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.

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 with neurophysiologic tests 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 disease-modifying therapies 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 will be cryopreserved to provide repository for further studies focusing on detection of biomarkers indicative of disease state, disease stage or response 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 and to provide normative immunological measures.

• Tresley RM, Stone LA, Fields N, Maloni H, McFarland H, Frank JA. Clinical safety of serial monthly administrations of gadopentetate dimeglumine in patients with multiple sclerosis: implications for natural history and early-phase treatment trials. Neurology. 1997 Apr;48(4):832-5.
• Calabresi PA, Stone LA, Bash CN, Frank JA, McFarland HF. Interferon beta results in immediate reduction of contrast-enhanced MRI lesions in multiple sclerosis patients followed by weekly MRI. Neurology. 1997 May;48(5):1446-8.
• Calabresi PA, Tranquill LR, Dambrosia JM, Stone LA, Maloni H, Bash CN, Frank JA, McFarland HF. Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b. Ann Neurol. 1997 May;41(5):669-74.

• INCLUSION CRITERIA - PATIENTS:

Diagnosis of MS based on combined MRI and clinical criteria OR, presentation with a clinically isolated syndrome consistent with MS and at least 2 abnormalities on MRI consistent with MS.

18-70 years of age.

Not currently receiving therapy for MS.

Able to give informed consent.

EXCLUSION CRITERIA - PATIENTS:

Diagnosis of neurological disease other than MS.

Significant medical condition other than MS.

Contraindication for MRI.

INCLUSION CRITERIA - HEALTHY VOLUNTEER:

Age between 18 and 70.

EXCLUSION CRITERIA - HEALTHY VOLUNTEER:

Systemic disorder or central nervous system diseases of any kind or other related risk factors.

Previous history of alcohol and substance abuse.

Medical contraindications for MRI.

Psychological contraindications for MRI.

Pregnancy.

Unable to provide informed consent.