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Multiple Sclerosis: HELP
Articles from Missouri
Based on 197 articles published since 2008

These are the 197 published articles about Multiple Sclerosis that originated from Missouri during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8
1 Guideline Interventional endovascular management of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a position statement by the Society of Interventional Radiology, endorsed by the Canadian Interventional Radiology Association. 2010

Vedantham, Suresh / Benenati, James F / Kundu, Sanjoy / Black, Carl M / Murphy, Kieran J / Cardella, John F / Anonymous5040671 / Anonymous5050671. ·Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Box 8131, St. Louis, MO 63110-1076, USA. vedanthams@mir.wustl.edu ·J Vasc Interv Radiol · Pubmed #20800776.

ABSTRACT: -- No abstract --

2 Editorial Declines in the diagnosis of primary progressive MS: A critical change in phenotype or critical measurement error? 2016

Cutter, Gary R / Salter, Amber / Marrie, Ruth Ann. ·Department of Biostatistics, School of Public Health, The University of Alabama at Birmingham, Birmingham, AL, USA cutterg@uab.edu. · Department of Biostatistics, Washington University in St. Louis, Saint Louis, MO, USA. · Departments of Internal Medicine and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Multiple Sclerosis Clinic, Winnipeg, MB, Canada. ·Mult Scler · Pubmed #27385768.

ABSTRACT: -- No abstract --

3 Editorial Linking Genotype to Clinical Phenotype in Multiple Sclerosis: In Search of the Holy Grail. 2016

Longbrake, Erin E / Hafler, David A. ·Department of Neurology, Yale School of Medicine, New Haven, Connecticut2Department of Neurology, Washington University in St Louis, St Louis, Missouri. · Department of Neurology, Yale School of Medicine, New Haven, Connecticut3Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut. ·JAMA Neurol · Pubmed #27244583.

ABSTRACT: -- No abstract --

4 Editorial Cortical Lesions in Multiple Sclerosis: Clinical Relevance for a Hidden Disease Burden. 2015

Naismith, Robert T. ·Department of Neurology, Washington University, St Louis, Missouri. ·JAMA Neurol · Pubmed #26191784.

ABSTRACT: -- No abstract --

5 Editorial Multiple sclerosis, immunomodulation, and immunizations: balancing the benefits. 2015

Goldman, Myla D / Naismith, Robert T. ·From the Department of Neurology (M.D.G.), University of Virginia, Charlottesville · and the Department of Neurology (R.T.N.), Washington University, St. Louis, MO. ·Neurology · Pubmed #25636716.

ABSTRACT: -- No abstract --

6 Editorial Antisense therapy: potential tool to reduce activity in MS via protein expression inhibition. 2014

Naismith, Robert T / Cross, Anne H. ·From the Department of Neurology (R.T.N., A.H.C.) and Hope Center for Neurological Disorders (A.H.C.), Washington University School of Medicine, St. Louis, MO. · From the Department of Neurology (R.T.N., A.H.C.) and Hope Center for Neurological Disorders (A.H.C.), Washington University School of Medicine, St. Louis, MO. crossa@neuro.wustl.edu. ·Neurology · Pubmed #25239837.

ABSTRACT: -- No abstract --

7 Editorial Active and progressive: a new duality of MS classification. 2014

Cross, Anne H / Wingerchuk, Dean M / Weinshenker, Brian G. ·From the Department of Neurology (A.H.C.), Washington University School of Medicine, St. Louis, MO · the Department of Neurology (D.M.W.), Mayo Clinic, Scottsdale, AZ · and the Department of Neurology (B.G.W.), Mayo Clinic, Rochester, MN. ·Neurology · Pubmed #24928117.

ABSTRACT: -- No abstract --

8 Editorial Natalizumab to fingolimod washout in patients at risk of PML: when good intentions yield bad outcomes. 2014

Giovannoni, Gavin / Naismith, Robert T. ·From the Queen Mary University of London (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK · and the Department of Neurology (R.T.N.), Washington University School of Medicine, St. Louis, MO. ·Neurology · Pubmed #24610331.

ABSTRACT: With more choices for multiple sclerosis (MS) disease-modifying therapies, data are urgently required to support clinical decisions regarding safe transitioning and sequencing of therapies. With more than 7 years of clinical experience, natalizumab has been confirmed as highly effective in reducing MS disease activity. However, natalizumab carries a risk of progressive multifocal leukoencephalopathy (PML),(1) with more than 400 cases of natalizumab-related PML to date.(2) Because 2 of the 3 initial natalizumab-associated PML cases were on the combination natalizumab plus interferon, the concern was that combining agents led to a heightened risk of infectious complications. In these early times, uncertainty revolved around 2 points: the theoretical risk of PML if natalizumab was transiently combined with another immune-altering agent and the value of transiently "reconstituting" CNS immune surveillance by washout of natalizumab in an effort to clear theoretical subclinical JC virus within the CNS.(3) The optimal length of natalizumab washout became the subject of intense consternation and debate, with no clear guidelines to inform practice. However, upon withdrawing natalizumab, resumption of disease activity was soon observed, beginning 3-4 months after the last dose of natalizumab.(4-10) Postnatalizumab return of disease raised concern that the washout may harm the patient by a severe relapse with incomplete recovery.

9 Editorial Themes from the special issue on neurodegenerative diseases: what have we learned, and where can we go from here? 2014

Foster, Erin R. ·Erin R. Foster, OTD, MSCI, OTR/L, is Assistant Professor, Program in Occupational Therapy, Departments of Neurology and Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO 63110; erfoster@wustl.edu. ·Am J Occup Ther · Pubmed #24367948.

ABSTRACT: -- No abstract --

10 Editorial BCG vaccine for clinically isolated syndrome and MS: infections and protective immunity. 2014

Bourdette, Dennis / Naismith, Robert T. ·From the Department of Neurology (D.B.), Oregon Health & Science University and Multiple Sclerosis Centers of Excellence-West, Veterans Affairs Medical Center, Portland · and the Department of Neurology (R.T.N.), Washington University, St. Louis, MO. ·Neurology · Pubmed #24306000.

ABSTRACT: -- No abstract --

11 Editorial The present efficacy of multiple sclerosis therapeutics: Is the new 66% just the old 33%? 2009

Klawiter, Eric C / Cross, Anne H / Naismith, Robert T. ·Department of Neurology,Washington University, St. Louis, MO 63110, USA. klawitere@neuro.wustl.edu ·Neurology · Pubmed #19770475.

ABSTRACT: A challenge for the clinician treating patients with multiple sclerosis (MS) is to determine the most effective treatment while weighing the benefits and risks. Results of the phase 2 and phase 3 studies on natalizumab were received with great interest, in part due to the "improved" risk reduction for relapse rate, disease progression, and MRI metrics observed in comparison to results in trials of beta-interferon and glatiramer acetate. However, comparison across trials is invalid, in large part due to differences in the study populations. The increased efficacy observed in more recent trials has also been attributed to a fundamental change in subjects with MS enrolled in recent trials compared with the prior decade. In this article, we debate the relative efficacy of natalizumab vs the older injectable therapies.

12 Review Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned. 2018

Major, Eugene O / Yousry, Tarek A / Clifford, David B. ·Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. · Division of Neuroradiology and Neurophysics, UCL Institute of Neurology, and Lysholm Department of Neuroradiology, London, UK. · Department of Neurology, Washington University School of Medicine, St Louis, MO, USA. Electronic address: clifforddb@wustl.edu. ·Lancet Neurol · Pubmed #29656742.

ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a rare, devastating demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in patients with compromised immune systems. Detection of PML in systemically immunocompetent patients with multiple sclerosis treated with natalizumab points to a role for this drug in the pathophysiology of PML. Emerging knowledge of the cellular and molecular biology of JCV infection and the pathogenesis of PML-including interplay of this common virus with the human immune system and features of natalizumab that might contribute to PML pathogenesis-provides new opportunities to monitor viral status and predict risk of JCV-associated disease. In the absence of an effective treatment for PML, early detection of the disease in patients with multiple sclerosis who are receiving natalizumab or other immunomodulatory treatments is vital to minimize CNS injury and avoid severe disability. Frequent MRI, stratified along a clinical and virus-specific immune risk profile, can be used to detect presymptomatic PML. Improved approaches to PML risk stratification are needed to guide treatment choices and surveillance of patients with multiple sclerosis.

13 Review The Gut Microbiome and Multiple Sclerosis. 2018

Ochoa-Repáraz, Javier / Kirby, Trevor O / Kasper, Lloyd H. ·Department of Biology, Eastern Washington University, Cheney, Washington 99004. · Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, New Hampshire 03756. ·Cold Spring Harb Perspect Med · Pubmed #29311123.

ABSTRACT: The microbiome can be defined as the sum of the microbial and host's genome. Recent information regarding this complex organ suggests that in animal models of multiple sclerosis (MS), the composition of the gut microbiome can be altered, giving rise to both the effector and regulatory phases of central nervous system (CNS) demyelination. Experimental findings during the past decade in animal models of MS have provided clear evidence for the significant role of gut microbes in both the effector and regulatory phase of this condition. There is mounting evidence in preliminary human studies suggesting that a dysbiotic MS gut microbiome could affect disease progression. We propose considering the gut microbiome as a key organ for the regulation of tolerance mechanisms and speculate that the gut microbiome is the major environmental risk factor for CNS demyelinating disease. Accordingly, we hypothesize that intervention of the gut microbiome could result in safer novel therapeutic strategies to treat MS.

14 Review Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate. 2018

Mayer, Lori / Fink, Mary Kay / Sammarco, Carrie / Laing, Lisa. ·Central Texas Neurology Consultants, Round Rock, TX, USA. lorimayerdnp@gmail.com. · The MS Center of St. Louis, St. Louis, MO, USA. · NYU Langone MS Comprehensive Care Center, New York, NY, USA. ·Drug Saf · Pubmed #29218681.

ABSTRACT: Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

15 Review Neuromodulation in multiple sclerosis. 2017

Abboud, Hesham / Hill, Eddie / Siddiqui, Junaid / Serra, Alessandro / Walter, Benjamin. ·Multiple Sclerosis and Neuroimmunology Program, University Hospitals of Cleveland, Cleveland, OH, USA/School of Medicine, Case Western Reserve University, Cleveland, OH, USA/Neurology Department, Alexandria University, Alexandria, Egypt. · School of Medicine, Case Western Reserve University, Cleveland, OH, USA. · Movement Disorders, University of Missouri- School of Medicine, Columbia, MO, USA. · Multiple Sclerosis and Neuroimmunology Program, University Hospitals of Cleveland, Cleveland, OH, USA/School of Medicine, Case Western Reserve University, Cleveland, OH, USA/Multiple Sclerosis Center of Excellence, Cleveland VA Medical Center Hub Site, East Cleveland, OH, USA. · School of Medicine, Case Western Reserve University, Cleveland, OH, USA/Parkinson's and Movement Disorders Center, University Hospitals of Cleveland, Cleveland, OH, USA. ·Mult Scler · Pubmed #29115915.

ABSTRACT: Neuromodulation, or the utilization of advanced technology for targeted electrical or chemical neuronal stimulation or inhibition, has been expanding in several neurological subspecialties. In the past decades, immune-modulating therapy has been the main focus of multiple sclerosis (MS) research with little attention to neuromodulation. However, with the recent advances in disease-modifying therapies, it is time to shift the focus of MS research to neuromodulation and restoration of function as with other neurological subspecialties. Preliminary research supports the value of intrathecal baclofen pump and functional electrical stimulation in improving spasticity and motor function in MS patients. Deep brain stimulation can improve MS-related tremor and trigeminal neuralgia. Spinal cord stimulation has been shown to be effective against MS-related pain and bladder dysfunction. Bladder overactivity also responds to sacral neuromodulation and posterior tibial nerve stimulation. Despite limited data in MS, transcranial magnetic stimulation and brain-computer interface are promising neuromodulatory techniques for symptom mitigation and neurorehabilitation of MS patients. In this review, we provide an overview of the available neuromodulatory techniques and the evidence for their use in MS.

16 Review New Insights into the Role of IL-1β in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. 2017

Lin, Chih-Chung / Edelson, Brian T. ·Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110. · Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 bedelson@path.wustl.edu. ·J Immunol · Pubmed #28583987.

ABSTRACT: Multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis, are neuroinflammatory diseases driven by autoreactive pathogenic T

17 Review Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface. 2017

Phan, Duc Tt / Bender, R Hugh F / Andrejecsk, Jillian W / Sobrino, Agua / Hachey, Stephanie J / George, Steven C / Hughes, Christopher Cw. ·1 Department of Molecular Biology & Biochemistry, University of California, Irvine, Irvine, CA 92697, USA. · 2 Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA. · 3 Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, USA. · 4 The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, CA 92697, USA. ·Exp Biol Med (Maywood) · Pubmed #28195514.

ABSTRACT: The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

18 Review "A new imaging modality to non-invasively assess multiple sclerosis pathology". 2017

Cross, Anne H / Song, Sheng-Kwei. ·Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis 63110, MO, USA. Electronic address: crossa@neuro.wustl.edu. · Department of Radiology, Washington University School of Medicine, Campus Box 8225, 660 S. Euclid Avenue, St. Louis 63110, MO, USA. ·J Neuroimmunol · Pubmed #27773433.

ABSTRACT: We describe a novel imaging method to assess central nervous system pathology called "Diffusion Basis Spectrum Imaging" (DBSI). Diffusion tensor imaging (DTI) has been widely used to estimate axonpathology and demyelination. However, in the settings of acute inflammation and chronic tissue loss asare common in multiple sclerosis, DTI signals can lead to false interpretations. DBSI is a computationallynovel method that separates isotropic from anisotropic components in imaging voxels. Isotropicdiffusion is believed to reflect inflammatory components (cells, edema), as well as intrinsic cells andextracellular space. DBSI enables the measurement of axial and radial diffusivities within the anisotropiccomponents of imaging voxels, which reflect the integrity of axon fibers and myelin, respectively.

19 Review The Emerging Role of the Gut Microbiome in Adult Patients With Multiple Sclerosis. 2016

Newland, Pamela K / Heitkemper, Margaret / Zhou, Yanjiao. ·Questions or comments about this article may be directed to Pamela K. Newland, PhD RN CMSRN, at Pamela.newland@bjc.org. She is an NRSA Postdoctoral Fellow, Nursing Faculty, Goldfarb School of Nursing, Barnes Jewish College, St. Louis, MO. Margaret Heitkemper, PhD, is Chair, Department of Biobehavioral Nursing and Health Systems, University of Washington School of Nursing, Seattle, WA. Yanjiao Zhou, PhD, Jackson Laboratory for Genomic Medicine, Farmington, CT. ·J Neurosci Nurs · Pubmed #27824805.

ABSTRACT: BACKGROUND: Approximately 2.3 million people worldwide are currently living with multiple sclerosis (MS). The pathophysiologic mechanism of MS is not well known. It has been suggested that alterations in the normal gut flora may contribute to MS etiology and symptoms. OBJECTIVE: The aims of this review are to describe the data suggesting a role for the gut microbiome in MS research and address its implications for practice. METHODS: A literature search of the following databases (PubMed, CINAHL, Cochrane library database, MEDLINE, Scopus, and Psychology and Behavioral Sciences) was conducted to find published studies relevant to gut microbiome in patients with MS. STUDY SELECTION: Five articles met the inclusion criteria of research studies of human gut microbiome in adults in English language and those receiving disease-modifying medications. Exclusion criteria were case reports and reviews. RESULTS: Human studies found that the gut microbiome was different among patients with MS, patients with MS who were treated with glatiramer acetate, and healthy controls. DISCUSSION: There is beginning evidence to suggest that the gut microbiota is related to autoimmunity and the pathology of MS. However, more research is necessary to clarify these mechanisms. IMPLICATIONS FOR PRACTICE: A better understanding of the role of the gut microbiota in MS may lead to the development of targeted individualized interventions affecting the gut microbiota. These interventions may emphasize symptom self-management strategies such as diet.

20 Review Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis. 2016

Hintzen, Rogier Q / Dale, Russell C / Neuteboom, Rinze F / Mar, Soe / Banwell, Brenda. ·From the Departments of Neurology (R.Q.H., R.F.N.) and Immunology (R.Q.H.), MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands · Institute for Neuroscience and Muscle Research (R.C.D.), The Kids Research Institute at the Children's Hospital at Westmead, Sydney Medical School, University of Sydney, Australia · Departments of Pediatric and Developmental Neurology (S.M.), Washington University School of Medicine, St. Louis, MO · and Division of Neurology (B.B.), The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania. ·Neurology · Pubmed #27572864.

ABSTRACT: Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS.

21 Review Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice. 2016

Kelsey, P J / Oliveira, M-C / Badoglio, M / Sharrack, B / Farge, D / Snowden, J A. ·Departments of Haematology and Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK. Electronic address: philippakelsey24@hotmail.com. · Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. · EBMT Study Office, Paris, France. · Departments of Haematology and Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK. · St. Louis hospital, Internal Medicine and Vascular Diseases Unit, Paris, France; INSERM 1160 Unit, Paris 7 Diderot University, Sorbonne Paris Cite 1, Paris, France. ·Curr Res Transl Med · Pubmed #27316390.

ABSTRACT: Based on animal studies and serendipitous clinical cases, haematopoietic stem cell transplantation (HSCT) has been used since 1995 as a specific treatment for patients with severe treatment-resistant autoimmune disease (ADs). Despite other clinical developments for autoimmune diseases, including biological therapies, there has been an ongoing requirement for HSCT in some diseases and several thousand procedures have been registered in databases for a wide variety of diseases, predominantly for treatment with autologous HSCT. Currently, the main indications are multiple sclerosis, systemic sclerosis and Crohn's disease, which are supported by large series and randomised controlled trials (RCTs), whereas retrospective registry analyses support benefit in a range of rarer indications. Research into mechanisms of action has provided insight into how tolerance may be achieved with an intensive one-off treatment. In addition to the profound anti-inflammatory and immunosuppressive effects provided by the cytotoxic regimen, long-term responses in some diseases may be explained by 'resetting' the immune system through thymic reprocessing and generation of increased T-regulatory cell activity. This review aims to summarise the gradual evolution of HSCT in severe autoimmune diseases over the last 20 years, focussing on the recent publication of clinical and scientific studies, as well as evidence-based guidelines and recommendations.

22 Review Central fatigue in multiple sclerosis: a review of the literature. 2016

Newland, Pamela / Starkweather, Angela / Sorenson, Matthew. ·a Office of Nursing Research, Goldfarb School of Nursing at Barnes Jewish College , St. Louis , MO , USA. · b Center for Advancement of Managing Pain, University of Connecticut School of Nursing , Storrs , CT , USA. · c DePaul University School of Nursing , Chicago , IL , USA. · d Department of Physical Medicine and Rehabilitation , Northwestern University Feinberg School of Medicine , Chicago , IL , USA. ·J Spinal Cord Med · Pubmed #27146427.

ABSTRACT: CONCEPT: Fatigue is a major concern for patients with multiple sclerosis (MS). A clear definition of MS-related fatigue is a prerequisite for appropriate instruments for fatigue assessment. In turn, accurate assessment of fatigue in MS will enhance exploration of plausible mechanisms underlying this common and distressing symptom. Content/Objectives: To provide an integrative review of the current literature on theoretical models used to study fatigue in MS, instruments used to assess fatigue and other factors that impact fatigue during the various phases of MS. DATA SOURCES: PUBMED, OVID, Ovid Health Star, Ovid MEDINE, CINAHL, Health and Psychosocial Instruments (HaPI), and PsycINFO. Seventeen articles fit the inclusion criteria and were included in the review. RESULTS: Definitions of MS-related fatigue are reviewed. Several studies found a link with neurotransmitter dysfunction, circadian rhythm, and the timing of fatigue. Central fatigue in MS is associated with neurotransmitters disruptions as well as circadian rhythm disorders, but the evidence is not strong. Perceptions of fatigue or fatigability may arise as either a primary or secondary manifestation of disease. Based on findings from the literature review, a theoretical model of fatigue in MS is proposed. CONCLUSION: Future research on MS-related fatigue may consider a longitudinal design with a carefully selected self-report instrument to advance understanding of the underlying pathological mechanisms.

23 Review Parenteral Treatment of Multiple Sclerosis: The Advent of Monoclonal Antibodies. 2016

Singer, Barry A. ·The MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, Missouri. ·Semin Neurol · Pubmed #27116720.

ABSTRACT: Improved disease control is critical for enhancing the lives of those living with multiple sclerosis. With specific immunologic targets, monoclonal antibody (mAb) treatments are highly effective options for relapsing forms of multiple sclerosis. The mechanism, efficacy, and current safety profiles are detailed for the two mAb therapies, natalizumab and alemtuzumab, with regulatory approval in multiple countries. Daclizumab, which targets the interleukin-2 receptor, and ocrelizumab, which depletes B cells, have convincing phase 3 clinical trial data and may very well provide new options in the near future. Trial results of other B-cell-directed therapies, ofatumumab and rituximab, are reviewed. Less-frequent dosing of glatiramer acetate and interferon β-1a highlight developments in the first generation of parenteral immunomodulatory therapy. Remyelination using mAbs has moved into clinical trials with the first agents, anti-LINGO-1, rHIgM22, and anti-SEMA 4D.

24 Review Effect of Multiple Sclerosis Disease-Modifying Therapies on B Cells and Humoral Immunity. 2016

Longbrake, Erin E / Cross, Anne H. ·Department of Neurology, Washington University, St Louis, Missouri. ·JAMA Neurol · Pubmed #26720195.

ABSTRACT: The unequivocal success of B-cell-depleting agents in reducing magnetic resonance imaging and clinical activity in therapeutic trials indicates that B cells play a vital role in mediating the clinical course of relapsing multiple sclerosis (MS). Although no agent that specifically targets B cells has yet been approved for clinical use, all existing disease-modifying therapies (DMTs) for MS modulate B-cell immunity to some degree. This review examines the effects of MS DMTs on B-cell immunity. Most MS DMTs induced a relative decrease in circulating memory B cells with concomitant expansion of circulating B-cell precursors and/or naive B cells. B-cell function was also altered; most DMTs induced B-cell production of the anti-inflammatory cytokine interleukin 10 while inhibiting B-cell expression of proinflammatory cytokines. The commonalities in the effects of approved DMTs on B-cell phenotype and function among treated patients with MS are striking and suggest that effects on B cells underlie part of their efficacy. More complete understanding of how the existing DMTs modulate B-cell immunity may identify future targets for therapeutic intervention.

25 Review Established and novel disease-modifying treatments in multiple sclerosis. 2014

Cross, A H / Naismith, R T. ·Department of Neurology, Washington University, St. Louis, MO, USA. ·J Intern Med · Pubmed #24444048.

ABSTRACT: 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.