RESUMEN
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.
Asunto(s)
Electroencefalografía , Magnetoencefalografía , Memoria a Corto Plazo , Esclerosis Múltiple , Humanos , Memoria a Corto Plazo/fisiología , Femenino , Masculino , Adulto , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/complicaciones , Persona de Mediana Edad , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Inhibición Neural/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
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.
Asunto(s)
Dedos , Esclerosis Múltiple , Humanos , Reproducibilidad de los Resultados , Teléfono Inteligente , Destreza Motora , Extremidad Superior , Esclerosis Múltiple/diagnósticoRESUMEN
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.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Esclerosis Múltiple , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Adulto , Vacunas contra la COVID-19/uso terapéutico , Estudios Retrospectivos , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Resultado del Tratamiento , Vacunación , Inmunosupresores/uso terapéuticoRESUMEN
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.
Asunto(s)
Esclerosis Múltiple , Enfermedades Neurodegenerativas , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/psicología , Cognición/fisiología , Benzodiazepinas/farmacología , Benzodiazepinas/uso terapéutico , BiomarcadoresRESUMEN
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.
Asunto(s)
Trastornos del Conocimiento , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Trastornos del Conocimiento/psicología , Velocidad de Procesamiento , Cognición/fisiología , Magnetoencefalografía/métodos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Encéfalo/patologíaRESUMEN
BACKGROUND: Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce. OBJECTIVE: To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening. METHODS: We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure. RESULTS: In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 ± 0.82 years, while p-NfL (HR = 1.046, p = 0.001), EDSS (HR = 1.24, p = 0.039), and disease duration (HR = 1.048, p = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP (p = 0.031) and 0.63 for p-NfL (p = 0.015). Kaplan-Meier curves showed similar patterns for both proteins. CONCLUSION: p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.
Asunto(s)
Esclerosis Múltiple , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Humanos , Filamentos Intermedios , Proteínas de Neurofilamentos , Estudios ProspectivosRESUMEN
The rapid and global spread of severe acute respiratory syndrome coronavirus 2, a viral pathogen responsible for the development of the "coronavirus disease of 2019" (COVID-19), has developed into an unprecedented health crisis with considerable case fatality rate. Patients with comorbidities are considered to be at higher risk for severe disease with acute respiratory failure, intensive care unit admission, and/or death. Particular vigilance has been warranted regarding the continuation of immunosuppressive treatments since viral clearing may be hampered in such cases. In contrast, it has also been hypothesized that overactive immune responses may trigger a cytokine storm associated with clinical deterioration, which has generated an interest in certain immunosuppressant drugs as potential treatment for COVID-19. We would like to present the first case report of a patient who was formally diagnosed with COVID-19 while being under disease-modifying treatment with rituximab, an anti-CD20 B cell depleting agent, for multiple sclerosis. The clinical picture was mild for which we have tried to provide an immunopathological framework.
Asunto(s)
Infecciones por Coronavirus/inmunología , Huésped Inmunocomprometido , Esclerosis Múltiple Recurrente-Remitente/virología , Neumonía Viral/inmunología , Adulto , Betacoronavirus , COVID-19 , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Pandemias , Rituximab/uso terapéutico , SARS-CoV-2RESUMEN
BACKGROUND: Telemedicine (TM) is currently flourishing in rural and emergency settings, but its implementation in the routine management of chronic neurological disorders has developed with more hesitation. Limited access to specialized care facilities and expanding patient populations, combined with unprecedented mobility restrictions imposed by the coronavirus disease pandemic, are currently stressing the need for remote solutions in this field. Studies in patients with multiple sclerosis (MS) have been heterogeneous in objectives and methodology but generally support the concept that TM interventions produce clinical benefits, cost-effectiveness, and user satisfaction. Nonetheless, data on live interaction between patients and health care providers for MS teleconsultation purposes remain scarce. OBJECTIVE: The aim of this study is to demonstrate the feasibility of planned real time audiovisual teleconsultation over the internet for patients with MS. METHODS: A total of 20 patients with MS presenting at a specialized MS center in Belgium were recruited for this study. One teleconsultation was scheduled for each participant. Patients were provided a unique hyperlink by mail in advance, leading them automatically and directly to the virtual waiting room, where they could accept or decline our incoming call. All teleconsultations were performed by a trained medical student with the intention to keep the conversation similar to what is usually discussed during a classic face-to-face MS consultation; no remote physical exams were performed. The approach was considered feasible if at least 80% of the planned TM visits could be successfully completed at the foreseen moment. Patient satisfaction (technical quality, convenience, and overall quality of care) was evaluated at the end of each teleconsultation by means of 5-point Likert scales containing the categories very unsatisfied, unsatisfied, neutral, satisfied, and highly satisfied. RESULTS: Out of 20 consultations, 17 were successfully completed (85%). Failures were due to patients not responding (n=2) and technical issues (n=1). Out of the 17 consultations, 17 patients declared themselves satisfied or highly satisfied for technical quality, 15 patients for convenience, and 16 patients for overall quality of care. CONCLUSIONS: Planned real time audiovisual teleconsultation over the internet is feasible and highly appreciated in patients with MS. Incorporation of such services in routine clinical MS practice is expected to improve access to specialized care facilities for affected patients.
Asunto(s)
Esclerosis Múltiple/terapia , Consulta Remota/métodos , Telemedicina/métodos , Adulto , Estudios de Factibilidad , Femenino , Humanos , Internet , Persona de Mediana Edad , Esclerosis Múltiple/patología , Proyectos PilotoRESUMEN
Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, and -degenerative disease that affects the brain's neurophysiological functioning through brain atrophy, a reduced conduction velocity and decreased connectivity. Currently, little is known on how MS affects the fast temporal dynamics of activation and deactivation of the different large-scale, ongoing brain networks. In this study, we investigated whether these temporal dynamics are affected in MS patients and whether these changes are induced by the pathology or by the use of benzodiazepines (BZDs), an important symptomatic treatment that aims at reducing insomnia, spasticity and anxiety and reinforces the inhibitory effect of GABA. To this aim, we employed a novel method capable of detecting these fast dynamics in 90 MS patients and 46 healthy controls. We demonstrated a less dynamic frontal default mode network in male MS patients and a reduced activation of the same network in female MS patients, regardless of BZD usage. Additionally, BZDs strongly altered the brain's dynamics by increasing the time spent in the deactivating sensorimotor network and the activating occipital network. Furthermore, BZDs induced a decreased power in the theta band and an increased power in the beta band. The latter was strongly expressed in those states without activation of the sensorimotor network. In summary, we demonstrate gender-dependent changes to the brain dynamics in the frontal DMN and strong effects from BZDs. This study is the first to characterise the effect of multiple sclerosis and BZDs in vivo in a spatially, temporally and spectrally defined way.
Asunto(s)
Encéfalo/patología , Esclerosis Múltiple/patología , Esclerosis Múltiple/terapia , Adulto , Benzodiazepinas/uso terapéutico , Ritmo beta/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Estudios de Cohortes , Femenino , Humanos , Hipnóticos y Sedantes/uso terapéutico , Imagen por Resonancia Magnética , Magnetoencefalografía , Masculino , Cadenas de Markov , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Red Nerviosa/efectos de los fármacos , Red Nerviosa/patología , Caracteres Sexuales , Ritmo Teta/efectos de los fármacosRESUMEN
BACKGROUND: The added value of brain volume measurements in the clinical practice of multiple sclerosis (MS) has been questioned. PURPOSE: To investigate the contribution of volume measures obtained with magnetic resonance scans performed as part of regular care to predict measures of cognitive and physical MS disability in a real-world setting. STUDY TYPE: Retrospective. SUBJECTS: In all, 470 adults with diagnosed MS. FIELD STRENGTH/SEQUENCE: 3D fluid attenuation inversion recovery (FLAIR) and 3D T1 -weighted MR images at 3.0T MR. ASSESSMENT: Lesion and brain volume were measured by an automated method, MSmetrix, developed by icometrix. STATISTICAL TESTS: We used stepwise linear regression models to assess the added value of a single volumetric assessment in predicting Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). Brain volumes categorized into quartiles were used as predictive variables in a time-to-event analysis and Cox proportional hazard regression with time to worsening from baseline as outcome measures. RESULTS: Brain and lesion volume in relapsing onset MS strongly contributed to the best models, with a substantial role for age in the EDSS model and a modest role for education in the SDMT model. Adding MR volumetric information increased the explained variance from 17% to 28% in the best model for EDSS and from 9% to 25% in the best model for SDMT. A significantly reduced hazard (P < 0.05) of SDMT worsening was found in the highest normalized brain volume quartiles (1375-1608 ml), compared with the lowest quartile (1201-1374 ml) in the total study population. DATA CONCLUSION: Our findings indicate that a single brain volumetric assessment contributes to the prediction of MS-related disability, with distinct patterns for EDSS as a measure of physical disability, and SDMT as a measure of cognitive disability. A threshold effect for the lowest brain volumes with regard to SDMT worsening over time was found. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1312-1321.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Anciano , Personas con Discapacidad , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Cognitive impairment affects half of the multiple sclerosis (MS) patient population and is an important contributor to patients' daily activities. Most cognitive impairment studies in MS are, however, cross-sectional or/and focused on the early disease stages. OBJECTIVE: We aim to assess the time course of decline of different cognitive domains. METHODS: We collected neuropsychological data on 514 MS patients to construct Kaplan-Meier survival curves of the tests included in the Neuropsychological Screening Battery for MS (NSBMS) and the Symbol Digit Modalities Test (SDMT). Cox-proportional hazard models were constructed to examine the influence of MS onset type, age at onset, gender, depression and level of education on the time course, expressed as age or disease. RESULTS: Survival curves of tests focusing on information processing speed (IPS) declined significantly faster than tests with less specific demands of IPS. Median age for pathological decline was 56.2 years (95% CI: 54.4-58.2) on the SDMT and 63.9 years (95% CI: 60-66.9) on the CLTR, a memory task. CONCLUSION: In conclusion, IPS is the cognitive domain not only most widely affected by MS but it is also the first cognitive deficit to emerge in MS.
Asunto(s)
Trastornos del Conocimiento/fisiopatología , Progresión de la Enfermedad , Esclerosis Múltiple/fisiopatología , Pruebas Neuropsicológicas/estadística & datos numéricos , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy has shown potential to counteract autoimmunity in multiple sclerosis (MS). METHODS: We compared the phenotype and T-cell stimulatory capacity of in vitro generated monocyte-derived DC from MS patients with those from healthy controls. RESULTS: Except for an increase in the number of C-C chemokine receptor 7-expressing DC from MS patients, no major differences were found between groups in the expression of maturation-associated membrane markers or in the in vitro capacity to stimulate autologous T cells. CONCLUSIONS: Our observations may pave the way for the development of patient-tailored DC-based vaccination strategies to treat MS.
Asunto(s)
Células Dendríticas/inmunología , Inmunoterapia , Activación de Linfocitos/inmunología , Esclerosis Múltiple/prevención & control , Receptores CCR7/biosíntesis , Adulto , Anciano , Diferenciación Celular/genética , Células Dendríticas/citología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/citología , Monocitos/metabolismo , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Receptores CCR7/inmunología , Linfocitos T/inmunología , VacunaciónRESUMEN
Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.
Asunto(s)
Microbioma Gastrointestinal , Esclerosis Múltiple , HumanosRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Trastornos del Conocimiento , Esclerosis Múltiple , Sustancia Blanca , Humanos , Imagen de Difusión Tensora/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Imagen de Difusión por Resonancia Magnética/métodos , Trastornos del Conocimiento/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Anisotropía , CogniciónRESUMEN
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.
Asunto(s)
Esclerosis Múltiple , Telerrehabilitación , Anciano , Cognición , Fatiga , Humanos , Esclerosis Múltiple/psicología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Telerrehabilitación/métodosRESUMEN
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.
Asunto(s)
Tendón Calcáneo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Adolescente , Adulto , Anciano , Encéfalo , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Cognición , Femenino , Humanos , Modelos Lineales , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Modelos Neurológicos , Red Nerviosa/fisiopatología , Reproducibilidad de los Resultados , Relación Señal-Ruido , Adulto JovenRESUMEN
Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon beta) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon beta alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon beta for at least 6 months were randomized to interferon beta + inosine or interferon beta + placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (Asunto(s)
Antiinflamatorios/uso terapéutico
, Inosina/uso terapéutico
, Interferón beta/uso terapéutico
, Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico
, Fármacos Neuroprotectores/uso terapéutico
, Adulto
, Antiinflamatorios/efectos adversos
, Bélgica
, Evaluación de la Discapacidad
, Progresión de la Enfermedad
, Método Doble Ciego
, Quimioterapia Combinada
, Femenino
, Humanos
, Inosina/efectos adversos
, Inosina/metabolismo
, Interferón beta-1a
, Interferon beta-1b
, Interferón beta/efectos adversos
, Estimación de Kaplan-Meier
, Masculino
, Persona de Mediana Edad
, Esclerosis Múltiple Recurrente-Remitente/sangre
, Esclerosis Múltiple Recurrente-Remitente/diagnóstico
, Fármacos Neuroprotectores/efectos adversos
, Fármacos Neuroprotectores/metabolismo
, Índice de Severidad de la Enfermedad
, Factores de Tiempo
, Resultado del Tratamiento
, Ácido Úrico/sangre
RESUMEN
BACKGROUND: Comorbidity and health behaviours may explain heterogeneity regarding cognitive performance in multiple sclerosis. Patient-reported cognitive difficulties have impact but do not consistently correlate with objective cognitive performance. Our study aims to investigate whether health status indicators including comorbidities, body mass index, physical activity, smoking, sleeping behaviour and consumption patterns for fish, alcohol and caffeinated drinks are associated with measures of subjective and objective cognitive performance. METHODS: Survey data on self-reported cognitive performance, assessed with the MS Neuropsychological Screening Questionnaire (MSNQ), were related to the presence of arterial hypertension, diabetes mellitus, cardiovascular and chronic renal diseases, hypercholesterolemia, depression based on 2-question screening tool, health and consumption behaviors. We included the Symbol Digit Modalities Test when available within 6 months as an objective, performance-based metric of cognitive processing speed. We investigated the interrelation between all variables with a Spearman correlation matrix and corrected for multiple testing. Regression models were built and controlled for age, sex and phenotype. RESULTS: We used available data from 751 patients with definite MS, including 290 SDMT scores within a time window of 6 months, to study relations between variables. MSNQ and SDMT scores were not significantly correlated. Correlation patterns for subjective and objective performance differed. Age, disease duration and physical disability correlated with SDMT scores only. Regression analyses could be performed for MSNQ scores in 595/751 (79.2%) and for SDMT scores in 234/751 (31.2%) participants. After restricting variables to avoid collinearity and adjusting for the number of variables, regression models explained 15% of the variance for subjective and 14% of the variance for objective cognitive performance. A higher number of physical comorbidities, reporting depressive symptoms, sleeping 9 h or more and daily use of sleeping medication were associated with lower subjective cognitive performance, whereas increasing age was associated with reduced processing speed. These associations persisted after correction for multiple testing. CONCLUSION: Increasing age is associated with reduced cognitive processing speed whereas comorbidities and sleep behaviors contribute to subjective cognitive performance.