Abstract
Objective To evaluate whether natalizumab treatment reduces microglial activation in MS.
Methods We measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [11C]PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest. MRI and disability measurements were performed for comparison. Evaluation was performed identically with 11 age- and sex-matched patients with MS who had no MS therapy.
Results Natalizumab treatment reduced microglial activation in the normal-appearing white matter (NAWM; baseline DVR vs DVR after 1 year of treatment 1.25 vs 1.22, p = 0.014, Wilcoxon) and at the rim of chronic lesions (baseline DVR vs DVR after 1 year of treatment 1.24 vs 1.18, p = 0.014). In patients with MS with no treatment, there was an increase in microglial activation at the rim of chronic lesions (1.23 vs 1.27, p = 0.045). No alteration was observed in microglial activation in gray matter areas. In the untreated patient group, higher microglial activation at baseline was associated with more rapid disability progression during an average of 4 years of follow-up.
Conclusions TSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells.
Glossary
- 3D=
- 3 dimensional;
- 9HPT=
- 9-Hole Peg Test;
- BPND=
- binding potential;
- DVR=
- distribution volume ratio;
- EDSS=
- Expanded Disability Status Scale;
- GM=
- gray matter;
- IQR=
- interquartile range;
- NAWM=
- normal-appearing white matter;
- ROI=
- region of interest;
- RRMS=
- relapsing-remitting MS;
- SPMS=
- secondary progressive MS;
- TSPO=
- translocator protein
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
Statistical analysis was conducted by Markus Matilainen, PhD, Marcus Sucksdorff, MD, and Jouni Tuisku, MSc, from Turku PET Centre, Turku University Hospital and University of Turku.
The Article Processing Charge was funded by Turku University Hospital/Research Services.
- Received December 19, 2018.
- Accepted in final form April 2, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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