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Cells May 2022Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is... (Review)
Review
Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.
Topics: Animals; Cognition; Encephalomyelitis, Autoimmune, Experimental; Glatiramer Acetate; Humans; Immunomodulation; Neuroprotection; Randomized Controlled Trials as Topic
PubMed: 35563884
DOI: 10.3390/cells11091578 -
Muscle & Nerve Jun 2016We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barré syndrome (GBS),... (Review)
Review
We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barré syndrome (GBS), psychotic symptoms are reported during early stages in 30% of patients. Typical associations include mechanical ventilation, autonomic dysfunction, inability to communicate, and severe weakness. Anxiety and depression are frequent comorbidities. Anxiety may increase post-hospital admissions and be a predictor of mechanical ventilation. Posttraumatic stress disorder may affect up to 20% of ventilated patients. Sleep disturbances are common in early-stage GBS, affecting up to 50% of patients. In chronic inflammatory demyelinating polyradiculoneuropathy, memory and quality of sleep may be impaired. An independent link between depression and pretreatment upper limb disability and ascites was reported in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin) syndrome, with an association with early death. Hematological treatment of POEMS appears effective on depression. Published literature on psychological/behavioral manifestations in inflammatory neuropathies remains scarce, and further research is needed. Muscle Nerve 54: 1-8, 2016.
Topics: Databases, Bibliographic; Guillain-Barre Syndrome; Humans; Mood Disorders; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Psychotic Disorders; Sleep Wake Disorders
PubMed: 26999767
DOI: 10.1002/mus.25112 -
BMC Neurology Dec 2023Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and...
BACKGROUND
Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination.
METHODS
We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies.
RESULTS
A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based.
CONCLUSION
COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.
Topics: Adult; Humans; Female; Male; COVID-19 Vaccines; COVID-19; Neuromuscular Diseases; Myasthenia Gravis; Guillain-Barre Syndrome; Bell Palsy; Facial Paralysis
PubMed: 38082244
DOI: 10.1186/s12883-023-03486-y -
The Cochrane Database of Systematic... May 2013This is an updated Cochrane review of the previous published version.Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated Cochrane review of the previous published version.Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients.
OBJECTIVES
The main objective was to assess the efficacy and safety of MX compared to a control group in relapsing-remitting (RRMS), progressive relapsing (PRMS) and secondary progressive (SPMS) MS participants.
SEARCH METHODS
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (June 2012) and reference lists of articles. We also undertook handsearching and contacted trialists and pharmaceutical companies.
SELECTION CRITERIA
Randomised, double-blinded, controlled trials (RCTs) comparing the administration of MX versus placebo or MX plus steroids treatment versus placebo plus steroids treatment were included.
DATA COLLECTION AND ANALYSIS
The review authors independently selected articles for inclusion. They independently extracted clinical, safety and magnetic resonance imaging (MRI) data, resolving disagreements by discussion. Risk of bias was evaluated to assess the quality of the studies. Treatment effect was measured using odds ratios (OR) with 95% confidence intervals (CI) for the binary outcomes and mean differences (MD) with 95% CI for the continuous outcomes. If heterogeneity was absent, a fixed-effect model was used.
MAIN RESULTS
Three trials were selected and 221 participants were included in the analyses. MX reduced the progression of disability at two years follow-up (proportion of participants with six months confirmed progression of disability (OR 0.30, 95% CI 0.09 to 0.99 and MD -0.36, 95% CI- 0.70 to -0.02; P = 0.04)). Significant results were found regarding the reduction in annualised relapse rate (MD -0.85, 95% CI -1.47 to -0.23; P = 0.007), the proportion of patients free from relapses at one year (OR 7.13, 95% CI 2.06 to 24.61; P = 0.002) and two years (OR 2.82, 95% CI 1.54 to 5.19; P = 0.0008), and the number of patients with active MRI lesions at six months or one year only (OR 0.24, 95% CI 0.10 to 0.57; P = 0.001). Side effects reported in the trials (amenorrhoea, nausea and vomiting, alopecia and urinary tract infections) were more frequent in treated patients than in controls, while no major adverse events have been reported. These results should be considered with caution because of the heterogeneous characteristics of included trials in term of drug dosage, inclusion criteria and quality of included trials. Moreover, it was not possible to estimate the long-term efficacy and safety of MX.
AUTHORS' CONCLUSIONS
MX shows a significant but partial efficacy in reducing the risk of MS progression and the frequency of relapses in patients affected by worsening RRMS, PRMS and SPMS in the short-term follow-up (two years). No major neoplastic events or symptomatic cardiotoxicity related to MX have been reported; however studies with longer follow-up (not included in this review) have raised concerns about the risk of systolic disfunction (˜12%) and therapy-related acute leukaemias (0.8%), which are increasingly reported in the literature.MX should be limited to treating patients with worsening RRMS and SPMS and with evidence of persistent inflammatory activity after a careful assessment of the individual patients' risk and benefit profiles. Assessment should also consider the present availability of alternative therapies with less severe adverse events.
Topics: Disease Progression; Humans; Immunosuppressive Agents; Mitoxantrone; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 23728638
DOI: 10.1002/14651858.CD002127.pub3 -
Cellular & Molecular Immunology Mar 2015Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study... (Meta-Analysis)
Meta-Analysis Review
Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case-control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Humans; Multiple Sclerosis; Polymorphism, Genetic; Receptors, Calcitriol; Risk Factors
PubMed: 24998351
DOI: 10.1038/cmi.2014.47 -
Journal of Neuroengineering and... Apr 2023This study aims to conduct a meta-analysis to assess the effect of virtual reality-based therapy (VRBT) on balance dimensions and fear of falling in patients with... (Meta-Analysis)
Meta-Analysis Review
Virtual reality-based therapy improves balance and reduces fear of falling in patients with multiple sclerosis. a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
This study aims to conduct a meta-analysis to assess the effect of virtual reality-based therapy (VRBT) on balance dimensions and fear of falling in patients with multiple sclerosis (PwMS). Secondarily, to determine the most recommendable dose of VRBT to improve balance.
METHODS
PubMed Medline, Web of Science, Scopus, CINAHL and PEDro were screened, without publication date restrictions, until September 30th, 2021. Randomized controlled trials (RCTs) comparing the effectiveness of VRBT against other interventions in PwMS were included. Functional and dynamic balance, confidence of balance, postural control in posturography, fear of falling and gait speed were the variables assessed. A meta-analysis was performed by pooling the Cohen's standardized mean difference (SMD) with 95% confidence interval (95% CI) using Comprehensive Meta-Analysis 3.0.
RESULTS
Nineteen RCTs, reporting 858 PwMS, were included. Our findings reported that VRBT is effective in improving functional balance (SMD = 0.8; 95%CI 0.47 to 1.14; p < 0.001); dynamic balance (SMD = - 0.3; 95%CI - 0.48 to - 0.11; p = 0.002); postural control with posturography (SMD = - 0.54; 95%CI - 0.99 to - 0.1; p = 0.017); confidence of balance (SMD = 0.43; 95%CI 0.15 to 0.71; p = 0.003); and in reducing fear of falling (SMD = - 1.04; 95%CI - 2 to - 0.07; p = 0.035); but not on gait speed (SMD = - 0.11; 95%CI: - 0.35 to 0.14; p = 0.4). Besides, the most adequate dose of VRBT to achieve the greatest improvement in functional balance was at least 40 sessions, five sessions per week and 40-45 min per sessions; and for dynamic balance, it would be between 8 and 19 weeks, twice a week and 20-30 min per session.
CONCLUSION
VRBT may have a short-term beneficial role in improving balance and reducing fear of falling in PwMS.
Topics: Humans; Accidental Falls; Randomized Controlled Trials as Topic; Physical Therapy Modalities; Multiple Sclerosis; Virtual Reality
PubMed: 37041557
DOI: 10.1186/s12984-023-01174-z -
Multiple Sclerosis and Related Disorders Dec 2023The effectiveness of electrical stimulation therapy (EST) for pain, depression, fatigue, disability, and quality of life in multiple sclerosis (MS) remains uncertain.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effectiveness of electrical stimulation therapy (EST) for pain, depression, fatigue, disability, and quality of life in multiple sclerosis (MS) remains uncertain. This study aims to analyze and discuss the efficacy of various EST treatments in alleviating pain among MS patients.
METHODS
The primary search was conducted using PubMed, Web of Science, Cochrane Library, Embase, and the Cumulative Index of Nursing and Allied Health Literature databases until September 25, 2023. Randomized controlled trials (RCTs) including patients with MS pain receiving EST compared with other therapies were included. Pain intensity, quality of life, and neuropsychiatric symptoms were reported. The mean difference (MD) with 95 % confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size.
RESULTS
Ten RCTs containing 315 participants were included. The pooled data from 8 trials including 267 participants showed that the EST was superior in alleviating pain (MD = -1.75, 95 % CI -2.85--0.64, P = 0.002, I=73 %) evaluated by the visual analog scale. In subgroup analysis, medium-term EST treatment showed the highest effect size compared to short-term and long-term treatment (MD = -2.17, 95 % CI -3.51--0.84, P = 0.001, I = 0 %). However, no significant differences were found in terms of pain-related quality of life, depression, fatigue, and pain-related disability. No adverse events related to EST were reported. A high risk of bias was identified in three of the ten included studies.
CONCLUSIONS
EST is effective and safe for alleviating pain in MS, but it should be noted that limited sample sizes and methodological issues were present in the included studies. More robust assessment criteria and high-quality RCTs are required for patients with MS.
TRIAL REGISTRATION
CRD42023406787. (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406787).
Topics: Humans; Electric Stimulation Therapy; Fatigue; Pain; Quality of Life; Multiple Sclerosis; Pain Management
PubMed: 37944194
DOI: 10.1016/j.msard.2023.105114 -
European Journal of Medical Research Aug 2023Multiple Sclerosis (MS) is a chronic debilitating disease that targets the central nervous system. Globally it is estimated that 2.8 million people live with MS (2018)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple Sclerosis (MS) is a chronic debilitating disease that targets the central nervous system. Globally it is estimated that 2.8 million people live with MS (2018) and as there is no known cure; therefore, identifying methods to increase a patient's quality of life (QoL) is of considerable importance. Non-pharmacological interventions are a viable and effective option to increase QoL in patients with MS, however, to date, the literature lacks a complete systematic review of these interventions.
METHODS
A literature search was conducted for studies published up until March 4th 2022 in Scopus, Web of Science, CINAHL Plus, The Cochrane Library, Medline, and Embase. Studies were included if they were randomized control trials (RCTs) assessing a non-pharmacological intervention in adults with MS and measured QoL using the MSQOL-54, SF-36 or MSQLI tools for at least two time points. Quality assessment of each study was completed as well as a review of publication bias. Where possible, meta-analysis was conducted using a random effects model and for other studies a qualitative synthesis was presented.
RESULTS
Thirty studies were included in the meta-analysis and eleven studies were summarized qualitatively. The pooled effects across all non-pharmacological interventions showed a modest improvement in both the physical and mental components of QoL, with a standardized mean difference (SMD) of 0.44 (95% CI 0.26-0.61) and 0.42 (95% CI 0.24-0.60), respectively. Non-pharmacological interventions based around a physical activity were found to be particularly effective in improving both the physical composite score (PCS) and mental composite score (MCS), with an SMD of 0.40 (95% CI 0.14-0.66) and 0.31 (95% CI 0.08-0.55), respectively. Interventions incorporating balance exercises presented a significant advantageous solution for improving QoL, with an SMD of 1.71 (95% CI 1.22, 2.20) and 1.63(95% CI 1.15-2.12) for PCS and MCS respectively.
CONCLUSIONS
This systematic review and meta-analysis identified that non-pharmacological interventions can be an effective method of improving QoL in patients with MS, especially modalities with a physical activity component and balance interventions.
Topics: Humans; Adult; Multiple Sclerosis; Central Nervous System; Quality of Life; Exercise; Randomized Controlled Trials as Topic
PubMed: 37608400
DOI: 10.1186/s40001-023-01185-5 -
Frontiers in Immunology 2023Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease... (Review)
Review
UNLABELLED
Inflammatory processes are involved in the pathophysiology of both Alzheimer's disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Topics: Humans; Aged; Alzheimer Disease; Biomarkers; Disease Progression; Multiple Sclerosis
PubMed: 37520580
DOI: 10.3389/fimmu.2023.1162340 -
European Journal of Medical Research Sep 2022In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.
METHOD
We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number.
RESULTS
IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [-0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD -0.08, 95% CI [-0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD -0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD -0.23, 95% CI [-0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls.
CONCLUSION
This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.
Topics: Adult; Anti-Inflammatory Agents; Cytokines; Exercise; Humans; Interleukin-6; Multiple Sclerosis; Tumor Necrosis Factor-alpha
PubMed: 36156182
DOI: 10.1186/s40001-022-00814-9