High‐frequency Oscillations after Status Epilepticus: Epileptogenesis and Seizure Genesis

Abstract

Summary:Purpose: To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus.Methods: Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 µg/0.2 µl) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for ≥30 days.Results: Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100-200 Hz); in others, HFOs were in the fast ripple frequency range (200-500 Hz), or a mixture of both oscillation frequencies was found.The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 ± 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures.Conclusions: A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic. Key Words: EpileptogenesisHigh-frequency oscillations-Dentate gyrus-Kainic acidRat.Processes leading to recurrent spontaneous seizures after an initial precipitating event remain obscure. After status epilepticus induced by intrahippocampal injection of kainic acid (KA), ∼50% of rats develop recurrent spontaneous seizures, which appear to arise from the region of the injected hippocampus and adjacent entorhinal cortex (1). The dentate gyrus (DG) is believed to play an important role in the mediation of seizure generation (2,3).High-frequency oscillations (HFOs) with a frequency range of 100 to 200 Hz, called ripples, occur in the normal rat hippocampus and entorhinal cortex, but not in DG (4-6). Evidence suggests that normal ripples reflect activity of interneurons that facilitate information transfer by

High-frequency changes during interictal spikes detected by time-frequency analysis

“…Distinct HFOs have been closely linked to areas of seizure onset and epileptogenic areas (Bragin et al, 2002b(Bragin et al, , 2004Jacobs et al, 2008Jacobs et al, , 2009a. Additionally, spikes co-occurring with HFOs were more exact in predicting the SOZ than spikes in general.…”

Astrocytes and Epilepsy

“…Abnormal epileptiform activity has been recorded from the EC region 91,92 and is reported to be the lead structure in the emergence of tonic discharges in mesial structures in a majority of patients with EC atrophy. 93,94 Some studies have reported neuronal loss and gliosis in superficial layers of the EC, 86 whereas others find no significant difference in neuronal densities in the EC of patients with and without hippocampal sclerosis.…”

Ictal and interictal high frequency oscillations in patients with focal epilepsy

“…They have been associated with epileptogenesis as they occur before the first seizure in the kainic acid rat model (Bragin et al, 2004a). HFOs appear to co-localize with the seizure onset zone (SOZ), which suggests that they are involved in seizure genesis (Bragin et al, 2004b;Jacobs et al, 2008).…”

“…Finally, removal of HFO generating tissue is related to good surgical outcome, more than spikes and the SOZ are (Jacobs et al, 2010), which supports their relation to epileptogenic tissue and potential clinical importance. The current hypothesis is that HFOs result from misconnected or disinhibited neuronal networks leading to highly synchronized neuronal activity over an area of brain tissue, which in turn results in seizure genesis after other areas or networks get involved (Bragin et al, 2004a;Engel et al, 2009;Ogren et al, 2009). …”