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Frontiers in Immunology 2021An individualized innovative disease management is of great importance for people with multiple sclerosis (pwMS) to cope with the complexity of this chronic,... (Review)
Review
An individualized innovative disease management is of great importance for people with multiple sclerosis (pwMS) to cope with the complexity of this chronic, multidimensional disease. However, an individual state of the art strategy, with precise adjustment to the patient's characteristics, is still far from being part of the everyday care of pwMS. The development of digital twins could decisively advance the necessary implementation of an individualized innovative management of MS. Through artificial intelligence-based analysis of several disease parameters - including clinical and para-clinical outcomes, multi-omics, biomarkers, patient-related data, information about the patient's life circumstances and plans, and medical procedures - a digital twin paired to the patient's characteristic can be created, enabling healthcare professionals to handle large amounts of patient data. This can contribute to a more personalized and effective care by integrating data from multiple sources in a standardized manner, implementing individualized clinical pathways, supporting physician-patient communication and facilitating a shared decision-making. With a clear display of pre-analyzed patient data on a dashboard, patient participation and individualized clinical decisions as well as the prediction of disease progression and treatment simulation could become possible. In this review, we focus on the advantages, challenges and practical aspects of digital twins in the management of MS. We discuss the use of digital twins for MS as a revolutionary tool to improve diagnosis, monitoring and therapy refining patients' well-being, saving economic costs, and enabling prevention of disease progression. Digital twins will help make precision medicine and patient-centered care a reality in everyday life.
Topics: Artificial Intelligence; Clinical Decision-Making; Health Status; Humans; Multiple Sclerosis; Patient-Centered Care; Patient-Specific Modeling; Precision Medicine; Prognosis
PubMed: 34012452
DOI: 10.3389/fimmu.2021.669811 -
Behavioural Neurology 2017Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Although cognitive impairment has been well established in adult patients with... (Review)
Review
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Although cognitive impairment has been well established in adult patients with MS, its occurrence in patients with pediatric-onset MS has recently been reported. In this review, I discuss the main features of cognitive impairment in pediatric MS as determined by long-term follow-up studies, neuropsychiatric test batteries, and the results of neuroradiological imaging studies that investigated the pathogenesis of pediatric MS. The most commonly affected cognitive domains in adults are attention, processing speed, and visuomotor skills; language and intelligence are also affected in pediatric MS. A young age at disease onset is the strongest risk factor for these impairments, which may be due to the effect of inflammatory demyelination and neurodegeneration on the developing central nervous system and neural networks in children. Cognitive impairment has long-term effects on patients' academic life and the quality of their social life. Therefore, all patients with pediatric MS should be screened and monitored for cognitive impairment. This review also highlights the need for neuropsychological test batteries that assess different cognitive domains in children and adolescents with multiple sclerosis and for cognitive rehabilitation programs to improve the quality of their academic and social life.
Topics: Adolescent; Child; Cognitive Dysfunction; Humans; Multiple Sclerosis
PubMed: 29434433
DOI: 10.1155/2017/1463570 -
Arquivos de Neuro-psiquiatria Oct 2016Multiple sclerosis (MS) prevalence is higher in Caucasian (CA) populations, narrowing the analysis of the impact of Afro-descendant (AD) populations in disease outcomes.... (Review)
Review
Multiple sclerosis (MS) prevalence is higher in Caucasian (CA) populations, narrowing the analysis of the impact of Afro-descendant (AD) populations in disease outcomes. Even so, recent studies observed that AD patients have a more severe course. The main objective of this study is to confirm and discuss, through a systematic review, that being AD is a risk factor for disability accumulation and/or severe progression in patients with MS. A systematic review of published data in the last eleven years was performed, which evaluated clinical aspects and long term disability in patients with MS. Fourteen studies were included. Of these fourteen articles, thirteen observed a relationship between ancestry and poorer outcome of MS. African ancestry is a condition inherent in the patient and should be considered as an initial clinical characteristic affecting prognosis, and influencing which therapeutic decision to make in initial phases.
Topics: Black People; Disability Evaluation; Disease Progression; Female; Humans; Male; Multiple Sclerosis; Prognosis; Risk Factors; Severity of Illness Index
PubMed: 27759810
DOI: 10.1590/0004-282X20160118 -
Frontiers in Immunology 2023Multiple Sclerosis (MS) has a complex pathophysiology that involves genetic and environmental factors. DNA methylation (DNAm) is one epigenetic mechanism that can...
INTRODUCTION
Multiple Sclerosis (MS) has a complex pathophysiology that involves genetic and environmental factors. DNA methylation (DNAm) is one epigenetic mechanism that can reversibly modulate gene expression. Cell specific DNAm changes have been associated with MS, and some MS therapies such as dimethyl fumarate can influence DNAm. Interferon Beta (IFNβ), was one of the first disease modifying therapies in multiple sclerosis (MS). However, how IFNβ reduces disease burden in MS is not fully understood and little is known about the precise effect of IFNβ treatment on methylation.
METHODS
The objective of this study was to determine the changes in DNAm associated with INFβ use, using methylation arrays and statistical deconvolutions on two separate datasets (total n = 64, n = 285).
RESULTS
We show that IFNβ treatment in people with MS modifies the methylation profile of interferon response genes in a strong, targeted, and reproducible manner. Using these identified methylation differences, we constructed a methylation treatment score (MTS) that is an accurate discriminator between untreated and treated patients (Area under the curve = 0.83). This MTS is time-sensitive and in consistent with previously identified IFNβ treatment therapeutic lag. This suggests that methylation changes are required for treatment efficacy. Overrepresentation analysis found that IFNβ treatment recruits the endogenous anti-viral molecular machinery. Finally, statistical deconvolution revealed that dendritic cells and regulatory CD4+ T cells were most affected by IFNβ induced methylation changes.
DISCUSSION
In conclusion, our study shows that IFNβ treatment is a potent and targeted epigenetic modifier in multiple sclerosis.
Topics: Humans; Interferon-beta; Multiple Sclerosis; Treatment Outcome
PubMed: 37325639
DOI: 10.3389/fimmu.2023.1162796 -
Nature Reviews. Neurology Dec 2017Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in... (Review)
Review
Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. However, trial design faces several obstacles: optimal clinical or paraclinical outcome measures to assess remyelination remain ill-defined, and identification of the ideal timing of therapy is also a crucial issue. In addition, realistic expectations are needed concerning the probable benefits of such therapies. Nevertheless, approaches that enhance remyelination are likely to be protective for axons and so could prevent long-term neurodegeneration. Future MS treatment paradigms, therefore, are likely to comprise a combinatorial approach that involves both immunomodulatory and regenerative treatments.
Topics: Animals; Humans; Multiple Sclerosis; Remyelination
PubMed: 29146953
DOI: 10.1038/nrneurol.2017.139 -
Behavioural Neurology 2018Multiple sclerosis (MS) affects cognition in the majority of patients. A major aspect of the disease is brain volume loss (BVL), present in all phases and types... (Review)
Review
Multiple sclerosis (MS) affects cognition in the majority of patients. A major aspect of the disease is brain volume loss (BVL), present in all phases and types (relapsing and progressive) of the disease and linked to both motor and cognitive disabilities. Due to the lack of effective pharmacological treatments for cognition, cognitive rehabilitation and other nonpharmacological interventions such as repetitive transcranial magnetic stimulation (rTMS) have recently emerged and their potential role in functional connectivity is studied. With recently developed advanced neuroimaging and neurophysiological techniques, changes related to alterations of the brain's functional connectivity can be detected. In this overview, we focus on the brain's functional reorganization in MS, theoretical and practical aspects of rTMS utilization in humans, and its potential therapeutic role in treating cognitively impaired MS patients.
Topics: Brain; Cognition; Cognition Disorders; Humans; Multiple Sclerosis; Neuroimaging; Transcranial Direct Current Stimulation
PubMed: 29568339
DOI: 10.1155/2018/8584653 -
Multiple Sclerosis (Houndmills,... Apr 2022
Topics: Comorbidity; Humans; Multiple Sclerosis; Patient Acceptance of Health Care
PubMed: 35296176
DOI: 10.1177/13524585221081985 -
BMC Neurology May 2013Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.
METHODS
We searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or "premorbid" (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or "surgery". We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.
RESULTS
We identified 33 case-control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I(2) = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I(2) = 0%) in individual's ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I(2) = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I(2) = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I(2) = 35%). The combined OR of 15 studies (N = 2,380) looking at "surgery" before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I(2) = 71%).
CONCLUSIONS
We found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.
Topics: Case-Control Studies; Databases, Factual; Humans; Multiple Sclerosis; Risk Factors
PubMed: 23648120
DOI: 10.1186/1471-2377-13-41 -
Neurologia I Neurochirurgia Polska 2022For the past four decades, multiple sclerosis (MS) has been a focus for clinical trial development and execution. Advances in translational neuroimmunology have led to...
For the past four decades, multiple sclerosis (MS) has been a focus for clinical trial development and execution. Advances in translational neuroimmunology have led to the development of effective disease-modifying therapies (DMTs) that greatly benefit patients with MS and mitigate their burden of disease. These achievements also stem from continued progress made in the definition and discovery of sensitive disease diagnostic criteria, objective disability assessment scales, precise imaging techniques, and disease-specific biomarkers. As a result, our knowledge of MS pathophysiology is more mature; the established clinical practice for the diagnosis and management of MS could serve as a roadmap to guide the development of more disease-specific interventions. In this article we briefly review the main achievements in the evolution of clinical trials for MS, and discuss opportunities for improvements.
Topics: Humans; Multiple Sclerosis
PubMed: 35712986
DOI: 10.5603/PJNNS.a2022.0041 -
Disease-a-month : DM Jan 1996Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be... (Review)
Review
Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be autoimmune in nature. The cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. MS generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. These tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. Treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. The frequency of relapses can be reduced with interferon-beta (Betaseron). Copolymer 1 and interferon-beta la are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of relapses in relapsing-remitting MS. Treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. Use of other agents is being investigated.
Topics: Adolescent; Adult; Animals; Combined Modality Therapy; Diagnosis, Differential; Disease Models, Animal; Humans; Multiple Sclerosis; Prognosis; Recurrence
PubMed: 8556963
DOI: 10.1016/s0011-5029(96)90012-7