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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]

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]

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]

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]

Machine learning (ML) has emerged as a powerful tool in multiple sclerosis (MS) research, enabling more accurate diagnosis, prognosis prediction, and treatment optimization. However, the complexity of developing and deploying ML models poses challenges for domain experts without extensive programming knowledge. We propose a novel domain-specific language (DSL) that simplifies the process of selecting features, choosing appropriate ML models, and defining training rules for MS research. The DSL offers three approaches: AutoML for automated model and feature selection, manual selection for expert-guided customization, and a customizable mode allowing for fine-grained control. The DSL was implemented and evaluated using real-world MS data. By establishing task-specific DSLs, we have successfully identified workflows that enhance the filtering of ML models and features. This method is crucial in determining the T2-related MRI features that accurately predict both process speed time and walk speed. We assess the effectiveness of using our DSL to enhance ML models and identify feature importance within our private data, aiming to reveal the relationships between features. The proposed DSL empowers domain experts to leverage ML in MS research without extensive programming knowledge. By integrating MLOps practices, it streamlines the ML lifecycle, promoting trustworthy AI through explainability, interpretability, and collaboration. This work demonstrates the potential of DSLs in democratizing ML in MS and paves the way for future research in adaptive and evolving DSL architectures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: While retinal vessel changes are evident in the eyes of patients with relapsing–remitting multiple sclerosis (RRMS), changes in the vasculature of possible MS mimics such as primary Sjögren's syndrome (pSS) remain to be determined. We investigated the potential of retinal optical coherence tomography (OCT) angiography (OCTA) as diagnostic tool to differentiate between patients with RRMS and pSS. Methods: This cross-sectional study included patients with RRMS (n = 36), pSS (n = 36) and healthy controls (n = 30). Participants underwent clinical examination, assessment of visual acuity, retinal OCT, OCTA, and serum markers of glial and neuronal damage. We investigated the associations between OCTA parameters, visual functions, and serum markers. Eyes with a history of optic neuritis (ON) were excluded from analysis. Results: We observed a significant thinning of the combined ganglion cell and inner plexiform layer in the eyes of patients with RRMS but not with pSS, when compared to healthy controls. Retinal vessel densities of the superficial vascular complex (SVC) were reduced in both patients with RRMS and pSS. However, retinal vessel rarefication of the deep vascular complex (DVC) was only evident in patients with pSS but not RRMS. Using multivariate regression analysis, we found that DVC vessel loss in pSS patients was associated with worse visual acuity. Conclusions: Compared to patients with RRMS, rarefication of deep retinal vessels is a unique characteristic of pSS and associated with worse visual function. Assuming a disease-specific retinal vessel pathology, these data are indicative of a differential affliction of the gliovascular complex in the retina of RRMS and pSS patients. [ABSTRACT FROM AUTHOR]

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<0.01). Conclusion: Mindfulness-based stress reduction is helpful for improving the SQ in patients with MS. [ABSTRACT FROM AUTHOR]

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... [ABSTRACT FROM AUTHOR]

(1) Background: Multiple sclerosis (MS) is a chronic, complex, and demyelinating disease closely associated with altered levels of trace elements. Although the first studies into the role of trace elements in MS were published in the 1970s, for five decades it has remained unknown whether trace elements can be part of this heterogeneous neurological disease. (2) Materials and methods: To drive toward at a potential solution, we conducted a systematic review and meta-analysis to elucidate whether there were differences in circulating levels of neurologically important essential trace elements (Zn, Fe, Co, Cu, Mn, and Se) between MS cases and controls. (3) Results: This study revealed significantly lower serum/plasma Zn and Fe levels and higher Cu levels in MS-affected individuals compared to controls. At the same time, no significant differences were found between the MS cases and controls regarding their serum/plasma levels of Co, Mn, or Se. Thus, the loss of Fe and Zn should be considered in supplementation/nutrition strategies for MS patients. On the other hand, since high serum Cu levels indicate a burden on the bloodstreams of MS patients, Cu should be excluded from mineral supplement strategies. Furthermore, all three trace elements (Fe, Zn, and Cu) should be considered from an etiological point of view, and, most importantly, their levels in the bloodstreams of MS patients should be monitored. (4) Conclusions: This study highlights the way for personalized and targeted strategies in the management of MS. [ABSTRACT FROM AUTHOR]

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.

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

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.

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.