Levetiracetam Reduces the Rate of Seizures and High-frequency Oscillations During the First Two Weeks After Lateral Fluid Percussion Injury: UCLA Data for the epibios4rx Project 2 Study
Abstract number :
3.032
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2022
Submission ID :
2204383
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Cesar Santana-Gomez, PhD – UCLA; Brian Rundle, PhD – Neurology – UCLA; Mohamad Shamas, PhD – Neurology – UCLA; Gregory Smith, PhD – Neurosurgery – UCLA; Pablo Casillas-Espinosa, PhD – Neuroscience – Monash University, Melbourne; Matt Hudson, PhD – Neuroscience – Monash University, Melbourne; Rhys Brady, PhD – Neuroscience – Monash University, Melbourne; Glenn Yamakawa, PhD Student – Neuroscience – Monash University, Melbourne; Juliana Silva, PhD Student – Neuroscience – Monash University, Melbourne; Idrish Ali, PhD – Neuroscience – Monash University, Melbourne; Sandy Shultz, PhD – Neuroscience – Monash University, Melbourne; Patricia Saletti, PhD – Neurology – Albert Einstein College of Medicine, Bronx, New York; Christos Lisgaras, PhD – Neurology – Albert Einstein College of Medicine, Bronx, New York; Florencia Chena-Becerra, PhD – Neurology – Albert Einstein College of Medicine, Bronx, New York; Nigel Jones, PhD – Neuroscience – Monash University, Melbourne; Solomon Moshé, PhD – Neurology – Albert Einstein College of Medicine, Bronx, New York; Aristea Galanopoulou, PhD – Neurology – Albert Einstein College of Medicine, Bronx, New York; Terence O’Brien, PhD – Neuroscience – Monash University, Melbourne; Neil Harris, PhD – Neurosurgery – UCLA; Jerome Engel, PhD – Neurology – UCLA; Richard Staba, PhD – Neurology – UCLA
Rationale: Traumatic brain injury (TBI) is a serious health problem that can produce posttraumatic seizures and pathological high-frequency oscillations (HFO). The development of new treatments to prevent posttraumatic epileptogenesis is hindered by a lack of biomarkers that would greatly facilitate treatment trials. To help facilitate the discovery of new therapies, the EpiBioS4Rx Project 2 multicenter study designed an early stage post-TBI screening protocol and in the current study, assessed the effects of levetiracetam (LEV), an anti-seizure drug commonly used in patients after a severe TBI, on potential EEG biomarkers of epileptogenesis, including early seizures, EEG slow activity, and HFO. Here we report the UCLA data.
Methods: Lateral fluid percussion injury (LFPI) was induced in adult male Sprague-Dawley rats (300-350 g at the time of the injury). LEV-treated rats (n=15) received a 200 mg/kg injection i.p. immediately after the injury, followed by a 200 mg/kg/day via sub-dermal osmotic pump for first 7 days. Vehicle-treated rats (VEH; n=16) underwent the same procedures except pumps contained 0.9% saline solution. EEG was recorded continuously for 14 days from bilateral frontal, central and occipital screws and two paired microelectrodes in the perilesional cortical and ipsilateral hippocampus. EEG was reviewed for early (< =7 d post-LFPI) and late (>7 d) seizures and delta-frequency slow activity. RippleLab was used to detect ripples (R, 80-200 Hz) and fast ripple (FR; 200-500 Hz) in 20-min EEG epochs during the light period on days 0, 6, and 13 post-LFPI. Neuroscore tests were performed to evaluate neuromotor deficits at baseline and 2, 7, and 14 days post-LFPI.
Results: There was no difference in the incidence of early seizures between LEV- (11 of 15) and VEH-treated rats (10 of 16; p=.70). One rat from each group had late seizures. The percentage of focal and generalized seizures was similar between the two groups. LEV-treated rats had fewer seizures per day (p=.047), and each seizure was longer in duration than VEH-treated rats (p< .001), but no difference in cumulative duration of seizures between groups (p=.12). There was no difference in incidence or pattern of EEG slow activity between LEV- and VEH-treated rats. HFOs were detected in all rats. The rates of FR on days 6 and 13 (p=.008 & p=.001) and R on day 13 (p=.016) were lower in LEV-treated than in VEH-treated rats. Neuroscore performance was similar between groups.
Basic Mechanisms