Natural History of Multiple Sclerosis and Its Mimickers
Natural History of Multiple Sclerosis and Its Mimickers
Background:

 - Magnetic resonance imaging (MRI) has been used for decades to help diagnose and monitor
 neurological disorders like multiple sclerosis (MS). Researchers want to improve how MRI
 pictures are taken. They also want to learn more about using newer MRIs with stronger magnets
 to get better pictures than standard MRIs provide.

 Objectives:

 - To collect data that will help researchers better understand MS and related diseases.

 Eligibility:

 -  Adults 18 and older with MS or MRI findings that appear similar to MS, or with other
 neurological diseases that may look or act like MS.

 -  Healthy adult volunteers.

 Design:

 -  Participants will be screened with a review of their medical records.

 -  Participants will have a baseline visit. It will include a physical exam, medical
 history, and neurological exam. They may have blood tests.

 -  The study will last indefinitely.

 -  Participants may have MRIs. Some MRIs may include a contrast dye. For this, a needle
 will be used to guide a thin plastic tube into an arm vein.

 -  Participants may have up to 2 lumbar punctures per year. Skin will be numbed and a
 needle inserted between back bones will remove fluid.

 -  Participants may give saliva samples and have an eye exam.

 -  Participants may have evoked potential tests. These measure how the nervous system
 responds to different types of stimulation. Participants may sit in front of a TV and
 watch pictures on the screen. Or they may wear earphones that make a clicking noise or
 static. Or they may get a small electrical shock that may tingle and cause a hand or
 foot twitch.

 -  Participants may have tests of strength, spasticity, sensations, balance, and/or
 walking.
Objectives.

 The goals of this protocol are to study the pathophysiology of multiple sclerosis (MS),
 primarily through small studies that utilize magnetic resonance imaging (MRI), and to
 correlate the results with clinical and biological measures. The protocol includes only
 techniques with minimal risk (standard and quantitative clinical evaluation, MRI, blood
 draws, saliva testing, urine and stool collection, visual evoked potentials, ophthalmologic
 evaluation) or more-than-minimal risk (injection of approved gadolinium-based contrast
 agents, lumbar punctures) that are appropriate and common in this study population. Under
 this protocol, we will conduct:

 -  Pilot substudies. These studies are exploratory and hypothesis generating. Once
 sufficient data are collected to justify a hypothesis-driven study and a formal power
 analysis, further work will continue under either a dedicated protocol or, if
 appropriate, a hypothesis-testing substudy. There are no enrollment limitations for
 pilot substudies.

 -  Hypothesis-testing substudy. These studies have a specific hypothesis that can be tested
 with at most 6 participants per arm. If additional participants are required, a memo
 will be sent to the Protocol Review Committee (PIRC) and its statistical reviewer to
 request review of a hypothesis-testing substudy for possible additional enrollment.The
 memo will also be forwarded to the IRB.

 -  Individual patient substudies. These studies seek to increase knowledge of a disease
 process or to assist in the diagnosis of an individual patient.

 -  Technique development substudies. These studies will lay the groundwork for new
 experimental paradigms, using the methods approved under this protocol, which can be
 further tested in the substudies listed above.

 -  Training of investigators. These studies will be done to train new investigators in
 techniques relevant to the studies under this protocol.

 Study Population

 Three groups of study participants will be enrolled:

 -  MS patients. Participants with definite, probable, or possible MS.

 -  Patient controls. Participants with diseases that share features with MS.

 -  Healthy volunteers.

 Design

 We will design small substudies as ideas arise in the course of our work that are pertinent
 to the theme of the pathophysiology of MS (or of diseases that share features with MS). If a
 hypothesis testing sub-study leads to results of interest and if a larger population is
 necessary to reach statistical significance, a separate protocol will be submitted with a
 priori hypotheses, specific study design and power analysis adapted from the pilot or
 exploratory substudies performed in the present protocol.

 Outcome Measures

 These will include MRI, clinical, and biological outcome measures consistent with the
 objectives of the study and its investigators. Imaging measures will focus on features
 related to the central nervous system (CNS), particularly focal lesions. Clinical measures
 will include standard and established MS disability scales as well as quantitative measures
 related to function. Biological measures will include genotype, gene expression, proteomics,
 virological studies, and immunological profiling.
-  INCLUSION CRITERIA:

 <TAB>

 -  One or more of the following:

 -  Diagnosis of MS, clinically isolated syndrome, or radiologically isolated
 syndrome.

 -  Presentation with clinical or neuroimaging findings that, in the best judgment of
 the investigators, are possibly consistent with central nervous system
 inflammatory demyelination.

 -  Healthy volunteer.

 -  Age greater than or equal to18.

 -  Able to participate in study procedures and provide high-quality clinical research
 data, in the best judgment of the investigators.

 -  Interest of the study investigators in performing one or more procedures under one or
 more of the substudies.

 EXCLUSION CRITERIA:

 <TAB>

 -  Unwilling to allow sharing and/or use in future studies of coded samples and data that
 are collected for this study.

 -  Inability to provide informed consent.