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Objective: To evaluate the reliability and validity of the dual-tasking questionnaire (DTQ), dual-task screening list (DTSL), and dual-task impact on daily life activities questionnaire (DIDA-Q)., Design: Multicenter, cross-sectional study SETTING: Persons with multiple sclerosis (pwMS) were recruited from 7 multiple sclerosis centers across 6 countries (Belgium, Chile, Italy, Israel, Spain, and Turkey)., Participants: A total of 356 pwMS (mean age 47.5±11.5y, expanded disability status scale, 3.79±1.83) were enrolled., Interventions: Not applicable MAIN OUTCOME MEASURES: The reliability (internal consistency, test-retest, and measurement error) and construct validity (structural and convergent) were assessed., Results: The DTQ, DTSL, and DIDA-Q demonstrated excellent test-retest reliability (intraclass correlation coefficients [95% CI], 0.84 [0.80-0.87] to 0.90 [0.87-0.92]) and internal consistency (Cronbach α: 0.86-0.96). As hypothesized, the 3 questionnaires showed a strong correlation with each other, moderate-to-strong correlations with other self-report questionnaires (perceived walking difficulties, fatigue, and fear of falling), and low-to-moderate correlations with cognitive information processing speed, manual dexterity, and dual-task walking performance (walking with word list generation task), showing convergent validity. The DIDA-Q exhibited systematically superior properties. These results were also verified in subsets from 6 different countries. In the structural validity analysis, all questionnaires displayed 2 main factors, allocated as "motor-driven" and "cognitive-driven" subscales., Conclusions: The DTQ, DTSL, and DIDA-Q have good-to-excellent measurement properties, with the highest properties observed in DIDA-Q. The use of these self-reported questionnaires can be used in research and clinical practice to assess the effect of dual-task difficulties on the daily life of ambulatory pwMS., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Higher cortical activity has been observed in people with multiple sclerosis (pwMS) during walking and dual-tasking. However, further studies in overground walking and considering pre-frontal cortex (PFC) sub-areas are necessary., Objectives: To investigate PFC activity during a cognitive-motor dual-task (DT) and its single component tasks, in combination with behavioral outcomes in pwMS., Methods: Fifteen pwMS (EDSS 3.5 [2-5.5], 42 ± 11 years) and 16 healthy controls (HC, 45.2 ± 13.2 years) performed 3 conditions: single motor-walking (SWT), single cognitive - subtracting sevens (SCT), and a DT. Meters walked and the number of correct answers were obtained from which, respectively, the motor (mDTC) and cognitive (cDTC) DT costs were calculated. A functional Near-Infrared Spectroscopy covering the frontopolar and dorsolateral PFC (DLPFC) areas was used to concentration of relative oxyhemoglobin (ΔHbO2) and deoxyhemoglobin (ΔHHb) in the PFC. A repeated 2-way ANOVA (group × conditions) was used to compare ΔHbO2/ΔHHb and behavioral outcomes., Results: PwMS walked shorter distances ( P  < .002) and answered fewer correct numbers ( P  < .03) than HC in all conditions, while cDTC and mDTC were similar between groups. PwMS presented higher ΔHbO2 in the frontopolar area than HC in the SWT ( P  < .001). HC increased ΔHbO2 in frontopolar during the SCT ( P  < .029) and DT ( P  < .037) compared with the SWT., Conclusion: Higher frontopolar activity in pwMS compared to HC in the SWT suggests reduced gait automaticity. Furthermore, it seems that only HC increased neural activity in the frontopolar in the SCT and DT, which might suggest a limit of cognitive resources to respond to DT in pwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Few studies on multiple sclerosis (MS) have explored the variability of percentage brain volume change (PBVC) measurements obtained from different clinical MRIs. In a retrospective multicentre cohort study, we quantified the variability of annualised PBVC in clinical MRIs., Methods: Clinical MRIs of relapse-onset MS patients were assessed by icobrain. Volumetric data were analysed on same-scanner and different-scanner MRI pairs if they passed quality control criteria. Alignment similarity between two images had to be comparable to same-scanner scan-rescan images., Results: Of 6826 MRIs, 85 % had appropriate volumetric sequences and 4446 serial MRI pairs were analysed. 3334 (75 %) MRI pairs from 1207 patients met the inclusions. The PBVC of included MRI pairs showed variance of 0.78 % for same-scanner pairs and 0.80 % for different-scanner pairs. Further selection of included MRI pairs with the best variance resulted in 1885 (42 %) MRI pairs with PBVC variance of 0.34 %. Excluded MRI pairs with poor alignment similarity had variances of 2.97 % for same-scanner pairs and 20.79 % for different-scanner pairs., Conclusion: Icobrain should be utilised for PBVC determination only on selected MRIs with the best alignment similarity. Applying strict selection criteria for the included MRI pairs and longitudinal imaging on the same scanner remain mandatory to reduce PBVC variability., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wim Van Hecke reports a relationship with Icometrix NV that includes: board membership and equity or stocks. Diana M. Sima reports a relationship with Icometrix NV that includes: employment. Guy Nagels reports a relationship with Icometrix NV that includes: consulting or advisory and equity or stocks. Femke Podevyn reports a relationship with Icometrix NV that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Many persons with multiple sclerosis (MS) are confronted with fatigue and difficulties with walking and even more so in persons with progressive subtypes of MS. Task-oriented training, and more specifically in the form of auditory-motor coupling, where persons are asked to synchronise their steps to beats in music and metronomes, is promising. However, it is currently not known whether persons with progressive MS (PwPMS) can synchronise their steps to beats in music and metronomes and if they can adapt their gait to slower and higher tempi., Methods: The study is a case control study where participants with progressive MS (PwPMS) and healthy controls (HCs) were asked to synchronise their steps during overground walking to beats in music and metronomes at five different tempi, ranging from slow (-8%, -4%), baseline (0%) and high (4%, 8%) while synchronisation, spatiotemporal parameters and gait dynamics were recorded. Mixed model analyses were performed on synchronisation outcome measures and spatiotemporal gait parameters. Additionally, a regression analysis was performed to identify clinical factors such as cognition and motor function influencing synchronisation consistency., Results: In total, 18 PwPMS (mean age = 52.4, median EDSS = 4.24) and 16 healthy controls (HCs) (mean age = 56.5) were included in the study. Results show that both groups were able to synchronise their steps to beats in music and metronomes, but highest synchronisation consistency was reached for metronome conditions compared to music conditions and for HCs compared to persons with progressive MS. Highest synchronisation consistency for persons with progressive MS was found at -4% and 0%. Additionally, more variability in inter-step-intervals and thus a more anti-persistent gait pattern was found for metronome compared to music conditions. Last, lower performance on the Timed Up & Go Test negatively impacted synchronisation consistency., Conclusion: PwPMS are able to synchronise steps to beats in music and metronomes. Overall, more consistent synchronisation is seen for metronome conditions. All participants are able to adapt their cadence to all tempi, yet, PwPMS struggle to adapt gait speed to high tempi. Noteworthy, participants walk with more random inter-step-interval fluctuations when walking to metronome compared to music conditions. Last, dynamic balance significantly impacted synchronisation consistency. These results show the potential of using auditory-motor coupling for walking related rehabilitation for PwPMS, however, tempo and auditory stimulation should be carefully considered., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

In multiple sclerosis (MS), working memory (WM) impairment can occur soon after disease onset and significantly affects the patient's quality of life. Functional imaging research in MS aims to investigate the neurophysiological underpinnings of WM impairment. In this context, we utilize a data-driven technique, the time delay embedded-hidden Markov model, to extract spectrally defined functional networks in magnetoencephalographic (MEG) data acquired during a WM visual-verbal n-back task. Here, we show that the activation of two networks is altered in relapsing remitting-MS patients. First, the activation of an early theta prefrontal network linked to stimulus encoding and attentional control significantly decreases in MS compared to HC. This diminished activation correlates with reduced accuracy and higher reaction time, suggesting that impaired attention control impacts task performance in MS patients. Secondly, a frontoparietal network characterized by beta coupling is activated between 300 and 600 ms post-stimulus, resembling the event-related P300, a cognitive marker extensively explored in EEG studies. The activation of this network is amplified in patients treated with benzodiazepine, in line with the well-known benzodiazepine-induced beta enhancement. Altogether, the TDE-HMM technique extracts task-relevant functional networks showing disease-specific and treatment-related alterations, revealing potential new markers to assess and track WM impairment in MS., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Distance walking fatigability (DWF) in people with multiple sclerosis (pwMS) is defined as a decrease in the distance walking over time. However, declines in gait quality (i.e., gait quality fatigability- GQF) may occur independently or alongside DWF., Objective: i) to investigate how walking fatigability manifests and its prevalence in pwMS; ii) to describe the temporal pattern of the changes of specific gait characteristics during the 6-minute walking test (6MWT) METHODS: Eighty-eight pwMS (EDSS 4[0-6.5], 49[21-70] years) and 47 healthy controls (HC- 46[25-60] years) performed the 6MWT wearing inertial measurement units. Gait characteristics (stride length, sensor-based gait speed, cadence, double support, step duration, stance phase, step duration asymmetry, step duration variability, foot-strike, toe-off, and leg circumduction) and walking distance were recorded in 1-minute intervals. A fatigability index was calculated by comparing the last and first minute of the 6MWT to identify abnormal worsening based on cutoff scores. The manifestation of walking fatigability was counted. The temporal pattern of worsening of gait characteristics during the 6MWT was examined in pwMS exceeding the cutoff values, compared to pwMS without abnormal changes and HC, using a two-way ANOVA (group vs. minutes) RESULTS: Thirty-five pwMS presented both DWF and GQF, 2 presented isolated DWF, 27 presented isolated GQF, and 24 presented non-walking fatigability. PwMS having GQF presented worsening in gait characteristics (cadence, step duration, step duration variability, or toe-off angle) from minute 2 onwards of the 6MWT, while HCs and pwMS without abnormal changes stabilized gait from minute 2 towards the end of the 6MWT., Conclusion: Walking fatigability in pwMS manifests not only as a decrease in walking distance but also as changes in gait quality. Understanding changes in gait characteristics during walking can help tailor rehabilitation interventions., Competing Interests: Declaration of competing interest The Author (s) declare (s) that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest Joke Raats: none. Ilse Lamers: none. Peter Feys, consultation fee paid to the institution for lectures for Roche. Mindy Levin: none. Griet Gysemberg: none. Sofie Ferdinand: none., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: An imbalance of excitatory and inhibitory synaptic transmission in multiple sclerosis (MS) may lead to cognitive impairment, such as impaired working memory. The 1/f slope of electroencephalography/magnetoencephalography (EEG/MEG) power spectra is shown to be a non-invasive proxy of excitation/inhibition balance. A flatter slope is associated with higher excitation/lower inhibition., Objectives: To assess the 1/f slope modulation induced by stimulus and its association with behavioral and cognitive measures., Methods: We analyzed MEG recordings of 38 healthy controls (HCs) and 79 people with multiple sclerosis (pwMS) while performing an n-back task including target and distractor stimuli. Target trials require an answer, while distractor trials do not. We computed the 1/f spectral slope through the fitting oscillations and one over f (FOOOF) algorithm within the time windows 1 second before and after each stimulus presentation., Results: We observed a flatter 1/f slope after distractor stimuli in pwMS compared to HCs. The 1/f slope was significantly steeper after stimulus for both HCs and pwMS and was significantly correlated with reaction times. This modulation in 1/f slope was significantly correlated with visuospatial memory assessed by the BVMT-R test., Conclusion: Our results suggest possible inhibitory mechanism deficits in pwMS during a working memory task., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: People with progressive multiple sclerosis (PMS) present motor (eg, walking) and cognitive impairments, and report fatigue. Fatigue encompasses fatigability which is objectively measured by the capacity to sustain a motor or cognitive task., Objective: To investigate the prevalence of walking and cognitive fatigability (CF) and the associated clinical characteristics in a large sample of PMS patients., Methods: PMS patients (25-65 years old) were included from 11 sites (Europe and North America), having cognitive impairment (1.28 standard deviation below normative data for the symbol digit modality test [SDMT]). Walking fatigability (WF) was assessed using the distance walk index (DWI) and CF using the SDMT (scores from the last 30 seconds compared to the first 30 seconds). Additional measures were: cognitive assessment-Brief International Cognitive Assessment for multiple sclerosis (MS), cardiorespiratory fitness, 6-minute walk, physical activity, depressive symptoms, perceived fatigue-Modified Fatigue Impact Scale (MFIS), MS impact-MSIS-29, and walking ability., Results: Of 298 participants, 153 (51%) presented WF (DWI = -28.9 ± 22.1%) and 196 (66%) presented CF (-29.7 ± 15%). Clinical characteristics (EDSS, disease duration, and use of assistive device) were worse in patients with versus without WF. They also presented worse scores on MSIS-29 physical, MFIS total and physical and reduced physical capacity. CF patients scored better in the MSIS-29 physical and MFIS psychosocial, compared to non-CF group. Magnitude of CF and WF were not related., Conclusions: Half of the cognitively-impaired PMS population presented WF which was associated with higher disability, physical functions, and fatigue. There was a high prevalence of CF but without strong associations with clinical, cognitive, and physical functions., Trial Registration Number: The "CogEx-study," www.clinicaltrial.gov identifier number: NCT03679468., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Gait characteristics and their changes during the 6-minute walking test (6MWT) in people with multiple sclerosis (pwMS) have been described in the literature, which one may refer to as walking fatigability in the body function level of the International Classification of Functioning, Disability, and Health. However, whether these metrics are reliable is unknown., Objective: To investigate the between-day reliability of the gait characteristics and their changes in pwMS and healthy controls (HCs)., Methods: Forty-nine pwMS (EDSS 4.82 ± 1.22 and 54.7 ± 9.36 years) and 23 HCs (50.6 ± 6.1 years) performed the 6MWT, as fast as possible but safely while wearing Inertial Measurement Units. Gait characteristics were measured in the pace, rhythm, variability, asymmetry, kinematics, coordination, and postural control domains and were obtained in intervals of 1 minute during the 6MWT. In addition, gait characteristics change in the last minute compared with the first minute were calculated for all gait variables using a fatigability index (ie, distance walking index). The intraclass correlation coefficient (ICC), Bland-Altman Plots, and Standard error of measurement were applied to investigate reliability., Results: Reliability of gait characteristics, minute-by-minute, and for their changes (ie, using the fatigability index) ranged from poor to excellent (pwMS: ICC 0.46-0.96; HC: ICC 0.09-0.97 and pwMS: ICC 0-0.72; HC: ICC 0-0.77, respectively)., Conclusion: Besides coordination, at least 1 variable of each gait domain showed an ICC of moderate or good reliability for gait characteristics changes in both pwMS and HC. These metrics can be incorporated into future clinical trials and research on walking fatigability. Clinical Trial Registration: NCT05412043., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by neuronal and synaptic loss, resulting in an imbalance of excitatory and inhibitory synaptic transmission and potentially cognitive impairment. Current methods for measuring the excitation/inhibition (E/I) ratio are mostly invasive, but recent research combining neurocomputational modeling with measurements of local field potentials has indicated that the slope with which the power spectrum of neuronal activity captured by electro- and/or magnetoencephalography rolls off, is a non-invasive biomarker of the E/I ratio. A steeper roll-off is associated with a stronger inhibition. This novel method can be applied to assess the E/I ratio in people with multiple sclerosis (pwMS), detect the effect of medication such as benzodiazepines, and explore its utility as a biomarker for cognition. We recruited 44 healthy control subjects and 95 pwMS who underwent resting-state magnetoencephalographic recordings. The 1/f spectral slope of the neural power spectra was calculated for each subject and for each brain region. As expected, the spectral slope was significantly steeper in pwMS treated with benzodiazepines (BZDs) compared to pwMS not receiving BZDs (p = .01). In the sub-cohort of pwMS not treated with BZDs, we observed a steeper slope in cognitively impaired pwMS compared to cognitively preserved pwMS (p = .01) and healthy subjects (p = .02). Furthermore, we observed a significant correlation between 1/f spectral slope and verbal and spatial working memory functioning in the brain regions located in the prefrontal and parietal cortex. In this study, we highlighted the value of the spectral slope in MS by quantifying the effect of benzodiazepines and by putting it forward as a potential biomarker of cognitive deficits in pwMS., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Upper limb intention tremor in persons with multiple sclerosis (pwMS) affects the ability to perform activities of daily life and is difficult to treat. The study investigated the effect of peripheral upper limb cooling on tremor severity and functional performance in MS patients with intention tremor. In experiment 1, 17 patients underwent two 15 min cooling conditions for the forearm (cold pack and cryomanchet) and one control condition. In experiment 2, 22 patients underwent whole arm cooling for 15 min using multiple cold packs. In both experiments, patients were tested at four time points (pre- and post-0, -25 and -50 min cooling) on unilateral tasks of the Test Evaluant les Membres supérieurs des Personnes Agées (TEMPA), Fahn's tremor rating scale (FTRS), Nine Hole Peg Test (NHPT). In experiment 1, the mean FTRS ranged from 13.2 to 14.1 across conditions. A two-way ANOVA showed mainly time effects, showing that cooling the forearm significantly reduced the FTRS, the performance on the NHPT, and three out of four items of the TEMPA, mostly independent of the cooling modality. In experiment 2, the mean FTRS was 13.1. A repeated measures ANOVA showed that cooling the whole arm reduced the FTRS and time needed to execute two out of four items of the TEMPA. These effects occurred immediately after cooling lasting at least 25 min. Cooling the whole upper limb led to a clinically noticeable effect on tremor severity and improved functional performance, which was pronounced during the first half-hour after cooling.

Background: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown., Objective: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level., Methods: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTC motor with clinical measures. Adjusted significance level was 0.01., Results: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTC motor of 15.8% and DTC cognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTC motor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTC cognitive did not differ from zero for any of the groups (p ≥ 0.039)., Conclusion: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear., Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS., Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up., Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n  = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n  = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n  = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically., Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Background: The COVID-19 pandemic has led to reorganization or reduction of neurorehabilitation services for people with multiple sclerosis (PwMS). The aim of this study was to explore the changes in the organizational framework and technology usage in physiotherapy services for PwMS during the COVID-19 pandemic., Methods: This international cross-sectional survey study was designed, developed, and disseminated by RIMS European Network for Best Practice and Research in Multiple Sclerosis Rehabilitation. Physiotherapists from nine countries (Australia, Belgium, Czech Republic, Ireland, Israel, Italy, Norway, Spain, Turkey) who provided physiotherapy services to PwMS, were invited to complete an online survey to compare physiotherapy delivery to PwMS prior to and during the pandemic period., Results: The survey was completed by 215 physiotherapists. Accessibility, the average number, length and perceived effectiveness of physiotherapy sessions provided to PwMS were significantly reduced during the COVID-19 pandemic (p=0.001). Physiotherapists increased the advice of mobile apps, recorded videos for rehabilitation and exercise websites during the pandemic (p<0.001) while the use of telerehabilitation and virtual reality technology did not change., Conclusion: There was of a reduction in the number, duration and perceived effectiveness of rehabilitation sessions for people with multiple sclerosis during the COVID-19 pandemic while use of remote technologies for physiotherapy did not change. To ensure the continuity of physiotherapy for PwMS with complex healthcare needs also during pandemics, the provision of guidelines and training in telehealth technologies in professional education becomes crucial., Competing Interests: Declaration of Competing Interests The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Advanced structural brain imaging techniques, such as diffusion tensor imaging (DTI), have been used to study the relationship between DTI-parameters and cognitive scores in multiple sclerosis (MS). In this study, we assessed cognitive function in 61 individuals with MS and a control group of 35 healthy individuals with the Symbol Digit Modalities Test, the California Verbal Learning Test-II, the Brief Visuospatial Memory Test-Revised, the Controlled Oral Word Association Test, and Stroop-test. We also acquired diffusion-weighted images (b = 1000; 32 directions), which were processed to obtain the following DTI scalars: fractional anisotropy, mean, axial, and radial diffusivity. The relation between DTI scalars and cognitive parameters was assessed through permutations. Although fractional anisotropy and axial diffusivity did not correlate with any of the cognitive tests, mean and radial diffusivity were negatively correlated with all of these tests. However, this effect was not specific to any specific white matter tract or cognitive test and demonstrated a general effect with only low to moderate individual voxel-based correlations of <0.6. Similarly, lesion and white matter volume show a general effect with medium to high voxel-based correlations of 0.5-0.8. In conclusion, radial diffusivity is strongly related to cognitive impairment in MS. However, the strong associations of radial diffusivity with both cognition and whole brain lesion volume suggest that it is a surrogate marker for general decline in MS, rather than a marker for specific cognitive functions., (© 2022. The Author(s).)

Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence health outcomes. Evidence indicates that health behaviours, comorbidities and disease-modifying therapies all contribute to multiple sclerosis (MS) outcomes; however, our knowledge of the effects of social determinants - that is, the 'risks of risks' - on health has not yet changed our approach to MS. Assessing and addressing social determinants of health could fundamentally improve health and health care in MS; this approach has already been successful in improving outcomes in other chronic diseases. In this narrative Review, we identify and discuss the body of evidence supporting an effect of many social determinants of health, including racial background, employment and social support, on MS outcomes. It must be noted that many of the published studies were subject to bias, and screening tools and/or practical interventions that address these social determinants are, for the most part, lacking. The existing work does not fully explore the potential bidirectional and complex relationships between social determinants of health and MS, and the interpretation of findings is complicated by the interactions and intersections among many of the identified determinants. On the basis of the reviewed literature, we consider that, if effective interventions targeting social determinants of health were available, they could have substantial effects on MS outcomes. Therefore, funding for and focused design of studies to evaluate and address social determinants of health are urgently needed., (© 2022. Springer Nature Limited.)

Background: The Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients., Methods: Diffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT., Results: Patients had decreased performance on the SDMT and decreased white matter volume (each p < 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST ( p < 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract ( r = 0.25, p < 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model., Conclusions: Processing speed in MS is associated with the structural integrity of frontoparietal white matter tracts., Competing Interests: MG received honoraria or speaking fees from Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva. IP has received honoraria for speaking at scientific meetings, serving on scientific advisory boards, and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Desitin, Sanofi-Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She has also received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. ML is a paid editor for the Thieme Verlag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grothe, Jochem, Strauss, Langner, Kirsch, Hoffeld, Penner, Nagels, Klepzig, Domin and Lotze.)

Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age- and gender-matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS., (© 2022 New York Academy of Sciences.)

Background: The impact of the COVID-19 pandemic on physical therapy services for people with multiple sclerosis (pwMS) is unknown. Therefore, the Special Interest Group for Mobility (SIG Mobility) of the European Network for Best Practice and Research in Multiple Sclerosis Rehabilitation (RIMS) has undertaken the initiative to examine the impact of the COVID-19 outbreak on physical therapy services and physical activity participation in pwMS across Europe, Israel and Australia., Objective: To describe the impact of the COVID-19 outbreak on physical therapy practice from the perspective of the therapist., Methods: An online survey was developed and conducted from December 2020 to July 2021. The survey (50 questions), included multiple-choice questions and open-ended responses., Results: In total, 215 physical therapists (PT's) from 9 countries (Australia, Belgium, the Czech Republic, Ireland, Israel, Italy, Norway, Spain, and Turkey) participated in the study. The therapy most affected during the pandemic was aerobic training/conditioning exercises; 33.5% reported that these activities were either reduced or unavailable. In contrast, 15% of the PTs reported increased use of relaxation/mind body techniques and/or fatigue management programs during the pandemic. PTs reported a mixture of positive and negative feelings about the therapeutic sessions offered during the pandemic. Most reported positive feelings included "positive" (26.5%), and "optimistic" (24.7%). Negative feelings most frequently reported included "worried" (30.7%), and "hesitant" (20.9%). The PTs reported a 10% decrease in the use of hands-on techniques and a 10% increase in the use of oral instructions when treating moderately and severely pwMS during as compared to before the pandemic., Conclusion: The COVID-19 pandemic has affected physical therapy services in pwMS internationally in terms of content, frequency of use and format., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Motor sequence learning in persons with multiple sclerosis (pwMS) and healthy controls (HC) under implicit or explicit learning conditions has not yet been investigated in a stepping task. Given the prevalent cognitive and mobility impairments in pwMS, this is important in order to understand motor learning processes and optimize rehabilitation strategies. Nineteen pwMS (the Expanded Disability Status Scale = 3.4 ± 1.2) and 18 HC performed a modified serial reaction time task by stepping as fast as possible on a stepping tile when it lit up, either with (explicit) or without (implicit) knowledge of the presence of a sequence beforehand. Motor sequence learning was studied by examining response time changes and differences between sequence and random blocks during the learning session (acquisition), 24 h later (retention), and in three dual-task (DT) conditions at baseline and retention (automaticity) using subtracting sevens, verbal fluency, and vigilance as concurrent cognitive DTs. Response times improved and were lower for the sequenced compared with the random blocks at the post- and retention tests (P's < 0.001). Response times during DT conditions improved after learning, but DT cost improved only for the subtracting sevens DT condition. No differences in learning were observed between learning conditions or groups. This study showed motor sequence learning, by acquisition and retention, in a stepping task in pwMS with motor impairments, to a similar degree as HC and regardless of learning conditions. Whether automaticity increased remains unclear., (© 2021 New York Academy of Sciences.)

Objective: Multiple sclerosis (MS) may result in activity and participation limitations, including the performance of activities of daily living (ADL). This study aims at systematically investigate ADL performance by using Assessment of Motor and Process Skills (AMPS) in people with MS (PwMS) of all disease types and within the Kurtzke Expanded Disability Status Scale (EDSS) range from 1.0 - 8.0., Methods: Eight multiple sclerosis (MS) centres participated in data collection of a consecutive sample of PwMS. Participants were referred for assessment to occupational therapy (OT) by treating physician or recruited from neurology department in each hospital and assessed by EDSS and AMPS. The AMPS is an observational, criterion referenced ADL assessment, providing values for a person's ADL performance in terms of motor and process skills. Criterion referenced cut-off scores were established at 2.0 for motor skills and at 1.0 for process skills and both values above the cut-off score indicate competent (independent, safe, efficient and effortless) ADL performance. Process skills refer to the act of carrying out a series of actions and is summarized in terms of efficiency, like initiating without pauses, continuing actions through to completion, performing actions in logical order (sequences), choosing, and completing the task as planned (heeds)., Results: Two hundred and ten PwMS were recruited (48 +/- 13 years of age, 145 women/65 men, average disease duration was 11.8 +/- 9.6 years, average EDSS was 4.8+/-1.8). Average motor skills score was 1.01+/- 1.12 (indicating need for assistance with evidence of increased clumsiness/physical effort) and average process skills score was 1.02 +/- 0.66 (risk zone, questionable efficiency and more likely to need assistance). Overall, motor skills and process skills decreased with increasing EDSS score. No need for assistance in motor skills was indicated in subjects with lower EDSS scores (1.0 - 2.5). In higher EDSS group (≥4.5), 57% of subjects needed assistance in motor skills and 27% in process skills. The competency in process skills was either questionable or reduced within all EDSS scores. However, 33-38% of subjects with higher EDSS scores (6.0-8.5) showed competent performance in process skills. Overall correlation between motor and process scores was moderate (r = 0.56, p<0.0001), but no significant relationships between motor and process skills were found in the lower EDSS (1-2.5) and high EDSS scores (8-8.5). Further, EDSS and disease type were significant predictors, explaining 52.7% of motor skills and 22.3% of process skills performance., Conclusion: Problems in ADL performance were found in EDSS categories 1.0 to 8.0 and in all disease types, therefore it is advisable to screen all PwMS for ADL deficits and provide relevant rehabilitation interventions., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cognitive-motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty., Objective: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC)., Methods: Nine cognitive-motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively., Results: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task ( p  < 0.001) and the walking condition ( p  ⩽ 0.002), while cognitive-DTC only varied between cognitive tasks with a large difference in difficulty ( p  ⩽ 0.005) and not between walking conditions ( p  ⩾ 0.125). None of the DTCs differed between groups., Conclusion: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

Background: Dysphagia is common in persons with multiple sclerosis (MS). Speech and language therapists give dysphagia recommendations to persons with MS and caregivers. Nonadherence to these recommendations can increase the risk of aspiration. We investigated current compliance with dysphagia recommendations among caregivers and kitchen staff and assessed improvement in compliance by increasing knowledge through tailored training., Methods: An observational cohort study was conducted over 4 weeks during which the compliance of the caregivers and kitchen staff in a rehabilitation center was monitored. A questionnaire was used to assess reasons for noncompliance. A 2-hour training session was provided for all caregivers and kitchen staff to improve their knowledge and skills. The compliance rate was observed again 1 and 6 months after the training. Compliance was defined by whether recommendations were followed., Results: Results showed a significant improvement after training for overall compliance by caregivers (from 58% to >81%, P < .001). This improvement was still observed 6 months later (80%). After training, significant differences were found in compliance with the following recommendations ( P ≤ .001): consistency of soup, consistency of liquids, food preparation, alertness, speed, amount, posture, and supervision. Recommendation for utensils did not improve ( P = .44). Compliance with diet modifications made by the kitchen staff improved significantly (from 74% to >86%, P = .002), and even more during follow-up (to >95%, P = .009)., Conclusions: Dysphagia training tailored to the needs of caregivers to improve knowledge significantly improves compliance with dysphagia recommendations and the quality of care., Competing Interests: Financial Disclosures: The authors declare no conflicts of interest., (© 2021 Consortium of Multiple Sclerosis Centers.)

Objective: To explore the ability of a self-report activity diary to measure the physical activity level (PAL) in female patients with chronic fatigue syndrome (CFS) and whether illness-related complaints, health-related quality of life domains (HRQOL) or demographic factors are associated with discrepancies between self-reported and objectively measured PAL., Methods: Sixty-six patients with CFS, recruited from the chronic fatigue clinic of a university hospital, and twenty matched healthy controls wore an accelerometer (Actical) for six consecutive days and registered their activities in an activity diary in the same period. Participants' demographic data was collected and all subjects completed the CFS Symptom List (illness-related complaints) daily and Short-Form-36 (HRQOL domains) during the first and second appointment., Results: A significant, but weak association between the activity diary and Actical was present in patients with CFS (r s  = 0.376 and r s  = 0.352; p < 0.001) and a moderately strong association in healthy controls (r s  = 0.605; and r s  = 0.644; p < 0.001) between week and weekend days, respectively. A linear mixed model identified a negative association between age and the discrepancy between the self-reported and objective measure of PA in both patients with CFS and healthy controls., Conclusion: The activity diary showed limited ability to register the PAL in female patients with CFS. The discrepancy between measures was not explained by illness-related complaints, HRQOL domains or demographic factors. The activity diary cannot replace objective activity monitoring measured with an accelerometer, but may provide additional information about the perceived activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Working memory (WM) problems are frequently present in people with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a visual-verbal 2-back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event-related fields and theta (4-8 Hz) and alpha (8-13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = .014). This theta power increase value correlated negatively with reaction time on the task in MS (r = -.32, p = .029). Evidence was provided that this relationship could not be explained by a 'common cause' confounding relationship with MS-related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Graph-theoretical analysis is a novel tool to understand the organisation of the brain.We assessed whether altered graph theoretical parameters, as observed in multiple sclerosis (MS), reflect pathology-induced restructuring of the brain's functioning or result from a reduced signal quality in functional MRI (fMRI). In a cohort of 49 people with MS and a matched group of 25 healthy subjects (HS), we performed a cognitive evaluation and acquired fMRI. From the fMRI measurement, Pearson correlation-based networks were calculated and graph theoretical parameters reflecting global and local brain organisation were obtained. Additionally, we assessed metrics of scanning quality (signal to noise ratio (SNR)) and fMRI signal quality (temporal SNR and contrast to noise ratio (CNR)). In accordance with the literature, we found that the network parameters were altered in MS compared to HS. However, no significant link was found with cognition. Scanning quality (SNR) did not differ between both cohorts. In contrast, measures of fMRI signal quality were significantly different and explained the observed differences in GTA parameters. Our results suggest that differences in network parameters between MS and HS in fMRI do not reflect a functional reorganisation of the brain, but rather occur due to reduced fMRI signal quality.

In multiple sclerosis, the interplay of neurodegeneration, demyelination and inflammation leads to changes in neurophysiological functioning. This study aims to characterize the relation between reduced brain volumes and spectral power in multiple sclerosis patients and matched healthy subjects. During resting-state eyes closed, we collected magnetoencephalographic data in 67 multiple sclerosis patients and 47 healthy subjects, matched for age and gender. Additionally, we quantified different brain volumes through magnetic resonance imaging (MRI). First, a principal component analysis of MRI-derived brain volumes demonstrates that atrophy can be largely described by two components: one overall degenerative component that correlates strongly with different cognitive tests, and one component that mainly captures degeneration of the cortical grey matter that strongly correlates with age. A multimodal correlation analysis indicates that increased brain atrophy and lesion load is accompanied by increased spectral power in the lower alpha (8-10 Hz) in the temporoparietal junction (TPJ). Increased lower alpha power in the TPJ was further associated with worse results on verbal and spatial working memory tests, whereas an increased lower/upper alpha power ratio was associated with slower information processing speed. In conclusion, multiple sclerosis patients with increased brain atrophy, lesion and thalamic volumes demonstrated increased lower alpha power in the TPJ and reduced cognitive abilities., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Symbol Digit Modalities Test (SDMT) is essential in the screening of cognitive impairments in multiple sclerosis (MS). Methodological adaptions of the SDMT on functional MRI exist, but without specific investigation of more cognitive components of information processing speed (IPS). Additionally, there is only limited data on functional differences between MS-patients and healthy controls (HC)., Methods: 20 MS-patients and 20 HC were investigated executing the original version of the SDMT on fMRI. We analyzed (1) neural networks as indicated in the methodological adaptions (i.e. frontal (Brodman area BA6, BA9), parietal (BA7), occipital (BA17) and cerebellar), (2) functional activations of cognitive components of IPS and (3) functional differences between MS and HC during SDMT., Results: MS patients performed worse during the SDMT. Both groups demonstrated activation on each region of interest. Cognitive component of IPS was driven by superior parietal and posterior cerebellar activation. MS-patients showed decreased cingulate activation during SDMT as compared to HC., Conclusion: The original SDMT task revealed comparable fMRI-activation sites as reported for previous adaptions. Cognitive components of IPS depend on superior parietal and medial posterior cerebellar regions known to process visuo-spatial integration and anticipation. Attention related areas in the cingulate cortex were decreased in MS-patients., Competing Interests: Declaration of Competing Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multi-item working memory (WM) is a complex cognitive function thought to arise from specific frequency band oscillations and their interactions. While some theories and consistent findings have been established, there is still a lot of unclarity about the sources, temporal dynamics, and roles of event-related fields (ERFs) and theta, alpha, and beta oscillations during WM activity. In this study, we performed an extensive whole-brain ERF and time-frequency analysis on n-back magnetoencephalography data from 38 healthy controls. We identified the previously unknown sources of the n-back M300, the right inferior temporal and parahippocampal gyrus and left inferior temporal gyrus, and frontal theta power increase, the orbitofrontal cortex. We shed new light on the role of the precuneus during n-back activity, based on an early ERF and theta power increase, and suggest it to be a crucial link between lower-level and higher-level information processing. In addition, we provide strong evidence for the central role of the hippocampus in multi-item WM behavior through the dynamics of theta and alpha oscillatory changes. Almost simultaneous alpha power decreases observed in the hippocampus and occipital fusiform gyri, regions known to be involved in letter processing, suggest that these regions together enable letter recognition, encoding and storage in WM. In summary, this study offers an extensive investigation into the spatial, temporal, and spectral characteristics of n-back multi-item WM activity., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background: Dual tasking constitutes a large portion of most activities of daily living; in real-life situations, people need to not only maintain balance and mobility skills, but also perform other cognitive or motor tasks at the same time. Interest toward dual-task training (DTT) is increasing as traditional interventions may not prepare patients to adequately face the challenges of most activities of daily living. These usually involve simultaneous cognitive and motor tasks, and they often show a decline in performance. Cognitive-motor interference (CMI) has been investigated in different neurological populations, but limited evidence is present for people with multiple sclerosis (MS). The use of computerized tools is mandatory to allow the application of more standardized assessment and rehabilitation intervention protocols and easier implementation of multicenter and multilanguage studies., Objective: To describe the design and development of CMI-APP, an adaptive and interactive technology tablet-based app, and to present the preliminary results of a multicenter pilot study involving people with MS performed in several European centers for evaluating the feasibility of and adherence to a rehabilitation program based on CMI-APP., Methods: CMI-APP includes user-friendly interfaces for personal data input and management, assessment of CMI, and DTT. A dedicated team developed CMI-APP for Android tablets above API level 14 (version 4.0), using C# as the programming language and Unity and Visual Studio as development tools. Three cognitive assessment tests for working memory, information processing speed, and sustained attention and four motor assessment tests for walking at different difficulty levels were implemented. Dual cognitive-motor tasks were performed by combining single cognitive and motor tasks. CMI-APP implements exercises for DTT involving the following 12 cognitive functions: sustained attention, text comprehension, verbal fluency, auditory discrimination, visual discrimination, working memory, information processing speed, auditory memory, visual memory, verbal analog reasoning, visual analog reasoning, and visual spatial planning, which can be performed during walking or stepping on the spot. Fifteen people with MS (mean age 52.6, SD 8.6 years; mean disease duration 9.4, SD 8.4 years; mean Expanded Disability Status Scale score 3.6, SD 1.1) underwent DTT (20 sessions). Adherence to the rehabilitation program was evaluated according to the percentage of performed sessions, perceived exertion during the training (Borg 15-point Ratings of Perceived Exertion [RPE] Scale), and subjective experience of the training (Intrinsic Motivation Inventory [IMI])., Results: The adherence rate was 91%. DTT was perceived as "somewhat difficult" (mean RPE Scale score 12.6, SD 1.9). IMI revealed that participants enjoyed the training and felt that it was valuable and, to some extent, important, without feelings of pressure. They felt competent, although they did not always feel they could choose the exercises, probably because the therapist chose the exercises and many exercises had few difficulty levels., Conclusions: CMI-APP is safe, highly usable, motivating, and well accepted for DTT by people with MS. The findings are fundamental for the preparation of future large-sample studies examining CMI and the effectiveness of DTT interventions with CMI-APP in people with MS., (©Andrea Tacchino, Renee Veldkamp, Karin Coninx, Jens Brulmans, Steven Palmaers, Päivi Hämäläinen, Mieke D'hooge, Ellen Vanzeir, Alon Kalron, Giampaolo Brichetto, Peter Feys, Ilse Baert. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 19.04.2020.)

The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed dual-task exercises using an interactive tablet-based application, while the SMT-group received conventional walking and balance exercises. Both interventions were supervised and identical in weeks (8) and sessions (20). Nine cognitive-motor dual-task conditions were assessed at baseline, after intervention and at 4-weeks follow-up (FU). The dual-task cost (DTC), percentage change of dual-task performance compared to single-task performance, was the primary outcome. Mobility and cognition were secondarily assessed. Mixed model analyses were done with group, time and the interaction between group and time as fixed factors and participants as random factors. Significant time by group interactions were found for the digit-span walk and subtraction walk dual-task conditions, with a reduction in DTC (gait speed) for the DTT maintained at FU. Further, absolute dual-task gait speed during walking over obstacles only improved after the DTT. Significant improvements were found for both groups in various motor and cognitive measures. However, the DTT led to better dual-task walking compared to the SMT.

Background and Purpose: Multiple sclerosis (MS) patients frequently report cognitive difficulties which impact daily functioning. The objective was to investigate the relationship between patient-reported cognitive impairment and depression, demographic and MS-related variables, and to clarify its impact on self-reported health measures and employment., Method: A large two-centre survey included the MS Neuropsychological Screening Questionnaire (MSNQ), the two-question screening tool for depression, vitality, health-related quality of life, the Health-Promoting Lifestyle Profile II and questions assessing social network satisfaction and employment status., Results: Of the 751 respondents (median age 54 years, median Expanded Disability Status Scale 5, 66.2% female), two-thirds reported perceived neuropsychological impairment or depressive symptoms. Whilst depressive symptoms were related to higher MSNQ scores, the MSNQ poorly predicted depression. After correcting for confounders, higher MSNQ scores and depressive symptoms decreased vitality, health-related quality of life and health-promoting behaviours and increased the probability of being socially dissatisfied. In participants below retirement age, higher MSNQ and Expanded Disability Status Scale scores increased the probability of unemployment, whilst depression did not., Conclusion: The contribution of the MSNQ to self-reported health measures and its unique explanatory power regarding unemployment suggest that subjective cognitive complaints are connected to subtle, yet meaningful, neuropsychological dysfunction., (© European Academy of Neurology 2019.)

Background: Cognitive dysfunction is a frequent manifestation of multiple sclerosis (MS) but its effect on locomotor rehabilitation is unknown., Objective: To study the impact of cognitive impairment on locomotor rehabilitation outcome in people with MS., Methods: We performed a retrospective analysis involving ambulatory patients with MS who were admitted for intensive, inpatient, multidisciplinary rehabilitation at the National Multiple Sclerosis Center of Melsbroek between the years 2012 and 2017. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used to determine the cognitive status of subjects as either impaired (COG-) or preserved (COG+). Locomotor outcome was compared between groups with the difference in 6-minute walk test (6MWT) measured at admission and discharge (Δ6MWT). In addition, individual test scores of the BRB-N for attention (Paced Auditory Serial Addition Test 2" and 3"), visuospatial learning/memory (7/24 Spatial Recall Test), verbal learning/memory (Selective Reminding Test) and verbal fluency (Controlled Oral Word Association Test) were correlated to the Δ6MWT., Results: A total of 318 complete and unique records were identified. Both groups showed a significant within-group Δ6MWT during hospitalization (COG+: 47.51 m; COG-: 40.97 m; P  < .01). In contrast, Δ6MWT values were comparable between groups. The odds of achieving a minimal clinical important difference on the 6MWT did not differ significantly between both groups. Only attention/concentration was significantly correlated with Δ6MWT (r = 0.16, P  = .013)., Conclusion: Cognitive impairment based on BRB-N results appears not to impede locomotor rehabilitation in ambulatory patients with MS. Attentional deficits are correlated to the extent of locomotor rehabilitation, suggesting the presence of a subtle effect of cognition., Competing Interests: Declaration of conflicting interests:The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)