Should We Stop Traumatic Seizures? Risks vs. Benefits of Anti-seizure Medications in a Gyrencephalic Model of Severe TBI
Abstract number :
2.571
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2024
Submission ID :
1527
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Aarush Patnala, – Massachusetts General Hospital
Tawny Stinson, BS – Massachusetts General Hospital
Benjamin Baskin, BS – Massachusetts General Hospital
Andrew Schwalb, n/a – Massachusetts General Hospital
Arihant Patel, n/a – Massachusetts General Hospital
Mark Mousad, n/a – Massachusetts General Hospital
Trevor Kim, n/a – Massachusetts General Hospital
Gabrielle Delinsky, n/a – Massachusetts General Hospital
Beth Costine-Bartell, PhD – Massachusetts General Hospital, Harvard Medical School
Rationale: Worse traumatic brain injury (TBI) results in more seizures. The standard of care is administration of anti-seizure medications (ASM’s) even in young children where GABA can be depolarizing. ASM’s have known cardiac risks. It is unknown if traumatic seizures drive tissue pathology or are a symptom tissue damage. In our multi-factorial, severe TBI model where tissue damage spreads throughout the cortical ribbon beyond the area of cortical impact, we hypothesized that 1.) seizure and subarachnoid hemorrhage (SAH) together drive the evolution of hypoxic-ischemic injury, and 2.) stopping seizures 1 hour after initiation with a standard pediatric intensive care ASM protocol reduces tissue pathology.
Methods: Yorkshire piglets (n = 33) aged 7 (“infants”) and 30 days (“toddlers”) were randomly assigned to treatment groups: full model, full model + ASM, seizure only, seizure + SAH, SAH only, and sham + ASM. The full model injuries included, scaled to brain volume, cortical impact, mass effect, placement of SAH with kainic acid mixed in, and brief apnea and hypoventilation. Prior to induction of SAH and seizure, piglets were weaned off isoflurane and switched to a mainly non-GABA acting sedation regimen. ASM’s included escalating midazolam and phenobarbital. Piglets were sedated, intubated, mechanically ventilated, and managed in an intensive care for 24 hours to allow for evolution and spread of tissue damage and to record EEG (6 channel bipolar montage).
Results: The seizure only group had several hours of seizure but no observable damage via hematoxylin and eosin staining. In the full model group, the percentage of SAH covering the cortex was highly correlated with tissue damage (P < 0.001)
Anti-seizure Medications