Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study.

BACKGROUND: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue. METHODS: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume. RESULTS: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume). CONCLUSIONS: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

MiRNA-based therapeutic potential in multiple sclerosis.

This review will briefly introduce microRNAs (miRNAs) and dissect their contribution to multiple sclerosis (MS) and its clinical outcomes. For this purpose, we provide a concise overview of the present knowledge of MS pathophysiology, biomarkers and treatment options, delving into the role of selectively expressed miRNAs in clinical forms of this disease, as measured in several biofluids such as serum, plasma or cerebrospinal fluid (CSF). Additionally, up-to-date information on current strategies applied to miRNA-based therapeutics will be provided, including miRNA restoration therapy (lentivirus expressing a specific type of miRNA and miRNA mimic) and miRNA inhibition therapy such as antisense oligonucleotides, small molecules inhibitors, locked nucleic acids (LNAs), anti-miRNAs, and antagomirs. Finally, it will highlight future directions and potential limitations associated with their application in MS therapy, emphasizing the need for improved delivery methods and validation of therapeutic efficacy.

User Experience of a Large-Scale Smartphone-Based Observational Study in Multiple Sclerosis: Global, Open-Access, Digital-Only Study.

BACKGROUND: The Floodlight Open app is a digital health technology tool (DHTT) that comprises remote, smartphone sensor-based tests (daily activities) for assessing symptoms of multiple sclerosis (MS). User acquisition, engagement, and retention remain a barrier to successfully deploying such tools. OBJECTIVE: This study aims to quantitatively and qualitatively investigate key user experience (UX) factors associated with the Floodlight Open app. METHODS: Floodlight Open is a global, open-access, digital-only study designed to understand the drivers and barriers in deploying a DHTT in a naturalistic setting without supervision and onboarding by a clinician. Daily activities included tests assessing cognition (Information Processing Speed and Information Processing Speed Digit-Digit), hand-motor function (Pinching Test and Draw a Shape Test), and postural stability and gait (Static Balance Test, U-Turn Test, and Two-Minute Walk Test [2MWT]). All daily activities except the 2MWT were taken in a fixed sequence. Qualitative UX was studied through semistructured interviews in a substudy of US participants with MS. The quantitative UX analysis investigated the impact of new UX design features on user engagement and retention in US participants for 3 separate test series: all daily activities included in the fixed sequence (DA), all daily activities included in the fixed sequence except the Static Balance Test and U-Turn Test (DAx), and the 2MWT. RESULTS: The qualitative UX substudy (N=22) revealed the need for 2 new UX design features: a more seamless user journey during the activation process that eliminates the requirement of switching back and forth between the app and the email that the participants received upon registration, and configurable reminders and push notifications to help plan and remind the participants to complete their daily activities. Both UX design features were assessed in the quantitative UX analysis. Introducing the more seamless user journey (original user journey: n=608; more seamless user journey: n=481) improved the conversion rate of participants who enrolled in the study and proceeded to successfully activate the app from 53.9% (328/608) to 74.6% (359/481). Introducing reminders and push notifications (with reminders and notifications: n=350; without reminders and notifications: n=172) improved continuous usage time (proportion of participants with ≥3 consecutive days of usage: DA and DAx: ~30% vs ~12%; 2MWT: ~30% vs ~20%); test completion rates (maximum number of test series completed: DA: 279 vs 64; DAx: 283 vs 126; 2MWT: 302 vs 76); and user retention rates (at day 30: DA: 53/172, 30.8% vs 34/350, 9.7%; DAx: 53/172, 30.8% vs 60/350, 17.1%; 2MWT: 39/172, 22.6% vs 22/350, 6.2%). Inactivity times remained comparable. CONCLUSIONS: The remote assessment of MS with DHTTs is a relatively nascent but growing field of research. The continued assessment and improvement of UX design features can play a crucial role in the successful long-term adoption of new DHTTs.

[Research progress on the relationship between TRAF6 and neurodegenerative diseases].

Given the increasing trend of aging population in the world, neurodegenerative diseases (NDDs), a common type of diseases that mostly occur in the elderly, have attracted much more attention. It has been shown that tumor necrosis factor receptor-associated factor 6 (TRAF6) is involved in the regulation of neuroinflammation, an important pathological feature of NDDs, and affects the occurrence and development of NDDs. Most importantly, the regulatory effect of TRAF6 is related to its ubiquitination. Therefore, in the present paper, the molecular structure, biological function, and ubiquitination mechanism of TRAF6, and its relationship with some common NDDs, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, were analyzed and summarized. The possible molecular mechanisms by which TRAF6 regulates the occurrence of NDDs were also elucidated, providing a theoretical basis for exploring the etiology and treatment of NDDs.

Multisensory mental imagery of fatigue in patients with multiple Sclerosis. Preliminary evidence from a fMRI study.

Fatigue, defined as a subjective lack of physical and/or mental energy, is a clinical symptom highly characterizing multiple sclerosis (MS). The present study utilized a novel approach to the study of fatigue, examining first person-mental imagery of the symptom. Eighteen right-handed patients with MS (14F, 4 M, mean age 45.8 ± 8.15 years) were evaluated and were compared to nineteen healthy controls (10F, 9 M, mean age 43.15 ± 8.34 years) Patients were all in relapsing remitting form and no patient had presented relapses in the 6 months prior to inclusion in the study. We evaluated their behavioral performance and fMRI activations. We used an fMRI paradigm used to trigger first person-mental imagery of fatigue, through short sentences describing the principal manifestations of fatigue. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. They made a vividness rating by pressing the corresponding button. Behaviorally, we found that patients' mean scores at the Multidimensional Fatigue Symptom Inventory for the general scale, physical scale, and mental scale were significantly higher than healthy controls (p = 0.05, p = 0.002, p = 0.006 respectively), but not for the emotional scale and for vigor scale (p = 0.207, n.s., p = 0.06, n.s.). In the imagery fMRI task, patients were significantly slower (mean reaction times and standard deviation: 2.24 s ± 0.33) than controls (mean reaction times and standard deviation: 1.918 s ± 0.455) for the SI task (Z=-2.058, p = 0.040), while no significant difference was found for the VI task. Regarding brain mapping, our main result is a group by task interaction. The SI task (vs. VI task) in healthy controls (relative to patients) increased activation in the left inferior parietal lobule. These preliminary results indicate that fatigue is related to dysfunctions in higher-order aspects of motor control, given the role of the posterior parietal lobe in motor planning and multisensory integration.

Assessing the visual afferent pathway with the multifocal visual evoked potentials in the radiologically isolated syndrome.

The early identification of individuals with radiologically isolated syndrome (RIS) who are at an elevated risk of progressing to multiple sclerosis (MS) is essential for making informed treatment decisions. This study aimed to evaluate the predictive potential of multifocal Visual Evoked Potentials (mfVEP) measures in individuals with RIS with respect to their conversion to MS. A prospective observational cohort study was conducted, involving 21 individuals with RIS recruited from a MS center. Baseline assessments, including mfVEP, magnetic resonance imaging (MRI), and clinical examinations, were performed, and participants were longitudinally followed for up to 24 months. The primary outcome measures were the conversion to MS. Over a clinical follow-up period of 24 months, five individuals (5/21) with RIS progressed to MS. MfVEP amplitude responses (interocular and monocular probability analysis) demonstrated abnormal cluster visual field defects in 47.6% of RIS eyes at baseline, whereas multifocal VEP latency analysis showed significant delays in 38.4%. A reduction in interocular amplitude [OR = 0.036, (95% CI 0.003-0.503); P = 0.014], monocular amplitude [OR = 0.083, (95% CI 0.007-0.982); P = 0.048], and a prolonged interocular latency [OR = 0.095, (95% CI 0.009-0.972); P = 0.047] were associated with a higher relative risk of clinical conversion at the 2-year follow-up. Multifocal VEP may serve as a novel and independent risk factor for predicting the conversion to MS in individuals with Radiologically Isolated Syndrome.

Osteopontin predicts late-time salience network-related functional connectivity in multiple sclerosis.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely utilized to investigate plasticity mechanisms and functional reorganization in multiple sclerosis (MS). Among many resting state (RS) networks, a significant role is played by the salience network (SN, ventral attention network). Previous reports have demonstrated the involvement of osteopontin (OPN) in the pathogenesis of MS, which acts as a proinflammatory cytokine ultimately leading to neurodegeneration. Concentration of serum OPN was related to MRI findings 10.22±2.84 years later in 44 patients with MS. Local and interhemispheric correlations (LCOR, IHC), ROI-to-ROI and seed-based connectivity analyses were performed using serum OPN levels as independent variable along with age and gender as nuisance variables. We found significant associations between OPN levels and local correlation in right and left clusters encompassing the central opercular- and insular cortices (p-FDR = 0.0018 and p-FDR = 0.0205, respectively). Moreover, a significant association was identified between OPN concentration and interhemispheric correlation between central opercular- and insular cortices (p-FDR = 0.00015). Significant positive associations were found between OPN concentration and functional connectivity (FC) within the SN (FC strength between the anterior insula ventral division and 3 other insular regions, F(2,13) = 7.84, p-FDR = 0.0117). Seed-based connectivity analysis using the seven nodes of the SN resulted in several positive and inverse associations with OPN level. Serum OPN level may predict FC alterations within the SN in 10 years.

The relationship between cognitive function and functional capacity, and cognitive reserve and reaction time in patients with multiple sclerosis.

BACKGROUND: Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with. OBJECTIVE: To investigate the relationship between aerobic capacity, strength, disability, depression, fatigue, and cognitive reserve and function. METHODS: The mobile applications Trail Making Test (TMT A-B), Digit Span Test (DST), Visuospatial Memory Test (VSMT), and Tap Fast were used in the cognitive function evaluation. Functional performance was assessed with the 6-minute walk test (6MWT), 5-Time Sit-to-Sand (5STS) test, and grip strength. Cognitive Reserve Index (CRI), Beck Depression Inventory, Fatigue Severity Scale (FSS), and Nottingham Health Profile were also used. RESULTS: A significant difference was found between the MS and control groups only in the 6MWT, STS-5, grip strength, TMT, VSMT, and Tap Fast. Good correlation was found between the TMT-A and 6MWT and physical mobility. A fair correlation was shown between grip strength, energy, and pain status. A good correlation was found between TMT-B and 6MWT, and a fair relationship with disability, cognitive reserve, and pain. Good correlation was observed between the DST and 6MWT, left grip strength, pain, and energy status; fair correlations were found between right grip strength, cognitive reserve, and physical mobility. Good correlation was found between the VSMT and energy. A fair relationship between disability, cognitive reserve, and pain was demonstrated. Good correlation was observed between the Tap Fast score and disability, 5STS, FSS, energy, and physical mobility. A fair relationship was found between pain and social isolation. CONCLUSION: It has been shown that cognitive performance in MS is related to disability, functional performance, cognitive reserve, fatigue, and general health. TRIAL REGISTRATION: NCT06084182.

ANTECEDENTES: A disfunção cognitiva é frequentemente observada na esclerose múltipla (EM). No entanto, existem resultados conflitantes sobre os fatores aos quais está associada. OBJETIVO: Investigar a relação entre capacidade aeróbica, força, incapacidade, depressão, fadiga e reserva e função cognitiva. MéTODOS: Os aplicativos móveis Trail Making Test (TMT A-B), Digit Span Test (DST), Visuoespacial Memory Test (VSMT) e Tap Fast foram utilizados na avaliação da função cognitiva. O desempenho funcional foi avaliado por meio do teste de caminhada de 6 minutos (TC6), Teste de Sentar-Levantar Cinco Vezes (TSL5) e força de preensão manual. Também foram utilizados Índice de Reserva Cognitiva (IRC), Inventário de Depressão de Beck, Escala de Gravidade de Fadiga (EGF) e Perfil de Saúde de Nottingham. RESULTADOS: Foi encontrada diferença significativa entre os grupos EM e controle apenas no TC6, TSL5, força de preensão, TMT, VSMT e Tap Fast. Foi encontrada boa correlação entre o TMT-A e o TC6 e a mobilidade física. Foi demonstrada uma correlação razoável entre força de preensão, energia e estado de dor. Foi encontrada uma boa correlação entre o TMT-B e o TC6, e uma relação razoável com incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o DST e o TC6, força de preensão esquerda, dor e estado energético; correlações justas foram encontradas entre força de preensão direita, reserva cognitiva e mobilidade física. Foi encontrada boa correlação entre o VSMT e a energia. Foi demonstrada uma relação justa entre incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o escore Tap Fast e incapacidade, TLS5, EGF, energia e mobilidade física. Foi encontrada uma relação justa entre dor e isolamento social. CONCLUSãO: Foi demonstrado que o desempenho cognitivo na EM está relacionado com incapacidade, desempenho funcional, reserva cognitiva, fadiga e saúde geral. REGISTRO DE TESTE: NCT06084182.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles' outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study.

OBJECTIVE: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute. MATERIALS AND METHODS: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART. RESULTS: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART. CONCLUSION: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Perceived physical and mental fatigability in older adults with and without multiple sclerosis.

BACKGROUND: Fatigue stands out as a prevalent and debilitating symptom in both Multiple Sclerosis (MS) and the aging population. Traditional methods for measuring perceived fatigue may not adequately account for individual activity differences, leading to varied prevalence rates. Perceived fatigability anchors fatigue to specific activities with predetermined intensity and duration, thereby mitigating self-pacing bias. Despite its potential, perceived fatigability is poorly understood in older adults, particularly those with neurological conditions, including MS. This study thus aimed to (1) investigate whether, among older adults, MS was associated with worse perceived physical and mental fatigability; (2) evaluate whether, among older adults with MS (OAMS), greater patient-reported disease-related disability was associated with worse perceived physical and mental fatigability. METHODS: Participants were 96 older adults with a physician-confirmed diagnosis of MS (mean age: 64.6 ± 4.2) and 110 healthy controls (mean age: 68.2 ± 7.2), all confirmed to be dementia-free through established case conference procedures. Physical and mental fatigability were measured using the Pittsburgh Fatigability Scale, a 10-item questionnaire (score range: 0 to 50) designed to assess fatigue levels that individuals expect to feel after engaging in a range of typical activities for older adults. MS disease-related disability was assessed with the Patient Determined Disease Steps scale, which ranges from 0 (normal) to 8 (bedridden), with scores ≥ 2 indicating worse MS-related disability after a median split. Separate linear regression models were performed to investigate associations between group status (MS vs. Control) as the predictor and perceived physical and mental fatigability scores as the outcome variables. Within the MS group, additional linear regression models were performed to explore the relationship between disease-related disability and fatigability levels. All models adjusted for age, sex, race, education, global health, general cognitive function, and depressive symptoms levels. RESULTS: The fully adjusted models yielded the following key findings: OAMS reported significantly higher levels of perceived physical fatigability (M = 25.11 ± 9.67) compared to controls (M = 17.95 ± 8.35) (p = 0.003). Similarly, the perceived mental fatigability in OAMS (M = 16.82 ± 11.79) was significantly greater than that in controls (M = 9.15 ± 7.12) (p = 0.003). Within the MS group, individuals with greater disease-related disability reported significantly greater levels of both physical (M = 30.13 ± 7.71 vs. 18.67 ± 8.00, p < 0.001) and mental fatigability (M = 20.31 ± 12.18 vs. 12.33 ± 9.69, p = 0.009) compared to those with lower MS-related disability. Of note, the significance of these findings persisted in models that adjusted for depressive symptoms. CONCLUSION: Our study provides compelling evidence that OAMS exhibit significantly higher perceived physical and mental fatigability compared to healthy controls. Additionally, worse MS-related disability correlates with worse physical and mental fatigability. These results persist after adjusting for confounders including depressive symptoms. Our findings underscore the necessity of holistic management strategies that cater to both physical and psychological aspects of MS, laying a foundation for future studies to uncover the pathophysiological mechanisms of fatigability in older adults with and without MS.

Creating an automated tool for a consistent and repeatable evaluation of disability progression in clinical studies for multiple sclerosis.

BACKGROUND: The lack of standardized disability progression evaluation in multiple sclerosis (MS) hinders reproducibility of clinical study results, due to heterogeneous and poorly reported criteria. OBJECTIVE: To demonstrate the impact of using different parameters when evaluating MS progression, and to introduce an automated tool for reproducible outcome computation. METHODS: Re-analyzing BRAVO clinical trial data (NCT00605215), we examined the fluctuations in computed treatment effect on confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) when varying different parameters. These analyses were conducted using the msprog package for R, which we developed as a tool for CDP assessment from longitudinal data, given a set of criteria that can be specified by the user. RESULTS: The BRAVO study reported a hazard ratio (HR) of 0.69 (95% confidence interval (CI): 0.46-1.02) for CDP. Using the different parameter configurations, the resulting treatment effect on CDP varied considerably, with HRs ranging from 0.59 (95% CI: 0.41-0.86) to 0.72 (95% CI: 0.48-1.07). The treatment effect on PIRA varied from an HR = 0.62 (95% CI: 0.41-0.93) to an HR = 0.65 (95% CI: 0.40-1.04). CONCLUSIONS: The adoption of an open-access tool validated by the research community, with clear parameter specification and standardized output, could greatly reduce heterogeneity in CDP estimation and promote repeatability of study results.

The interaction between exercise and neurofilament light chain in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Exercise in patients with multiple sclerosis (pwMS) found to improve symptom management and regain function. Whether exercise lowers neurofilament light chain (NfL), neuroaxonal injury biomarker, in MS remains unknown with conflicting findings. In this study, we aimed to assess the interaction between exercise and NfL levels in pwMS. METHODS: Systematic search of Medline, CENTRAL, Embase, and Web of Science was conducted until March 2024 to identify relevant reports. We included studies that investigated the mean change in NfL levels pre- and post-training programs and compared them to different exercise programs or no exercise activity control groups. A standardized mean difference (SMD) with a 95 % confidence interval were applied using a random-effects model. RESULTS: Of 222 articles, 7 studies met the inclusion criteria. Patients who underwent structured exercise programs had a significant decrease in blood NfL levels post-training (SMD -0.55; 95 % CI -1.00, -0.09). Specifically, outdoor Pilates and home-based trainings were significantly associated with blood NfL reduction (SMD -2.08; 95 % CI -2.99, -1.17) and (SMD -1.46; 95 % CI -2.28, -0.64), respectively. Patients in the control group did not show significant differences in blood NfL levels between the baseline and at the end of the study (SMD 0.04; 95 % CI -0.17, 0.24). Subgroup analysis based on duration revealed that 8 weeks of exercise significantly reduced blood NfL levels (SMD -0.73; 95 % CI -1.35, -0.11). CONCLUSION: Our study provides preliminary evidence for the potential role of training in reducing blood NfL levels in pwMS. However, more rigorous, and well-designed studies are warranted to confirm these findings.

Psychometric properties of the modified reaching performance scale in persons with multiple sclerosis.

BACKGROUND: A valid and reliable assessment tool to describe the quality of the movement pattern of reaching can provide valuable insights into motor performance deficits in persons with MS (pwMS). The Reaching Performance Scale, developed for stroke, is a promising scale to assess movement patterns in pwMS. However, psychometric properties of the scale are lacking in pwMS. OBJECTIVES: Firstly, to investigate the content validity of the modified Reaching Performance Scale for application in patients with MS (mRPS). Secondly, to investigate the psychometric properties (within- and between-session reliability and concurrent validity) of the mRPS for pwMS. METHODS: Forty-five pwMS (mean EDSS 6.6 pt, IQR 6-7.5) executed the mRPS that rates the quality of movement patterns and compensations during reach to grasp tasks. The content validity was determined by an expert panel based on observations of subjects performing the RPS. The reliability was based on five repetitions within one day, and between two days. For the concurrent validity, outcome measures at two levels of the International Classification of Functioning were correlated with the mRPS: Body Structure and Function level: Fugl-Meyer Assessment of the Upper Limb (FMA-UL), maximal isometric hand grip strength (HGS; Activity level: Action Research Arm Test (ARAT), Box and Blocks Test (BBT), Nine Hole Peg Test (NHPT) and Trunk Impairment Scale 2.0 (TIS 2.0) as well as perceived performance by the Manual Ability Measure-36 (MAM-36). RESULTS: Scale modifications were made only on the ratings of the trunk displacement subscale. The mRPS had excellent agreement scores for within-session reliability (range of Kappa between 0.85 and 0.98) and moderate-to-excellent agreement scores for between-session reliability (K: 0.66-1.00). Regarding validity, the mRPS was highly correlated with the ARAT (rho=0.74, p < 0.001), followed by moderate correlations with trunk performance (TIS 2.0, rho= 0.61, p < 0.001), hand function (BBT: rho=0.64, p < 0.001; NHPT: rho=-0.61, p < 0.001) and perceived performance (MAM36 rho= 0.53, p < 0.001). CONCLUSION: The mRPS is a reliable measurement tool to describe the movement pattern quality and motor compensations used during reaching in pwMS. Concerning concurrent validity, the mRPS is partially related to other measures of upper limb and trunk performance.

Comparative analysis of cognitive and physical characteristics in late-onset, adult-onset and early-onset multiple sclerosis patients.

BACKGROUND: Late-onset multiple sclerosis (LOMS or L; MS) and early-onset MS (EOMS or E) are less common, and their prognosis can be different. To characterize the demographic and clinical features, and clinical outcomes of LOMS and EOMS patients, comparing them to adult-onset MS (AOMS or A) patients. METHODS: The study was conducted as a secondary analysis of a prospective study. The participants were divided into three groups according to age of MS onset: early onset (<18 years of age), adult-onset (20-40 years of age), and late-onset (>55 years of age). Demographic variables, oligoclonal bands, IgG index, and Expanded Disability Status Scale (EDSS) score in admission, first year, second year and current EDSS were evaluated. The Timed 25-Foot Walk Test (T25FW), Timed Up and Go (TUG), Multiple Sclerosis Walking Scale-12, Single Leg Standing Test, Activity-Specific Balance Confidence Scale, Nine-Hole Peg Test, Epworth Sleepiness Scale and Restless Legs Syndrome Severity Scale were performed. Appropriate statistical analysis was made. RESULTS: A total of 658 pwMS was included in the study and divided into three groups: EOMS (n = 117), AOMS (n = 499), and LOMS (n = 42). Statistically significant differences were determined between groups in terms of age [L (mean:59.86±5.45 years-y-)> A (36.87±9.12 y)> E(26.56±8.85 y), p < 0.001], education level, current EDSS score (L > E, p < 0.001), EDSS score in first admission, EDSS score in the first year, EDSS score in the second year (L > A > E, p < 0.001), reached an EDSS score 6 (E > L p = 0.001, E > A p = 0.015), disease duration (E > A, E > L, mean E = 11.66±9.7 y, A = 7.99±7.4 y, L = 6.31±4.67 y) time switching second-line treatment to the third line (E > L p < 0.001, A > L p = 0.002, mean E = 171.73±83.29 months-m-, A = 136.13±65.75 m, L = 65.85±45.96 m), number of relapses (A > E > L, median E = 4.0, A = 3.0, L = 2.0), distribution of MS type and oligoclonal band types. Significant differences were found in T25FW and TUG. Post-hoc analysis showed that participants in the LOMS group have longer T25FW (mean L = 7.8 ± 6.11, A = 6.25±5.09, E = 5.72±3.13, p = 0.011) and TUG (mean L = 11.01±5.53, A = 9.57±8.04, E = 8.38±5.51, p = 0.007) times than the AOMS and EOMS groups. CONCLUSION: Our result revealed that individuals with LOMS face elevated disability levels and a heightened propensity to transition from first-line treatments to more advanced therapeutic interventions. LOMS have worse lower extremity functional status than AOMS and EOMS patient. Clinical evaluations and treatment choices require more attention in LOMS. However, according to the low number of LOMS in our cohort, these results were considered cautious, and more wide and multi-center studies must be designed.

Predictors of six-month change in health-related quality of life in people with multiple sclerosis: A secondary data analysis of a randomized controlled trial.

BACKGROUND: Symptomatic treatment in people with multiple sclerosis (pwMS) requires multidisciplinary rehabilitation to alleviate disease progression and increasing health-related quality of life (HRQoL). However, the participant- and disease-specific factors that predict sustained improvement in HRQoL in pwMS undergoing inpatient rehabilitation remain unclear. Identifying these factors can help individually tailor inpatient rehabilitation programmes. Therefore, the aim of this study was to identify factors of pwMS at clinic entry for a three-week multidisciplinary inpatient rehabilitation that predict the change in physical and mental HRQoL over six months. METHODS: This is a secondary data analysis of a randomized controlled trial (NCT04356248) conducted at the Valens Rehabilitation Centre, Switzerland. HRQoL was assessed with the Medical Outcome Study 36-item Short Form Health Survey (SF-36) at clinic entry (T0; baseline) and six months after (T3; six-month follow-up). Data for 99 pwMS (mean age in years: 49.60 ± 10.17 SD, mean Expanded Disability Status Scale (EDSS) score: 4.62 ± 1.33 SD, 68.7 % female) were analysed using multiple linear regression. Outcome variables were six-month change in SF-36 Physical (ΔPCS) and Mental Component Scale (ΔMCS) scores. Predictor variables included baseline scores of PCS or MCS, fatigue, anxiety, depressive mood, cardiorespiratory fitness (V̇O2peak/kg), self-efficacy, smoking status, education level, age, EDSS, sex, time since diagnosis and MS phenotype. RESULTS: The regression model with ΔPCS as outcome variable explained 18.6 % of the variance of the ΔPCS score (p = .003). Lower PCS score (p < .001) and lower depressive mood (p = .032) at baseline predicted higher ΔPCS score. The regression model with ΔMCS as outcome variable explained 26.8 % of the variance of the ΔMCS score (p < .001). Lower MCS score (p < .001) and longer time since diagnosis (p = .048) at baseline predicted higher ΔMCS score. CONCLUSION: PwMS with lower physical HRQoL and better mood at clinic entry improved most in physical HRQoL over six months. PwMS with lower mental HRQoL and longer time since diagnosis at clinic entry improved most in mental HRQoL over six months. The results of this study contribute to the development of individualized rehabilitation programmes with the aim of maintaining and/or improving HRQoL of pwMS beyond the inpatient rehabilitation stay.

Contribution of dual-tasking to social participation in persons with multiple sclerosis: A structural equation modeling approach.

INTRODUCTION: This study aimed to explore the patterns of association between dual-tasking, cognition, ambulation disability, fatigue, and self-efficacy and their pathways in predicting social participation in persons with multiple sclerosis (MS). METHODS: Adults with MS (n = 1162) completed an online survey. Social participation was assessed by the Quality of Life in Neurological Disorders. The Dual-task Impact on Daily-Living Activities Questionnaire, Multiple Sclerosis Walking Scale-12v2, and Modified Fatigue Impact Scale measured dual-tasking, ambulation, and fatigue, respectively. Fall Efficacy Scale-International and Self-Efficacy for Community Mobility were assessed and modeled as a latent variable for efficacy. RESULTS: The correlation matrix showed significant associations of social participation with dual-tasking, cognition, ambulation, efficacy, and fatigue (all p < 0.001) and interrelationships among the independent variables (p < 0.05). The final model showed excellent global model fit (CFI = 0.99, TLI = 0.96), with all variables significantly predicting social participation either directly or indirectly. Efficacy significantly mediated the effects of dual-tasking (ß=-0.32, p < 0.001) and ambulation disability (ß=-0.42, p < 0.001) on social participation. CONCLUSION: This study indicated that dual-tasking, ambulation disability, fatigue, and efficacy play important roles in social participation in persons with MS. The findings can help provide insight into factors that may underpin social participation and offer targets for interventions in persons with MS.

Validity and reliability of the Six-Minute Pegboard Ring Test for assessing functional capacity and upper limb function in persons with multiple sclerosis.

BACKGROUND: The timed walk test is essential for assessing the functional capacity of persons with multiple sclerosis (MS). When a decline in ambulation ability and loss of function in the later stages of MS is observed, it is imperative to utilize alternative methods for measuring functional capacity. OBJECTIVE: To investigate the validity and reliability of the Six-Minute Pegboard Ring Test (6PBRT) in persons with MS. METHODS: Forty-three persons with MS were included in this study. Disease severity was quantified using the Expanded Disability Status Scale (EDSS). The 6PBRT was employed to assess upper extremity function during exercise stress, and vital signs were monitored pre- and post-test. Muscle strength was measured using a digital dynamometer for shoulder flexor, shoulder abductor, and grip strength, in addition to a hand dynamometer. Manual dexterity was evaluated through the 9-Hole Peg Test (9HPT), and walking endurance was assessed using the 2-Minute Walk Test (2MWT). Test-retest reliability was computed using the intraclass correlation coefficient (ICC). RESULTS: The ICC value for the 6PBRT was 0.96 (95% CI 0.92-0.97), indicating excellent test-retest reliability. Significant differences in vital signs were observed before and after conducting the 6PBRT (p < 0.05). A strong negative correlation was found between the 6PBRT score and EDSS (r = -0.650, p < 0.001). The 9HPT of the dominant side demonstrated a moderate correlation with the 6PBRT score (r = -0.502, p = 0.001), whereas no significant correlation was shown between the non-dominant side 9HPT and the 6PBRT score (p > 0.05). Moreover, a positive moderate correlation was shown between the performance on the 2MWT and the 6PBRT score (r = 0.413, p = 0.006). However, no significant correlation was detected between the proximal muscle strength of the upper extremity, handgrip strength, and the 6PBRT score in individuals with multiple sclerosis (p > 0.05). CONCLUSION: The 6PBRT is a reliable and valid tool to evaluate upper extremity function and exercise capacity in persons with MS.

Exercise-induced heat sensitivity in patients with multiple sclerosis: Definition, prevalence, etiology, and management-A scoping review.

BACKGROUND: For persons with multiple sclerosis (pwMS), exercise is known to be safe and effective at treating several symptoms and it may even be disease-modifying. However, exercise can trigger heat intolerance, exercise-induced heat sensitivity (EIHS), which may cause some pwMS to refrain from exercise. No review has yet summarized the existing knowledge on EIHS in pwMS. Therefore, the purpose of the present review was to clarify the terminology, summarize both the prevalence of EIHS and the current knowledge of underlying mechanisms, and provide an overview of existing treatment options and clinical management of EIHS in pwMS. METHODS: A scoping review was performed. RESULTS: As no clear definition could be identified in the literature, we propose a definition of EIHS. Aspects related to EIHS are reported in 29-80 % of all pwMS. The mechanisms underlying EIHS are not well understood but seem to include axon demyelination, CNS lesions, abnormal sudomotor function and sweating, abnormal afferent thermosensory function, disease stability, and abnormal neuropsychological responses. The severity of EIHS depends on the applied exercise modality, intensity, and format, and can be further reduced when applying different cooling interventions or garments before and/or during exercise. CONCLUSION: EIHS appears frequently in pwMS, but the underlying mechanisms are still only sparsely understood. EIHS severity depends on exercise-related factors and can be reduced by cooling interventions.

The agreement between face-to-face and tele-assessment of balance tests in patients with multiple sclerosis.

BACKGROUND: To investigate the reliability of balance tests administered using a tele-assessment method in patients with multiple sclerosis (MS). METHODS: The participants were assessed both online and face-to-face. The assessments were performed synchronously by two physiotherapists. The first method to used to evaluate the participants was determined through randomization. The Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and Timed Up and Go (TUG) were used in the evaluations. Three days were left between the assessment methods. Online platforms were used for tele-assessment. The agreement between and correlation of face-to-face and tele-assessments was analyzed by applying intra-class correlation coefficients (ICC), limits of agreement, and Pearson's correlation coefficient. RESULTS: This study included 39 individuals with MS with an EDSS score of 3.03 ± 1.41. Intra-rater reliability of the tele-assessment was excellent (ICCBBS = 0.96; ICCDGI = 0.97; ICCTUG = 0.97). Very high correlations were observed in all BBS, DGI, and TUG measurements between face-to-face and tele-assessment methods according to the first and second assessors (rBBS1 = 0.92; rBBS2 = 0.93; rDGI1 = 0.94; rDGI2 = 0.95; rTUG1 = 0.94; rTUG2 = 0.95, respectively). The inter-rater reliability of tele-assessments (ICCBBS = 0.97; ICCDGI = 0.97; ICCTUG = 1.00) achieved excellent reliability. CONCLUSION: BBS, DGI, and TUG are reliable and agreed tests that can be used with tele-assessments, offering similar data to face-to-face methods.