Abstract Details

Title Altered Permeability of Blood-CSF Barriers in Migraine

Topic Headache

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-026

Objective We tested the hypothesis that a combination of blood and cerebrospinal fluid (CSF) biomarkers of inflammation, cell adhesion, blood-brain barrier (BBB), and blood-CSF barrier (BCSFB) dysfunction will distinguish migraine from non-headache controls, with changes related to migraine frequency.

Background Biochemical and imaging studies provide conflicting evidence for disruption of the BCSFB/BBB in migraine. Because of the pathophysiology and therapeutic implications, further evaluation of the BCSFB and BBB will better evaluate if there is leakage from blood to the CNS.

Design/Methods Twelve non-headache controls and 53 migraineurs (age and sex matched) were studied with specific ELISA assays of blood plasma and CSF biomarkers.

Results A CSF cytokine panel showed no detectable inflammation. CSF levels of matrix metalloproteinase-9 MMP-9, and soluble platelet-derived growth factor receptor ß (sPDGFRß from pericytes) did not differ between the groups, indicating a lack of obvious endothelial or pericyte cell injury in migraine. However, compared to controls, migraineurs had higher CSF-blood quotients of albumin (Q_alb 5.6 ± 2.3 vs. 4.1 ± 1.9) and fibrinogen (Q_fib 162 vs. 86), and higher levels of soluble VCAM-1 in CSF (5.7 ± 2.3 vs. 4.7 ± 1.5 ng/mL). A migraine dose response based on increasing headache frequency revealed Q_fib values were 61 % lower (p = 0.004) and sVCAM-1 values were 63 % higher (p = 0.004) in those with more frequent migraine in the past year, while Q_alb, MMP-9, and sPDGFRß levels did not differ with headache frequency.

Conclusions Though altered albumin, fibrinogen, and sVCAM-1 cannot distinguish between the BBB and BCSFB dysfunction, recent experiments that identify a choroid plexus Na,K-ATPase role in an animal migraine model support our working hypothesis that the BCSFB is altered in migraineurs. Further studies, including imaging, are needed to resolve regional BBB and BCSFB barrier changes.

Authors/Disclosures
Robert Cowan, MD, FAAN (Stanford Neurosciences Health Center) PRESENTER	Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Cowan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for lundbeck. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biohavenn. Dr. Cowan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbviie. Dr. Cowan has stock in Percept. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received intellectual property interests from a discovery or technology relating to health care. Dr. Cowan has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
Liz Ekpo, MD (UC Davis Medical Center)	Dr. Ekpo has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Alfred Fonteh	No disclosure on file
Berislav V. Zlokovic, MD, PhD (University of Rochester Medical Center)	No disclosure on file
Michael G. Harrington, MD (Molecular Neurology, HMRI)	No disclosure on file

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