Abstract Details

Title Feasibility Trial of Spreading Depolarization Monitoring to Guide Management of Severe Traumatic Brain Injury: Initial Results

Topic Neuro Trauma and Critical Care

Presentation(s) N4 - Neuroscience in the Clinic: Waves of Change in Neurology: Rethinking Cortical Spreading Depolarization (CSD) (2:05 PM-2:15 PM)

Poster/Presentation
Number 002

Objective To determine the feasibility of real-time monitoring of spreading depolarizations (SD) to guide management of severe traumatic brain injury (TBI).

Background

SDs are waves of mass depolarization that propagate slowly through cerebral gray matter in response to injury and are a known causal mechanism of lesion development. Clinical studies have shown that SDs occur with high incidence in TBI and are associated with worse outcomes, but real-time diagnosis of SDs to guide intensive care management has not been tested.

Design/Methods We are conducting a prospective interventional study of patients who undergo electrocorticography (ECoG) as standard care for surgically treated TBI. Patients with SDs are randomized 1:1 to (A) standard care with blinding to further SDs or (B) a three-tiered intervention protocol aimed at SD prevention and suppression. Tier1 includes targets for physiological variables while Tiers2-3 add ketamine infusion at 1 and 2-4 mg/kg/hr.

Results Since January 2023, 48 patients were enrolled at 3 sites and 26 (54%) with SDs were randomized. Prior to randomization, the rate of SDs was 6.4 SDs/day in the control group (n=12) and 7.5 SDs/day in the treatment group (n=13). After randomization, the control group had 10.2 SDs/day over 4.0 days (median) of ECoG, while the treatment group had 4.7 SDs/day over 5.6 days. Nearly all patients (12/13) in the treatment group were escalated to Tier2, and 8/13 were escalated to Tier3 due to continuing SDs. Median SD rates for Tiers 1-3 were 5.6, 2.8, and 3.0 SD/day, respectively. Individual cases evidenced a strong efficacy of ketamine to block SDs in Tiers 2-3, though some patients were more refractory.

Conclusions Results to date suggest that a conservative, tiered treatment protocol can reduce SD incidence during intensive care by 54% (10.2 to 4.7 SD/day). The study aims to randomize 42 total patients, and outcomes are being collected.

Authors/Disclosures
Jed Hartings, PhD (University of Cincinnati) PRESENTER	Dr. Hartings has nothing to disclose.
Laura B. Ngwenya, MD, PhD	Dr. Ngwenya has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sophysa, USA. The institution of Dr. Ngwenya has received research support from NINDS/NIH. The institution of Dr. Ngwenya has received research support from Abbott.
Jennifer Goldthwait, RN	Ms. Goldthwait has nothing to disclose.
Danielle Sandsmark, MD	The institution of Dr. Sandsmark has received research support from NINDS. The institution of Dr. Sandsmark has received research support from BrainBox Solutions Inc. The institution of Dr. Sandsmark has received research support from Department of Defense.
Edilberto Amorim, MD	The institution of Dr. Amorim has received research support from American Heart Association. The institution of Dr. Amorim has received research support from Society of Critical Care Medicine. The institution of Dr. Amorim has received research support from Zoll Foundation. The institution of Dr. Amorim has received research support from Hellman Foundation. The institution of Dr. Amorim has received research support from Regents of the University of California. The institution of Dr. Amorim has received research support from Citizens United Against Epilepsy. The institution of Dr. Amorim has received research support from Regents of the University of California. The institution of Dr. Amorim has received research support from American Heart Association. The institution of Dr. Amorim has received research support from NIH. The institution of Dr. Amorim has received research support from Department of Defense. The institution of Dr. Amorim has received research support from Department of Defense. The institution of Dr. Amorim has received research support from American Heart Association.
Britta Lindquist, MD, PhD (UCSF Neurology)	The institution of Dr. Lindquist has received research support from National Institutes of Health NINDS.
Anthony DiGiorgio (University of California San Francisco)	No disclosure on file
Jens P. Dreier, MD	Prof. Dreier has nothing to disclose.
Brandon P. Foreman, MD (University of Cincinnati)	Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma Inc. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell, Inc. Dr. Foreman has received personal compensation in the range of $0-$499 for serving as a Consultant for Natus Medical Incorporated. Dr. Foreman has received personal compensation in the range of $0-$499 for serving as a Consultant for Immedica, Inc. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sophysa, Inc. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sage Therapeutics. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus Pharmaceuticals. Dr. Foreman has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for UCB Pharma Inc.. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Reminger Co, LPA. The institution of Dr. Foreman has received research support from DOD/AMRMC. The institution of Dr. Foreman has received research support from Biogen, Inc.. The institution of Dr. Foreman has received research support from DOD/AFRL. The institution of Dr. Foreman has received research support from NSF SCH:INT. The institution of Dr. Foreman has received research support from NIH/NIBIB. The institution of Dr. Foreman has received research support from DOD/JWMRP. The institution of Dr. Foreman has received research support from Marinus Pharmaceuticals. The institution of Dr. Foreman has received research support from PCORI. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as a Honoraria with Natus Medical Incorporated. Dr. Foreman has received personal compensation in the range of $500-$4,999 for serving as a Honoraria with Ceribell, Inc.. Dr. Foreman has received personal compensation in the range of $0-$499 for serving as a Peer-to-peer program honoraria with Marinus Pharmaceuticals.

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