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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 -
Journal of Clinical Medicine Dec 2023This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple... (Review)
Review
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
PubMed: 38137679
DOI: 10.3390/jcm12247610 -
Journal of the Neurological Sciences Nov 2023Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have demonstrated that people with multiple sclerosis (pwMS) experience visual impairments and neurodegenerative retinal processes. The disability progression in pwMS may be associated with retinal changes assessed with optical coherence tomography (OCT). This meta-analysis aims at synthesizing the correlations between OCT measurements of disability in pwMS.
METHODS
We systematically searched four databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) from inception to November 2022, then conducted a meta-analysis using a random effects model to determine the pooled correlation coefficient(r) between OCT measurements and disability scales by R version 4.2.3 with the meta version 6.2-1 package.
RESULTS
From 3129 studies, 100 studies were included. Among 9051 pwMS, the female-to-male ratio was 3.15:1, with a mean age of 39.57 ± 6.07 years. The mean disease duration and Expanded Disability Status Scale (EDSS) were 8.5 ± 3.7 and 2.7 ± 1.1, respectively. Among the pooled subgroup analyses, macular ganglion cell inner plexiform layer (mGCIPL) in patients with relapsing-remitting (pwRRMS) and peripapillary retinal nerve fiber layer (pRNFL) in patients with progressive MS (pwPMS) had strong correlations with EDSS, r = -0.33 (95% CI: -0.45 to -0.20, I = 45%, z-score = -4.86, p < 0.001) and r = -0.20 (95% CI:-0.58 to 0.26, I = 76%, z-score = -0.85, p = 0.395), respectively. According to subgroup analysis on pwMS without optic neuritis (ON) history, the largest correlation was seen between EDSS and macular ganglion cell complex (mGCC): r = -0.39 (95% CI: -0.70 to 0.04, I = 79%, z-score = -1.79, p = 0.073).
CONCLUSION
OCT measurements are correlated with disability in pwMS, and they can complement the comprehensive neurological visit as an additional paraclinical test.
Topics: Humans; Male; Female; Adult; Middle Aged; Multiple Sclerosis; Retinal Ganglion Cells; Tomography, Optical Coherence; Retina; Multiple Sclerosis, Chronic Progressive; Optic Neuritis
PubMed: 37924591
DOI: 10.1016/j.jns.2023.120847 -
Journal of Neuroradiology = Journal de... Feb 2024In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease.
METHODS
A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled.
RESULTS
Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16).
CONCLUSION
In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Brain; Gray Matter; White Matter; Disability Evaluation
PubMed: 38172026
DOI: 10.1016/j.neurad.2023.11.007 -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
Multiple Sclerosis (Houndmills,... Dec 2023Persons with multiple sclerosis (pwMS) might be particularly well suited to benefit from digital health applications because they are, on average, younger and less... (Review)
Review
BACKGROUND
Persons with multiple sclerosis (pwMS) might be particularly well suited to benefit from digital health applications because they are, on average, younger and less severely disabled than patients with many other chronic diseases. Many digital health applications for pwMS have been developed.
OBJECTIVES
Analysis of the evidence of digital health applications to improve health outcomes from a patient perspective.
METHODS
A systematic review was performed on all randomized controlled trials (RCTs) that have studied mobile health interventions for pwMS, that is, which can be applied with a smartphone, tablet, or laptop to improve patient-reported outcomes.
RESULTS
Of the 1127 articles identified in the literature search, 13 RCTs fit the inclusion criteria. Two trials studied messaging systems, two depression interventions, one addressed MS fatigue, five cognition, and three mobility issues, of which two focused on spasticity management. One trial aimed to enhance physical activity. Most were pilot studies that cannot yield definitive conclusions regarding efficacy. One depression intervention and one fatigue intervention showed significant results across several outcomes.
CONCLUSION
Several mobile self-guided digital health applications for pwMS have been tested in RCTs, and two interventions targeting depression and fatigue have demonstrated significant effects. Challenges remain regarding implementation into routine care.
Topics: Humans; Smartphone; Chronic Disease; Multiple Sclerosis; Telemedicine; Fatigue
PubMed: 37897326
DOI: 10.1177/13524585231201089 -
Multiple Sclerosis and Related Disorders Dec 2023The effectiveness of electrical stimulation therapy (EST) for pain, depression, fatigue, disability, and quality of life in multiple sclerosis (MS) remains uncertain.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effectiveness of electrical stimulation therapy (EST) for pain, depression, fatigue, disability, and quality of life in multiple sclerosis (MS) remains uncertain. This study aims to analyze and discuss the efficacy of various EST treatments in alleviating pain among MS patients.
METHODS
The primary search was conducted using PubMed, Web of Science, Cochrane Library, Embase, and the Cumulative Index of Nursing and Allied Health Literature databases until September 25, 2023. Randomized controlled trials (RCTs) including patients with MS pain receiving EST compared with other therapies were included. Pain intensity, quality of life, and neuropsychiatric symptoms were reported. The mean difference (MD) with 95 % confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size.
RESULTS
Ten RCTs containing 315 participants were included. The pooled data from 8 trials including 267 participants showed that the EST was superior in alleviating pain (MD = -1.75, 95 % CI -2.85--0.64, P = 0.002, I=73 %) evaluated by the visual analog scale. In subgroup analysis, medium-term EST treatment showed the highest effect size compared to short-term and long-term treatment (MD = -2.17, 95 % CI -3.51--0.84, P = 0.001, I = 0 %). However, no significant differences were found in terms of pain-related quality of life, depression, fatigue, and pain-related disability. No adverse events related to EST were reported. A high risk of bias was identified in three of the ten included studies.
CONCLUSIONS
EST is effective and safe for alleviating pain in MS, but it should be noted that limited sample sizes and methodological issues were present in the included studies. More robust assessment criteria and high-quality RCTs are required for patients with MS.
TRIAL REGISTRATION
CRD42023406787. (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406787).
Topics: Humans; Electric Stimulation Therapy; Fatigue; Pain; Quality of Life; Multiple Sclerosis; Pain Management
PubMed: 37944194
DOI: 10.1016/j.msard.2023.105114 -
Journal of the Neurological Sciences Nov 2023Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical... (Review)
Review
INTRODUCTION
Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical manifestations and imaging patterns need further elucidation.
OBJECTIVE/AIMS
To investigate the clinical profiles, antibody associations, neuroimaging patterns, treatments, and outcomes of PNS and AIE.
METHODS
A systematic review of 379 articles published between 2014 and 2023 was conducted. Of the 55 studies screened, 333 patients were diagnosed with either PNS or AIE and tested positive for novel antibodies. Data on demographics, symptoms, imaging, antibodies, cancer associations, treatment, and outcomes were extracted.
RESULTS
The study included 333 patients (mean age 54 years, 67% males) with PNS and AIE positive for various novel antibodies. 84% had central nervous system issues like cognitive impairment (53%), rhombencephalitis (17%), and cerebellar disorders (24%). Neuroimaging revealed distinct patterns with high-risk antibodies associated with brainstem lesions in 98%, cerebellar in 91%, hippocampal in 98%, basal ganglia in 75%, and spinal cord in 91%, while low/intermediate-risk antibodies were associated with medial temporal lobe lesions in 71% and other cortical/subcortical lesions in 55%. High-risk antibodies were associated with younger males, deep brain lesions, and increased mortality of 61%, while low/intermediate-risk antibodies were associated with females, cortical/subcortical lesions, and better outcomes with 39% mortality. Associated cancers included seminomas (23%), lung (19%), ovarian (2%), and breast (2%). Treatments included IVIG, chemotherapy, and plasmapheresis. Overall mortality was 25% in this cohort.
CONCLUSION
PNS and AIE have distinct clinical and radiological patterns based on antibody profiles. High-risk antibodies are associated with increased mortality while low/intermediate-risk antibodies are associated with improved outcomes. Appropriate imaging and antibody testing are critical for accurate diagnosis.
Topics: Male; Female; Humans; Middle Aged; Nervous System Diseases; Paraneoplastic Syndromes, Nervous System; Autoantibodies; Neoplasms; Neuroimaging
PubMed: 37856996
DOI: 10.1016/j.jns.2023.120830 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
Journal of Family & Reproductive Health Dec 2023Multiple sclerosis is an autoimmune disease of central nervous system (CNS). There are a few articles studying the risk factors of developing MS in men. Male infertility... (Review)
Review
OBJECTIVE
Multiple sclerosis is an autoimmune disease of central nervous system (CNS). There are a few articles studying the risk factors of developing MS in men. Male infertility can stem from a range of etiological factors such as genetics or environment. In the context of MS, research suggests a potential link, possibly due to shared immunological and inflammatory mechanisms. Therefore, we designed this study to evaluate the relationship between male infertility and MS development.
MATERIALS AND METHODS
We systematically searched PubMed, Embase, Scopus, web of science, Google scholar and gray literature including references of the references as well as conference papers which were published up to June 2021. The search strategy in PubMed was ("Infertility, Male"[Mesh] OR [Male Infertility] OR [Sterility, Male] OR [Male Sterility] OR [Subfertility, Male] OR [Male Subfertility] OR [Sub-Fertility, Male] OR [Male Sub-Fertility] OR [Sub Fertility, Male]) AND ("Multiple Sclerosis"[Mesh] OR [Sclerosis, Multiple] OR [Sclerosis, disseminated] OR [Disseminated Sclerosis] OR [MS] OR [Multiple Sclerosis, Acute Fulminating]) AND ("Testicular Diseases"[Mesh] OR [Disease, Testicular] OR [Diseases, Testicular] OR [Testicular Disease]) AND ("Multiple Sclerosis"[Mesh] OR [Sclerosis, Multiple] OR [Sclerosis, disseminated] OR [Disseminated Sclerosis] OR [Multiple Sclerosis, Acute Fulminating] OR [MS]).
RESULTS
The literature search revealed 197 articles, after deleting duplicates 109 remained. For the meta-analysis, 3 studies were included. Totally, 2090 MS cases as well as 3895562 healthy subjects were enrolled. One hundred and fourteen infertile men were in MS group and 139716 infertile men were in controls. The pooled OR for male factor infertility and odds of developing MS was1.87 (95% CI: 0.89-3.94) (I=86.1%, P=0.001).
CONCLUSION
The results of this systematic review and meta-analysis show that there is no relationship between male factor infertility and risk of MS.
PubMed: 38807619
DOI: 10.18502/jfrh.v17i4.14590