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The New England Journal of Medicine Jan 2018
Review
Topics: Antibodies, Monoclonal; Biomarkers; Brain; Glatiramer Acetate; Humans; Immunologic Factors; Interferon-beta; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 29320652
DOI: 10.1056/NEJMra1401483 -
Neurologia May 2019The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. (Review)
Review
BACKGROUND
The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors.
AIMS
To analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease.
METHODS
We conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for 'multiple sclerosis', 'MS', 'EAE', 'pregnancy', 'hormonal factors', 'treatment', and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts.
RESULTS AND CONCLUSIONS
We provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, fetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data.
Topics: Female; Humans; Infant, Newborn; Multiple Sclerosis; Postpartum Period; Pregnancy; Pregnancy Complications; Women's Health
PubMed: 27546613
DOI: 10.1016/j.nrl.2016.06.005 -
Brain : a Journal of Neurology Sep 2022Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study...
Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins and the extent to which multiple sclerosis therapies delay disability accumulation. Using the Novartis-Oxford multiple sclerosis (NO.MS) data pool spanning all multiple sclerosis phenotypes and paediatric multiple sclerosis, we evaluated ∼200 000 Expanded Disability Status Scale (EDSS) transitions from >27 000 patients with ≤15 years follow-up. We analysed three datasets: (i) A full analysis dataset containing all observational and randomized controlled clinical trials in which disability and relapses were assessed (n = 27 328); (ii) all phase 3 clinical trials (n = 8346); and (iii) all placebo-controlled phase 3 clinical trials (n = 4970). We determined the relative importance of RAW and PIRA, investigated the role of relapses on all-cause disability worsening using Andersen-Gill models and observed the impact of the mechanism of worsening and disease-modifying therapies on the time to reach milestone disability levels using time continuous Markov models. PIRA started early in the disease process, occurred in all phenotypes and became the principal driver of disability accumulation in the progressive phase of the disease. Relapses significantly increased the hazard of all-cause disability worsening events; following a year in which relapses occurred (versus a year without relapses), the hazard increased by 31-48% (all P < 0.001). Pre-existing disability and older age were the principal risk factors for incomplete relapse recovery. For placebo-treated patients with minimal disability (EDSS 1), it took 8.95 years until increased limitation in walking ability (EDSS 4) and 18.48 years to require walking assistance (EDSS 6). Treating patients with disease-modifying therapies delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and 3.09 years (2.60, 3.72), respectively. In patients with relapsing-remitting multiple sclerosis, those who worsened exclusively due to RAW events took a similar length of time to reach milestone EDSS values compared with those with PIRA events; the fastest transitions were observed in patients with PIRA and superimposed relapses. Our data confirm that relapses contribute to the accumulation of disability, primarily early in multiple sclerosis. PIRA begins in relapsing-remitting multiple sclerosis and becomes the dominant driver of disability accumulation as the disease evolves. Pre-existing disability and older age are the principal risk factors for further disability accumulation. The use of disease-modifying therapies delays disability accrual by years, with the potential to gain time being highest in the earliest stages of multiple sclerosis.
Topics: Disabled Persons; Disease Progression; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence
PubMed: 35104840
DOI: 10.1093/brain/awac016 -
Current Opinion in Neurology Jun 2016We discuss new paradigms for understanding the immunopathology of multiple sclerosis through the recent development of high throughput genetic analysis, emergence of... (Review)
Review
PURPOSE OF REVIEW
We discuss new paradigms for understanding the immunopathology of multiple sclerosis through the recent development of high throughput genetic analysis, emergence of numerous candidate biomarkers, and the broadening of the treatment arsenal.
RECENT FINDINGS
The recent use of genome wide association studies provide new tools for a better understanding of multiple sclerosis etiology. Genome-wide association studies have identified many genes implicated in immune regulation and the next step will be to elucidate how those genetic variations influence immune cell function to drive disease development and progression. Furthermore, patient care has seen the emergence of new biomarkers for monitoring disease progression and response to treatment. Finally, the introduction of numerous immunomodulatory treatments will likely improve clinical outcome of multiple sclerosis patients in the future.
SUMMARY
Breakthroughs in the field of multiple sclerosis have led to a better understanding of the physiopathology of the disease, follow up, and treatment of the patients that develop relapsing remitting multiple sclerosis. The next challenge for multiple sclerosis will be to press forward to model and decipher multiple sclerosis progression, which will help both to develop therapeutics and generate knowledge about mechanisms of neurodegeneration.
Topics: Biomarkers; Disease Progression; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Immunologic Factors; Multiple Sclerosis
PubMed: 27058221
DOI: 10.1097/WCO.0000000000000319 -
Seminars in Neurology Aug 2016It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in... (Review)
Review
It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients.
Topics: Diagnosis, Differential; Humans; Multiple Sclerosis; United States
PubMed: 27643903
DOI: 10.1055/s-0036-1585456 -
Journal of Neurology, Neurosurgery, and... Jun 2019Fatigue is one of the most common symptoms in multiple sclerosis (MS), with a major impact on patients' quality of life. Currently, treatment proceeds by trial and error... (Review)
Review
Fatigue is one of the most common symptoms in multiple sclerosis (MS), with a major impact on patients' quality of life. Currently, treatment proceeds by trial and error with limited success, probably due to the presence of multiple different underlying mechanisms. Recent neuroscientific advances offer the potential to develop tools for differentiating these mechanisms in individual patients and ultimately provide a principled basis for treatment selection. However, development of these tools for differential diagnosis will require guidance by pathophysiological and cognitive theories that propose mechanisms which can be assessed in individual patients. This article provides an overview of contemporary pathophysiological theories of fatigue in MS and discusses how the mechanisms they propose may become measurable with emerging technologies and thus lay a foundation for future personalised treatments.
Topics: Brain; Cognition; Fatigue; Humans; Multiple Sclerosis
PubMed: 30683707
DOI: 10.1136/jnnp-2018-320050 -
European Journal of Neurology Jan 2023Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been... (Review)
Review
BACKGROUND AND PURPOSE
Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians. This article examines how the diagnostic definitions of progressive MS impact clinical research, the design of clinical trials and, ultimately, treatment decisions.
METHODS
We carried out an extensive review of the literature highlighting differences in the definition of progressive forms of MS, and the importance of assessing the extent of the ongoing inflammatory component in MS when making treatment decisions.
RESULTS
Inconsistent results in phase III clinical studies of treatments for progressive MS, may be attributable to differences in patient characteristics (e.g., age, clinical and radiological activity at baseline) and endpoint definitions. In both primary and secondary progressive MS, patients who are younger and have more active disease will derive the greatest benefit from the available treatments.
CONCLUSIONS
We recommend making treatment decisions based on the individual patient's pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. Because the definition of progressive MS differs across clinical studies, careful selection of eligibility criteria and study endpoints is needed for future studies in patients with progressive MS.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Disease Progression; Longitudinal Studies; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36209464
DOI: 10.1111/ene.15593 -
Biomedical Journal 2014
Topics: Animals; Central Nervous System; Humans; Multiple Sclerosis
PubMed: 24732656
DOI: 10.4103/2319-4170.130317 -
BMC Neurology Mar 2018Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population.... (Review)
Review
BACKGROUND
Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS.
METHODS
The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice.
RESULTS
The revised International Pediatric MS group diagnostic criteria improved the accuracy of diagnosis. Identification of red flags and mimickers (e.g. acute disseminated encephalomyelitis and neuromyelitis optica) are vital before establishing a definitive diagnosis. Possible etiology and mechanisms including both environmental and genetic risk factors are highlighted. Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age. Although no therapeutic randomized clinical trials were conducted in pediatric cohorts, open-label multi-center studies reported efficacy and safety results with beta interferons, glatiramer acetate and natalizumab in similar adult cohorts. Several randomized clinical trials assessing the efficacy and safety of oral disease-modifying therapies are ongoing in pediatric MS patients.
CONCLUSION
Pediatric MS has been increasingly recognized to have a more inflammatory course with frequent infratentorial presentations at onset, which would have important implications in the future management of pediatric cohorts while awaiting the results of ongoing clinical trials.
Topics: Adolescent; Child; Female; Humans; Male; Multiple Sclerosis; Risk Factors
PubMed: 29523094
DOI: 10.1186/s12883-018-1026-3 -
Autoimmunity Reviews Nov 2023Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system, characterized by inflammatory demyelination. It is primarily found... (Review)
Review
Multiple sclerosis (MS) is an autoimmune-mediated degenerative disease of the central nervous system, characterized by inflammatory demyelination. It is primarily found in women of childbearing age, making pregnancy a significant concern for both patients with MS and clinicians. To assist these patients in achieving their desire for pregnancy, reducing MS relapses during all stages of pregnancy, preventing the progression of MS, mitigating the impact of MS treatment on the course and outcome of pregnancy, and a thorough understanding of the relationship between pregnancy and MS, as well as specific management and the application of relevant medications for MS patients at each stage of pregnancy, are essential. This article provides an update on pregnancy-related issues in women with MS, including the general recommendations for management at each stage of pregnancy.
Topics: Pregnancy; Humans; Female; Multiple Sclerosis; Pregnancy Complications; Recurrence
PubMed: 37741528
DOI: 10.1016/j.autrev.2023.103449