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Seminars in Neurology Apr 2020Multiple sclerosis is being increasingly recognized and diagnosed in children. In the past several years, advances have been made in diagnosing multiple sclerosis in... (Review)
Review
Multiple sclerosis is being increasingly recognized and diagnosed in children. In the past several years, advances have been made in diagnosing multiple sclerosis in children, identifying new genetic and environmental risk factors, delineating underlying immunobiology, characterizing imaging findings, and implementing new treatment strategies. In this review, we discuss these advances. Future research into the determinants of multiple sclerosis in children and into new treatment options will be aided by continued international collaboration.
Topics: Child; Humans; Multiple Sclerosis
PubMed: 32294785
DOI: 10.1055/s-0040-1703000 -
Developmental Medicine and Child... Sep 2019Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults,... (Review)
Review
Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-A antibodies (AQP4-Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long-term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow-up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long-term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short- and long-term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon-β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. WHAT THIS PAPER ADDS: Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody-mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.
Topics: Child; Humans; Immunosuppressive Agents; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Prognosis
PubMed: 30932181
DOI: 10.1111/dmcn.14212 -
International Journal of Molecular... Feb 2020Calcium ions are vital for maintaining the physiological and biochemical processes inside cells. The central nervous system (CNS) is particularly dependent on calcium... (Review)
Review
Calcium ions are vital for maintaining the physiological and biochemical processes inside cells. The central nervous system (CNS) is particularly dependent on calcium homeostasis and its dysregulation has been associated with several neurodegenerative disorders including Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD), as well as with multiple sclerosis (MS). Hence, the modulation of calcium influx into the cells and the targeting of calcium-mediated signaling pathways may present a promising therapeutic approach for these diseases. This review provides an overview on calcium channels in neurons and glial cells. Special emphasis is put on MS, a chronic autoimmune disease of the CNS. While the initial relapsing-remitting stage of MS can be treated effectively with immune modulatory and immunosuppressive drugs, the subsequent progressive stage has remained largely untreatable. Here we summarize several approaches that have been and are currently being tested for their neuroprotective capacities in MS and we discuss which role calcium could play in this regard.
Topics: Animals; Calcium; Calcium Channels; Humans; Multiple Sclerosis; Neuroprotection
PubMed: 32121306
DOI: 10.3390/ijms21051663 -
Frontiers in Immunology 2019Over the past two decades, the field of multiple sclerosis (MS) has been transformed by the rapidly expanding arsenal of new disease modifying therapies (DMTs). Current... (Review)
Review
Over the past two decades, the field of multiple sclerosis (MS) has been transformed by the rapidly expanding arsenal of new disease modifying therapies (DMTs). Current DMTs for MS aim to modulate innate and adaptive immune responses toward a less inflammatory phenotype. Since the immune system is also critical for identifying and eliminating malignant cells, immunosuppression from DMTs may predictably increase the risk of cancer development in MS patients. Compared with healthy controls, patients with autoimmune conditions, such as MS, may already have a higher risk of developing certain malignancies and this risk may further be magnified by DMT treatments. For those patients who develop both MS and cancer, these comorbid presentations create a challenge for clinicians on how to therapeutically address management of cancer in the context of MS autoimmunity. As there are currently no accepted guidelines for managing MS patients with prior history of or newly developed malignancy, we undertook this review to evaluate the molecular mechanisms of current DMTs and their potential for instigating and treating cancer in patients living with MS.
Topics: Animals; Humans; Multiple Sclerosis; Neoplasms
PubMed: 31998289
DOI: 10.3389/fimmu.2019.02954 -
Journal of Child Neurology Nov 2012Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in... (Review)
Review
Pediatric multiple sclerosis has been increasingly recognized in the past 10 to 15 years; 3% to 5% of all multiple sclerosis patients experience their first attack in childhood. Childhood multiple sclerosis has a relapsing-remitting disease course. The first attack, or "acquired demyelinating syndrome," consists of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and monofocal or polyfocal neurological deficits. The diagnosis of multiple sclerosis necessitates the clinical or magnetic resonance imaging confirmation of dissemination in space and time and exclusion of other disorders. The morbidity of childhood multiple sclerosis is significant; within the first 2 years from onset, 30% of children have significant cognitive impairment, 50% show signs of depression, and 75% are fatigued. The relapse rate in children with multiple sclerosis is higher than in adult-onset disease. Following acute treatment, recovery after the first attacks is usually excellent, but patients with childhood-onset multiple sclerosis reach permanent disability or enter the secondary progressive disease course 10 years younger than patients with adult-onset multiple sclerosis.
Topics: Age of Onset; Central Nervous System; Child; Cognition Disorders; Diagnosis, Differential; Disabled Persons; Disease Progression; Humans; Immunotherapy; Magnetic Resonance Imaging; Multiple Sclerosis; Prognosis; Recurrence; Risk Factors
PubMed: 22914372
DOI: 10.1177/0883073812452784 -
Neurodegenerative Disease Management Oct 2015There is compelling epidemiological evidence that the risk of developing multiple sclerosis is increased in association with low levels of sun exposure, possibly because... (Review)
Review
There is compelling epidemiological evidence that the risk of developing multiple sclerosis is increased in association with low levels of sun exposure, possibly because this is associated with low vitamin D status. Recent work highlights both vitamin D and non-vitamin D effects on cellular immunity that suggests that higher levels of sun exposure and/or vitamin D status are beneficial for both MS risk and in ameliorating disease progression. Here we review this recent evidence, focusing on regulatory cells, dendritic cells, and chemokines and cytokines released from the skin following exposure to ultraviolet radiation.
Topics: Animals; Humans; Multiple Sclerosis; Ultraviolet Rays; Vitamin D
PubMed: 26477548
DOI: 10.2217/nmt.15.33 -
Annals of Physical and Rehabilitation... Mar 2020
Topics: Cognition Disorders; Humans; Multiple Sclerosis
PubMed: 32171789
DOI: 10.1016/j.rehab.2020.03.001 -
Multiple Sclerosis and Related Disorders Nov 2023Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several...
BACKGROUND
Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue.
METHODS
In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only.
RESULTS
Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue.
CONCLUSION
We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.
Topics: Humans; Multiple Sclerosis; Immunosuppressive Agents; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Cross-Sectional Studies; Quality of Life
PubMed: 37708819
DOI: 10.1016/j.msard.2023.104993 -
Arquivos de Neuro-psiquiatria Jun 2017The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment,... (Review)
Review
The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment, despite the apparent preservation of motor function. The objective of this study was to review and analyze a number of publications that discuss the general aspects of this disease form, such as the definition criteria, prevalence, and clinical and neuroimaging markers. A systematic review of published data on BMS up to October 2015 was performed. Thirty-one published articles were analyzed. The estimated frequency of BMS varied between 6% and 73%. Cognitive impairment was recognized as affecting 17% to 47% of the subjects and presented significant correlation with neuroimaging, such as brain atrophy, increased lesion volume in T2 magnetic resonance assay, and regional grey matter atrophy. The current criteria overestimated the frequency of BMS and, for that reason, this highlights the importance of validating the diagnostic methods practiced.
Topics: Cognition Disorders; Humans; Multiple Sclerosis; Neuroimaging
PubMed: 28658410
DOI: 10.1590/0004-282X20170043 -
Neurology Aug 2016Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater... (Review)
Review
Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater than 24 hours, in the absence of intercurrent illness, and occur with a higher frequency early in the disease as compared to adult-onset RRMS. Most pediatric patients with MS recover well from these early relapses, and cumulative physical disability is rare in the first 10 years of disease. Brainstem attacks, poor recovery from a single attack, and a higher frequency of attacks portend a greater likelihood of future disability. Although prospective pediatric-onset MS cohorts have been established in recent years, there remains very limited prospective data detailing the longer-term clinical outcome of pediatric-onset MS into adulthood. Whether the advent of MS therapies, and the largely off-label access to such therapies in pediatric MS, has improved prognosis is unknown. MS onset during the key formative academic years, concurrent with active cognitive maturation, is an important determinant of long-term outcome, and is discussed in detail in another article in this supplement. Finally, increasing recognition of pediatric MS worldwide, recent launch of phase III trials for new agents in the pediatric MS population, and the clear imperative to more fully appreciate health-related quality of life in pediatric MS through adulthood highlight the need for standardized, validated, and robust outcome measures.
Topics: Child; Humans; Multiple Sclerosis; Pediatrics; Treatment Outcome
PubMed: 27572865
DOI: 10.1212/WNL.0000000000003028