Abstract Details

Title An imaging signature in choroid plexuses in pre-symptomatic multiple sclerosis

Topic Multiple Sclerosis

Presentation(s) P15 - Poster Session 15 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-005

Background In-vivo evidence of CP involvement in MS has been recently shown, but whether CP changes are detectable by imaging before symptom onset, at the stage sometimes identified as radiologically isolated syndrome, needs to be investigated.

Objective To assess choroid plexus (CP) alterations in pre-symptomatic multiple sclerosis (MS).

Design/Methods 27 pre-symptomatic MS subjects, 97 clinically definite MS (CDMS) patients and 53 healthy controls (HC) underwent 3T-MRI; of which, 37 MS, 19 HC and one pre-symptomatic MS underwent translocator protein ¹⁸F-DPA-714 PET. T2-hyperintense lesions were contoured using Jim, while CPs were manually segmented on 3DT1-weighted images for volumetric analysis. Whole brain and lateral ventricle volume were extracted with Freesurfer. CP ¹⁸F-DPA-714 uptake, reflecting inflammation, was calculated as the average standardized uptake value (SUV). Oligoclonal band (OCB) status, duration of follow-up and conversion to CDMS were collected for the pre-symptomatic cohort. Multivariable regressions adjusted for age, sex, ventricular and brain volume were fitted to test CP volume differences: i) between pre-symptomatic subjects and MS or HC; ii) within the pre-symptomatic group, between OCB-positive versus OCB-negative subjects, and converters versus non-converters (additionally accounting for the length of follow-up). For the single pre-symptomatic case who also had ¹⁸F-DPA-714-PET, CP SUV differences with MS and HC were assessed through Crawford-Howell test.

Results CP volume was 29% higher in pre-symptomatic MS subjects compared with HC, even when accounting for brain and lateral ventricle volume (ß=0.31, p=.009), and was not different from MS (p=.21). Within the pre-symptomatic group, CP volume did not differ on the basis of the OCB or the converter status. Moreover, in the single pre-symptomatic case, CP ¹⁸F-DPA-714 binding was 33% higher than HC’s (p=.045).

Conclusions Our findings identify an imaging signature in CPs before symptom onset, encouraging investigations on its role as biomarker and arguing for the early involvement of the CPs’ blood-cerebrospinal fluid barrier in MS development.

Authors/Disclosures
Vito A. Ricigliano (ICM) PRESENTER	Mr. Ricigliano has received personal compensation in the range of $500-$4,999 for serving as a Expert with M3 global research, Biogen and Atheneum Partners.
	No disclosure on file
Andrea Lazzarotto	Dr. Lazzarotto has nothing to disclose.
Michel Bottlaender (Centre Hospitalier Frederic Joliot)	Michel Bottlaender has nothing to disclose.
Benedetta Bodini, MD	Dr. Bodini has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche . Dr. Bodini has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Bodini has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bodini has received research support from Biogen.
Celine Louapre (Hôpital Pitié Salpêtrière, APHP)	Celine Louapre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Celine Louapre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Celine Louapre has received personal compensation in the range of $0-$499 for serving as a Consultant for Roche. Celine Louapre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Celine Louapre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Celine Louapre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TEVA. The institution of Celine Louapre has received research support from Biogen. The institution of Celine Louapre has received research support from Neuratris.
Bruno Stankoff (Hopital De La Pitie Salpetriere)	Bruno Stankoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi, Teva, Novartis, Biogen. The institution of Bruno Stankoff has received research support from Roche, Sanofi, Serono .