1,721,251 research outputs found
CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis
No full textBackground 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.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Sanofi Genzyme, and grants of the Belgian Charcot Foundation, Research Foundation Flanders (FWO), and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium.
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Tapping to music and metronome ticks at high and low tempi in persons with progressive MS
No full textMotor evoked potentials for multiple sclerosis, a multiyear follow-up dataset
No full textMultiple sclerosis (MS) is a chronic disease affecting millions of people worldwide. Through the demyelinating and axonal pathology of MS, the signal conduction in the central nervous system is affected. Evoked potential measurements allow clinicians to monitor this process and can be used for decision support. We share a dataset that contains motor evoked potential (MEP) measurements, in which the brain is stimulated and the resulting signal is measured in the hands and feet. This results in time series of 100 milliseconds long. Typically, both hands and feet are measured in one hospital visit. The dataset contains 5586 visits of 963 patients, performed in day-to-day clinical care over a period of 6 years. The dataset consists of approximately 100,000 MEP. Clinical metadata such as the expanded disability status scale, sex, and age is also available. This dataset can be used to explore the role of evoked potentials in MS research and patient care. It may also be used as a benchmark for time series analysis and predictive modelling
A real-world single-centre analysis of the safety and efficacy of cladribine tablets for relapsing multiple sclerosis
No full textIntroduction: Damage of frontal cortico-subcortical networks contributes to fatigue and dual-task impairment in multiple sclerosis (MS). However, the mechanisms underlying these clinical deficits in progressive (P) MS still need to be fully explored. Objectives and Aims: In this study, we investigated the associations between structural and functional MRI abnormalities of frontal cortico-subcortical circuits and fatigue and dual-task performance in PMS. Methods: Brain structural and functional MRI scans, Modified Fatigue Impact Scale (MFIS) and dual-task performances were obtained from 57 PMS patients with impaired processing speed from 4 centers and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connecting tracts and their resting state effective connectivity (RS EC) with fatigue, single-and dual-task performances were investigated. Results: Compared to HC, PMS patients had higher fatigue (p⩽0.027) and worse dual-task performance (p<0.001). Compared to non-fatigued (MFIS<38), PMS patients with fatigue (MFIS⩾38) had lower RS EC from left-caudate nucleus to left-DLPFC (p=0.007). In PMS, higher MFIS-physical and MFIS-psychosocial scores were predicted by lower RS EC from left-caudate nucleus to left-DLPFC (R 2 =0.112, p=0.027) and higher RS EC from right-thalamus to right-DLPFC (R 2 =0.102, p=0.046), respectively. Dual-task motor performances were predicted by lower RS EC from left-DLPFC to left-thalamus (R 2 ⩾0.137, p⩽0.032). Several structural MRI measures independently predicted dual-task correct response rates (R 2 =0.307, p⩽0.010) and dual-task cognitive cost (R 2 =0.188, p=0.002). Fatigue impact was not associated with single-and dual-task performances. Conclusions: Frontal cortico-subcortical structural and functional MRI abnormalities differently contribute to fatigue impact and single-and dual-task performance in PMS
A real-world single-centre analysis of the safety and efficacy of cladribine tablets for relapsing multiple sclerosis
No full textIntroduction: Damage of frontal cortico-subcortical networks contributes to fatigue and dual-task impairment in multiple sclerosis (MS). However, the mechanisms underlying these clinical deficits in progressive (P) MS still need to be fully explored. Objectives and Aims: In this study, we investigated the associations between structural and functional MRI abnormalities of frontal cortico-subcortical circuits and fatigue and dual-task performance in PMS. Methods: Brain structural and functional MRI scans, Modified Fatigue Impact Scale (MFIS) and dual-task performances were obtained from 57 PMS patients with impaired processing speed from 4 centers and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connecting tracts and their resting state effective connectivity (RS EC) with fatigue, single-and dual-task performances were investigated. Results: Compared to HC, PMS patients had higher fatigue (p⩽0.027) and worse dual-task performance (p<0.001). Compared to non-fatigued (MFIS<38), PMS patients with fatigue (MFIS⩾38) had lower RS EC from left-caudate nucleus to left-DLPFC (p=0.007). In PMS, higher MFIS-physical and MFIS-psychosocial scores were predicted by lower RS EC from left-caudate nucleus to left-DLPFC (R 2 =0.112, p=0.027) and higher RS EC from right-thalamus to right-DLPFC (R 2 =0.102, p=0.046), respectively. Dual-task motor performances were predicted by lower RS EC from left-DLPFC to left-thalamus (R 2 ⩾0.137, p⩽0.032). Several structural MRI measures independently predicted dual-task correct response rates (R 2 =0.307, p⩽0.010) and dual-task cognitive cost (R 2 =0.188, p=0.002). Fatigue impact was not associated with single-and dual-task performances. Conclusions: Frontal cortico-subcortical structural and functional MRI abnormalities differently contribute to fatigue impact and single-and dual-task performance in PMS
Diagnostic accuracy and psychometric properties of patient-reported outcome measures for pain in multiple sclerosis
No full textBart Van Wijmeersch received research and travel grants, honoraria for MS-Expert advisor and Speaker fees from Almirall, Biogen, BMS, Imcyse, Janssen, Sanofi, Merck, Novartis, Roche and Teva. Peter Feys provided lectures for Roch
Machine learning analysis of motor evoked potential time series to predict disability progression in multiple sclerosis
No full textBackground 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 (Delta AUC = 0.02 for RF and Delta AUC = 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.Funding
TB is supported by the Fonds voor Wetenschappelijk Onderzoek (FWO), project R4859. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government - department EWI. This research received funding from the Flemish Government under the “Onderzoeksprogramma Artificiële Intelligentie (AI) Vlaanderen” programme. The funding bodies played no role in the design of the study, in writing the manuscript, nor in the collection, analysis, or interpretation of the data
Perceived and actual arm performance in multiple sclerosis: relationship with clinical tests according to hand dominance
No full textBACKGROUND: The real-life relevance of frequently applied clinical arm tests is not well known in multiple sclerosis (MS). OBJECTIVE: This study aimed to determine the relation between real-life arm performance and clinical tests in MS. METHODS: Thirty wheelchair-bound MS patients and 30 healthy controls were included. Actual and perceived real-life arm performance was measured by using accelerometry and a self-reported measure (Motor Activity Log). Clinical tests on 'body functions & structures' (JAMAR handgrip strength, Motricity Index (MI), Fugl Meyer (FM)) and 'activity' level (Nine Hole Peg Test (NHPT), Action Research Arm test) of the International Classification of Functioning were conducted. Statistical analyses were performed separately for current dominant and non-dominant arm. RESULTS: For all outcome measures, MS patients scored with both arms significantly lower than the control group. Higher correlations between actual arm performance and clinical tests were found for the non-dominant arm (0.63-0.80). The FM (55%) was a good predictor of actual arm performance, while the MI (46%) and NHPT (55%) were good predictors of perceived arm performance. CONCLUSIONS: Real-life arm performance is decreased in wheelchair-bound MS patients and can be best predicted by measures on 'body functions & structures' level and fine motor control. Hand dominance influenced the magnitude of relationships.sponsorship: Ilse Lamers is supported by a PhD fellowship from the Research council of Hasselt University (BOF-grant). The equipment (accelerometers) were funded by WOMS (Wetenschappelijk Onderzoek in Multiple Sclerosis) and by a Belgian Charcot Foundation equipment grant. (Research council of Hasselt University (BOF-grant), WOMS (Wetenschappelijk Onderzoek in Multiple Sclerosis), Belgian Charcot Foundation)status: Publishe
Diagnostic accuracy and psychometric properties of patient-reported outcome measures for pain in multiple sclerosis
No full textBart Van Wijmeersch received research and travel grants, honoraria for MS-Expert advisor and Speaker fees from Almirall, Biogen, BMS, Imcyse, Janssen, Sanofi, Merck, Novartis, Roche and Teva. Peter Feys provided lectures for Roch
Application of step and beat alignment approaches and its effect on gait in progressive multiple sclerosis with severe cerebellar ataxia : a proof of concept case study
No full textBackground: In a case report of a progressive multiple sclerosis with cerebellar impairments, we reported that synchronisation of steps to beats was possible only at −12% of usual walking cadence during 1 minute of walking.
Objectives and methods: Here, we investigate the effect of synchronisation using two different alignment approaches on the patient’s gait pattern over 2 minutes of walking, compared to walking in silence.
Results and conclusion: This proof of concept showed that the adaptive approach was successful resulting in an improved gait pattern compared to the other conditions, providing preliminary evidence to support a full-scale intervention study
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