Overproduction of Pro-inflammatory Cytokines in New-Onset Refractory Status Epilepticus (NORSE) (S35.002)

Abstract

<h3>Objective:</h3> To investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with New-Onset Refractory Status Epilepticus. <h3>Background:</h3> Patients with New-Onset Refractory Status Epilepticus without explanation after initial evaluation (NORSE) often haven poor outcomes. Understanding the pathophysiological mechanisms underlying NORSE and its long-term consequences is crucial to improve NORSE management and prevent secondary neuronal injury. Several arguments suggest NORSE is a disorder of immunity or inflammation, likely post-infectious. Nonetheless, previous studies were conducted on insufficient patient cohorts to definitively identify biomarkers of inflammation in NORSE patients. <h3>Design/Methods:</h3> Patients with NORSE (n=61) were compared to patients with other refractory SE (RSE, n=37), and control patients without SE (n=52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead-based immunoassay detection (BD Biosciences). Cytokine levels were compared between patients with and without SE, and between NORSE and other RSE patients. Correlation between cytokine levels, demographic and clinical data were evaluated for patients with NORSE. <h3>Results:</h3> A significant increase of innate (IL6, TNFa, IL8, CCL2, MIP1a) and adaptative (Th1 IL12p70) pro-inflammatory cytokines/chemokines in SE patients was observed when compared to patients without SE, in serum and CSF. Innate pro-inflammatory cytokines/chemokines (blood: IL8, CCL2, MIP1a; CSF: IL1beta) were significantly increased in NORSE compared to other RSE patients. Patients with higher blood and CSF cytokine levels had worse outcome several months after SE ended. In contrast, T-cell-associated cytokines (IL12p70, IL17A) did not differ between patients with NORSE and other RSE and were not associated with outcome. <h3>Conclusions:</h3> Significant differences in serum and CSF cytokine/chemokine profiles between patients with NORSE and other RSE patients were identified. The elevation of innate pro-inflammatory cytokines in NORSE patients correlated with patient’s outcome at discharge and at long-term. These findings highlight the involvement of innate inflammation in the pathogenesis of NORSE and suggest the importance of anti-inflammatory interventions to improve outcomes. <b>Disclosure:</b> Dr. Hanin has nothing to disclose. Mr. Cespedes has nothing to disclose. Dr. Dorgham has nothing to disclose. Dr. Gopaul has nothing to disclose. 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. Vincent Navarro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Vincent Navarro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI pharma. Vincent Navarro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Angelini. The institution of Vincent Navarro has received research support from Fondation de l’AP-HP, Paris, France. Prof. Gaspard has nothing to disclose. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Hirsch has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for marinus. Dr. Hirsch has received personal compensation in the range of $0-$499 for serving as a Consultant for Medtronic. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Hirsch has received personal compensation in the range of $0-$499 for serving as a Consultant for Accure. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuropace. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rafa Laboratories, Ltd. Dr. Hirsch has received publishing royalties from a publication relating to health care. Dr. Hirsch has received publishing royalties from a publication relating to health care. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Neuropace. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Natus. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a speaker with UCB.