Protocol Number: 09-N-0032

Title:

Comprehensive Multimodal Analysis of Patients with Neuroimmunological Diseases of the CNS

Number:

09-N-0032

Summary:

Objective: The goal of this study 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 study 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.

Study Population: Patients with evidence of immune-mediated CNS injury will be enrolled. In addition, healthy volunteers will be included as controls for immunological and neuroimaging biomarkers.

Design: We will collect, in a standardized manner, multimodal data (clinical/functional, neuroimaging and molecular/immunological data) during the diagnostic work-up of untreated patients with varied disorders of the CNS in which immune-mediated processes are expected to play a pathophysiological role.

For the patient cohort, a comprehensive initial evaluation will be performed in order to establish a definitive diagnosis, but also to collect consistent multimodal research data. This evaluation will include a standardized clinical exam, functional tests quantifying clinical disability, MRI and other neuroimaging modalities, CSF and serological studies, and lymphapheresis. Additional diagnostic tests, tailored to individual patients, may be performed if required for the diagnostic process.

The protocol stipulates a one-year mandatory follow-up for all patients inclusive of clinical and MRI imaging, as well as repetition of any additional imaging or functional testing performed during the initial evaluation. Depending on the specific diagnosis, treatment decisions and clinical/research needs, patients may be offered additional follow-up visits The maximum frequency of the follow-up visits and research samples to be collected is specified in order to ensure patient safety is not compromised.

The volunteer cohort will provide sex and age-matched normative values for the immunological and imaging parameters.

Outcome Measures: Clinical, MRI and immunological measures will be the outcome measures. However, no pre-defined research questions will be addressed other than to establish the diagnosis, determine the level of disease activity, and monitor the natural history.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Presentation with a clinical syndrome consistent with immune-mediated CNS disorder and/or

2. Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS disease

3. 18-70 years of age

4. Able to give informed consent

5. Able to undergo complex diagnostic work-up, including lumbar puncture and MRI imaging

6. Able to undergo related research procedures, such as lymphocytapheresis for collection of peripheral blood mononuclear cells (PBMC) samples

Health Volunteers

1. Age between 18 and 70

2. Vital signs are found within normal range at the time of the screening visit

3. Able to give informed consent

4. Able to undergo related research procedures, such as blood draw or lymphocytapheresis for collection of peripheral blood mononuclear cells (PBMC) samples

EXCLUSION CRITERIA:

1. Significant medical condition that would make participation in diagnostic and research part of evaluation impossible or risky

2. Medical contraindications for MRI (ie- 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)

3. Unable to provide informed consent

4. Unwilling to consent for collection of biological samples or their cryopreservation

Healthy Volunteer

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

2. Previous history of alcohol and substances abuse

3. 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)

4. Psychological contraindications for MRI (i.e. claustrophobia). This will be assessed at the time the medical history is collected

5. Pregnancy or current breastfeeding

6. Unable to provide informed consent

7. Any contraindications to having study procedures done

8. History of auditory disorder (i.e. hearing impairment, known impaired acoustic reflex, tinnitus)

Special Instructions:

Currently Not Provided

Keywords:

Inflammation

Multiple Sclerosis

Neuroimmunology

Immune Disorder

Neuroimaging

Recruitment Keyword(s):

None

Condition(s):

Central Nervous System Disease

Multiple Sclerosis

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Andrews HE, Nichols PP, Bates D, Turnbull DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis. Med Hypotheses. 2005; 64(4):669-77.

Arnett HA, Wang Y, Matsushima GK, Suzuki K, Ting JP. Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J Neurosci. 2003 Oct 29;23(30):9824-32.

Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest. 2006 Dec; 116(12):3252-7. Epub 2006 Nov 9

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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