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01-03-2007 | ORIGINAL COMMUNICATION

A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis

Authors: Derek Soon, Daniel R. Altmann, Kryshani T.M. Fernando, Garin Giovannoni, Frederick Barkhof, Chris H. Polman, Paul O’Connor, Bruce Gray, Michael Panzara, David H. Miller

Published in: Journal of Neurology | Issue 3/2007

Abstract

Natalizumab, an anti-α4 integrin antibody, significantly reduces the number of visibly enhancing multiple sclerosis (MS) lesions. In this substudy of a 2-year trial of natalizumab monotherapy versus placebo, contrast-enhanced imaging investigated for subtle blood brain barrier (BBB) leakage in relapsing remitting (RRMS) patients, and whether such leakage is modified by natalizumab. After 24 weeks on treatment, 40 patients from 3 centres (27 on natalizumab and 13 on placebo) were studied. T₁ weighted images were obtained before and at set timepoints up to 46 minutes after gadolinium (Gd)-DTPA (0.3mmol/kg to 18 patients, 0.15mmol/kg to 22). Paired regions of interest were placed around non-enhancing lesions and contralateral normal appearing white matter (NAWM). BBB leakage was inferred through post-Gd T₁ weighted signal intensity (SI) change. SI change was greater in T₂ non-enhancing lesions than paired NAWM at all timepoints (P < 0.005), indicating BBB leakage in lesions. No significant difference in inferred BBB leakage was observed between treatment arms as measured by SI change of lesions (P > 0.05 for all timepoints, joint test P = 0.24), or in SI change of NAWM (joint test P = 0.37). T₁ hypointense and isointense lesions exhibited similar SI changes (joint test P = 0.12). There is evidence of a subtle BBB leakage within visibly non-enhancing lesions in RRMS that was not modified by α4 integrin blockade in this substudy cohort.

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Title: A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis
Authors: Derek Soon
Daniel R. Altmann
Kryshani T.M. Fernando
Garin Giovannoni
Frederick Barkhof
Chris H. Polman
Paul O’Connor
Bruce Gray
Michael Panzara
David H. Miller
Publication date: 01-03-2007
Publisher: Steinkopff-Verlag
Published in: Journal of Neurology / Issue 3/2007
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-006-0356-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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