Abstracts

Rationale: Compromised placental gas exchange in preterm infants can lead to perinatal cerebral hypoxia-ischemia (PHI) predisposing the infant to later-in-life neurological deficits, such as impaired cognition, cerebral palsy, and epilepsy. The PHI-induced spontaneous recurrent seizures (SRS's) begin as early as 2 months post-injury and are progressive in nature, steadily becoming more frequent and severe as the rat ages. These seizures routinely last 35-100 sec, and the convulsive seizures are generally longer than the non-convulsive seizures. In the process of further characterization of the latent period between injury and SRS, it was discovered that a new phenotype of short-lasting convulsive seizure was present in a single animal. Methods: A two-channel miniature wireless telemetry device was implanted in neonatal rat pups at P6 prior to induction of PHI at P7 using the Rice-Vannucci model. The single rat pup (n=1 out of a total n=24 PHI and sham-treated rats) was continuously video-EEG monitored while simultaneously being reared by its dam. At P21 the animal was weaned and video-EEG monitored for a total of 72 days. Blinded analysis of the EEG was done partially (50%) with a custom-written computer algorithm based on auto-correlation, and partially (50%) by manual visual inspection. Results: Stereotypical Racine grade 3 seizures exhibiting immobility with forelimb clonus and lordotic posturing were detected by the custom-written computer algorithm prior to 3 months of age. Electrographic activity consisted of a large-amplitude sentinel spike indicating onset of the seizure, followed by rhythmic spiking activity that increased in amplitude with duration before ending in a period of post-ictal depression. More commonly found were seizures lasting as short as 10 sec identified prior to 2 months of age within a single animal. These short-duration seizures began with an ipsilateral large-amplitude sentinel spike. The middle portion of the seizure consisted of a few repetitive bilateral high-amplitude spikes followed by low-amplitude synchronous spike-and-wave activity predominantly on the ipsilateral side. There was no discernable post-ictal phase at the end of the seizure. Although short in duration, these seizures were not similar to traditional spike-and-wave discharges. All of the brief seizures were convulsive with corresponding electrographic activity that was an attenuated version of the longer seizures. These short-duration seizures were not detected by the auto-correlation algorithm and were only identified manually by visual inspection. Conclusions: We have monitored SRS's in a variety of animal models including kainate, pilocarpine, traumatic brain injury and PHI where animals develop convulsive seizures after an injury. A similar phenotype of seizures present in all these models involves convulsive seizures lasting no less than 20 seconds. The single animal in this study is the first animal we have discovered to have brief convulsive seizures lasting only 10 seconds. The brief electrographic recordings could be a result of the seizure activity occurring distant to the recording electrodes. However, the placement of these recording electrodes have detected longer seizure within the same animal, suggesting that this is not the case. Further evidence that the brief seizures are not simply an artifact is that the convulsive component was also only 10 sec in duration. Although this is an n=1, this distinctive seizure phenotype is a novel finding that illustrates the heterogeneity of seizure types in these animals, even though it is a rare occurrence. Funding: NIH Grant# NS079274