Studies performed under 89-N-0045 are designed to examine the natural history of multiple sclerosis (MS) using MRI and immunological measures. In addition to studying the natural history of untreated patients, the natural history of patients receiving approved disease-modifying therapies of MS will be examined. In both cohorts of patients levels of disease activity on MRI will be compared with immunological characteristics in order to help identify disease mechanism. Patients with either definite MS (based either on clinical or combined clinical and MRI criteria) or with an initial presentation of neurological dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI will be assessed using several MRI measures of disease activity including the number of contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to assess axonal damage. Patients will be assessed clinically and correlations between immunological and genetic factors and disease activity as seen clinically or by MRI will be studied. A second cohort of patients starting the use of approved therapy will also be examined. Patients referred to NIH prior to beginning approved therapy will be assessed with a series of three monthly MRIs to determine the level of pretreatment disease activity. After beginning approved therapy under the direction of their private physician, patients will be followed similarly to the natural history cohort. Immunological and genetic findings will be accessed before and during therapy in order to help establish the mechanisms of action of the therapies and to identify mechanisms accounting for either a response or lack of response to therapy. Part of the collected samples willl be cryopreserved to provide respository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or repsonse to therapies. Additionally, a cohort of normal volunteers will be studied. The studies in the normal volunteers will be used to establish the most appropriate imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging sequences for studying normal white matter in MS patients using magnetization transfer (MT) imaging and to provide normative immunological measures. ...

Population

-MS/CIS/RIS population-Patients with a diagnosis of MS or who have typical imaging abnormalities associated with MS.-Non-MS comparison populations-Patients with disorders of the CNS, to include patients with diseases that share mechanisms of tissue damage with MS, such as mitochondrial disorders, leukodystrophies, neurodegenerative diseases that may cause axonal loss or oxidative stress, and chronic small vessel disease.-Healthy volunteers-Healthy volunteers for technique development and comparison with the patient populations.

Brief Title

Magnetic Resonance Imaging (MRI) to Evaluate Activity of Multiple Sclerosis (MS)

Official Title

Evaluation of Progression in Multiple Sclerosis by Magnetic Resonance Imaging (MRI)

Brief Summary

Studies performed under 89-N-0045 are designed to examine the natural history of multiple <br /> sclerosis (MS) using MRI and immunological measures. In addition to studying the natural <br /> history of untreated patients, the natural history of patients receiving approved <br /> disease-modifying therapies of MS will be examined. In both cohorts of patients levels of <br /> disease activity on MRI will be compared with immunological characteristics in order to help <br /> identify disease mechanism. Patients with either definite MS (based either on clinical or <br /> combined clinical and MRI criteria) or with an initial presentation of neurological <br /> dysfunction consistent with MS will be studied longitudinally by MRI. Disease activity on MRI <br /> will be assessed using several MRI measures of disease activity including the number of <br /> contrast enhancing lesions, the overall burden of disease, brain atrophy and measures to <br /> assess axonal damage. Patients will be assessed clinically and correlations between <br /> immunological and genetic factors and disease activity as seen clinically or by MRI will be <br /> studied. <br /> <br /> A second cohort of patients starting the use of approved therapy will also be examined. <br /> Patients referred to NIH prior to beginning approved therapy will be assessed with a series <br /> of three monthly MRIs to determine the level of pretreatment disease activity. After <br /> beginning approved therapy under the direction of their private physician, patients will be <br /> followed similarly to the natural history cohort. Immunological and genetic findings will be <br /> accessed before and during therapy in order to help establish the mechanisms of action of the <br /> therapies and to identify mechanisms accounting for either a response or lack of response to <br /> therapy. Part of the collected samples willl be cryopreserved to provide respository for <br /> further studies focusing on detection of biomarkers indicative of disease state, disease <br /> stage or repsonse to therapies. <br /> <br /> Additionally, a cohort of normal volunteers will be studied. The studies in the normal <br /> volunteers will be used to establish the most appropriate imaging sequences for studying <br /> normal white matter in MS patients using magnetization transfer (MT) imaging sequences for <br /> studying normal white matter in MS patients using magnetization transfer (MT) imaging and to <br /> provide normative immunological measures. <br /> <br /> ...

Detailed Description

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.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.