Genetic and Environmental Determinants of Multiple Sclerosis Activity and Progression:The Role of Neuroimaging

When Nov 01, 2011
from 03:00 PM to 04:00 PM
Where G202 MBRB
Contact Name
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Charles R.G. Guttman, M.D.

Center for Neurological Imaging, Departments of Radiology and Neurology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, U.S.A. 

White matter in brain and spinal cord is affected in the context of several diseases, with potentially diverse cellular and molecular targets, and through diverse inflammatory and neurodegenerative mechanisms and pathways. Genetically determined predisposition towards specific diseases affecting CNS white matter, such as multiple sclerosis (MS), has been explored by searching for susceptibility genes. In the example of MS, disease susceptibility alleles have been identified, but elevate the relative risk of contracting the disease only slightly. The prevalence of MS remains largely unexplained.

More recently, genetic explorations have focused on identifying trait-related genes, that modulate the activity and severity of MS. It is in this context that the current role of imaging is pre-eminent, in describing endo-phenotypes reflecting the progression and activity of disease with much higher sensitivity than feasible with routine clinical assessment. The exploitation of serial imaging through measurement of change enables subclinical detection of disease activity.

The limited specificity of currently available imaging methods deployable at the large scale necessary for these analyses, limits the search to coarse aspects of inflammation, degeneration, and repair. Routinely deployable methods for the specific assessment of cellular and molecular white matter components (eg, microglia and microglial activation markers; re-myelination markers) are needed. Sophisticated image analysis strategies of multi-modal imaging studies are useful in dissecting the relative impact of genetic or exogenous factors on distinct brain compartments (eg, cortical grey matter vs. sub-cortical grey matter nuclei vs. white matter fiber tracts).

Finally, it is important to recognize that genetic susceptibility to disease or to enhanced/diminished disease progression is likely modulated by exogenous factors, mandating large-scale studies combining imaging-based characterization of endo-phenotypes with extensive assessment of environmental factors in the context of the genetic background of individual patients.

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