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Clinical Medicine (London, England) Dec 2016This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic... (Review)
Review
This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development.
Topics: Humans; Multiple Sclerosis
PubMed: 27956442
DOI: 10.7861/clinmedicine.16-6-s53 -
Handbook of Clinical Neurology 2018Multiple sclerosis is a potentially progressive, autoimmune neurologic disorder of the central nervous system, resulting from an autoimmune attack on central nervous... (Review)
Review
Multiple sclerosis is a potentially progressive, autoimmune neurologic disorder of the central nervous system, resulting from an autoimmune attack on central nervous system white matter. It is a leading cause of neurologic symptoms in young adults, with no known cure. Emerging disease-modifying therapies aim to control symptoms, with increasingly sophisticated immune function modulation. Though several environmental exposures increase the risk of developing the disease, a large fraction of overall risk is heritable and can be attributed to hundreds of common genetic variants influencing gene regulation in specific immune subsets. Here, we review the history of the disease, the realization that risk is heritable, and the recent revelation of hundreds of genetic variants driving this risk by international consortia studying tens of thousands of patients. Finally, we discuss how these results are revealing the specific pathobiology of multiple sclerosis and how this knowledge is transforming drug discovery.
Topics: Central Nervous System; Genetic Association Studies; Humans; Multiple Sclerosis; White Matter
PubMed: 29478610
DOI: 10.1016/B978-0-444-64076-5.00046-6 -
Seminars in Neurology Apr 2018Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a... (Review)
Review
Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune etiology, mediated by activated T cells with evolving evidence of a significant contribution from B cells and cells of the innate immune system. The disease is thought to be due to a complex interaction between different genetic and environmental factors. The prevalence of MS is rising all over the world, due on one hand to earlier diagnosis and prolonged survival, and on the other to a true increase in incidence of the disease. The diagnosis of MS remains clinical despite recent advances in diagnostics and relies on demonstrating dissemination in space and time while excluding alternative diagnoses. The Mc Donald diagnostic criteria, with their recent 2017 revision, are currently widely accepted in the MS community. Although no cure is yet available, many disease-modifying therapies (DMTs) have shown different levels of efficacy in preventing relapses, accumulation of lesions on magnetic resonance imaging (MRI), and disability progression. Current treatment strategies include gradual escalation based on clinical and radiological criteria that determine treatment response, or initial induction with high efficacy DMTs especially in patients with an early aggressive course.
Topics: Anti-Inflammatory Agents; Disease Management; Humans; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 29791948
DOI: 10.1055/s-0038-1649502 -
Australian Journal of General Practice Apr 2022Multiple sclerosis (MS) is a multifocal inflammatory central nervous system disorder. There are now many highly effective disease-modifying therapies (DMTs) available as... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a multifocal inflammatory central nervous system disorder. There are now many highly effective disease-modifying therapies (DMTs) available as treatment options, which have a significant impact on disease activity and long-term disability.
OBJECTIVE
The aim of this article is to provide a concise overview of the diagnosis, DMTs and prognosis of MS.
DISCUSSION
The diagnosis of MS is made on clinicoradiological grounds to prove dissemination of disease in both time and space in the nervous system. While the expanding options of DMTs have had a significant impact on disability, they make medication selection for individual patients more complicated. Patients with MS often have a model of care shared between the neurologist and the general practitioner. This review article summarises the key aspects of the diagnosis, DMTs and prognosis of MS relevant to the general practitioner.
Topics: Humans; Multiple Sclerosis; Prognosis
PubMed: 35362004
DOI: 10.31128/AJGP-07-21-6103 -
The Lancet. Neurology Jan 2023Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors-relapsing-remitting, secondary progressive, and primary progressive-for patient... (Review)
Review
Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors-relapsing-remitting, secondary progressive, and primary progressive-for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. The apparent evolution to a progressive course reflects a partial shift from predominantly localised acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination. Ageing increases neural susceptibility to injury and decreases resilience. These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making.
Topics: Humans; Multiple Sclerosis; Aging; Inflammation; Disease Progression; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36410373
DOI: 10.1016/S1474-4422(22)00289-7 -
Postepy Higieny I Medycyny... Jun 2017Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.
Topics: Evoked Potentials, Visual; Female; Humans; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Oligoclonal Bands
PubMed: 28665284
DOI: 10.5604/01.3001.0010.3836 -
Lancet (London, England) Oct 2008Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons....
Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.
Topics: Disease Progression; Female; Genetics, Population; Humans; Male; Multiple Sclerosis; Prevalence
PubMed: 18970977
DOI: 10.1016/S0140-6736(08)61620-7 -
The Lancet. Neurology Oct 2020Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on... (Review)
Review
Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on instrumental activities of daily living. The prevalence of cognitive impairment in multiple sclerosis varies across the lifespan and might be difficult to distinguish from other causes in older age. MRI studies show that widespread changes to brain networks contribute to cognitive dysfunction, and grey matter atrophy is an early sign of potential future cognitive decline. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains. Narrowing evaluation to these core areas permits brief, routine assessment in the clinical setting. Owing to its brevity, reliability, and sensitivity, the Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity. The Symbol Digit Modalities Test can also be used in clinical trials, and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.
Topics: Adolescent; Aged, 80 and over; Cognitive Dysfunction; Disease Management; Female; Humans; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 32949546
DOI: 10.1016/S1474-4422(20)30277-5 -
Brain and Behavior Sep 2015Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after... (Review)
Review
BACKGROUND
Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma.
DISCUSSION
The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain.
CONCLUSION
An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented.
Topics: Brain; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Spinal Cord
PubMed: 26445701
DOI: 10.1002/brb3.362 -
Cold Spring Harbor Perspectives in... Sep 2018The 1996 originally established multiple sclerosis (MS) subtypes, based solely on clinical impression and consensus, were revised in 2013 to review potential imaging and... (Review)
Review
The 1996 originally established multiple sclerosis (MS) subtypes, based solely on clinical impression and consensus, were revised in 2013 to review potential imaging and biological correlates and to reflect recently identified clinical aspects of MS. As a result, potential new disease phenotypes, radiologically isolated syndrome, and clinically isolated syndrome were considered along with the addition of two new descriptor subtypes: activity and progression applied to relapsing remitting and progressive MS phenotypes. In this way, the description of an individual patient's disease course is refined and provides temporal information about the ongoing disease process. There is still a lack of imaging and biological markers that would distinguish MS phenotypes and prognosticate the disease course on an individual patient's level, creating a pressing need for large collaborative research efforts in this field.
Topics: Biomarkers; Clinical Trials as Topic; Consensus; Disease Progression; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Societies, Medical
PubMed: 29358317
DOI: 10.1101/cshperspect.a028928