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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 -
Multiple Sclerosis and Related Disorders May 2024To compare the efficacy of treatment of optic neuritis (ON) with corticosteroids (CTC) alone, CTC+plasmapheresis (PLP), and CTC+intravenous immunoglobulin (IVIG). (Meta-Analysis)
Meta-Analysis Comparative Study Review
Efficacy and comparison of corticosteroids only and corticosteroids with plasmapheresis or intravenous immunoglobulin for the treatment of optic neuritis in demyelinating disease: A systematic review and network meta-analysis.
PURPOSE
To compare the efficacy of treatment of optic neuritis (ON) with corticosteroids (CTC) alone, CTC+plasmapheresis (PLP), and CTC+intravenous immunoglobulin (IVIG).
DESIGN
After an episode of ON, although visual recovery is usually good, some patients may have significant visual sequelae. While the efficacy of first-line CTC is now indisputable, there is no consensus on the nature of second-line treatment. To date, no systematic review has compared the efficacy of treatment of ON with CTC alone, CTC+plasmapheresis (PLP), and CTC+intravenous immunoglobulin (IVIG). A meta-analysis is needed to compare the efficacy of PLP and IVIG in steroid-resistant ON.
METHODS
This systematic review included all studies comparing at least two of the three treatments for steroid-resistant ON (CTC alone, CTC+PLP, and CTC+IVIG). From all articles published on PubMed between January 2000 and June 2022, two independent ophthalmologists selected studies of interest using the PRISMA method. Methodology, patient characteristics, and outcomes were identified. A network metaanalysis was then performed to compare the efficacy of the three treatments.
RESULTS
Six comparative studies were included, representing 209 patients. The percentage of significant visual recovery after CTC alone, CTC+PLP, and CTC+IVIG in the acute treatment of steroid-resistant ON was 30 %, 45 %, and 77 %, respectively. Comparison of CTC+IVIG vs CTC alone, CTC+PLP vs CTC only, and CTC+PLP vs CTC+IVIG yielded odds ratios of 12.81, 2.47, and 0.19 respectively.
CONCLUSION
Treatment of steroid-resistant ON with CTC+PLP or CTC+IVIG is more effective than treatment with CTC alone. Although no study has directly compared the two treatments, IVIG may be more effective than PLP.
Topics: Optic Neuritis; Humans; Immunoglobulins, Intravenous; Adrenal Cortex Hormones; Plasmapheresis; Network Meta-Analysis; Combined Modality Therapy; Immunologic Factors; Demyelinating Diseases
PubMed: 38457882
DOI: 10.1016/j.msard.2024.105521 -
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 -
International Journal of Molecular... Sep 2022Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of... (Review)
Review
Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015-2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.
Topics: Alzheimer Disease; Biomarkers; Humans; Lacrimal Apparatus Diseases; Multiple Sclerosis; Parkinson Disease; Tears
PubMed: 36077520
DOI: 10.3390/ijms231710123 -
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 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 -
Multiple Sclerosis (Houndmills,... May 2023Multiple sclerosis patients experience 3-6 times more seizures than the general population, but observations vary among studies. Seizure risk in disease-modifying... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis patients experience 3-6 times more seizures than the general population, but observations vary among studies. Seizure risk in disease-modifying therapy recipients remains unknown.
OBJECTIVE
The objective of this study was to compare seizure risk in multiple sclerosis patients receiving disease-modifying therapy versus placebo.
METHODS
MEDLINE(OVID), Embase, CINAHL, and ClinicalTrials.gov were searched from database inception until August 2021. Phase 2-3 randomized, placebo-controlled trials reporting efficacy and safety data for disease-modifying therapies were included. Network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using Bayesian random effects model for individual and pooled (by drug target) therapies. Main outcome was log seizure risk ratios [95% credible intervals]. Sensitivity analysis included meta-analysis of non-zero-event studies.
RESULTS
A total of 1993 citations and 331 full-texts were screened. Fifty-six included studies (29,388 patients-disease-modifying therapy = 18,909; placebo = 10,479) reported 60 seizures (therapy = 41; placebo = 19). No individual therapy was associated with altered seizure risk ratio. Exceptions were daclizumab (-17.90 [-65.31; -0.65]) and rituximab (-24.86 [-82.71; -1.37]) trending toward lower risk ratio; cladribine (25.78 [0.94; 4.65]) and pegylated interferon-beta-1a (25.40 [0.78; 85.47]) trended toward higher risk ratio. Observations had wide credible intervals. Sensitivity analysis of 16 non-zero-event studies revealed no difference in risk ratio for pooled therapies (l0.32 [-0.94; 0.29]).
CONCLUSION
No evidence of association was found between disease-modifying therapy and seizure risk-this informs seizure management in multiple sclerosis patients.
Topics: Humans; Multiple Sclerosis; Network Meta-Analysis; Bayes Theorem; Seizures; Cladribine; Anticonvulsants
PubMed: 36802988
DOI: 10.1177/13524585231151400 -
Medicina (Kaunas, Lithuania) Dec 2022: Recent findings demonstrate that the transmigration of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) to the nervous system implicates severe neurotropic... (Meta-Analysis)
Meta-Analysis Review
: Recent findings demonstrate that the transmigration of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) to the nervous system implicates severe neurotropic pathologies, including the onset of the rare disease called Guillain-Barré syndrome (GBS) which is characterized by immune-mediated polyneuropathy. This study aimed to identify the predisposing factors and the clinical features of coronavirus disease 2019 (COVID-19)-induced GBS. : We have performed an analysis of 147 cases. A systematic review of the published research work was performed per the PRISMA statement to obtain individual participant data (IPD) for the meta-analysis. The search was conducted through PubMed, using the combined search terms "Guillain-Barré syndrome" and "COVID-19". All case reports and series in the English language with accessed full text were included in the search. : A systematic database search led to the retrieval of 112 peer-reviewed articles published between 1 April 2020, and 8 February 2022. The articles comprised 16 case series and 96 case reports containing IPD for 147 patients. Our findings showed that 77.6% of all cases were 40 years or older. Males comprised most of the cases (65.3%; = 96). The intensive care unit (ICU) admission was 44.9%, and the need for mechanical ventilation (MV) was 38.1%. The patients presented with hyporeflexia or areflexia (84.4%; = 124), lower limb strength and sensation impairment (93.2%; = 138), upper limb strength and sensation impairment (85.7; = 126), and somatic sensation impairment (72.8%; = 107). The patients presented with increased cerebral spinal fluid (CSF) protein levels (92%; = 92) and the presence of CSF albuminocytological dissociation (83.5%; = 71). The most common variant of GBS observed was acute inflammatory demyelinating polyneuropathy (AIDP). We found that predisposing factors concomitant with COVID-19 and GBS were male gender and older age. Among the cases, patient mortality was 10.9%. : A gap of knowledge exists regarding the complete spectrum of clinical characteristics of COVID-19-related GBS. Recent findings suggest that SARS-CoV-2 triggers GBS, as it follows a similar para-infectious pattern as the other viral agents contributing to the onset of GBS.
Topics: Humans; Male; Female; COVID-19; Guillain-Barre Syndrome; SARS-CoV-2; Intensive Care Units; Rare Diseases
PubMed: 36557036
DOI: 10.3390/medicina58121835 -
Neuroimmunomodulation 2022The association between air pollution and multiple sclerosis (MS) is not entirely clear. This meta-analysis was aimed at determining the correlation between particulate... (Meta-Analysis)
Meta-Analysis
The association between air pollution and multiple sclerosis (MS) is not entirely clear. This meta-analysis was aimed at determining the correlation between particulate matter (PM)2.5, PM10, and MS incidence/relapse. The literature search was performed in EMBASE, Web of Science, PubMed, and the gray literature. Sixteen articles were retrieved, and ten articles were included and evaluated. Three measures of association were used for the meta-analysis: odds ratio (cross-sectional and case-control studies), incidence rate ratio, or hazard ratio (cohort studies). Meta-analysis of those 3 studies on PM2.5 indicated that exposure to PM2.5 was associated with MS relapse and incidence ([95% confidence interval; CI] 1.178 [1.102, 1.279]), p > 0.05. Also, assessment of risk ratio for all studies showed a correlation between PMs (PM10 and PM2.5) and MS incidence and relapse ([95% CI] 1.28, [1.13-1.43]) p < 0.05. Collectively, we found that PM exposure (PM10 and PM2.5) in MS patients associates with the occurrence and relapse of disease.
Topics: Air Pollutants; Cross-Sectional Studies; Environmental Exposure; Humans; Multiple Sclerosis; Particulate Matter; Recurrence
PubMed: 34134109
DOI: 10.1159/000516559 -
Journal of Neurology Mar 2023Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies report mixed associations between the retinal nerve fiber layer (RNFL) thickness with cognitive and physical disability in persons with multiple sclerosis (PwMS). Systematic synthesis of these findings is crucial in deriving credible conclusions.
METHODS
Five databases were searched from their inception to March 2022. The inclusion criteria for studies were MS-specific and required RNFL and cognitive performance data in order to be analyzed. The selection processes followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The systematic review yielded 31 studies that investigated the association between RNFL thickness and cognitive performance. Twenty-two studies reported positive associations, and nine did not. The meta-analysis included 11 studies with a total of 782 PwMS with mean age of 40.5 years, mean Expanded Disability Status Scale (EDSS) of 2.7, and disease duration of 11.3 years. RNFL thickness was significantly associated Symbol Digit Modalities Test (pooled r = 0.306, p < 0.001), Paced Auditory Serial Addition Test (pooled r = 0.374, p < 0.001) and Word List Generation (WLG, pooled r = 0.177, p < 0.001). RNFL was also significantly correlated with visuospatial learning and memory tests (pooled r = 0.148, p = 0.042) and verbal learning and memory tests (pooled r = 0.245, p = 0.005). Within three eligible studies, no significant association between ganglion cell inner-plexiform layer and SDMT 0.083 (95% CI - 0.186, 0.352) was noted. The heterogeneity was high in all correlation studies (I > 63% and p < 0.008) except for the WLG and visuospatial memory findings.
CONCLUSION
RNFL thickness is associated with cognitive processing speed, verbal learning and memory, visual learning and memory, as well as verbal fluency in PwMS. The number of studies included in the meta-analyses were limited due to non-standardized reporting.
Topics: Humans; Adult; Multiple Sclerosis; Nerve Fibers; Tomography, Optical Coherence; Retina; Cognition
PubMed: 36396812
DOI: 10.1007/s00415-022-11449-5