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Scientific Reports Mar 2024Socio-cognitive impairment is frequent in multiple sclerosis (MS). However, little is known about the relationship between other potentially relevant clinical symptoms... (Meta-Analysis)
Meta-Analysis
Socio-cognitive impairment is frequent in multiple sclerosis (MS). However, little is known about the relationship between other potentially relevant clinical symptoms (i.e., cognition, depression, fatigue) and the degree of socio-cognitive impairment, and neural mechanisms underlying socio-cognitive deficits in MS. Therefore, we meta-analytically quantified socio-cognitive impairment in MS. A systematic literature search in MEDLINE Ovid, Web of Science Core Collection, CENTRAL, and PsycInfo was conducted until December 2022. Studies investigating affective or cognitive theory of mind (a/cToM), visual perspective taking (VPT) and social decision making (SDM) in MS patients relative to healthy controls were included. Risk-of-bias (RoB) was assessed using the CLARITY group "Tool for Assessing RoB in Cohort Studies". Mediation analysis investigated the contribution of clinical symptoms to socio-cognitive impairment. In total, n = 8534 studies were screened, 58 were included in the systematic review, 27 in the meta-analyses. Most studies were rated with a moderate RoB. Meta-analyses confirmed impairment of both aToM and cToM in MS patients, with larger effect sizes for aToM. Mediation analysis demonstrated that higher levels of fatigue selectively predicted the degree of cToM impairment. There was insufficient data available to quantify impairment in other socio-cognitive domains. Fourteen structural and functional imaging studies were identified and characterized by substantial heterogeneity. Summarized, this study confirmed substantial socio-cognitive impairment in MS and highlights the potential exacerbating role of comorbid clinical symptoms. We identify several evidence gaps that need to be addressed in future large-scale studies using comprehensive and coordinated assessments of socio-cognitive parameters, potential mediators, and neural correlates.Trial registration: The pre-registered review protocol can be assessed at www.crd.york.ac.uk/PROSPERO/ (ID: CRD42020206225).
Topics: Humans; Sclerosis; Cognitive Dysfunction; Cognition; Cognition Disorders; Multiple Sclerosis
PubMed: 38528009
DOI: 10.1038/s41598-024-53750-5 -
Stem Cells Translational Medicine May 2024Stem cell therapy holds promise for multiple sclerosis (MS), with efficacy of different stem cell types reported across a range of preclinical MS animal models. While... (Meta-Analysis)
Meta-Analysis
Stem cell therapy holds promise for multiple sclerosis (MS), with efficacy of different stem cell types reported across a range of preclinical MS animal models. While stem cell therapy has been approved for a small number of diseases in humans, extracellular vesicles (EVs) may provide an efficacious, cost-effective, and safer alternative to stem cell therapy. To this end, we conducted a systematic review with meta-analysis to assess the effectiveness of stem cell-derived secretome (EV and conditioned media (CM)) in animal models of MS. The data were extracted to calculate standardized mean differences for primary outcome measure of disease severity, using a random effect model. Additionally, several subgroup analyses were conducted to assess the impact of various study variables such as stem cell type and source, stem cell modification, route and time of administration, number of animals and animal's age, and EV isolation methods on secondary outcome. Publication quality and risk of bias were assessed. Overall, 19 preclinical studies were included in the meta-analysis where stem cell EV/CM was found to significantly reduce disease severity in EV-treated (SMD = 2, 95% CI: 1.18-2.83, P < .00001) and CM-treated animals (SMD = 2.58, 95% CI: 1.34-3.83, P < .00001) compared with controls. Our analysis indicated that stem cell secretome has a positive effect on reducing demyelination, systemic neuroinflammation, and disease severity in preclinical models of MS. These findings indicate a potential therapeutic effect that merits investigation and validation in clinical settings.
Topics: Multiple Sclerosis; Extracellular Vesicles; Animals; Humans; Stem Cells; Disease Models, Animal; Stem Cell Transplantation
PubMed: 38507620
DOI: 10.1093/stcltm/szae011 -
European Journal of Medical Research Mar 2024Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of... (Review)
Review
BACKGROUND
Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.
METHODS
The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.
RESULTS
The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.
CONCLUSIONS
Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.
Topics: Adult; Humans; Leukodystrophy, Metachromatic; Quality of Life; Cost of Illness
PubMed: 38494502
DOI: 10.1186/s40001-024-01771-1 -
International Journal of Molecular... Feb 2024Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis... (Review)
Review
Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.
Topics: Humans; Cytokines; Interleukin-13; Interleukin-33; Interleukin-4; Interleukin-6; Interleukins; Multiple Sclerosis
PubMed: 38473835
DOI: 10.3390/ijms25052589 -
Acta Neurologica Belgica Apr 2024Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS, has been explored for its off-label extended interval dosing (EID), suggesting a potential reduction in the risk of progressive multifocal leukoencephalopathy (PML) compared to standard interval dosing (SID). Our objective was to assess the efficacy and safety of EID in comparison to SID for natalizumab treatment in patients with MS.
METHODS
We searched PubMed, Embase, WOS, Scopus, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library. Our assessed outcomes were clinical relapses, MRI activity, change in expanded disability status scale [EDSS], and the risk of PML. The EID group was defined as 5 to 8 weeks [EID (Q5-8W)]. The analysis was conducted using RevMan ver. 5.4. The effect estimates were presented as a risk ratio [RR] or mean difference with 95% confidence intervals [CI] using SID group as the reference for comparisons.
RESULTS
Fourteen studies met our inclusion criteria: 2 RCTs, 1 switched single-arm trial, and 12 observational studies. No significant differences were found in all efficacy outcomes of interest. Risk of clinical relapses [RR = 0.90, (95%CI 0.80, 1.02)], risk of new or newly enlarging T2 hyperintense MRI lesions [RR = 0.78, (95%CI 0.59, 1.04)], risk gadolinium enhancing lesions [RR = 1.30, (95%CI 0.98, 1.72)], change in EDSS [MD = 0.09 (95%CI - 0.57, 0.76)], risk of PML [RR = 1.09, 95%CI (0.24, 4.94)].
CONCLUSION
In summary, our meta-analysis indicates that natalizumab maintains its effectiveness under extended interval dosing [up to 8 weeks], presenting comparable risks for clinical relapses, MRI lesions, EDSS, and PML. Caution is advised given study limitations and heterogeneity. Robust conclusions necessitate well-designed high-quality prospective studies.
Topics: Humans; Natalizumab; Multiple Sclerosis; Prospective Studies; Antibodies, Monoclonal; Leukoencephalopathy, Progressive Multifocal; Recurrence; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Observational Studies as Topic
PubMed: 38457005
DOI: 10.1007/s13760-024-02480-6 -
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 -
Brain Research Jun 2024A biomarker of cognition in Multiple Sclerosis (MS) that is independent from the response of people with MS (PwMS) to test questions would provide a more holistic... (Review)
Review
A biomarker of cognition in Multiple Sclerosis (MS) that is independent from the response of people with MS (PwMS) to test questions would provide a more holistic assessment of cognitive decline. One suggested method involves event-related potentials (ERPs). This systematic review tried to answer five questions about the use of ERPs in distinguishing PwMS from controls: which stimulus modality, which experimental paradigm, which electrodes, and which ERP components are most discriminatory, and whether amplitude or latency is a better measure. Our results show larger pooled effect sizes for visual stimuli than auditory stimuli, and larger pooled effect sizes for latency measurements than amplitude measurements. We observed great heterogeneity in methods and suggest that future research would benefit from more uniformity in methods and that results should be reported for the individual subtypes of PwMS. With more standardised methods, ERPs have the potential to be developed into a clinical tool in MS.
Topics: Humans; Electroencephalography; Evoked Potentials; Cognition; Cognitive Dysfunction; Multiple Sclerosis; Evoked Potentials, Auditory
PubMed: 38403040
DOI: 10.1016/j.brainres.2024.148827 -
Clinical Neurology and Neurosurgery Mar 2024Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the... (Review)
Review
INTRODUCTION
Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. Our work aims to investigate the incidence of GBS after COVID-19 vaccination, and describe its clinical characteristics and potential confounders.
METHODS
An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports and case series describing after COVID-19 vaccine administration. All published articles from inception until November 1st, 2022 were included. Differences between groups were assessed using Pearson chi-square test. Modified Erasmus GBS Outcome Score (mEGOS) for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS.
RESULTS
About 103 studies describing 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ±18.83 years, with AMSAN occurring in a rather older group (63.88 ±20.87 years, p=0.049). The AstraZeneca vaccine was associated with AIDP (n=38, 21.71%) more than other vaccines, p=0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Dysesthesias was the most reported sensory complication (60%, p=0.349). Most GBS patients survived (96%, p=0.036), however, most patients had low mEGOS scores (4 ±3.57, p<0.01). On average, patients developed GBS at 13.43 ±11.45 days from vaccination (p=0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p<0.01). Intravenous immunoglobulins (p=0.03) along with rehabilitation (p=0.19) were the most commonly used treatment.
CONCLUSION
This work investigates the incidence of Guillain-Barré Syndrome after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca or Pfizer vaccines, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines. No specific predisposing or prognostic factor was identified, and the relation between the COVID-19 vaccines and GBS remain unclear.
Topics: Humans; Adult; Middle Aged; Aged; Guillain-Barre Syndrome; COVID-19 Vaccines; COVID-19; Vaccination; Immunoglobulins, Intravenous
PubMed: 38401232
DOI: 10.1016/j.clineuro.2024.108183 -
Orphanet Journal of Rare Diseases Feb 2024Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA...
BACKGROUND
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. Late-infantile, juvenile and adult clinical subtypes are defined by symptom onset at ≤ 2.5, > 2.5 to < 16 and ≥ 16 years, respectively. Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug.
METHODS
To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. Where possible, results were stratified by clinical subtype. Data were extracted from non-interventional studies (clinical trials, non-clinical studies and case reports were excluded; reviews were used for snowballing only).
RESULTS
Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia-Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31-1.12 per 100,000 live births). The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.
CONCLUSIONS
This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.
Topics: Adult; Humans; Cerebroside-Sulfatase; Europe; Leukodystrophy, Metachromatic; Lysosomal Storage Diseases; Prevalence
PubMed: 38383398
DOI: 10.1186/s13023-024-03044-w -
Frontiers in Neurology 2024Guillain-Barré syndrome (GBS) is a rare disease that affects almost 0.8-1.9 cases per 100,000 people worldwide every year. This is the most prevalent cause of subacute... (Review)
Review
INTRODUCTION
Guillain-Barré syndrome (GBS) is a rare disease that affects almost 0.8-1.9 cases per 100,000 people worldwide every year. This is the most prevalent cause of subacute flaccid paralyzing illness today. It is a subacute inflammatory demyelinating polyradiculoneuropathy; the typical scenario involves ascending symmetrical flaccid paralysis, but in some circumstances, sensory, autonomic, and cranial neuropathy may also be involved. Several vaccines have been found to have complications since the previous century. Numerous case reports of GBS in the literature have been reported following COVID-19 vaccines in recent times.
OBJECTIVE
This study aimed to conduct a comprehensive examination of GBS cases that have been reported after COVID-19 vaccines; to analyze the descriptive statistical analysis of data gathered regarding clinical, laboratory, electrophysiological, and radiological characteristics; to discuss, based on the available evidence, whether the disease has a preference for a particular vaccine type; and to speculate on the potential pathogenesis.
METHODOLOGY
This review has been carried out by recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULT
Reviewing 60 case reports illustrated that most of them are from the USA (18.1%) and the majority of affected individuals were males (60%). The results favored the association between vector-based SARS-CoV-2 vaccine, particularly AstraZeneca vaccine, and the GBS. The mean of symptoms onset is 11.4 days. The results of diagnostic tests such as LP are consistent mostly with albumin-cytological dissociation (81.81%), where brain and spine MRI was unremarkable in 59.52%. Regarding electrodiagnostic tests, AIDP is the most common variant (61.81%). The management was not consistent among the case reports. However, IVIG is the most frequent way of treating these patients (68.33%). The functional outcome was documented in 47 patients; 65% improved with medical management.
CONCLUSION
This study aimed to conduct a systematic review of reported cases of GBS following COVID-19 vaccines and descriptive statistical analysis of collected data on clinical, laboratory, electrophysiological, and radiological features, to discuss, based on available results, whether the disease has a predilection to a specific vaccine type and to speculate the potential pathogenesis.
PubMed: 38352138
DOI: 10.3389/fneur.2024.1332364