Epub: Politis M et al.ncreased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology. 2012 Jul 3.OBJECTIVE: Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.
METHODS: Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).
RESULTS: Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS.
CONCLUSIONS: Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in post-mortem SPMS cortical GM.
With modern imaging techniques to see specific cell tyeps in action during MS, it will help use to know better what is occurring over time and will help us match up the imaging with the pathology. This is important as we think that the microglia are important in damage and repair during MS.
In this study they utilized brain PET and the radioligand (11)C-PK11195 (Radio-active carbon version of PK11195 that binds to a peripheral benzodiazipine receptor called the translocator protein 18 kD (TSPO) as a marker of activated microglia in a cohort of 18 patients with multiple sclerosis (MS) and 8 healthy controls. In MSers they found that increased PK11195 binding occurred in the cortical gray matter (GM), but not white matter (WM) and this correlated with Expanded Disability Status Scale (EDSS) scores (r = 0.54......which means there was no real correlation of any meaningful way), but when just the SPMSers were looked at the GM signal and EDSS score (n = 8) was r = 0.84 (Now you are talking..remember r=1 means perfect correlation the more EDSS the more microglial activation), whereas there was no relationship in patients with relapsing-remitting MS (RRMS). GM PK11195 binding values did not correlate with duration of disease.
Interestingly, the binding patterns suggested regional pathology, with RRMS patients having more binding in the back bits of the brain (post-central, middle frontal, anterior orbital, fusiform, and parahippocampal gyri) and patients with SPMS additionally having more binding in the front bits of the brain (precentral, superior parietal, lingual and anterior superior, and medial and inferior temporal gyri) as compared to controls. The precentral gyrus binding values were associated with EDSS in SPMS (r = 0.9), whereas only post-central binding values correlated with EDSS in RRMS (r = 0.73). No associations were found between GM binding and cortical volume or WM binding and clinical disability scores. This means that glial activation in certain brain regions correlate more with disability in RR verses SPMS, where the latter have more regions being attacked and it would therefore be consistent with ongoing diasability problems.