Abstract Details

Title Lower Cerebral Arterial Blood Flow is Associated with Greater Serum Neurofilament Light Chain Levels in Multiple Sclerosis Patients

Topic Multiple Sclerosis

Presentation(s) S19 - MS Biomarkers and Symptom Management (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Background Cerebral hypoperfusion, vascular pathology, and cardiovascular risk factors have been associated with disease activity in MS patients.

Objective To assess the relationship between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL), a biomarker of neuronal damage in heterogeneous population of multiple sclerosis (MS) patients.

Design/Methods Total CABF was measured in 137 MS patients (86 clinically isolated syndrome (CIS)/relapsing-remitting (RR) and 51 progressive MS (PMS) patients) and 48 healthy controls (HCs) using echo-color Doppler ultrasound. Levels of sNfL were quantitated using a single molecule assay (SIMOA). MRI examination on a 3.0T GE Signa Excite scanner allowed quantification of T2 lesion burden and whole brain volume (WBV). Linear regression models determined the sNfL variance explained by total CABF after correction for demographic and MRI-based effects.

Results CABF was associated with sNfL levels in MS patients (r=-0.291, p=0.001) but not in the matched HCs (r=-0.0.31, p=0.837). This relationship was specifically present in CIS/RRMS group (r=-0.305, p=0.004), but not in the PMS (r=-0.309, p=0.029, non-significant after Benjamini-Hochberg correction). After adjustment for age, sex and BMI, CABF explained additional 2.6% of sNfL variance (standardized β=-0.167, p=0.044). CABF remained significant predictor (standardized β=0.18, p=0.034) despite including T2 lesion burden and WBV effects to the previous model. MS patients within the lowest CABF quartile (CABF ≤760.6mL/min) had significantly higher sNfL levels (34.55pg/mL versus 23.88pg/mL, age and BMI-adjusted p=0.042) when compared to MS patients within the highest CABF quartile (CABF ≥1130.6mL/min).

Conclusions Lower CABF is associated with increased levels of sNfL in CIS/RRMS patients, highlighting the relationship between cerebral hypoperfusion and increased axonal pathology.

Authors/Disclosures
Dejan Jakimovski, MD, PhD (Buffalo Neuroimaging Analysis Center, University at Buffalo) PRESENTER	Dr. Jakimovski has nothing to disclose.
Niels Bergsland (Buffalo Neuroimaging Analysis Center / State University of New York At Buffalo)	Prof. Bergsland has nothing to disclose.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center)	Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
	No disclosure on file
	No disclosure on file
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Filterlex. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for 3D Communications. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurology Live. The institution of Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen.