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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 and Related Disorders May 2024Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS.
METHODS
This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software.
RESULTS
Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05).
DISCUSSION
Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic.
FUNDING AND REGISTRATION
The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625).
Topics: Humans; Cognitive Dysfunction; Multiple Sclerosis; Lipids
PubMed: 38522226
DOI: 10.1016/j.msard.2024.105530 -
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 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
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 -
Multiple Sclerosis and Related Disorders Jul 2024Although many people with MS (pwMS) modify their diet after diagnosis, there is still no consensus on dietary recommendations for pwMS. A number of observational studies...
BACKGROUND
Although many people with MS (pwMS) modify their diet after diagnosis, there is still no consensus on dietary recommendations for pwMS. A number of observational studies have explored associations of diet and MS progression, but no studies have systematically reviewed the evidence. This systematic review aimed to provide an objective synthesis of the evidence for associations between diet and MS progression, including symptoms and clinical outcomes from observational studies.
METHODS
We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic database searches were performed for studies completed up to 26 July 2023 using PubMed (Medline), Web of Science, CINAHL, Embase (Ovid), and Scopus, followed by citation and reference list checking. We included studies using diet quality scores or dietary indices. Studies assessing individual foods, nutrients, or dietary supplements were excluded. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies.
RESULTS
Thirty-two studies met the inclusion criteria. Of these, 20 were cross-sectional and 12 prospective. The most frequent outcomes assessed were disability (n = 19), quality of life (n = 12), fatigue (n = 12), depression (n = 9), relapse (n = 8), anxiety (n = 3), and magnetic resonance imaging (MRI) outcomes (n = 4). Based on prospective studies, this review suggests that diet might be associated with quality of life and disability. There were also potential effects of higher diet quality scores on improved fatigue, disability, depression, anxiety, and MRI outcomes but more evidence is needed from prospective studies.
CONCLUSIONS
Observational studies show some evidence for an association between diet and MS symptoms, particularly quality of life and disability. However, the impact of diet on other MS outcomes remains inconclusive. Ultimately, our findings suggest more evidence is needed from prospective studies and well-designed tailored intervention studies to confirm associations.
Topics: Humans; Diet; Disease Progression; Multiple Sclerosis; Observational Studies as Topic
PubMed: 38678968
DOI: 10.1016/j.msard.2024.105636 -
Nitric Oxide : Biology and Chemistry Apr 2024Multiple sclerosis (MS) is a chronic and immune-mediated disease of unknown etiology and leading to a physical and cognitive disability. Different studies suggest that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic and immune-mediated disease of unknown etiology and leading to a physical and cognitive disability. Different studies suggest that nitrosative stress may play a pivotal role in the pathogenesis and disability in MS. Besides, reports evaluated NO and their metabolites, expressed by nitrite and nitrate (NOx) levels of MS patients compared with other pathologies, but did not evaluate disability and relapse/remission phases.
OBJECTIVE
Thus, this study aimed to conduct a systematic review and meta-analysis of NOx levels in MS patients in relapse/remission phases and its involvement in patient disability.
METHODS
The protocol was registered in PROSPERO (CRD42022327161). We used GRADE to estimate the articles' quality and evaluated the publication bias using Egger's and Begg's tests.
RESULTS
Here, through a search in the Pubmed, Scopus, and EMBASE databases, 5.276 studies were found, and after the selection process, 20 studies were included in this systematic review and meta-analysis. The studies included data from 1.474 MS patients and 1.717 healthy controls, 1.010 RRMS and 221 primary progressive MS (PPMS).
CONCLUSION
NOx levels are increased in relapsing-remitting MS (RRMS) patients in the relapse phase. Also, NOx levels were increased in MS patients with higher disability. However, further studies are still needed to control lifestyle habits, pain, and MS treatment effects in biased NOx levels.
Topics: Humans; Multiple Sclerosis; Nitric Oxide; Multiple Sclerosis, Relapsing-Remitting; Nitrates; Recurrence
PubMed: 38331311
DOI: 10.1016/j.niox.2024.01.006 -
Journal of Neuroimmunology Jun 2024A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift... (Review)
Review
A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs). In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic. The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group. Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies. De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies. Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.
Topics: Humans; Multiple Sclerosis; Aged; Aging; Immunologic Factors
PubMed: 38761652
DOI: 10.1016/j.jneuroim.2024.578368 -
Frontiers in Immunology 2024The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple... (Review)
Review
The research & development (R&D) of novel therapeutic agents for the treatment of autoimmune diseases is challenged by highly complex pathogenesis and multiple etiologies of these conditions. The number of targeted therapies available on the market is limited, whereas the prevalence of autoimmune conditions in the global population continues to rise. Mathematical modeling of biological systems is an essential tool which may be applied in support of decision-making across R&D drug programs to improve the probability of success in the development of novel medicines. Over the past decades, multiple models of autoimmune diseases have been developed. Models differ in the spectra of quantitative data used in their development and mathematical methods, as well as in the level of "mechanistic granularity" chosen to describe the underlying biology. Yet, all models strive towards the same goal: to quantitatively describe various aspects of the immune response. The aim of this review was to conduct a systematic review and analysis of mathematical models of autoimmune diseases focused on the mechanistic description of the immune system, to consolidate existing quantitative knowledge on autoimmune processes, and to outline potential directions of interest for future model-based analyses. Following a systematic literature review, 38 models describing the onset, progression, and/or the effect of treatment in 13 systemic and organ-specific autoimmune conditions were identified, most models developed for inflammatory bowel disease, multiple sclerosis, and lupus (5 models each). ≥70% of the models were developed as nonlinear systems of ordinary differential equations, others - as partial differential equations, integro-differential equations, Boolean networks, or probabilistic models. Despite covering a relatively wide range of diseases, most models described the same components of the immune system, such as T-cell response, cytokine influence, or the involvement of macrophages in autoimmune processes. All models were thoroughly analyzed with an emphasis on assumptions, limitations, and their potential applications in the development of novel medicines.
Topics: Humans; Autoimmune Diseases; Models, Theoretical; Multiple Sclerosis; Immunity; T-Lymphocytes
PubMed: 38550585
DOI: 10.3389/fimmu.2024.1371620 -
Multiple Sclerosis and Related Disorders Dec 2023This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy.... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis summarize the efficacy and safety of Tocilizumab (TCZ) in treating NMOSD and investigates the factors that affect its efficacy. TCZ is the first monoclonal antibody against the IL-6 receptor for treating NMOSD, and its efficacy and safety vary in different studies. We collected English-language research literature until January 1, 2023, by searching databases such as PubMed, MEDLINE, Embase, Cochrane Library, and clinicaltrials.gov, and identified 9 studies involving 153 patients (139 female and 14 male) that met our inclusion criteria. In these studies, the average ARR ratio and EDSS score reduction values in the TCZ treatment group were -1.34 (95 % CI, -1.60 to -1.09) and -0.81 (95 % CI, -1.04 to -0.58), respectively. Based on the data we have collected, compared to the AQP4-IgG negative NMOSD patients, TCZ demonstrates a more pronounced effectiveness in AQP4-IgG positive NMOSD patients. The study also found that the effectiveness of TCZ in reducing NMOSD patients' ARR ratio was related to gender, race, and TCZ dosage, while the effectiveness of reducing EDSS score was not related to these factors. Among the 153 patients receiving TCZ treatment, 101 (66 %) experienced mild adverse reactions, and one patient experienced a severe adverse reaction (facial cellulitis). The comprehensive data indicate that TCZ treatment can reduce the frequency of NMOSD relapses, improve patients' neurological function, and have good safety. The effectiveness of TCZ in reducing NMOSD patients' ARR ratio is related to multiple factors.
Topics: Humans; Male; Female; Neuromyelitis Optica; Antibodies, Monoclonal, Humanized; Disability Evaluation; Immunoglobulin G; Aquaporin 4
PubMed: 37866020
DOI: 10.1016/j.msard.2023.105062