Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Self-reported health promotion and disability progression in multiple sclerosis

<p>Background: Health behavior may be associated with disability progression in multiple sclerosis (MS).</p><p>Objectives: To investigate health-promoting behavior as measured by the Health-Promoting Lifestyle Profile II, which includes the subscales of health responsibility, physical activity, nutrition, spiritual growth, interpersonal relationships and stress management.</p><p>Methods: We conducted a cross-sectional survey among individuals with MS, registered by the Flemish MS society, Belgium. Scores for the total scale and subscales were categorized into quintiles. A time-to-event analysis and Cox proportional hazard regression were performed with time to Expanded Disability Status Score (EDSS) of 6 (requires a cane) as an outcome measure. Hazard ratios for the time from onset and the time from birth were adjusted for gender, age at onset and immunomodulatory treatment. The first category was the reference group (first quintile).</p><p>Results: Data on 1372 respondents with definite MS were collected. Subjects with relapsing onset MS and higher scores for overall health-promoting behavior, and the subscales of physical activity, nutrition and spiritual growth, had a reduced risk of reaching EDSS 6 compared to the reference group. No associations were found for the subscales of health responsibility, stress management and interpersonal relations. In progressive onset MS, no significant associations were obtained.</p><p>Conclusion: Our study shows an association of self-reported health promoting behavior with disability progression in subjects with relapsing onset MS. (C) 2012 Elsevier B.V. All rights reserved.</p>

Brain dysconnectivity relates to disability and cognitive impairment in multiple sclerosis

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The effect of task modality and stimulus frequency in paced serial addition tests on functional brain activity.

The paced serial addition test (PSAT) is regularly used to assess cognitive deficits in various neuropsychiatric conditions. Being a complex test, it reflects the status of multiple cognitive domains such as working memory, information processing speed and executive functioning. Two versions of the PSAT exist. One uses auditory stimuli through spoken numbers and is known as the PASAT, while the other one presents patients with visual stimuli and is called PVSAT. The PASAT is considered more frustrating by patients, and hence the visual version is usually preferred. Research has suggested that an interference might exist between patients' verbal answers and the auditory presentation of stimuli. We therefore removed the verbal response in this study, and aimed to investigate differences in functional brain activity through functional magnetic resonance imaging.Fifteen healthy controls performed the two test versions inside an MRI scanner-switching between stimulus modality (auditory vs. visual) as well as inter-stimulus frequency (3s vs. 2s). We extracted 11 independent components from the data: attentional, visual, auditory, sensorimotor and default mode networks. We then performed statistical analyses of mean network activity within each component, as well as inter-network connectivity of each component pair during the different task types.Unsurprisingly, we noted an effect of modality on activity in the visual and auditory components. However, we also describe bilateral frontoparietal, anterior cingulate and insular attentional network activity. An effect of frequency was noted only in the sensorimotor network. Effects were found on edges linking visual and auditory regions. Task modality influenced an attentional-sensorimotor connection, while stimulus frequency had an influence on sensorimotor-default mode connections.Scanner noise during functional MRI may interfere with brain activation-especially during tasks involving auditory pathways. The question whether to use PVSAT or PASAT for an fMRI study is, therefore, an important one. Specific effects of both modalities should be known to study designers. We conclude that both tests should not be considered interchangeable, as significant changes were brought to light during test performance in different modalities

Impact of a 5-day expedition to machu picchu on persons with multiple sclerosis

Persons with multiple sclerosis (MS) are less physically active than nondiseased persons and often report low self-efficacy levels. In the context of an awareness project to promote physical activity and participation in MS, we addressed the impact of training for and participation in a unique expedition. Medical events, relapses, and self-reported neurological worsening were followed from 6 months before and up to 4 months afterwards. Validated patient-reported outcome measures were used to assess fatigue, self-efficacy in exercising, walking abilities, and illness perception. Nine participants completed the training, expedition, and observational study. Minor events, relapses, and/or neurological worsening were reported in six participants. The three participants with mild disability and no cardiovascular risk factors or comorbidities were free of medical and neurological events. We found a significant reduction of motor fatigue at last when compared with the first assessment. The reduction tended to be more evident in participants with mild disability (Expanded Disability Status Scale (EDSS) <4 at baseline). Cognitive fatigue, self-efficacy, and self-reported walking abilities did not change significantly. Illness perceptions tended to be reduced over time in the domains of consequences, identity, and concerns. Overall, no major adverse events occurred.status: publishe

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

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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Spatiotemporal and spectral dynamics of multi-item working memory as revealed by the n-back task using MEG.

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.info:eu-repo/semantics/publishe

Increased brain atrophy and lesion load is associated with stronger lower alpha MEG power in multiple sclerosis patients

Data de publicació electrònica: 17-03-2021In 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.JVS is funded by an FWO post-doc grant (12I1817N, www.fwo.be). LC is funded by an FWO aspirant grant (11B7218N) and GN is supported by an FWO “Fundamenteel klinisch mandaat” (1805620 N). Martin Sjøgård was supported by the Wiener-Anspach Foundation (Brussels, Belgium and Oxford, UK) and is supported by the “Marc Errens” Research Convention of the Fonds Erasme (Fonds Erasme, Brussels, Belgium). Xavier De Tiège is Postdoctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). Data collection was enabled by a grant provided by the Belgian Charcot foundation awarded on Jan 16, 2015, by an FWO “Krediet aan Navorser” grant (1501218 N, www.fwo.be) granted to JVS, by an unrestricted researcher initiated grant provided by Genzyme-Sanofi to GN, and by the “Marc Errens” Research Convention of the Fonds Erasme (Fonds Erasme, Brussels, Belgium). The MEG project at the CUB – Hôpital Erasme is financially supported by the Fonds Erasme pour la Recherche Médicale (Research Convention “Les Voies du Savoir”, Brussels, Belgium). DV is supported by a Novonordisk Hallas-Møller Emerging Investigator Award (0054895), and a Horizon 2020 ERC Starting Grant (850404). The publication was supported by the Belgian Universitary Foundation (Universitaire Stichting)