-
Multiple Sclerosis and Related Disorders Jul 2023Epidemiological studies have shown conflicting results between antibiotic use and multiple sclerosis (MS) risks. The present systematic review and meta-analysis were... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epidemiological studies have shown conflicting results between antibiotic use and multiple sclerosis (MS) risks. The present systematic review and meta-analysis were conducted to assess the association between antibiotic use and the risk of MS.
METHODS
PubMed, Scopus, Embase, Web of Science, and Google Scholar as well as reference lists of retrieved studies were searched systematically to identify studies were assessed the relationship between antibiotic use and MS up to September 24, 2022. Random-effects model was used for the calculation of pooled Odds ratio (OR) and 95% confidence intervals (CI).
RESULTS
Five independent studies containing 47,491 participants were included in the meta-analysis. The overall results of included studies showed a non-significant positive association between antibiotic use (OR overall=1.01, 95%CI: 0.75-1.37) and a non-significant negative association between penicillin use (OR overall= 0.83; 95%CI: 0.62-1.13) and MS risk. Heterogeneity was (I=90.1, P < 0.001) and (I=90.7, P < 0.001) in antibiotics and penicillin use groups respectively.
CONCLUSION
Our meta-analysis did not show a significant association between antibiotic or penicillin use with the risk of MS. However, due to the limitations of this study, further well-designed studies are required to confirm our findings.
Topics: Humans; Anti-Bacterial Agents; Multiple Sclerosis; Penicillins; Odds Ratio
PubMed: 37209499
DOI: 10.1016/j.msard.2023.104765 -
Nature Reviews. Neuroscience Jul 2024Chronic low-grade inflammation and neuronal deregulation are two components of a smoldering disease activity that drives the progression of disability in people with... (Review)
Review
Chronic low-grade inflammation and neuronal deregulation are two components of a smoldering disease activity that drives the progression of disability in people with multiple sclerosis (MS). Although several therapies exist to dampen the acute inflammation that drives MS relapses, therapeutic options to halt chronic disability progression are a major unmet clinical need. The development of such therapies is hindered by our limited understanding of the neuron-intrinsic determinants of resilience or vulnerability to inflammation. In this Review, we provide a neuron-centric overview of recent advances in deciphering neuronal response patterns that drive the pathology of MS. We describe the inflammatory CNS environment that initiates neurotoxicity by imposing ion imbalance, excitotoxicity and oxidative stress, and by direct neuro-immune interactions, which collectively lead to mitochondrial dysfunction and epigenetic dysregulation. The neuronal demise is further amplified by breakdown of neuronal transport, accumulation of cytosolic proteins and activation of cell death pathways. Continuous neuronal damage perpetuates CNS inflammation by activating surrounding glia cells and by directly exerting toxicity on neighbouring neurons. Further, we explore strategies to overcome neuronal deregulation in MS and compile a selection of neuronal actuators shown to impact neurodegeneration in preclinical studies. We conclude by discussing the therapeutic potential of targeting such neuronal actuators in MS, including some that have already been tested in interventional clinical trials.
Topics: Humans; Multiple Sclerosis; Animals; Neurons; Inflammation
PubMed: 38789516
DOI: 10.1038/s41583-024-00823-z -
JAMA Neurology Jan 2024Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are...
IMPORTANCE
Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair.
OBJECTIVE
To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS).
DESIGN, SETTING, AND PARTICIPANTS
This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register.
MAIN OUTCOMES AND MEASURES
The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors.
EXPOSURES
Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT.
RESULTS
After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001).
CONCLUSIONS AND RELEVANCE
PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.
Topics: Adult; Child; Humans; Female; Male; Multiple Sclerosis; Cohort Studies; Disease Progression; Chronic Disease; Recurrence; Multiple Sclerosis, Relapsing-Remitting
PubMed: 38010712
DOI: 10.1001/jamaneurol.2023.4455 -
Disease-a-month : DM Sep 2023
Topics: Humans; Multiple Sclerosis; Diabetic Neuropathies; Polyneuropathies; Diabetes Mellitus
PubMed: 36266117
DOI: 10.1016/j.disamonth.2022.101496 -
The New England Journal of Medicine Feb 2024
Topics: Humans; Multiple Sclerosis
PubMed: 38354146
DOI: 10.1056/NEJMe2314434 -
Immunopharmacology and Immunotoxicology Jun 2024Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females,... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis.
METHODS
We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy.
RESULTS
Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression.
CONCLUSION
MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS.
Topics: Humans; Multiple Sclerosis; Animals; Immunotherapy
PubMed: 38634438
DOI: 10.1080/08923973.2024.2330642 -
Current Neurology and Neuroscience... Sep 2023Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is... (Review)
Review
PURPOSE OF REVIEW
Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy.
RECENT FINDINGS
Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis. People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient.
Topics: Humans; Inappropriate Prescribing; Deprescriptions; Polypharmacy; Prevalence; Multiple Sclerosis
PubMed: 37523105
DOI: 10.1007/s11910-023-01289-9 -
JPMA. the Journal of the Pakistan... Aug 2023
Topics: Humans; Pakistan; Multiple Sclerosis
PubMed: 37697744
DOI: 10.47391/JPMA.23-55 -
Current Neurology and Neuroscience... Nov 2023Multiple sclerosis is a chronic inflammatory disease of the central nervous system. When seen in children and adolescents, crucial stages of brain development and... (Review)
Review
PURPOSE OF REVIEW
Multiple sclerosis is a chronic inflammatory disease of the central nervous system. When seen in children and adolescents, crucial stages of brain development and maturation may be affected. Prompt recognition of multiple sclerosis in this population is essential, as early intervention with disease-modifying therapies may change developmental trajectories associated with the disease. In this paper, we will review diagnostic criteria for pediatric multiple sclerosis, outcomes, differential diagnosis, and current therapeutic approaches.
RECENT FINDINGS
Recent studies have demonstrated the utility of newer structural and functional metrics in facilitating early recognition and diagnosis of pediatric MS. Knowledge about disease-modifying therapies in pediatric multiple sclerosis has expanded in recent years: important developmental impacts of earlier therapeutic intervention and use of highly effective therapies have been demonstrated. Pediatric MS is characterized by highly active disease and high disease burden. Advances in knowledge have led to early identification, diagnosis, and treatment. Lifestyle-related interventions and higher efficacy therapies are currently undergoing investigation.
Topics: Adolescent; Humans; Child; Multiple Sclerosis; Diagnosis, Differential; Disease Progression
PubMed: 37792206
DOI: 10.1007/s11910-023-01300-3 -
Multiple Sclerosis and Related Disorders Sep 2023The relation of sarcopenia and disability in MS is unknown.
BACKGROUND
The relation of sarcopenia and disability in MS is unknown.
OBJECTIVE
To investigate the relation of temporal muscle thickness (TMT) and disability.
METHODS
A cohort of 132 people who presented with a clinically isolated syndrome (CIS) suggestive of MS at a mean age of 30.0 years, were prospectively followed clinically and with MRI over 30-years. TMT and expanded disability status scale (EDSS) were assessed at baseline, one- five- ten- fourteen- twenty- and thirty-year follow-up.
RESULTS
At 30-years, 27 participants remained classified as having had a CIS, 34 converted to relapsing remitting MS, 26 to secondary progressive MS, and 16 had died due to MS. Using linear mixed effect models with subject nested in time, greater annualized TMT-thinning was seen in individuals who developed MS (-0.04 mm/a, 95%CI: -0.07 to -0.01, p = 0.023). In those who converted to MS, a thinner TMT was reached at 14- (p = 0.008), 20- (p = 0.002) and 30-years (p< 0.001). TMT was negatively correlated with EDSS at 20-years (R=-0.18, p = 0.032) and 30-years (R-0.244, p = 0.005). Longitudinally, TMT at earlier timepoints was not predictive for 30-year clinical outcomes.
CONCLUSION
TMT thinning is accelerated in MS and correlated with disability in later disease stages, but is not predictive of future disability.
Topics: Humans; Adult; Multiple Sclerosis; Sarcopenia; Demyelinating Diseases; Magnetic Resonance Imaging; Linear Models; Multiple Sclerosis, Relapsing-Remitting; Disability Evaluation; Disease Progression; Multiple Sclerosis, Chronic Progressive
PubMed: 37442077
DOI: 10.1016/j.msard.2023.104855