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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 -
Association of chronic periodontitis with multiple sclerosis: A systematic review and meta-analysis.Multiple Sclerosis and Related Disorders Sep 2023Chronic periodontitis (CP) is a multifactorial, chronic inflammatory disease of microbial etiology that manifests as a result of the dysfunction of the immune mechanism,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic periodontitis (CP) is a multifactorial, chronic inflammatory disease of microbial etiology that manifests as a result of the dysfunction of the immune mechanism, culminating in the destruction of the alveolar bone of the jaws. Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system (CNS), leads to demyelination and degeneration of nerve axons and often causes severe physical and/or cognitive impairment. As CP and MS involve inflammatory mechanisms and immune dysfunction, researchers have attempted to study the association between them.
AIM
To systematically review the literature on the epidemiological association between CP and MS in adults.
METHODS
PRISMA 2020 statement was used in the study protocol. The design was done according to the Cochrane methodology. A comprehensive literature search was performed in PubMed, Scopus and Cochrane databases; a manual search and evaluation of the gray literature was also performed. The meta-analysis was performed by Review Manager (RevMan) 5.4. Odds ratio (OR) with 95% confidence interval (CI) was defined as the effect size of the outcome. Heterogeneity was assessed by Chi-square and I. The articles evaluated were written in English, without a time limit, concern observational studies (patient-controls) and report the diagnostic criteria of the diseases. Duplicate entries were excluded. To evaluate the reliability of the results of each study, Newcastle-Ottawa Scale (NOS) and GRADE tools were used. Two independent reviewers did all evaluations with a resolution of discrepancies by a third.
RESULTS
Meta-analysis included three observation studies examined 3376 people. MS patients are significantly more likely to be diagnosed with CP than healthy controls (OR 1.93, 95% CI 1.54-2.42, p<0.0001).
CONCLUSION
A high prevalence of CP was found among MS patients compared with healthy controls. Healthcare professionals should be aware of the association between these pathological entities to provide patients with high-quality care through an effective and holistic diagnostic and therapeutic approach.
Topics: Adult; Humans; Chronic Periodontitis; Multiple Sclerosis; Reproducibility of Results; Autoimmune Diseases; Chronic Disease
PubMed: 37478676
DOI: 10.1016/j.msard.2023.104874 -
Reviews in Medical Virology Jan 2024Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the... (Meta-Analysis)
Meta-Analysis Review
Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta-analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta-analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta-Analysis. The Confidence Interval of effect size was 95% in meta-analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS-CoV-2, Epstein-Barr virus (EBV), Hepatitis B virus, varicella-zoster virus (VZV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, HSV-1, HSV-2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS-CoV-2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV-6, HSV-2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS-CoV-2 is the culprit. Hence, it was necessary to investigate the effects of SARS-CoV-2 and EBV on MS.
Topics: Humans; Multiple Sclerosis; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Virus Diseases; Viruses; Herpesvirus 3, Human
PubMed: 38010852
DOI: 10.1002/rmv.2494 -
Journal of the Neurological Sciences Oct 2023Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease involving immune-mediated damage. Iron deposition in deep gray matter (DGM) structures... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease involving immune-mediated damage. Iron deposition in deep gray matter (DGM) structures like the thalamus and basal ganglia have been suggested to play a role in MS pathogenesis. Magnetic Resonance Imaging (MRI) imaging methods like T2 and T2* imaging, susceptibility-weighted imaging, and quantitative susceptibility mapping can track iron deposition storage in the brain primarily from ferritin and hemosiderin (paramagnetic iron storage proteins) with varying levels of tissue contrast and sensitivity. In this systematic review, we evaluated the role of DGM iron deposition as detected by MRI techniques in relation to MS-related neuroinflammation and its potential as a novel therapeutic target. We searched through PubMed, Embase, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, against predetermined inclusion and exclusion criteria. We included 89 articles (n = 6630 patients), and then grouped them into different categories: i) methodological techniques to measure DGM iron, ii) cross-sectional and group comparison of DGM iron content, iii) longitudinal comparisons of DGM iron, iv) associations between DGM iron and other imaging and neurobiological markers, v) associations with disability, and vi) associations with cognitive impairment. The review revealed that iron deposition in DGM is independent yet concurrent with demyelination, and that these iron deposits contribute to MS-related cognitive impairment and disability. Variability in iron distributions appears to rely on a positive feedback loop between inflammation, and release of iron by oligodendrocytes. DGM iron seems to be a promising prognostic biomarker for MS pathophysiology.
Topics: Humans; Gray Matter; Neurodegenerative Diseases; Cross-Sectional Studies; Multiple Sclerosis; Magnetic Resonance Imaging; Brain; Inflammation; Iron
PubMed: 37827008
DOI: 10.1016/j.jns.2023.120816 -
European Journal of Neurology Aug 2023Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed.
METHODS
The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted.
RESULTS
Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%).
CONCLUSION
This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Immunoglobulins, Intravenous; Immunosuppressive Agents; Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation
PubMed: 37170791
DOI: 10.1111/ene.15857 -
European Journal of Neurology May 2023Non-(acute disseminated encephalomyelitis) (non-ADEM) encephalitis and/or fluid attenuated inversion recovery hyperintense lesions in... (Review)
Review
BACKGROUND AND PURPOSE
Non-(acute disseminated encephalomyelitis) (non-ADEM) encephalitis and/or fluid attenuated inversion recovery hyperintense lesions in anti-myelin-oligodendrocyte-glycoprotein-associated encephalitis with seizures (FLAMES) are rarely described in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs). The aim was (i) to describe the clinical features and disease course of children and adults with non-ADEM encephalitis and/or FLAMES associated with MOG Abs and (ii) to describe their association with other central nervous system autoantibodies.
METHODS
This was a systematic review following the PRISMA guidelines. Patients fulfilled criteria for non-ADEM encephalitis and/or FLAMES, and all were MOG Ab positive.
RESULTS
In total, 83 (79%) patients with non-ADEM encephalitis (48 also had FLAMES) and 22 (21%) with isolated FLAMES were included. At the first episode, children (n = 45) had more infections (11/45, 24.4%; p = 0.017) and more of the phenotype consisting of non-ADEM encephalitis (42/45, 93.3%; p = 0.014) than adults (n = 38). Children had more episodes consistent with working memory deficits (25/54, 46.3%; p = 0.014) but fewer psychiatric symptoms (16/54, 29.6%; p = 0.002). Twenty-eight (40.6%) of 69 patients had N-methyl-d-aspartate receptor (NMDAR) Abs in cerebrospinal fluid (CSF), being more frequent in adults (19/29, 65.5%; p < 0.001). Compared to negatives, positive CSF NMDAR Abs had more relapses (14/20, 70%; p = 0.050), required ventilatory support more frequently (8/34, 23.5%; p = 0.009) and had more psychiatric episodes (28/34, 82%; p < 0.001) or abnormal movements (14/34, 41.2%; p = 0.008). Apart from an older age in FLAMES, positive and negative CSF NMDAR Ab groups shared similar features.
CONCLUSION
Non-ADEM encephalitis patients with MOG Abs show specific clinical and radiological features, depending on the age at first episode. The presence of MOG Abs in non-ADEM encephalitis patients should not rule out to test other autoantibodies, especially concomitant NMDAR Abs in patients with suggestive symptoms such as behavioural or movement alterations.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Encephalitis; Encephalomyelitis, Acute Disseminated; Disease Progression; Autoantibodies
PubMed: 36704861
DOI: 10.1111/ene.15684 -
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 -
Annals of Clinical and Translational... Feb 2022Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are two autoimmune diseases that seriously affect patients' quality of life. Previous studies have established an association between MS and IBD, including Crohn's disease (CD) and ulcerative colitis (UC), but the results were inconsistent. The aim of this study was to quantify the prevalences of and the association between MS and IBD.
METHODS
The PubMed, Web of Science, and Embase databases were searched through November 2020 for studies reporting data on MS among patients with IBD and vice versa. The main outcomes were the proportion of MS in patients with IBD and vice versa, as well as the association (risk ratio [RR]) of IBD in MS and that of MS in IBD.
RESULTS
Based on the analysis of 17 studies, the prevalence of MS in patients with IBD was 0.2% (95% CI 0.1-0.4%), while the prevalence of IBD in patients with MS was 0.6% (95% CI 0.4-0.9%). Patients with MS had a higher prevalence of IBD than controls (RR = 1.53, 95% CI 1.38-1.70, p < 0.00001). There was a similarly high risk of developing CD (RR 1.41, 95% CI 1.14-1.74, p = 0.001) or UC (RR 1.42, 95% CI 1.17-1.71, p = 0.0003) in patients with MS (p for subgroup differences: 0.97). Patients with IBD had a higher prevalence of MS than controls (RR = 1.91, 95% CI 1.06-3.45, p = 0.03).
CONCLUSIONS
Clinicians should be aware of the increased risk of IBD or MS comorbidity during the diagnostic process. Systematic diagnosis and management at an earlier stage are suggested.
Topics: Comorbidity; Humans; Inflammatory Bowel Diseases; Multiple Sclerosis
PubMed: 35092169
DOI: 10.1002/acn3.51495 -
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 -
The association between brain volume loss and disability in multiple sclerosis: A systematic review.Multiple Sclerosis and Related Disorders Jun 2023Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, degenerative disease of the central nervous system that affects approximately 2.8 million people... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, degenerative disease of the central nervous system that affects approximately 2.8 million people worldwide. Compelling evidence from observational studies and clinical trials indicates a strong association between brain volume loss (BVL) and the accumulation of disability in MS. However, the considerable heterogeneity in study designs and methods of assessment of BVL invites questions concerning the generalizability of the reported findings. Therefore, we conducted this systematic review to characterize the relationship between BVL and physical disability in patients with MS.
METHODS
A systematic literature search of MEDLINE and EMBASE databases was performed supplemented by gray literature searches. The following study designs were included: prospective/retrospective cohort, cross-sectional and case-control. Only English language articles published from 2010 onwards were eligible for final inclusion. There were no restrictions on MS subtype, age, or ethnicity. Of the 1620 citations retrieved by the structured searches, 50 publications met our screening criteria and were included in the final data set.
RESULTS
Across all BVL measures, there was considerable heterogeneity in studies regarding the underlying study population, the definitions of BVL and image analysis methodologies, the physical disability measure used, the measures of association reported and whether the analysis conducted was univariable or multivariable. A total of 36 primary studies providing data on the association between whole BVL and physical disability in MS collectively suggest that whole brain atrophy is associated with greater physical disability progression in MS patients. Similarly, a total of 15 primary studies providing data on the association between ventricular atrophy and physical disability in MS suggest that ventricular atrophy is associated with greater physical disability progression in MS patients. Along similar lines, the existing evidence based on a total of 13 primary studies suggests that gray matter atrophy is associated with greater physical disability progression in MS patients. Four primary studies suggest that corpus callosum atrophy is associated with greater physical disability progression in MS patients. The majority of the existing evidence (6 primary studies) suggests no association between white matter atrophy and physical disability in MS. It is difficult to assign a relationship between basal ganglia volume loss and physical disability as well as medulla oblongata width and physical disability in MS due to very limited data.
CONCLUSION
The evidence gathered from this systematic review, although very heterogeneous, suggests that whole brain atrophy is associated with greater physical disability progression in MS patients. Our review can help define future imaging biomarkers for physical disability progression and treatment monitoring in MS.
Topics: Humans; Multiple Sclerosis; Retrospective Studies; Cross-Sectional Studies; Prospective Studies; Magnetic Resonance Imaging; Brain; Atrophy
PubMed: 37068369
DOI: 10.1016/j.msard.2023.104714