Overview
The central hypothesis of this protocol is that it is possible, using First Degree Relatives (FDRs) of patients with Multiple Sclerosis (MS) and assessing a variety of both known and unknown risk factors for MS, to define a risk algorithm for earliest signs of development of MS. The plan will be to do an abbreviated brain Magnetic Resonance Imaging (MRI) scan in asymptomatic, young FDRs, analyze blood for a variety of immunological, genetic, neuroaxonal damage, metabolic, viral serology and other markers, and have FDRs fill out a detailed bioscreen questionnaire about lifestyle factors and perform a cognitive screening test. The investigators will then compare the results of the various blood/other studies in FDRs with and without an MRI showing signs signs concerning for MS, as well as age-and sex-matched NON-FDRs who will have blood drawn and fill out the questionnaire. With this preliminary cross-sectional study, the investigators hope to begin to identify a risk stratification model for those at highest risk of developing MS, ie FDRs, with a long-term goal of developing a longitudinal study to increase sensitivity and specificity of the risk model.
Description
Specific Aims, among asymptomatic first degree relatives (FDRs), aged 18-30, of multiple sclerosis (MS) patients:
- Determine the prevalence of brain MRI lesions disseminated in space (DIS), consistent with MS
- Gather data on potential risk factors or early signs related to MS development, including markers for: genes, immunological function, environmental factors, neuroaxonal damage, Vitamin D levels, lipid metabolism, activity levels, mood abnormalities, and cognitive function. From this, develop a risk factor score, incorporating all relevant potential markers of increased risk of DIS.
- To use this pilot, cross-sectional study as a base for development of a long-term, longitudinal, multi-center study to determine genetic and environmental risks for pre-symptomatic MS
- To create and maintain a biobank of specimens for future analysis as other potential biomarkers become available.
- Evaluate for potential dissemination in time (DIT) and dissemination in space (DIS) in asymptomatic FDRs through longitudinal assessment.
Sequences to include
- Whole brain T1-weighted images acquired using 3-Dimensional fast spoiled-gradient recalled acquisitions (T1-3D-FSPGR) with 1 mm slice thickness and isotropic voxel dimensions.
- Whole brain 3-Dimensional Double Inversion Recovery (DIR) acquisition with 1.5 mm slice thickness.
- Whole brain T2-weighted Fluid Attenuated Inversion Recovery (FLAIR ) images with 1 mm slice thickness and isotropic voxel dimensions will be combined with
- Whole brain T2-weighted segmented echo-planar imaging (segEPI) images with <=1 mm slice thickness and isotropic voxel dimensions to obtain FLAIR images.
Blood analysis for:
- Single Nucleotide Polymorphism analysis of greater than 200 known mutations associated with risk of MS, and do an human leukocyte antigen (HLA) analysis
- CD20 on CD4+ cell analysis
- B Cell Anergy analysis Lipid levels
- Viral serologies (HSV, EBV, CMV, VZV)
- Neurofilament Light
- Vitamin D levels
Bioscreen analysis based on that from the Diabetes Autoimmunity Study in the Young (DAISY); and to include the Godin Leisure-Time Exercise Questionnaire (GLTEQ), which has been validated in both adults and children and a validated dietary/food frequency questionnaire. In addition perform a cognitive screen with a Symbol Digit Modality test.
Blood will also be stored for future potential analysis, including peripheral blood mononuclear cells, serum, and Ribonucleic acid (RNA).
Eligibility
Inclusion Criteria:
- FDR Inclusion Criteria
- Male and female
- All races and ethnicities
- Ages 18-30
- Must have a parent, sibling or child with MS fulfilling McDonald 2017 criteria
- No symptoms suggestive of MS on formal screen
- Ability to undergo a non-contrast MRI and venipuncture, and perform an environmental screen, mood screen and cognitive test
- Non-FDR Inclusion Criteria
- Male and female
- All races and ethnicities
- Ages 18-30
- Must NOT have a FDR (parent, sibling, child) or second degree relative (grandparent, aunt or uncle) with MS fulfilling McDonald 2017 criteria
- No symptoms suggestive of MS on formal screen
- Ability to undergo venipuncture and perform an environmental screen.
Exclusion Criteria:
- FDR Exclusion Criteria
- Symptoms suggestive of MS on formal screen
- Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's
- Non-FDR Exclusion Criteria
- Symptoms suggestive of MS on formal screen
- Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's