Abstracts

Rationale: We have previously reported that about 90% rats with lateral fluid-percussion injury (FPI) -induced traumatic brain injury (TBI) and post-impact electrode implantation will develop acute post-injury seizures. However, seizures after electrode implantation were found also in sham-operated controls and naïve animals. These observations raised a question whether (a) electrode implantation -related anesthesia and surgery caused the acute seizures rather than TBI and (b) if so, would electrode implantation -related seizures compromise the epilepsy diagnosis in TBI animals at chronic phase? The acute post-implantation seizures have largely remained unrecognized as the video-EEG monitoring is often started 1 week after implantation. Our objective was to investigate whether the characteristics of acute post-implantation seizures differed from the “late unprovoked post-TBI seizures” used to diagnose post-traumatic epilepsy. Methods: We investigated the occurrence and characteristics of seizures during the 1st week after electrode implantation which was performed under isoflurane anesthesia in 38 Sprague-Dawley rats. All animals were implanted with four epidural screw electrodes and three bipolar intracerebral electrodes. Group 1: electrode implantation immediately after induction of lateral FPI (n=14). Group 2: implantation at 5 months post-TBI (n=14). Group 3: sham-operated experimental controls (craniotomy) with electrode implantation immediately (n=4) or 5 months after craniotomy (n=4). Group 4: six naïve rats with immediate electrode implantation. A 10-d video-EEG monitoring (vEEG) was initiated immediately after electrode implantation. On the 6th month, all animals were epilepsy-phenotyped with 1-month 24/7 vEEG. Results: Electrode implantation -related seizures were found both at acute post-TBI time period (90%, 9/10) as well as when implantation was done at chronic post-TBI time point (50%, 7/14). They often occurred in clusters of 4-9. Seizures were detected for up to 80 h after electrode-implantation surgery with the peak around 24-30 h post-implantation. On average, TBI rats had 15.4, sham-operated experimental controls 7.0 and naïve 14.3 seizures/80 h. Seizure duration varied between 16-259 sec, and the behavioral manifestations were typically non-convulsive. Even though the first post-implantation seizure was usually shorter than the later ones, no systematic prolongation in duration of successive seizures within a cluster was found. Our preliminary analysis suggests that electrode-implantation –related seizures were usually focal or focal with slow secondary generalization. The diagnostic late post-TBI seizures typically showed a fast generalization. Conclusions: Video-EEG, requiring electrode implantation under anesthesia, is necessary for seizure detection in animal models. Our data show that electrode implantation surgery under isoflurane anesthesia can trigger seizures. These seizures can complicate epilepsy diagnosis, for example, after TBI. Moreover, they need to be considered as a possible confounding factor in biomarker analysis or behavioral testing during the first week after electrode implantation surgery. Funding: This work was supported by the Academy of Finland and the National Institute of Neurological Disorders and Stroke (NINDS) Centers without Walls [grant number U54 NS100064].