Diet and omega-3 and vitamin D supplement use predict five-year fatigue and disability trajectories in people with multiple sclerosis.

BACKGROUND: Fatigue and disability are indicators of disease progression experienced by many people with multiple sclerosis (pwMS). Understanding trajectories of these outcomes, and their predictors, may provide insight to potential interventions for MS management. METHODS: Survey data from 839 pwMS from the Health Outcomes and Lifestyle in pwMS study were analysed. Fatigue was defined as mean Fatigue Severity Scale >5, and severe disability as Patient Determined Disease Steps >5. Group-based trajectory modelling was used to identify fatigue and disability trajectories over five-years. Dietary predictors associated with outcome trajectory group membership were assessed using log-binomial regression. Demographic and clinical characteristics were considered in multivariable models. RESULTS: Distinct trajectories for fatigue and disability were identified. For fatigue, 58 % of pwMS were assigned to low-, and 42 % to high-, fatigue trajectory groups. For disability, 85 % of pwMS were assigned to low-, and 15 % to high-, disability groups. Baseline high-quality diet, and omega-3 and vitamin D supplement use, were associated with reduced risk of being in high-fatigue and high-disability trajectories, while meat and dairy consumption were associated with increased risk. CONCLUSIONS: A high-quality diet, avoiding meat and dairy, and omega-3 and vitamin D supplement use, individually predict better fatigue and disability trajectories. Dietary modifications should be considered in MS management.

Nervonic Acid Synthesis Substrates as Essential Components in Profiled Lipid Supplementation for More Effective Central Nervous System Regeneration.

Central nervous system (CNS) damage leads to severe neurological dysfunction as a result of neuronal cell death and axonal degeneration. As, in the mature CNS, neurons have little ability to regenerate their axons and reconstruct neural loss, demyelination is one of the hallmarks of neurological disorders such as multiple sclerosis (MS). Unfortunately, remyelination, as a regenerative process, is often insufficient to prevent axonal loss and improve neurological deficits after demyelination. Currently, there are still no effective therapeutic tools to restore neurological function, but interestingly, emerging studies prove the beneficial effects of lipid supplementation in a wide variety of pathological processes in the human body. In the future, available lipids with a proven beneficial effect on CNS regeneration could be included in supportive therapy, but this topic still requires further studies. Based on our and others' research, we review the role of exogenous lipids, pointing to substrates that are crucial in the remyelination process but are omitted in available studies, justifying the properly profiled supply of lipids in the human diet as a supportive therapy during CNS regeneration.

The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.

The Study of Remyelinating Therapies in Multiple Sclerosis: Visual Outcomes as a Window Into Repair.

INTRODUCTION: Amelioration of disability in multiple sclerosis requires the development of complementary therapies that target neurodegeneration and promote repair. Remyelination is a promising neuroprotective strategy that may protect axons from damage and subsequent neurodegeneration. METHODS: A review of key literature plus additional targeted search of PubMed and Google Scholar was conducted. RESULTS: There has been a rapid expansion of clinical trials studying putative remyelinating candidates, but further growth of the field is limited by the lack of consensus on key aspects of trial design. We have not yet defined the ideal study population, duration of therapy, or the appropriate outcome measures to detect remyelination in humans. The varied natural history of multiple sclerosis, coupled with the short time frame of phase II clinical trials, requires that we develop and validate biomarkers of remyelination that can serve as surrogate endpoints in clinical trials. CONCLUSIONS: We propose that the visual system may be the most well-suited and validated model for the study potential remyelinating agents. In this review, we discuss the pathophysiology of demyelination and summarize the current clinical trial landscape of remyelinating agents. We present some of the challenges in the study of remyelinating agents and discuss current potential biomarkers of remyelination and repair, emphasizing both established and emerging visual outcome measures.

Vulnerability of Thalamic Nuclei at CSF Interface During the Entire Course of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Thalamic atrophy can be used as a proxy for neurodegeneration in multiple sclerosis (MS). Some data point toward thalamic nuclei that could be affected more than others. However, the dynamic of their changes during MS evolution and the mechanisms driving their differential alterations are still uncertain. METHODS: We paired a large cohort of 1,123 patients with MS with the same number of healthy controls, all scanned with conventional 3D-T1 MRI. To highlight the main atrophic regions at the thalamic nuclei level, we validated a segmentation strategy consisting of deep learning-based synthesis of sequences, which were used for automatic multiatlas segmentation. Then, through a lifespan-based approach, we could model the dynamics of the 4 main thalamic nuclei groups. RESULTS: All analyses converged toward a higher rate of atrophy for the posterior and medial groups compared with the anterior and lateral groups. We also demonstrated that focal MS white matter lesions were associated with atrophy of groups of nuclei when specifically located within the associated thalamocortical projections. The volumes of the most affected posterior group, but also of the anterior group, were better associated with clinical disability than the volume of the whole thalamus. DISCUSSION: These findings point toward the thalamic nuclei adjacent to the third ventricle as more susceptible to neurodegeneration during the entire course of MS through potentiation of disconnection effects by regional factors. Because this information can be obtained even from standard T1-weighted MRI, this paves the way toward such an approach for future monitoring of patients with MS.

Effects of dry needling on spasticity, cortical excitability, and range of motion in a patient with multiple sclerosis: a case report.

BACKGROUND: Dry needling is an intervention used by physiotherapists to manage muscle spasticity. We report the effects of three sessions of dry needling on ankle plantar flexor muscle spasticity and cortical excitability in a patient with multiple sclerosis. CASE PRESENTATION: The patient was a 40-year-old Iranian woman with an 11-year history of multiple sclerosis. The study outcomes were measured by the modified modified Ashworth scale, transcranial magnetic stimulation parameters, and active and passive ankle range of motion. They were assessed before (T0), after three sessions of dry needling (T1), and at 2-week follow-up (T2). Our result showed: the modified modified Ashworth scale was improved at T2 from, 2 to 1. The resting motor threshold decreased from 63 to 61 and 57 at T1 and T2, respectively. The single test motor evokes potential increased from 76.2 to 78.3. The short intracortical inhibition increased from 23.6 to 35.4 at T2. The intracortical facilitation increased from 52 to 76 at T2. The ankle active and passive dorsiflexion ROM increased ~ 10° and ~ 6° at T2, respectively. CONCLUSION: This case study presented a patient with multiple sclerosis who underwent dry needling of ankle plantar flexors with severe spasticity, and highlighted the successful use of dry needling in the management of spasticity, ankle dorsiflexion, and cortical excitability. Further rigorous investigations are warranted, employing randomized controlled trials with a sufficient sample of patients with multiple sclerosis. Trial registration IRCT20230206057343N1, registered 9 February 2023, https://en.irct.ir/trial/68454.

Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?

The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.

Essential trace element levels in multiple sclerosis: Bridging demographic and clinical gaps, assessing the need for supplementation.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disorder intricately linked to perturbations in trace element levels. While previous studies have explored circulating trace elements in a limited sample, understanding the impact of demographic and clinical variables on the elemental profile within a larger cohort remains elusive. METHODS: This study aimed to evaluate essential trace elements (Cr, Mn, Co, Cu, Zn, and Se) in the sera of 215 MS patients compared to a meticulously matched control group of 100 individuals with similar gender and age. Our main objective was to identify potential variations in elemental profiles based on demographic and clinical parameters among MS patients, elucidating the prospective relevance of supplementing specific essential trace elements. RESULTS: Data indicated a significant decrease in serum levels of Mn, Co, Zn, and Se, and an increase in Cr in MS patients compared to controls. These trace elements not only discriminated between MS patients and controls but also exhibited distinctive capabilities among demographic subgroups. Gender, smoking habits, and age strata (20-40 years and 41-60 years) revealed discernible variations in elemental profiles between MS patients and their control counterparts. Se demonstrated the singular ability to stratify cases of extreme MS severity, mild relapsing-remitting MS (RRMS) and highly severe secondary progressive MS (SPMS). In contrast, Co significantly differentiated RRMS from primary progressive MS (PPMS), while Cu significantly differentiated SPMS from PPMS. Additionally, Cu showed a negative correlation with MSSS, while Mn and Zn showed a positive correlation with EDSS. CONCLUSION: These findings underscore a substantive deficiency in Mn, Co, Zn, and Se in the MS cohort, supporting targeted supplementation with these trace elements. This study provides a comprehensive understanding of the intricate relationship between essential trace elements and MS, paving the way for further research into personalized nutritional interventions for this complex neurological disorder.

Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders.

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.

Transcutaneous tibial nerve stimulation in patients with multiple sclerosis and overactive bladder: a real-life clinical and urodynamic assessment.

AIMS: The aims of the present study were to assess the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on overactive bladder (OAB) symptoms and on urodynamic parameters in patients with multiple sclerosis (PwMS) and to seek predictive factors of satisfaction. METHODS: All PwMS who performed 12-24 weeks of TTNS and who underwent urodynamic assessment before and after treatment between June 2020 and October 2022 were included retrospectively. Data collected were bladder diaries, symptoms assessed with Urinary Symptoms Profile (USP), and urodynamic parameters (bladder sensations, detrusor overactivity, and voiding phase). Patients with improvement rated as very good or good on Patient Global Impression of Improvement (PGI-I) score were considered as responders. RESULTS: Eighty-two patients were included (mean age: 47.1 ± 11.5 years, 67 (82%) were women). The mean USP OAB sub-score decreased from 7.7 ± 3.5 to 6.0 ± 3.4 (p < 0.0001). On bladder diaries, voided volumes, void frequency, and the proportion of micturition done at urgent need to void significantly improved with TTNS (p < 0.05). No significant change was found in urodynamic parameters. According to the PGI-I, 34 (42.5%) patients were good responders. The only parameter associated with higher satisfaction was the percentage of micturition done at urgent need to void before the initiation of the treatment (39.8% ± 30.5 in the responder group vs 25.1% ± 25.6 in the low/no responder group; p = 0.04). CONCLUSION: TTNS improves OAB symptoms in PwMS, without significant changes on urodynamics. A high rate of strong or urgent need to void in daily life was associated with higher satisfaction.

The effect of lower back and lower-extremity kinesiology taping on static balance and physical function performance in people with multiple sclerosis: A pilot study.

INTRODUCTION: Multiple sclerosis (MS) can lead to numerous deficits in body functions, including balance and mobility impairment. This study examined the effect of lower back and lower extremity kinesiology tape (KT) application on static balance and physical functioning performance in people with MS (pwMS) and compared that to a non-elastic tape. METHODS: This pilot randomized study recruited and enrolled 10 participants with MS that were allocated into two groups: kinesio (n = 6) and non-elastic (n = 4) tape. Participants were assessed with and without the respective tape on static balance with eyes open and closed and various physical function tests. RESULTS: Effect sizes for the Kinesio tape intervention were found to be small, while effect sizes for the sham tape/place condition varied from small to high. For both groups, the tendency was to reduce or maintain performance on the tests comparing tape and no tape. A subsequent, mixed-factor ANOVA revealed no significant difference between KT or sham tape/placebo. CONCLUSION: Our findings suggest that KT applied on lower back and lower extremity muscles does not seem to improve static balance and physical function performance in pwMS.

Does non-invasive brain stimulation improve spatiotemporal gait parameters in people with multiple sclerosis? A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease that causes progressive functional impairment, mainly in walking tasks. Noninvasive brain stimulation (NIBS) could influence the motor function and improving gait ability of patients. OBJECTIVE: The aim was to analyze the effects of NIBS (transcranial direct current stimulation [tDCS] or transcranial magnetic stimulation [TMS] on functional locomotion in people with multiple sclerosis (PwMS). METHODS: A search was conducted for randomized controlled trials published up to November 2023 comparing the application of NIBS versus a sham or control group. The primary outcome were spatiotemporal gait parameters and functional mobility. Two review authors independently assessed the risk of bias in the included studies, and we used the Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty of the evidence for each outcome. A meta-analysis was performed by pooling the appropriate data using RevMan Web. RESULTS: A total of four clinical trials were included for metanalysis. We observed that there is no statistically significant difference in overall effect in gait speed (MD = 0.08; 95% CI: -0.08-0.24; p = 0.32), and cadence (MD = 0.22; 95% CI: -11.54-11.98; p = 0.97%) between groups. But there was a statistically significant difference in overall effect in stride length between groups (MD:0.19; 95% CI: 0.07-0.31; p = 0.002), mainly when the intervention performed by multiple sessions and associated with motor rehabilitation (MD = 0.29; 95% CI: 0.14-0.44; p = 0.0002). CONCLUSIONS: tDCS applied by multiple session and combined with motor rehabilitation (i.e., aerobic and/or resistance training) can improve stride length in PwMS.

Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(ß-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

Patient-reported benefits from nabiximols treatment in multiple sclerosis-related spasticity exceed conventional measures.

Aim: This prospective, multicenter, open-label, noninterventional 12-week study investigated the effectiveness and tolerability of add-on nabiximols oromucosal spray (Sativex®) in the real-world setting in Germany. Patients & methods: The main analysis set comprised 51 adult patients (49 nabiximols responders) with multiple sclerosis (MS) spasticity. Results: The mean overall goal attainment scale score (primary outcome measure) increased by 46% from baseline to week 12 (35.2 vs 51.4; p < 0.001). Mean gait speed was improved by 23% at 4 and 12 weeks. Clinically meaningful improvements in mean 0-10 numerical rating scale scores for spasticity, pain, sleep quality and urinary bladder dysfunction were recorded at 4 and 12 weeks. Conclusion: Nabiximols is a useful therapeutic option for patients with MS spasticity.

People with multiple sclerosis (MS) spasticity experience a variety of symptoms and have individual expectations about a new treatment. This study investigated patients' perceptions about the effectiveness and tolerability of nabiximols oromucosal spray (Sativex^®) when added to current medications for spasticity. Common treatment goals for patients (n = 51) were less pain, better walking and improved sleep. After 12 weeks of treatment, 62% of selected treatment goals were achieved 'as expected' or 'better than expected' and 65% of patients considered their spasticity to be 'much improved'. Meaningful improvements were recorded in spasticity-related symptoms of pain, sleep quality and bladder problems. Few side effects were reported. Nabiximols may be useful for MS patients with a poor response to usual spasticity medications.

Dietary Supplementation with 23-Hydroxy Ursolic Acid Reduces the Severity and Incidence of Acute Experimental Autoimmune Encephalomyelitis (EAE) in a Murine Model of Multiple Sclerosis.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2% wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between the groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN-γ between 23-OH UA-fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T cell responses. In summary, our findings in EAE mice strongly suggest that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

Sex Differences under Vitamin D Supplementation in an Animal Model of Progressive Multiple Sclerosis.

A central role for vitamin D (VD) in immune modulation has recently been recognized linking VD insufficiency to autoimmune disorders that commonly exhibit sex-associated differences. Similar to other autoimmune diseases, there is a higher incidence of multiple sclerosis (MS) in women, but a poorer prognosis in men, often characterized by a more rapid progression. Although sex hormones are most likely involved, this phenomenon is still poorly understood. Oxidative stress, modulated by VD serum levels as well as sex hormones, may act as a contributing factor to demyelination and axonal damage in both MS and the corresponding preclinical models. In this study, we analyzed sex-associated differences and VD effects utilizing an animal model that recapitulates histopathological features of the progressive MS phase (PMS). In contrast to relapsing-remitting MS (RRMS), PMS has been poorly investigated in this context. Male (n = 50) and female (n = 46) Dark Agouti rats received either VD (400 IU per week; VD+) or standard rodent food without extra VD (VD-) from weaning onwards. Myelination, microglial activation, apoptotic cell death and neuronal viability were assessed using immunohistochemical markers in brain tissue. Additionally, we also used two different histological markers against oxidized lipids along with colorimetric methods to measure protective polyphenols (PP) and total antioxidative capacity (TAC) in serum. Neurofilament light chain serum levels (sNfL) were analyzed using single-molecule array (SIMOA) analysis. We found significant differences between female and male animals. Female rats exhibited a better TAC and higher amounts of PP. Additionally, females showed higher myelin preservation, lower microglial activation and better neuronal survival while showing more apoptotic cells than male rats. We even found a delay in reaching the peak of the disease in females. Overall, both sexes benefitted from VD supplementation, represented by significantly less cortical, neuroaxonal and oxidative damage. Unexpectedly, male rats had an even higher overall benefit, most likely due to differences in oxidative capacity and defense systems.

Development of an in vitro peptide-stimulated T cell assay to evaluate immune effects by cannabinoid compounds.

Previous studies demonstrated that cannabinoids exhibit immunosuppressive effects in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). To ask questions about treatment timing and investigate mechanisms for immune suppression by the plant-derived cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), an in vitro peptide stimulation of naive splenocytes (SPLC) was developed to mimic T cell activation in EAE. The peptide was derived from the myelin oligodendrocyte glycoprotein (MOG) protein, which is one component of the myelin sheath. MOG peptide is typically used with an immune adjuvant to trigger MOG-reactive T cells that attack MOG-containing tissues, causing demyelination and clinical disease in EAE. To develop the in vitro model, naïve SPLC were stimulated with MOG peptide on day 0 and restimulated on day 4. Cytokine analyses revealed that CBD and THC suppressed MOG peptide-stimulated cytokine production. Flow cytometric analysis showed that intracellular cytokines could be detected in CD4+ and CD8+ T cells. To determine if intracellular calcium was altered in the cultures, cells were stimulated for 4 days to assess the state of the cells at the time of MOG peptide restimulation. Both cannabinoid-treated cultures had a smaller population of the calcium-positive population as compared to vehicle-treated cells. These results demonstrate the establishment of an in vitro model that can be used to mimic MOG-reactive T cell stimulation in vivo.

Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study.

BACKGROUND: Multiple studies have highlighted elevated rates of depression among individuals with Multiple Sclerosis (MS), with its associated symptoms posing a significant threat to overall well-being. Moreover, existing literature suggests a potential interconnection between depressive manifestations and the decline of physical functionalities in the context of MS. OBJECTIVE: to examine the viability of the Eye Movement Desensitization Reprocessing (EMDR) therapy protocol for the treatment of depressive disorders (DeprEND) for alleviating depression in individuals with MS. METHODS: We conducted a process-outcome study to examine the feasibilty and effectiveness DeprEND enrolling 13 individuals with MS and depressive symtpoms. Psychological and physical assessment pre-, post-intervention and 3-month follow-up were included. Pre- and post-magnetic resonance imaging (MRI) scans were conducted to analyze potential alterations in brain function. RESULTS: The EMDR DeprEND treatment showed a high level of adherence and feasibility. Significant reductions in depressive symptoms were found at post-intervention and at 3 months follow-up. No significant differences were observed in terms of physical symptoms. A significant modulation observed in parietal and premotor areas when examining negative valence stimuli post-treatment was found. CONCLUSION: for The EMDR DeprEND protocol may represent a feasible and cost-effective treatment for reducing depressive symptoms in MS patients and improving their mental well-being.

Effects of a full-body electrostimulation garment application in a cohort of subjects with cerebral palsy, multiple sclerosis, and stroke on upper motor neuron syndrome symptoms.

OBJECTIVES: Dysfunction of the central nervous system may inflict spastic movement disorder (SMD). Electrical stimuli were identified as promising therapeutic option. Electrical stimulation provided by a 58-electrode full body garment was investigated based on data from regular trial fittings. METHODS: Data from 72 testees were investigated. Age averages 36.6 (19.8) ys with 44 females. The cohort spans infantile cerebral paresis (CP) (n=29), multiple sclerosis (MS) (n=23) and stroke (n=20). Data were stratified by etiology and an entry BBS Score<45. RESULTS: Effect sizes (Cohen`s d) related BBS, TUG, FGA, 10mWT, WMFT, EQ5D5L and Pain. Significance levels are indicated by *: p<0.05, **: p<0.01, ***: p<0.001, (t): p<0.1: CP: 1.64***, 0.29*, 1.59***, 0.76(t), 1.00***, 0.5*, 1.28***; MS: 1.83***, 0.83***, 1.28**, 1.07***, 0.93*, 1,11**, 0.78*; Stroke: 1.28**, 0.78**, 0.89, 0.92**, 0.71, 1.26*, 0.78*. CONCLUSIONS: Multi-site transcutaneous electrical stimulation may increase ambulation related skills in subjects with SMD stemming from CP, MS and stroke. The results indicate effects on static and dynamic balance, fall risk, mobility, upper extremity improvement and an overall increase in health utility and a reduction in spasticity related pain. Effects are immediate as well as sustained. These results may inspire individual trial fittings and inform further controlled trials.

Huangqi-Guizhi-Wuwu decoction regulates differentiation of CD4+ T cell and prevents against experimental autoimmune encephalomyelitis progression in mice.

BACKGROUND: Multiple sclerosis (MS) is a demyelination disorder caused by an overactive immune response. Its pathological characteristics include CNS inflammation, white matter demyelination, glial cell proliferation, and so on. Huangqi-Guizhi-Wuwu Decoction (HGWD), which is recorded in the Synopsis of the Golden Chamber, is used clinically for the therapy of MS, but its mechanism is still elusive. PURPOSE: This study was aimed to investigate the impact of HGWD on the classical animal model for MS, experimental autoimmune encephalomyelitis (EAE), and explore the underlying action mechanism. RESULTS: HGWD ameliorated the pathogenesis of EAE mice, and improved their neurobehavior and pathological tissue damage. Network pharmacology predictions revealed the action mechanism of HGWD in EAE mice might be related to its effect on the immune system of mice. HGWD effectively suppressed the inflammatory infiltration in CNS, while also preventing the elevation of CD4+T cells of mice with EAE. HGWD could increase the ratio of Treg cells, up-regulate the secretion of IL-10 and Foxp3 mRNA expression, inhibit the ratio of Th1 and Th17 cells, down-regulate the IFN-γ and IL-17 protein expression, as well as the RORγT and T-bet gene expression in EAE mice. In addition, HGWD-containing serum modulated Th1/Th17/Treg cell differentiation in vitro. Moreover, HGWD inhibited the p-JAK1, p-JAK2, p-STAT1, p-STAT3 and p-STAT4 proteins and elevated the p-STAT5 protein in lymphoid tissues of EAE mice. CONCLUSION: HGWD improved the progress of EAE by regulating the proportion of CD4+T cell subtype differentiation, which might be exerted through JAK/STAT signaling pathway, providing a pharmacological basis for the clinical treatment of MS.