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The American Journal of Medicine Dec 2020Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system, and the leading cause of nontraumatic neurological... (Review)
Review
Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system, and the leading cause of nontraumatic neurological disability in young adults. Effective management requires a multifaceted approach to control acute attacks, manage progressive worsening, and remediate bothersome or disabling symptoms associated with this illness. Remarkable advances in treatment of all forms of MS, and especially for relapsing disease, have favorably changed the long-term outlook for many patients. There also has been a conceptual shift in understanding the immune pathology of MS, away from a purely T-cell-mediated model to recognition that B cells have a key role in pathogenesis. The emergence of higher-efficacy drugs requiring less frequent administration have made these preferred options in terms of tolerability and adherence. Many experts now recommend use of these as first-line treatment for many patients with early disease, before permanent disability is evident.
Topics: Antibodies, Monoclonal; Humans; Immunosuppressive Agents; Multiple Sclerosis; Physical Therapy Modalities
PubMed: 32682869
DOI: 10.1016/j.amjmed.2020.05.049 -
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 -
Neurodegenerative Disease Management Feb 2023The multiple sclerosis (MS) neurotherapeutic landscape is rapidly evolving. New disease-modifying therapies (DMTs) with improved efficacy and safety, in addition to an... (Review)
Review
The multiple sclerosis (MS) neurotherapeutic landscape is rapidly evolving. New disease-modifying therapies (DMTs) with improved efficacy and safety, in addition to an expanding pipeline of agents with novel mechanisms, provide more options for patients with MS. While treatment of MS neuroinflammation is well tailored in the existing DMT armamentarium, concerted efforts are currently underway for identifying neuropathological targets and drug discovery for progressive MS. There is also ongoing research to develop agents for remyelination and neuroprotection. Further insights are needed to guide DMT initiation and sequencing as well as to determine the role of autologous stem cell transplantation in relapsing and progressive MS. This review provides a summary of these updates.
Topics: Humans; Multiple Sclerosis; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Multiple Sclerosis, Chronic Progressive; Neuroprotection; Multiple Sclerosis, Relapsing-Remitting
PubMed: 36314777
DOI: 10.2217/nmt-2021-0058 -
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 -
Nutrients Mar 2022Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent... (Review)
Review
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent clinical features include visual loss and sensorimotor symptoms and mainly affects those of young age. Some of the factors affecting its pathogenesis are genetic and/or environmental including viruses, smoking, obesity, and nutrition. Current research provides evidence that diet may influence MS onset, course, and quality of life of the patients. In this review, we address the role of nutrition on MS pathogenesis as well as dietary interventions that show promising beneficial results with respect to MS activity and progression. Investigation with large prospective clinical studies is required in order to thoroughly evaluate the role of diet in MS.
Topics: Central Nervous System; Diet; Humans; Multiple Sclerosis; Prospective Studies; Quality of Life
PubMed: 35334810
DOI: 10.3390/nu14061150 -
Frontiers in Immunology 2022Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron's axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8 T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.
Topics: Animals; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin Sheath; Th17 Cells
PubMed: 36211343
DOI: 10.3389/fimmu.2022.996469 -
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 -
Medicine Feb 2024Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination, inflammation, neuronal loss, and gliosis (scarring). Our object to review MS pathophysiology... (Review)
Review
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination, inflammation, neuronal loss, and gliosis (scarring). Our object to review MS pathophysiology causes and treatment. A Narrative Review article was conducted by searching on Google scholar, PubMed, Research Gate about relevant keywords we exclude any unique cases and case reports. The destruction of myelinated axons in the central nervous system reserves this brunt. This destruction is generated by immunogenic T cells that produce cytokines, copying a proinflammatory T helper cells1-mediated response. Autoreactive cluster of differentiation 4 + cells, particularly the T helper cells1 subtype, are activated outside the system after viral infections. T-helper cells (cluster of differentiation 4+) are the leading initiators of MS myelin destruction. The treatment plan for individuals with MS includes managing acute episodes, using disease-modifying agents to decrease MS biological function of MS, and providing symptom relief. Management of spasticity requires physiotherapy, prescription of initial drugs such as baclofen or gabapentin, secondary drug options such as tizanidine or dantrolene, and third-line treatment such as benzodiazepines. To treat urinary incontinence some options include anticholinergic medications such as oxybutynin hydrochloride, tricyclic antidepressants (such as amitriptyline), and intermittent self-catheterization. When it comes to bowel problems, one can try to implement stool softeners and consume a high roughage diet. The review takes about MS causes Pathophysiology and examines current treatment strategies, emphasizing the advancements in disease-modifying therapies and symptomatic treatments. This comprehensive analysis enhances the understanding of MS and underscores the ongoing need for research to develop more effective treatments.
Topics: Humans; Multiple Sclerosis; Treatment Outcome; Chronic Disease; Muscle Spasticity
PubMed: 38394496
DOI: 10.1097/MD.0000000000037297 -
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