Abstract Details

Title Microglia Activation in Clinically Isolated Syndrome: 11C11195PK-PET Change within Normal Appearing White Matter and Deep Grey Matter Structures

Topic MS and Related Diseases

Presentation(s) P06 - (-)

Poster/Presentation
Number 109

Objective

Background BACKGROUND: In a previous PET study with 11C11195PK, a specific ligand for activated microglia, we have demonstrated abnormal levels of activated microglia in NAWM and GM of subjects with Multiple Sclerosis (MS). Here we have applied 11C11195PK-PET methodology to study the GM and NAWM changes in CIS subjects.

Design/Methods DESIGN/METHODS: Eighteen subjects with CIS and 8 healthy controls (HC) subjects have been enrolled. The baseline visit included history, neurological examination, MRI and PKPET scans. All the assessments apart from the PET scanning were repeated at one year follow-up. We used the SUPERPK method of analysis, which measures the binding (PKBP) relative to the non-specific volume.

Results RESULTS: Global NAWM PKBP in the CIS group was higher than in the HC group (p=0.019) with a positive correlation with the number of T2 MRI lesions (p=0.0376; r=0.493). Also in CIS patients with T2 MRI lesions (as compared to CISs without lesions), levels of PKBP in NAWM correlated with the EDSS (p=0.007; r=0.6725). In the GM of central structures PKBP was higher in the CIS group than in HCs (p=0.0062). In the CIS subjects who developed MS at one year (N=7), there was a correlation between baseline EDDS and PKBP in NAWM of temporal lobe (p=0.0127; r=0.8617). Moreover, these subjects showed at baseline higher PKBP in putamen (p=0.0025 and p=0.0205) in comparison to HCs.

Conclusions CONCLUSIONS: Microglial activation in the NAWM of CIS subjects is globally increased in comparison to HCs and correlates positively with the number of WM lesions. GM changes in levels of activated microglia in CISs are localized in central areas. Both NAWM and GM changes in microglia of CIS could provide prognostic values for developing MS.

Authors/Disclosures
Paolo Giannetti PRESENTER	No disclosure on file
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia)	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Marios Politis, MD (Neurodegeneration Imaging Group)	No disclosure on file
	No disclosure on file
	No disclosure on file
Omar Malik, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Richard S. Nicholas, FRCP (Imperial College Healthcare Trust)	Dr. Nicholas has nothing to disclose.
Paola Piccini, MD (Hammersmith Hospital)	No disclosure on file

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