Download or read book Biological Markers in Multiple Sclerosis Related to Disease Activity and Progression written by Margreet Judith Eikelenboom and published by . This book was released on 2007 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Biomarkers and Disease Activity in Multiple Sclerosis written by Irene Håkansson and published by Linköping University Electronic Press. This book was released on 2019-10-07 with total page 78 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis focuses on disease activity in clinically isolated syndrome (CIS) and newly diagnosed relapsing remitting multiple sclerosis (RRMS). The papers are based on data from 41 patients in a prospective longitudinal cohort study. All patients were untreated at baseline. Age- and sex-matched healthy controls (n=22) for blood and cerebrospinal fluid (CSF) samples were recruited from blood donors. Paper I evaluated the prognostic value of baseline levels of CXCL1, CXCL8, CXCL10, CXCL13, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9) and osteopontin in CSF in relation to disease activity during the first two years of follow-up. Disease activity was defined as clinical relapses, new T2 lesions in brain magnetic resonance imaging (MRI) and/or sustained Expanded Disability Status Scale (EDSS) progression. Absence of these three signs of disease activity was called no evidence of disease activity (NEDA-3). Logistic regression analysis showed that NFL in CSF was the best predictive marker of disease activity and correctly classified 93% of the patients with evidence of disease activity during two years of follow-up and 67% of those without. Paper II presented four year follow-up data from the cohort and also included brain volume data as well as serum levels of NFL. The correlation between NFL in CSF and serum was fairly strong (r=0.74, p<0.001). NFL in CSF was associated with new T2 lesions as well as with brain volume loss, whereas CHI3L1 in CSF was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22 and MMP-9 in CSF were mainly associated with new T2 lesions. Taken together, paper I and II confirm and extend the knowledge of NFL as a useful biomarker in CIS and RRMS and suggests that NFL, rather than total brain volume loss, could be included in an expanded NEDA concept and used in clinical monitoring of disease activity/treatment effect. Although serum levels of NFL were correlated with the corresponding CSF levels, CSF-NFL showed a stronger association to subsequent disease activity (NEDA-3). Paper III addressed the patients´ self-reported Modified Fatigue Impact Scale (MFIS) scores in relation to other cohort study data. MFIS scores correlated with other self-assessment questionnaire data (Hospital Anxiety and Depression scale (HAD), Multiple Sclerosis Impact Scale 29 (MSIS-29) and Short Form 36 (SF-36) scores (Spearman´s rho 0.45-0.78, all p?0.01)) but not with EDSS ratings, number of T2 lesions, total brain volume or NFL levels, indicating that subjective fatigue scores are not well reflected by some commonly used and objectively measurable disease parameters. Paper IV focused on the complement factors C1q, C3, C3a and sC5b-9 in CSF and plasma. CSFC1q was significantly higher in patients than in controls at baseline. The subgroup of patients with ongoing relapse at baseline also had higher levels of CSF-C3a than controls. Baseline levels of CSF-C1q and CSF-C3a correlated significantly with several pro-inflammatory chemokines as well as with MMP-9, CHI3L1 and NFL in CSF. Baseline CSF-C3a also correlated significantly with the number of T2 lesions and Gadolinium enhancing lesions in brain MRI at baseline, as well as with the number of new T2 lesions during follow-up. This study indicates that the complement system is involved already at early stages of MS. It also suggests that especially CSF-C1q and CSF-C3a levels are associated with other neuroinflammatory and neurodegenerative markers and that CSF-C3a levels may carry some prognostic information.

Download or read book Multiple Sclerosis written by Institute of Medicine and published by National Academies Press. This book was released on 2001-08-10 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.

Download or read book Biomarkers in Multiple Sclerosis written by U. Utz and published by IOS Press. This book was released on 2006-11 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt: Several processes are presumed to sequentially or simultaneously contribute to the pathophysiology of multiple sclerosis (MS). This work examines the potential of biomarkers in the context of MS. It explores the state of biomarker research for MS, barriers to progress and possible solutions and priorities.

Download or read book White Matter Diseases written by Massimo Filippi and published by Springer Nature. This book was released on 2020-02-13 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides cutting-edge information on the epidemiology, etiopathogenesis, clinical manifestations, diagnostic procedures and treatment approaches for the main white matter (WM) disorders of the central nervous system (CNS). WM lesions are associated with many neurological conditions, and with aging. The diagnostic work-up of neurological diseases characterized by the presence of these lesions has changed dramatically over the past few years. This is mainly due on the one hand to the discovery of specific pathogenetic factors in some of these conditions, and on the order to the optimized use of diagnostic tools. All of this has resulted in new diagnostic algorithms, and in the identification of new neurological conditions. The book offers neurologists essential guidance in the diagnosis and treatment of the most frequent WM conditions, promoting their correct and cost-saving diagnosis and management. By integrating neurological, laboratory and imaging concepts with the demands of accurate diagnosis, this reference guide provides a state-of-the-art overview of the current state of knowledge on these conditions, as well as practical guidelines for their diagnosis and treatment.

Download or read book Multiple Sclerosis written by Ian S. Zagon and published by . This book was released on 2017 with total page 137 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book McAlpine s Multiple Sclerosis written by Alastair Compston and published by . This book was released on 1998 with total page 620 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the latest edition of the classic book on the subject of multiple sclerosis. An international group of authors has been involved in updating this edition which features more information on imaging and investigations, and a new chapter on neurobiology and glial development.

Download or read book Assessing Disease Activity in Multiple Sclerosis written by Joel Benjamin Raffel and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Primary Progressive Multiple Sclerosis written by M. Filippi and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 188 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Why are there no effective treatments for my condition? Why do researchers exclude patients with primary progressive multiple sclerosis from enrolling in clinical trials? Please let me know if you hear of studies that I might be allowed to enter or treatments that I could try for my condition. " Thus, in recent years, the sad lament of the patient with primary progressive MS (PPMS). This variant, often in the guise of a chronic progressive myelopathy or, less commonly, progressive cerebellar or bulbar dysfunction, usually responds poorly to corticosteroids and rarely seems to benefit to a significant degree from intensive immunosuppressive treatments. In recent years, most randomized clin ical trials have excluded PPMS patients on two counts. Clinical worsening devel ops slowly in PPMS and may not be recognized during the course of a 2-or 3-year trial even in untreated control patients. This factor alone adds to the potential for a type 2 error or, at the very least, inflates the sample size and duration of the trial. In addition, there is mounting evidence that progressive axonal degeneration and neuronal loss (rather than active, recurrent inflammation) may be important components of the pathology in this form of the disease. Although contemporary trials are evaluating whether PPMS patients may benefit from treatment with the ~-interferons and glatiramer acetate, preliminary, uncontrolled clinical experi ence suggests that the results may not be dramatic.

Download or read book Biomarkers in Multiple Sclerosis written by Valentina Ignatova and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Clinical, biological, and radiological evidence are currently needed to diagnose MS, but lack of preclinical biomarkers hinders the earliest possible diagnosis and treatment. Conventional biomarkers target immunity, blood-brain barrier disruption, demyelination, and neuronal and axonal damage, as well as mitochondrial activity. An increase of specific brain metabolites with 30,Äì40% is registered before detection of MRI lesions in MS. Potential lipid biomarkers are fatty acids, phospholipids, and oxysterols. The role of proteoforms in the pathogenesis of MS was confirmed. Serum neurofilament light chains (sNfL) are currently being studied as a readily available biomarker for prognosis and response to treatment in MS. The sNfL levels reflect ongoing neuroaxonal damage caused by inflammation, and the sNfL levels predict disease activity over the next few years. The retinal nerve fiber layer (RNFL) thinning is reliable as a biomarker of disability worsening. The neutrophil-to-lymphocyte ratio and CRP are also MS biomarkers. The development of rationally targeted therapeutic agents that allow preventive treatment to stop the disease is also delayed without definite biomarkers.

Download or read book Identifying Biomarkers for Monitoring Disease Progression of Multiple Sclerosis written by Erica Saenz-Trevino and published by . This book was released on 2014 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is the most common debilitating, progressive neurological disorder which afflicts over 400,000 Americans. Currently, determining clinical and sub-clinical progression for MS patients is a significant obstacle due to the lack of specific and sensitive laboratory tests. Recently, our lab has developed a technique called Microwave & Magnetic (M 2 ) proteomics, which is a rapid quantitative approach ideal for identifying putative protein biomarkers and therapeutic targets of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model for MS research. Notably we identified a number of putative-biomarkers which correlated with different stages of a monophasic EAE disease course. The objective of our research is to identify protein biomarkers correlated to disease progression using the progressive EAE disease model in non-obese diabetic (NOD) mice. We hypothesize that during the disease several key central nervous system (CNS) disease specific proteins will be released into blood and changes of these proteins can be used to determine disease progression. Using EAE NOD mice, we verified putative biomarkers in EAE NOD mice, followed by ELISA to detect these proteins in serum samples harvested at different time points throughout the disease course. We identified several potential biomarkers from CNS samples that correlate with different stages of EAE. These candidates were further investigated by ELISA in serum samples. Our study identified potential prognostic biomarkers for disease progression using the EAE NOD mouse model. This research will provide a proof-of-principle for the development of novel prognostic tests in MS patients.

Download or read book Neurodegeneration in Multiple Sclerosis written by M. Filippi and published by Springer Science & Business Media. This book was released on 2008-02-01 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by world-renowned scientists, the volume provides a state-of-the-art on the most recent MRI techniques related to MS, and it is an indispensable tool for all those working in this field. The context in which this book exists is that there is an increasing perception that modern MR methodologies should be more extensively employed in clinical trials to derive innovative information.

Download or read book Autonomic Innervation of the Heart written by Riemer H.J.A. Slart and published by Springer. This book was released on 2015-01-30 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

Download or read book Opioid Growth Factor As A Candidate Biomarker For Multiple Sclerosis written by Michael Ludwig and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. The disease etiology remains unknown and the initial diagnosis of MS is difficult. Currently, the diagnostic criteria for MS rely heavily on Magnetic Resonance Imaging (MRI) as there is no reliable set of serum factors and no requirement for a blood test. A biomarker specific for MS that is also responsive to disease progression that could be easily obtained and quantified facilitate prognostic testing between MRI scans, supplement the initial diagnosis, and possibly serve as an indicator for therapeutic efficacy. One potential biomarker is Opioid Growth Factor (OGF, chemically termed [Met5]-enkephalin). Previous research on this endogenous pentapeptide demonstrates that OGF inhibits DNA synthesis of normal and neoplastic cells in a receptor-mediated manner by OGFr. Exogenous OGF is an effective treatment for experimental autoimmune encephalomyelitis (EAE), the mouse models of MS. Treatment initiated at the time of visible clinical disease reversed the progression of behavioral defects, restored sensitivity to normal, and decreased associated neuropathology. Low doses of naltrexone (LDN) a general opioid antagonist, also has an anti-proliferative effect through increasing endogenous OGF, and currently is a popular and well tolerated treatment for the fatigue associated with MS, as well as an alternative, stand-alone therapy for MS. Based on the research that both exogenous OGF, as well as the endogenous stimulation of OGF following LDN therapy, reverse the course of relapsing-remitting EAE, chronic progressive EAE, and the positive effects noted by MS patients receiving LDN therapy, the overall hypothesis for this research was developed such that that the OGF-OGFr axis becomes dysregulated during the onset and development of MS and EAE, and one or more components of this pathway may serve as specific biomarker(s) for the progression of disease and response to therapy. To assess OGFs potential as a biomarker for MS, the following specific aims were completed using the chronic experimental autoimmune encephalomyelitis (Ch-EAE) model of MS and MS subjects at Penn State Hershey Neurology Clinic. Specific Aim 1: to determine the serum enkephalin levels in Ch-EAE mice, both untreated and treated with either OGF or LDN and correlate those levels with disease severity, motor activity, and sensitivity. Specific Aim 2: to determine the serum enkephalin levels in MS patients receiving either conventional disease modifying therapies (DMTs) and/or LDN. Specific Aim 3: to determine the inflammatory cytokine levels in the serum of Ch-EAE mice treated with OGF or LDN, over the course of 20 days. Specific Aim 4: to utilize MRI to observe pathological changes in Ch-EAE mice, and determine the effect of OGF treatment on pathology, as seen by MRI. Serum enkephalin levels were analyzed by ELISA. Ch-EAE mice were treated with either exogenous OGF (10mg/kg) or low doses of naltrexone (LDN, 0.1mg/kg), whereas MS patients received glatiramer acetate (Copaxone) and/or LDN. In the first study, mice immunized with MOG35-55 to induce Ch-EAE were shown at the onset of disease symptoms (day 9 post immunization) to have significantly reduced serum OGF concentrations. By the peak of Ch-EAE disease (day 18), mice had further declines in serum OGF concentrations. The reductions in the serum OGF levels were inversely correlated with disease severity as measured by behavior such that an increase in disease severity correlated with a decrease in the serum enkephalin levels. Treatment of mice with Ch-EAE with exogenous OGF restored serum OGF levels to normal levels within 6 days of treatment. In the second study, the effect of LDN on serum enkephalin levels was investigated. Within 7 days of MOG immunization, prior to the onset of disease symptoms, OGF levels in serum were reduced. However, daily LDN treatment of Ch-EAE mice restored serum OGF levels to normal. . LDN treatment had no significant effect on serum -endorphin levels in Ch-EAE mice or on OGF levels in non-immunized, normal mice. In our clinical studies, LDN was also shown to increase serum OGF levels in MS when compared to MS subjects receiving Copaxone therapy.In the third study, the inflammatory cytokine profile of the Ch-EAE mouse model, both untreated and treated with LDN or OGF, was investigated at 10 and 20 days following induction of EAE and treatment. Based on a multiplex analysis of inflammatory cytokines, within ten days of disease, cytokines in the serum of Ch-EAE mice were increased in comparison to those measured in normal mice. Compared to cytokine levels in Ch-EAE mice receiving saline, mice treated with LDN and OGF had reduced levels of IL-10, TNF, and IFN. IL-6 expression was increased over the disease state after ten days of treatment with OGF and LDN. The multiplex data were validated with serum samples collected at six days of disease in addition to human serum samples. In the Ch-EAE mice at six days of disease, IL-10 was increased over the normal, but was not increased in LDN and OGF treated mice. In the MS subjects, cytokine levels were comparable between the Copaxone treated and LDN treated subjects. In the final study, MRI was evaluated as a disease monitoring protocol for Ch-EAE. T2 and DTI scans were performed longitudinally across a 40-day disease time course, in order to track the progression of the disease damage. Upon visual inspection, T2 scans showed intensities that increased throughout the disease progression. At day 40, Ch-EAE mice were humanely euthanized and spinal columns were removed for ex-vivo scanning. The increased resolution in the ex vivo scans allowed for more accurate localization of the T2 intensities. Upon visual inspection, these intensities were localized to the lumbar regions of the spinal cord, comparable to those areas of demyelination measured by Luxol Fast Blue staining. These pilot- methodological studies warrant further research on the Ch-EAE mouse model utilizing MRI.In summary, these studies provide evidence for the potential use of OGF, along with inflammatory cytokines, as a biomarker panel for MS and EAE, paving the way for future, more clinically relevant or more mechanistic research.

Download or read book The Biology of Multiple Sclerosis written by Gregory Atkins and published by Cambridge University Press. This book was released on 2012-11-08 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is the most common debilitating neurological disease in people under the age of forty in the developed world. Many publications cover medical and clinical approaches to the disease; however, The Biology of Multiple Sclerosis provides a clear and concise up-to-date overview of the scientific literature on the various theories of MS pathogenesis. Covering the main elements of scientific research into multiple sclerosis, the book contains chapters on the neuropathology of the disease as well as an account of the most extensively used animal model experimental autoimmune encephalomyelitis. The book contains chapters regarding the role of viruses in the development of multiple sclerosis. Viruses have long been implicated and chapters on animal models based on virus infection, as well as their possible role in the etiology of MS, are included. Of interest to MS researchers, the book is written to also be of value to postgraduate and medical students.

Download or read book The Neurobiology of Multiple Sclerosis written by and published by Academic Press. This book was released on 2007-06-07 with total page 759 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is an immune-mediated neurodegenerative disorder of the human central nervous system (CNS) which usually affects young adults with certain genetic backgrounds who are then exposed to certain precipitating environmental antigen(s). Despite major advances of the past two decades in understanding the pathophysiology of MS, and in spite of the introduction of new immunomodulatory and immuno-suppressive agents which may slow down disease progression and delay the onset of disability, the “cause and the “cure for MS remain elusive. This volume of International Review of Neurobiology focuses on MS and related disorders. The volume can be divided into various sections with the main emphasis on MS pathogenesis, clinical features and epidemiology, neuroimaging, and treatment. The ultimate goal of this book is to encourage further research into the pathogenesis of this elusive disease.

Download or read book Quantitative Magnetic Resonance Imaging written by Nicole Seiberlich and published by Academic Press. This book was released on 2020-11-18 with total page 1094 pages. Available in PDF, EPUB and Kindle. Book excerpt: Quantitative Magnetic Resonance Imaging is a ‘go-to’ reference for methods and applications of quantitative magnetic resonance imaging, with specific sections on Relaxometry, Perfusion, and Diffusion. Each section will start with an explanation of the basic techniques for mapping the tissue property in question, including a description of the challenges that arise when using these basic approaches. For properties which can be measured in multiple ways, each of these basic methods will be described in separate chapters. Following the basics, a chapter in each section presents more advanced and recently proposed techniques for quantitative tissue property mapping, with a concluding chapter on clinical applications. The reader will learn: The basic physics behind tissue property mapping How to implement basic pulse sequences for the quantitative measurement of tissue properties The strengths and limitations to the basic and more rapid methods for mapping the magnetic relaxation properties T1, T2, and T2* The pros and cons for different approaches to mapping perfusion The methods of Diffusion-weighted imaging and how this approach can be used to generate diffusion tensor maps and more complex representations of diffusion How flow, magneto-electric tissue property, fat fraction, exchange, elastography, and temperature mapping are performed How fast imaging approaches including parallel imaging, compressed sensing, and Magnetic Resonance Fingerprinting can be used to accelerate or improve tissue property mapping schemes How tissue property mapping is used clinically in different organs Structured to cater for MRI researchers and graduate students with a wide variety of backgrounds Explains basic methods for quantitatively measuring tissue properties with MRI - including T1, T2, perfusion, diffusion, fat and iron fraction, elastography, flow, susceptibility - enabling the implementation of pulse sequences to perform measurements Shows the limitations of the techniques and explains the challenges to the clinical adoption of these traditional methods, presenting the latest research in rapid quantitative imaging which has the possibility to tackle these challenges Each section contains a chapter explaining the basics of novel ideas for quantitative mapping, such as compressed sensing and Magnetic Resonance Fingerprinting-based approaches