Analysis of Seizure Onset on the Basis of Wideband EEG Recordings

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1 Epilepsia, (Suppl. ):9, 00 Blackwell Publishing, Inc. C International League Against Epilepsy Ictogenesis Analysis of Seizure Onset on the Basis of Wideband EEG Recordings Anatol Bragin, Charles L. Wilson, Tony Fields, Itzhak Fried, and Jerome Engel, Jr. Departments of Neurology, Neurobiology, Neurosurgery, and the Brain Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A. Summary: Seventy-five seizure onsets recorded with depth electrodes in the frequency band from 0. to 0 Hz were analyzed in 9 patients with intractable temporal lobe epilepsy. It was shown that 89% of low-voltage fast-type seizures contained an initial slow wave, whereas hypersynchronous-type seizures did not show an initial slow wave. Voltage depth profile analysis illustrated that the peak amplitude of the initial slow-wave onset was in white matter, whereas the peak amplitude of hypersynchronous onset was in deep temporal areas (hippocampus, entorhinal cortex, or amygdala). The difference in voltage depth profiles suggests that these two types of seizure onsets have different mechanisms of generation. The absence of phase reversal of the initial slow wave in white matter or at the border of deep temporal areas indicates a possible nonneuronal mechanism of generation. Key Words: Temporal lobe epilepsy Seizure onset Human Entorhinal cortex Hippocampus EEG. Classification of seizure types is the first step in understanding mechanisms of seizure genesis. It helps neurologists to diagnose the site of origin of seizures and to prescribe proper medical treatment. In spite of some differences in approaches and criteria for classification of seizures, a majority of the existing data dealing with the classification of the seizures of temporal lobe epilepsy (TLE) separate them into two major types: low-voltage fast (LVF) onset and hypersynchronous onset ( ). The LVF seizure onset usually begins with an initial amplitude suppression of electrical activity and a parallel increase in frequency ( 8). The hypersynchronous seizure onset consists of regional high-amplitude EEG spikes with frequency < Hz, lasting > s(). These classifications were based on conventional depth electrode EEG recordings with a frequency band ranging between and 0 Hz. However, several publications reported that electrical activity in lower (9 ) and higher ( ) frequency ranges exist at seizure onset and may play an important role in the localization of the epileptogenic zone, as well as provide additional information about possible mechanisms of seizure genesis. These frequencies of electrical activity have been ignored in most studies of seizure classification. Address correspondence and reprint requests to Dr. A. Bragin at Department of Neurology, UCLA School of Medicine, 0 Westwood Plaza, Los Angeles, CA 9009, U.S.A. abragin@ucla.edu The goal of this presentation is to analyze seizure onsets in patients with TLE who underwent depth electrode implantation for localization of the epileptogenic zone by using wideband recordings ranging from 0. to 0 Hz. METHODS Subjects Interictal and ictal depth electrode recordings were obtained from patients with medically intractable complex partial seizures who were being evaluated for surgical treatment. Before clinically required depth electrode implantation for the localization and characterization of the epileptogenic region, patients gave their informed consent for participation in these research studies under the approval of the Internal Review Board of the UCLA Office for Protection of Research Subjects. Each patient was surgically implanted with eight to flexible polyurethane clinical depth electrodes with platinum contacts stereotactically targeted to clinically relevant brain areas. EEG from these electrodes was monitored continuously in days in an attempt to localize those brain areas in which spontaneous seizure activity first appeared (). Identification of epileptogenic regions was based on criteria from electrographic seizure recordings, magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), neurocognitive 9

2 0 A. BRAGIN ET AL. testing, and other clinical features (8). Electrographic seizure onsets were recorded during the patient s depth electrode telemetry monitoring, and attending neurologists in the UCLA Seizure Disorders Center identified locations of seizure onset based on the recording of multiple seizure occurrences during an average of weeks in the hospital. A single neuroradiologist at UCLA evaluated every patient s MRI scans for the presence or absence of hippocampal atrophy and its location as part of the clinical evaluation. Electrodes and localization Wideband EEG was recorded from the seven-contact clinical depth electrodes (.-mm diameter) manufactured by AdTech Medical Instruments (Racine, WI, U.S.A.). Electrode tips were localized by using the combined information from postimplant computerized tomography (CT) co-registered with preimplant.-t MRI. The imaging software used (Brain Navigator; Grass-Telefactor Corp., Philadelphia, PA, U.S.A.) allowed visualization and highlighting of electrode tip locations on CT, which were automatically registered to the MRI scans. Anatomic FIG.. Examples of initial slow wave (A) and hypersynchronous (B) seizure onsets. RA, RAC, RAH, REC, RPH, RSM, and RSO correspond to right amygdala, anterior cingular cortex, anterior hippocampus, entorhinal cortex, posterior hippocampus, supplementary motor, and superior occipital. LPG and LOF correspond to left posterior hippocampal gyrus and left orbitofrontal cortex. Numbers indicate electrode contact, where are deepest (mesial);, middle; and are superficial contacts.

3 SEIZURE ONSET IN TLE PATIENTS microvolts A B RA RAH RPS + _ electrode number deep surface 0. s mv Am+peak Am-peak Hip+peak Hip-peak EC+peak EC-peak FIG.. A: An average of five initial slow-wave seizure onsets in one patient. Numbers indicate electrode contacts, where is deepest and is superficial. + and between two dashed lines indicate positive and negative peak for voltage-depth profiles presented in B. Am, amygdala; Hip, hippocampus; EC, entorhinal cortex. boundaries were based on references of mesial temporal lobe anatomy by Amaral and Insausti (9) and Duvernoy (0). All recordings were performed by using subdural stainless steel suture. Bipolar montages used recordings of pairs of adjacent electrode contacts. Data analysis Three independent interpreters reviewed EEG records, and decisions about seizure types were made on the basis of consensus between all of them. Averaging of seizure Amplitude (%) A B Am Hip EC Am Hip EC Neo- Cortex -0 electrode number deep surface 00ms mv Am-ISW Hip-ISW EC-ISW Am-Hyp Hip-Hyp EC-Hyp FIG.. Averages of five spikes of the hypersynchronous seizure onset shown in Fig. B (A), and normalized voltage-depth profiles of ISW onset (solid symbols) and hypersynchronous onset (open symbols) (B). RA, right amygdala; RAH, right anterior hippocampus; RPS, right posterior subiculum. onsets and analysis of amplitude was performed by using Datapac K software, RUN Technologies (Mission Viejo, CA, U.S.A.). An initial wave or EEG spike in the EEG followed by the development of seizure activity was taken as a hallmark of seizure onset. RESULTS Sixty-six seizures in 9 patients were analyzed in this study, from two to five seizures from each patient (mean,.). In agreement with previous publications, we found two major types of electrographic seizure onsets:

4 A. BRAGIN ET AL. hypersynchronous (.%) and LVF (9.%), but.% of the seizures did not fall into either of these two categories. Examples of hypersynchronous and LVF onsets are presented in Fig. A and B). An initial slow-wave (ISW) shift was found in 89% of LVF seizures. The duration of ISW varied between 0. s and s (mean,. ± 0. s). Figure A illustrates an ISW at the onset of a LVF seizure. The ISW could be generalized as in Fig. A, or regional (not shown). A single EEG spike or oscillations with frequencies of 0 Hz were superimposed on some ISWs (Fig. A). Hypersynchronous seizure onsets did not show ISW shifts. However, slow-wave shifts occurred during % of hypersynchronous seizures, not at the onset, but several seconds later. In these cases, the slow-wave shift occurred after a period of increasing frequency of EEG spike discharges during evolution of LVF 0- to 0-Hz activity. Voltage versus depth profile analysis showed that the ISW shift has its smallest amplitude at superficial electrode contacts located in neocortex. In some cases, ISWs show reversal at the most superficial electrodes [see negative peak for right posterior hippocampus (RAH) and right posterior subiculum (RPS) in Fig. B]. In this figure, the amplitude of ISW reaches its maximum in electrodes, which are located in the white matter between deep temporal brain areas and neocortex. In % of cases, ISWs did change polarity at the deepest electrode contacts that were located in the hippocampus or entorhinal cortex. This change of polarity correlated with the position of the deepest electrode contact in the ventricle. We never observed change in polarity of ISWs at the border between gray and white matter (Fig. B), although some EEG interictal spikes did reverse polarity between white and gray matter. Conversely, voltage depth profiles of hypersynchronous seizure onsets show a maximum in the deep electrode contacts with continuous decrement of amplitude toward the most superficial contacts in the neocortex (Fig. A and B). DISCUSSION Our data reveal new features of seizure onsets in depth electrode EEG recordings with a wider than conventional frequency bandwidth. A high percentage of seizures previously classified as LVF onset (but not seizures with hypersynchronous onset) show an ISW (89%). Similar ISWs have been described before, but for some reason, they have not attracted attention for further analysis ( 8). This is probably because conventional EEG recordings in the frequency band of to 0 Hz reduce the initial slow wave to a single delta transient, which might have been considered a coincidental event. The relation of the ISWs to other known electrographic patterns and mechanisms of seizure generation is unclear. It may reflect the DC shift that has been described in number of earlier studies (9 ). However, the duration of the DC shift in these studies usually varied from several seconds to several tens of seconds, whereas the mean duration of the ISW is only. s. The mechanisms of generation of the ISW may be similar to the mechanisms of generation of K-complexes described in several publications from the laboratory of Steriade (); however, further studies are required to confirm or reject this hypothesis. In this case, the ISW could reflect a normal synchronizing event that precipitates the seizure onset rather than the onset of the seizure itself. Voltage-depth profiles of ISWs did not show reversal between gray and white matter indicating the absence of a dipole, which should exist if these waves are generated by neuronal populations in the area of recording. It might be, therefore, that ISWs are not generated by neuronal populations in the neocortex. 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