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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 -
European Journal of Neurology Aug 2023Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed.
METHODS
The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted.
RESULTS
Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%).
CONCLUSION
This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.
Topics: Humans; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Immunoglobulins, Intravenous; Immunosuppressive Agents; Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation
PubMed: 37170791
DOI: 10.1111/ene.15857 -
Neurologia Mar 2024To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal... (Review)
Review
OBJECTIVE
To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal and the specific characteristics of euthanasia in some of these diseases, and to show the evolution of euthanasia figures.
METHODS
We conducted a systematic literature review.
RESULTS
Dementia, motor neuron disease, multiple sclerosis, and Parkinson's disease are the neurological diseases that most frequently motivate requests for euthanasia or assisted suicide. Requests related to dementia constitute the largest group, are growing, and raise additional ethical and legal issues due to these patients' diminished decision-making capacity. In some countries, the ratios of euthanasia requests to all cases of multiple sclerosis, motor neuron disease, or Huntington disease are higher than for any other disease.
CONCLUSIONS
After cancer, neurological diseases are the most frequent reason for requesting euthanasia or assisted suicide.
Topics: Humans; Suicide, Assisted; Euthanasia; Nervous System Diseases; Huntington Disease; Multiple Sclerosis; Motor Neuron Disease
PubMed: 38272260
DOI: 10.1016/j.nrleng.2024.01.007 -
Neuroscience and Biobehavioral Reviews Nov 2023Chronic pain is the most disability symptom related to multiple sclerosis (MS) brain lesions and can also generate anxiety and depression. There are no updated reports... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of neuropathic pain in multiple sclerosis: Prevalence, clinical types, sex dimorphism, and increased depression and anxiety symptoms.
Chronic pain is the most disability symptom related to multiple sclerosis (MS) brain lesions and can also generate anxiety and depression. There are no updated reports of the general prevalence of neuropathic pain, MS clinical types, sex dimorphism, and its association with depression and anxiety. The protocol was listed in PROSPERO (CRD42022303571). The article selection resulted in 24 studies with a low risk of bias. The prevalence of neuropathic pain in MS patients was 26.8% with higher levels of depression and anxiety. We also observed that female patients (74.2%) have a higher prevalence of neuropathic pain than males (28.9%). We showed the enhanced prevalence of neuropathic pain using the female and male data (58.9%) compared to the total prevalence (26.8%). In addition, the SPMS (40.3%) presented an increased prevalence of neuropathic pain compared to PPMS (15.6%). Thus, we demonstrated the association between neuropathic pain, depression and anxiety symptoms and the influence of diagnosis, age, disease score, and disease duration in the increased prevalence of neuropathic pain in MS patients.
Topics: Humans; Male; Female; Multiple Sclerosis; Prevalence; Depression; Sex Characteristics; Neuralgia; Anxiety
PubMed: 37777076
DOI: 10.1016/j.neubiorev.2023.105401 -
Multiple Sclerosis and Related Disorders Nov 2023Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard... (Review)
Review
INTRODUCTION
Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS). We conducted a systematic review to 1) understand whether fatigue is included as an outcome in MS trials of DMTs; 2) determine the effects on fatigue of treating MS with DMTs and 3) assess the quality of MS trials including fatigue as an outcome.
METHODS
Two independent researchers systematically searched MEDLINE, EMBASE and ClinicalTrials.gov from 1993 to January 2023 for RCTs that measured fatigue as an outcome. Adherence to reporting standards was assessed with the Consolidated Standards of Reporting Trials (CONSORT)-Patient-Reported Outcomes (PRO), while the risk of bias (RoB) was assessed with the RoB 2 tool by the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review protocol was registered in PROSPERO (CRD42022383321).
RESULTS
The search strategy identified 130 RCTs of DMTs of which 7 (5%) assessed fatigue as an outcome. Of the 7 trials, only two presented statistically significant results. In addition, the reporting of fatigue among RCTs was suboptimal with a mean adherence to the CONSORT-PRO Statement of 36% across all trials. Of the 7 trials included, four were assessed as 'high' RoB..
CONCLUSIONS
Fatigue has a major impact on PwMS yet there is limited trial-based evidence on the impact of DMTs on fatigue. Assessment of fatigue as an outcome is underrepresented in trials of DMTs and the reporting of PRO trial data is suboptimal. Thus, it is imperative that MS researchers conduct RCTs that include fatigue as an outcome, to support clinicians and people with MS (PwMS) to consider the impact of the different DMTs on fatigue.
Topics: Humans; Fatigue; Multiple Sclerosis; Patient Reported Outcome Measures; Reference Standards; Systematic Reviews as Topic
PubMed: 37839365
DOI: 10.1016/j.msard.2023.105065 -
Inflammopharmacology Dec 2023The use of anti-CD20 monoclonal antibodies, such as rituximab and ocrelizumab, has emerged as a matter of concern, in patients with coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of anti-CD20 monoclonal antibodies, such as rituximab and ocrelizumab, has emerged as a matter of concern, in patients with coronavirus disease 2019 (COVID-19).
OBJECTIVE
We aimed to summarize the overall evidence on the pre-admission/pre-diagnosis use of anti-CD20 among patients with COVID-19 with regards to mortality and severe illness outcomes.
METHODS
A systematic literature search with no language restriction was performed in electronic databases, including PubMed, Google Scholar, Scopus, and preprint servers (medRxiv, Research Square, SSRN), to identify eligible studies published up to June 13, 2023. The outcomes of interest were the development of severe illness and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio for outcomes of interest using anti-CD20 monoclonal antibodies relative to non-use of anti-CD20 monoclonal antibodies, at 95% confidence intervals.
RESULTS
Our systematic review and meta-analysis revealed significantly increased odds for development of severe illness (pooled odds ratio 2.95; 95% confidence interval 2.30, 3.78; n = 534,349) and significantly increased odds for mortality (pooled odds ratio 2.14; 95% confidence interval 1.37, 3.35; n = 333,462) with the use of anti-CD20 monoclonal antibodies, relative to non-use of anti-CD20 monoclonal antibodies, in patients with COVID-19.
CONCLUSION
Healthcare practitioners should exercise caution when prescribing these anti-CD20 monoclonal antibodies during the COVID-19 pandemic to patients who are indicated for these agents, particularly those with underlying conditions like multiple sclerosis or rheumatoid arthritis.
Topics: Humans; COVID-19; Pandemics; Antibodies, Monoclonal; Antineoplastic Agents; Multiple Sclerosis
PubMed: 37804462
DOI: 10.1007/s10787-023-01349-z -
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 -
Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035