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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 -
Multiple Sclerosis and Related Disorders May 2024To look for any potential association of headache disorders with multiple sclerosis (MS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To look for any potential association of headache disorders with multiple sclerosis (MS).
BACKGROUND
The prevalence of headache disorders has been found to be increased in people with MS (pwMS), however, an association has not been established. Existing studies have provided conflicting results mostly because of methodological differences.
METHODS
PubMed, Embase and Scopus were searched to identify eligible studies. Studies were included if they were cross-sectional, case-control or cohort. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the included studies. Case-control, cross sectional or cohort studies that used the International Classification of Headache Disorders (ICHD)-2 or-3 criteria for headache diagnosis and Mc Donald or Poser criteria for MS diagnosis were included. Data were extracted using standardized data collection form. Meta-analysis was conducted by calculating the overall prevalence of headache disorders in pwMS as well as the association of headache disorders with MS. The Newcastle-Ottawa Scale (NOS), a tool for assessing the quality of non-randomized studies, was used to assess the quality of the included studies.
RESULTS
Twenty-three studies were included yielding a total of 5,440 MS patients and 28,0958 controls. The majority of them scored a NOS score between 5 and 6 (max 9), which indicates that they did not rank high in terms of quality, because most studies were cross-sectional and uncontrolled, and only one was prospective, controlled, and longitudinal, but with small population size. Pooled prevalence for all headache disorders, migraine and tension-type headache (TTH) in pwMS was 58 % (95 % CI 0.54-0.61), 30 % (95 % CI 0.25-0.34) and 19 % (95 % CI 0.15-0.23) respectively. A significant association between migraine and MS was found (OR = 2.02, 95 % CI = 1.14-3.57).
CONCLUSION
PwMS are twice as likely to experience migraine as controls, but the results need to be translated with caution since most of the studies included in the meta-analysis were of low or moderate quality. Larger prospective cohort, controlled, longitudinal studies are needed to confirm whether there is indeed an association between MS and migraine.
Topics: Humans; Multiple Sclerosis; Headache Disorders; Comorbidity
PubMed: 38489946
DOI: 10.1016/j.msard.2024.105536 -
Multiple Sclerosis and Related Disorders May 2024Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by relapses of inflammation and demyelination primarily affecting the optic nerve and the spinal cord. C5 complement inhibition is an effective therapeutic approach in the treatment of NMOSD. In this systematic review and meta-analysis, we aimed to determine the role of C5 inhibitors in the treatment of patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG) NMOSD.
METHODS
This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Relevant articles were systematically searched through Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases until October 6th, 2023. We included randomized clinical trials (RCTs) that investigated the treatment with C5 inhibitors compared to placebo in patients with seropositive NMOSD. The primary endpoint was the rates of first adjudicated relapse. Secondary endpoints included different disability and quality of life measures. The random-effects model was used for all statistical analyses.
RESULTS
Two RCTs with a total of 201 patients were included. C5 inhibitors demonstrated significant reduction of first adjudicated relapse (risk ratio (RR) = 0.05, 95 % CI 0.01-0.15) and Hauser Ambulation Index (HAI) (mean difference (MD): -0.79, 95 % CI -1.27 to -0.31). There was no significant difference between the two groups in Expanded Disability Status Scale (EDSS) (MD -0.23, 95 % CI -0.54-0.08). C5 inhibitors significantly improved the mean change in EQ-5D index (MD 0.08, 95 % CI 0.01-0.14; P = 0.02); however, no significant difference was shown in the mean change in EQ-5D VAS (MD 3.79, 95 % CI -1.61 to 9.19; P = 0.17). Safety measures were comparable between C5 inhibitors and placebo.
CONCLUSION
NMOSD Patients with AQP4+IgG receiving C5 inhibitors have lower rate of relapses and improved levels of disability and quality of life. Real-world studies are warranted to establish the long-term safety of C5 inhibitors.
Topics: Neuromyelitis Optica; Humans; Aquaporin 4; Autoantibodies; Complement C5; Randomized Controlled Trials as Topic
PubMed: 38479045
DOI: 10.1016/j.msard.2024.105524 -
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 -
Journal of Neurology Jun 2024The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune... (Comparative Study)
Comparative Study
BACKGROUND
The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune checkpoint inhibitors (ICI), is not well characterized. We aim to describe the clinical spectrum of melanoma-associated neurological autoimmunity.
METHODS
A systematic review of the literature combined with patients from French databases of paraneoplastic neurological syndromes was conducted. All melanoma patients with a possible immune-mediated neurologic syndrome were included and classified according to whether they had previously been exposed to ICI (ICI-neurotoxicity) or not (ICI-naïve) at first neurological symptoms.
RESULTS
Seventy ICI-naïve (literature: n = 61) and 241 ICI-neurotoxicity patients (literature: n = 180) were identified. Neuromuscular manifestations predominated in both groups, but peripheral neuropathies were more frequent in ICI-neurotoxicity patients (39.4% vs 21.4%, p = 0.005) whereas myositis was more frequent in ICI-naïve patients (42.9% vs 18.7%, p < 0.001). ICI-naïve patients had also more frequent central nervous system (CNS) involvement (35.7% vs 23.7%, p = 0.045), classical paraneoplastic syndrome (25.7% vs 5.8%, p < 0.001), and more frequently positive for anti-neuron antibodies (24/32, 75.0% vs 38/90, 42.2%, p = 0.001). Although more ICI-neurotoxicity patients died during the acute phase (22/202, 10.9% vs 1/51, 2.0%, p = 0.047), mostly myositis patients (14/22, 63.6%), mortality during follow-up was higher in ICI-naïve patients (58.5% vs 29.8%, p < 0.001). There was no significant difference in the frequency of life independence (mRS ≤ 2) in the surviving patients in both groups (95.5% vs 91.0%, p = 0.437).
CONCLUSIONS
Melanoma-associated PNS appear remarkably rare. The clinical similarities observed in neurological autoimmunity between ICI-treated and ICI-naïve patients, characterized predominantly by demyelinating polyradiculoneuropathy and myositis, suggest a potential prior immunization against melanoma antigens contributing to ICI-related neurotoxicity.
Topics: Humans; Melanoma; Immune Checkpoint Inhibitors; Paraneoplastic Syndromes, Nervous System; Autoimmunity; Male; Female
PubMed: 38467790
DOI: 10.1007/s00415-024-12252-0 -
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 -
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 Bodywork and Movement... Jan 2024Multiple sclerosis (MS) is a chronic autoimmune disease that causes progressive functional impairment, mainly in walking tasks. Noninvasive brain stimulation (NIBS)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic autoimmune disease that causes progressive functional impairment, mainly in walking tasks. Noninvasive brain stimulation (NIBS) could influence the motor function and improving gait ability of patients.
OBJECTIVE
The aim was to analyze the effects of NIBS (transcranial direct current stimulation [tDCS] or transcranial magnetic stimulation [TMS] on functional locomotion in people with multiple sclerosis (PwMS).
METHODS
A search was conducted for randomized controlled trials published up to November 2023 comparing the application of NIBS versus a sham or control group. The primary outcome were spatiotemporal gait parameters and functional mobility. Two review authors independently assessed the risk of bias in the included studies, and we used the Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty of the evidence for each outcome. A meta-analysis was performed by pooling the appropriate data using RevMan Web.
RESULTS
A total of four clinical trials were included for metanalysis. We observed that there is no statistically significant difference in overall effect in gait speed (MD = 0.08; 95% CI: -0.08-0.24; p = 0.32), and cadence (MD = 0.22; 95% CI: -11.54-11.98; p = 0.97%) between groups. But there was a statistically significant difference in overall effect in stride length between groups (MD:0.19; 95% CI: 0.07-0.31; p = 0.002), mainly when the intervention performed by multiple sessions and associated with motor rehabilitation (MD = 0.29; 95% CI: 0.14-0.44; p = 0.0002).
CONCLUSIONS
tDCS applied by multiple session and combined with motor rehabilitation (i.e., aerobic and/or resistance training) can improve stride length in PwMS.
Topics: Humans; Multiple Sclerosis; Transcranial Direct Current Stimulation; Gait; Walking; Brain
PubMed: 38432828
DOI: 10.1016/j.jbmt.2023.11.043 -
Multiple Sclerosis and Related Disorders Apr 2024Fear of falling (FOF) is a common concern among persons with multiple sclerosis (MS) and affects the performance of their daily living activities. Falls may result in... (Review)
Review
BACKGROUND
Fear of falling (FOF) is a common concern among persons with multiple sclerosis (MS) and affects the performance of their daily living activities. Falls may result in FOF, leading to worsening of symptoms of MS, physical deconditioning, and exposure to future falls. This may trigger a vicious cycle between FOF and falls. A better understanding of the relationship between FOF and symptoms of MS may be helpful to develop a conceptual model to guide fall prevention interventions.
OBJECTIVE
To synthesize the correlational and predictive relationships between FOF and common symptoms of MS.
METHODS
Databases including PubMed, Embase, Web of Science, Scopus, CINHAL, PsycINFO, and SPORTDiscuss were searched from inception to October 2023. Studies examining correlations and/or predictions between FOF and common MS symptoms that include measures of gait, postural control, fatigue, cognition, pain, sleep, depression, and anxiety were identified by two independent reviewers. Both reviewers also conducted the methodological quality assessment of the included studies.
RESULTS
Twenty-three studies with a total of 2819 participants were included in the review. Correlational findings indicated that increased FOF was significantly associated with greater walking deficits (lower gait speed, smaller steps), reduced mobility, and poorer balance. Increased FOF was also significantly correlated with higher cognitive impairments, more fatigue, sleep disturbances, and depression. Decreased gait parameters, reduced balance, lower physical functions, cognitive impairments, and sleep deficits were found as significant predictors of increased FOF.
CONCLUSION
Evidence indicates significant correlational and bidirectional predictive relationships exist between FOF and common MS symptoms. A comprehensive conceptual framework accounting for the interaction between FOF and MS symptoms is needed to develop effective falls prevention strategies.
Topics: Humans; Multiple Sclerosis; Depression; Fear; Cognition; Fatigue; Postural Balance
PubMed: 38422635
DOI: 10.1016/j.msard.2024.105506