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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 -
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 -
Journal of Clinical Neuroscience :... Jan 2024Considering the different results regarding the correlation between Magnetic Resonance Imaging (MRI) structural measures and cognitive dysfunction in patients with MS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Considering the different results regarding the correlation between Magnetic Resonance Imaging (MRI) structural measures and cognitive dysfunction in patients with MS, we aimed to perform a systematic review and meta-analysis study to investigate the correlation between T1 and T2 weighted lesions and cognitive scores to find the most robust MRI markers for cognitive function in MS population.
METHODS
The literature of this paper was identified through a comprehensive search of electronic datasets including PubMed, Scopus, Web of Science, and Embase in February 2022. Studies that reported the correlation between cognitive status and T1 and T2 weighted lesions in MS patients were selected.
RESULTS
21 studies with a total of 3771 MS patients with mean ages ranging from 30 to 57 years were entered into our study. Our analysis revealed that the volume of T1 lesions was significantly correlated with Symbol Digit Modality test (SDMT) (r: -0.30, 95 %CI: -0.59, -0.01) and Paced Auditory Serial-Addition Task (PASAT) scores (r: -0.23, 95 %CI: -0.36, -0.10). We investigated the correlation between T2 lesions and cognitive scores. The pooled estimates of z scores were significant for SDMT (r: -0.27, 95 %CI: -0.51, -0.03) and PASAT (r: -0.27, 95 %CI: -0.41, -0.13).
CONCLUSION
In conclusion, our systematic review and meta-analysis study provides strong evidence of the correlation between T1 and T2 lesions and cognitive function in MS patients. Further research is needed to explore the potential mechanisms underlying this relationship and to develop targeted interventions to improve cognitive outcomes in MS patients.
Topics: Humans; Adult; Middle Aged; Multiple Sclerosis; Cognition; Cognitive Dysfunction; Magnetic Resonance Imaging; Neuropsychological Tests
PubMed: 37952373
DOI: 10.1016/j.jocn.2023.11.014 -
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 -
BMC Neurology Nov 2023Fatigue is the most disabling symptom for individuals with multiple sclerosis (MS), which can significantly affect postural control (PC) by impairing the ability of the...
BACKGROUND
Fatigue is the most disabling symptom for individuals with multiple sclerosis (MS), which can significantly affect postural control (PC) by impairing the ability of the central nervous system to modulate sensory inputs and coordinate motor responses. This systematic review aimed to investigate the effect of fatigue on PC in individuals with MS..
METHODS
This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and registered in PROSPERO with ID CRD42022376262. A systematic search was performed in the Web of Science, PubMed, Scopus, and Google Scholar until January 2023, and a manual search was performed using the reference lists of included studies. Two authors independently selected the studies, extracted data, and evaluated their methodological quality using the Downs and Black checklist. The process was later discussed with a third author..
RESULTS
Five studies were included in this review, of which consistent evidence investigating a direct relationship between fatigue and PC in individuals with MS. All the studies reported negative effects on PC. Four studies employed walking tests as their primary protocol for inducing fatigue, while one study implemented a strength testing protocol for both legs, serving as a fatigue-inducing activity.
CONCLUSIONS
The evidence suggests that individuals with MS may experience PC deficits due to fatigue. However, the present body of literature exhibits limitations regarding its quality and methodology. Gender differences, balance, fatigue task, and muscle function are essential factors that need to be considered when investigating the relationship between fatigue and PC deficits in MS. Further high-quality research is necessary to comprehend the complex interplay between MS-related fatigue and PC deficits after physical activity.
Topics: Humans; Exercise; Multiple Sclerosis; Fatigue; Postural Balance
PubMed: 37978449
DOI: 10.1186/s12883-023-03464-4 -
Vaccines Jul 2023The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central... (Review)
Review
BACKGROUND
The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination.
METHODS
We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology.
RESULTS
A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, = 0.03).
CONCLUSIONS
Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients.
PubMed: 37515041
DOI: 10.3390/vaccines11071225 -
Journal of the Peripheral Nervous... Jun 2024Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid...
Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.
Topics: Humans; Chemokines; Cytokines; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 38600685
DOI: 10.1111/jns.12622 -
Applied Neuropsychology. Adult Aug 2023Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory and demyelinating disease that affects the Central Nervous System (CNS). It is the most common disabling... (Review)
Review
Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory and demyelinating disease that affects the Central Nervous System (CNS). It is the most common disabling neurological disease in young patients not caused by traumatic shock. Depending on how symptoms appear and how often they occur, there are different subtypes of MS. One of them is the relapsing-remitting phenotype (R-R), which the symptoms appear in the form of isolated outbreaks which, little by little, are causing the increase of the disease and its sequelae. MS encompasses a wide variety of symptoms, including possible cognitive impairment. In the literature there is no clear methodology and a defined and structured consensus to carry out neuropsychological rehabilitation processes in this group. This study aims to review and synthesize the available scientific evidence about the neuropsychological intervention on cognitive impairment of people with multiple sclerosis, relapsing-remitting subtype. Keywords for database search (Pubmed and Wos) were established, as well as inclusion and exclusion criteria. Then, the articles were selected according to inclusion and exclusion criteria; methodological quality criteria were applied. Articles published in the last 10 years were included. Fifteen articles that met the established criteria were selected. Most of these studies identify as effective their cognitive rehabilitation programs, some of them showed changes in neural structures after rehabilitation. It seems that cognitive rehabilitation is effective in influencing cognitive deterioration in R-R MS. This highlights the importance of neuropsychological evaluation and intervention from the early stages of the disease.
PubMed: 37641201
DOI: 10.1080/23279095.2023.2248642 -
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 -
European Journal of Neurology Feb 2024The association between Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is debated. This study reappraises, after three... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The association between Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is debated. This study reappraises, after three pandemic years, the epidemiological data and the features of GBS in SARS-CoV-2 patients.
METHODS
A systematic review and meta-analysis of case reports/series and cohort studies published between 1 January 2020 and 19 April 2023 was performed.
RESULTS
In all, 209 case reports/series (304 patients) and 26 cohort studies were included. The risk of GBS in northern Italy during the first pandemic wave was 2.85 times increased (95% confidence interval [CI] 1.54; 5.25) whereas in some countries the risk during the first pandemic year was 0.17 times reduced (risk ratio 0.83, 95% CI 0.75; 0.93). The incidence of GBS in SARS-CoV-2 Italian hospitalized cohorts was 8.55 per 1000 (95% CI 5.33; 12.49) with an estimated incidence of 0.13 GBS per 1000 in the SARS-CoV-2 infected population. In European cohorts the pooled rate of GBS with SARS-CoV-2 infection was 61.3% of the total. GBS patients with SARS-CoV-2 infection showed more frequently, but not differently from non-infected patients, the classical clinical presentation and the demyelinating subtype. Cranial nerves were more frequently involved in SARS-CoV-2 infected patients.
CONCLUSIONS
An increased risk of GBS occurred in northern Italy during early COVID-19 pandemic. The recognition of the 'Italian factor' reconciles contrasting results of the epidemiological studies. The slightly reduced GBS risk in other countries and the relatively high frequency of GBS associated with SARS-CoV-2 infection can be explained by the adopted health measures that decreased the circulation of other GBS infective antecedents.
Topics: Humans; COVID-19; SARS-CoV-2; Guillain-Barre Syndrome; Pandemics; Italy
PubMed: 37823707
DOI: 10.1111/ene.16094