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Reviews in the Neurosciences Aug 2021Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.
Topics: Biomarkers; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Neurodegenerative Diseases; Neuroglia
PubMed: 33594840
DOI: 10.1515/revneuro-2020-0145 -
Multiple Sclerosis and Related Disorders Jan 2023Seizures in people with multiple sclerosis (MS) are reported; however, the risk of epilepsy in adults with MS remains poorly defined. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Seizures in people with multiple sclerosis (MS) are reported; however, the risk of epilepsy in adults with MS remains poorly defined.
METHODS
We performed a systematic review and meta-analysis to evaluate the incidence and prevalence of epilepsy in adults (≥ 18 years) with MS compared to those without. We searched MEDLINE and EMBASE from inception to July 1, 2022 to include observational studies that reported the prevalence or incidence of epilepsy in adults with MS and a comparator group, consisting of adults without MS or the general population. We used the Newcastle Ottawa Scale to evaluate quality of the included studies. We performed random-effects meta-analyses to determine the prevalence and incidence of epilepsy in adults with MS compared to the non-MS group.
RESULTS
We identified 17 studies consisting of 192,850 adults with MS, across nine countries. Most studies were of moderate quality as they did not specify the MS type or type of seizures. Compared to a comparison group, both the prevalence (pooled OR 2.04; 95% confidence interval 1.59-2.63, I = 95.4, n = 12) and the incidence of epilepsy (pooled RR 3.34; 3.17-3.52, I = 4.6%, n = 6) was higher in people with MS. Heterogeneity in estimates was not explained by additional analyses.
CONCLUSIONS
MS is an independent risk factor for both incident and prevalent epilepsy, suggesting variation in grey matter involvement over the disease course. Longitudinal studies are required to help identify patient and disease characteristics associated with epilepsy.
Topics: Adult; Humans; Multiple Sclerosis; Epilepsy; Seizures; Risk Factors; Incidence
PubMed: 36434909
DOI: 10.1016/j.msard.2022.104421 -
Journal of Psychosomatic Research Sep 2022Adverse Childhood Experiences (ACEs), such as physical, emotional, and sexual abuse trigger inflammatory changes and have been associated with many causes of morbidity... (Review)
Review
OBJECTIVE
Adverse Childhood Experiences (ACEs), such as physical, emotional, and sexual abuse trigger inflammatory changes and have been associated with many causes of morbidity and mortality, including autoimmune diseases. Although Multiple Sclerosis (MS) is a debilitating neurological autoimmune disease, literature linking ACEs and MS is understudied. The aim of this review was to examine the 1) state of the literature, and 2) relationships between childhood adversity and the prevalence and physical clinical features of MS (e.g., age at onset, relapses, pain, fatigue, disability).
METHODS
A comprehensive search was preformed through five databases and by hand using the ancestry and descendancy approach for connections to papers published through January 20th, 2022. Studies were screened by independent reviewers using Rayyan.ai, and critically appraised for both quality and reporting transparency.
RESULTS
Twelve studies examined relationships between any ACE(s) and the prevalence or physical clinical features of MS. There was considerable variance in the measurement of stressors, confounders, and categorization of MS; however most studies (n = 10) demonstrated an association between ACEs and MS (alone or grouped with other similar diagnoses), or physical clinical features.
CONCLUSION
Although there are few studies in this area, it is of quickly growing interest. These results should be cautiously interpreted, yet highlight the need for continued work to disentangle and discern true associations.
Topics: Adverse Childhood Experiences; Age of Onset; Child; Child Abuse; Humans; Multiple Sclerosis; Prevalence
PubMed: 35779440
DOI: 10.1016/j.jpsychores.2022.110981 -
Neurological Sciences : Official... May 2023To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between... (Review)
Review
OBJECTIVE
To exp lore changes in immunoglobulin (Ig) levels for people with relapsing-multiple sclerosis (RMS) treated with ocrelizumab or ofatumumab and the relationship between Ig levels and infections.
METHODS
A systematic literature review (SLR) was conducted to identify clinical trials and real-world evidence (RWE) studies on Ig levels over time and studies on associations with infections for ocrelizumab and ofatumumab for people with RMS through 10 September 2021. Searches were conducted in Embase, MEDLINE, Cochrane Library, trial registries, and recent conference abstracts.
RESULTS
Of 1,580 articles identified, 30 reporting on 11 trials and 5 RWE studies were included. Ocrelizumab trials (n = 4) had 24-336 weeks of follow-up and reported decreasing Ig G (IgG) levels, while RWE (n = 5) had 52-78 weeks of follow-up and reported IgG to be stable or decrease only slightly. IgG levels were stable in ofatumumab trials (n = 5; 104-168 weeks of follow-up), but no RWE or longer-term studies were identified. No apparent association between decreased Ig levels and infections was observed during ofatumumab treatment (ASCLEPIOS I/II), while for ocrelizumab, the only data on apparent associations between decreased IgG levels and serious infection rates were for a pooled population of people with RMS or primary progressive MS.
CONCLUSION
Decreasing IgG levels have been correlated with increased infection risk over time. IgG levels appeared to decrease over time in ocrelizumab trials but remained relatively stable over time in ofatumumab trials. Additional research is needed to understand differences between ocrelizumab and ofatumumab and identify people at risk of decreasing IgG levels and infection.
Topics: Humans; Multiple Sclerosis; Antibodies, Monoclonal; Antineoplastic Agents; Immunoglobulin G; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36648561
DOI: 10.1007/s10072-022-06582-y -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs.
MAIN RESULTS
We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL. Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer.
AUTHORS' CONCLUSIONS
For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.
Topics: Fingolimod Hydrochloride; Glatiramer Acetate; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Rituximab; Young Adult
PubMed: 34748215
DOI: 10.1002/14651858.CD013874.pub2 -
Journal of Neurology Oct 2023Multiple sclerosis is a neuro-inflammatory disease that affects adults and children and causes somatic and cognitive symptoms. Diagnosis after the first clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis is a neuro-inflammatory disease that affects adults and children and causes somatic and cognitive symptoms. Diagnosis after the first clinical symptoms is challenging, involves laboratory and magnetic resonance imaging work-up and is often inconclusive unless subsequent clinical attacks occur. Neurofilament light chains are structural proteins within neurons. Levels of this marker in cerebrospinal fluid, plasma and serum are consistently higher in patients with an initial clinical demyelinating attack that later go on to develop multiple sclerosis. Evidence concerning serum levels of this biomarker in children with multiple sclerosis is scarce. Our aim is to review and analyze the evidence available for patients with multiple sclerosis, under the age of 18.
METHODS
We conducted a systematic search of PubMed/Medline, Embase, Cochrane Database, and ProQuest. Human studies that provided data on serum levels of Neurofilament light chains in pediatric patients with MS, measured at the time of the first demyelinating attack and before treatment were included in meta-analysis.
RESULTS
Three studies satisfied the inclusion criteria. 157 pediatric patients with multiple sclerosis and 270 hospital-based controls that did not present with this condition were included in the analysis. A fixed effects meta-analysis showed that the standardized mean difference between patients and controls is 1.82, with a 95% confidence interval of [1.56-2.08].
CONCLUSION
Pediatric patients with multiple sclerosis show higher levels of serum neurofilament light chains at their first clinical demyelinating attack compared to pediatric hospital-based controls.
Topics: Adult; Humans; Child; Multiple Sclerosis; Intermediate Filaments; Biomarkers; Neurofilament Proteins; Magnetic Resonance Imaging
PubMed: 37394516
DOI: 10.1007/s00415-023-11841-9 -
Neuroscience and Biobehavioral Reviews Nov 2023Chronic pain is the most disability symptom related to multiple sclerosis (MS) brain lesions and can also generate anxiety and depression. There are no updated reports... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of neuropathic pain in multiple sclerosis: Prevalence, clinical types, sex dimorphism, and increased depression and anxiety symptoms.
Chronic pain is the most disability symptom related to multiple sclerosis (MS) brain lesions and can also generate anxiety and depression. There are no updated reports of the general prevalence of neuropathic pain, MS clinical types, sex dimorphism, and its association with depression and anxiety. The protocol was listed in PROSPERO (CRD42022303571). The article selection resulted in 24 studies with a low risk of bias. The prevalence of neuropathic pain in MS patients was 26.8% with higher levels of depression and anxiety. We also observed that female patients (74.2%) have a higher prevalence of neuropathic pain than males (28.9%). We showed the enhanced prevalence of neuropathic pain using the female and male data (58.9%) compared to the total prevalence (26.8%). In addition, the SPMS (40.3%) presented an increased prevalence of neuropathic pain compared to PPMS (15.6%). Thus, we demonstrated the association between neuropathic pain, depression and anxiety symptoms and the influence of diagnosis, age, disease score, and disease duration in the increased prevalence of neuropathic pain in MS patients.
Topics: Humans; Male; Female; Multiple Sclerosis; Prevalence; Depression; Sex Characteristics; Neuralgia; Anxiety
PubMed: 37777076
DOI: 10.1016/j.neubiorev.2023.105401 -
Acta Neurologica Scandinavica Apr 2022Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle... (Review)
Review
Management of multiple sclerosis (MS) may comprise clinical interventions and self-management strategies, including complementary therapies and modifiable lifestyle factors such as exercise and smoking cessation. Lifestyle modifications and complementary therapies with proven safety and efficacy are essential as part of best-practice MS management, especially when faced with limited access to healthcare services. However, it is unclear to what extent MS clinical practice guidelines and consensus statements address these strategies. A systematic review was conducted, wherein MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, guideline databases and developer sites were searched for guidelines and consensus statements that addressed lifestyle modifications and complementary therapies of interest. Two researchers independently screened articles, extracted data and assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation version II. Thirty-one guidelines and consensus statements were included. Quality was high for 'clarity of presentation' (77%) and 'scope and purpose' (73%), moderate for 'stakeholder development' (56%), 'rigour of development' (48%) and 'editorial independence' (47%), and low for 'applicability' (29%). Two guidelines, related to physical activity and exercise, mindfulness, smoking cessation, and vitamin D and polyunsaturated fatty acid supplementation, scored high in all domains. These guidelines were two of only four guidelines intended for use by people with MS. High-quality guidelines and consensus statements to guide lifestyle modifications and complementary therapies in MS management are limited. Our findings indicate the need for more guidelines intended for use by people with MS, and a further focus on implementation resources.
Topics: Complementary Therapies; Consensus; Humans; Life Style; Multiple Sclerosis; Smoking Cessation
PubMed: 35037722
DOI: 10.1111/ane.13574 -
Reviews on Environmental Health Dec 2021Some studies have shown that environmental risk factors, including air pollution, might be related to the incidence or recurrence of multiple sclerosis (MS). This... (Review)
Review
OBJECTIVES
Some studies have shown that environmental risk factors, including air pollution, might be related to the incidence or recurrence of multiple sclerosis (MS). This systematic review was conducted to investigate the relation between air pollution and MS.
METHODS
A systematic search was conducted in PubMed, Scopus, Science Direct, Embase, and Web of Science; until January 2020 with no restrictions. The search strategy was conducted with air pollution key words such as CO, PM, PM, SO, and NO, for exposure and the key word "Multiple sclerosis" as the outcome.
RESULTS
Eventually, after applying the inclusion and exclusion criteria, 17 articles were included. The methodologies and outcomes reported were heterogeneous and different metrics had been used in the results; therefore conducting a meta-analysis was not possible. Eight studies had analyzed the relation between particulate matter (PM) and the prevalence or relapse of MS and had observed a significant relation. NO and NOx were associated with recurrence or prevalence of MS in three studies. But, in three cohort studies, no association was observed between air pollution and recurrence or occurrence of MS.
CONCLUSIONS
The results of this systematic review show that outdoor air pollution, especially PM and nitrogen oxides might be related to the prevalence or relapse of MS.
Topics: Air Pollutants; Air Pollution; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter
PubMed: 34821118
DOI: 10.1515/reveh-2020-0079 -
Multiple Sclerosis and Related Disorders Nov 2023Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard... (Review)
Review
INTRODUCTION
Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS). We conducted a systematic review to 1) understand whether fatigue is included as an outcome in MS trials of DMTs; 2) determine the effects on fatigue of treating MS with DMTs and 3) assess the quality of MS trials including fatigue as an outcome.
METHODS
Two independent researchers systematically searched MEDLINE, EMBASE and ClinicalTrials.gov from 1993 to January 2023 for RCTs that measured fatigue as an outcome. Adherence to reporting standards was assessed with the Consolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO), while the risk of bias (RoB) was assessed with the RoB 2 tool by the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review protocol was registered in PROSPERO (CRD42022383321).
RESULTS
The search strategy identified 130 RCTs of DMTs of which 7 (5%) assessed fatigue as an outcome. Of the 7 trials, only two presented statistically significant results. In addition, the reporting of fatigue among RCTs was suboptimal with a mean adherence to the CONSORT-PRO Statement of 36% across all trials. Of the 7 trials included, four were assessed as 'high' RoB..
CONCLUSIONS
Fatigue has a major impact on PwMS yet there is limited trial-based evidence on the impact of DMTs on fatigue. Assessment of fatigue as an outcome is underrepresented in trials of DMTs and the reporting of PRO trial data is suboptimal. Thus, it is imperative that MS researchers conduct RCTs that include fatigue as an outcome, to support clinicians and people with MS (PwMS) to consider the impact of the different DMTs on fatigue.
Topics: Humans; Fatigue; Multiple Sclerosis; Patient Reported Outcome Measures; Reference Standards; Systematic Reviews as Topic
PubMed: 37839365
DOI: 10.1016/j.msard.2023.105065