Neurobehavioral mechanisms of fear and anxiety in multiple sclerosis

BackgroundThere is growing recognition that communication can be affected in multiple sclerosis (MS) and can negatively impact relationships, employment and psychological well‐being. Some persons with MS (PwMS) implement strategies to facilitate their communication; however, some do not. Most PwMS who report communication changes do not engage with speech–language pathology (SLP) services. This raises concerns that a large portion of communication changes associated with MS go under‐recognized and unmanaged. Little is known about what PwMS want and need to facilitate effective communication.AimTo explore what PwMS want and need to better manage their communication changes.Methods & ProceduresThree focus groups were conducted online using Zoom, with a total of 12 PwMS. Participants were an opportunistic sample of PwMS within Australia recruited via advertisements distributed to various MS organizations and clinics. Data were transcribed verbatim and analysed using thematic content analysis to provide a qualitative analysis of the data.Outcomes & ResultsTwo main themes emerged: (1) accessible knowledge and a holistic approach; and (2) partnerships. Specifically, the identified wants and needs of participants included: (1) assessment; (2) information; (3) raising awareness; (4) support groups; (5) a whole‐person approach to intervention; (6) geographically and economically accessible and navigable services; (7) effective patient–physician interactions; and (8) a multidisciplinary team‐based approach (e.g., SLP, psychology, neuropsychology, occupational therapy).Conclusions & ImplicationsThis study identified a wide range of unmet wants and needs of PwMS related to communication changes. Participants wanted improved collaborative partnerships with healthcare professionals to better manage their communication changes. For example, healthcare professionals could ask PwMS about potential communication changes, provide education and make appropriate referrals. Education and information provision could focus on communication changes in MS, factors that trigger or exacerbate communication changes, impacts, self‐management strategies, and available supports and services. Specific implications for clinical practice and future research are suggested in this paper, including ideas for patient education materials and content, suggestions for communication‐specific screening and information that could be shared in patient–physician interactions, the development of guidelines to systematically screen, assess, manage and monitor communication changes in MS, and the design of evidence‐based communication interventions for this clinical population. The results from this study can be used to guide the design of supports and services to help PwMS better manage communication changes, with the aim to reduce the negative impacts.What this paper addsWhat is already known on this subjectPwMS can experience communication changes across a range of domains, including speech, voice, fluency, expressive and receptive language, and cognitive–linguistic functions. These changes can have profound and far‐reaching negative impacts on educational and vocational outcomes, social participation, relationships, psychological well‐being, and quality of life. Most PwMS who report communication changes do not engage with SLP services. There has been little research exploring what PwMS want and need to help manage their communication changes.What this paper adds to the existing knowledgeThis research is the first study of its kind that sets out specifically to explore what PwMS want and need to better manage their communication changes. This study increases our understanding of, and provides valuable insights into, the specific types of supports and services PwMS desire to access, and the partnerships and kinds of interactions PwMS dream of having with healthcare professionals to manage these changes. This information can facilitate the development of future interventions to manage communication changes in MS.What are the potential or actual clinical implications of this work?PwMS wanted healthcare professionals to ask about potential communication changes, provide education and make appropriate referrals. When providing education and information on communication changes in MS, healthcare professionals should focus on covering symptoms, triggers, impacts, self‐management strategies, and available supports and services. There is a timely need to develop guidelines and interventions to manage communication changes in MS to reduce their negative impacts.

Background Fatigue is one of the most distressing symptoms among persons with multiple sclerosis (PwMS). The experience of fatigue is inherently interoceptive, yet no study to date has explicitly investigated the insular cortex (IC) as a primary goal in the experience of fatigue in PwMS. In addition, it is unknown how brain regions such as IC play a role in state or trait fatigue. Objective Assess the involvement of the IC in trait fatigue and state fatigue in PwMS with and without clinical fatigue. Methods Trait and state fatigue, cognitive status, and structural MRI were assessed in 27 PwMS. PwMS were stratified into nonclinical fatigue (nF-MS, FSS ≤ 4.0) (n = 10) and clinical fatigue (F-MS, FSS ≥ 5.0) (n = 10). Voxel-based morphometry analysis (VBM) for the whole sample (n = 20) and for the two groups was performed. Anatomical covariance analysis (ACA) analysis was conducted by selecting different volumes included in the corticostriatal network (CoStN) and analyzing interhemispheric correlations between those volumes to explore the state of the CoStN in both groups. Results In the VBM analysis, when considering the whole sample of PwMS, higher levels of trait fatigue were negatively associated with grey matter (GM) volume in the left dorsal anterior insula (dAI) (rho = −0.647; p = 0.002; R2 = 0.369). When comparing nF-MS versus F-MS, significant differences were found in the left dAI, where the F-MS group showed less GM volume in the left dAI. In the ACA analysis, the F-MS group showed fewer significant interhemispheric correlations in comparison with the Low-FSS group. Conclusions The present results provide support to the interoceptive component of self-reported fatigue and suggest that changes in the relationship between the different anatomical regions involved in the CoStN are present even in nonclinical trait fatigue. Those changes might be responsible for the experience of trait fatigue in PwMS. Future studies with larger samples and multimodal MRI acquisitions should be considered to fully understand the changes in the CoStN and the specific role of the IC in trait fatigue.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system that predominantly affects women of reproductive age. With ongoing therapeutic advances, ending common misconceptions related to the disease and pregnancy in MS is crucial for the adherence to MS treatment. The aim of our research was to assess the level of knowledge of MS as a disease in general, to estimate the awareness of reproductive issues in MS, and to evaluate the primary sources of information in persons with MS (PwMS) and persons without MS. The study included female PwMS aged 18-49 years and male PwMS aged 18-65 years, who were matched with persons without MS of the same age, gender, and education. After obtaining informed consent, participants filled out an online questionnaire distributed via electronic mail between November 1st, 2022 and November 1st, 2023. The questionnaire consisted of a different statements regarding the clinical aspects of MS, pregnancy and reproductive health, primary source of information and subjective assessment of the knowledge. The study included 410 PwMS and 400 persons without MS. The survey has shown higher levels of knowledge related to the disease in the PwMS group. Seven in ten PwMS disagreed with the false statement that all PwMS at some point lose the ability to walk, while 39.2% of persons without MS agreed. On the other hand, the most common answer, for all study participants, related to reproductive issues in MS was "I do not know". Over two-thirds of PwMS did not have an answer to the question related to the benefits of breastfeeding. The primary source of information for the PwMS group were neurologists (82.7%) and for persons without MS the Internet (54.4%). Persons with MS additionally received information from MS nurses. Both PwMS and persons without MS subjectively evaluated their level of knowledge as an inadequate (49.3% vs. 77.5%). People with MS still have a low level of information concerning reproductive issues while a considerable number of respondents recognized a deficit of adequate information regarding MS. Availability and validity of information are key aspects to consider in the future. Improvements in access to verified information is needed with an emphasis on reproductive issues.

Motor fatigability after low-intensity hand grip exercises in persons with multiple sclerosis

Aerobic capacity (VO2max) is a strong health and performance predictor and is regarded as a key physiological measure in the healthy population and in persons with multiple sclerosis (PwMS). However, no studies have tried to synthesize the existing knowledge regarding VO2max in PwMS. The objectives of this study were to (1) systematically review the psychometric properties of the VO2max test; (2) systematically review the literature on VO2max compared with healthy populations; (3) summarize correlates of VO2max; and (4) to review and conduct a meta-analysis of longitudinal exercise studies evaluating training-induced effects on VO2max in PwMS. A systematic literature search of six databases (PubMed, EMBASE, Cochrane Library, PEDro, CINAHL and SPORTDiscus) was performed. To be included, the study had to (1) enrol participants with definite MS according to defined criteria; (2) assess aerobic capacity (VO2max) by means of a graded exercise test to voluntary exhaustion; (3) had undergone peer review; and (4) be available in English, Danish or Dutch. The psychometric properties of the VO2max test in PwMS were reviewed with respect to reliability, validity and responsiveness. Simple Pearson correlation analysis was used to assess the relation between key study characteristics and the reported mean VO2max. The methodological quality of the intervention studies was evaluated using the original 11-item Physiotherapy Evidence Database (PEDro) scale. A random coefficient model was used to summarize individual, weighted, standardized effects of studies that assessed the effects of exercise on aerobic capacity in PwMS. A total of 40 studies, covering 165 healthy controls and 1,137 PwMS, fulfilled the inclusion criteria. VO2max testing in PwMS can be considered a valid measure of aerobic capacity, at least in PwMS having low-to-mild disability, and an ∼10% change between two tests performed on separate days can be considered the smallest reliable change (with 95% certainty) in VO2max in PwMS. The average body-weight-adjusted VO2max was significantly lower in PwMS (25.5 ± 5.2 mL·kg(-1)·min(-1)) compared with healthy controls (30.9 ± 5.4 mL·kg(-1)·min(-1)). The analysis of VO2max correlates revealed associations with a variety of outcomes covering all levels of the International Classification of Functioning, Disability and Health (ICF) model. The meta-analysis showed that aerobic training in PwMS may improve VO2max by as much as 3.5 mL·kg(-1)·min(-1). A valid and reliable test can be performed, in at least ambulant PwMS, by the gold standard whole-body maximal exercise test. Aerobic capacity in PwMS is impaired compared with healthy people, and is significantly associated with factors on all levels of the ICF model, including disease severity. Aerobic training can improve aerobic capacity in PwMS to a degree that is associated with secondary health benefits.

The Transcallosal Highway: The ipsilateral silent period as a neural biomarker for impaired corpus callosum communication in multiple sclerosis

Background Depression and anxiety are common in multiple sclerosis (MS), significantly affecting quality of life. Previous studies on exercise interventions for mental health in persons with MS (PwMS) have shown mixed results, partly due to inconsistent adherence to the Physical Activity Guidelines for Multiple Sclerosis (PAG-MS). Objective This study aimed to evaluate the effects of PAG-MS-compliant exercise on depression and anxiety outcomes in PwMS. Methods A systematic search was performed in EMBASE, PsycINFO, Web of Science, SPORTDiscuss, PubMed, Scopus, and CINAHL through October 2024 to identify randomized controlled trials (RCTs). Eligible studies involved adults with MS and focused on exercise regimens compliant with PAG-MS. Comparisons were made with non-PAG-MS exercise regimens or no exercise at all. Two independent reviewers screened studies, extracted data, and assessed the risk of bias. Depression and anxiety outcomes were analyzed using meta-analyses, incorporating minimal clinically important difference (MCID) thresholds to determine clinical significance. Results Twelve RCTs involving 458 participants we included. Depression outcomes showed significant improvement (MD: −4.46 [95% CI: −6.90, −2.01], P ˂ 0.01), exceeding the MCID threshold of 3.00 points on the Beck Depression Inventory scale. Anxiety outcomes, analyzed from two RCTs, showed non-significant improvement (SMD: −0.87 [95% CI: −2.46, 0.72], p = .29). Overall, 58.33% of studies had a high risk of bias. Conclusion Interventions that meet PAG-MS demonstrate clinically meaningful improvements in depression, supporting their use as a non-pharmacological treatment strategy. However, given the limited data on anxiety outcomes, further research is needed to clarify the potential benefits in this domain.

Self-reported longitudinal COVID-19 vaccination reactogenicity profiles in persons with multiple sclerosis.

The effect of Fampridine (4-aminopyridine) in physical activity during weekdays and weekends in persons with multiple sclerosis

During the process of the multiple sclerosis (MS), persons with multiple sclerosis (PwMS) may experience drooling (sialorrhea) issues that are frequently disregarded. The exact cause of drooling in PwMS is poorly understood. This study aims to assess potential risk factors for drooling seen in PwMS. The study included 20 PwMS with drooling and 19 PwMS without drooling. The participants’ sociodemographic data and clinical parameters were noted. To evaluate dysphagia, fatigue, and hypersalivation, the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS), the Fatigue Severity Scale (FSS), and objective saliva flow rate measurement with cottons placed in Stensen ducts and under the tongue (swab test) were used, respectively. The study employed univariate and multivariate logistic regression models to identify the risk factors linked to drooling. Gender, age, disease duration, MS type, and Expanded Disability Status Scale scores did not differ between the two groups. There was a significant increase in the DYMUS and submandibular/sublingual (SM/SL) saliva flow rate values in PwMS with drooling (p = 0.009 and p = 0.019, respectively). However, in our study, hypersalivation was not observed in PwMS with or without drooling. In the univariate model, DYMUS, SM/SL saliva flow rate, and FSS were found to be risk factors for drooling in PwMS. But only DYMUS was shown to be a significant risk factor in the multivariate model obtained by the backward (Wald) elimination method (p = 0.023). Finally, our research is the first to demonstrate the relationship between drooling and the presence of dysphagia symptoms in PwMS. This is a very important study to determine the nature of drooling in PwMS. This finding shows that our study will serve as a reference for choosing the best method for drooling treatment.

BackgroundThe energy cost of walking (ECw) is an important indicator of walking dysfunction in persons with multiple sclerosis (PwMS). However, its underlying causes and its relation with ankle push-off and walking speed are not well understood. Research questionWhat is the contribution of ankle push-off and walking speed to increased ECw in PwMS? MethodsTen PwMS with walking limitations and 10 individually gender- and age-matched healthy controls (HC) were included. All participants performed two 6-min walking trials on a treadmill at comfortable walking speed (CWS of PwMS) and fast walking speed (FWS, 130 % of CWS of PwMS). Kinetics and metabolic cost were evaluated. Generalized estimating equations were performed to investigate effects of group and walking speed, and their interaction. Spearman correlations were conducted to examine whether ECw was related to ankle push-off in PwMS, controlling for differences in walking speed in PwMS. ResultsECw at matched walking speed was significantly higher in PwMS compared to HC. Kinetic parameters were not different between the most impaired leg in PwMS and HC at matched walking speed, but asymmetry between both legs of PwMS was observed. At FWS, ECw reduced and ankle push-off increased similarly in both groups. ECw was inversely related to peak ankle power of the most impaired leg in PwMS at CWS. SignificanceSlow walking speed is one factor that contributes to increased ECw in PwMS. Furthermore, PwMS who had a higher ECw showed a lower peak ankle power, independent of walking speed. This indicates that ankle push-off could be a contributor to increased ECw.

The functional performance status during weekdays and weekends in persons with multiple sclerosis

The assessment of the functional performance status of persons with multiple sclerosis (PwMS) is a useful tool to optimize healthcare. This concept does not seem to be extensively explored in this population. This study aimed to determine the level of activity of PwMS during weekdays and weekends, and to establish associations between clinical parameters. Forty-one PwMS and 16 healthy persons participated in this study. Their physical activity in real-life conditions was assessed with an accelerometer. For the clinical evaluations, the quality of life, fatigue, gait, and balance were assessed. The level of activity between PwMS for weekdays, weekends, Saturdays, and Sundays was significantly reduced compared with the reference group (p = 0.001–0.00001, d = 0.95–1.76). PwMS had a constant level of activity throughout the week, whereas the reference group increased its level of activity on Saturdays (p = 0.04, d = 0.69). The level of activity was correlated in descending order with multiple sclerosis disability, body mass index, gait velocity, six-minute walk test, and timed up and go test. This study showed that PwMS had a stable level of activity throughout the week, contrary to healthy persons. It could be necessary to develop programs to facilitate physical activity and participation during the weekdays, but especially during weekends.

Mental Disorders in Mexican Patients With Multiple Sclerosis

Background: Walking disorders represent the most disabling condition in persons with Multiple Sclerosis (PwMS). Several studies showed good reliability of the 6-min walk test (6MWT) (i.e., especially distance traveled), but little is known about the reliability of the Spatio-temporal (ST) variables in the 6MWT. Objective: To evaluate the test-retest reliability of ST variables and perceived exertion during the 6MWT in PwMS and comparable healthy persons. Methods: We explored three 1-min intervals (initial: 0′–1′, middle: 2′30″–3′30″, end: 5′–6′) of the 6MWT. Six ST variables and perceived exertion were measured (respectively, using the GAITRite system and the Borg Scale). These measurements were performed twice, 1 week apart. The test-retest effects were assessed using the intraclass correlation coefficient (ICC) or the weighted kappa. Results: Forty-five PwMS and 24 healthy persons were included. The test-retest reliability of ST variables values was good-to-excellent for PwMS (ICC range: 0.858–0.919) and moderate-to-excellent for healthy persons (ICC range: 0.569–0.946). The test-retest reliability values of perceived exertion were fair for PwMS (weighted kappa range: 0.279–0.376) and substantial for healthy persons (weighted kappa range: 0.734–0.788). Conclusion: The measurement of ST variables during these 6MWT intervals is reliable and applicable in clinical practice and research to adapt rehabilitation care in PwMS.