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Multiple Sclerosis and Related Disorders Jul 2024Magnetic resonance imaging [MRI] findings in Neuromyelitis optica spectrum disorder [NMOSD] and Multiple Sclerosis [MS] patients could lead us to discriminate toward... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnetic resonance imaging [MRI] findings in Neuromyelitis optica spectrum disorder [NMOSD] and Multiple Sclerosis [MS] patients could lead us to discriminate toward them. For instance, U-fiber and Dawson's finger-type lesions are suggestive of MS, however linear ependymal lesions raise the possibility of NMOSD. Recently, artificial intelligence [AI] models have been used to discriminate between NMOSD and MS based on MRI features. In this study, we aim to systematically review the capability of AI algorithms in NMOSD and MS discrimination based on MRI features.
METHOD
We searched PubMed, Scopus, Web of Sciences, Embase, and IEEE databases up to August 2023. All studies that used AI-based algorithms to discriminate between NMOSD and MS using MRI features were included, without any restriction in time, region, race, and age. Data on NMOSD and MS patients, Aquaporin-4 antibodies [AQP4-Ab] status, diagnosis criteria, performance metrics (accuracy, sensitivity, specificity, and AUC), artificial intelligence paradigm, MR imaging, and used features were extracted. This study is registered with PROSPERO, CRD42023465265.
RESULTS
Fifteen studies were included in this systematic review, with sample sizes ranging between 53 and 351. 1,362 MS patients and 1,118 NMOSD patients were included in our systematic review. AQP4-Ab was positive in 94.9% of NMOSD patients in 9 studies. Eight studies used machine learning [ML] as a classifier, while 7 used deep learning [DL]. AI models based on only MRI or MRI and clinical features yielded a pooled accuracy of 82% (95% CI: 78-86%), sensitivity of 83% (95% CI: 79-88%), and specificity of 80% (95% CI: 75-86%). In subgroup analysis, using only MRI features yielded an accuracy, sensitivity, and specificity of 83% (95% CI: 78-88%), 81% (95% CI: 76-87%), and 84% (95% CI: 79-89%), respectively.
CONCLUSION
AI models based on MRI features showed a high potential to discriminate between NMOSD and MS. However, heterogeneity in MR imaging, model evaluation, and reporting performance metrics, among other confounders, affected the reliability of our results. Well-designed studies on multicentric datasets, standardized imaging and evaluation protocols, and detailed transparent reporting of results are needed to reach optimal performance.
Topics: Humans; Neuromyelitis Optica; Magnetic Resonance Imaging; Multiple Sclerosis; Artificial Intelligence; Algorithms; Diagnosis, Differential
PubMed: 38781885
DOI: 10.1016/j.msard.2024.105682 -
Neurotoxicology May 2024The global coronavirus 2019 (COVID-19) pandemic began in early 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mid-2020 the CIAO...
BACKGROUND
The global coronavirus 2019 (COVID-19) pandemic began in early 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In mid-2020 the CIAO (Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway Framework) project was established, bringing together over 75 interdisciplinary scientists worldwide to collaboratively investigate the underlying biological mechanisms of COVID-19 and consolidate the data using the Adverse Outcome Pathway (AOP) Framework. Neurological symptoms such as anosmia and encephalitis have been frequently reported to be associated with infection with SARS-CoV-2.
OBJECTIVE
Within CIAO, a working group was formed to conduct a systematic scoping review of COVID-19 and its related neurological symptoms to determine which key events and modulating factors are most commonly reported and to identify knowledge gaps.
DESIGN
LitCOVID was used to retrieve 86,075 papers of which 10,244 contained relevant keywords. After title and abstract screening, 2,328 remained and their full texts were reviewed based on predefined inclusion and exclusion criteria. 991 studies fulfilled the inclusion criteria and were retrieved to conduct knowledge synthesis.
RESULTS
The majority of publications reported human observational studies. Early key events were less likely to be reported compared to middle and late key events/adverse outcomes. The majority of modulating factors described related to age or sex. Less recognised COVID-19 associated AO or neurological effects of COVID-19 were also identified including multiple sclerosis/demyelination, neurodegeneration/cognitive effects and peripheral neuronal effects.
CONCLUSION
There were many methodological and reporting issues noted in the reviewed studies. In particular, publication abstracts would benefit from clearer reporting of the methods and endpoints used and the key findings, to ensure relevant papers are included when systematic reviews are conducted. The information extracted from the scoping review may be useful in understanding the mechanisms of neurological effects of COVID-19 and to further develop or support existing AOPs linking COVID-19 and its neurological key events and adverse outcomes. Further evaluation of the less recognised COVID-19 effects is needed.
PubMed: 38763473
DOI: 10.1016/j.neuro.2024.05.003 -
Journal of Neuroimmunology Jun 2024A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift... (Review)
Review
A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs). In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic. The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group. Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies. De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies. Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.
Topics: Humans; Multiple Sclerosis; Aged; Aging; Immunologic Factors
PubMed: 38761652
DOI: 10.1016/j.jneuroim.2024.578368 -
Clinical Neurophysiology : Official... Jul 2024This systematic review aimed to evaluate if event-related potentials (ERPs) can be a relevant tool for cognitive dysfunction diagnosis in Multiple Sclerosis (MS). (Review)
Review
OBJECTIVE
This systematic review aimed to evaluate if event-related potentials (ERPs) can be a relevant tool for cognitive dysfunction diagnosis in Multiple Sclerosis (MS).
METHODS
Four databases were consulted (PubMed, Embase, Scielo, and Web of Science). The included studies should include adults with clear MS diagnoses, independently of having cognitive complaints, and all should have been submitted to ERPs (P300, N400 or mismatch negativity (MMN)). The main outcomes evaluated were ERPs' amplitude and/or latency.
RESULTS
425 studies were obtained initially from all databases, with 26 studies fulfilling the eligibility criteria. P300 was the most used ERP (25 studies), showing a reduced amplitude or an increased latency in 84% of those. N400 was evaluated in one study, showing also abnormal results. MMN was addressed in two studies with inconsistent findings. Some studies further suggest that ERPs may show earlier abnormal results compared with neuropsychological tests.
CONCLUSIONS
Most MS patient groups revealed ERP abnormalities, suggesting that these neurophysiological tests may be a relevant and appropriate diagnostic aid method for cognitive impairment in MS.
SIGNIFICANCE
The use of ERPs in MS patients seems able to demonstrate cognitive impairment and its use should be considered as part of the regular patient evaluation.
Topics: Humans; Multiple Sclerosis; Evoked Potentials; Cognitive Dysfunction; Electroencephalography
PubMed: 38759513
DOI: 10.1016/j.clinph.2024.04.024 -
Multiple Sclerosis and Related Disorders Jul 2024Multiple sclerosis (MS) is a disabling neurological disease that causes cognitive impairment and mental problems that occur in all MS phenotypes but are most common in... (Meta-Analysis)
Meta-Analysis
Effects of virtual reality-based rehabilitation on cognitive function and mood in multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Multiple sclerosis (MS) is a disabling neurological disease that causes cognitive impairment and mental problems that occur in all MS phenotypes but are most common in patients with secondary progressive MS. Various degrees of cognitive impairment and mental health concerns are common among patients with MS (PwMS). Virtual reality (VR)-based rehabilitation is an innovative approach aimed at enhancing cognitive function and mood in PwMS. This study aims to perform a meta-analysis to assess the effects of VR-based rehabilitation on cognitive function and mood in PwMS.
METHODS
Using PubMed, Embase, the Cochrane Library, Web of Science, and the Physiotherapy Evidence Database (PEDro), a thorough database search was performed to identify randomized controlled trials (RCTs) examining the effects of VR on PwMS. Trials published until October 31, 2023, that satisfied our predetermined inclusion and exclusion criteria were included. Data were extracted, literature was examined, and the methodological quality of the included trials was assessed. StataSE version 16 was used for the meta-analysis.
RESULTS
Our meta-analysis included 461 patients from 10 RCTs.
PRIMARY OUTCOMES
The Montreal Cognitive Assessment (MoCA) (weighted mean difference [WMD]=1.93, 95 % confidence interval [CI]=0.51-3.36, P = 0.008, I² = 75.4 %) the Spatial Recall Test (SPART) (WMD=3.57, 95 % CI=1.65-5.50, P < 0.001, I² = 0 %), immediate recall (standard mean difference [SMD]=0.37, 95 % CI=0.10-0.64, P = 0.007, I² = 0 %) and delayed recall ([SMD]=0.30, 95 % CI=0.06-0.54, P = 0.013, I² = 35.4 %) showed improvements in comparison to the control group in terms of global cognitive function immediate recall, delayed recall, and visuospatial abilities.
SECONDARY OUTCOMES
Compared to the control group, anxiety improved (standard mean difference [SMD]=0.36, 95 % CI=0.10-0.62, P = 0.007, I² = 43.1 %). However, there were no significant differences in processing speed, attention, working memory or depression.
CONCLUSIONS
This systematic review provides valuable evidence for improving cognitive function and mood in PwMS through VR-based rehabilitation. In the future, VR-based rehabilitation may be a potential method to treat cognitive function and emotional symptoms of MS.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO; identifier: CRD42023474467.
Topics: Humans; Affect; Cognition; Cognitive Dysfunction; Multiple Sclerosis; Neurological Rehabilitation; Randomized Controlled Trials as Topic; Virtual Reality; Virtual Reality Exposure Therapy
PubMed: 38735202
DOI: 10.1016/j.msard.2024.105643 -
Neurologia I Neurochirurgia Polska 2024Multiple sclerosis (MS) is a central nervous system (CNS) disease associated with inflammation, demyelination, and neurodegeneration. It affects more than 2 million...
INTRODUCTION
Multiple sclerosis (MS) is a central nervous system (CNS) disease associated with inflammation, demyelination, and neurodegeneration. It affects more than 2 million people globally, and usually occurs in young adults, three-quarters of whom are women. Importantly, accurate diagnosis and treatment are essential, as this disease can lead to the rapid development of disability. The choroid plexus (CP) is a structure widely known as the main cerebrospinal fluid source. However, it is also involved in immune cell trafficking to the cerebrospinal fluid, which is increased in different neurological disorders, particularly those associated with neuroinflammation. As MS is generally thought to be caused by an autoimmune process, it has been suggested that the choroid plexus may play a significant role in its pathogenesis, manifesting via changes in imaging characteristics.
MATERIAL AND METHODS
Although research regarding this topic has been very limited, the results of the available studies appear promising. To further investigate this subject, we performed a systematic literature review according to the PRISMA 2020 guidelines. The PubMed and Embase databases were searched for relevant articles, and after thorough analysis, 16 studies were included in our review.
RESULTS
CP volume was significantly increased in MS patients compared to healthy individuals. Furthermore, some studies found that CP enlargement occurs even before a definite diagnosis. Moreover, a few articles reported correlations between CP volume and brain atrophy, or even disease severity.
CONCLUSIONS
Our findings show that CP imaging has the potential to become a novel and valuable tool in multiple sclerosis management.
Topics: Humans; Multiple Sclerosis; Choroid Plexus; Magnetic Resonance Imaging; Female; Neuroimaging; Adult
PubMed: 38721672
DOI: 10.5603/pjnns.98706 -
Pharmacoepidemiology and Drug Safety May 2024Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological... (Review)
Review
BACKGROUND
Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real-world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing-remitting multiple sclerosis as an example.
STUDY DESIGN AND SETTING
A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta-analysis together with posterior predictive distributions, the drug-specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies.
RESULTS
Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease-modifying therapies.
CONCLUSION
In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing-remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population.
Topics: Humans; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic; Observational Studies as Topic; Treatment Outcome; Research Design
PubMed: 38720409
DOI: 10.1002/pds.5810 -
Clinical and Translational Science May 2024No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and... (Review)
Review
No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.
Topics: Humans; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; Adult; Multiple Sclerosis, Relapsing-Remitting; Child; Research Design; Endpoint Determination; Randomized Controlled Trials as Topic
PubMed: 38708586
DOI: 10.1111/cts.13794 -
Midwifery Jul 2024Little is known regarding the impact of multiple sclerosis (MS) on maternal and neonatal outcomes. Consequently, this systematic review and meta-analysis aimed to study... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Little is known regarding the impact of multiple sclerosis (MS) on maternal and neonatal outcomes. Consequently, this systematic review and meta-analysis aimed to study the impacts of MS on maternal and neonatal outcomes in pregnant women with a history of MS.
METHODS
This review was designed in line with the PRISMA guidelines. Two researchers conducted independent reviews of the literature without time restrictions until January 2023 using international databases, including PubMed, Web of Science, CINAHL Plus, Embase, Scopus, Science Direct, and Google Scholar. A random-effect meta-analysis, using the db metan command in Stata 17.2, was used to calculate the pooled measure of association.
RESULTS
The meta-analysis identified 15 studies involving 33,174,541 pregnant women (32,191 with MS and 33,142,350 as controls). The findings indicate that women with a history of MS are at an increased risk of cesarean delivery (OR=1.28, 95% Confidence Intervals [CI]: 1.14-1.45, p-value: 0.042). Also, these women are at higher risk of neonatal outcomes, such as preterm birth (OR= 1.39, 95% CI: 1.08-1.78, p-value: 0.02), congenital malformations (OR=1.32, 95%CI: 1.16-1.50, p-value: 0.031), Apgar score <7 (OR=2.13, 95% CI: 1.19-3.79, p-value: 0.03), and small for gestational age (OR=1.27, 95% CI: 1.08-1.51, p-value: 0.040).
CONCLUSION
Pregnant women with MS have a greater chance of adverse pregnancy results than pregnant women without MS. Consequently, pregnant women with MS should create detailed before and after pregnancy plans, in consultation with their doctors, spouses, families, and friends, regarding the necessary care and supplements. Future studies applying a prospective cohort design that control for potential confounders are needed to further validate the findings.
Topics: Humans; Pregnancy; Female; Multiple Sclerosis; Pregnancy Outcome; Infant, Newborn; Pregnant Women; Pregnancy Complications; Adult
PubMed: 38703425
DOI: 10.1016/j.midw.2024.104004 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971