Giannetti P, Politis M, Su P, Turkheimer FE, Malik O, Keihaninejad S, Wu K, Waldman A, Reynolds R, Nicholas R, Piccini P. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain. 2014 Nov 21. pii: awu331. [Epub ahead of print]
The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with 11C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years.
We show a global increase of normal-appearing white matter PK11195 binding in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions (as a indicator of MS diagnosis) had higher PK11195 binding in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 binding levels correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 binding in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 binding was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 binding. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically isolated syndrome normal-appearing white matter is also higher in those subjects who developed multiple sclerosis at 2 years. Our finding, if replicated in a larger study, could be of prognostic value and aid early treatment decisions in clinically isolated syndrome.
This is further evidence that on balance “hot” microglia detected by positron emission tomography using a radioactive (radioactive carbon) probe (PK11195) that binding microglia. There was evidence of microglial activation around the myelin and this was more noticeable at the first major symptom in people whoconvert to MS.