Studies performed under 89-N-0045 are primarily designed to examine the evolving natural history of multiple sclerosis (MS) and its mimickers, viewed through the window of neuroimaging (especially magnetic resonance imaging or MRI). The protocol has four other important objectives: (1) Screening prospective participants for selected NINDS Neuroimmunology Clinic trials; (2) Performing studies to help define the mechanism of action and cause of side effects of disease modifying therapies (DMT); (3) Studying healthy volunteers for comparison with patients and for development of new experimental technologies; and (4) Comparing MS to other neurological diseases that share imaging features. To the extent possible, scheduled testing performed under this protocol will coincide with standard-of-care evaluations for diagnosis and longitudinal clinical management, thereby reducing the burden of research participation by participants. Such testing may involve state-of-the-art research methods. Additional pure-research visits may be scheduled to further investigate findings observed on scheduled visits and/or outside studies. Disease activity on MRI will be assessed using several MRI measures, including the detection of new on-study lesions, quantification of contrast-enhancing lesions, the total number and/or volume of MRI-visible lesions, brain volume and brain volume change, and more advanced MRI measures of tissue damage, such as quantitative magnetic relaxation mapping, diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI), and MR spectroscopy (MRS). Participants may be assessed with other imaging modalities, including optical coherence tomography (OCT), and they will be asked to provide research samples (generally blood, but also saliva and cerebrospinal fluid) and be studied clinically. In order to obtain comparative data for proper interpretation of the results in MS, two control cohorts one consisting of patients, the other of healthy volunteers will be studied. The patient control cohort will include patients with other CNS diseases that may share pathophysiological processes with MS patients (e.g. other inflammatory conditions of the central nervous system, mitochondrial disorders, leukodystrophies, neurodegenerative diseases that may cause axonal loss or oxidative stress, or cerebral small vessel disease). Enrollment of these control patient populations will help to answer the question of whether the identified MRI findings and/or pathophysiological mechanisms are MS-specific or generalizable.
- INCLUSION CRITERIA: - One of the following: - Diagnosis of MS or clinically isolated syndrome based on currently accepted diagnostic criteria. - Presentation with neuroimaging features consistent with MS. - Diagnosis of another disease of the CNS - Healthy volunteer. - Age greater than or equal to 18. - Able to give informed consent. NIH employees are eligible to participate. EXCLUSION CRITERIA: - Contraindication to MRI. - Pregnancy. - Unwilling to allow coded samples to be processed offsite or unwilling to have coded samples used in other studies.