Prevention of cognitive decline in Multiple Sclerosis (MS) is of major importance. We explored the effect of a 6 months computerized game training program on cognitive performance in MS patients with ...mild cognitive impairment.
This was a single-center, randomized prospective study. We enrolled in this study 100 eligible MS patients treated with Interferon-beta-1a (Rebif). All had mild cognitive impairment in either executive function or information processing speed. Patients were randomized 1:1 to either use the cognitive games platform by HappyNeuron (HN) or receive no intervention. Executive function and information processing speed scores were measured at 3 and 6 months from baseline to evaluate the effect of game training on cognitive scores.
In both executive function and information processing speed, the game Training group showed significant improvement after 3 and 6 months. The Non-Training group showed mild deterioration in both domains at 3 months, and further deterioration that became significant at 6 months in executive function. Furthermore, at 6 months, the percent of patients in the Training group that improved or remained stable in both cognitive domains was significantly higher compared to the Non-Training group.
Our findings suggest that cognitive game training has a beneficial effect on cognitive performance in MS patients suffering from mild cognitive impairment. While further evaluation is required to assess the longevity of that effect, we nonetheless recommend to MS patients to be engaged in cognitive gaming practice as part of a holistic approach to treating their condition.
Background and objectives:
Alemtuzumab demonstrated superior efficacy versus subcutaneous interferon (IFN) beta-1a in participants with relapsing-remitting multiple sclerosis in the 2-year CARE-MS I ...and II trials. Efficacy was maintained in the 4-year CARE-MS extension, during which alemtuzumab-treated participants (‘alemtuzumab-only’) could receive additional courses upon disease activity, and IFN-treated participants switched to alemtuzumab (‘IFN-alemtuzumab’). Participants who completed the CARE-MS extension could enroll in the open-label TOPAZ study which assessed safety and efficacy for 5–7 years (11–13 years after alemtuzumab/IFN initiation).
Methods:
Participants received additional alemtuzumab courses as needed. Assessments included adverse events (AEs; primary outcome), annualized relapse rate (ARR), 6-month confirmed disability worsening CDW; ⩾1.0-point Expanded Disability Status Scale (EDSS) score increase or ⩾1.5 if baseline EDSS = 0, and 6-month confirmed disease improvement CDI; >1.0-point EDSS decrease (baseline score ⩾2.0).
Results:
43.5% of alemtuzumab-only participants from CARE-MS II and 54.2% from CARE-MS I received no additional alemtuzumab courses; 30.0% and 20.9%, respectively, received one additional course (the median). Incidences of AEs, including thyroid AEs and infections, declined over time. The safety profile of alemtuzumab was similar for participants who received zero, one, or two additional courses. For CARE-MS II participants, who had inadequate response to previous treatment, ARR remained low during Years 3–13 for the alemtuzumab-only 0.17; 95% confidence interval (CI) 0.15–0.20 and IFN-alemtuzumab (0.14; 0.11–0.17) groups. At Year 11, the proportions of participants who were either free from CDW or who had CDI were higher in the alemtuzumab-only group (58% and 49%, respectively) than in the IFN-alemtuzumab group (51% and 37%). For CARE-MS I participants, who were previously treatment-naïve, clinical outcomes remained improved, and no between-group differences were apparent.
Conclusion:
Safety risks associated with alemtuzumab treatment declined over time. Clinical benefits were maintained up to 11–13 years, and most participants did not require more than one additional course.
Clinicaltrials.gov identifiers:
NCT00530348; NCT00548405; NCT00930553; NCT02255656
Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and ...European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing–remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.
JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national ...multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49.5% in patients < 30 years of age to 66.5% in patients ≥ 60 years of age; p < 0.0001 comparing all age categories), was lower in females than in males (55.8% versus 61.9%; p < 0.0001) and was not affected by prior immunosuppressant or natalizumab use.
To assess whether cerebellar volumes changes could represent a sensitive outcome measure in primary-progressive MS.
Changes in cerebellar volumes over one-year follow-up, estimated in 26 ...primary-progressive MS patients and 20 controls with Freesurfer longitudinal pipeline, were assessed using Wilcoxon test and tested for their correlation with disability worsening by a logistic regression. Clinical worsening was defined as EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test scores at follow-up. Sample sizes for given treatment effects and power were calculated. The findings were validated in an independent cohort of 20 primary-progressive MS patients.
Significant changes were detected in brain T1 lesion volume (p<0.01), cerebellar T2 and T1 lesion volume (p<0.01 and p<0.05), cerebellar volume, cerebellar cortex volume, and cerebellar WM volume (p<0.001). Only cerebellar volume and cerebellar cortex volume percentage change were significantly reduced in clinically progressed patients when compared to patients who did not progress (p<0.01; respectively AUC of 0.91 and 0.96). Cerebellar volume percentage changes were consistent in the exploration and validation cohorts (cerebellar volume -1.90±1.11% vs -1.47±2.30%; cerebellar cortex volume -1.68±1.41% vs -1.56±2.23%). Based on our results the numbers of patients required to detect a 30% effect are 81 per arm for cerebellar volume and 162 per arm for cerebellar cortex volume (90% power, type 1 error alpha = 0.05).
Our results suggest a role for cerebellar cortex volume and cerebellar volume as potential short-term imaging metrics to monitor treatment effect in primary-progressive MS clinical trials.
Background
Multiple sclerosis (MS) is a common nontraumatic, neurological, disabling disease that often presents with upper limb dysfunction. Exercise training has resulted in improvement for ...patients; however, there can be a lack of compliance due to access because of location and lack of MS experts. Virtual reality (VR) is a promising technology that can offer exercise therapy/rehabilitation at a distance. This type of remote training can be motivational and effective for patients with MS and can improve range of motion and muscle strength for those with upper limb dysfunction.
Objective
The aim of this study is to evaluate the safety and feasibility of the XRHealth software and the Oculus Rift Station for patients with MS with upper limb motor dysfunction.
Methods
A single-center, prospective, feasibility study was conducted with patients with MS who had upper limb motor dysfunction. Patients participated in a single 45-minute digital environment session with VR and completed a questionnaire about the quality of the training and fatigability. The clinician also completed a questionnaire to evaluate the suitability and safety of the training.
Results
Overall, 30 patients were enrolled between the ages of 20 and 81 years. Patients reported that the training sessions within the digital environment were helpful, challenging, fun, and simple to understand, and that they would be willing to repeat the sessions again. The physical therapist that oversaw the patients reported that the training was suitable for 87% (n=26) of the patients. Anticipated adverse events were fatigue, temporary dizziness, and temporary nausea. The operator complications included that the cable of the head-mounted display interrupted the training (n=2, 7%) and fatigue that caused cessation of the VR training session (n=2, 7%). No serious adverse events were reported.
Conclusions
These preliminary results demonstrated that the use of the XRHealth software and Oculus Rift Station platform is feasible, safe, and engaging for patients, and has the potential to improve the functionality of the upper limbs in patients with MS. This study provides support for future studies of implementing a series of training sessions with virtual reality in a home-based environment.
Abstract Molecular mechanisms that influence susceptibility to multiple sclerosis are poorly understood. We analyzed peripheral blood gene expression profiles in nine healthy subjects up to nine ...years before the onset of multiple sclerosis in comparison with 11 age-, gender-, and origin-matched healthy subjects who remained multiple sclerosis-free, and 31 subjects during the first clinical episode of multiple sclerosis. Within the 1051 highly variable genes that differentiated between multiple sclerosis-to-be and multiple sclerosis-free subjects, we identified activation of TCR signaling that triggered the Cbl and MAPK cascade in concert with downstream synergic over-expression of NFAT and MEF2B, but failed to augment the expression of the nuclear receptor gene family members NR4A1, NR2F1, VDR and MEF2B, that further resulted in impaired apoptotic machinery. Comparison between multiple sclerosis-to-be and first clinical onset of multiple sclerosis operating module networks demonstrated the evolution of altered regulation of nuclear receptor-dependent apoptosis. Our findings demonstrating a silent multiple sclerosis trait that is associated with suppressed expression of the nuclear receptor network and inhibited apoptosis of activated T-cells support the role of these transcription signals in the evolution of the autoimmune processes that operate in the pre-disease stage of multiple sclerosis.
Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may ...affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.
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Gut microbiota and metabolites profiles of individuals with MS differ from healthy controlsIndividuals with MS have reduced serum levels of indolepropionateIndividuals with MS have reduced serum levels of indolelactate and its producing bacteriaIndividuals with MS have lower levels of species and genes involved in butyrate production
Levi et al. perform a coupled analysis of gut microbiota, untargeted metabolomics, gene expression, nutritional records, and clinical data of individuals with MS. The results suggest that increasing the levels of butyrate-producing species and the levels of the tryptophan metabolites indolepropionate and indolelactate in individuals with MS may have potential benefits.
Rehabilitation via virtual reality (VR) training tools allows repetitive, intensive, and task-specific practice in a controlled and safe environment. Our goal was to develop and validate a novel ...immersive VR system based on the practice of real-life activities in a kitchen environment in people with multiple sclerosis (pwMS) with upper-limb dysfunction. The novel immersive VR kitchen application includes several tasks, i.e., tidying up the kitchen, preparing a hamburger and soup meal, and dish washing. Following the development phase, the system was tested for an 8-week intervention period on a small sample of pwMS suffering from upper-limb dysfunction. The Suitability Evaluation Questionnaire for VR systems served as the primary outcome. The scores for enjoyment, sense of comfort with the system, feelings of success and control, realism, easy-to-understand instructions, assists in rehabilitation therapy, were between 4.0 and 4.6, indicating a high satisfaction. The scores for eye discomfort, dizziness, nausea, and disorientation during practice were between 2.8 and 1.3, indicating a low-to-moderate interference of the system. The virtual kitchen training system is feasible and safe for upper-limb training in pwMS and paves the way for future RCTs to examine the benefits of the system compared with standard care, thus improving the functionality of the upper limbs in pwMS.
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