Publications by authors named "Bart Van Wijmeersch"

59 Publications

Differential effects and discriminative validity of motor and cognitive tasks varying in difficulty on cognitive-motor interference in persons with multiple sclerosis.

Mult Scler 2021 Feb 10:1352458520986960. Epub 2021 Feb 10.

REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium.

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 ( < 0.001) and the walking condition ( ⩽ 0.002), while cognitive-DTC only varied between cognitive tasks with a large difference in difficulty ( ⩽ 0.005) and not between walking conditions ( ⩾ 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.
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http://dx.doi.org/10.1177/1352458520986960DOI Listing
February 2021

Clinical manifestation and perceived symptoms of walking-related performance fatigability in persons with multiple sclerosis.

Int J Rehabil Res 2021 Jan 29. Epub 2021 Jan 29.

REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium Department of Nutrition and Movement Sciences, School of Nutrition and Translational Research inMetabolism, Maastricht Universitair Medisch Centrum, The Netherlands IPEM Institute of Psychoacoustics and Electronic Music, Faculty of Arts and Philosophy, Gent University, Gent, Belgium Departement of Physiotherapy, NMSC, Nationaal Multiple Sclerose centrum, Melsbroek Noorderhart, Rehabilitation and MS Center, Boemerangstraat 2, Overpelt, Belgium Faculty of Physical Education, University of Brasilia, Brasilia - DF, Brazil.

Fatigue and walking difficulties are common impairments and activity limitations in persons with multiple sclerosis (PwMS). Walking fatigability (WF) can be measured by a Distance Walked Index and is defined as a decline in walking distance of 10% or more during the six-minute walking test (6MWT). However, the clinical manifestation and perceived symptoms related to fatigability are still not well documented. Forty-nine PwMS [Expanded Disability Status Scale (EDSS) ≤6] and 28 healthy controls (HC) performed a 6MWT. The perceived severity of 11 common symptoms was rated on a visual analogue scale of 0-10 before, immediately after, and 10, 20 and 30 minutes after the 6MWT by means of the symptom inventory. Short motor impairment screening tests at baseline together with other descriptive measures were performed. Twenty pwMS were categorized in the WF group and were more disabled (EDSS: 4.16 ± 1.41) than the non-walking fatigability group (n = 29, EDSS: 2.62 ± 1.94). PwMS showed exacerbations of several perceived symptoms in MS, where most symptoms returned to baseline within 10 minutes after the walking test. The WF group showed significantly more muscle weakness and gait impairment, together with balance problems, and experienced an increase in spasticity, pain and dizziness after 6MWT. Our findings showed that perceived severity of symptoms are higher in pwMS presenting WF, and increase temporally after the 6MWT. Future research with quantitative measurement during and after walking is recommended.
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http://dx.doi.org/10.1097/MRR.0000000000000457DOI Listing
January 2021

Determinants of therapeutic lag in multiple sclerosis.

Mult Scler 2021 Jan 11:1352458520981300. Epub 2021 Jan 11.

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.

Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.

Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.

Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).

Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.
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http://dx.doi.org/10.1177/1352458520981300DOI Listing
January 2021

Multiple Sclerosis Data Alliance - A global multi-stakeholder collaboration to scale-up real world data research.

Mult Scler Relat Disord 2021 Jan 21;47:102634. Epub 2020 Nov 21.

Institute of Experimental Neurology, Ospedale San Raffaele, Via Olgettina, 48, 20132, Milan, Italy.

The Multiple Sclerosis Data Alliance (MSDA), a global multi-stakeholder collaboration, is working to accelerate research insights for innovative care and treatment for people with multiple sclerosis (MS) through better use of real-world data (RWD). Despite the increasing reliance on RWD, challenges and limitations complicate the generation, collection, and use of these data. MSDA aims to tackle sociological and technical challenges arising with scaling up RWD, specifically focused on MS data. MSDA envisions a patient-centred data ecosystem in which all stakeholders contribute and use big data to co-create the innovations needed to advance timely treatment and care of people with MS.
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http://dx.doi.org/10.1016/j.msard.2020.102634DOI Listing
January 2021

Comparing 16 Different Dual-Tasking Paradigms in Individuals With Multiple Sclerosis and Healthy Controls: Working Memory Tasks Indicate Cognitive-Motor Interference.

Front Neurol 2020 28;11:918. Epub 2020 Aug 28.

Faculty of Rehabilitation Sciences, REVAL Rehabilitation Research Center, Hasselt University, Hasselt, Belgium.

Cognitive-motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis (MS). We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty. In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 ± 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive-motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC). Two-way analyses of variance showed the main effect of cognitive task yielded an ratio of = 72.35, < 0.01, for mean gait velocity, and an ratio of = 17.12, < 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS_B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded an ratio of = 84.32, < 0.001, with the lowest average accuracy for DS_B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% ( = 13.65, = 0.001) of variance in a model predicting the highest mDTC. Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task.
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http://dx.doi.org/10.3389/fneur.2020.00918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485559PMC
August 2020

The use of alemtuzumab in patients with relapsing-remitting multiple sclerosis: the Gulf perspective.

Ther Adv Neurol Disord 2020 16;13:1756286420954119. Epub 2020 Sep 16.

Sanofi Genzyme, Dubai, United Arab Emirates.

Over the past decade, the development of high-efficacy disease-modifying therapies (DMTs) has been responsible for more effective management of relapsing-remitting multiple sclerosis (RRMS). However, the gaps in optimal care for this complex disease remain. Alemtuzumab (Lemtrada®) is a highly efficacious DMT that shows better patient outcomes and therapeutic benefits, but its use is under-recognized in the Gulf region. Experts in the care of multiple sclerosis shared their opinions based on study data and daily clinical experience in identifying the appropriate patient profile suitable for alemtuzumab's therapeutic benefits. Age, disease activity and severity, disability status, physician experience, and economic condition are some of the key indicators for alemtuzumab use.
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http://dx.doi.org/10.1177/1756286420954119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498833PMC
September 2020

Delay from treatment start to full effect of immunotherapies for multiple sclerosis.

Brain 2020 09;143(9):2742-2756

CORe, Department of Medicine, University of Melbourne, Melbourne, 3050, Australia.

In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag.
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http://dx.doi.org/10.1093/brain/awaa231DOI Listing
September 2020

CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis.

Ther Adv Chronic Dis 2020 21;11:2040622320947378. Epub 2020 Aug 21.

Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan Building C, Diepenbeek, 3590, Belgium.

Background And Aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing-remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model.

Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters.

Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice.

Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.
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http://dx.doi.org/10.1177/2040622320947378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443992PMC
August 2020

Effect of Multiple Sclerosis on Daily Activities, Emotional Well-being, and Relationships: The Global vsMS Survey.

Int J MS Care 2020 Jul-Aug;22(4):158-164. Epub 2019 Aug 28.

Background: The vsMS survey was conducted to better understand the negative effects of fatigue, cognitive impairment, emotional burden, and decreased physical functioning on the personal, professional, and social lives of individuals with multiple sclerosis (MS).

Methods: The vsMS survey was an online survey conducted in Australia, Canada, France, Italy, Spain, the United Kingdom, and the United States that assessed the impact of MS on individuals' daily activities, emotional well-being, relationships, and employment.

Results: The survey included 1075 participants with relapsing-remitting MS. Almost 42% of participants reported that their ability to perform and manage daily activities had worsened during the previous 2 years. More than 50% reported limitations in daily activities due to fatigue, physical weakness, problems with balance/coordination, heat/cold sensitivity, memory problems, numbness/tingling, trouble concentrating, impaired movement/muscle stiffness, and impaired sleeping. Participants also reported a negative effect on emotional and social factors, including self-esteem, general outlook, well-being, maintaining/starting relationships, ability to progress in their career/keep their job, and ability to cope with life roles.

Conclusions: These data highlight the importance of addressing the impact of MS and the social and emotional disease burdens on daily activities when planning the care of patients with MS.
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http://dx.doi.org/10.7224/1537-2073.2018-087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446625PMC
August 2019

Deciphering the Morphology of Motor Evoked Potentials.

Front Neuroinform 2020 14;14:28. Epub 2020 Jul 14.

I-Biostat, Data Science Institute, Hasselt University, Diepenbeek, Belgium.

Motor Evoked Potentials (MEPs) are used to monitor disability progression in multiple sclerosis (MS). Their morphology plays an important role in this process. Currently, however, there is no clear definition of what constitutes a normal or abnormal morphology. To address this, five experts independently labeled the morphology (normal or abnormal) of the same set of 1,000 MEPs. The intra- and inter-rater agreement between the experts indicates they agree on the concept of morphology, but differ in their choice of threshold between normal and abnormal morphology. We subsequently performed an automated extraction of 5,943 time series features from the MEPs to identify a valid proxy for morphology, based on the provided labels. To do this, we compared the cross-validation performances of one-dimensional logistic regression models fitted to each of the features individually. We find that the approximate entropy (ApEn) feature can accurately reproduce the majority-vote labels. The performance of this feature is evaluated on an independent test set by comparing to the majority vote of the neurologists, obtaining an AUC score of 0.92. The model slightly outperforms the average neurologist at reproducing the neurologists consensus-vote labels. We can conclude that MEP morphology can be consistently defined by pooling the interpretations from multiple neurologists and that ApEn is a valid continuous score for this. Having an objective and reproducible MEP morphological abnormality score will allow researchers to include this feature in their models, without manual annotation becoming a bottleneck. This is crucial for large-scale, multi-center datasets. An exploratory analysis on a large single-center dataset shows that ApEn is potentially clinically useful. Introducing an automated, objective, and reproducible definition of morphology could help overcome some of the barriers that are currently obstructing broad adoption of evoked potentials in daily care and patient follow-up, such as standardization of measurements between different centers, and formulating guidelines for clinical use.
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http://dx.doi.org/10.3389/fninf.2020.00028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381179PMC
July 2020

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study.

CNS Drugs 2020 09;34(9):973-988

MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO, USA.

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously.

Objectives: In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm.

Methods: Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition.

Results: In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0-2 and 0.16 in years 3-9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was - 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9.

Conclusions: Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No safety signals were observed over 9 years that were unique to the HAD populations. CLINICALTRIALS.

Gov Identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656.
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http://dx.doi.org/10.1007/s40263-020-00749-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447657PMC
September 2020

Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score.

Mult Scler 2020 Jul 8:1352458520936823. Epub 2020 Jul 8.

CORe, Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia/ Melbourne MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.

Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing-remitting multiple sclerosis (RRMS) treated with interferon-β.

Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions.

Methods: This RRMS MSBase cohort study ( = 2293) used a Cox model to examine the prognostic value of relapses, MRI activity and the MAGNIMS score for disability worsening during treatment with interferon-β and three other DMTs.

Results: Three new T2 lesions (hazard ratio (HR) = 1.60,  = 0.028) or two relapses (HR = 2.24,  = 0.002) on interferon-β (for 12 months) were predictive of disability worsening over 4 years. MAGNIMS score = 2 (1 relapse and ⩾3 T2 lesions or ⩾2 relapses) was associated with a greater risk of disability worsening on interferon-β (HR = 2.0,  = 0.001). In pooled cohort of four DMTs, similar associations were seen (MAGNIMS score = 2: HR = 1.72,  = 0.001). Secondary analyses demonstrated that the addition of Gd+ to the MAGNIMS did not materially improve its prediction of disability worsening.

Conclusion: We have validated the MAGNIMS score in RRMS and extended its application to three other DMTs: 1 relapse and ⩾3 T2 lesions or ⩾2 relapses predicted worsening of disability. Contrast-enhancing lesions did not substantially improve the prognostic score.
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http://dx.doi.org/10.1177/1352458520936823DOI Listing
July 2020

Machine learning analysis of motor evoked potential time series to predict disability progression in multiple sclerosis.

BMC Neurol 2020 Mar 21;20(1):105. Epub 2020 Mar 21.

I-Biostat, Data Science Institute, Hasselt University,, Diepenbeek, Belgium.

Background: Evoked potentials (EPs) are a measure of the conductivity of the central nervous system. They are used to monitor disease progression of multiple sclerosis patients. Previous studies only extracted a few variables from the EPs, which are often further condensed into a single variable: the EP score. We perform a machine learning analysis of motor EP that uses the whole time series, instead of a few variables, to predict disability progression after two years. Obtaining realistic performance estimates of this task has been difficult because of small data set sizes. We recently extracted a dataset of EPs from the Rehabiliation & MS Center in Overpelt, Belgium. Our data set is large enough to obtain, for the first time, a performance estimate on an independent test set containing different patients.

Methods: We extracted a large number of time series features from the motor EPs with the highly comparative time series analysis software package. Mutual information with the target and the Boruta method are used to find features which contain information not included in the features studied in the literature. We use random forests (RF) and logistic regression (LR) classifiers to predict disability progression after two years. Statistical significance of the performance increase when adding extra features is checked.

Results: Including extra time series features in motor EPs leads to a statistically significant improvement compared to using only the known features, although the effect is limited in magnitude (ΔAUC = 0.02 for RF and ΔAUC = 0.05 for LR). RF with extra time series features obtains the best performance (AUC = 0.75±0.07 (mean and standard deviation)), which is good considering the limited number of biomarkers in the model. RF (a nonlinear classifier) outperforms LR (a linear classifier).

Conclusions: Using machine learning methods on EPs shows promising predictive performance. Using additional EP time series features beyond those already in use leads to a modest increase in performance. Larger datasets, preferably multi-center, are needed for further research. Given a large enough dataset, these models may be used to support clinicians in their decision making process regarding future treatment.
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http://dx.doi.org/10.1186/s12883-020-01672-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085864PMC
March 2020

Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies.

Mult Scler 2020 11 1;26(13):1719-1728. Epub 2019 Nov 1.

University of Lille, INSERM U995, CHU Lille, FHU Imminent, Lille, France.

Background: Alemtuzumab is administered as two annual courses for relapsing-remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen.

Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers).

Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension.

Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1-2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: -0.67% (CARE-MS I); -0.47% (CARE-MS II)) declined after Course 2 (Year 6: -0.24%; -0.13%).

Conclusion: Early relapsers' outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit.

Clinicaltrials.gov Registration Numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.
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http://dx.doi.org/10.1177/1352458519881759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604550PMC
November 2020

Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab.

Neurol Neuroimmunol Neuroinflamm 2020 01 29;7(1). Epub 2019 Oct 29.

From the University of Münster (H.W.), Münster, Germany; Novant Health (M.C.), Charlotte, NC; University Vita-Salute San Raffaele (G.C.), Milan, Italy; Virgen Macarena University Hospital (G.I.), Seville, Spain; Research Institute and Hospital of National Cancer Center (H.J.K.), Goyang, South Korea; NIHR Sheffield Biomedical Research Centre, Sheffield Teaching Hospitals, University of Sheffield (B.S.), Sheffield, United Kingdom; Georgetown University Medical Center (C.T.), Washington, DC; Sanofi (N.D., L.C., A.K.J.), Cambridge, MA; Eloquent Scientific Solutions (R.J.H.), Sydney, NSW, Australia; Eloquent Scientific Solutions (L.V.W.), Philadelphia, PA; and Rehabilitation & MS-Centre Overpelt (B.V.W.), BIOMED, Hasselt University, Hasselt, Belgium.

Objective: To examine the association between peripheral blood lymphocyte pharmacodynamics and autoimmune adverse events (AEs) or return of disease activity in alemtuzumab-treated patients with relapsing-remitting MS.

Methods: Patients received 2 alemtuzumab courses (12 mg/d IV; 5 days at baseline, 3 days 12 months later) in the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis studies (NCT00530348 and NCT00548405) and could then receive as-needed alemtuzumab or other disease-modifying therapy in a 4-year extension (NCT00930553). Lymphocytes were phenotyped quarterly over 2 years using fluorescence-activated cell sorting. Pharmacodynamic assessments included counts of total lymphocytes, CD3 T cells, CD4/CD8 T cells (total/naive/memory/regulatory [T]), and CD19 B cells (total/immature/mature/memory) and ratios of CD19 (total/immature/mature/memory) to T (CD4/CD8) counts. Assessed autoimmune AEs included immune thrombocytopenia, nephropathies, and thyroid events. Efficacy assessments included relapses, 6-month confirmed disability worsening (CDW), and MRI disease activity.

Results: Lymphocyte repopulation patterns, including ratios between distinct lymphocyte subsets (e.g., CD19 to T cell count ratios), showed no significant differences over 2 years in patients developing/not developing autoimmune AEs, relapses, CDW, or MRI activity through 6 years following alemtuzumab. Lymphocyte kinetics were also unrelated to multiple autoimmune AEs or extreme clinical phenotypes.

Conclusions: Repopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response.
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http://dx.doi.org/10.1212/NXI.0000000000000635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865853PMC
January 2020

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Mult Scler 2020 01 9;26(1):79-90. Epub 2019 Aug 9.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia/L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.

Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02,  < 0.001), longer disease duration (HR = 1.01,  = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30,  < 0.001), more rapid disability trajectory (HR = 2.82,  < 0.001) and greater number of relapses in the previous year (HR = 1.07,  = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62,  = 0.039) and disease-modifying therapy exposure (HR = 0.71,  = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
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http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020

Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgDCD27 Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients.

J Immunol 2019 09 7;203(6):1650-1664. Epub 2019 Aug 7.

Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3500 Hasselt, Belgium.

IgDCD27 double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgDCD27 class-switched memory (CSM) and IgDCD27 naive B cells of HC ( = 48) and MS patients ( = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients ( = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95 and IgA cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.
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http://dx.doi.org/10.4049/jimmunol.1801236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736705PMC
September 2019

A pilot study of the effects of running training on visuospatial memory in MS: A stronger functional embedding of the hippocampus in the default-mode network?

Mult Scler 2020 10 18;26(12):1594-1598. Epub 2019 Jul 18.

Department of Anatomy & Neurosciences, MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background/objective: Endurance exercise can improve memory function in persons with multiple sclerosis (pwMS), but the effects on hippocampal functioning are currently unknown. We investigated the effects of a running intervention on memory and hippocampal functional connectivity in pwMS.

Methods/results: Memory and resting-state functional magnetic resonance imaging (fMRI) data were collected in a running intervention ( = 15) and waitlist group ( = 14). Visuospatial memory improvement was correlated to increased connectivity between the hippocampus and the default-mode network (DMN) in the intervention group only.

Conclusion: As a result of endurance exercise, improvements in visuospatial memory may be mediated by a stronger functional embedding of the hippocampus in the DMN.
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http://dx.doi.org/10.1177/1352458519863644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575292PMC
October 2020

Walking to Music and Metronome at Various Tempi in Persons With Multiple Sclerosis: A Basis for Rehabilitation.

Neurorehabil Neural Repair 2019 06 13;33(6):464-475. Epub 2019 May 13.

1 Hasselt University, REVAL Rehabilitation Research Center, Hasselt, Belgium.

. Mobility dysfunctions are prevalent in persons with multiple sclerosis (PwMS), thus novel rehabilitation mechanisms are needed toward functional training. The effect of auditory cueing is well-known in Parkinson's disease, yet the application of different types of auditory stimuli at different tempi has not been investigated yet. . Investigating if PwMS, compared with healthy controls (HC), can synchronize their gait to music and metronomes at different tempi during walking and the effects of the stimuli on perceived fatigue and gait. Additionally, exploring if cognitive impairment would be a factor on the results. . The experimental session consisted of 2 blocks, music and metronomes. Per block, participants walked 3 minutes per tempi, with instructions to synchronize their steps to the beat. The tempi were 0%, +2%, +4% +6%, +8%, +10% of preferred walking cadence (PWC). . A total of 28 PwMS and 29 HC participated. On average, participants were able to synchronize at all tempi to music and metronome. Higher synchronization was obtained for metronomes compared with music. The highest synchronization for music was found between +2% and +8% of PWC yet pwMS perceived less physical and cognitive fatigue walking to music compared with metronomes. Cognitive impaired PwMS (n = 9) were not able to synchronize at tempi higher than +6%. . Auditory-motor coupling and synchronization was feasible in HC and PwMS with motor and cognitive impairments. PwMS walked at higher tempi than their preferred walking cadence, and lower fatigue perception with music. Coupling walking to music could be a promising functional walking training strategy.
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http://dx.doi.org/10.1177/1545968319847962DOI Listing
June 2019

Best Practices for Long-Term Monitoring and Follow-Up of Alemtuzumab-Treated MS Patients in Real-World Clinical Settings.

Front Neurol 2019 22;10:253. Epub 2019 Mar 22.

Rehabilitation & MS-Centre Overpelt, Hasselt University, Hasselt, Belgium.

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405). Efficacy with alemtuzumab was maintained over 7 years in subsequent extension studies (NCT00930553; NCT02255656), in the absence of continuous treatment and with a consistent safety profile. There is an increased incidence of autoimmune events in patients treated with alemtuzumab (mainly thyroid events, but also immune thrombocytopenia and nephropathy), which imparts a need for mandatory safety monitoring for 4 years following the last treatment. The risk management strategy for alemtuzumab-treated patients includes laboratory monitoring and a comprehensive patient education and support program that enables early detection and effective management of autoimmune events, yielding optimal outcomes for MS patients. Here we provide an overview of tools and techniques that have been implemented in real-world clinical settings to reduce the burden of monitoring for both patients and healthcare providers, including customized educational materials, the use of social media, and interactive online databases for managing healthcare data. Many practices are also enhancing patient outreach efforts through coordination with specialized nursing services and ancillary caregivers. The best practice recommendations for safety monitoring described in this article, based on experiences in real-world clinical settings, may enable early detection and management of autoimmune events, and help with implementation of monitoring requirements while maximizing the benefits of alemtuzumab treatment for MS patients.
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http://dx.doi.org/10.3389/fneur.2019.00253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439479PMC
March 2019

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

Mult Scler 2020 01 20;26(1):48-56. Epub 2019 Feb 20.

Department of Haematology, University Hospitals Leuven, Leuven, Belgium.

Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk.

Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials.

Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion.

Results: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials.

Conclusion: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.
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http://dx.doi.org/10.1177/1352458518816612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950888PMC
January 2020

Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis.

J Neurol Neurosurg Psychiatry 2019 04 13;90(4):458-468. Epub 2019 Jan 13.

Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Objective: Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.

Methods: We identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).

Results: The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).

Conclusion: The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.
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http://dx.doi.org/10.1136/jnnp-2018-319831DOI Listing
April 2019

Multidisciplinary data infrastructures in multiple sclerosis: Why they are needed and can be done!

Mult Scler 2019 04 1;25(4):500-509. Epub 2018 Nov 1.

Biomedical Research Institute, Hasselt University, Hasselt, Belgium.

Personalized treatment is highly desirable in multiple sclerosis (MS). We believe that multidisciplinary measurements including clinical, functional and patient-reported outcome measures in combination with extensive patient profiling can enhance personalized treatment and rehabilitation strategies. We elaborate on four reasons behind this statement: (1) MS disease activity and progression are complex and multidimensional concepts in nature and thereby defy a one-size-fits-all description, (2) functioning, progression, treatment, and rehabilitation effects are interdependent and should be investigated together, (3) personalized healthcare is based on the dynamics of system biology and on technology that confirms a patient's fundamental biology and (4) inclusion of patient-reported outcome measures can facilitate patient-relevant healthcare. We discuss currently available multidisciplinary MS data initiatives and introduce joint actions to further increase the overall success. With this topical review, we hope to drive the MS community to invest in expanding towards more multidisciplinary and longitudinal data collection.
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http://dx.doi.org/10.1177/1352458518807076DOI Listing
April 2019

Walking endurance and perceived symptom severity after a single maximal exercise test in persons with mild disability because of multiple sclerosis.

Int J Rehabil Res 2018 Dec;41(4):316-322

Fit Up Physiotherapy Centre Kontich, Kontich, Belgium.

People with multiple sclerosis (PwMS) are less physically active compared with the general population. This might also be because of the perception of temporary worsening of symptoms during physical activity. Forty-two PwMS with a mild level of disability underwent a maximal exercise test on a bicycle ergometer. Fifteen minutes before and 15 and 75 min after the maximal exercise test, the 6-minute walking test was conducted and the rate of perceived exertion was recorded. Twice before and three times after the maximal exercise test, participants rated the symptom inventory, including symptom domains of general fatigue, muscle fatigue, balance, gait pattern, muscle weakness, spasticity, pain, sensory disturbance, dizziness, and visual impairment. The visual analogue scale was used to rate the perceived symptoms from 0 (no intensity) to 10 (maximal intensity). The 6-minute walking test distance increased significantly over time, whereas the rate of perceived exertion increased temporarily after the maximal exercise test. Immediately after the maximal exercise test, significant temporary increases were found in balance, gait pattern, muscle weakness, and visual impairment. General and muscle fatigue were elevated, compared with the baseline, till 15 and 75 min after the maximal exercise test, respectively. A short-term impact of a single maximal exercise test was considered as the temporary worsening of perceived symptoms, especially (muscle) fatigue and the gait pattern, in PwMS with a mild level of disability. However, a recovery was observed after 75 min. Walking endurance was not affected by the maximal exercise test.
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http://dx.doi.org/10.1097/MRR.0000000000000305DOI Listing
December 2018

Improving fatigue in multiple sclerosis by smartphone-supported energy management: The MS TeleCoach feasibility study.

Mult Scler Relat Disord 2018 May 27;22:90-96. Epub 2018 Mar 27.

National MS Center, Neurology, Vanheylenstraat 16, Melsbroek and Vrije Universiteit Brussel (VUB), Center for Neurosciences, Laarbeeklaan 103, 1090 Brussel, Belgium. Electronic address:

Background: Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period. The goal of the MS TeleCoach, conceived as a combination of monitoring, self-management and motivational messages, is to enhance levels of physical activity thereby improving fatigue in pwMS in an accessible and interactive way, reinforcing self-management of patients.

Methods: We conducted a prospective, open-label feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status Scale ≤ 4 and moderate to severe fatigue as measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess the baseline activity level per patient, the target number of activity counts was gradually increased over the 12-week period through telecoaching. The primary efficacy outcome was change in FSMC total score from baseline to study end. A subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire, to evaluate the satisfaction with the MS TeleCoach device and the experienced service.

Results: Seventy-five patients were recruited from 16 centres in Belgium, of which 57 patients (76%) completed the study. FSMC total score (p = 0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively) decreased from baseline to week 12, indicating an improvement in fatigue. One third of participants with severe fatigue changed to a lower FSMC category for both FSMC total score and subscores. The post-study evaluation of patient satisfaction showed that the intervention was well accepted and that patients were very satisfied with the quality of the professional services.

Conclusion: Using MS TeleCoach as a self-management tool in pwMS suffering from mild disability and moderate to severe fatigue appeared to be feasible, both technically and from a content perspective. Its use was associated with improved fatigue levels in the participants who completed the study. The MS Telecoach seems to meet the need for a low-cost, accessible and interactive self-management tool in MS.
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http://dx.doi.org/10.1016/j.msard.2018.03.020DOI Listing
May 2018

A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis.

Acta Neurol Belg 2018 Jun 13;118(2):161-168. Epub 2018 Mar 13.

Department of Hematology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium.

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis.
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http://dx.doi.org/10.1007/s13760-018-0905-0DOI Listing
June 2018

Thyroid disorders in alemtuzumab-treated multiple sclerosis patients: a Belgian consensus on diagnosis and management.

Acta Neurol Belg 2018 Jun 25;118(2):153-159. Epub 2018 Jan 25.

Department of Endocrinology, Cliniques Universitaires St Luc, Brussels, Belgium.

This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events.
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http://dx.doi.org/10.1007/s13760-018-0883-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971042PMC
June 2018

Twelve Weeks of Medium-Intensity Exercise Therapy Affects the Lipoprotein Profile of Multiple Sclerosis Patients.

Int J Mol Sci 2018 Jan 8;19(1). Epub 2018 Jan 8.

BIOMED, School of Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium.

Multiple sclerosis (MS) is an inflammatory auto-immune disease of the central nervous system (CNS). Serum glucose alterations and impaired glucose tolerance (IGT) are reported in MS patients, and are commonly associated with the development of cardio-metabolic co-morbidities. We previously found that a subgroup of MS patients shows alterations in their lipoprotein profile that are similar to a pre-cardiovascular risk profile. In addition, we showed that a high-intensity exercise training has a positive effect on IGT in MS patients. In this study, we hypothesize that exercise training positively influences the lipoprotein profile of MS patients. To this end, we performed a pilot study and determined the lipoprotein profile before (controls, = 40; MS patients, = 41) and after ( = 41 MS only) 12 weeks of medium-intensity continuous training (MIT, = 21, ~60% of VO) or high-intensity interval training (HIT, = 20, ~100-200% of VO) using nuclear magnetic resonance spectroscopy (NMR). Twelve weeks of MIT reduced intermediate-density lipoprotein particle count ((nmol/L); -43.4%; < 0.01), low-density lipoprotein cholesterol (LDL-c (mg/dL); -7.6%; < 0.05) and VLDL size ((nm); -6.6%; < 0.05), whereas HIT did not influence the lipoprotein profile. These results show that MIT partially normalizes lipoprotein alterations in MS patients. Future studies including larger patient and control groups should determine whether MIT can reverse other lipoprotein levels and function and if these alterations are related to MS disease progression and the development of co-morbidities.
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http://dx.doi.org/10.3390/ijms19010193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796142PMC
January 2018

Does including the full CVLT-II and BVMT-R improve BICAMS? Evidence from a Belgian (Dutch) validation study.

Mult Scler Relat Disord 2017 Nov 7;18:33-40. Epub 2017 Sep 7.

Center for Neurosciences, Vrije Universiteit Brussel, Belgium; Faculté de Psychologie et des Sciences de l'Education, Université de Mons, Belgium; National MS Center Melsbroek, Belgium.

Background: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a fast, easy-to-administer and already widely validated neuropsychological battery for cognition in multiple sclerosis.

Objective: The goals of our study were to validate the BICAMS in a Belgian Dutch-speaking population and to investigate to what extent including extensive versions of two of the three BICAMS subtests improved its psychometric qualities.

Methods: Ninety-seven persons with MS and ninety-seven healthy controls were included and group-matched on age, education level and gender. All participants performed the BICAMS with an extensive version of the CVLT-II and BVMT-R.

Results: The SDMT and BVMT-R were able to dissociate between the MS and healthy control group, while the CVLT-II was not. Distributions of CVLT-II scores suggest learning effects in the MS group, indicating the need for alternative word lists or the construction of an adapted version fitted for repeated administration. Including the full CVLT-II and BVMT-R did not markedly improve the psychometric qualities of the BICAMS.

Conclusion: This study validates the BICAMS in a Belgian Dutch-speaking population and facilitates the use of it in clinical practice, while providing evidence that including full versions of the CVLT-II and BVMT-R does not increase its psychometric qualities markedly.
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http://dx.doi.org/10.1016/j.msard.2017.08.018DOI Listing
November 2017

Effects of an individual 12-week community-located "start-to-run" program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis.

Mult Scler 2019 01 8;25(1):92-103. Epub 2017 Nov 8.

Fit Up, Physiotherapy Centre, Kontich, Belgium.

Background: Exercise therapy studies in persons with multiple sclerosis (pwMS) primarily focused on motor outcomes in mid disease stage, while cognitive function and neural correlates were only limitedly addressed.

Objectives: This pragmatic randomized controlled study investigated the effects of a remotely supervised community-located "start-to-run" program on physical and cognitive function, fatigue, quality of life, brain volume, and connectivity.

Method: In all, 42 pwMS were randomized to either experimental (EXP) or waiting list control (WLC) group. The EXP group received individualized training instructions during 12 weeks (3×/week), to be performed in their community aiming to participate in a running event. Measures were physical (VO, sit-to-stand test, Six-Minute Walk Test (6MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12)) and cognitive function (Rao's Brief Repeatable Battery (BRB), Paced Auditory Serial Attention Test (PASAT)), fatigue (Fatigue Scale for Motor and Cognitive Function (FSMC)), quality of life (Multiple Sclerosis Impact Scale-29 (MSIS-29)), and imaging. Brain volumes and diffusion tensor imaging (DTI) were quantified using FSL-SIENA/FIRST and FSL-TBSS.

Results: In all, 35 pwMS completed the trial. Interaction effects in favor of the EXP group were found for VO, sit-to-stand test, MSWS-12, Spatial Recall Test, FSMC, MSIS-29, and pallidum volume. VO improved by 1.5 mL/kg/min, MSWS-12 by 4, FSMC by 11, and MSIS-29 by 14 points. The Spatial Recall Test improved by more than 10%.

Conclusion: Community-located run training improved aerobic capacity, functional mobility, visuospatial memory, fatigue, and quality of life and pallidum volume in pwMS.
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http://dx.doi.org/10.1177/1352458517740211DOI Listing
January 2019