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Frontiers in Public Health 2024A growing body of studies have examined the effect of exercise in people with multiple sclerosis (MS), while findings of available studies were conflicting. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing body of studies have examined the effect of exercise in people with multiple sclerosis (MS), while findings of available studies were conflicting. This meta-analysis aimed to explore the effects of exercise on balance, walking ability, walking endurance, fatigue, and quality of life in people with MS.
METHODS
We searched PubMed, Web of Science, Scopus, and Cochrane databases, through March 1, 2024. Inclusion criteria were: (1) RCTs; (2) included an intervention and control group; (3) had people with MS as study subjects; (4) had balance, walking ability, walking endurance, fatigue, or quality of life as the outcome measures. Exclusion criteria were: (1) non-English publications; (2) animal model publications; (3) review articles; and (4) conference articles. A meta-analysis was conducted to calculate weighted mean difference (WMD) and 95% confidence interval (CI). Cochrane risk assessment tool and Physiotherapy Evidence Database (PEDro) scale were used to evaluate the methodological quality of the included studies.
RESULTS
Forty studies with a total of 56 exercise groups ( = 1,300) and 40 control groups ( = 827) were eligible for meta-analysis. Exercise significantly improved BBS (WMD, 3.77; 95% CI, 3.01 to 4.53, < 0.00001), TUG (WMD, -1.33; 95% CI, -1.57 to -1.08, < 0.00001), MSWS-12 (WMD, -2.57; 95% CI, -3.99 to -1.15, = 0.0004), 6MWT (WMD, 25.56; 95% CI, 16.34 to 34.79, < 0.00001), fatigue (WMD, -4.34; 95% CI, -5.83 to -2.84, < 0.00001), and MSQOL-54 in people with MS (WMD, 11.80; 95% CI, 5.70 to 17.90, = 0.0002) in people with MS. Subgroup analyses showed that aerobic exercise, resistance exercise, and multicomponent training were all effective in improving fatigue in people with MS, with resistance exercise being the most effective intervention type. In addition, a younger age was associated with a larger improvement in fatigue. Furthermore, aerobic exercise and multicomponent training were all effective in improving quality of life in people with MS, with aerobic exercise being the most effective intervention type.
CONCLUSION
Exercise had beneficial effects in improving balance, walking ability, walking endurance, fatigue, and quality of life in people with MS. Resistance exercise and aerobic exercise are the most effective interventions for improving fatigue and quality of life in people with MS, respectively. The effect of exercise on improving fatigue was associated with the age of the participants, with the younger age of the participants, the greater the improvement in fatigue.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371056, identifier: CRD42022371056.
Topics: Humans; Multiple Sclerosis; Quality of Life; Fatigue; Exercise Therapy; Walking; Exercise; Postural Balance
PubMed: 38660348
DOI: 10.3389/fpubh.2024.1387658 -
BMC Neurology Apr 2024Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early...
BACKGROUND
Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized.
METHODS
We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes.
RESULTS
From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization.
CONCLUSION
Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.
Topics: Young Adult; Humans; Adult; Hereditary Autoinflammatory Diseases; Neurologists; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Familial Mediterranean Fever; Cryopyrin-Associated Periodic Syndromes; Fever; Phenotype; Meningitis
PubMed: 38632524
DOI: 10.1186/s12883-024-03621-3 -
PloS One 2024Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls.
METHODS
In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls.
RESULTS
Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls.
CONCLUSION
Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.
Topics: Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Multiple Sclerosis; Insulin-Like Peptides; Insulin-Like Growth Factor Binding Proteins
PubMed: 38630771
DOI: 10.1371/journal.pone.0297091 -
PloS One 2024Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and...
INTRODUCTION
Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and cognitive decline. Currently, there are no specific imaging parameters available for the prediction of longitudinal disability in MS patients. Magnetic resonance imaging (MRI) has linked imaging anomalies to clinical and cognitive deficits in MS. In this study, we aimed to evaluate the effectiveness of MRI in predicting disability, clinical progression, and cognitive decline in MS.
METHODS
In this study, according to PRISMA guidelines, we comprehensively searched the Web of Science, PubMed, and Embase databases to identify pertinent articles that employed conventional MRI in the context of Relapsing-Remitting and progressive forms of MS. Following a rigorous screening process, studies that met the predefined inclusion criteria were selected for data extraction and evaluated for potential sources of bias.
RESULTS
A total of 3028 records were retrieved from database searching. After a rigorous screening, 53 records met the criteria and were included in this study. Lesions and alterations in CNS structures like white matter, gray matter, corpus callosum, thalamus, and spinal cord, may be used to anticipate disability progression. Several prognostic factors associated with the progression of MS, including presence of cortical lesions, changes in gray matter volume, whole brain atrophy, the corpus callosum index, alterations in thalamic volume, and lesions or alterations in cross-sectional area of the spinal cord. For cognitive impairment in MS patients, reliable predictors include cortical gray matter volume, brain atrophy, lesion characteristics (T2-lesion load, temporal, frontal, and cerebellar lesions), white matter lesion volume, thalamic volume, and corpus callosum density.
CONCLUSION
This study indicates that MRI can be used to predict the cognitive decline, disability progression, and disease progression in MS patients over time.
Topics: Humans; Multiple Sclerosis; Brain; Gray Matter; White Matter; Magnetic Resonance Imaging; Atrophy; Multiple Sclerosis, Relapsing-Remitting
PubMed: 38626023
DOI: 10.1371/journal.pone.0300415 -
Journal of Neurology Jun 2024Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of... (Review)
Review
BACKGROUND
Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS).
METHODS
Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as "quality of life" were searched in PubMed and ClinicalTrials.gov.
RESULTS
We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1-3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen's d 1.02; IQR 0.3-1.7; median Hedges' g 1.01; IQR 0.3-1.69) and ranged between d 0.14 and 2.91.
CONCLUSIONS
Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS.
Topics: Humans; Quality of Life; Multiple Sclerosis; Randomized Controlled Trials as Topic; Outcome Assessment, Health Care; Immunologic Factors
PubMed: 38625399
DOI: 10.1007/s00415-024-12366-5 -
Complementary Therapies in Medicine Jun 2024Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients.
METHODS
Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION".
RESULTS
three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation.
CONCLUSIONS
Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.
Topics: Humans; Biomarkers; Exercise; Exercise Therapy; Inflammation; Multiple Sclerosis
PubMed: 38608788
DOI: 10.1016/j.ctim.2024.103040 -
Journal of Clinical Medicine Feb 2024Currently, it is essential to adopt physical therapy strategies, such as resistance training, to enhance muscle strength and gait in middle-aged individuals (ages... (Review)
Review
Currently, it is essential to adopt physical therapy strategies, such as resistance training, to enhance muscle strength and gait in middle-aged individuals (ages 45-65) suffering from Multiple Sclerosis. This is crucial in combating the typical symptoms of neurodegenerative diseases associated with functional loss. The objective of this study is to determine the effects of resistance training interventions on walking and muscle strength in middle-aged people with Multiple Sclerosis. A systematic review with meta-analysis was conducted by searching specific keywords in the PubMed, Scopus, Cochrane, and Web of Science databases. For inclusion, studies had to incorporate resistance training as a primary or significant component of the overall intervention for middle-aged patients with MS. Out of the 3675 articles identified, 12 randomized clinical trials met the criteria for inclusion in the review, with resistance training being a consistent feature in all of them. Muscle strength and gait were evaluated as the main variables, with fatigue and the quality of life as secondary variables. This review reveals that resistance training significantly improves muscle strength. Resistance training achieves modest and non-significant improvements in gait. Notably, studies combining resistance training with motor control exercises achieve results of greater clinical significance in terms of gait. However, resistance training yields variable positive effects on perceived fatigue and the quality of life. Resistance training is useful for improving muscle strength; however, walking needs to be combined with motor control training.
PubMed: 38592200
DOI: 10.3390/jcm13051378 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
PloS One 2024Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression...
Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS.
Topics: Humans; Brain; Depression; Fatigue; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Quality of Life; Adult
PubMed: 38551913
DOI: 10.1371/journal.pone.0299634 -
Frontiers in Immunology 2024The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple... (Review)
Review
The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.
Topics: Humans; Autoimmune Diseases; Models, Theoretical; Multiple Sclerosis; Immunity; T-Lymphocytes
PubMed: 38550585
DOI: 10.3389/fimmu.2024.1371620