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Nature Reviews. Neurology Aug 2021A prodrome is an early set of signs, symptoms or other findings that occur before the onset of typical symptoms of a disease. Prodromal phases are well recognized in... (Review)
Review
A prodrome is an early set of signs, symptoms or other findings that occur before the onset of typical symptoms of a disease. Prodromal phases are well recognized in several neurological and inflammatory diseases, but the possibility of a prodrome in multiple sclerosis (MS) has received relatively little attention until the past few years. In this Perspective, we summarize what is currently known about the MS prodrome, including its possible duration, clinical features and potential biomarkers. We also consider what insights and lessons can be learned from knowledge of and research into the prodromal phases of other diseases. A better understanding of the MS prodrome could have profound clinical implications as it could enable earlier recognition of MS and earlier initiation of treatments that reduce relapse rates and long-term disability. Knowledge of the MS prodrome could also affect research into the causes of MS, and putative risk factors must be re-evaluated in light of the MS prodrome. We conclude by outlining the major knowledge gaps and propose future initiatives.
Topics: Biomarkers; Cognitive Dysfunction; Humans; Multiple Sclerosis; Neuroimaging; Prodromal Symptoms; Risk Factors
PubMed: 34155379
DOI: 10.1038/s41582-021-00519-3 -
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 -
Seminars in Immunopathology Nov 2019Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting... (Review)
Review
Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting multiple sclerosis (RRMS), the most common initial presentation (85%) among which, if not treated, about half will transform, into the secondary progressive multiple sclerosis (SPMS) and the primary progressive MS (PPMS) (15%) that is directly progressive without superimposed clinical relapses. Inflammation is present in all subsets of MS. The relapsing/remitting form could represent itself a particular interest for the study of inflammation resolution even though it remains incomplete in MS. Successful resolution of acute inflammation is a highly regulated process and dependent on mechanisms engaged early in the inflammatory response that are scarcely studied in MS. Moreover, recent classes of disease-modifying treatment (DMTs) that are effective against RRMS act by re-establishing the inflammatory imbalance, taking advantage of the pre-existing endogenous suppressor. In this review, we will discuss the active role of regulatory immune cells in inflammation resolution as well as the role of tissue and non-hematopoietic cells as contributors to inflammation resolution. Finally, we will explore how DMTs, more specifically induction therapies, impact the resolution of inflammation during MS.
Topics: Animals; Biomarkers; Disease Management; Disease Susceptibility; Humans; Immune System; Immunomodulation; Inflammation; Multiple Sclerosis
PubMed: 31732775
DOI: 10.1007/s00281-019-00765-0 -
Neuron Nov 2022Microglia are implicated in all stages of multiple sclerosis (MS). Microglia alterations are detected by positron emission tomography in people living with MS prior to... (Review)
Review
Microglia are implicated in all stages of multiple sclerosis (MS). Microglia alterations are detected by positron emission tomography in people living with MS prior to the formation of structural lesions determined through magnetic resonance imaging. In histological specimens, clusters of microglia form in normal-appearing tissue likely predating the development of lesions. Features of degeneration-associated/pro-inflammatory states of microglia increase with chronicity of MS. However, microglia play many beneficial roles including the removal of neurotoxins and in fostering repair. The protector-gone-rogue microglia in MS is featured herein. We consider mechanisms of microglia neurotoxicity and discuss factors, including aging, osteopontin, and iron metabolism, that cause microglia to lose their protective states and become injurious. We evaluate medications to affect microglia in MS, such as the emerging class of Bruton's tyrosine kinase inhibitors. The framework of microglia-turned-destroyers may instigate new approaches to counter microglia-driven neurodegeneration in MS.
Topics: Humans; Microglia; Multiple Sclerosis; Positron-Emission Tomography; Magnetic Resonance Imaging; Aging
PubMed: 35882229
DOI: 10.1016/j.neuron.2022.06.023 -
Frontiers in Immunology 2023Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic... (Review)
Review
Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.
Topics: Humans; Multiple Sclerosis; Quality of Life; Comorbidity; Cerebrovascular Disorders; Peripheral Vascular Diseases
PubMed: 37325663
DOI: 10.3389/fimmu.2023.1197195 -
Tremor and Other Hyperkinetic Movements... 2022Multiple sclerosis (MS), a subset of chronic primary inflammatory demyelinating disorders of the central nervous system, is closely associated with various movement... (Review)
Review
BACKGROUND
Multiple sclerosis (MS), a subset of chronic primary inflammatory demyelinating disorders of the central nervous system, is closely associated with various movement disorders. These disorders may be due to MS pathophysiology or be coincidental. This review describes the full spectrum of movement disorders in MS with their possible mechanistic pathways and therapeutic modalities.
METHODS
The authors conducted a narrative literature review by searching for 'multiple sclerosis' and the specific movement disorder on PubMed until October 2021. Relevant articles were screened, selected, and included in the review according to groups of movement disorders.
RESULTS
The most prevalent movement disorders described in MS include restless leg syndrome, tremor, ataxia, parkinsonism, paroxysmal dyskinesias, chorea and ballism, facial myokymia, including hemifacial spasm and spastic paretic hemifacial contracture, tics, and tourettism. The anatomical basis of some of these disorders is poorly understood; however, the link between them and MS is supported by clinical and neuroimaging evidence. Treatment options are disorder-specific and often multidisciplinary, including pharmacological, surgical, and physical therapies.
DISCUSSION
Movements disorders in MS involve multiple pathophysiological processes and anatomical pathways. Since these disorders can be the presenting symptoms, they may aid in early diagnosis and managing the patient, including monitoring disease progression. Treatment of these disorders is a challenge. Further work needs to be done to understand the prevalence and the pathophysiological mechanisms responsible for movement disorders in MS.
Topics: Chorea; Dyskinesias; Humans; Movement Disorders; Multiple Sclerosis; Tremor
PubMed: 35601204
DOI: 10.5334/tohm.671 -
Viruses Jun 2020Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested,... (Review)
Review
Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested, including environmental, genetic and gender components. However, underlying infectious triggers to the disease are also suspected. There is an increasing abundance of evidence supporting a viral etiology to MS, including the efficacy of interferon therapy and over-detection of viral antibodies and nucleic acids when compared with healthy patients. Several viruses have been proposed as potential triggering agents, including Epstein-Barr virus, human herpesvirus 6, varicella-zoster virus, cytomegalovirus, John Cunningham virus and human endogenous retroviruses. These viruses are all near ubiquitous and have a high prevalence in adult populations (or in the case of the retroviruses are actually part of the genome). They can establish lifelong infections with periods of reactivation, which may be linked to the relapsing nature of MS. In this review, the evidence for a role for viral infection in MS will be discussed with an emphasis on immune system activation related to MS disease pathogenesis.
Topics: Animals; Humans; Multiple Sclerosis; Virulence; Virus Diseases; Virus Physiological Phenomena; Viruses
PubMed: 32545816
DOI: 10.3390/v12060643 -
Nature Reviews. Neurology Dec 2022Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence... (Review)
Review
Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence health outcomes. Evidence indicates that health behaviours, comorbidities and disease-modifying therapies all contribute to multiple sclerosis (MS) outcomes; however, our knowledge of the effects of social determinants - that is, the 'risks of risks' - on health has not yet changed our approach to MS. Assessing and addressing social determinants of health could fundamentally improve health and health care in MS; this approach has already been successful in improving outcomes in other chronic diseases. In this narrative Review, we identify and discuss the body of evidence supporting an effect of many social determinants of health, including racial background, employment and social support, on MS outcomes. It must be noted that many of the published studies were subject to bias, and screening tools and/or practical interventions that address these social determinants are, for the most part, lacking. The existing work does not fully explore the potential bidirectional and complex relationships between social determinants of health and MS, and the interpretation of findings is complicated by the interactions and intersections among many of the identified determinants. On the basis of the reviewed literature, we consider that, if effective interventions targeting social determinants of health were available, they could have substantial effects on MS outcomes. Therefore, funding for and focused design of studies to evaluate and address social determinants of health are urgently needed.
Topics: Humans; Multiple Sclerosis; Social Determinants of Health; Social Support
PubMed: 36369488
DOI: 10.1038/s41582-022-00735-5 -
Frontiers in Immunology 2022Multiple evidence from epidemiological studies has suggested association between physical activity and risk of multiple sclerosis (MS). However, the conclusion was still...
Multiple evidence from epidemiological studies has suggested association between physical activity and risk of multiple sclerosis (MS). However, the conclusion was still controversial between studies, and whether the association was causal or confounded is elusive. To evaluate the role of physical activity with different intensities in the risk of MS, we first estimated their genetic correlation, and then conducted two-sample and multivariable Mendelian randomization analyses based on summary statistics from previous large genome-wide association studies. A significant genetic correlation was identified between moderate physical activity and the risk of MS (genetic correlation: -0.15, SE=0.05, P=2.9E-03). Meanwhile, higher moderate physical activity was significantly associated with a reduced risk of MS (OR:0.87, 95% CI:0.80-0.96, P=3.45E-03). Such association was further verified using summary statistics from another study on overall physical activity (OR:0.36, 95% CI:0.17-0.76, P=6.82E-03). The results were robust under all sensitivity analyses. Current results suggested moderate physical activity could reduce the risk of MS. These findings help better understand the role of physical activity in MS, and provide some lifestyle recommendations for individuals susceptible to MS.
Topics: Exercise; Genome-Wide Association Study; Humans; Life Style; Mendelian Randomization Analysis; Multiple Sclerosis
PubMed: 36211369
DOI: 10.3389/fimmu.2022.872126 -
Autoimmunity Reviews May 2023More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of... (Review)
Review
More than 10 disease-modifying therapies (DMT) are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of multiple sclerosis (MS) and new therapeutic options are on the horizon. Due to different underlying therapeutic mechanisms, a more individualized selection of DMTs in MS is possible, taking into account the patient's current situation. Therefore, concomitant treatment of various comorbid conditions, including autoimmune mediated disorders such as rheumatoid arthritis, should be considered in MS patients. Because the pathomechanisms of autoimmunity partially overlap, DMT could also treat concomitant inflammatory diseases and simplify the patient's treatment. In contrast, the exacerbation and even new occurrence of several autoimmune diseases have been reported as a result of immunomodulatory treatment of MS. To simplify treatment and avoid disease exacerbation, knowledge of the beneficial and adverse effects of DMT in other autoimmune disorders is critical. Therefore, we conducted a literature search and described the beneficial and adverse effects of approved and currently studied DMT in a large number of comorbid autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, cutaneous disorders including psoriasis, Sjögren´s syndrome, systemic lupus erythematosus, systemic vasculitis, autoimmune hepatitis, and ocular autoimmune disorders. Our review aims to facilitate the selection of an appropriate DMT in patients with MS and comorbid autoimmune diseases.
Topics: Humans; Multiple Sclerosis; Autoimmunity; Autoimmune Diseases; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic
PubMed: 36924922
DOI: 10.1016/j.autrev.2023.103312