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Introducción: Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados: Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión: El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.(AU)
Introduction: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. Material and methods: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. Results: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. Conclusion: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.(AU)
Subject(s)
Humans , Male , Female , Multiple Sclerosis/epidemiology , Clinical Record , Medical Records , Latin America/epidemiology , Neurology , Nervous System DiseasesABSTRACT
Introducción: Más de un 50% de los pacientes diagnosticados con esclerosis múltiple (EM) comunican problemas con la función manipulativa e impedimentos en su vida diaria a causa de esta alteración. Por ello, el objetivo del presente estudio es determinar la afectación que la fuerza de pinza, la fuerza de presa y la destreza manipulativa ejercen sobre la calidad de vida y la autonomía personal de las personas diagnosticadas de EM, y estudiar si existe diferencia de estos aspectos entre los distintos tipos de esta enfermedad. Sujetos y métodos: Se contó con una muestra total de 126 participantes, de los cuales 57 fueron controles, y 69, casos. A todos ellos se les evaluó con el Multiple Sclerosis Quality of Life-54, el Nine-Hole Peg Test, la dinamometría de pinza y de presa para la medición de la fuerza, y el índice de Barthel para la evaluación de las actividades básicas de la vida diaria. Resultados: Las personas con EM presentaron peores fuerza de pinza, fuerza de presa, destreza manipulativa, desempeño en actividades básicas de la vida diaria y calidad de vida (p < 0,001). La fuerza de presa es un factor condicionante en el desempeño de actividades básicas y calidad de vida en personas con EM. En cuanto al tipo de EM, el tipo remitente-recurrente presentó mejores valores (p < 0,001).Conclusiones: Los hallazgos de este estudio apuntan a que los pacientes diagnosticados con EM presentan una disminución en la fuerza de pinza, la fuerza de presa, la destreza manipulativa, la calidad de vida y la autonomía en las actividades de la vida diaria en comparación con la población sana.(AU)
Introduction: More than 50% of patients diagnosed with multiple sclerosis report problems with manipulative function and impairments in their daily lives due to this disorder. Therefore, the aim of the present study is to determine how pinch strength, prey strength and manipulative dexterity affect the quality of life and personal autonomy of people diagnosed with multiple sclerosis and to study whether there is a difference in these aspects between different types of multiple sclerosis.Subjects and methods: There was a total sample of 126 participants, of which 57 were controls and 69 cases. All of them were assessed with a Multiple Sclerosis Quality of Life-54 test, Nine-Hole Peg Test and Barthel Index.Results: People with multiple sclerosis have worse pinch strength, prey strenght, manipulative dexterity, performance in basic activities of daily living and quality of life (p < 0.001). Prey strength is a conditioning factor for performance and quality of life in people with multiple sclerosis. As for the type of multiple sclerosis, relapsing-remitting multiple sclerosis presented better values (p < 0.001).Conclusions: The findings of this study point to the fact that patients diagnosed with multiple sclerosis have a decrease in prey strength, pinch strength, manipulative dexterity, quality of life and autonomy in activities of daily living compared to the healthy population.(AU)
Subject(s)
Humans , Female , Quality of Life , Multiple Sclerosis , Health Status , Activities of Daily Living , Neurology , Nervous System DiseasesABSTRACT
OBJECTIVE: This study investigated the prevalence and correlates of fibromyalgia and insomnia in a sample of Women with Multiple Sclerosis (WMS). METHODS: The study was cross-sectional in design and recruited a sample of 163 women with Relapsing-Remitting Multiple Sclerosis (RRMS). Fibromyalgia was assessed using the Patient Self-Report Survey (PSRS), following criteria outlined by the American College of Rheumatology. Insomnia was measured using the Arabic version of the Insomnia Severity Index (ISI-A). RESULTS: The prevalence of fibromyalgia and insomnia was 28.2% (n = 46) and 46.3% (n = 76), respectively. Multivariate analyses were used to determine significant independent correlates. Fibromyalgia was associated with age above 40 years (OR = 2.29, 95% CI = 1.01-5.18, P = .04), high school education (OR = 3.69, 95% CI = 1.62-8.37, P = .002), and non-use of analgesics (OR = .02, 95% CI = .004-.21, P = .001). Insomnia symptoms were significantly associated only with age above 40 years (OR = 2.16, 95% CI = 1.16-4.04, P = .01). CONCLUSION: These findings highlight the need for increased attention by primary care physicians towards diagnosing and treating fibromyalgia and insomnia among women with RRMS in Jordan, particularly among older women.
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BACKGROUND: The long-term effect of high efficacy disease modifying therapy (DMT) on neurodegeneration in people with multiple sclerosis (pwMS) is largely unknown. The aim of this study was to evaluate the long-term effect of natalizumab (NTZ) or fingolimod (FTY) therapy on the evolution of brain atrophy compared to moderate efficacy DMT in a real-world clinical setting. METHODS: A total of 438 pwMS with 2,439 MRI exams during treatment were analyzed: 252 pwMS treated with moderate efficacy DMT, 130 with NTZ and 56 with FTY. Evolution of brain atrophy was analyzed over an average follow-up of 6.6 years after treatment initiation. Brain segmentation was performed on clinical 3D-FLAIRs using SynthSeg and regional brain volume changes over time were compared between the treatment groups. RESULTS: Total brain, white matter and deep gray matter atrophy rates did not differ between moderate efficacy DMTs, NTZ and FTY. Annualized ventricle growth rates were lower in pwMS treated with NTZ (1.1 %/year) compared with moderate efficacy DMT (2.4 %/year, p < 0.001) and similar to FTY (2.0 %/year, p = 0.051). Cortical atrophy rates were lower in NTZ (-0.08 %/year) compared with moderate efficacy DMT (-0.16 %/year, p = 0.048). CONCLUSION: In a real-world clinical setting, pwMS treated with NTZ had slower ventricular expansion and cortical atrophy compared to those treated with moderate efficacy DMT.
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Multiple sclerosis (MS) is a chronic demyelinating autoimmune neurodegenerative disorder for which no specific blood biomarker is available. MicroRNAs (miRNAs) have been investigated for their diagnostic potential in MS. However, MS-associated miRNAs are rarely replicated in different MS populations, thus impeding their use in clinical testing. Here, we evaluated the fold expression of seven reported MS miRNAs associated with MS incidence and clinical characteristics in 76 MS patients and 75 healthy control plasma samples. We found miR-23a-3p to be upregulated in relapsing-remitting MS (RRMS), while miR-326 was downregulated. MiR-150-5p and -320a-3p were significantly downregulated in secondary progressive MS (SPMS) patients compared to RRMS. High disability was associated with low miR-320a-3p, whereas low BDNF levels were associated with upregulation of miR-150-5p and downregulation of miR-326 expression in the total cohort. MiR-23a-3p and miR-326 showed significant diagnostic sensitivity, specificity, and accuracy for RRMS diagnosis. In addition, miR-150-5p and miR-320a-3p had comparable significant diagnostic test performance metrics distinguishing SPMS from RRMS. Therefore, there is potential for including miR-23a-3p and miR-326 in an RRMS diagnostic miRNA panel. Moreover, we have shown that miR-150-5p and miR-320a-3p could be novel RRMS conversion to SPMS biomarkers. The use of these miRNAs in MS diagnosis and prognosis warrants further investigation.
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BACKGROUND: Neurodegenerative changes are observed in relapsing-remitting multiple sclerosis (RRMS) and are prominent in secondary progressive MS (SPMS). However, whether neurodegenerative changes accelerate and are altered after the transition into SPMS or in the presence of relapses remains uncertain. METHODS: In this study, 73 patients with MS (seven with relapsing RRMS, 56 with relapse-free RRMS, and 10 with relapse-free SPMS) were evaluated for brain segmental volume changes over a 2-year follow-up period. Volume change was calculated using a within-subject unbiased longitudinal image analysis model. RESULTS: The rates of brain volume change in the 11 brain regions evaluated were relatively similar among different brain regions. Moreover, they were similar among the relapsing RRMS, relapse-free RRMS, and SPMS groups, even after adjusting for age. CONCLUSIONS: The relatively constant brain segmental atrophy rate throughout the disease course, regardless of relapse episodes, suggests that RRMS and SPMS are continuous, uniform, and silent progressing brain atrophy diseases on a spectrum.
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BACKGROUND: Deep learning (DL) is an artificial intelligence technology that has aroused much excitement for predictive medicine due to its ability to process raw data modalities such as images, text, and time series of signals. OBJECTIVES: Here, we intend to give the clinical reader elements to understand this technology, taking neuroinflammatory diseases as an illustrative use case of clinical translation efforts. We reviewed the scope of this rapidly evolving field to get quantitative insights about which clinical applications concentrate the efforts and which data modalities are most commonly used. METHODS: We queried the PubMed database for articles reporting DL algorithms for clinical applications in neuroinflammatory diseases and the radiology.healthairegister.com website for commercial algorithms. RESULTS: The review included 148 articles published between 2018 and 2024 and five commercial algorithms. The clinical applications could be grouped as computer-aided diagnosis, individual prognosis, functional assessment, the segmentation of radiological structures, and the optimization of data acquisition. Our review highlighted important discrepancies in efforts. The segmentation of radiological structures and computer-aided diagnosis currently concentrate most efforts with an overrepresentation of imaging. Various model architectures have addressed different applications, relatively low volume of data, and diverse data modalities. We report the high-level technical characteristics of the algorithms and synthesize narratively the clinical applications. Predictive performances and some common a priori on this topic are finally discussed. CONCLUSION: The currently reported efforts position DL as an information processing technology, enhancing existing modalities of paraclinical investigations and bringing perspectives to make innovative ones actionable for healthcare.
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Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.
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Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A 'disease in a dish' can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, '-omics' analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells.
Subject(s)
Autoimmune Diseases , Induced Pluripotent Stem Cells , Humans , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Animals , Drug Discovery , Cell- and Tissue-Based Therapy/methodsABSTRACT
Several evidences, including increased serum titers of Epstein-Barr virus (EBV)-specific antibodies and the presence of EBV DNA in brain of patients suggest a possible role of this virus in the pathogenesis of Multiple Sclerosis (MS), a chronic neurodegenerative disease with an unknown etiopathology. Aim of the present study is to verify if the expression of LMP2A and EBNA-1, two EBV genes, is altered in MS patients. EBV viral load, LMP2A and EBNA-1 gene expression and EBNA-1 antibodies titers were evaluated in blood of EBV-seropositive MS patients (n = 57; 31 relapsing remitting -RRMS- and 26 progressive -PMS-patients) and age- and sex-matched healthy controls (HC, n = 49). Results showed that EBNA-1 and VCA antibodies titers are significantly augmented in MS patients compared to HC (p < 0.05 for both antibodies); detection of EBV DNA was more frequent as well in MS patients compared to HC, although without reaching statistical significance. Regarding viral gene expression, LMP2A was significantly more frequently detected and more expressed in MS patients compared to HC (p < 0.005) whereas no differences were observed for EBNA-1. Considering patients alone, EBNA-1 was significantly more frequent in PMS compared to RRMS (p < 0.05), whereas no differences were observed for LMP2A. Increased expression of the LMP2A latency-associated gene in MS patients supports the hypothesis that EBV plays a role in disease etiopathology.
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Background: Immune checkpoint inhibitors (ICIs) represent a novel class of agents approved for the treatment of several cancers and progressive multifocal leukoencephalopathy (PML). However, due to the risk of autoimmune side effects, their use in people with autoimmune diseases such as multiple sclerosis (MS) has been limited. Objective: To characterize outcomes in a cohort of adults with MS who received ICIs. Methods: A single-center retrospective review of medical record data was performed for people with MS treated with ICIs. Results: Seven people with MS were identified, with a mean (SD) age at ICI use of 55.4 (13.7) years and a mean MS duration of 18.2 (12.2) years. Six were treated for cancer; 1 was treated for PML. After mean (SD) follow-up of 1.76 (2.15) years after ICI, outcomes are: no evidence of disease (2), residual metastatic disease (1), death due to cancer (1), death due to PML (1), and lost to follow-up (2). Notably, 0 out of 7 patients experienced an MS relapse; two out of six had new asymptomatic demyelinating magnetic resonance imaging lesions. In the three patients with expanded disability status scale (EDSS) scores at baseline and follow-up, EDSS remained stable (mean delta 0.13). Conclusion: In this cohort, no people with MS experienced clinical relapses and one-third experienced asymptomatic radiological activity following ICI treatment.
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Background: Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established. Methods: From the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done. Results: We discovered that a higher relative abundance of the genus Ruminococcus2 (OR: 1.213, 95% CI: 1.006-1.462, p = 0.043, PFDR = 0.048) and the genus Roseburia (OR: 1.255, 95% CI: 1.012-1.556, p = 0.038, PFDR = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class Mollicutes (OR: 3.016, 95% CI: 1.228-7.411, p = 0.016, PFDR = 0.021), the genus Eubacterium (hallii group) (OR: 2.787, 95% CI: 1.140-6.816, p = 0.025, PFDR = 0.025), and the phylum Tenericutes (OR: 3.016, 95% CI: 1.228-7.411, p = 0.016, PFDR = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus Ruminococcaceae UCG005 (OR: 2.450, 95% CI: 1.072-5.598, p = 0.034, PFDR = 0.036), the genus Holdemania (OR: 2.437, 95% CI: 1.215-4.888, p = 0.012, PFDR = 0.024), genus Lachnoclostridium (OR: 3.681, 95% CI: 1.288-10.521, p = 0.015, PFDR = 0.025) and the genus Eubacterium (ruminantium group) (OR: 2.157, 95% CI: 1.211-3.843, p = 0.003, PFDR = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality. Conclusion: Our findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.
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BACKGROUND: There is insufficient data on severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) infection in Chinese patients with multiple sclerosis (pwMS). This study aims to explore the manifestation of pwMS during the Coronavirus disease 2019 (COVID-19) pandemic and the effect of SARS-CoV-2 infection on the prognosis of MS in northern China. METHODS: In this cross-sectional study, an online self-administered questionnaire and telephone interviews were conducted among pwMS of northern China. Clinical correlation of SARS-CoV-2 infection since the onset of the COVID-19 pandemic in northern China was analyzed. RESULTS: 164 patients with an average age of 38.9 ± 12.2 years were included, of which 57.3% had a disease course ≤ 5 years. 33.5% of the patients were COVID-19 vaccinated. 87.2% received disease-modifying therapy (DMT), and the average immunotherapy duration was 1.9 ± 1.6 years. 83.5% were SARS-CoV-2 infected, 14.6% reported worsening of their original condition after infection, and 5.1% had a relapse of MS. Shorter disease course was independently related to infection risk (P = 0.046), whereas increasing age was related to aggravated behavioral symptoms (P = 0.008). However, gender, vaccination, and DMT were not associated with susceptibility or poor prognosis. CONCLUSION: A shorter disease course is independently associated with an increased risk of SARS-CoV-2 infection, and age is associated with worsening disability. It seems to be safe and necessary to use DMT during the pandemic, however, the use of B cell-depletion agents should be approached with caution.
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Introduction and objective: Autologous hematopoietic stem cell transplantation (aHSCT) is a promising treatment option for persons with multiple sclerosis (pwMS). Patients undergoing aHSCT face unique challenges in all aspects of life. In this study, we explored the lived experiences of pwMS undergoing aHSCT. Methods: Semi-structured interviews of 12 pwMS treated with aHSCT were conducted using a maximum variation sampling strategy. Interviews were transcribed verbatim and analyzed thematically using inductive and deductive categories. Results: Three major themes were identified: (1) preparing for aHSCT, (2) experiencing the procedure, and (3) post-treatment time. A difficult decision-making process, organizational effort, and funding difficulties characterized the preparation for transplantation. AHSCT was seen as a life-changing event accompanied by both psychological and physical stress, with an associated feeling of regaining control. The transplantation had a lasting positive effect on the lives of the interviewed pwMS. However, the early post-treatment time was characterized by successes and failures alike. Particularly the independently organized medical aftercare was perceived as challenging. Retrospective revaluation has led most pwMS to wish for earlier information provision about the treatment option of aHSCT during their treatment history. Conclusion: AHSCT had a clear impact on patients' physical and psycho-social health, influencing their perception of life and its quality. Assessing and attending to unmet needs of patients before, during, and after transplantation may positively influence their experience of aHSCT.
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OBJECTIVES: Our systematic review and meta-analysis aimed to uncover the relationship between UPFs intake and neurodegenerative disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), cognitive impairment, and dementia. SETTING: A systematic search was conducted using the Scopus, PubMed/MEDLINE, and ISI Web of Science databases without any limitation until June 24, 2023. Relative risk (RR) and 95% confidence interval (CI) were pooled by using a random-effects model, while validated methods examined quality and publication bias via Newcastle-Ottawa Scale, Egger's regression asymmetry, and Begg's rank correlation tests, respectively. RESULTS: Analysis from 28 studies indicated that a higher UPFs intake was significantly related to an enhanced risk of MS (RR = 1.15; 95% CI: 1.00, 1.33; I2 = 37.5%; p = 0.050; n = 14), PD (RR = 1.56; 95% CI: 1.21, 2.02; I2 = 64.1%; p = 0.001; n = 15), and cognitive impairment (RR = 1.17; 95% CI: 1.06, 1.30; I2 = 74.1%; p = 0.003; n = 17), although not AD or dementia. We observed that a 25 g increment in UPFs intake was related to a 4% higher risk of MS (RR = 1.04; 95% CI: 1.01, 1.06; I2 = 0.0%; p = 0.013; n = 7), but not PD. The non-linear dose-response relationship indicated a positive non-linear association between UPF intake and the risk of MS (Pnonlinearity = 0.031, Pdose-response = 0.002). This association was not observed for the risk of PD (Pnonlinearity = 0.431, Pdose-response = 0.231). CONCLUSION: These findings indicate that persistent overconsumption of UPFs may have an adverse impact on neurodegenerative conditions, potentially leading to a decline in quality of life and reduced independence as individuals age.
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BACKGROUND: People with multiple sclerosis (MS) have an increased incidence of atherosclerotic disease, including ischemic heart disease and stroke, compared to people without MS even after accounting for risk factors such as hypertension, dyslipidemia, diabetes and smoking. We compared carotid intima media thickness (CIMT), a surrogate of atherosclerosis, in people with MS and in two groups of people without MS (rheumatoid arthritis [RA]; all other participants). METHODS: We used data from participants in the Canadian Longitudinal Study on Aging (CLSA) who did not have known vascular disease (ischemic heart disease, stroke, transient ischemic attack, peripheral vascular disease) and who underwent carotid ultrasound for assessment of CIMT. We selected participants with MS, RA and controls who did not have MS or RA. Using age and gender-stratified norms for average CIMT in the CLSA, we identified participants in each cohort with a CIMT ≥75th percentile (subclinical atherosclerosis). We also calculated ten-year level of cardiovascular risk using the Framingham Risk Score (FRS). We tested the association between cohort membership (MS, RA, controls) and atherosclerosis using logistic regression, adjusted for FRS, abdominal obesity, excess alcohol intake, education and elevated symptoms of depression. We adjusted all analyses for the stratified sampling design. RESULTS: We included 78 participants with MS, 364 participants with RA and 13,891 controls. Overall, the average (SE) CIMT was 0.699 (0.002), and this did not differ between cohorts. Logistic regression analyses revealed that cohort membership was not associated with atherosclerosis based on the average CIMT in unadjusted or adjusted models. However, a 1-point higher FRS was associated with 1.032 (95 %CI: 1.021, 1.043) increased odds of atherosclerosis. CONCLUSION: Average CIMT does not differ between people with MS, people with RA and people without these diseases. Subclinical atherosclerosis as defined by a CIMT ≥75 % is not observed in people with MS at an increased rate beyond what FRS would predict. Further evaluation is needed to determine what mechanisms underlie the increased rates of cardiovascular disease and stroke in MS.
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BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.
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BACKGROUND: The importance of undertaking physical activity for functioning of patients with multiple sclerosis (MS) has been repeatedly highlighted. However, the research on the role of physical activity in shaping the quality of life of patients with different disease duration is scarce. OBJECTIVE: The aim of this study was to identify the mediating role of physical activity in the relationship between health locus of control (HLoC) and health-related quality of life in MS patients with varying disease duration. METHODS: The study included 339 patients with MS from rehabilitation centers. The Multiple Sclerosis Impact Scale (MSIS-29) was used to measure health-related quality of life, physical activity was assessed by the Godin Leisure Time Exercise Questionnaire (GLTEQ) and the Health Locus of Control Questionnaire was used to measure HLoC. RESULTS: Physical activity has been shown to be a mediator in the relationship between intrinsic HLoC and health-related quality of life particularly in patients with longer disease duration. Intrinsic HLoC was positively associated with engaging in physical activity, which in turn was positively associated with the physical component of quality of life in patients with longer (indirect effect: ß = -0.077, p < 0.05) and moderate (ß = -0.040, p < 0.05) duration of illness. CONCLUSION: The results highlight the importance of psychological resources for undertaking quality-of-life-related physical activity by MS patients with long disease duration. Particularly important here is the internal HLoC, which promotes physical activity that increases the chance of a high quality of life.
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Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94â¯cm H2O⯱ 26.12 standard deviation (SD) to 21.07â¯cm H2O⯱ 17.32 SD (Pâ¯< 0.001, nâ¯= 34). Maximum bladder pressure (MBC) increased by 34% from 260.45â¯ml⯱ 200.26 SD to 348.45â¯ml⯱ 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.
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OBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein-1 (AP-1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP-1 as biomarkers for the discrimination of IIH and MS. METHODS: AP-1, TNF-α, and IL-6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP-1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-α, IL-6, CSF, and serum biochemistry analyses. However, it was determined that the AP-1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP-1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP-1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-α and IL-6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP-1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31).
