Genetic Model of MS Severity

The goal of "Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the CNS" is to define the pathophysiological mechanisms underlying the development of disability in immune-mediated disorders of the central nervous system (CNS) and to distinguish these from physiological (and often beneficial) responses of the human immune system to CNS injury. The long-term objective of the trial is to acquire knowledge that would allow us to therapeutically inhibit the pathogenic mechanisms and enhance repair mechanisms in immune-mediated CNS diseases, thereby minimizing the extent of CNS tissue damage and promoting recovery. To date, 460 patients with a confirmed diagnosis of multiple sclerosis (MS) have been enrolled into the natural history clinical trial. In addition to standardized clinical, functional, neuroimaging and molecular/immunological data, blood samples were also collected for genetic research. However, only 299 study participants with confirmed MS currently have whole genome sequencing data available. In addition to the genome-wide data available for the 299 MS patients, this dbGaP submission provides demographic and phenotypic information for each subject collected at various points throughout the trial. We include race and family history of MS collected at the baseline visit as well as age and measures of disease severity collected at the most recent visit. As these data were randomized into discovery and validation cohorts, we also indicate the assigned group in the phenotypic data. It is hoped that these data may be applied to the development of clinically-useful tools such as diagnostic tests and new, sensitive scales of neurological disability, disease severity and CNS tissue destruction.]]>
PATIENT INCLUSION CRITERIA (for participation in the whole protocol): Presentation with a clinical syndrome consistent with immune-mediated CNS disorder, and/or Neuroimaging evidence of inflammatory and/or demyelinating/dysmyelinating CNS disease At least 12 years old at the time of enrollment Adults: able to give informed consent on their own or via a Legally Authorized Representative (LAR) or Durable Power of attorney (DPA), or Minors: parent or legal guardian able to give consent, with child willing to give assent, if reasonable based on their age and assent capacity, able to give assent with consent given by their parent or legal guardian Able to undergo the required procedures for diagnostic work-up, including lumbar puncture MRI and clinical/functional evaluations. PATIENT EXCLUSION CRITERIA (for participation in the whole protocol): Significant medical condition that would make participation in diagnostic and research part of evaluation impossible or risky Medical contraindications for MRI (i.e., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects or body piercings that cannot be removed) Unable to provide informed consent Unwilling to consent for collection of biological samples or their cryopreservation]]>
Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the CNS Patient Timeline: Initial evaluation visit at NIH Clinical Center Procedures & Data collected: a minimum of three brain MRIs and one spinal cord MRI, diagnostic lumbar puncture, brain and vision activity tests, blood and tissue samples All study participants will return for a follow-up visit 1 year after the initial evaluation visit Following 1-year evaluation, subjects are scheduled on an ad-hoc basis]]>