Abstract

The focus of this project is the use of MRI to understand the pathophysiology of multiple sclerosis (MS) and to determine whether disease activity is altered by various immunomodulatory treatments and to investigate the natural history of lesions. In a relatively small cohort of patients being treated with interferon beta-1b we have observed that high neutralizing antibody (Nab) titers to interferon may affect disease activity as determined by MRI but does not seem to alter MS disease progression when compared to patients not developing Nabs. T1- black holes (BHs) on MRI represent either areas of edema, axonal loss or astrogliosis and correlate with disability in patients with MS. We investigated the heterogeneity of BHs' appearance over 48 consecutive months in relapsing remitting MS patients, the role of contrast enhancing lesions (CEL) on BHs' formation, (iii) the role of CEL duration on BHs' duration over time and observed that formation of BHs is related to the amount of CEL. However the duration of BH once those lesions have been formed is most likely a consequence of the duration of the enhancement and blood brain barrier disruption. This new observation on persistent BH overtime indicated that it is possible that axonal loss and gliotic scars can resolve on MRI about 21 months following their initial appearance coinciding with an acute inflammatory lesion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL090001-12
Application #
7006035
Study Section
(LDRR)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chiu, Annie W; Richert, Nancy; Ehrmantraut, Mary et al. (2009) Heterogeneity in response to interferon beta in patients with multiple sclerosis: a 3-year monthly imaging study. Arch Neurol 66:39-43
Chiu, A W; Ehrmantraut, M; Richert, N D et al. (2007) A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging. Clin Exp Immunol 150:61-7
Simon, J H; Li, D; Traboulsee, A et al. (2006) Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines. AJNR Am J Neuroradiol 27:455-61
Richert, N D; Howard, T; Frank, J A et al. (2006) Relationship between inflammatory lesions and cerebral atrophy in multiple sclerosis. Neurology 66:551-6
Li, D K B; Held, U; Petkau, J et al. (2006) MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability. Neurology 66:1384-9
Morgen, K; Crawford, A L T; Stone, R D et al. (2005) Contrast-enhanced MRI lesions during treatment with interferonbeta-1b predict increase in T1 black hole volume in patients with relapsing-remitting multiple sclerosis. Mult Scler 11:146-8
Kirk, Shauna; Frank, Joseph A; Karlik, Stephen (2004) Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon? J Neurol Sci 217:125-30
Morgen, Katrin; Kadom, Nadja; Sawaki, Lumy et al. (2004) Training-dependent plasticity in patients with multiple sclerosis. Brain 127:2506-17
Frank, J A; Richert, N; Bash, C et al. (2004) Interferon-beta-1b slows progression of atrophy in RRMS: Three-year follow-up in NAb- and NAb+ patients. Neurology 62:719-25
Morgen, Katrin; Kadom, Nadja; Sawaki, Lumy et al. (2004) Kinematic specificity of cortical reorganization associated with motor training. Neuroimage 21:1182-7

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