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Multiple Sclerosis and Related Disorders Nov 2023Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the... (Review)
Review
BACKGROUND
Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the discrepancy between brain atrophy and cognitive functioning outcomes in multiple sclerosis (MS). CR in MS is typically investigated by assessing an individual's pre- and/or post-diagnosis enrichment, which includes premorbid intellectual abilities, educational level, occupational attainment, and engagement in cognitively enriching leisure activities. Common MS symptoms (e.g., physical disability, fatigue, depression, anxiety) may impact an individual's ability to engage in various CR-enhancing activities post-diagnosis. It is unknown to what extent these MS symptoms have been taken into account in MS research on CR. As such, we identified whether studies assessed CR using measures of premorbid or continuous (including post-diagnosis) enrichment. For studies investigating continuous enrichment, we identified whether studies accounted for MS-impact, which MS symptoms were accounted for, and how, and whether studies acknowledged MS symptoms as potential CR-confounds.
METHODS
Three electronic databases (PsycINFO, PubMed, Scopus) were searched. Eligible studies investigated CR proxies (e.g., estimated premorbid intellectual abilities, vocabulary knowledge, educational level, occupational attainment, cognitively enriching leisure activities, or a combination thereof) in relation to cognitive, brain atrophy or connectivity, or daily functioning outcomes in adult participants with MS. We extracted data on methods and measures used, including any MS symptoms taken into account. Objectives were addressed using frequency analyses and narrative synthesis.
RESULTS
115 studies were included in this review. 47.8% of all studies investigated continuous enrichment. Approximately half of the studies investigating continuous enrichment accounted for potential MS-impact in their analyses, with only 31.0% clearly identifying that they treated MS symptoms as potential confounds for CR-enhancement. A narrative synthesis of studies which investigated CR with and without controlling statistically for MS-impact indicated that accounting for MS symptoms may impact findings concerning the protective nature of CR.
CONCLUSION
Fewer than half of the studies investigating CR proxies in MS involved continuous enrichment. Just over half of these studies accounted for potential MS-impact in their analyses. To achieve a more complete and accurate understanding of CR in MS, future research should investigate both pre-MS and continuous enrichment. In doing so, MS symptoms and their potential impact should be considered. Establishing greater consistency and rigour across CR research in MS will be crucial to produce an evidence base for the development of interventions aimed at improving quality of care and life for pwMS.
Topics: Adult; Humans; Multiple Sclerosis; Cognitive Reserve; Brain; Depression; Anxiety; Atrophy; Fatigue
PubMed: 37806233
DOI: 10.1016/j.msard.2023.105017 -
Scientific Reports May 2024Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a... (Meta-Analysis)
Meta-Analysis
Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.
Topics: Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Treatment Outcome
PubMed: 38822024
DOI: 10.1038/s41598-024-62726-4 -
Tremor and Other Hyperkinetic Movements... 2023To describe the state of literature regarding prevalence, clinical types of tremor in Multiple Sclerosis and associated disability. (Review)
Review
OBJECTIVE
To describe the state of literature regarding prevalence, clinical types of tremor in Multiple Sclerosis and associated disability.
BACKGROUND
Tremor has long been recognized as an important symptom of multiple sclerosis. This can be intention and postural tremor that affects the upper limbs. Patients with multiple sclerosis who experience tremor of any severity typically retire early or lose their jobs due to disability.
METHODS
This systematic review was performed up to September 9, 2022. Article selection was performed by searching the MEDLINE (PubMed) and EMBASE electronic bibliographic databases. The search strategy was not limited by study design but only for articles in the English language.
RESULTS
A total of nine full-text articles were included in the analysis. Six studies were cross-sectional studies; one each was a prospective observational study, a case-control study, a community-based cohort. The prevalence of tremor in the multiple sclerosis (MS) population among studies ranged widely, between 12.5% and 68.9%. The presence of severe tremor ranged from 3% to 33%. Younger age was a significant predictor of tremor in two studies. The most common tremor subtype was action tremor. Upper extremities were the most common site involved in the majority of our studies, followed by head and neck.
CONCLUSIONS
Prevalence of tremor ranged from 12.5% to 68.9% in the MS population with severe tremor being an infrequent complication. Severity of tremor correlated with increasing disability. Upper limb action tremor was the most common with rare occurrences of resting and rubral tremor.
Topics: Humans; Case-Control Studies; Multiple Sclerosis; Prevalence; Tremor; Head; Observational Studies as Topic
PubMed: 37719089
DOI: 10.5334/tohm.776 -
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 -
JAMA Network Open Oct 2023Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and...
IMPORTANCE
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
OBJECTIVE
To evaluate the efficacy and safety of urea for the treatment of SIADH.
EVIDENCE REVIEW
A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.
FINDINGS
Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.
CONCLUSIONS AND RELEVANCE
In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.
Topics: Adult; Humans; Urea; Inappropriate ADH Syndrome; Vasopressins; Demyelinating Diseases; Sodium
PubMed: 37902751
DOI: 10.1001/jamanetworkopen.2023.40313 -
Frontiers in Public Health 2023We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple Sclerosis.
METHODS
A systematic, comprehensive literature search was performed in four electronic academic databases. We included any case-control study that enrolled working-age subjects and compared the proportion of MS cases with controls who were not exposed to an occupational risk factor. The primary outcome was the occurrence of MS. The quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies, developed, and validated by the Joanna Briggs Institute. All the selection process was also carried out by two independent and previously trained researchers.
RESULTS
Overall, the total sample included 19,004 people with MS and 4,164,162 controls. Agricultural workers (OR = 1.44, 95% CI 1.13-1.83), offshore workers (OR = 3.56, 95% CI 2.74-4.61), and hairdressers (OR = 8.25, 95% CI 1.02-66.52) were associated with a higher probability of being diagnosed with MS. In parallel, workers exposed to toxic fumes from oil wells (OR = 16.80, 95% CI 8.33-33.90), low-frequency magnetic fields (OR = 1.71, 95% CI 1.03-2.72), and pesticides (OR = 3.17, 95% CI = 2.53-3.99) also had an increased likelihood of having MS.
CONCLUSION
Our study has the potential to influence more assertive public policies. Nevertheless, future studies on how the occupational setting may contribute to the incidence of MS are highly recommended.
SYSTEMATIC REVIEW REGISTRATION
The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257).
Topics: Humans; Occupational Diseases; Multiple Sclerosis; Case-Control Studies; Occupational Exposure; World Health Organization; Cost of Illness; Risk Factors
PubMed: 38054069
DOI: 10.3389/fpubh.2023.1285103 -
Annals of Medicine Dec 2023To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica... (Review)
Review
OBJECTIVES
To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD).
METHODS AND ANALYSIS
We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data.
RESULTS
Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543).
CONCLUSIONS
There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD.
Topics: Humans; Plasma Exchange; Neuromyelitis Optica; Optic Neuritis; Outcome Assessment, Health Care
PubMed: 37387119
DOI: 10.1080/07853890.2023.2227422 -
Journal of Medical Internet Research Jul 2023Wearable sensor technologies have the potential to improve monitoring in people with multiple sclerosis (MS) and inform timely disease management decisions. Evidence of... (Review)
Review
BACKGROUND
Wearable sensor technologies have the potential to improve monitoring in people with multiple sclerosis (MS) and inform timely disease management decisions. Evidence of the utility of wearable sensor technologies in people with MS is accumulating but is generally limited to specific subgroups of patients, clinical or laboratory settings, and functional domains.
OBJECTIVE
This review aims to provide a comprehensive overview of all studies that have used wearable sensors to assess, monitor, and quantify motor function in people with MS during daily activities or in a controlled laboratory setting and to shed light on the technological advances over the past decades.
METHODS
We systematically reviewed studies on wearable sensors to assess the motor performance of people with MS. We scanned PubMed, Scopus, Embase, and Web of Science databases until December 31, 2022, considering search terms "multiple sclerosis" and those associated with wearable technologies and included all studies assessing motor functions. The types of results from relevant studies were systematically mapped into 9 predefined categories (association with clinical scores or other measures; test-retest reliability; group differences, 3 types; responsiveness to change or intervention; and acceptability to study participants), and the reporting quality was determined through 9 questions. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines.
RESULTS
Of the 1251 identified publications, 308 were included: 176 (57.1%) in a real-world context, 107 (34.7%) in a laboratory context, and 25 (8.1%) in a mixed context. Most publications studied physical activity (196/308, 63.6%), followed by gait (81/308, 26.3%), dexterity or tremor (38/308, 12.3%), and balance (34/308, 11%). In the laboratory setting, outcome measures included (in addition to clinical severity scores) 2- and 6-minute walking tests, timed 25-foot walking test, timed up and go, stair climbing, balance tests, and finger-to-nose test, among others. The most popular anatomical landmarks for wearable placement were the waist, wrist, and lower back. Triaxial accelerometers were most commonly used (229/308, 74.4%). A surge in the number of sensors embedded in smartphones and smartwatches has been observed. Overall, the reporting quality was good.
CONCLUSIONS
Continuous monitoring with wearable sensors could optimize the management of people with MS, but some hurdles still exist to full clinical adoption of digital monitoring. Despite a possible publication bias and vast heterogeneity in the outcomes reported, our review provides an overview of the current literature on wearable sensor technologies used for people with MS and highlights shortcomings, such as the lack of harmonization, transparency in reporting methods and results, and limited data availability for the research community. These limitations need to be addressed for the growing implementation of wearable sensor technologies in clinical routine and clinical trials, which is of utmost importance for further progress in clinical research and daily management of people with MS.
TRIAL REGISTRATION
PROSPERO CRD42021243249; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=243249.
Topics: Humans; Reproducibility of Results; Sclerosis; Wearable Electronic Devices; Gait; Exercise; Multiple Sclerosis
PubMed: 37498655
DOI: 10.2196/44428 -
Multiple Sclerosis (Houndmills,... Nov 2023A review of the safety profile of exercise training in multiple sclerosis (MS) has not been conducted since 2013. (Meta-Analysis)
Meta-Analysis
BACKGROUND
A review of the safety profile of exercise training in multiple sclerosis (MS) has not been conducted since 2013.
OBJECTIVE
We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) of exercise training published since 2013 and quantified estimated population risks of clinical relapse, adverse events (AE) and serious adverse event (SAE).
METHODS
Articles reporting safety outcomes from comparisons of exercise training with non-exercise among persons with MS were identified. The risk of bias was established from study's internal validity assessed using Physiotherapy Evidence Database (PEDro). Rates and estimated mean population relative risks (RRs; 95% confidence interval (CI)) of safety outcomes were calculated, and random-effects meta-analysis estimated the mean RR.
RESULTS
Forty-six interventions from 40 RCTs ( = 1780) yielded 46, 40 and 39 effects for relapse, AE, adverse effects and SAE, respectively. The mean population RRs ((95% CI), -value) for relapse, AE and SAE were 0.95 ((0.61, 1.48), = 0.82), 1.40 ((0.90, 2.19), = 0.14) and 1.05 ((0.62, 1.80), = 0.85), respectively. No significant heterogeneity is observed for any outcome.
CONCLUSION
In studies that reported safety outcomes, there was no higher risk of relapse, AE, adverse effects or SAE for exercise training than the comparator. Exercise training may be promoted as safe and beneficial to persons with MS.
Topics: Humans; Exercise; Exercise Therapy; Chronic Disease; Multiple Sclerosis; Recurrence
PubMed: 37880997
DOI: 10.1177/13524585231204459 -
BMC Neurology Sep 2023Menopause is a physiologic phase in women's lives. Findings regarding multiple sclerosis (MS) course through menopause are diverse. So, we designed this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Menopause is a physiologic phase in women's lives. Findings regarding multiple sclerosis (MS) course through menopause are diverse. So, we designed this systematic review and meta-analysis to estimate the impact of menopause on relapse rate, and disability status in women with MS.
METHODS
PubMed, Scopus, EMBASE, Web of Science, and google scholar were systematically searched by two independent researchers on January 1st, 2023. They also evaluated conference abstracts, and references of the included studies. In addition, data regarding the total number of participants, name of the first author of the publication, publication year, country of origin, disease duration, disease type, annual relapse rate, and Expanded Disability Status Scale (EDSS) before and after menopause were recorded.
RESULTS
A literature search revealed 1024 records. Twenty-one full texts were evaluated, and finally, four studies were included for meta-analysis. Mean ARR before menopause ranged between 0.21 and 0.37, and after menopause ranged between 0.13 and 0.08. The SMD of mean ARR ranged between - 1.04, and - 0.29, while the pooled SMD was estimated as -0.52(95% CI: -0.88, -0.15) (I = 73.6%, P = 0.02). The mean EDSS before menopause ranged between 1.5 and 2, and after menopause ranged between 2 and 3.1. The SMD of EDSS ranged between 0.46, and 0.71. The pooled SMD of EDSS change (after menopause-before menopause) estimated as 0.56(95% CI: 0.38, 0.73)(I = 0, P = 0.4).
CONCLUSION
The result of this systematic review and meta-analysis show that menopause can be associated with relapse rate reduction, unlike increase in disease-related disability in women with MS.
Topics: Humans; Female; Multiple Sclerosis; Menopause; Patients; Chronic Disease
PubMed: 37667181
DOI: 10.1186/s12883-023-03332-1