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The prevalence of multiple sclerosis (MS) and the age of affected patients are increasing owing to increased longevity of the general population and the availability of effective disease-modifying therapies. However, ageing presents unique challenges in patients with MS largely as a result of their increased frequency of age-related and MS-related comorbidities as well as transition of the disease course from an inflammatory to a neurodegenerative phenotype. Immunosenescence (the weakening of the immune system associated with natural ageing) might be at least partly responsible for this transition, which further complicates disease management. Currently approved therapies for MS are effective in preventing relapse but are not as effective in preventing the accumulation of disability associated with ageing and disease progression. Thus, ageing patients with MS represent a uniquely challenging population that is currently underserved by existing therapeutic regimens. This Review focuses on the epidemiology of MS in ageing patients. Unique considerations relevant to this population are discussed, including the immunology and pathobiology of the complex relationship between ageing and MS, the safety and efficacy of disease-modifying therapies, when discontinuation of treatment might be appropriate and the important role of approaches to support wellness and cognition.

Background: Previous studies demonstrated an association between motor and cognitive performance in multiple sclerosis (MS). However, disease-related brain damage might represent a common substrate to both phenomena, which was not considered before., Objective: Aim of this study is to investigate whether the association between cognition and motor function is beyond structural damage in patients with MS., Methods: Eighty-one healthy controls and 106 relapsing-remitting (RR) MS patients underwent a 3.0 T MRI with quantification of T2-lesion volumes, T1-lesion volumes and normalized brain volumes. A functional examination [Nine-Hole Peg Test (9-HPT), Timed 25-Foot Walk test (T25FW) and Expanded Disability Status Scale] and a neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests) were also administered. Association between demographic, clinical, cognitive, MRI and functional measures were analysed with univariate analyses and hierarchical linear regression., Results: In RRMS patients, Spatial Recall Test and Symbol Digit Modalities Test were positively correlated with 9-HPT (p < 0.001) and T25FW (p ≤ 0.035); Paced Auditory Serial Addition Test (PASAT) correlated with 9-HPT (p ≤ 0.009). 9-HPT and T25FW were significantly associated with normalized brain volumes (p ≤ 0.016), T2- and T1-lesion volumes (p ≤ 0.009). Hierarchical regression models selected age and normalized deep gray matter volume as predictors of T25FW (adjusted-R 2  = 0.109). Younger age, female sex, higher normalized gray matter volume and higher PASAT 2″ scores predicted higher 9-HPT scores (adjusted-R 2  = 0.337)., Conclusions: In RRMS patients, deficit in information processing speed and executive function may contribute to hand motor dysfunction beyond the effect of structural disease-related burden, supporting the integration of motor and cognitive assessment in clinical settings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle factors such as exercise and smoking cessation. Lifestyle modifications and complementary therapies with proven safety and efficacy are essential as part of best-practice MS management, especially when faced with limited access to healthcare services. However, it is unclear to what extent MS clinical practice guidelines and consensus statements address these strategies. A systematic review was conducted, wherein MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, guideline databases and developer sites were searched for guidelines and consensus statements that addressed lifestyle modifications and complementary therapies of interest. Two researchers independently screened articles, extracted data and assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation version II. Thirty-one guidelines and consensus statements were included. Quality was high for 'clarity of presentation' (77%) and 'scope and purpose' (73%), moderate for 'stakeholder development' (56%), 'rigour of development' (48%) and 'editorial independence' (47%), and low for 'applicability' (29%). Two guidelines, related to physical activity and exercise, mindfulness, smoking cessation, and vitamin D and polyunsaturated fatty acid supplementation, scored high in all domains. These guidelines were two of only four guidelines intended for use by people with MS. High-quality guidelines and consensus statements to guide lifestyle modifications and complementary therapies in MS management are limited. Our findings indicate the need for more guidelines intended for use by people with MS, and a further focus on implementation resources., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multiple sclerosis (MS), especially in its progressive phase, involves early axonal and neuronal damage resulting from a combination of inflammatory mediators, demyelination, and loss of trophic support. During progressive disease stages, a microenvironment is created within the central nervous system (CNS) favoring the arrival and retention of inflammatory cells. Active demyelination and neurodegeneration have also been linked to microglia (MG) and astrocyte (AST)-activation in early lesions. While reactive MG can damage tissue, exacerbate deleterious effects, and contribute to neurodegeneration, it should be noted that activated MG possess neuroprotective functions as well, including debris phagocytosis and growth factor secretion. The progressive form of MS can be modeled by the prolonged administration to cuprizone (CPZ) in adult mice, as CPZ induces highly reproducible demyelination of different brain regions through oligodendrocyte (OLG) apoptosis, accompanied by MG and AST activation and axonal damage. Therefore, our goal was to evaluate the effects of a reduction in microglial activation through orally administered brain-penetrant colony-stimulating factor-1 receptor (CSF-1R) inhibitor BLZ945 (BLZ) on neurodegeneration and its correlation with demyelination, astroglial activation, and behavior in a chronic CPZ-induced demyelination model. Our results show that BLZ treatment successfully reduced the microglial population and myelin loss. However, no correlation was found between myelin preservation and neurodegeneration, as axonal degeneration was more prominent upon BLZ treatment. Concomitantly, BLZ failed to significantly offset CPZ-induced astroglial activation and behavioral alterations. These results should be taken into account when proposing the modulation of microglial activation in the design of therapies relevant for demyelinating diseases. Cover Image for this issue: https://doi.org/10.1111/jnc.15394., (© 2021 International Society for Neurochemistry.)

Gray matter atrophy in multiple sclerosis (MS) is thought to be associated with disability and cognitive impairment, but previous studies have sometimes had discordant results, and the atrophy patterns of relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) remain to be clarified. We conducted a meta-analysis using anisotropic effect-size-based algorithms (AES-SDM) to identify consistent findings from whole-brain voxel-based morphometry (VBM) studies of gray matter volume (GMV) in 924 RRMS patients and 204 PPMS patients. This study is registered with PROSPERO (number CRD42019121319). Compared with healthy controls, RRMS and PPMS patients showed gray matter atrophy in the cortico-striatal-thalamic network, sensorimotor network, and bilateral insula. RRMS patients had a larger GMV in the left insula, cerebellum, right precentral gyrus, and bilateral putamen as well as a smaller GMV in the bilateral cingulate, caudate nucleus, right thalamus, superior temporal gyrus and left postcentral gyrus than PPMS patients. The disease duration, Expanded Disability Status Scale score, Paced Auditory Serial Addition Test z-score, and T2-weighted lesion load were associated with specific gray matter regions in RRMS or PPMS. Alterations in the cortico-striatal-thalamic networks, sensorimotor network, and insula may be involved in the common pathogenesis of RRMS and PPMS. The deficits in the cingulate gyrus and caudate nucleus are more apparent in RRMS than in PPMS. The more severe cerebellum atrophy in PPMS may be a brain feature associated with its neurological manifestations. These imaging biomarkers provide morphological evidence for the pathophysiology of MS and should be verified in future research., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

This review hypothesizes that the neurologist represents the linchpin of exercise behavior change within comprehensive multiple sclerosis (MS) care settings. This is based on a series of recent articles that developed actionable practice models for accomplishing such behavior change through the neurologist as the primary agent. This provides tangible, next steps for exercise promotion in MS., (Copyright © 2021 by the American College of Sports Medicine.)

Background/objectives: Associations between patterns of food intake and health in people with multiple sclerosis (MS) are of increasing global interest; however, Australian data are lacking. This study aimed to assess the dietary habits and associations with health outcomes of Australians with MS., Subjects/methods: This cross-sectional study used 2016 survey data from the Australian MS Longitudinal Study, including the Dietary Habits Questionnaire, Hospital Anxiety and Depression Scale, Assessment of Quality of Life, Fatigue Severity Scale, Patient-Determined Disease Steps Scale and 13 MS symptoms scales. Regression models were constructed using directed acyclic graphs., Results: Almost all (94.3%) of the 1490 participants reported making an effort to eating healthy with 21.2% following one or more specific diets, although often not strictly. Overall, 7.9% reported not eating meat, 8.1% reported not consuming dairy, and 4.0% consumed neither food group. A healthier diet score was associated with better mental, physical and total quality of life, and lower depression, and pain scores, and fewer cognition, vision and bowel symptoms. Higher reported fibre, fruit, vegetable and healthy fat scores were positively associated with most health outcomes., Conclusions: Healthier overall diet scores and higher fibre, fruit and vegetable scores were associated with better health outcomes in this sample of Australians adults with MS. However, the proportion of participants avoiding dairy and meat, or adhering to a specific MS diet was much lower than previously reported. Prospective dietary studies are needed to further understand whether dietary change is feasible and affects health outcomes over time., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Background and Purpose: Assessing functional status in people with multiple sclerosis (PwMS) has a major role in determining how to help patients to reach their optimal level of living independently in the community. The Frenchay Activity Index (FAI) is a commonly used scale to evaluate functional status in rehabilitation research and practice settings. The aim of this study was to translate the FAI into the standard Arabic language through the process of cross-cultural adaptation and to explore the internal consistency and construct validity of the produced Arabic version of FAI (A-FAI) among a sample of Arabic-speaking PwMS., Method: The English version of the FAI was translated into Arabic according to the published guidelines. Cronbach's α was used to assess the internal consistency of the A-FAI, and principal factor analysis was conducted to explore the construct validity., Results: Hundred and six subjects participated in the study. The A-FAI has acceptable internal consistency as Cronbach's α was 0.70. The principal factor analysis revealed that the instrument has four main factors: domestic chore, leisure, hobbies, and work, rather than the original three factors scale., Discussion: The A-FAI has acceptable internal consistency and validity. A-FAI provides essential information about the participation level in instrumental activities of daily living activities among PwMS speaking the Arabic language., (© 2021 John Wiley & Sons Ltd.)

People with multiple sclerosis (PwMS) demonstrate gait impairments that are related to falls. However, redundancy exists when reporting gait outcomes. This study aimed to develop an MS-specific model of gait and examine differences between fallers and non-fallers. 122 people with relapsing-remitting MS and 45 controls performed 3 timed up-and-go trials wearing inertial sensors. 21 gait parameters were entered into a principal component analysis (PCA). The PCA-derived gait domains were compared between MS fallers (MS-F) and MS non-fallers (MS-NF) and correlated to cognitive, clinical, and quality-of-life outcomes. Six distinct gait domains were identified: pace, rhythm, variability, asymmetry, anterior-posterior dynamic stability, and medial-lateral dynamic stability, explaining 79.15% of gait variance. PwMS exhibited a slower pace, larger variability, and increased medial-lateral trunk motion compared to controls (p < 0.05). The pace and asymmetry domains were significantly worse (i.e., slower and asymmetrical) in MS-F than MS-NF (p < 0.001 and p = 0.03, respectively). Fear of falling, cognitive performance, and functional mobility were associated with a slower gait (p < 0.05). This study identified a six-component, MS-specific gait model, demonstrating that PwMS, particularly fallers, exhibit deficits in pace and asymmetry. Findings may help reduce redundancy when reporting gait outcomes and inform interventions targeting specific gait domains.

Fatigue and walking difficulties are common impairments and activity limitations in persons with multiple sclerosis (PwMS). Walking fatigability (WF) can be measured by a Distance Walked Index and is defined as a decline in walking distance of 10% or more during the six-minute walking test (6MWT). However, the clinical manifestation and perceived symptoms related to fatigability are still not well documented. Forty-nine PwMS [Expanded Disability Status Scale (EDSS) ≤6] and 28 healthy controls (HC) performed a 6MWT. The perceived severity of 11 common symptoms was rated on a visual analogue scale of 0-10 before, immediately after, and 10, 20 and 30 minutes after the 6MWT by means of the symptom inventory. Short motor impairment screening tests at baseline together with other descriptive measures were performed. Twenty pwMS were categorized in the WF group and were more disabled (EDSS: 4.16 ± 1.41) than the non-walking fatigability group (n = 29, EDSS: 2.62 ± 1.94). PwMS showed exacerbations of several perceived symptoms in MS, where most symptoms returned to baseline within 10 minutes after the walking test. The WF group showed significantly more muscle weakness and gait impairment, together with balance problems, and experienced an increase in spasticity, pain and dizziness after 6MWT. Our findings showed that perceived severity of symptoms are higher in pwMS presenting WF, and increase temporally after the 6MWT. Future research with quantitative measurement during and after walking is recommended., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Slowed information processing speed is among the earliest markers of cognitive impairment in multiple sclerosis (MS) and has been associated with white matter (WM) structural integrity. Localization of WM tracts associated with slowing, but not significant impairment, on specific cognitive tasks in pediatric and young age onset MS can facilitate early and effective therapeutic intervention. Diffusion tensor imaging data were collected on 25 MS patients and 24 controls who also underwent the Symbol Digit Modalities Test (SDMT) and the computer-based Cogstate simple and choice reaction time tests. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivities were correlated voxel-wise with processing speed measures. All DTI metrics of several white matter tracts were significantly different between groups (p < 0.05). Notably, higher MD, RD, and AD, but not FA, in the corpus callosum correlated with lower scores on both SDMT and simple reaction time. Additionally, all diffusivity metrics in the left corticospinal tract correlated negatively with SDMT scores, whereas only MD in the right superior fronto-occipital fasciculus correlated with simple reaction time. In conclusion, subtle slowing of processing speed is correlated with WM damage in the visual-motor processing pathways in patients with young age of MS onset., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Canada has one of the highest rates of multiple sclerosis (MS) in the world, affecting 1 in every 385 individuals. This neurodegenerative condition is unpredictable and variable in symptom profile and disease course making it difficult to manage. Canadians with MS are high users of healthcare services; however, they report multiple unmet needs, high disease burden, and low satisfaction with healthcare. Access to healthcare is vital to health maintenance and may explain these poor experiences. Access is often measured using utilisation as a proxy, which may fail to capture the complexities of access experiences that this population faces. The Candidacy Framework offers an alternative to utilisation measures, by examining the process of accessing care, while considering the impact of social patterning and health system environments on this process. The aim of the current study is to align the experiences of persons with MS in accessing healthcare services with the stages of the Candidacy Framework. Forty-eight individuals with MS living across Ontario were recruited to participate in one of five focus groups or ten individual interviews. Analysis included a first inductive phase, using constant comparative methods, followed by a deductive phase, using content analysis. The Candidacy Framework was not able to capture all experiences shared by persons with MS, including patient-centred care, past experiences and outcome expectation, and care outcomes. We propose these concepts be included as refinements to the current Framework, providing a more thorough explanation of the experiences of persons with MS in accessing care to manage their condition., (© 2021 John Wiley & Sons Ltd.)

Objectives: Notorious for its unpredictable nature, Multiple sclerosis (MS) can have a profound impact on all areas of a person's life, as well as the lives of their family. The aim of this qualitative study was to develop an in-depth understanding of the experiences of individuals living with MS and its impact upon the family system from the perspective of the person with M., Methods: Qualitative data were collected through semi-structured interviews conducted with 14 people living with MS (pwMS). Interviews lasted for approx. 1 hr, were digitally recorded and transcribed verbatim. Anonymized data were then analysed using thematic analysis (Braun & Clarke, 2006, Qualitative Research in Psychology, 3, 77)., Results: The themes identified within participant narratives reflected the turbulent emotions experienced by pwMS after diagnosis and the impact upon their family. Three key themes were identified with six subthemes. The central themes were feeling let down by health care, fears for the future, and finding a way forward. Fears about loss of autonomy and independence characterized the narratives that notably focussed upon impact on the self, despite the study emphasis. Discussions of suicide also featured., Conclusions: The data demonstrate the psychosocial impact of living with MS as life-changing, encompassing traumatic losses and adaptation that was ongoing. The findings highlight the important role of health professionals and the dynamic impact of illness identity and engulfment. Opportunities to improve patient care by acknowledging the emotional impact of MS are discussed. Targeted and timely interventions to enhance psychological well-being, and areas for future research are considered., (© 2020 The British Psychological Society.)

Background: Patient-generated index (PGI) is one of the individualized measures used to measure the quality of life (QOL) in people with different chronic conditions including multiple sclerosis (MS). However, the psychometric properties of the Arabic version of the PGI have not been fully established in Jordanian living with MS. Therefore, the objective of this study is to identify what matters to Jordanian living with MS and to contribute evidence toward the psychometric properties of the Arabic version of the PGI., Methods: A total of 75 participants with MS completed three QOL measures; PGI, the patient determined disease steps (PDDS), and EQ-5D. Generalized estimating equations were used to compare the total score of three QOL measures. Bland-Altman plot and Spearman's correlation coefficient were used to study the relationships and differences between the PGI and the other study measures (PDDS and EQ-5D)., Results: Only 66 (88%) of the participants were able to complete the PGI. Overall, 36 areas of QOL concern were nominated by the participants using the PGI with the top three areas were emotional function (47%), involuntary movement reaction functions (45.5%), and walking (44 %). The average global score of the PGI was lower (34 ± 22) than the global score of the EQ-5D (69 ± 23), and the PDDS (68 ± 24). PGI had a moderate correlation with EQ-5D and PPDS., Conclusion: The Arabic version of the PGI is a feasible, acceptable, and valid measure among Jordanians with MS. PGI also captures more important areas that contribute to QOL than EQ-5D and PDDS. PGI could improve the decision making and guide healthcare professionals to provide appropriate intervention programs to reduce the burdens from MS disease and improve QOL., (© 2021 John Wiley & Sons Ltd.)

Standardization is necessary to ensure the reliability of clinical data and to enable longitudinal and cross-sectional comparisons of data obtained in different centres and countries. In patients with multiple sclerosis (MS), standardized clinical data are needed for monitoring of disability and for collecting real-world evidence for use in research. This Perspective describes attempts to improve the standardization and digitization of clinical data in MS, including digital electronic health recording systems and applications that attempt to offer a comprehensive assessment of patients' neurological deficits and their effects on daily life. Despite the challenges raised by regulatory, ethical and data-privacy considerations, the standardization and digitization of clinical data in MS is expected to generate new insights into the pathophysiology of the disease and to contribute to personalized patient care.

Multiple sclerosis (MS) is a neurological disease characterized by neuroinflammation, demyelination and axonal degeneration along with loss of function in the central nervous system. For many years, research in MS has focused on the efficacy of pharmacological treatments. However, during the last years, many publications have been dedicated to the study of the efficacy of non-pharmacological strategies, such as physical exercise and cognitive training. Beneficial effects of the combination of both strategies on cognitive function have been described in both ageing adults and patients with neurodegenerative diseases, such as MS. The analysis of combining both physical and cognitive stimulation can be summarized by the environmental enrichment (EE) experiments, which are more suitable for animal models. EE refers to housing conditions consisting of exercise and cognitive and social stimulation. In this review, we will summarize the available studies that describe the influence of EE in both MS patients and MS animal models.

With the proposal of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, the need to screen for cognitive deficits within standard clinical care of patients with multiple sclerosis (MS) has been acknowledged. Data regarding how patient characteristics might predict low cognitive performance and therefore require particularly close monitoring is, however, limited so far. We investigated a large, nationwide patient cohort from ambulatory settings, representing the typical distribution of different subtypes, levels of physical disability, and disease durations. Besides cognitive testing with BICAMS, additional sampling of multiple demographics and clinical variables allowed us to characterize general and domain-specific prevalence patterns of cognitive impairment (CI) as well as to delineate which factors are associated with cognitive performance. In a total of 1,094 patients, CI was present in 28% (using a conservative cut-off of the 5th percentile below normative values), with information-processing speed being most frequently affected. Impairment was overall higher in patients with primary progressive (PPMS) and secondary progressive MS than in patients with relapsing-remitting (RR)MS. Regression modelling revealed that disease subtype (i.e., PPMS), long disease duration, high physical disability, unemployment, low educational level, high age, male sex, and the absence of current disease-modifying treatment were important predictors for worse BICAMS' test performance. These results emphasize the importance of continuous cognitive assessment during regular neurological follow-up visits, with a particular focus on patients being identified as high-risk subjects for CI according to the reported factors., (© 2020 The British Psychological Society.)

Although both multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases, their psychiatric disturbances may differ given differences in the neurological manifestations. We used subjective and objective measurements to compare the psychiatric disturbances in patients with MS and NMO.Psychiatric disturbances were assessed in 24 MS and 35 NMO patients using the Beck Hopelessness Scale, Symptom Checklist-95 and the brief version of World Health Organization Quality of Life. Personality was assessed using the Big Five Inventory-10. Disease-related function was assessed using the Fatigue Severity Scale, Short-Form McGill Pain Questionnaire, and the Global Assessment of Function. Positivity offset (PO) and negativity bias (NB) and heart rate variability (HRV) were measured using a modified implicit affect test and photoplethysmograph, respectively. Data were analyzed using analysis of covariance with age and sex as covariates.MS patients had higher levels of depression, anxiety, panic attacks, obsessive-compulsiveness, aggression, paranoia, interpersonal sensitivity, self-regulation problems, stress vulnerability, and lower psychological quality of life (QOL) compared with NMO patients. The PO and NB and HRV values were not significantly different between groups. However, NMO patients had lower QOL, and higher levels of hopelessness, suicidality, and fatigue than the normal range. Disease duration was associated with hopelessness in NMO patients and with several psychiatric disturbances, but not hopelessness, in MS patients.Subjective psychiatric disturbances were more severe in patients with MS than in those with NMO, whereas PO and NB and HRV in patients with NMO were comparable with those of MS patients. Our findings highlight the need for different clinical approaches to assess and treat psychiatric disturbances in patients with MS and NMO.

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a progressive disease course from the onset. The pathological hallmark of MS is the formation of demyelinating lesions in the brain and spinal cord, which can be associated with neuro-axonal damage. Focal lesions are thought to be caused by the infiltration of immune cells, including T cells, B cells and myeloid cells, into the central nervous system parenchyma, with associated injury. MS is associated with a substantial burden on society owing to the high cost of the available treatments and poorer employment prospects and job retention for patients and their caregivers.

This study examined the associations among cardiovascular comorbidities, symptoms of depression and anxiety, and physical activity in persons with multiple sclerosis. Participants with multiple sclerosis (N = 217) completed demographic, cardiovascular comorbidity, depression, and anxiety self-report measures, and wore an accelerometer for 7 days. We examined the bivariate, non-parametric correlations among the variables and conducted parametric, independent samples t-tests when examining the differences in variables based on cardiovascular comorbidity status. Bivariate correlation analysis indicated that there were statistically significant associations between anxiety scores, but not depression scores, and cardiovascular comorbidities. Physical activity, especially moderate-to-vigorous physical activity (MVPA), was correlated with cardiovascular comorbidities. There were small significant differences based on hyperlipidemia status in anxiety scores (p = 0.015, d = -0.42), MVPA (p < 0.001, d = 0.44), and steps/day (p < 0.001, d = 0.50), and based on hypertension status in anxiety scores (p = 0.010, d = -0.35), depression scores (p = 0.046, d = -0.26), MVPA (p = 0.003, d = 0.41), and steps/day (p < 0.001, d = 0.53). The findings indicate that there are significant associations among cardiovascular comorbidities, symptoms of depression and anxiety, and physical activity in persons with multiple sclerosis. Physical activity, specifically MVPA, may be a target for managing those outcomes in persons with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS) that can be tracked through biomarkers of disease status. We investigated the effects of exercise on MS biomarkers associated with CNS status including imaging, blood–brain barrier (BBB) function and neurotrophic factors. Methods: We conducted open‐dated searches of Scopus, Medline, EMBASE and the Cochrane Library. We included studies written in English describing interventions of exercise that measured one or more of the biomarkers associated with MS published up to October 2018. Results: We located a total of 3012 citations through searches in electronic databases. Of these, 16 studies were eligible for review; six studies focused on magnetic resonance imaging (MRI) markers, nine studies focused on neurotrophic factors and three studies focused on BBB function markers. It is of note that two studies included both neurotrophic factor and BBB function markers and are therefore included across categories of biomarkers in this review. The existing evidence from MRI studies confirmed that exercise training can improve CNS integrity and function. There is evidence of a positive effect of exercise training on modulation of BBB permeability markers and brain‐derived neurotrophic factor. Conclusions: Exercise successfully improves MRI outcomes and peripheral biomarkers (i.e. brain‐derived neurotrophic factor) in people with MS. This suggests that exercise can be recommended as an adjuvant therapy for MS treatment. This conclusion is tempered by some methodological limitations including small sample sizes and high drop‐out rates in the reviewed studies. [ABSTRACT FROM AUTHOR]

Objective: This study examined body fatness and its association with cardiorespiratory fitness (CRF) in persons with multiple sclerosis (pwMS) accounting for disability status. Materials and Methods: This study involved a secondary data analysis from a previous study of 62 pwMS. Body fatness was indirect measured as body mass index (BMI), and CRF was measured as peak oxygen consumption from an incremental exercise test with spirometry. Participants were allocated into 3 different groups based on established BMI categories (ie, normal, overweight, and obese), and data were analyzed using SPSS. Results: The average BMI was 27.0 (6.7) kg/m2, and CRF was 19.5 (7.2) mL/kg/min. There was an inverse correlation (pr = ‐.38 [−.57; −.14]; P = .003) between BMI and CRF controlling for age, sex, disease duration, and disability level. ANCOVA with linear contrast analysis revealed a statistical significant reduction in CRF between groups of different BMI categories; normal weight 20.8 (0.85); overweight 19.8 (1.13); and obese 16.9 (1.73) mL/kg/min; F (2, 55) = 3.33, P = .043; η2 = .11. Conclusions: The findings suggest that BMI has a negative impact on CRF in pwMS, with a marked reduction in CRF for those classified as obese compared to those in the normal and overweight category. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on the prevalence and distribution of sedentary behavior (SB) in multiple sclerosis (MS). Objective: The objective of this paper is to describe sitting time as a metric of SB in a large national sample of people with MS. Methods: A total of 8004 individuals from the North American Research Committee on MS (NARCOMS) Registry completed the sitting time question from the International Physical Activity Questionnaire in spring 2015. We present descriptive data on sitting time for the total sample and across sociodemographic, clinical, and behavioral characteristics. Results: The final sample included 6483 individuals. Of these, 36.7% were classified with mild disability, 24.7% with moderate disability, and 38.6% with severe disability. Median sitting time for the total sample was 480 min/day (P25 = 310 min/day, P75 = 720 min/day). Sitting time was highest for individuals with MS who were male (540 min/day), not married (540 min/day), had a disease duration >30 years (540 min/day), were underweight (540.5 min/day), had an annual income of <$15,000 (585 min/day), presented with a progressive form of MS (600 min/day), were classified as insufficiently active (600 min/day), or presented with severe disability (661 min/day). Conclusion: Sitting time is twice as high in individuals with MS compared to the general population (240 min/day). [ABSTRACT FROM AUTHOR]

Objectives This study aimed to investigate whether neurological disability status, heart rate variability ( HRV), cardiorespiratory fitness ( CRF) explained the variance in depressive symptoms in multiple sclerosis ( MS). Methods Associations between CRF (via maximal oxygen uptake; VO2peak), HRV indices of normalized ultra-low ( nULF) and very low frequency domains ( nVLF), neurological disability status and depressive symptoms (using the Depression subscale of the Hospital Anxiety Depression Scale; HADS-D) were assessed in 53 participants with MS and 17 matched controls. Hierarchical linear regression analysis was conducted within the MS subsample to examine the variance explained by neurological disability alone and CRF. Results The groups were similar in mean age ( MS=52.0 years, Control=51.1 years) and sex ( MS=72% female, Control=77% female). Among individuals with MS, HADS-D scores significantly correlated with disability status (sample mean score=4) and VO2peak ( r=−.62, P<.001), whereas VO2peak only correlated with nVLF ( r=0.29, P<.05), but not nULF ( r=0.26, P=.06). The hierarchical linear regression indicated that VO2peak ( P<.05) attenuated the effect of disability status on HADS-D scores such that disability was no longer a predictor of depressive symptomology at step 2 ( P>.05). Conclusion Heart rate variability does not seem to significantly differ between individuals with MS and healthy controls. When accounting for CRF, disability status no longer explains significant variance in depressive symptoms in MS. Accordingly, targeting CRF might be an effective approach for effectively managing depressive symptoms in individuals with MS. [ABSTRACT FROM AUTHOR]

Individuals with multiple sclerosis (MS) are more sedentary than the general population, increasing their propensity for reduced functional ability, mobility, and activities of daily living. Self-efficacy has been one of the most consistent determinants of physical activity across populations, including those with MS. However, no studies exist that have attempted to influence self-efficacy in MS patients, in an effort to improve physical activity participation. We conducted a three-month randomised, controlled trial (n=26), contrasting the effects of an efficacy-enhancement exercise condition and a control exercise condition on exercise adherence, well-being, and affective responses to exercise. Analyses indicated that individuals in the efficacy enhancement condition attended more exercise sessions, reported greater levels of well-being and exertion, and felt better following exercise than individuals in the standard care condition. Regardless of treatment condition, individuals with a stronger sense of exercise self-efficacy, who reported more enjoyment following the exercise sessions, demonstrated significantly greater adherence with the exercise program. We believe this to be the first empirical attempt to change physical activity behavior in persons with MS using a well-established theoretical framework to drive the intervention. Continued examination of self-efficacy as a determinant of behavior change in individuals with MS is needed. [ABSTRACT FROM AUTHOR]

Objectives: Multiple sclerosis (MS) is a neurological disease that commonly results in physical and cognitive dysfunction. Accordingly, MS might impact the ability to safely cross the street. The purpose of this study was to examine the feasibility of a simulated street-crossing task in persons with MS and to determine differences in street-crossing performance between persons with MS and non-MS controls.Methods: 26 participants with MS (median Expanded Disability Status Scale [EDSS] score = 3.5) and 19 controls completed 40 trials of a virtual street-crossing task. There were 2 crossing conditions (i.e., no distraction and phone conversation), and participants performed 20 trials per condition. Participants were instructed that the goal of the task was to cross the street successfully (i.e., without being hit be a vehicle). The primary outcome was task feasibility, assessed as completion and adverse events. Secondary outcomes were measures of street-crossing performance.Results: Overall, the simulated street-crossing task was feasible (i.e., 90% completion, no adverse events) in participants with MS. Participants with MS waited longer and were less attentive to traffic before entering the street compared with controls (all P < .05). Participants with MS also took longer to cross the street and were closer to oncoming vehicles when exiting the street compared to controls (all P < .05). When distracted, all participants took longer to initiate crossing, took longer to cross the street, and made more head turns while crossing (all P < .05). There were no significant group by condition interaction effects (all P > .05).Conclusions: A virtual street-crossing task is feasible for studying street-crossing behavior in persons with mild MS and most individuals with moderate MS. Virtual street-crossing performance is impaired in persons with MS compared to controls; however, persons with MS do not appear to be more vulnerable to a distracting condition. The virtual reality environment presents a safe and useful setting for understanding pedestrian behavior in persons with MS. [ABSTRACT FROM AUTHOR]

The uptake and benefits of the Canadian Physical Activity Guidelines for Adults with Multiple Sclerosis (PAGs) have been validated, but there is limited understanding regarding the knowledge, needs, and preferences of people with multiple sclerosis (MS) for implementing the PAGs outside of clinical research. The authors conducted online, semistructured interviews with 40 persons with MS from across the United States seeking information on awareness of and potential approaches for increasing the uptake of the PAGs. They identified first impressions and potential approaches for increasing the uptake of the PAGs through inductive, semantic thematic analysis. Participants perceived the PAGs as a good introduction for structured exercise but desired more information on how to meet the PAGs. Participants further believed that modifying the PAGs for inclusivity and applying a multifaceted approach for dissemination and implementation may increase uptake of exercise behavior. Physical activity research in MS should include both analyzing the effects of exercise and the unique challenges faced by persons with MS in putting the PAGs into practice. [ABSTRACT FROM AUTHOR]

Three hundred and sixty-three older adults with multiple sclerosis completed a cross-sectional study examining hierarchical correlates of physical activity using a social cognitive theory perspective within a social ecological model (i.e., built environment, social environment, and individual social cognitive theory variables). Hierarchical linear regression analyses were conducted, wherein significant associations were noted for built environment (i.e., land-use mix diversity and aesthetics) and physical activity in Step 1 (R2 =.09). Social and built environment were significant correlates in Step 2 (R2 =.15). Finally in Step 3, individual social cognitive theory variables (i.e., self-efficacy and outcome expectations) were the only significant correlates of total physical activity (R2 =.38). Results were comparable for health-promoting physical activity; however, self-efficacy was the only significant correlate in Step 3 (R2 =.36). This study provides guidance for researchers and practitioners on relevant targets for tailoring interventions for older adults with multiple sclerosis and supports an emphasis on self-efficacy as a primary predictor of health behavior change. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the dual-task cost of both motor and cognitive performances in patients with multiple sclerosis (PwMS) and in healthy controls and to determine their relationships with clinical features in PwMS. The participants performed motor tasks (postural stability, walking, and manual dexterity) and cognitive tasks (mental tracking and verbal fluency) under single- and dual-task conditions. The results showed that postural stability under dual-task conditions did not change, whereas walking and manual dexterity deteriorated, regardless of the concurrent cognitive task, in PwMS (median Expanded Disability Status Scale score: 1) and the healthy controls. Verbal fluency decreased during postural stability, whereas it increased during walking, and it was maintained during manual dexterity in both groups. Mental tracking did not change during walking; it declined during manual dexterity in both groups. Mental tracking during postural stability deteriorated in PwMS, while it did not change in the healthy controls. In general, dual-task costs were associated with baseline performances of tasks rather than clinical features. Therefore, baseline performances of both tasks should be increased for improving dual-task performance in PwMS. [ABSTRACT FROM AUTHOR]

Background Persons with multiple sclerosis ( MS) engage in substantially less overall physical activity than healthy controls, but there is little information on public health rates of physical activity necessary for health benefits. Purpose This study examined the rates of insufficient, moderate, and sufficient physical activity in persons with MS compared with healthy controls. Method Secondary analysis of data from participants with MS ( n = 1521) and healthy controls ( n = 162) who completed the Godin Leisure-Time Exercise Questionnaire ( GLTEQ) as part of a questionnaire battery in 14 previous investigations. Results There were statistically significant differences in overall GLTEQ scores ( F1,1666 = 96.8, P < 0.001, d = 0.83) and rates of physical activity ( χ2 (2, N = 1683) = 94.2, P < 0.001) between MS and control groups. The rates of insufficient, moderate, and sufficient physical activity in the MS group were 58.0%, 15.2%, and 26.8%, respectively. Those with MS were 2.5 times more likely to report insufficient physical activity and 2.3 times less likely to report sufficient physical activity than controls. Conclusion The majority of persons with MS were insufficiently physically active, and this segment represents the largest opportunity for successful behavior change and accumulation of associated health benefits. [ABSTRACT FROM AUTHOR]

Objective Accelerometry has been identified as a possible ecologically valid and objective approach for measuring community ambulation in multiple sclerosis ( MS). This study provides a validation of accelerometer output based on associations with Expanded Disability Status Scale ( EDSS), Patient Determined Disease Steps ( PDDS) Scale, and Multiple Sclerosis Walking Scale-12 ( MSWS-12) scores, timed 25-foot walk (T25 FW) and 6-min walk (6 MW) performance, oxygen cost ( O2 cost) of walking, and spatial and temporal parameters of gait. Materials and Methods 256 persons with MS completed the PDDS and MSWS-12, underwent an examination for the generation of an EDSS score, undertook two T25 FW tests and a 6 MW while wearing a portable metabolic unit for measuring the O2 cost of walking, completed two trials of comfortable walking on a GAITRite electronic walkway for measuring spatial and temporal parameters of gait, and then wore an Actigraph accelerometer during the waking hours of a 7-day period. Results The accelerometer output was significantly correlated with EDSS (ρ = −0.522), PDDS (ρ = −0.551), and MSWS-12 (ρ = −0.617) scores, T25 FW (ρ = −0.595) and 6 MW (ρ = 0.630) performance, and O2 cost of walking (ρ = −0.457). Regarding gait parameters, the accelerometer output was significantly correlated with velocity (ρ = 0.420), cadence (ρ = 0.349), step time (ρ = −0.353), step length (ρ = 0.395), double support (ρ = −0.424), and single support (ρ = 0.400). Conclusion We provide comprehensive evidence from a large sample of persons with MS that further supports accelerometry as a measure of walking behavior. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify why multiple sclerosis exercise research is not translating into real-world participation. To lay the foundations of strong clinical research, considering the translational element of implementation science at the feasibility phase of a trial is vital. Methods: Document analysis was used to examine document sources on exercise activity interventions designed for people living with multiple sclerosis. Document sources focused on multiple sclerosis research that incorporated exercise prescription elements and behaviour change and were feasibility studies incorporating aspects of implementation science. Results: Implementation science should come much earlier than the efficacy or effectiveness research pipeline. An alternate view is outlined where feasibility and implementation science should meet based on case examples that have not yet shown strong efficacy or effectiveness. Findings from our key themes indicate a need for a cyclical iterative approach to the translational process. Multiple aspects of feasibility and how it can be assessed using an implementation science lens to support more successful interventions are provided. The determination of feasibility in behaviour change should involve implementation science as feasibility is drawn on for theory development, optimising the intervention design and quality of implementation strategies, and identifying those delivering the intervention before conducting efficacy and effectiveness research. Conclusions: Document analysis methodology is underused in qualitative research and was appropriate to use as it was a very resource, time-efficient and an unobtrusive process that could track change and development to explore the integration of implementation science at the feasibility phase, with the findings indicating the earlier implementation science is introduced into multiple sclerosis exercise interventions the better. [ABSTRACT FROM AUTHOR]

Objectives There is increasing recognition that physical activity has beneficial consequences among persons with multiple sclerosis ( MS), but there is concern regarding the current degree of physical inactivity in this population because of limitations with previous research and increased recognition of health behaviors in MS. This study compared physical activity levels between large samples of persons with mild MS and matched controls using validated measures of physical activity. Materials and methods The sample included 77 cases of MS and 77 controls matched on age, height, weight, and gender. Physical activity was assessed using five measures, namely the Godin Leisure-Time Exercise Questionnaire ( GLTEQ), International Physical Activity Questionnaire ( IPAQ), and activity counts per day, step counts per day, and time spent in moderate-to-vigorous physical activity ( MVPA) per day by accelerometry. Results There were statistically significant differences between groups in accelerometer activity counts ( t = −3.87, P = 0.0001), accelerometer step counts ( t = −4.29, P = 0.0001), time spent in MVPA ( t = −2.39, P = 0.01), GLTEQ scores ( t = −3.83, P = 0.0001), and IPAQ scores ( t = −3.42, P = 0.0001). The average effect size across all five measures was d = −0.59 and indicated that persons with MS overall were moderately less physically active than the matched controls. Conclusions The primary finding was a moderate reduction in physical activity among those with MS, but the magnitude was substantially smaller than reported in a published meta-analysis. Importantly, the degree of physical inactivity can likely be overcome through the delivery of behavioral interventions for increasing physical activity and this should translate into meaningful consequences for persons with MS. [ABSTRACT FROM AUTHOR]

Motl RW, Goldman M. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Acta Neurol Scand: 2011: 123: 98-104. © 2010 John Wiley & Sons A/S. We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (V̄O) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Study 1 indicated that V̄O was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that V̄O was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = −0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = −0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = −0.40) had statistically significant associations with V̄O. The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. [ABSTRACT FROM AUTHOR]

There is debate in the literature regarding the magnitude, nature, and influence of cognitive impairment in individuals with relapsing-remitting multiple sclerosis (RRMS). Therefore, we conducted a meta-analysis that quantified the overall magnitude of cognitive impairment in individuals with RRMS and identified the domains of cognition and clinical/demographic variables that were moderators of the overall effect. We included 57 studies with 3891 participants that yielded a total of 755 effect sizes. Overall, there was a moderate decline in cognitive functioning in individuals with RRMS compared with healthy controls. Larger effects were observed in cognitive domains of motor functioning, mood status and memory and learning. Regarding demographic and clinical variables, age and gender were moderators of cognitive impairment in all cognitive domains, whereas neurological disability and disease duration primarily moderated performance on tasks assessing memory and learning. [ABSTRACT FROM AUTHOR]

Using meta-analytic procedures, this study examined the overall effect of exercise training interventions on quality of life (QOL) among individuals with multiple sclerosis (MS). We searched MEDLINE, PSYCHINFO and CURRENT CONTENTS PLUS for the period of 1960 to November 2006 using the key words exercise, physical activity and physical fitness in conjunction with QOL and MS. We further conducted a manual search of bibliographies of the retrieved papers as well as literature reviews and contacted study authors about additional studies. Twenty-five journal articles were located and reviewed, and only 13 provided enough data to compute effect sizes expressed as Cohen's d. One hundred and nine effect sizes were retrieved from the 13 studies with 484 MS participants and yielded a weighted mean effect size of g = 0.23 (95% CI = 0.15, 0.31). There were larger effects associated with MS-specific measures of QOL and fatigue as an index of QOL. The nature of the exercise stimulus further influenced the magnitude of the mean effect size. The cumulative evidence supports that exercise training is associated with a small improvement in QOL among individuals with MS. [ABSTRACT FROM AUTHOR]

Background: We reported that a social cognitive theory-based (SCT), Internet-delivered behavioral intervention increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). This paper examined the pattern and predictors of heterogeneity in change for MVPA. Based on previous research, we hypothesized that mild MS disability, fewer MS symptoms, lower baseline MVPA, and positive SCT characteristics (e.g., high exercise self-efficacy) would be associated with greater change in MVPA. Method: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions that were administered via Internet websites and supported with behavioral coaching. Demographic, clinical, symptom, behavioral, and SCT data were from before the 6-month period of delivering the conditions, and MVPA data were from before and after the 6-month period. We examined heterogeneity based on waterfall plots, box plots, and the Levene statistic. We identified predictors of MVPA change using bivariate correlation and multiple, linear regression analyses per condition. Results: The Levene statistic indicated statistically significant heterogeneity of variances for MVPA change between conditions (p =.003), and the waterfall plots and box plots indicated greater heterogeneity in MVPA change for the behavioral intervention. MVPA change score was correlated with baseline MVPA (r = −.33 and r = −.34, p =.0004 and p =.0001) in both conditions and walking impairment (r = −.188, p =.047) and race (r =.233, p =.014) in the behavioral intervention condition. The regression analysis indicated that baseline MVPA (Standardized B = −.449, p =.000002), self-reported walking impairment (Standardized B = −.310, p =.0008), and race (Standardized B =.215, p =.012) explained 25.6% of variance in MVPA change for the behavioral intervention condition. Conclusion: We provide evidence for walking impairment, baseline MVPA, and race as predictors of the heterogeneity in the pattern of MVPA change with a behavioral intervention. [ABSTRACT FROM AUTHOR]

Purpose: As people with long-standing disabling conditions age, the interplay between pre-existing conditions and new comorbidities can present unique challenges. Therefore, the current study explored relationships between resilience and health, health promotion, and quality of life among older adults living with multiple sclerosis (MS). Method: Adults recruited from National MS Society chapters completed a mailed survey about their health, health promotion, and well-being. Results: The 147 respondents (mean age = 72 years) reported an average of three additional comorbidities and had been diagnosed with MS for 35 years on average. Resilience scores were most highly correlated with depressive symptoms, spiritual growth, social support, incapacity status, and quality of life. Resilience scores significantly improved prediction of emotional health, after controlling for other functional and psychosocial variables. Conclusion: Nurses can help patients with chronic conditions, such as MS, develop strategies for regulating their emotional health to adapt to new health challenges. [Journal of Gerontological Nursing, 51(1), 15–23.] [ABSTRACT FROM AUTHOR]

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal–midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS. [ABSTRACT FROM AUTHOR]

Aim: Cannabis-based medication has recently been made available in the NHS for reducing pain and spasticity in patients with multiple sclerosis (MS). The currently available preparation of Sativex (nabiximols) contains a combination of botanical cannabis extracts with cannabidiol (CBD) and tetrahydrocannabinol (THC) with almost equal amounts in addition to minor cannabinoids and terpenoids and is delivered via an oro-mucosal spray. The present study aims to examine the use and trends in prescribing cannabinoid-based Sativex to control pain in patients diagnosed with MS. Methods: Primary care prescribing data for cannabinoid-based Sativex (2013-2022) from the Prescription Cost Analysis were extracted and analysed. Linear regression analyses were performed to examine prescription trends and prescription costs (average change per year). Results: There was a general increasing trend in the number of prescriptions each year, from 4.42 items dispensed per 100,000 people in 2013 to 5.15 in 2022. Overall, prescription items for cannabinoid-based Sativex increased by 0.34% per year (95% CI:−3.98, 4.67, p = 0.860) on average between 2013 and 2022. On average, a 2.43% (95% CI: −5.78, 0.92, p = 0.133) increase per year was observed for the costs of cannabinoid-based Sativex from 2013 to 2022. Conclusion: The results suggested that cannabinoid-based Sativex should be considered an option due to its effectiveness, acceptable tolerance, and safety profile in the prescribing of Sativex. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fatigue is the most prevalent symptom among people with multiple sclerosis (PwMS). Although exercise effectively reduces fatigue, the relationship between daily physical activity and fatigue has only recently been demonstrated. OBJECTIVE: The aim of this study was to evaluate the prevalence of fatigue and to understand the relationship with several variables in French PwMS. METHODS: Data were collected from 191 PwMS using Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) for fatigue, and the Godin Leisure-Time Exercise Questionnaire (GLTEQ) for physical activity. RESULTS: 110 PwMS (57%), 35 PwMS (18%) and 46 PwMS (24%) were considered as fatigued, non-fatigued and in the grey zone, respectively. Greater physical activity was observed in non-fatigued PwMS (20.2±19.8) compared to fatigued PwMS (12.5±14.1). FSS and MFIS scores were associated with physical activity (r = –0.28 and r = –0.25, respectively, p < 0.05). Using multivariate analysis, disability, physical activity and being unemployed explained 21% of the variance of the MFIS. CONCLUSIONS: The present study confirms that physical activity and fatigue are associated. Disability and unemployment status should also to be consider when assessing fatigue. Activity-oriented health policies should be redesigned to improve fatigue among PwMS. [ABSTRACT FROM AUTHOR]

The present study examined the relationship between the worsening of symptoms across a 3-5-year period of time and self-reported physical activity in a sample of 51 individuals with multiple sclerosis (MS). Of the 51 participants, 35 reported a worsening of symptoms over the 3-5-year period of time. The worsening of symptoms was associated with significantly and moderately lower levels of selfreported physical activity independent of depression and EDSS scores and MS-disease course (P=0.04). This study provides novel evidence that a worsening of symptoms is associated with lower levels of physical activity in individuals with MS. [ABSTRACT FROM AUTHOR]

Background: Dysfunctions of the hypothalamic‐pituitary‐adrenal (HPA) axis can trigger multiple sclerosis (MS) symptoms. Mood disorders comorbid with MS are implicated in the HPA axis activation in most people with MS (pwMS). This study purposed to examine salivary cortisol (SC) levels and their association with mood disorders in pwMS. Methods: Forty‐three men as pwMS and sixteen men as healthy controls (HC) were included in this study. pwMS and HC completed the Beck Depression Inventory (BDI), 36‐Item Short Form Survey (SF‐36), Fatigue Severity Scale (FSS), Depression Anxiety and Stress Scale, and Hospital Anxiety and Depression Scale questionnaires. SC levels were also measured in pwMS and HC. A linear regression model was used to analyze the relationship between the Expanded Disability Status Scale (EDSS) and mood disorders and SC levels. Pearson's or Spearman's tests examined the correlation between SC levels and mood disorders. Results: The SC level, anxiety, depression, fatigue, and stress were significantly higher in pwMS than in HC (p < 0.05). pwMS also showed significant correlations between SC levels and role physical (r = 0.3, p < 0.05) and emotional (r = 0.34, p < 0.05) in SF‐36. Among SF‐36 domains, only general health (β = −0.72, p < 0.05) and physical functioning (β = −1.61, p < 0.05) were negatively associated with disease duration. No correlation was found between SC levels and anxiety, depression, and fatigue (p > 0.05). Conclusions: The pwMS showed mild to moderate depression, anxiety, and fatigue. Only general health and physical functioning as aspects of quality of life were related to disease duration, while SC levels, mood disorders, and other quality‐of‐life domains were not associated with clinical characteristics. Also, this study failed to find a significant role for SC as a valuable marker in approaching mood disorders in pwMS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system CNS characterized by demyelination, inflammation, and neurodegenerative changes, making it the most common nontraumatic disabling neurological disease in young adults. While current pharmacological treatments primarily target immunomodulation or immunosuppression, exercise is gaining increasing attention from the scientific community as an adjunctive therapy. This review explores the potential biological mechanisms of exercise in animal models of MS, focusing on its effects on neuroprotection and inflammation. The review examines how exercise inhibits pro-inflammatory microglial reactivity, stabilizes the blood–brain barrier, and enhances neurotrophic factor expression in animal studies. Future research directions are proposed by summarizing the evidence and limitations of existing animal models of MS, emphasizing the need to further validate these mechanisms in humans to better integrate exercise into the comprehensive management of MS. Additionally, investigating exercise-induced biomarkers for MS symptom reduction may provide a scientific basis for new therapeutic strategies. [ABSTRACT FROM AUTHOR]