Innate Immune Cell–Related Pathology in the Thalamus Signals a Risk for Disability Progression in Multiple Sclerosis
Our aim was to investigate whether 18-kDa translocator protein (TSPO) radioligand binding in gray matter (GM) predicts later disability progression in multiple sclerosis (MS). In this prospective imaging study, innate immune cells were investigated in the MS patient brain using PET imaging. The dist...
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| Published in: | Neurology : neuroimmunology & neuroinflammation Vol. 9; no. 4 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Lippincott Williams & Wilkins
01-07-2022
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| Online Access: | Get full text |
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| Summary: | Our aim was to investigate whether 18-kDa translocator protein (TSPO) radioligand binding in gray matter (GM) predicts later disability progression in multiple sclerosis (MS).
In this prospective imaging study, innate immune cells were investigated in the MS patient brain using PET imaging. The distribution volume ratio (DVR) of the TSPO-binding radioligand [
C]PK11195 was determined in 5 GM regions: thalamus, caudate, putamen, pallidum, and cortical GM. Volumetric brain MRI parameters were obtained for comparison. The Expanded Disability Status Scale (EDSS) score was assessed at baseline and after follow-up of 3.0 ± 0.3 (mean ± SD) years. Disability progression was defined as an EDSS score increase of 1.0 point or 0.5 point if the baseline EDSS score was ≥6.0. A forward-type stepwise logistic regression model was constructed to compare multiple imaging and clinical variables in their ability to predict later disability progression.
The cohort consisted of 66 patients with MS and 18 healthy controls. Patients with later disability progression (n = 17) had more advanced atrophy in the thalamus, caudate, and putamen at baseline compared with patients with no subsequent worsening. TSPO binding was significantly higher in the thalamus among the patients with later worsening. The thalamic DVR was the only measured imaging variable that remained a significant predictor of disability progression in the regression model. The final model predicted disability progression with 52.9% sensitivity and 93.9% specificity with an area under the curve value of 0.82 (receiver operating characteristic curve).
Increased TSPO radioligand binding in the thalamus has potential in predicting short-term disability progression in MS and seems to be more sensitive for this than GM atrophy measures. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Submitted and externally peer reviewed. The handling editor was Friedemann Paul, MD. Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article. The Article Processing Charge was funded by the authors. |
| ISSN: | 2332-7812 2332-7812 |
| DOI: | 10.1212/NXI.0000000000001182 |