Analysis of Initial Slow Waves (ISWs) at the Seizure Onset in Patients with Drug Resistant Temporal Lobe Epilepsy

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Epilepsia (Impact Factor: 4.58). 11/2007; 48(10):1883-94. DOI: 10.1111/j.1528-1167.2007.01149.x
Source: PubMed

ABSTRACT The goal of this study is to analyze initial slow waves (ISWs) at seizure onset in patients with refractory temporal lobe epilepsy. ISWs are a specific type of ictal EEG pattern characterized by a slow wave at the seizure onset followed by low voltage fast activity.
Investigations were carried out on 14 patients from the UCLA hospital (USA) and 10 from the Ghent University Hospital (Belgium) implanted with depth and grid electrodes for localization of the epileptogenic zone.
Sixty-one seizures in the UCLA group and 30 seizures in the Ghent group were analyzed. Fourteen UCLA and seven Ghent patients had ISWs at seizure onset. The duration of ISWs varied between 0.3 to 6.0 s and maximum amplitude varied from 0.2 to 1.4 mV. ISWs in three of 14 UCLA patients (30% of seizures) had a consistent positive polarity at the deepest contacts that were located in the amygdala, hippocampus, or entorhinal cortex and reversed polarity outside of these brain areas (ISWs1). ISWs in 11 of 14 UCLA patients (70% of seizures) had negative polarity at the deepest electrodes and their amplitude increased toward the recording contacts located in the white matter or neocortex (ISWs2). All ISWs from the seven Ghent patients were negative in the depth contacts (ISWs2) and positive on grid electrodes at the cortical surface. ISWs1 were associated with EEG spikes at the onset and on increase in amplitude of 10-20 Hz sinusoidal activity. In contrast, ISWs2 were associated with suppression of EEG amplitude, an increase in frequency in the range of 20-50 Hz, and did not have EEG spikes at the onset. Multiunit neuronal activity showed strong synchronization of neuronal discharges during interictal spikes, but multiunit synchronization was not obvious during ISWs2.
The existence of EEG spikes and phase reversal with ISWs1 indicates this type of seizure may be triggered by hypersynchronous neuronal discharges; however, seizures with ISWs2 at the onset may be triggered by different mechanisms, perhaps nonneuronal.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone (EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography (EEG). Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo-EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists. In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80-120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ. Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries.
    Epilepsia 01/2014; 55(2). DOI:10.1111/epi.12507 · 4.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of inhibitory neuronal activity in the transition to seizure is unclear. On the one hand, seizures are associated with excessive neuronal activity that can spread across the brain, suggesting run-away excitation. On the other hand, recent in vitro studies suggest substantial activity of inhibitory interneurons prior to the onset of evoked seizure-like activity. Yet little is known about the behavior of interneurons before and during spontaneous seizures in chronic temporal lobe epilepsy. Here, we examined the relationship between the on-going local field potential (LFP) and the activity of populations of hippocampal neurons during the transition to spontaneous seizures in the pilocarpine rat model of epilepsy. Pilocarpine treated rats that exhibited spontaneous seizures were implanted with drivable tetrodes and an LFP electrode and recordings were obtained from the CA3 region. For each recorded seizure, identified single units were classified into putative interneurons or pyramidal cells based on average firing rate, autocorrelation activity and spike morphology. The onset of sustained ictal spiking, a consistent seizure event that occurred within seconds after the clinically defined seizure onset time, was used to align data from each seizure to a common reference point. Ictal spiking, in this paper, refers to spiking activity in the low-pass filtered LFP during seizures and not the neuronal action potentials. Results show that beginning minutes before the onset of sustained ictal spiking in the local field, subpopulations of putative interneurons displayed a sequence of synchronous behaviors. This includes progressive synchrony with local field oscillations at theta, gamma, and finally ictal spiking frequencies, and an increased firing rate seconds before the onset of ictal spiking. Conversely, putative pyramidal cells did not exhibit increased synchrony or firing rate until after ictal spiking had begun. Our data suggest that the transition to spontaneous seizure in this network is not mediated by increasing excitatory activity, but by distinct changes in the dynamical state of putative interneurons. While these states are not unique for seizure onset, they suggest a series of state transitions that continuously increase the likelihood of a seizure. These data help to interpret the link between in vitro studies demonstrating interneuron activation at the transition to seizure, and human studies demonstrating heterogeneous neuronal firing at this time.
    Experimental Neurology 05/2013; 248. DOI:10.1016/j.expneurol.2013.05.004 · 4.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. In models of temporal lobe epilepsy and in patients with this pathology, high frequency oscillations called fast ripples (FRs, 250-600 Hz) can be observed. FRs are considered potential biomarkers for epilepsy and, in the light of many in vitro and in silico studies, we thought that electrical synapses mediated by gap junctions might possibly modulate FRs in vivo. Methods. Animals with spontaneous recurrent seizures induced by pilocarpine administration were implanted with movable microelectrodes in the right anterior and posterior hippocampus to evaluate the effects of gap junction blockers administered in the entorhinal cortex. The effects of carbenoxolone (50 nmoles) and quinine (35 pmoles) on the mean number of spontaneous FR events (occurrence of FRs), as well as on the mean number of oscillation cycles per FR event and their frequency, were assessed using a specific algorithm to analyze FRs in intracranial EEG recordings. Results. We found that these gap junction blockers decreased the mean number of FRs and the mean number of oscillation cycles per FR event in the hippocampus, both during and at different times after carbenoxolone and quinine administration. Conclusion. These data suggest that FRs may be modulated by gap junctions, although additional experiments in vivo will be necessary to determine the precise role of gap junctions in this pathological activity associated with epileptogenesis.
    BioMed Research International 09/2014; 2014:282490. DOI:10.1155/2014/282490 · 2.71 Impact Factor

Full-text (2 Sources)

Available from
Oct 27, 2014