Defining the clinical course of multiple sclerosis: the 2013 revisions.
ABSTRACT: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
Project description:Cardiovascular conditions remain the leading cause of mortality and morbidity worldwide, with genotype being a significant influence on disease risk. Cardiac imaging-genetics aims to identify and characterize the genetic variants that influence functional, physiological, and anatomical phenotypes derived from cardiovascular imaging. High-throughput DNA sequencing and genotyping have greatly accelerated genetic discovery, making variant interpretation one of the key challenges in contemporary clinical genetics. Heterogeneous, low-fidelity phenotyping and difficulties integrating and then analyzing large-scale genetic, imaging and clinical datasets using traditional statistical approaches have impeded process. Artificial intelligence (AI) methods, such as deep learning, are particularly suited to tackle the challenges of scalability and high dimensionality of data and show promise in the field of cardiac imaging-genetics. Here we review the current state of AI as applied to imaging-genetics research and discuss outstanding methodological challenges, as the field moves from pilot studies to mainstream applications, from one dimensional global descriptors to high-resolution models of whole-organ shape and function, from univariate to multivariate analysis and from candidate gene to genome-wide approaches. Finally, we consider the future directions and prospects of AI imaging-genetics for ultimately helping understand the genetic and environmental underpinnings of cardiovascular health and disease.
Project description:BACKGROUND:Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also gained attention in the field of MS. In fact, MS is a complex disease and several processes can be selected as a target for PET imaging. The use of PET with several different tracers has been mainly evaluated in the research setting to investigate disease pathophysiology (i.e. phenotypes, monitoring of progression) or to explore its use a surrogate end-point in clinical trials. RESULTS:We have reviewed PET imaging studies in MS in humans and animal models. Tracers have been grouped according to their pathophysiological targets (ie. tracers for myelin kinetic, neuroinflammation, and neurodegeneration). The emerging clinical indication for brain PET imaging in the differential diagnosis of suspected tumefactive demyelinated plaques as well as the clinical potential provided by PET images in view of the recent introduction of PET/MR technology are also addressed. CONCLUSION:While several preclinical and fewer clinical studies have shown results, full-scale clinical development programs are needed to translate molecular imaging technologies into a clinical reality that could ideally fit into current precision medicine perspectives.
Project description:<h4>Objective</h4>To reach consensus about the most relevant comorbidities to study in multiple sclerosis (MS) with respect to incidence, prevalence, and effect on outcomes; review datasets that may support studies of comorbidity in MS; and identify MS outcomes that should be prioritized in such studies.<h4>Methods</h4>We held an international workshop to meet these objectives, informed by a systematic review of the incidence and prevalence of comorbidity in MS, and an international survey regarding research priorities for comorbidity.<h4>Results</h4>We recommend establishing age- and sex-specific incidence and prevalence estimates for 5 comorbidities (depression, anxiety, hypertension, hyperlipidemia, and diabetes); evaluating the effect of 7 comorbidities (depression, anxiety, hypertension, diabetes, hyperlipidemia, chronic lung disease, and autoimmune diseases) on disability, quality of life, brain atrophy and other imaging parameters, health care utilization, employment, and mortality, including age, sex, race/ethnicity, socioeconomic status, and disease duration as potential confounders; harmonizing study designs across jurisdictions; and conducting such studies worldwide. Ultimately, clinical trials of treating comorbidity in MS are needed.<h4>Conclusion</h4>Our recommendations will help address knowledge gaps regarding the incidence, prevalence, and effect of comorbidity on outcomes in MS.
Project description:Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by a genome wide association study (GWAS) conducted by the International Multiple Sclerosis Genetic Consortium in a multinational cohort prompting the discovery of 57 non-MHC MS-associated common genetic variants. Hitherto, few of these newly reported variants have been replicated in larger independent patient cohorts. We genotyped a cohort of 1033 MS patients and 644 healthy controls with a consistent genetic background for the 57 non-MHC variants reported to be associated with MS by the first large GWAS as well as the HLA DRB1*1501 tagging SNP rs3135388. We robustly replicated three of the 57 non-MHC reported MS-associated single nucleotide polymorphisms (SNPs). In addition, our study revealed several genotype-genotype combinations with an evidently higher degree of disease association than the genotypes of the single SNPs. We further correlated well-defined clinical phenotypes, i.e. ataxia, visual impairment due to optic neuritis and paresis with single SNPs and genotype combinations, and identified several associations. The results may open new avenues for clinical implications of the MS associated genetic variants reported from large GWAS.
Project description:The Disease Ontology (DO) enables cross-domain data integration through a common standard of human disease terms and their etiological descriptions. Standardized disease descriptors that are integrated across mammalian genomic resources provide a human-readable, machine-interpretable, community-driven disease corpus that unifies the representation of human common and rare diseases. The DO is populated by consensus-driven disease data descriptors that incorporate disease terms utilized by genomic and genetic projects and resources engaged in studies to understand the genetics of human disease through the study of model organisms. The DO project serves multiple roles for the model organism community by providing: (1) a structured "backbone" of disease concepts represented among the model organism databases; (2) authoritative disease curation services to researchers and resource providers; and (3) development of subsets of the DO representative of human diseases annotated to animal models curated within the model organism databases.
Project description:BACKGROUND: Interventions for preventing falls in older people often involve several components, multidisciplinary teams, and implementation in a variety of settings. We have developed a classification system (taxonomy) to describe interventions used to prevent falls in older people, with the aim of improving the design and reporting of clinical trials of fall-prevention interventions, and synthesis of evidence from these trials. METHODS: Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus. Robust techniques were used including literature reviews, expert presentations, and structured consensus workshops moderated by experienced facilitators. The taxonomy was refined using an international test panel of five health care practitioners. We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 randomly selected published papers describing a variety of fall-prevention interventions. RESULTS: The taxonomy consists of four domains, summarized as the "Approach", "Base", "Components" and "Descriptors" of an intervention. Sub-domains include; where participants are identified; the theoretical approach of the intervention; clinical targeting criteria; details on assessments; descriptions of the nature and intensity of interventions. Chance corrected agreement of the final version of the taxonomy was good to excellent for all items. Further independent evaluation of the taxonomy is required. CONCLUSIONS: The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention. Investigators are encouraged to use the taxonomy to report their interventions.
Project description:BACKGROUND:There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. OBJECTIVE:Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. METHODS:Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). RESULTS AND CONCLUSION:We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.
Project description:Standardized magnetic resonance imaging (MRI) protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS). The Consortium of Multiple Sclerosis Centers (CMSC) convened an international panel of MRI experts to review and update the current guidelines. The objective was to update the standardized MRI protocol and clinical guidelines for diagnosis and follow-up of MS and develop strategies for advocacy, dissemination, and implementation. Conference attendees included neurologists, radiologists, technologists, and imaging scientists with expertise in MS. Representatives from the CMSC, Magnetic Resonance Imaging in MS (MAGNIMS), North American Imaging in Multiple Sclerosis Cooperative, US Department of Veteran Affairs, National Multiple Sclerosis Society, Multiple Sclerosis Association of America, MRI manufacturers, and commercial image analysis companies were present. Before the meeting, CMSC members were surveyed about standardized MRI protocols, gadolinium use, need for diffusion-weighted imaging, and the central vein sign. The panel worked to make the CMSC and MAGNIMS MRI protocols similar so that the updated guidelines could ultimately be accepted by international consensus. Advocacy efforts will promote the importance of standardized MS MRI protocols. Dissemination will include publications, meeting abstracts, educational programming, webinars, "meet the expert" teleconferences, and examination cards. Implementation will require comprehensive and coordinated efforts to make the protocol easy to access and use. The ultimate vision, and goal, is for the guidelines to be universally useful, usable, and used as the standard of care for patients with MS.
Project description:Seventeen genera and 48 species, in five subtribes, are recognized in Thailand. These include 15 endemic taxa, half of which are in the largest genus, Acilepis, with others in the genera Camchaya, Koyamasia, and Okia. A new monotypic genus, Pulicarioidea, is established with P. annamica, the new name for the species formerly known as Vernonia pulicarioides. New combinations are also made for Acilepis kerrii, Cyanthillium montanum, Koyamasia curtisii and Okia pseudobirmanica. Forty-six characters including habit, leaf, flower, achene and pollen morphology were analyzed using UPGMA. Five clusters of taxa were identified. Keys to genera, species and varieties, descriptions, vernacular names, ecological data and illustrations are provided.
Project description:Abnormal phenotypes have played significant roles in the discovery of gene function, but organized collection of phenotype data has been overshadowed by developments in sequencing technology. In order to study phenotypes systematically, large-scale projects with standardized objective assessment across populations are considered necessary. The report of the 2006 Human Variome Project meeting (Cotton et al, 2007) recommended documentation of phenotypes through electronic means by collaborative groups of computational scientists and clinicians using standard, structured descriptions of disease-specific phenotypes. In this report, we describe progress over the past decade in three-dimensional (3D) digital imaging and shape analysis of the face, and future prospects for large-scale facial phenotyping. Illustrative examples are given throughout using a collection of 1,107 3D face images of healthy controls and individuals with a range of genetic conditions involving facial dysmorphism.