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Multiple Sclerosis and Related Disorders Mar 2024A large body of evidence has tested the effect of exercise interventions on mental health and health-related quality of life (HRQoL) in individuals with multiple... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A large body of evidence has tested the effect of exercise interventions on mental health and health-related quality of life (HRQoL) in individuals with multiple sclerosis (PwMS).
OBJECTIVE
To determine the effect of exercise interventions on mental health and HRQoL in PwMS.
METHODS
We searched four databases up to April 2023, and included randomized controlled trials that: 1) involved PwMS ≥18 years old; 2) delivered an exercise intervention; 3) measured subjective well-being, psychological well-being, social well-being, or HRQoL as outcomes. We reported standardized differences in means (d) with a 95 % confidence interval (CI), for continuous outcomes and an incidence rate ratio (IRR) with a 95 % CI for dichotomous outcomes.
RESULTS
Forty-nine studies (n = 2,057 participants) were included. Exercise improved overall well-being (d = 0.78; 95 % CI 0.483, 1.077; moderate certainty evidence), subjective well-being (d = 0.666; 95 % CI 0.405, 0.928; moderate certainty evidence), social well-being (d = 1.046; 95 % CI 0.569, 1.523; low certainty evidence), and HRQoL (d = 0.568; 95 % CI 0.396, 0.74; moderate certainty evidence).
CONCLUSION
Exercise interventions can improve well-being and HRQoL in PwMS. Future studies should focus on PwMS ≥ 65 years or with higher level of impairments.
Topics: Humans; Adolescent; Quality of Life; Mental Health; Multiple Sclerosis; Exercise
PubMed: 38320418
DOI: 10.1016/j.msard.2024.105473 -
Neurologia Mar 2024To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal... (Review)
Review
OBJECTIVE
To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal and the specific characteristics of euthanasia in some of these diseases, and to show the evolution of euthanasia figures.
METHODS
We conducted a systematic literature review.
RESULTS
Dementia, motor neuron disease, multiple sclerosis, and Parkinson's disease are the neurological diseases that most frequently motivate requests for euthanasia or assisted suicide. Requests related to dementia constitute the largest group, are growing, and raise additional ethical and legal issues due to these patients' diminished decision-making capacity. In some countries, the ratios of euthanasia requests to all cases of multiple sclerosis, motor neuron disease, or Huntington disease are higher than for any other disease.
CONCLUSIONS
After cancer, neurological diseases are the most frequent reason for requesting euthanasia or assisted suicide.
Topics: Humans; Suicide, Assisted; Euthanasia; Nervous System Diseases; Huntington Disease; Multiple Sclerosis; Motor Neuron Disease
PubMed: 38272260
DOI: 10.1016/j.nrleng.2024.01.007 -
Journal of Neurology Mar 2024Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported.
METHODS
A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model.
RESULTS
Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases.
CONCLUSIONS
Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.
Topics: Humans; COVID-19; COVID-19 Vaccines; Guillain-Barre Syndrome; mRNA Vaccines; Vaccination
PubMed: 38233678
DOI: 10.1007/s00415-024-12186-7 -
Annals of Clinical and Translational... Mar 2024Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values.
METHODS
The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies."
RESULTS
In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS.
INTERPRETATION
Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.
Topics: Adult; Child; Humans; Multiple Sclerosis; Cognition Disorders; Cognitive Dysfunction; Neuropsychological Tests; Phenotype
PubMed: 38212940
DOI: 10.1002/acn3.51976 -
The Cochrane Database of Systematic... Jan 2024Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015.
OBJECTIVES
To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS.
SEARCH METHODS
CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top-up search was conducted on 8 August 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta-analysis. Certainty of the evidence was assessed by the GRADE approach.
MAIN RESULTS
We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo-controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk). Placebo was used as the common comparator for network analysis. Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high-certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate-certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate-certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate-certainty evidence) probably result in a large reduction of people with relapses at 12 months. Relapses over 24 months: data were reported in 28 studies (19,869 participants). Cladribine (RR 0.53, 95% CI 0.44 to 0.64; high-certainty evidence), alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68; high-certainty evidence) and natalizumab (RR 0.56, 95% CI 0.48 to 0.65; high-certainty evidence) result in a large decrease of people with relapses at 24 months. Fingolimod (RR 0.54, 95% CI 0.48 to 0.60; moderate-certainty evidence), dimethyl fumarate (RR 0.62, 95% CI 0.55 to 0.70; moderate-certainty evidence), and ponesimod (RR 0.58, 95% CI 0.48 to 0.70; moderate-certainty evidence) probably result in a large decrease of people with relapses at 24 months. Glatiramer acetate (RR 0.84, 95%, CI 0.76 to 0.93; moderate-certainty evidence) and interferon beta-1a (Avonex, Rebif) (RR 0.84, 95% CI 0.78 to 0.91; moderate-certainty evidence) probably moderately decrease people with relapses at 24 months. Relapses over 36 months findings were available from five studies (3087 participants). None of the treatments assessed showed moderate- or high-certainty evidence compared to placebo. Disability worsening over 24 months was assessed in 31 studies (24,303 participants). Natalizumab probably results in a large reduction of disability worsening (RR 0.59, 95% CI 0.46 to 0.75; moderate-certainty evidence) at 24 months. Disability worsening over 36 months was assessed in three studies (2684 participants) but none of the studies used placebo as the comparator. Treatment discontinuation due to adverse events data were available from 43 studies (35,410 participants). Alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (OR 0.39, 95% CI 0.19 to 0.79; moderate-certainty evidence). Daclizumab (OR 2.55, 95% CI 1.40 to 4.63; moderate-certainty evidence), fingolimod (OR 1.84, 95% CI 1.31 to 2.57; moderate-certainty evidence), teriflunomide (OR 1.82, 95% CI 1.19 to 2.79; moderate-certainty evidence), interferon beta-1a (OR 1.48, 95% CI 0.99 to 2.20; moderate-certainty evidence), laquinimod (OR 1.49, 95 % CI 1.00 to 2.15; moderate-certainty evidence), natalizumab (OR 1.57, 95% CI 0.81 to 3.05), and glatiramer acetate (OR 1.48, 95% CI 1.01 to 2.14; moderate-certainty evidence) probably result in a slight increase in the number of people who discontinue treatment due to adverse events. Serious adverse events (SAEs) were reported in 35 studies (33,998 participants). There was probably a trivial reduction in SAEs amongst people with RRMS treated with interferon beta-1b as compared to placebo (OR 0.92, 95% CI 0.55 to 1.54; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.
Topics: Adult; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Glatiramer Acetate; Interferon beta-1a; Fingolimod Hydrochloride; Natalizumab; Interferon beta-1b; Cladribine; Alemtuzumab; Dimethyl Fumarate; Daclizumab; Network Meta-Analysis; Immunologic Factors; Recurrence
PubMed: 38174776
DOI: 10.1002/14651858.CD011381.pub3 -
Frontiers in Public Health 2023People with Multiple Sclerosis (PwMS) are vulnerable to unfavorable occupational outcomes and the COVID-19 pandemic brought major consequences on people's professional... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with Multiple Sclerosis (PwMS) are vulnerable to unfavorable occupational outcomes and the COVID-19 pandemic brought major consequences on people's professional lives. In this view, we decided to investigate the occupational outcomes of PwMS during the COVID-19 pandemic.
METHODS
We performed a systematic review with meta-analysis searching key terms in four databases. We initially included any peer-reviewed original article that enrolled adult patients with the diagnosis of MS and assessed any occupational variable during the COVID-19 pandemic. There were no time limits and no language restrictions. The primary outcomes were the prevalence of unemployment, retirement and employment status change among people with MS during the COVID-19 pandemic. Other outcomes included the modality and characteristics of work: type of work, full-time work, part-time work and remote work. We also searched for data from studies that addressed any change in the work status due to the COVID-19 outbreak.
RESULTS
We identified 49 eligible articles comprising a total sample size of 17,364 individuals with MS. The pooled prevalence of unemployment and retirement was 0.47 (95% CI = 0.42-0.53). The pooled prevalence of PwMS who were unemployed or retired was positively associated with the progressive phenotype of the disease ( = 0.017) and the use of glatiramer acetate ( = 0.004), but negatively associated with hospitalization due to COVID-19 ( = 0.008) and the use of immunosuppressants ( = 0.032), siponimod ( < 0.001), and cladribine ( = 0.021). The pooled proportion of PwMS that reported any change of the employment status during the COVID-19 pandemic was 0.43 (95% CI = 0.36-0.50) while the pooled prevalence of PwMS who worked remotely during this period was 0.37 (95% CI = 0.15-0.58). The change in employment status was negatively associated with the duration of MS ( = 0.03) but positively associated with the progressive phenotype of the disease ( < 0.001).
CONCLUSION
Our seminal review may serve as an example of how patients with neurological diseases or disabilities in general may have their jobs impacted in a pandemic and foster the context of global socio-economic crisis.
Topics: Adult; Humans; COVID-19; Multiple Sclerosis; Pandemics; Disease Outbreaks
PubMed: 38089033
DOI: 10.3389/fpubh.2023.1217843 -
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 -
Journal of Managed Care & Specialty... Dec 2023People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population.
OBJECTIVE
To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS.
METHODS
MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs.
RESULTS
We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers.
CONCLUSIONS
The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.
Topics: Humans; Bone Density; Prospective Studies; Anticonvulsants; Anti-Anxiety Agents; Retrospective Studies; Cross-Sectional Studies; Glucocorticoids; Multiple Sclerosis; Fractures, Bone; Antidepressive Agents; Immunologic Factors
PubMed: 38058136
DOI: 10.18553/jmcp.2023.29.12.1331 -
Frontiers in Public Health 2023We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple Sclerosis.
METHODS
A systematic, comprehensive literature search was performed in four electronic academic databases. We included any case-control study that enrolled working-age subjects and compared the proportion of MS cases with controls who were not exposed to an occupational risk factor. The primary outcome was the occurrence of MS. The quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies, developed, and validated by the Joanna Briggs Institute. All the selection process was also carried out by two independent and previously trained researchers.
RESULTS
Overall, the total sample included 19,004 people with MS and 4,164,162 controls. Agricultural workers (OR = 1.44, 95% CI 1.13-1.83), offshore workers (OR = 3.56, 95% CI 2.74-4.61), and hairdressers (OR = 8.25, 95% CI 1.02-66.52) were associated with a higher probability of being diagnosed with MS. In parallel, workers exposed to toxic fumes from oil wells (OR = 16.80, 95% CI 8.33-33.90), low-frequency magnetic fields (OR = 1.71, 95% CI 1.03-2.72), and pesticides (OR = 3.17, 95% CI = 2.53-3.99) also had an increased likelihood of having MS.
CONCLUSION
Our study has the potential to influence more assertive public policies. Nevertheless, future studies on how the occupational setting may contribute to the incidence of MS are highly recommended.
SYSTEMATIC REVIEW REGISTRATION
The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257).
Topics: Humans; Occupational Diseases; Multiple Sclerosis; Case-Control Studies; Occupational Exposure; World Health Organization; Cost of Illness; Risk Factors
PubMed: 38054069
DOI: 10.3389/fpubh.2023.1285103 -
Epigenetics Insights 2023Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive... (Review)
Review
Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.
PubMed: 38033465
DOI: 10.1177/25168657231213195