Multiple Sclerosis Symptoms Research Articles

Self-reported restrictions in different life domains and associated factors among people with multiple sclerosis in Sweden.

The heterogeneous symptoms of multiple sclerosis (MS) can considerably impact the lives of people with MS (PwMS). The aim of this study was to describe the extent of restrictions in different life domains that PwMS experience in relation to their symptoms and level of disability. A cross-sectional survey was conducted among working-age PwMS in Sweden. The 4052 participants who answered the questions on restrictions in work and private life domains (family, leisure activities, and contact with friends/acquaintances) were included. Predictors of restrictions in the four domains were determined through multinomial logistic regression. Approximately one-third of the PwMS reported no restrictions in the domains of work (35.7%), family (38.7%), leisure activities (31.1%) or contact with friends/acquaintances (40.3%), the remaining participants reported moderate to severe restrictions. Tiredness/fatigue was the most commonly reported most-limiting symptom (49.5%). PwMS with Expanded Disability Status Scale (EDSS) scores of zero reported restrictions in life domains ranging from 39.6% (friends/acquaintances) to 45.7% (leisure activities). Age, sex, education, type of living area, MS type, type of most-limiting symptom, and EDSS score predicted restrictions in work and private life domains. Most PwMS reported similar levels of restrictions in both their work and private lives. Restrictions in these life domains were also reported by PwMS with low disability levels (EDSS = 0) and were often associated with invisible symptoms such as fatigue. Even in a contemporary MS cohort, close to 90% of PwMS report limitations due to MS.

Gut microbiome-modulated dietary strategies in EAE and multiple sclerosis.

Over the last few decades, the incidence of multiple sclerosis has increased as society's dietary habits have switched from a whole foods approach to a high fat, high salt, low dietary fiber, and processed food diet, termed the "Western diet." Environmental factors, such as diet, could play a role in the pathogenesis of multiple sclerosis due to gut microbiota alterations, gut barrier leakage, and subsequent intestinal inflammation that could lead to exacerbated neuroinflammation. This mini-review explores the gut microbiome alterations of various dietary strategies that improve upon the "Western diet" as promising alternatives and targets to current multiple sclerosis treatments. We also provide evidence that gut microbiome modulation through diet can improve or exacerbate clinical symptoms of multiple sclerosis, highlighting the importance of including gut microbiome analyses in future studies of diet and disease.

Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) Add-On Therapy to a Standard Treatment in Individuals with Multiple Sclerosis and Concomitant Symptoms of Depression-Results from a Randomized Clinical Trial and Pilot Study.

Compared to the general population, persons with multiple sclerosis (MS) are at increased risk of suffering from major depressive disorder (MDD). Repetitive Transcranial Magnetic Stimulation (rTMS) was used successfully to treat individuals with MDD. Here, we conducted a randomized clinical trial and pilot study, and tested the effectiveness of rTMS adjuvant to a standard pharmacological treatment among persons with MS, compared to a sham condition. A total of 40 persons with MS (mean age: 32 years; 42.5% females; median EDSS score: 4) and with moderate to severe symptoms of depression were randomly assigned to the rTMS or to the rTMS sham condition, always as adjuvant intervention to the standard treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI). rTMS consisted of 10 sessions each of 37.5 min; the sham condition was identical to the active condition except for the absence of rTMS stimuli. At the beginning and two weeks after the end of the study, participants reported on their fatigue, while experts rated the severity of participants' depressive symptoms (Montgomery-Asberg Depression Rating Scale; MADRS), cognitive performance (Montreal Cognitive Assessment; MoCA), and degree of disability (Expanded Disability Status Scale; EDSS). Data were analyzed per intent-to-treat. Scores for depression, fatigue, and EDSS declined significantly over time (large effect sizes), but more so in the rTMS condition than in the sham condition (large effect sizes for the time by group-interactions). Compared to the sham condition, scores for depression were significantly lower in the rTMS condition. Scores for cognition improved over time in both study conditions (large effect size). Compared to a sham condition, adjuvant rTMS to a standard pharmacological treatment ameliorated typical MS-related symptoms (depression; fatigue; EDSS scores). Results from this pilot study suggested that rTMS might be routinely applied in persons with MS displaying symptoms of depression and fatigue.

Exercise Therapy in Early Multiple Sclerosis Improves Physical Function But Not Cognition: Secondary Analyses From a Randomized Controlled Trial

Background Exercise positively affects multiple sclerosis (MS) symptoms, physiological systems, and potentially cognition. However, an uninvestigated “window of opportunity” exists for exercise therapy early in the disease. Objective This study presents secondary analyses from the Early Multiple Sclerosis Exercise Study, and aims to investigate the efficacy of exercise on physical function, cognition, and patient-reported measures of disease and fatigue impact early in the disease course of MS. Methods This randomized controlled trial (n = 84, time since diagnosis <2 years) included 48 weeks of aerobic exercise or an active control condition (health education) and between-group changes are based on repeated measurement mixed regression models. Physical function tests included measures of aerobic fitness, walking (6-minute walk, Timed 25-foot walk, Six-spot step test), and upper-limb dexterity. Tests of processing speed and memory evaluated cognition. The questionnaires Multiple Sclerosis Impact Scale and Modified Fatigue Impact Scale assessed perception of disease and fatigue impact. Results Following early exercise aerobic fitness showed superior between-group physiological adaptations (4.0 [1.7; 6.3] ml O2/min/kg; large effect size [ES = 0.90]). No other outcomes showed significant between-group differences, yet all measures of walking and upper-limb function showed small-to-medium effect sizes in favor of exercise (ES = 0.19−0.58). Overall disability status as well as cognition were unaffected by exercise, whereas perception of disease and fatigue impact were reduced in both groups. Conclusion In early MS, 48 weeks of supervised aerobic exercise seem to positively modify physical function, but not cognitive function. Perception of disease and fatigue impact may be modifiable by exercise in early MS. Trial registration: Clinicaltrials.gov (identifier: NCT03322761).

Neural bases of motor fatigue in multiple sclerosis: A multimodal approach using neuromuscular assessment and TMS-EEG

Motor fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. Previous studies suggested that increased motor fatigue in MS may arise at the central nervous system level. However, the mechanisms underlying central motor fatigue in MS are still unclear.This paper investigated whether central motor fatigue in MS reflects impaired corticospinal transmission or suboptimal primary motor cortex (M1) output (supraspinal fatigue). Furthermore, we sought to identify whether central motor fatigue is associated with abnormal M1 excitability and connectivity within the sensorimotor network.Twenty-two patients affected by relapsing-remitting MS and 15 healthy controls (HCs) performed repeated blocks of contraction at different percentages of maximal voluntary contraction with the right first dorsal interosseus muscle until exhaustion. Peripheral, central, and supraspinal components of motor fatigue were quantified by a neuromuscular assessment based on the superimposed twitch evoked by peripheral nerve and transcranial magnetic stimulation (TMS). Corticospinal transmission, excitability and inhibition during the task were tested by measurement of motor evoked potential (MEP) latency, amplitude, and cortical silent period (CSP). M1 excitability and connectivity was measured by TMS-evoked electroencephalography (EEG) potentials (TEPs) elicited by M1 stimulation before and after the task.Patients completed fewer blocks of contraction and showed higher values of central and supraspinal fatigue than HCs. We found no MEP or CSP differences between MS patients and HCs. Patients showed a post-fatigue increase in TEPs propagation from M1 to the rest of the cortex and in source-reconstructed activity within the sensorimotor network, in contrast to the reduction observed in HCs. Post-fatigue increase in source-reconstructed TEPs correlated with supraspinal fatigue values.To conclude, MS-related motor fatigue is caused by central mechanisms related explicitly to suboptimal M1 output rather than impaired corticospinal transmission. Furthermore, by adopting a TMS-EEG approach, we proved that suboptimal M1 output in MS patients is associated with abnormal task-related modulation of M1 connectivity within the sensorimotor network. Our findings shed new light on the central mechanisms of motor fatigue in MS by highlighting a possible role of abnormal sensorimotor network dynamics. These novel results may point to new therapeutical targets for fatigue in MS.

Metabolic costs of walking and arm reaching in persons with mild multiple sclerosis.

Movement slowness is a common and disruptive symptom of multiple sclerosis (MS). A potential cause is that individuals with MS slow down to conserve energy as a behavioral adjustment to heightened metabolic costs of movement. To investigate this prospect, we measured the metabolic costs of both walking and seated arm reaching at five speeds in persons with mild MS (pwMS; n = 13; 46.0 ± 7.7 yr) and sex- and age-matched controls (HCs; n = 13; 45.8 ± 7.8 yr). Notably, the cohort of pwMS was highly mobile and no individuals required a cane or aid when walking. We found that the net metabolic power of walking was approximately 20% higher for pwMS across all speeds (P = 0.0185). In contrast, we found no differences in the gross power of reaching between pwMS and HCs (P = 0.492). Collectively, our results suggest that abnormal slowness of movement in MS-particularly reaching-is not the consequence of heightened effort costs and that other sensorimotor mechanisms are playing a considerable role in slowing.NEW & NOTEWORTHY Individuals with multiple sclerosis (MS) often move more slowly than those without the disease. A possible cause is that movements in MS are more energetically expensive and slowing is an adaptation to conserve metabolic resources. Here, we find that while walking is more costly for persons with MS, arm-reaching movements are not. These results bring into question the driving force of movement slowness in MS and implicate other motor-related networks contributing to slowing.

The radiologically isolated syndrome: revised diagnostic criteria.

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.

Cognitive Imapirment in Multiple Sclerosis: Relation to Dysability, Duration and Type of Disease.

Cognitive dysfunctions are often presented as a symptom in multiple sclerosis which is associated with both structural and functional imapirments of neuronal networks in the brain. The aim of the study was to evaluate the influence of dysability, duration and type of disesase on cognitive functions in multiple sclerosis patients. This study included 60 MS patients treated at the Department of Neurology, Clinical Center University of Sarajevo. Inclusion criteria were clinically definite diagnosis of multiple sclerosis, 18 years of age or older and were able to give written informed consent. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCa) screening test. Mann-Whitney and Kruskal-Wallis test were used for comparisons between clinical characteristics and MoCa test scores. Out of 63.33% of patients had EDSS <=4.5. Disease lasted longer than 10 years in 30% of patients. 80% had relapsing-remitting MS and 20% had secondary progressive MS. 84,2 % of patients with EDSS ≤ 4.5 had cognitive dysfunction. Higher disability (rho=0,306, p<0,05), progressive type of disease (rho=0,377, p< 0,01) and longer disease duration (rho=0,282, p<0,05) were associated with worse overall cognitive functions. Level of disability showed statistical significant correlation with the executive functions and language domains of cognition (p<0.01). Longer disease duration was significant correlated with executive functions (p<0,01) and language domains (p<0,01), while progressive type of disease was signifacant correlated only with executive functions domain (p<0,01). MoCa score variables did not show a statistically significant difference in relation to the number of relapses per year and the use of imunoterapy. Statistically significant negative correlation was obtained between executive functions domain and level of disability, disease duration and progressive type of disease, while language domain significantly correlated only with disability level and progressive type of disease. High percentage of MS patients has cognitive impairment. Patients with higher disability were presented with lower cognitive abilities, especially in executive functions and language domains. Higher frequency of cognitive impairment were presented in progessive forms of disaese and longer disease duration with strong influence on executive functions domains of cognition.

Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison.

Ozanimod and ponesimod are sphingosine 1-phosphate receptor modulators approved by the U.S. Food and Drug Administration for treatment of relapsing forms of multiple sclerosis (MS). Given that no head-to-head trials have assessed these two treatments, we performed a matching-adjusted indirect comparison (MAIC) to compare efficacy and safety outcomes between ozanimod and ponesimod for MS. A MAIC compared efficacy and safety of ozanimod and ponesimod at 2 years. Outcomes included annualized relapse rate (ARR) and percentage change from baseline in brain volume loss (BVL) as well as rates of any treatment-emergent adverse events (TEAEs), serious adverse events (AEs), AEs leading to discontinuation, and other safety outcomes. Individual patient-level data were obtained for ozanimod from the RADIANCE-B trial, while aggregate-level patient data were obtained for ponesimod from the OPTIMUM trial. The MAIC was not anchored owing to lack of a common comparator across the two trials. The following characteristics were matched between the trials' populations: age, sex, time since MS symptom onset, relapses in prior year, Expanded Disability Status Scale score, disease-modifying therapies received in the prior 2 years, absence of gadolinium-enhancing T1 lesions, and percentage of patients from Eastern Europe. After matching, key baseline characteristics were balanced between patients receiving ozanimod and ponesimod. Compared with ponesimod, ozanimod had a numerically lower ARR (rate ratio: 0.80 [95% CI: 0.57, 1.10]) and was associated with a significant reduction in BVL (% change difference: 0.20 [95% CI: 0.05, 0.36]). Additionally, ozanimod was associated with a significantly lower risk of TEAEs (risk difference: -11.9% [95% CI: -16.8%, -7.0%]), AEs leading to discontinuation (-6.1% [95% CI: -8.9%, -3.4%]), and lymphocyte count <0.2K/μL (-2.3% [95% CI: -4.2%, -0.5%]). There were no statistically significant differences in the other safety outcomes. The MAIC results suggest that, compared with ponesimod, ozanimod is more effective in preserving brain volume, is comparable in terms of reducing relapse rates, and has a favorable safety profile.

Multiple Sclerosis and Sodium Toxicity: Controversy and Future Directions for Low-Salt Interventions

Salt intake is associated with multiple sclerosis; however, controversial findings that challenge this association rely primarily on methods that do not measure total sodium storage within the body, such as food surveys and urinary sodium excretion. In contrast, tissue sodium concentrations measured with sodium MRI confirm high sodium levels in multiple sclerosis, suggesting a role for sodium toxicity as a risk factor for the disease. Research on demyelination in the central nervous system has identified myelin phase transitions associated with increased salinity, which cause structural instabilities of myelin sheaths and add further evidence implicating sodium toxicity as a causative factor in multiple sclerosis. Inflammatory and immune responses in multiple sclerosis are also related to high sodium intake. In addition, salt is a potential mediating factor associating multiple sclerosis with comorbidities, including systemic lupus erythematosus, rheumatic arthritis, inflammatory bowel disease, and cardiovascular disease. Current confusion exists over classifying dietary sodium intake levels as low, normal, and high, and questions remain over levels of sodium restriction necessary for disease prevention. To reduce multiple sclerosis symptoms and prevent disease progression in patients, future research should investigate low-salt interventions with levels of sodium intake associated with ancestral hunter-gatherer tribes.

Comparing Two Protocols of Exercise on Physical Fitness and Psychological Factors of Mild to Moderate Multiple Sclerosis Patients

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Previous studies have shown that aerobic activity is inversely related to MS symptoms and may be restorative and possibly protective. Objectives: This study aimed to compare the effects of high-intensity functional training (HIFT) protocols and aerobic exercise on functional fitness as well as the cognitive aspect of female patients with multiple sclerosis. Methods: This quasi-experimental and applied clinical trial study consisted of all patients with MS registered in an MS clinic. Among eligible individuals, 30 female RRMS patients were randomly and equally divided into three groups high-intensity functional training (n = 10); aerobic exercise (n = 10), and control group (n = 10). The forearm test, the 30-second standing test, and single leg stance test (SLST), the timed up and go (TUG), Expanded Disability Status Scale (EDSS) were performed to assess physical factors as well as the 21-DAS questionnaire to assess cognitive aspects. Results: This study showed a meaningful difference between the intervention groups and the control group (P &lt; 0.05), in the level of power in the upper body (P = 0.001), lower torso strength (P = 0.001), static balance (P = 0.001), dynamic balance (P = 0.001). the psychological and behavioral components. Conclusions: Present study suggests that aerobic exercise and HIFT in women with MS can improve and further enhance physical function plus psychological and behavioral factors.

Effect of Carvacrol on histological analysis and expression of genes involved in an animal model of multiple sclerosis.

The most common non-traumatic neurological disease in young- and middle-aged adults is multiple sclerosis (MS), leading to central nervous system (CNS) atrophy and neurological disorders with loss of myelin and axonal degeneration. Due to the inadequate efficiency of common treatments, some natural products with antioxidant properties such as Carvacrol have been considered. the present study aimed to investigate carvacrol's anti-inflammatory and therapeutic effects on MS symptoms in healthy and experimental autoimmune encephalomyelitis (EAE) induced female Lewis rats. The study was performed in three groups of Lewis rats: control group, EAE model, and EAE treated with carvacrol (carvacrol-treated group). The treatment group received 25mg/kg of carvacrol intraperitoneally daily. Histologic examination and expression analysis of pro-inflammatory genes (Interleukin-1 and 17 (IL-1 and IL-17), Nuclear Factor Kappa B Cells (NF-κB) and Tumor Necrosis Factor-α (TNF-α)), myelin repair, and also regeneration genes (Myelin basic protein (MBP), Oligodendrocyte Transcription Factor 2 (OLIG2) and Platelet-Derived Growth Factor Receptor α (PDGFR-α)) were carried out. Gene studies, Hematoxylin and Eosin (H&E), and Luxol fast blue stain were performed in the lumbar region of the spinal cord. The EAE clinical scores in the carvacrol-treated group were lower than in untreated rats (P<0.001). The expression of two genes, IL-17 and MBP, was confirmed using fluorescence immunohistochemistry (FIHC). A significant decrease was observed in NF-κB and IL-17, and IL-1 gene expression. The MBP and OLIG2 gene expression was increased in the carvacrol-treated group (p<0.001). In EAE, PDGFR-α expression increased about four times. However, carvacrol administration did not affect PDGFR-α and TNF-α gene expression. In this treatment, H&E staining of spinal cord regions showed a significant decrease in inflammatory cell infiltration. Moreover, immunostaining analysis demonstrated a considerable increase in MBP and a reduction in IL-17 secretion. The results showed that carvacrol administration reduces the entry of inflammatory cells into the CNS by stimulating myelination-related processes employing increasing the expression of genes involved in myelin repair and reducing the expression of inflammatory genes. Our findings confirm that carvacrol improves the clinical and pathological symptoms of EAE through its therapeutic and modification properties as a potential adjunctive therapy and needs to be studied more.

Multiple sclerosis-related heat sensitivity linked to absence of DMT prescription and subjective hand impairment but not autonomic or corticospinal dysfunction.

Heat sensitivity (HS) describes a temporary worsening of multiple sclerosis (MS) symptoms with increased body temperature. The pathophysiology may relate to central nervous system conduction deficits and autonomic dysfunction. We conducted deep clinical phenotyping of a cohort of persons with MS to identify predictors of HS. We recruited 59 MS participants with HS or No HS. Participants self-reported symptom severity (Hospital Anxiety and Depression Scale, Multiple Sclerosis Impact Scale, and fatigue visual analog scale) and underwent maximal exercise and transcranial magnetic stimulation testing to characterize autonomic and corticospinal function. We examined associations with HS using binomial logistic regression. People with HS (36/59) had significantly greater disability, depression, fatigue, and physical and psychological functional effects of MS. They also had significantly lower corticospinal excitability but not conduction. After controlling for disease-modifying therapy (DMT), disability, and disease type, self-reported difficulty using hands in everyday tasks was significantly associated with a large increase in the odds of HS. Autonomic and corticospinal dysfunction were not associated with HS. Lack of DMT use alone was also associated with a large increase in the odds of HS. Following a comprehensive assessment of plausible contributors to HS, HS was most strongly associated with lack of a DMT prescription and self-reported hand dysfunction. Surprisingly, objective measurement of autonomic and corticospinal integrity did not contribute to HS.

Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort.

Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort. Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors. Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4). Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.

Participant Perspectives on Community Qigong for People with Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neurodegenerative disorder affecting motor and nonmotor function including physical and cognitive decline, fatigue, anxiety, and depression. Qigong is a mind-body self-care practice with the potential to address MS symptoms. Publicly available community qigong classes may provide opportunities for people with MS to access qigong, but little is known about the risks and benefits. A mixed methods study of community qigong was conducted for people with MS. In this article, the results of this qualitative analysis to identify benefits and challenges faced by people with MS attending community qigong classes were presented. Qualitative data were collected from an exit survey of 14 study participants with MS who enrolled in a pragmatic trial of community qigong classes for 10 weeks. Participants were new to community-based classes offered but some had experience with qigong/tai chi/other martial arts or yoga. Data were analyzed using reflexive thematic analysis. Seven common themes were identified from this analysis: (1) physical function, (2) motivation/energy, (3) learning, (4) dedicating time for self, (5) meditation/centering/focus, (6) relaxation/stress relief, and (7) psychological/psychosocial. These themes reflected both positive and negative experiences with community qigong classes and home practice. Self-reported benefits centered around improved flexibility, endurance, energy, and focus; stress relief; and psychological/psychosocial benefits. Challenges included physical discomfort including short-term pain, balance difficulty, and heat intolerance. The qualitative findings provide evidence to support qigong as a self-care practice that may benefit people with MS. The challenges identified in the study will help to inform future clinical trials of qigong for MS. ClinicalTrials.gov (CTR#: NCT04585659).

Formative evaluation of an exercise training program for persons with multiple sclerosis who are wheelchair users

Exercise training is an effective and safe second-line therapy for improving multiple sclerosis (MS) symptoms and disease progression among adults. This study aimed to determine the appropriateness of a novel exercise training program for wheelchair users with MS. Ten wheelchair users with MS were recruited from a previous cross-sectional research study to attend one of three focus groups with 3–4 participants that lasted between 69 and 87 min. The focus groups were conducted online using a semi-structured format and participants were invited to complete an evaluation survey. During the focus groups, participants provided qualitative feedback regarding the exercise prescription, exercise modes (resistance and aerobic), training manual, exercise equipment, fitness tracker, rating scale, newsletters, logbook, and coaching. Most feedback focused on minor considerations such as avoiding the color red as it can be an issue for individuals with optic neuritis. Among quantitative evaluation survey ratings, coaching calls were rated the highest 4.7 ± 0.4 on a 5-point scale, followed by the exercise prescription (4.4 ± 0.8) and fitness tracker (4.3 ± 0.9). Focus group participants provided invaluable feedback for finalizing a novel exercise training program for wheelchair users with MS and provided focal suggestions for further improvements.

Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers.

Multiple sclerosis (MS), a distinct autoimmune neuroinflammatory disorder, affects millions of people worldwide, including Saudi Arabia. Changes in the gut microbiome are linked to the development of neuroinflammation via mechanisms that are not fully understood. Prebiotics and probiotics in camel milk that has been fermented have a variety of health benefits. In this study, Bacillus amyloliquefaciens-supplemented camel milk (BASY) was used to assess its preventive effect on MS symptoms in a myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6J mice model. To this end, MOG-induced experimental autoimmune encephalomyelitis (EAE) was established and the level of disease index, pathological scores, and anti-inflammatory markers of BASY-treated mice using macroscopic and microscopic examinations, qPCR and immunoblot were investigated. The results demonstrate that BASY significantly reduced the EAE disease index, increased total microbial load (2.5 fold), and improved the levels of the short-chain fatty acids propionic, butyric and caproic acids in the diseased mice group. Additionally, myeloperoxidase (MPO) proinflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α) and anti-inflammatory cytokines (TGF-β) were regulated by BASY treatment. Significant suppression of MPO and VCAM levels were noticed in the BASY-treated group (from 168 to 111 µM and from 34 to 27 pg/mL, respectively), in comparison to the EAE group. BASY treatment significantly reduced the expression of inflammatory cytokines, inflammatory progression related transcripts, and inflammatory progression protein markers. In conclusion, BASY significantly reduced the symptoms of EAE mice and may be used to develop a probiotic-based diet to promote host gut health. The cumulative findings of this study confirm the significant neuroprotection of BASY in the MOG-induced mice model. They could also suggest a novel approach to the treatment of MS-associated disorders.

The experience of psychological therapies for people with multiple sclerosis: A mixed‐methods study towards a patient‐centred approach to exploring processes of change

AbstractPsychological therapies are effective for managing multiple sclerosis (MS) symptoms such as depression, pain and fatigue. Cognitive behavioural therapy (CBT), mindfulness and other theory‐led approaches have been applied and were found to have moderate effects. The present study adopts a patient‐led approach to investigate people with MS' (PwMS) experiences of psychological therapies and the change processes they identify. In this naturalistic, mixed‐methods design, semistructured interviews were conducted and three questionnaires were administered to 20 PwMS at two different times. Qualitative data collection and analysis followed the interpretative phenomenological analysis (IPA) guidelines, and quantitative data were analysed using paired t tests. Four superordinate themes described the participants' experiences of change as related to their psychological therapy: from despair to relief; from feeling their body as alien to becoming acquainted with an unpredictable new body; from helplessness to empowerment; and from punishment to forgiveness. Quantitative results showed that physical function and general health perception improved, and anxiety was significantly reduced. Despite seeking help from diverse psychological therapy modalities, the analysis revealed common themes that the participants found significant in their therapy stories. Following a patient‐centred approach, the development of psychological therapies for PwMS should focus on their relationships, everyday lives, body perception, losses, shame and guilt. PwMS also need to be understood and acknowledged beyond their condition.

Novel evaluation indicators of MOG35∼55 induced experimental autoimmune encephalomyelitis in C57BL/6J mice

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. Despite a long period of research on the immune mechanisms involved in CNS diseases, the etiology of MS remains unknown. MS may present with different clinical and pathological manifestations due to the involvement of different pathogenic processes, including balance and mobility disorders, psychiatric abnormalities, and intestinal dysfunction. We used an animal model of MS, experimental autoimmune encephalomyelitis (EAE), to assess clinical symptoms of MS with the aim of creating new indicators for the assessment of EAE. Our results show that EAE mice develop severe bone loss, anxiety-like moods, and intestinal inflammation in addition to clinical phenomena such as inflammatory infiltration and demyelination of the spinal cord. Our new indicators aim to provide a more comprehensive assessment of MS to avoid the pitfalls of a single intervention and also to provide a more systematic assessment of the effectiveness of drugs used to treat MS.

Neuropathic pain, cognitive fusion, and alexithymia in patients with multiple sclerosis: Cross-sectional evidence for an explanatory model of anxiety symptoms.

This preliminary study explored a novel model for anxiety symptoms in PwMS, including neuropathic pain (NeP), cognitive fusion (CF), experiential avoidance (EA), and alexithymia as explanatory factors. This cross-sectional study integrated two independent convenience samples: 107 PwMS recruited from the Portuguese Society for Multiple Sclerosis and 97 age- and gender-matched participants without the MS diagnosis (no-MS sample) recruited from the Portuguese general population. Self-report questionnaires that measured the constructs included in the model were administered to both groups. PwMS showed significantly higher values regarding anxiety symptoms and their explanatory variables (NeP, CF, EA, alexithymia) in comparison to non-MS participants. In the MS sample, no correlations were found between anxiety symptoms and sociodemographic and clinical characteristics. NeP, CF, and alexithymia showed significant correlations with anxiety symptoms and significantly explained this symptomatology in simple linear regression models. Thus, these variables were retained in the multiple linear regression model and emerged as significant regressors that together explained 38% of the variance in anxious symptomatology in PwMS. This preliminary study provides novel evidence on NeP and some maladaptive emotion regulation strategies related to EA/psychological inflexibility, as vulnerability to anxiety in PwMS can be considerably increased by CF and alexithymia. Clinical implications were discussed.