conclusions Based on the research results, it seems that PWMS experience a kind of alienation at the level of self-mental representations. This research can be helpful in modifying MS interventions and increasing the engagement of support systems.

Despite the considerable progress in mesenchymal stem/stromal cells (MSCs)-based novel intervention of multiple sclerosis (MS), yet the disease-modifying effect of VCAM-1− MSCs and novel VCAM-1+ counterpart is largely obscure. In this study, we took advantage of the EAE mouse model and VCAM-1+ human umbilical cord-derived MSCs (hUC-MSCs) for the evaluation of the therapeutic effect of systematic MSCs infusion. On the one hand, we compared the protective effect of VCAM-1− and VCAM-1+ hUC-MSCs against the clinical symptoms, demyelination, active glia cells and neuroinflammation in EAE mice by conducting multifaceted detections upon spinal cord and brain tissues. On the other hand, we conducted RNA-sequencing (RNA-SEQ) and multidimensional bioinformatics analyses for the evaluation of the transcriptomic features of spinal cord tissue in EAE mice after systematic hUC-MSCs infusion. Compared to those with VCAM-1− hUC-MSCs injection, VCAM-1+ mice showed further remission in clinical manifestations, and in particular, the inflammatory infiltration and active glial cells. Mice in all groups revealed conservations in overall gene expression profiling and somatic mutation spectrum. The differentially expressed genes (DEGs) between EAE mice and those with hUC-MSCs infusion were mainly involved in neuroinflammation and inflammatory response. Our findings indicated the feasibility of VCAM-1+ hUC-MSCs for multiple sclerosis treatment, which would supply new references for the development of novel VCAM-1+ MSCs-based cytotherapy in future. [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) is an inflammatory condition that affects the optic nerve and may be associated with various central nervous system demyelinating conditions, infectious diseases, and systemic autoimmune syndromes. This manuscript sheds light on the epidemiologic patterns and diverse clinical features of ON, emphasizing the importance of early detection and prompt treatment. Various studies have revealed geographic and ethnic variations across ON subtypes, which are likely related to the incidence and prevalence of co-associated disorders. Distinguishing ON subtypes may be challenging and requires use of paraclinical tools. Treatment strategies differ depending on the etiology, further highlighting the importance of accurately identifying specific ON subtypes in a timely manner.

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics’ Target 96 Inflammation panel and correlated the resulting analytes with respect to (1) disease subtype, (2) patient age and sex, (3) extent of clinical disability, and (4) MRI segmental brain volumes. We found that intrathecal IL-4 correlated with higher Expanded Disability Status Scale (EDSS) scores and longer 25-foot walk times, and CD8A correlated with decreased thalamic volumes and longer 9-hole peg test times. Male sex was associated with higher FGF-19 expression, and Tumefactive MS with elevated CCL4. Several inflammatory markers were correlated with older age at the time of LP. Finally, higher intrathecal IL-33 correlated with increased MS lesion burden and multi-compartment brain atrophy. This study confirms immune heterogeneity underlying CSF profiles in MS, but also identifies several inflammatory protein biomarkers that may be of use for predicting clinical outcomes in future algorithms.

Background and Aim: Multiple Sclerosis (MS) is a chronic autoimmune disease that destroys the myelin of the central nervous system, gradually impairing bodily functions and balance. This study aims to predict rumination based on anxiety sensitivity and alexithymia, with lifestyle acting as a mediating factor in women with MS. Methods: This correlational descriptive study employed a simple random sampling method to select 158 women with MS from the Iranian MS Patients Association in Tehran, Iran, in 2022. Participants completed the Ruminative Response Scale (Nolen-Hoeksema & Morrow, 1991), Anxiety Sensitivity Index (Reiss et al., 1986), Toronto Alexithymia Scale (TAS-20, Bagby et al., 1994), and Laali et al. lifestyle questionnaires. Data were analyzed using Pearson's correlation coefficient tests, hierarchical regression analysis in SPSS version 26, and path analysis in Lisrel version 10. Results: In women with MS, anxiety sensitivity and alexithymia showed a positive correlation with rumination, while lifestyle had a negative correlation with rumination (P < 0.001). Lifestyle played a mediating role in the relationship between anxiety sensitivity, alexithymia, and rumination (P < 0.001). Conclusion: Anxiety sensitivity and alexithymia, through their influence on lifestyle, contribute to the rumination experienced by women with MS. To reduce rumination in this population, it is suggested that healthcare professionals specializing in MS should address anxiety sensitivity and alexithymia while promoting a healthy lifestyle among their patients.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, which is a primary cause of neurological disability in young and middle‐aged individuals in economically developed nations. Although MS is more prevalent and of ever‐increasing incidence in developed countries, patients with MS in developing nations confront unique challenges marked by significant economic and social burdens due to their limited access to the advanced diagnostic and treatment resources that are available in developed regions. Timely diagnosis is paramount for effective intervention in MS cases. Regrettably, there is limited availability of neuroimaging evaluations in low‐ and middle‐income nations, prompting the need to obtain alternative diagnostic approaches. In this article, we provide an overview of the worldwide epidemiology of MS, delving into associated risk factors, and examining serological biomarkers as alternatives to imaging. It is, therefore, imperative that strategies for the early diagnosis and treatment of MS are implemented in low‐ and middle‐income countries. This will lead to improved prognoses and quality of life, with a particular focus on enhancing outcomes. [ABSTRACT FROM AUTHOR]

Background: Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. Objectives: We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Methods: Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. Results: A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). Conclusions: This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by central nervous system demyelination and axonal degeneration. Fatigue affects a major portion of MS patients, significantly impairing their daily activities and quality of life. Despite its prevalence, the mechanisms underlying fatigue in MS are poorly understood, and measuring fatigue remains a challenging task. This study evaluates the efficacy of automated speech analysis in detecting fatigue in MS patients. MS patients underwent a detailed clinical assessment and performed a comprehensive speech protocol. Using features from three different free speech tasks and a proprietary cognition score, our support vector machine model achieved an AUC on the ROC of 0.74 in detecting fatigue. Using only free speech features evoked from a picture description task we obtained an AUC of 0.68. This indicates that specific free speech patterns can be useful in detecting fatigue. Moreover, cognitive fatigue was significantly associated with lower speech ratio in free speech (p = -0.283, p = 0.001), suggesting that it may represent a specific marker of fatigue in MS patients. Together, our results show that automated speech analysis, of a single narrative free speech task, offers an objective, ecologically valid and low-burden method for fatigue assessment. Speech analysis tools offer promising potential applications in clinical practice for improving disease monitoring and management. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics’ Target 96 Inflammation panel and correlated the resulting analytes with respect to (1) disease subtype, (2) patient age and sex, (3) extent of clinical disability, and (4) MRI segmental brain volumes. We found that intrathecal IL-4 correlated with higher Expanded Disability Status Scale (EDSS) scores and longer 25-foot walk times, and CD8A correlated with decreased thalamic volumes and longer 9-hole peg test times. Male sex was associated with higher FGF-19 expression, and Tumefactive MS with elevated CCL4. Several inflammatory markers were correlated with older age at the time of LP. Finally, higher intrathecal IL-33 correlated with increased MS lesion burden and multi-compartment brain atrophy. This study confirms immune heterogeneity underlying CSF profiles in MS, but also identifies several inflammatory protein biomarkers that may be of use for predicting clinical outcomes in future algorithms. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting predominantly adults. It is a complex disease associated with both environmental and genetic risk factors. Although over 230 risk single‐nucleotide polymorphisms have been associated with MS, all are common human variants. The mechanisms by which they increase the risk of MS, however, remain elusive. We hypothesized that a complex genetic phenotype such as MS could be driven by coordinated expression of genes controlled by transcriptional regulatory networks. We, therefore, constructed a gene coexpression network from microarray expression analyses of five purified peripheral blood leukocyte subsets of 76 patients with relapsing remitting MS and 104 healthy controls. These analyses identified a major network (or module) of expressed genes associated with MS that play key roles in cell‐mediated cytotoxicity which was downregulated in monocytes of patients with MS. Manipulation of the module gene expression was achieved in vitro through small interfering RNA gene knockdown of identified drivers. In a mouse model, network gene knockdown modulated the autoimmune inflammatory MS model disease—experimental autoimmune encephalomyelitis. This research implicates a cytotoxicity‐associated gene network in myeloid cells in the pathogenesis of MS. [ABSTRACT FROM AUTHOR]

The aim of the current research is to explore the impact of cognitive reserve (CR) and disease duration on the cognitive performance in multiple sclerosis patients. The research sample included (40) MS outpatients were recruited, their average age was (32.13), with a standard deviation of 8.41 years, same as females (62.5%). CR was assessed by the vocabulary test and level of education. Cognitive assessment was performed using the Wechsler Adult Intelligence Scale - fourth edition (WAIS-IV) as a neuropsychological instrument tool to evaluate Verbal Comprehension Index, perceptual reasoning, working memory and processing speed. The results showed low performance in intelligence among (87.50%) of the sample, and the prevalence of cognitive dysfunction associated with multiple sclerosis was characterized by poor performance on the indicators of working memory and processing speed, as they occupied the highest level of prevalence rates (81.25%), followed by the Perceptual Reasoning Index (75%), then the Verbal Comprehension Index (68.75%). Cognitive impairment (CI) was found in all performance indicators in approximately (43.75%) of patients, and in three indicators in more than a third of patients (37.50%). Furthermore, 12.5% of patients had low performance on at least one or two indicators. Both the total disease duration and the CR factor - specifically measured by level of education - contributed to explaining the score on the Neuropsychological Performance Indicators in MS patients. [ABSTRACT FROM AUTHOR]

Abstract: The psychotherapeutic care of people with multiple sclerosis (MS) is highly relevant. In addition to the obvious motor and sensory dysfunctions, the quality of life of those affected is also limited by the so-called "invisible symptoms" of MS. These invisible symptoms include depressive symptoms, fatigue, anxiety, pain, and cognitive deficits. This review provides an overview of the psychotherapeutic treatment options for evidence-based interventions regarding each symptom as well as a recommendation for action for treating (neuro-)psychologists and therapists. We conducted a (nonsystematic) literature search via PubMed for this purpose. The review shows that cognitive behavioral therapy (CBT) and mindfulness-based interventions (AIs) are potentially effective methods for reducing the symptoms mentioned, but that high-quality studies with sufficient sample sizes are still lacking in this field of research. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association. [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) is an inflammatory condition that affects the optic nerve and may be associated with various central nervous system demyelinating conditions, infectious diseases, and systemic autoimmune syndromes. This manuscript sheds light on the epidemiologic patterns and diverse clinical features of ON, emphasizing the importance of early detection and prompt treatment. Various studies have revealed geographic and ethnic variations across ON subtypes, which are likely related to the incidence and prevalence of co-associated disorders. Distinguishing ON subtypes may be challenging and requires use of paraclinical tools. Treatment strategies differ depending on the etiology, further highlighting the importance of accurately identifying specific ON subtypes in a timely manner. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that Qigong (QG), a mind-body therapy, may help address symptoms of multiple sclerosis (MS), but the heterogeneity of QG content and delivery may affect its feasibility, acceptability, and efficacy. Objective: To survey researchers, clinicians, and QG instructors with experience working with people with MS to identify key components of MS-specific QG guidelines and protocols. Methods: We conducted an online survey to identify QG forms and movements considered helpful for MS, reasons for selection, characteristics of effective learning environments, and recommended dosage and frequency of practice. Quantitative data were analyzed using summary statistics. Qualitative data were analyzed using reflexive thematic analysis. Results: Forty-seven experts, including QG instructors, clinicians, and QG and MS researchers, completed the survey. Respondents had a mean (SD) of 20 (11) years of QG teaching experience, 26 (12) years of clinical practice, 24 (9) years of QG research experience, 13 (5) years of MS research experience, and worked with at least 3 (2) people with MS. Approximately 125 QG forms/movements were recommended. Some forms were specifically recommended to address MS symptoms (e.g., emotional regulation, balance and coordination, muscle strength and flexibility, immune regulation, and circulation). Some respondents felt that any QG form could be beneficial if basic principles were met (e.g., intentional movement, posture, focused awareness, rhythmic breathing/movement, and a relaxed mind and body). Instructor qualities included the ability to convey information clearly, being caring and compassionate, proficient in QG, and having basic knowledge of MS. To promote confidence in learning QG, recommendations included having simple, easy-to-learn movements with modifications based on physical ability. We provide a sample protocol based on these recommendations. Conclusions: This study provides expert guidance for developing a QG protocol for an MS population, including content and delivery recommendations. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients. [ABSTRACT FROM AUTHOR]

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and an immune response, which is associated with the development of neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). The activation of both innate and adaptive immune responses, involving microglia, macrophages, and T and B cells, while required for efficient viral control within the CNS, is also associated with neuropathology. Under pathological events, such as CNS viral infection, microglia/macrophage undergo a reactive response, leading to the infiltration of immune cells from the periphery into the brain, disrupting CNS homeostasis and contributing to the pathogenesis of disease. The Theiler's murine encephalomyelitis virus (TMEV)- induced demyelination disease (TMEV-IDD), which serves as a mouse model of MS. This murine model made significant contributions to our understanding of the pathophysiology of MS following subsequent to infection. Microglia/macrophages could be activated into two different states, classic activated state (M1 state) and alternative activated state (M2 state) during TMEV infection. M1 possesses the capacity to initiate inflammatory response and secretes pro-inflammatory cytokines, and M2-liked microglia/macrophages are antiinflammatory characterized by the secretion of anti-inflammatory cytokines. This review aims to discuss the roles of microglia/macrophages M1/M2-liked polarization during TMEV infection, and explore the potential therapeutic effect of balancing M1/M2-liked polarization of microglia/macrophages on MS. [ABSTRACT FROM AUTHOR]

Purpose: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes. Methods: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. Results: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings. Conclusion: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the brain and spinal cord with both inflammatory and neurodegenerative features. Although advances in imaging techniques, particularly magnetic resonance imaging (MRI), have improved the process of diagnosis, its cause is unknown, a cure remains elusive and the evidence base to guide treatment is lacking. Computational techniques like machine learning (ML) have started to be used to understand MS. Published MS MRI-based computational studies can be divided into five categories: automated diagnosis; differentiation between lesion types and/or MS stages; differential diagnosis; monitoring and predicting disease progression; and synthetic MRI dataset generation. Collectively, these approaches show promise in assisting with MS diagnosis, monitoring of disease activity and prediction of future progression, all potentially contributing to disease management. Analysis quality using ML is highly dependent on the dataset size and variability used for training. Wider public access would mean larger datasets for experimentation, resulting in higher-quality analysis, permitting for more conclusive research. This narrative review provides an outline of the fundamentals of MS pathology and pathogenesis, diagnostic techniques and data types in computational analysis, as well as collating literature pertaining to the application of computational techniques to MRI towards developing a better understanding of MS.

BackgroundEmerging evidence underscores the comorbidity mechanisms among autoimmune diseases (AIDs), with innovative technologies such as single-cell RNA sequencing (scRNA-seq) significantly advancing the explorations in this field. This study aimed to investigate the shared genes among three AIDs—Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA) using bioinformatics databases, and to identify potential biomarkers for early diagnosis.MethodsWe retrieved transcriptomic data of MS, SLE, and RA patients from public databases. Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify disease-associated modules. Functional enrichment analyses and Protein-Protein Interaction (PPI) network was constructed. We used machine learning algorithms to select candidate biomarkers and evaluate their diagnostic value. The Cibersort algorithm was and scRNA-seq analysis was performed to identify key gene expression patterns and assess the infiltration of immune cells in MS patients. Finally, the biomarkers’ expression was validated in human and mice experiments.ResultsSeveral shared genes among MS, SLE, and RA were identified, which play crucial roles in immune responses and inflammation regulation. PPI network analysis highlighted key hub genes, some of which were selected as candidate biomarkers through machine learning algorithms. Receiver Operating Characteristic (ROC) curve analysis indicated that some genes had high diagnostic value (Area Under the Curve, AUC >0.7). Immune cell infiltration pattern analysis showed significant differences in the expression of various immune cells in MS patients. scRNA-seq analysis revealed clusters of genes that were significantly upregulated in the single cells of cerebrospinal fluid in MS patients. The expression of shared genes was validated in the EAE mose model. Validation using clinical samples confirmed the expression of potential diagnostic biomarkers.ConclusionThis study identified shared genes among MS, SLE, and RA and proposed potential early diagnostic biomarkers. These genes are pivotal in regulating immune responses, providing new targets and theoretical basis for the early diagnosis and treatment of autoimmune diseases.

BackgroundA strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment.MethodsIn this retrospective cross-sectional study, 258 serum samples were included consisting of EBV-negative (n = 25) and EBV-positive (n = 36) controls, 192 MS samples including untreated relapsing-remitting MS (RRMS) with and without relapses, secondary progressive MS (SPMS) and primary progressive MS (PPMS) patients, and 106 patients on 8 different treatment regimens. IgG and IgM antibody titers against EBV docking/fusion proteins (gp350, gh/gp42, gh/gL/gp42), immediate early antigen (BZLF1), early antigens (EA p85, EA P138, EA P54), capsid antigens (VCA P18, VCA P23, VCA gp125) and late antigens (EBNA1) were measured. Specific EBNA1 and GlialCAM, CRYAB and ANO2 peptides were synthesized and also incorporated in our custom magnetic bead based multiplex assay.ResultsWe observed significantly elevated IgG antibody titers in EBV-positive controls, RRMS with and without relapse, SPMS and PPMS patients for all lifecycle antigens except for several early antigens when compared to EBV-negative controls. Significantly higher IgG antibody titers were observed in RRMS patients for fusion proteins and EBNA1 peptides when compared to EBV-positive controls. An MS specific response was observed for ANO2 but not for GlialCAM or CRYAB. No significant treatment effects or a specific IgM response were detectable.ConclusionThe MS-specific, differential antibody response to EBV antigens confirms an altered immunological response to EBV in MS patients. EBV reactivation does not appear to play an important role in MS pathogenesis and no differential antibody signatures were observed between MS disease phases. The MS-specific anti-ANO2 antibody response suggests a potential role for EBNA1 as an antigenic driver, although the exact role of anti-ANO2 antibodies needs to be determined. The precise pathophysiological role of EBV in MS remains uncertain and requires further investigation.

Abstract Background Small RNA molecules known as microRNAs (miRNAs) regulate gene expression during the post-translational steps. miRNAs are essential for many physiological processes, such as cell division, growth, and proliferation, as well as development and metabolism. Aims To review the developments in investigations on miR-155 and miR-146a as possible biomarkers for multiple sclerosis (MS) disease diagnosis and prognosis. Methods A comprehensive analysis of the available literature was carried out by searching databases including PubMed, Scopus, and Web of Science for papers published between 2011 and 2023 years. Only original articles written in the English language were considered for inclusion in this review. Results A total of 29 studies were initially identified, with 14 meeting the inclusion criteria. Conclusion The present study underscores the crucial role of microRNAs, particularly miR-155 and miR-146a, in the etiology and progression of multiple sclerosis (MS). Through an extensive analysis of the literature, we have found compelling evidence linking aberrations in the expression and function of these microRNAs to MS pathogenesis. Specifically, our synthesis suggests that miR-155 and miR-146a hold promise as valuable biomarkers for both the diagnosis and prognosis of MS. Despite the challenges posed by the heterogeneity of MS subtypes, the non-invasive accessibility of miRNAs in various bodily fluids, including serum, peripheral blood, cerebrospinal fluid, and extracellular vesicles, presents a promising avenue for the development of robust diagnostic and prognostic tools. By elucidating the intricate roles of miR-155 and miR-146a in MS, our findings contribute to advancing our understanding of the disease mechanisms and pave the way for the development of more effective diagnostic and therapeutic strategies.

Highlights • Intravenous corticosteroid treatment followed by oral clinical treatment can reduce the incidence of post-treatment optic neuritis recurrenc • Visual acquisition increases at one-month post-treatment. Abstract Background: The clinical picture of autoimmune optic neuropathy, known as neuritis, is strongly influenced by the unique structure of the human anterior visual pathway. The central nervous system autoimmune is related to multiple sclerosis (MS). Optic neuropathy is an injury that frequently results in acute inflammatory damage. Objective: This study aimed to determine the clinical manifestations of autoimmune optic neuropathy in multiple sclerosis and identify diseases with appropriate corticosteroid therapy using systematic review methods. Material and Method: This study used a systematic review method to analyze topic-related kinds of literature on Scopus, PubMed, and Google Scholar databases. The literature screening process was carried out based on the PRISMA 2020 guidelines. Result: Regarding the post-treatment recurrence rate of optic neuritis, the use of intravenous corticosteroids alone and intravenous corticosteroid followed by oral administration may clinically reduce the incidence of recurrence in the patients compared those receiving placebo and oral administration. This suggests that intravenous corticosteroid followed by oral corticosteroid treatment is effective in helping to reduce the incidence of recurring optic neuritis. Conclusion: Intravenous corticosteroid treatment followed by oral administration may clinically reduce the incidence of post-treatment recurrence of optic neuritis in multiple sclerosis (MS) patients.

Background: Poor sleep quality (SQ) is a common problem in patients with multiple sclerosis (MS), which may reduce the quality of life and mood state and cause neuropsychological issues. Objectives: This study aimed to investigate the effectiveness of mindfulness-based stress reduction (MBSR) on the SQ in women who suffer from MS. Materials & Methods: From the patients with MS diagnosed by neurologists, 48 were selected by convenient sampling and randomly assigned to MBSR and control groups. The participants of two groups filled out the Pittsburgh sleep quality questionnaire as a pre-test, 8 weeks later as a post-test, and 1 month later as a follow-up. The MBSR group received 8 sessions of group therapy, while the control group did not receive any psychotherapy. The data were analyzed using variance analysis. Results: The results showed that the SQ of the MBSR group improved in all aspects significantly (P

Purpose: Fatigue, imbalance, and walking disorder were commonly observed in patients with multiple sclerosis (MS) as debilitating symptoms. Therefore, the present study aims to examine the effect of transcranial direct current stimulation (tDCS) separately and in combination with virtual reality (VR) training on fatigue, balance, and walking (speed and stride length) in patients with MS. Methods: The present clinical trial research was conducted with 30 MS patients aged 18-55 years (including 21 women and 9 men). The random assignment of subjects was assessed into one of three groups, tDCS group, VR group, and combined tDCS-VR training group. In the tDCS group, the M1 motor cortex was stimulated by direct electrical current in five sessions, and VR training patients participated in the VR program for six sessions. In the combination intervention, participants were delivered tDCS before each VR session. Fatigue severity scale (FSS), Berg balance scale (BBS), and 25-foot walk test (T25-FW) were used to evaluate the fatigue, balance, and walking speed respectively as pre and post-tests. Statistical analysis of covariance (ANCOVA) was used to compare the results between the three groups. Results: Our results showed a significant effect of tDCS, VR, and tDCS-VR on fatigue and a significant effect of VR and tDCS-VR on balance and walking speed in patients with MS (P0.05). Conclusion: Despite the positive effect of fatigue, we found VR and tDCS-VR to be a more effective method for treating balance and walking of the patient. The combination effect of tDCS with VR therapy, should be investigated further.

Optic neuritis (ON) is a common cause of acute visual loss due to optic neuropathy in adults. Although typical demyelinating ON usually recovers, some forms of autoimmune inflammatory ON may result in permanent disability. The relatively recent discovery of novel autoantibodies and their roles in the pathogenesis of ON, including aquaporin 4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody in MOG-associated disease (MOGAD) has led to paradigm shifts in both the acute and chronic management of ON. We performed a comprehensive literature review to assess current and upcoming perspectives on ON by searching for contemporary articles (from 2015 to 2024) for articles that reported updates in diagnostic tools and methods, such as antibody testing. This monograph reviews these recent advances in the evaluation and management of ON.

Abstract Background Limited studies of multiple sclerosis (MS) exist whereby magnetic resonance imaging (MRI) of the brain with consistent imaging protocols occurs at the same time points as collection of healthy lifestyle measures. The aim of this study was to test the feasibility, acceptability and preliminary efficacy of acquiring MRI data as an objective, diagnostic and prognostic marker of MS, at the same time point as brain-healthy lifestyle measures including diet. Methods Participants living with relapsing remitting MS partook in one structural MRI scanning session of the brain, completed two online 24-hour dietary recalls and demographic and self-reported lifestyle questionnaires (e.g. self-reported disability, comorbidities, physical activity, smoking status, body mass index (BMI), stress). Measures of central tenancy and level of dispersion were calculated for feasibility and acceptability of the research protocols. Lesion count was determined by one radiologist and volumetric analyses by a data analysis pipeline based on FreeSurfer software suite. Correlations between white matter lesion count, whole brain volume analyses and lifestyle measures were assessed using Spearman’s rank-order correlation coefficient. Results Thirteen female participants were included in the study: eligibility rate 90.6% (29/32), recruitment rate 46.9% (15/32) and compliance rate 87% (13/15). The mean time to complete all required tasks, including MRI acquisition was 115.86 minutes $$($$ ( ± 23.04), over 4 days. Conversion to usual dietary intake was limited by the small sample. There was one strong, negative correlation between BMI and brain volume (r s = −0.643, p = 0.018) and one strong, positive correlation between physical activity and brain volume (r s = 0.670, p = 0.012) that were both statistically significant. Conclusions Acquiring MRI brain scans at the same time point as lifestyle profiles in adults with MS is both feasible and accepted among adult females living with MS. Quantification of volumetric MRI data support further investigations using semi-automated pipelines among people living with MS, with pre-processing steps identified to increase automated feasibility. This protocol may be used to determine relationships between elements of a brain-healthy lifestyle, including dietary intake, and measures of disease burden and brain health, as assessed by T1-weighted and T2-weighted lesion count and whole brain volume, in an adequately powered sample. Trial registration The study protocol was retrospectively registered in the Australia New Zealand Clinical Trials Registry (ACTRN12624000296538).

Introduction: Multiple sclerosis (MS) is a complex neurodegenerative disorder that affects the brain and spinal cord. In this study, we applied a deep learning-based approach using the StyleGAN model to explore patterns related to MS and predict disease progression in magnetic resonance images (MRI). Methods: We trained the StyleGAN model unsupervised using T1-weighted GRE MR images and diffusion-based ADC maps of MS patients and healthy controls. We then used the trained model to resample MR images from real input data and modified them by manipulations in the latent space to simulate MS progression. We analyzed the resulting simulation-related patterns mimicking disease progression by comparing the intensity profiles of the original and manipulated images and determined the brain parenchymal fraction (BPF). Results: Our results show that MS progression can be simulated by manipulating MR images in the latent space, as evidenced by brain volume loss on both T1-weighted and ADC maps and increasing lesion extent on ADC maps. Conclusion: Overall, this study demonstrates the potential of the StyleGAN model in medical imaging to study image markers and to shed more light on the relationship between brain atrophy and MS progression through corresponding manipulations in the latent space.

Abstract This study aims to develop an AI-enhanced methodology for the expedited and accurate diagnosis of Multiple Sclerosis (MS), a chronic disease affecting the central nervous system leading to progressive impairment. Traditional diagnostic methods are slow and require substantial expertise, underscoring the need for innovative solutions. Our approach involves two phases: initially, extracting features from brain MRI images using first-order histograms, the gray level co-occurrence matrix, and local binary patterns. A unique feature selection technique combining the Sine Cosine Algorithm with the Sea-horse Optimizer is then employed to identify the most significant features. Utilizing the eHealth lab dataset, which includes images from 38 MS patients (mean age 34.1 ± 10.5 years; 17 males, 21 females) and matched healthy controls, our model achieved a remarkable 97.97% detection accuracy using the k-nearest neighbors classifier. Further validation on a larger dataset containing 262 MS cases (199 females, 63 males; mean age 31.26 ± 10.34 years) and 163 healthy individuals (109 females, 54 males; mean age 32.35 ± 10.30 years) demonstrated a 92.94% accuracy for FLAIR images and 91.25% for T2-weighted images with the Random Forest classifier, outperforming existing MS detection methods. These results highlight the potential of the proposed technique as a clinical decision-making tool for the early identification and management of MS.

Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4+ (p=0,0028) and CD8+ T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8+ T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages. [ABSTRACT FROM AUTHOR]