Abstracts

Rationale: Severe traumatic brain injury (TBI) induces multiple seizures or status epilepticus (SE) in 20-30% of patients while EEG-monitored in intensive care unit at acute phase. We hypothesized that similar to humans, severe TBI in rats induced with lateral fluid-percussion injury (FPI) will trigger post-impact SE. Methods: Thirty-nine adult Sprague-Dawley male rats were anesthetized with 4% isoflurane and randomized into sham-operated experimental control (n=6) or lateral FPI-induced severe TBI groups (n=33). Four epidural skull electrodes were implanted right after induction of TBI (<48 h mortality 24%). All 25 surviving rats (19 TBI, 6 controls) were monitored 24/7 for 1 month using gage-specific video and time-locked EEG recordings. Fourteen TBI and 5 sham-operated controls had high quality EEG and were included in the final analysis. Results: During the first 48 h post-TBI, all injured rats included in the analysis (14/14) showed epileptiform EEG patterns, including, Occipital intermittent rhythmic delta activity (OIRDA), lateralized or generalized periodic discharges, spike-and-wave complex, poly-spikes, poly-spikes-and-waves complex, generalized continuous spiking, burst suppression, or suppression. The type, duration, and sequence of this EEG patterns varied between animals. Almost all (98%) of the electrographic seizures were recorded during 0-72 h post-TBI (23.2 ± 17.4 seizures/rat, median 16, range 2-56). Mean latency from the impact to the first electrographic seizure was 18.4 ± 15.1 h (median 16.1 h, range 2.4-53.1 h). The mean seizure duration was 86 ± 57 s (median 88 s, range 13-490 s). Analysis of high-resolution videos indicated that 96% of video-monitored electrographic seizures that were intermingled with other epileptiform EEG patterns associated with subtle behavioural abnormalities such as head nodding, head turning, unilateral eye blinking, piloerection, unilateral whisker movements, unilateral forepaw clonus, wet-dog shakes, non-meaningful “eating”, climbing, or circling behaviour. Only few of the electrographic seizures had behavioural symptoms that reached stages 3-4 in Racine’s scale. In most of the rats, epileptiform EEG patterns started to decay spontaneously on days 5-6 after TBI. In 36% (5/14) of injured animals, epileptiform EEG patterns were still present on day 7 d (144-168 h) post-TBI. Conclusions: Our data demonstrates that lateral FPI induced TBI results in non-convulsive SE with subtle behavioural manifestations, explaining why it has remained undiagnosed until now. The model provides a novel platform for testing treatments to stop post-injury SE in a clinically relevant context. Funding: This study was supported by the Medical Research Council of the Academy of Finland (Grants 272249 and 273909) and NINDS Center Without Walls, U54 NS100064 (EpiBioS4Rx).