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

Mark Walterfang; Maria A Di Biase; Vanessa L Cropley; Andrew M Scott; Graeme O'Keefe; Dennis Velakoulis; Kunthi Pathmaraj; Uwe Ackermann; Christos Pantelis

doi:10.1212/WNL.0000000000009287

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

Neurology. 2020 Apr 21;94(16):e1716-e1725. doi: 10.1212/WNL.0000000000009287. Epub 2020 Mar 24.

Authors

Mark Walterfang¹, Maria A Di Biase¹, Vanessa L Cropley¹, Andrew M Scott¹, Graeme O'Keefe¹, Dennis Velakoulis¹, Kunthi Pathmaraj¹, Uwe Ackermann¹, Christos Pantelis²

Affiliations

¹ From the Neuropsychiatry Unit (M.W., D.V.), Royal Melbourne Hospital; Melbourne Neuropsychiatry Centre (M.W., M.A.D., V.L.C., D.V., C.P.), The University of Melbourne & North Western Mental Health; The Florey Institute of Neuroscience and Mental Health (M.W., C.P.), Department of Psychiatry (M.W., M.A.D., V.L.C., D.V., C.P.), and Centre for Neural Engineering, Department of Electrical and Electronic Engineering (C.P.), The University of Melbourne; Department of Molecular Imaging and Therapy (A.M.S., G.O., K.P., U.A.), Austin Health and The University of Melbourne, Heidelberg; Olivia Newton John Cancer Centre and La Trobe University (A.M.S., G.O., U.A.), Melbourne; and Cooperative Centre for Mental Health Research (C.P.), Carlton, Australia.
² From the Neuropsychiatry Unit (M.W., D.V.), Royal Melbourne Hospital; Melbourne Neuropsychiatry Centre (M.W., M.A.D., V.L.C., D.V., C.P.), The University of Melbourne & North Western Mental Health; The Florey Institute of Neuroscience and Mental Health (M.W., C.P.), Department of Psychiatry (M.W., M.A.D., V.L.C., D.V., C.P.), and Centre for Neural Engineering, Department of Electrical and Electronic Engineering (C.P.), The University of Melbourne; Department of Molecular Imaging and Therapy (A.M.S., G.O., K.P., U.A.), Austin Health and The University of Melbourne, Heidelberg; Olivia Newton John Cancer Centre and La Trobe University (A.M.S., G.O., U.A.), Melbourne; and Cooperative Centre for Mental Health Research (C.P.), Carlton, Australia. mark.walterfang@mh.org.au.

PMID: 32209649
DOI: 10.1212/WNL.0000000000009287

Abstract

Objective: 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.

Method: 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).

Results: 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.

Conclusions: Our findings suggest that neuroinflammation-particularly in white matter-may underpin some structural and degenerative changes in patients with NPC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anisotropy
Brain / diagnostic imaging*
Brain / metabolism
Case-Control Studies
Cross-Sectional Studies
Female
Gray Matter / diagnostic imaging*
Gray Matter / metabolism
Gray Matter / pathology
Humans
Inflammation / diagnostic imaging*
Inflammation / metabolism
Isoquinolines
Magnetic Resonance Imaging
Male
Niemann-Pick Disease, Type C / diagnostic imaging*
Niemann-Pick Disease, Type C / metabolism
Organ Size
Positron Emission Tomography Computed Tomography
White Matter / diagnostic imaging*
White Matter / metabolism
Young Adult

Substances

Isoquinolines
PK 11195