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International Journal of Molecular... Oct 2021Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical... (Review)
Review
Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.
Topics: Animals; Biomarkers; Humans; Metabolome; Metabolomics; Multiple Sclerosis; Prognosis
PubMed: 34681773
DOI: 10.3390/ijms222011112 -
European Neurology 2014Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal loss. The etiology of MS is unknown;... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal loss. The etiology of MS is unknown; however, environmental and genetic factors play a key role in the development of MS. Diagnostic criteria have been adapted to facilitate earlier diagnosis with increased sensitivity and specificity. Our understanding of the pathophysiology of MS has deepened considerably in recent years, resulting in different therapies to modify the disease course. Furthermore, several drugs have lately shown efficacy in phase III studies and their approval is expected in the near future. As treatment options expand, a future challenge will be to find the optimal treatment for the individual patient.
SUMMARY
This mini-review gives an overview of the current knowledge of MS with emphasis on the latest diagnostic criteria and both current and upcoming treatment options. Key Messages: Treatment of MS changes rapidly as the knowledge and therapeutic options in MS expand. Clinical Impact: Diagnosis of MS is based on McDonald criteria. MS therapy can be divided into relapse, disease-modifying and symptomatic treatment. Relapses are commonly treated with intravenous methylprednisolone. First-line therapy consists of either interferon-β, glatiramer acetate or teriflunomide. In general, agents used as escalation therapies (natalizumab, fingolimod and mitoxantrone) are more potent than the agents used for first-line therapy; however, these have potentially serious side effects and should be used with care.
Topics: Central Nervous System; Humans; Immunologic Factors; Multiple Sclerosis
PubMed: 25095894
DOI: 10.1159/000360528 -
Journal of Internal Medicine Apr 2014Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New... (Review)
Review
Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e.g. fingolimod or natalizumab if JC virus antibody-negative). The aim of this review is to discuss the clinical benefits, mechanisms of action, safety profiles and monitoring strategies of current MS disease-modifying therapies in clinical practice and of those expected to enter the market in the near future.
Topics: Algorithms; Antibodies, Monoclonal; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Immunologic Factors; Immunosuppressive Agents; Mesenchymal Stem Cell Transplantation; Multiple Sclerosis; Secondary Prevention; Severity of Illness Index; Treatment Outcome
PubMed: 24444048
DOI: 10.1111/joim.12203 -
Neurological Sciences : Official... Aug 2022In 2018, the first list of rare diseases was published by the National Health Council of China, and multiple sclerosis (MS) was included in this list. Since then, the... (Review)
Review
In 2018, the first list of rare diseases was published by the National Health Council of China, and multiple sclerosis (MS) was included in this list. Since then, the Chinese government and neurologists have made efforts to improve the clinical outcomes of patients with MS. During last few years, the incidence of MS in China was also investigated. The early and accurate diagnosis of MS was improved due to the application and promotion of magnetic resonance imaging and new diagnosis criteria. The market for and medical insurance access to disease-modifying therapies (DMTs) has been greatly accelerated, which has provided more treatment options and improved clinical outcomes for patients with MS, as well as reduced treatment cost. The pattern of MS in China is gradually changing, from delayed to early diagnosis, and from no treatment to treatment with DMTs during remission. This narrative review aimed to summarize an update to the status of MS in China, including incidence and prevalence, diagnosis, and available treatments. This would help to better understand the diagnosis and treatment gap between mainland China and other Asian regions, demonstrating the necessity of accurate diagnosis and optimized treatment of MS in China.
Topics: China; Health Care Costs; Humans; Incidence; Multiple Sclerosis; Prevalence
PubMed: 35583839
DOI: 10.1007/s10072-022-06126-4 -
Current Opinion in Oncology Mar 2011Immunomodulatory medications for multiple sclerosis provide only modest control of this potentially debilitating auto-immune disease of the central nervous system. The... (Review)
Review
PURPOSE OF REVIEW
Immunomodulatory medications for multiple sclerosis provide only modest control of this potentially debilitating auto-immune disease of the central nervous system. The immunosuppression provided by high-dose chemotherapy has been studied to address treatment-refractory disease. In this review, we discuss the recent significant work in this field and its associated controversies.
RECENT FINDINGS
Conclusive evidence for the efficacy of high-dose chemotherapy with stem cell rescue is lacking given the lack of uniform patient populations and varying treatment protocols. Moreover, the significant toxicity associated with this procedure has dampened enthusiasm for its widespread use. High-dose chemotherapy without stem cell rescue has been trialed as a less toxic approach that eliminates the possibility of re-infusing autoreactive lymphocytes found in the stem cell product.
SUMMARY
Before high-dose chemotherapy with or without stem cell rescue can be adopted for clinical practice, both approaches require testing in randomized clinical trials. Both procedures have the possibility of decreasing disease activity but high-dose chemotherapy without stem cell rescue having a more favorable safety profile, may prove a more significant advance in the field of high-dose therapy for multiple sclerosis.
Topics: Combined Modality Therapy; Humans; Multiple Sclerosis; Stem Cell Transplantation
PubMed: 21169833
DOI: 10.1097/CCO.0b013e328342c6b3 -
Eastern Mediterranean Health Journal =... Dec 2022Multiple sclerosis is a complex and intractable neurological disease associated with substantial morbidity, healthcare utilization, management cost, and loss of...
BACKGROUND
Multiple sclerosis is a complex and intractable neurological disease associated with substantial morbidity, healthcare utilization, management cost, and loss of productivity. There has been an alarming increase in the number of multiple sclerosis cases in Arab countries in recent years, which has spurred an increase in local research.
AIMS
To analyse the multiple sclerosis research profile in Arab countries.
METHODS
A total of 781 publications focusing on multiple sclerosis research in Arab countries from 1983 to 2021 were extracted from the Web of Science database and analysed using bibliometric techniques.
RESULTS
Publication on multiple sclerosis research increased sharply in the last decade, globally and in the Arab countries. However, Arab countries have only contributed 0.8% of the overall number of publications. Keyword pattern analysis showed that magnetic resonance imaging, optical coherence tomography, expanded disability status, demyelination, and epidemiology were the major themes of multiple sclerosis research in Arab countries. Case-control, cohort, and descriptive studies were the most prevalent study designs. However, there was a notable paucity of meta-analyses, randomized controlled trials, and clinical trials.
CONCLUSION
Arab countries can improve their regional expertise and add a wealth of knowledge to global multiple sclerosis resources by diversifying their current research initiatives, and tracking recent advances in pathogenesis, diagnosis, and management of multiple sclerosis.
Topics: Humans; Multiple Sclerosis; Arabs; Biomedical Research; Middle East; Bibliometrics
PubMed: 36573566
DOI: 10.26719/emhj.22.092 -
Acta Medica Portuguesa Aug 2016
Topics: Child; Humans; Multiple Sclerosis
PubMed: 27914150
DOI: 10.20344/amp.8054 -
International Journal of Molecular... Aug 2015Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various,... (Review)
Review
Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases.
Topics: Animals; Central Nervous System; Disease Models, Animal; Humans; Immune System; Immunomodulation; Kynurenine; Metabolic Networks and Pathways; Multiple Sclerosis; Neuroimmunomodulation
PubMed: 26287161
DOI: 10.3390/ijms160818270 -
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