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Journal of Neuroinflammation Feb 2024Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination...
Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.
Topics: Humans; Multiple Sclerosis; Osteopontin; Vitamin D-Binding Protein; Biomarkers; Chitinases; Recurrence
PubMed: 38368354
DOI: 10.1186/s12974-024-03036-4 -
Current Neurology and Neuroscience... Sep 2023Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune... (Review)
Review
PURPOSE OF REVIEW
Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly considered a treatment option for patients with multiple sclerosis (MS), an autoimmune demyelinating and degenerative disease of the central nervous system (CNS). AHSCT persistently suppresses inflammation and improves the disease course in large proportions of patients with relapsing-remitting (RR) MS. Aim of this article is to review the relevant new knowledge published during the last 3 years.
RECENT FINDINGS
Laboratory studies reported confirmatory and new insights into the immunological and biomarker effects of AHSCT. Retrospective clinical studies confirmed excellent outcomes in RRMS, showing possible superior effectiveness over standard therapies and suggesting a possible benefit in early secondary progressive (SP) MS with inflammatory features. New data on risks of infertility and secondary autoimmunity were also reported. Further evidence on the high effectiveness and acceptable safety of AHSCT strengthens its position as a clinical option for aggressive RRMS. Further research is needed to better define its role in treatment-naïve and progressive forms of MS, ideally within randomised clinical trials (RCTs).
Topics: Humans; Multiple Sclerosis; Retrospective Studies; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Hematopoietic Stem Cell Transplantation
PubMed: 37589918
DOI: 10.1007/s11910-023-01290-2 -
Journal of Neurology Aug 2023Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS), which also affects the autonomic nervous system (ANS).... (Review)
Review
Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS), which also affects the autonomic nervous system (ANS). Manifestations of MS in the ANS include urological, sexual, gastrointestinal, cardiovascular, and thermoregulatory disorders as well as increased fatigue. These problems are common yet are often underestimated due to the non-specificity of the symptoms and the limited evaluation of the ANS in the usual clinical practice. Most of these symptoms seem to be related to localized lesions in the CNS. However, the mechanisms by which these disorders are caused in MS have not been fully investigated, thus preventing any focused etiological treatment. The most common disorders of the ANS in MS represent a challenge for clinicians due to the variability of the clinical picture and our minimal data on their diagnosis and treatment. Early diagnosis and initiation of individualized treatment regimens, often in need of multiple approaches, seem to yield the best results in managing ANS dysfunction in MS patients.
Topics: Humans; Multiple Sclerosis; Autonomic Nervous System Diseases; Autonomic Nervous System; Central Nervous System
PubMed: 37084150
DOI: 10.1007/s00415-023-11725-y -
The Lancet. Neurology Mar 2024Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability... (Review)
Review
Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying progression remains a daunting and ongoing challenge. Since 2014, several immunomodulatory approaches that have modest but clinically meaningful effects have been approved for the management of progressive multiple sclerosis, primarily for people who have active inflammatory disease. The approval of these drugs required large phase 3 trials that were sufficiently powered to detect meaningful effects on disability. New classes of drug, such as Bruton tyrosine-kinase inhibitors, are coming to the end of their trial stages, several candidate neuroprotective compounds have been successful in phase 2 trials, and innovative approaches to remyelination are now also being explored in clinical trials. Work continues to define intermediate outcomes that can provide results in phase 2 trials more quickly than disability measures, and more efficient trial designs, such as multi-arm multi-stage and futility approaches, are increasingly being used. Collaborations between patient organisations, pharmaceutical companies, and academic researchers will be crucial to ensure that future trials maintain this momentum and generate results that are relevant for people living with progressive multiple sclerosis.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Immunomodulation; Forecasting
PubMed: 38365380
DOI: 10.1016/S1474-4422(24)00027-9 -
Multiple Sclerosis and Related Disorders Aug 2023
Topics: Humans; Artificial Intelligence; Multiple Sclerosis
PubMed: 37385082
DOI: 10.1016/j.msard.2023.104851 -
Current Opinion in Neurology Jun 2024Research in multiple sclerosis (MS) has long been predicated on clinical groupings that do not reflect the underlying biologic heterogeneity apparent within patient... (Review)
Review
PURPOSE OF REVIEW
Research in multiple sclerosis (MS) has long been predicated on clinical groupings that do not reflect the underlying biologic heterogeneity apparent within patient populations. This review explicates the various levels of explanation through which the spectrum of disease is described and investigated both above and below the clinical threshold of detection, as framed by the topographical model of MS, to help advance a cogent mechanistic framework.
RECENT FINDINGS
Contemporary evidence has amended the view of MS as consisting of sequential disease phases in favor of a spectrum of disease with an admixture of interdependent and dynamic pathobiological axes driving tissue injury and progression. Recent studies have shown the presence of acute and compartmentalized inflammation and mechanisms of neurodegeneration beginning early and evolving throughout the disease continuum. Still, the gap between the understanding of immunopathologic processes in MS and the tools used to measure relevant molecular, laboratory, radiologic, and clinical metrics needs attention to enable better prognostication of disease and monitoring for changes along specific pathologic axes and variable treatment outcomes.
SUMMARY
Aligning on a consistently-applied mechanistic framework at distinct levels of explanation will enable greater precision across bench and clinical research, and inform discourse on drivers of disability progression and delivery of care for individuals with MS.
Topics: Humans; Multiple Sclerosis; Disease Progression
PubMed: 38535979
DOI: 10.1097/WCO.0000000000001262 -
Multiple Sclerosis (Houndmills,... Aug 2023There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple...
OBJECTIVE
There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS).
METHODS
We used a population-based case-control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary habits 5 years prior to MS diagnosis were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Adjustment was made for a large number of environmental and lifestyle habits, including ancestry, smoking, alcohol consumption, body mass index, physical activity, and sun exposure habits.
RESULTS
Mediterranean diet was associated with lower risk of developing MS (adjusted OR = 0.54, 95% CI: 0.34-0.86, = 0.009), compared with Western-style diet. There was no significant association between vegetarian/vegan diet and MS risk (adjusted OR = 0.96, 95% CI: 0.75-1.24, = 0.976), nor between diet with low glycemic index and MS risk (adjusted OR = 0.93, 95% CI: 0.60-1.42, = 0.518).
CONCLUSIONS
Mediterranean diet may exert a protective influence regarding the risk of subsequently developing MS compared with Western-style diet.
Topics: Humans; Multiple Sclerosis; Diet, Mediterranean; Risk Factors; Case-Control Studies; Diet; Alcohol Drinking
PubMed: 37366345
DOI: 10.1177/13524585231181841 -
Multiple Sclerosis (Houndmills,... Apr 2024
Topics: Humans; Infectious Mononucleosis; Multiple Sclerosis; Risk Factors
PubMed: 38511833
DOI: 10.1177/13524585241237708 -
The Libyan Journal of Medicine Dec 2023Multiple sclerosis (MS) is a debilitating disease that causes inflammation of the central nervous system, resulting in myelin damage and axon degeneration. Although the...
Multiple sclerosis (MS) is a debilitating disease that causes inflammation of the central nervous system, resulting in myelin damage and axon degeneration. Although the cause of MS remains unknown, various factors such as sex, latitude, sun exposure, serum vitamin D levels, Epstein Barr Virus infection, diet, microbiota and ethnicity are being studied for their potential roles in the development of the disease. While chronobiological factors such as circadian rhythm and seasonality have been explored for their potential influence on the onset, exacerbation, and/or relapses of MS, the potential influence of the lunar cycle on MS has yet to be studied. Therefore, the authors of this letter call for future studies to investigate the possible effects of the lunar cycle on MS activity and course, given evidence suggesting that the lunar cycle may affect sleep, fatigue, melatonin secretion, and mood state in humans. A deeper understanding of the chronobiology of MS could have practical implications for the development of chronotherapeutic strategies and the prevention or mitigation of MS relapses, potentially improving the quality of life of MS patients.
Topics: Humans; Multiple Sclerosis; Epstein-Barr Virus Infections; Quality of Life; Moon; Herpesvirus 4, Human; Recurrence
PubMed: 37476952
DOI: 10.1080/19932820.2023.2238354 -
Neurologic Clinics Feb 2024The unprecedented scope of the coronavirus disease 2019 (COVID-19) pandemic resulted in numerous disruptions to daily life, including for people with multiple sclerosis... (Review)
Review
The unprecedented scope of the coronavirus disease 2019 (COVID-19) pandemic resulted in numerous disruptions to daily life, including for people with multiple sclerosis (PwMS). This article reviews how disruptions in multiple sclerosis (MS) care prompted innovations in delivery of care (eg, via telemedicine) and mobilized the global MS community to rapidly adopt safe and effective practices. We discuss how our understanding of the risks of COVID-19 in PwMS has evolved along with recommendations pertaining to disease-modifying therapies and vaccines. With lessons learned during the COVID-19 pandemic, we examine potential questions for future research in this new era of MS care.
Topics: Humans; COVID-19; Multiple Sclerosis; Pandemics; Telemedicine
PubMed: 37980121
DOI: 10.1016/j.ncl.2023.06.006