Abstract Details

Title Cerebrospinal Fluid Lymphocytic Pleocytosis is Associated With Enhanced Blood-Brain Barrier Breakdown at the Time of Multiple Sclerosis Diagnosis

Topic Multiple Sclerosis

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

Poster/Presentation
Number 12-007

Background During MS exacerbations, patients undergo blood-brain barrier breakdown characterized by the presence of contrast-enhancing magnetic resonance imaging (MRI) lesions. We hypothesized that CSF profiles would correlate with the level of gadolinium enhancement on MRI; we anticipated that individuals with highly inflammatory MRIs would also exhibit CSF immune activation.

Objective To assess the pathophysiologic, clinical, and radiologic significance of lymphocytic pleocytosis in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients at the time of diagnosis.

Design/Methods This is a single-center, retrospective cohort study. The electronic medical record was queried for all individuals seen at Yale who had a first diagnosis of MS, clinically isolated syndrome, transverse myelitis, demyelination, or optic neuritis recorded between 2015 and 2020. Charts were manually reviewed for individuals who were (1) > 14 years old, (2) diagnosed with relapsing-remitting MS based on McDonald 2017 criteria, and (3) had undergone CSF and MRI of the brain within 60 days of their presenting symptoms. Approximately 200 qualifying patients were identified; preliminary analysis was performed on 55 patients. Updated numbers will be presented.

Results 22/55 (40.23%) of MS patients had CSF lymphocytic pleocytosis (> 5 lymphocytes/µl) at the time of diagnosis. These patients tended to be younger and have a shorter time since first neurologic symptoms compared to those without pleocytosis (p<0.005). They were also more likely to exhibit an elevated IgG index (mean-1.02, p<0.001) and CSF-restricted oligoclonal bands (20/22; 90.9%; p<0.05). Patients with lymphocytic pleocytosis were more likely to demonstrate either >4 brain gadolinium-enhancing lesions or gadolinium-enhancing lesions within the cervical spine.

Conclusions We observed a positive correlation between CSF lymphocytic pleocytosis and heightened immune response and increased blood-brain barrier breakdown at the time of MS diagnosis. Study of such CSF cells may give insight into the pathophysiology of MS relapses.

Authors/Disclosures
Dinesh Keran Sivakolundu, MD, PhD (Yale New Haven Hospital) PRESENTER	Dr. Sivakolundu has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
Hebatalla Elhusseiny, MD (University of Mississippi Medical Center)	Dr. Elhusseiny has nothing to disclose.
	No disclosure on file
David A. Hafler, MD, FAAN (Yale University School of Medicine, Dept of Neurology)	Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genetech. Dr. Hafler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Hafler has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Joint Commission International.
Erin Longbrake, MD, PhD, FAAN (Yale University)	Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Longbrake has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Longbrake 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. Longbrake 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. Longbrake has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ACTRIMS. Dr. Longbrake has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Longbrake has received research support from Genentech. The institution of Dr. Longbrake has received research support from Race to Erase MS. The institution of Dr. Longbrake has received research support from NINDS K23. The institution of Dr. Longbrake has received research support from Robert Patterson Leet Trust. The institution of Dr. Longbrake has received research support from Biogen. The institution of Dr. Longbrake has received research support from National MS Society. Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Programmatic Review with Department of Defense (CDMRP). Dr. Longbrake has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with National Institute of Health .