Stimulus-related modulation in the 1/f spectral slope suggests an impaired inhibition during a working memory task in people with multiple sclerosis.

BACKGROUND: An imbalance of excitatory and inhibitory synaptic transmission in multiple sclerosis (MS) may lead to cognitive impairment, such as impaired working memory. The 1/f slope of electroencephalography/magnetoencephalography (EEG/MEG) power spectra is shown to be a non-invasive proxy of excitation/inhibition balance. A flatter slope is associated with higher excitation/lower inhibition. OBJECTIVES: To assess the 1/f slope modulation induced by stimulus and its association with behavioral and cognitive measures. METHODS: We analyzed MEG recordings of 38 healthy controls (HCs) and 79 people with multiple sclerosis (pwMS) while performing an n-back task including target and distractor stimuli. Target trials require an answer, while distractor trials do not. We computed the 1/f spectral slope through the fitting oscillations and one over f (FOOOF) algorithm within the time windows 1 second before and after each stimulus presentation. RESULTS: We observed a flatter 1/f slope after distractor stimuli in pwMS compared to HCs. The 1/f slope was significantly steeper after stimulus for both HCs and pwMS and was significantly correlated with reaction times. This modulation in 1/f slope was significantly correlated with visuospatial memory assessed by the BVMT-R test. CONCLUSION: Our results suggest possible inhibitory mechanism deficits in pwMS during a working memory task.

Clinical effectiveness of coronavirus disease 2019 vaccination in patients with multiple sclerosis stratified by disease-modifying treatment.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) vaccination has been associated with a dampened humoral and/or cellular immune response in patients with multiple sclerosis (MS) who were concurrently on disease-modifying treatment (DMT) with B-cell depleting agents or sphingosine-1-phosphate receptor modulators (S1PRMs). Our main goal was to investigate the impact of these DMT classes on the clinical effectiveness of COVID-19 vaccination. METHODS: Since March 2020, demographics and clinical data of patients with MS who developed COVID-19 have been collected at the Belgian National MS Centre in Melsbroek. Patients were considered to be 'protected by vaccination' if they were (i) fully vaccinated and (ii) tested positive for COVID-19 in the period ranging from 14 days to 6 months after the last administered vaccine. RESULTS: On 19 December 2022, 418 COVID-19 cases were retrospectively identified in 389 individual patients. Hospitalization and mortality rates resulting from the infection were 10.8% and 2.4%, respectively. Being 'unprotected by vaccination' was significantly associated with a worse COVID-19 outcome (i.e., hospitalization and/or death) in the total cohort (N = 418, odds ratio [OR] 3.96), in patients on ongoing DMT other than anti-CD20 agents or S1PRMs (N = 123, OR 31.75) and in patients without DMT (N = 182, OR 5.60), but not in those receiving anti-CD20 agents (N = 91, OR 0.39); the S1PRMs subgroup was considered too small (22 infections) for any meaningful analysis. CONCLUSIONS: Coronavirus disease 2019 vaccination protects against severe infection in patients with MS but it was not possible to confirm this effect in those on DMT with B-cell depleting agents.

A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial.

Introduction: Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS. The objective of this clinical trial is to evaluate whether metformin, as add-on treatment, is superior to placebo in delaying disease progression in patients with non-active PMS. Methods and analysis: MACSiMiSE-BRAIN is a multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled clinical trial, conducted at five sites in Belgium. Enrollment of 120 patients with non-active PMS is planned. Each participant will undergo a screening visit with assessment of baseline magnetic resonance imaging (MRI), clinical tests, questionnaires, and a safety laboratory assessment. Following randomization, participants will be assigned to either the treatment (metformin) or placebo group. Subsequently, they will undergo a 96-week follow-up period. The primary outcome is change in walking speed, as measured by the Timed 25-Foot Walk Test, from baseline to 96 weeks. Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) and hand function (9-Hole Peg test). Annual brain MRI will be performed to assess evolution in brain volumetry and diffusion metrics. As patients may not progress in all domains, a composite outcome, the Overall Disability Response Score will be additionally evaluated as an exploratory outcome. Other exploratory outcomes will consist of paramagnetic rim lesions, the 2-minute walking test and health economic analyses as well as both patient- and caregiver-reported outcomes like the EQ-5D-5L, the Multiple Sclerosis Impact Scale and the Caregiver Strain Index. Ethics and dissemination: Clinical trial authorization from regulatory agencies [Ethical Committee and Federal Agency for Medicines and Health Products (FAMHP)] was obtained after submission to the centralized European Clinical Trial Information System. The results of this clinical trial will be disseminated at scientific conferences, in peer-reviewed publications, to patient associations and the general public. Trial registration: ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00.

The Finger Dexterity Test: Validation study of a smartphone-based manual dexterity assessment.

BACKGROUND: The Nine-Hole Peg Test (9HPT) is the golden standard to measure manual dexterity in people with multiple sclerosis (MS). However, administration requires trained personnel and dedicated time during a clinical visit. OBJECTIVES: The objective of this study is to validate a smartphone-based test for remote manual dexterity assessment, the icompanion Finger Dexterity Test (FDT), to be included into the icompanion application. METHODS: A total of 65 MS and 81 healthy subjects were tested, and 20 healthy subjects were retested 2 weeks later. RESULTS: The FDT significantly correlated with the 9HPT (dominant: ρ = 0.62, p < 0.001; non-dominant: ρ = 0.52, p < 0.001). MS subjects had significantly higher FDT scores than healthy subjects (dominant: p = 0.015; non-dominant: p = 0.013), which was not the case for the 9HPT. A significant correlation with age (dominant: ρ = 0.46, p < 0.001; non-dominant: ρ = 0.40, p = 0.002), Expanded Disability Status Scale (EDSS, dominant: ρ = 0.36, p = 0.005; non-dominant: ρ = 0.31, p = 0.024), and disease duration for the non-dominant hand (ρ = 0.31, p = 0.016) was observed. There was a good test-retest reliability in healthy subjects (dominant: r = 0.69, p = 0.001; non-dominant: r = 0.87, p < 0.001). CONCLUSIONS: The icompanion FDT shows a moderate-to-good concurrent validity and test-retest reliability, differentiates between the MS subjects and healthy controls, and correlates with clinical parameters. This test can be implemented into routine MS care for remote follow-up of manual dexterity.

The spectral slope as a marker of excitation/inhibition ratio and cognitive functioning in multiple sclerosis.

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

Cerebrospinal fluid inflammatory biomarkers for disease progression in Alzheimer's disease and multiple sclerosis: a systematic review.

Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.

Reduced alpha2 power is associated with slowed information processing speed in multiple sclerosis.

OBJECTIVE: Cognitive impairment is common in multiple sclerosis (MS), significantly impacts daily functioning, is time-consuming to assess, and is prone to practice effects. We examined whether the alpha band power measured with magnetoencephalography (MEG) is associated with the different cognitive domains affected by MS. METHODS: Sixty-eight MS patients and 47 healthy controls underwent MEG, T1- and FLAIR-weighted magnetic resonance imaging (MRI), and neuropsychological testing. Alpha power in the occipital cortex was quantified in the alpha1 (8-10 Hz) and alpha2 (10-12 Hz) bands. Next, we performed best subset regression to assess the added value of neurophysiological measures to commonly available MRI measures. RESULTS: Alpha2 power significantly correlated with information processing speed (p < 0.001) and was always retained in all multilinear models, whereas thalamic volume was retained in 80% of all models. Alpha1 power was correlated with visual memory (p < 0.001) but only retained in 38% of all models. CONCLUSIONS: Alpha2 (10-12 Hz) power in rest is associated with IPS, independent of standard MRI parameters. This study stresses that a multimodal assessment, including structural and functional biomarkers, is likely required to characterize cognitive impairment in MS. Resting-state neurophysiology is thus a promising tool to understand and follow up changes in IPS.

Neuronal activity and NIBS in developmental myelination and remyelination - Current state of knowledge.

Oligodendrocytes are responsible for myelinating central nervous system (CNS) axons and rapid electrical transmission through saltatory conduction of action potentials. Myelination and myelin repair rely partially on oligodendrogenesis, which comprises oligodendrocyte precursor cell (OPC) migration, maturation, and differentiation into oligodendrocytes (OL). In multiple sclerosis (MS), demyelination occurs due to an inflammatory cascade with auto-reactive T-cells. When oligodendrogenesis fails, remyelination becomes aberrant and conduction impairments are no longer restored. Although current disease modifying therapies have achieved results in modulating the faulty immune response, disease progression continues because of chronic inflammation, neurodegeneration, and failure of remyelination. Therapies have been tried to promote remyelination. Modulation of neuronal activity seems to be a very promising strategy in preclinical studies. Additionally, studies in people with MS (pwMS) have shown symptom improvement following non-invasive brain stimulation. (NIBS) techniques. The aforementioned mechanisms are yet unknown and probably involve both the activation of neurons and glial cells. Noting neuronal activity contributes to myelin plasticity and that NIBS modulates neuronal activity; we argue that NIBS is a promising research horizon for demyelinating diseases. We review the hypothesized pathways through which NIBS may affect both neuronal activity in the CNS and how the resulting activity can affect oligodendrogenesis and myelination.

Advances in Neurodegenerative Diseases.

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population [...].

Occurrence and Severity of Coronavirus Disease 2019 Are Associated With Clinical Disability Worsening in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Large-scale observational studies have shown that, in patients with multiple sclerosis (MS), the risk of becoming more severely ill from coronavirus disease 2019 (COVID-19) is determined by older age, male sex, cardiovascular comorbidities, African American ethnicity, progressive disease, recent use of corticosteroids, and B cell-depleting disease-modifying treatment. In contrast, the effect of COVID-19 on the disease course of MS has been studied much less extensively. Our main goal was to explore whether COVID-19 is associated with accelerated clinical disability worsening in patients with MS. METHODS: Since March 2020, demographics and infectious outcome (categorized as ambulatory, hospitalized, and/or death) of patients with MS who developed COVID-19 have been collected at the Belgian National MS Center in Melsbroek. On February 28, 2022, this database was locked and complemented with clinical disability measures-Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk Test (T25FWT), 9-Hole Peg Test (9HPT), and Symbol Digit Modalities Test (SDMT)-that were available from a larger local database, obtained during routine medical follow-up. For each parameter, the first 2 assessments before COVID-19 diagnosis (T0 and T1; T1 is the closest to COVID-19 diagnosis), and the first thereafter (T2), were retrieved. RESULTS: We identified 234 unique cases of COVID-19. Thirty-one patients were hospitalized (13.2%), and 5 died (2.1%) as a result of their infection. Among survivors with complete EDSS results (N = 138), mean annualized T1-to-T2 EDSS worsening was more pronounced, compared with the respective change between T0 and T1 (0.3 ± 0.9 vs 0.1 ± 0.9, p = 0.012). No such differences were found for the T25FWT, 9HPT, and SDMT scores. Severe COVID-19 (hospitalization) was associated with clinically relevant T1-to-T2 EDSS worsening (OR 2.65, p = 0.042). Vaccination coverage in the total cohort was 53.8%. Being unprotected by vaccination at the time of infection was associated with a worse COVID-19 outcome (hospitalization and/or death; OR 3.52, p = 0.002) but not with clinically relevant T1-to-T2 EDSS worsening. DISCUSSION: The occurrence and severity of COVID-19 are both associated with clinical disability worsening in patients with MS. Vaccination protects against a more severe course of COVID-19 in this specific population. TRIAL REGISTRATION INFORMATION: The study has been registered at ClinicalTrials.gov (study registration number: NCT05403463).

Radial diffusivity reflects general decline rather than specific cognitive deterioration in multiple sclerosis.

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

Cognitive-motor telerehabilitation in multiple sclerosis (CoMoTeMS): study protocol for a randomised controlled trial.

BACKGROUND: The management of cognitive impairment is an important goal in the treatment of multiple sclerosis (MS). While cognitive rehabilitation has been proven to be effective in improving cognitive performance in MS, research in the elderly indicates a higher effectiveness of combined cognitive-motor rehabilitation. Here, we present the protocol of a randomised controlled clinical trial to assess whether a combined cognitive-motor telerehabilitation programme is more effective in improving working memory than only cognitive or motor training. METHODS/DESIGN: The CoMoTeMS-trial is a two-centre, randomised, controlled and blinded clinical trial. A total of 90 patients with MS will receive 12 weeks of either a combined cognitive-motor telerehabilitation programme or only cognitive or motor training. The primary outcome is a change in the digit span backwards. Secondary outcomes are other cognitive changes (Brief International Cognitive Assessment for Multiple Sclerosis and Backward Corsi), Expanded Disability Status Scale (EDSS), 6-Min Walk Test, 25-Foot Walk Test, 9-Hole Peg Test, anxiety and depression, fatigue, quality of life, cognitive and physical activity level, electroencephalography and magnetic resonance imaging of the brain. DISCUSSION: We hypothesise that the improvement in digit span backwards after 12 weeks of treatment will be significantly higher in the group treated with the combined cognitive-motor telerehabilitation programme, compared to the groups receiving only cognitive and only motor training. TRIAL REGISTRATION: ClinicalTrials.gov NCT05355389. Registered on 2 May 2022.

Brain age as a surrogate marker for cognitive performance in multiple sclerosis.

BACKGROUND AND PURPOSE: Data from neuro-imaging techniques allow us to estimate a brain's age. Brain age is easily interpretable as 'how old the brain looks' and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility by investigating the relationship between brain age and cognitive performance in multiple sclerosis (MS). METHODS: A linear regression model was trained to predict age from brain magnetic resonance imaging volumetric features and sex in a healthy control dataset (HC_train, n = 1673). This model was used to predict brain age in two test sets: HC_test (n = 50) and MS_test (n = 201). Brain-predicted age difference (BPAD) was calculated as BPAD = brain age minus chronological age. Cognitive performance was assessed by the Symbol Digit Modalities Test (SDMT). RESULTS: Brain age was significantly related to SDMT scores in the MS_test dataset (r = -0.46, p < 0.001) and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r = -0.24, p < 0.001) and a significant weight (-0.25, p = 0.002) in a multivariate regression equation with age. CONCLUSIONS: Brain age is a candidate biomarker for cognitive dysfunction in MS and an easy to grasp metric for brain health.

Innovating Care in Multiple Sclerosis: Feasibility of Synchronous Internet-Based Teleconsultation for Longitudinal Clinical Monitoring.

The 'coronavirus disease of 2019' crisis has recently forced an expedited adoption of teleconsultation (TC) in most medical domains. Short-term digital interventions have generally been associated with feasibility, clinical benefits, user satisfaction, and cost-effectiveness in patients with multiple sclerosis (MS) but outcomes after repeated utilization over extended periods need to be further evaluated. In this feasibility study, 60 subjects with MS were 1:1 randomized to receive standard care augmented by four TCs using an audiovisual Internet platform (intervention) versus standard care alone (controls), over a period of 12 months. Effects on functional status, medical costs, and satisfaction were explored as secondary outcomes. Eighty-nine out of 108 scheduled TCs (82.4%) were completed, and 26 patients could complete at least one TC (86.7%), meeting our prespecified feasibility target of 80%. The intervention did not lead to significant differences in functional status (with the potential exception of fatigue) nor medical costs. Most interventional patients declared themselves to be (very) satisfied about the quality of care and technical aspects associated with the TCs. Our results demonstrate that longitudinal clinical monitoring using real-time audiovisual TC over the Internet is feasible and well-received by patients with MS. Such an approach can be a promising new care strategy.

Brain Volume Loss Can Occur at the Rate of Normal Aging in Patients with Multiple Sclerosis Who Are Free from Disease Activity.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disorder of the central nervous system. Accelerated brain volume loss (BVL) has emerged as a promising magnetic resonance imaging marker (MRI) of neurodegeneration, correlating with present and future clinical disability. We have systematically selected MS patients fulfilling 'no evidence of disease activity-3' (NEDA-3) criteria under high-efficacy disease-modifying treatment (DMT) from the database of two Belgian MS centers. BVL between both MRI scans demarcating the NEDA-3 period was assessed and compared with a group of prospectively recruited healthy volunteers who were matched for age and gender. Annualized whole brain volume percentage change was similar between 29 MS patients achieving NEDA-3 and 24 healthy controls (-0.25 ± 0.49 versus -0.24 ± 0.20, p = 0.9992; median follow-up 21 versus 33 months; respectively). In contrast, we found a mean BVL increase of 72%, as compared with the former, in a second control group of MS patients (n = 21) whom had been excluded from the NEDA-3 group due to disease activity (p = 0.1371). Our results suggest that neurodegeneration in MS can slow down to the rate of normal aging once inflammatory disease activity has been extinguished and advocate for an early introduction of high-efficacy DMT to reduce the risk of future clinical disability.

Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience.

BACKGROUND: This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. METHODS: Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. RESULTS: Mean 0-10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks' range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. CONCLUSIONS: More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

Signal quality as Achilles' heel of graph theory in functional magnetic resonance imaging in multiple sclerosis.

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

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

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

CSF and Blood Neurofilament Levels in Athletes Participating in Physical Contact Sports: A Systematic Review.

OBJECTIVE: To evaluate whether participating in physical contact sports is associated with a release of neurofilaments and whether such release is related to future clinical neurologic and/or psychiatric impairment. METHODS: We performed a systematic review of the PubMed, MEDLINE, and Cochrane Library databases using a combination of the search terms neurofilament(s)/intermediate filament and sport(s)/athletes. Original studies, written in English, reporting on neurofilaments in CSF and/or serum/plasma of contact sport athletes were included. This review was conducted following the Preferred Reporting Items for Systematic Review and Analyses guidelines. RESULTS: Eighteen studies in 8 different contact sports (i.e., boxing, American football, ice hockey, soccer, mixed martial arts, lacrosse, rugby, and wrestling) matched our criteria. Elevated light chain neurofilament (NfL) levels were described in 13/18 cohorts. Most compelling evidence was present in boxing and American football, where exposure-related increases were appreciable at the intraindividual level (up to 4.1- and 2.0-fold, respectively) in well-defined groups. Differences in exposure severity (including previous cumulative effects), sampling/measurement time points (with regard to expected peak values), and definitions of the baseline setting are considered as main contributors to the variability in findings. No studies were encountered that have investigated the relationship with the targeted clinical end points; therefore no NfL cutoffs exist that are associated with a poor outcome. CONCLUSION: NfL release can be seen, as a potential marker of neuronal brain damage, in participants of physical contact sports, particularly boxing and American football. The exact significance regarding the risk for future clinical impairment remains to be elucidated.