Imaging of neuroinflammation in adult Niemann-Pick type C disease: A cross-sectional study.

2020-03-24

Walterfang, Mark

Di Biase, Maria A

Cropley, Vanessa L

Scott, Andrew M

O'Keefe, Graeme J

Velakoulis, Dennis

Pathmaraj, Kunthi

Ackermann, Uwe

Pantelis, Christos

Journal Article

0000-0002-1389-3691

0000-0002-7100-651X

0000-0003-0029-1525

0000-0002-6656-295X

0000-0002-8842-8479

0000-0002-9565-0238

10.1212/WNL.0000000000009287

To test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls. We scanned all participants with the PET radioligand 11C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA). We found increased binding of 11C-(R)-PK-11195 in total white matter compared to controls (p < 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus (p < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls (p < 0.001). A significant correlation between 11C-(R)-PK11195 binding and FA was shown (p = 0.002), driven by the NPC patient group. Our findings suggest that neuroinflammation-particularly in white matter-may underpin some structural and degenerative changes in patients with NPC.

link

Neurology 2020; online first: 24 March

Neurology