A1 Refereed original research article in a scientific journal

Microglial activation, white matter tract damage, and disability in MS




AuthorsRissanen E, Tuisku J, Vahlberg T, Sucksdorff M, Paavilainen T, Parkkola R, Rokka J, Gerhard A, Hinz R, Talbot PS, Rinne JO, Airas L

PublisherLIPPINCOTT WILLIAMS & WILKINS

Publication year2018

JournalNeurology, Neuroimmunology and Neuroinflammation

Journal name in sourceNEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION

Journal acronymNEUROL-NEUROIMMUNOL

Article numberARTN e443

Volume5

Issue3

Number of pages9

ISSN2332-7812

DOIhttps://doi.org/10.1212/NXI.0000000000000443

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/32494467


Abstract
ObjectiveTo investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS.MethodsPatients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [C-11](R)-PK11195. Clinical assessment and structural and quantitative MRI including diffusion tensor imaging (DTI) were performed for comparison.Results[C-11](R)-PK11195 binding was significantly higher in the normal-appearing white matter (NAWM) of patients with secondary progressive vs relapsing MS and healthy controls, in the thalami of patients with secondary progressive MS vs controls, and in the perilesional area among the progressive compared with relapsing patients. Higher binding in the NAWM was associated with higher clinical disability and reduced white matter (WM) structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity, and increased WM lesion load. Increasing age contributed to higher microglial activation in the NAWM among patients with MS but not in healthy controls.ConclusionsPET can be used to quantitate microglial activation, which associates with MS progression. This study demonstrates that increased microglial activity in the NAWM correlates closely with impaired WM structural integrity and thus offers one rational pathologic correlate to diffusion tensor imaging (DTI) parameters.

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