Interictal spikes and epileptic seizures: their relationship and underlying rhythmicity (original) (raw)
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Clinical Neurophysiology, 2013
In patients with temporal or extratemporal epilepsy interictal spikes can be observed in the intracranial EEG over multiple areas of the hemisphere ipsilateral to the seizure onset area. The single brain area with the highest number of interictal spikes, or interictal spike rate, is not a reliable indicator of the seizure onset area. The spatial distribution of spike rates over the multiple areas of the ipsilateral hemisphere is strongly related to the seizure onset area and may hold value for its localization.
Annals of biomedical engineering, 2014
The relation between epileptic spikes and seizures is an important but still unresolved question in epilepsy research. Preclinical and clinical studies have produced inconclusive results on the causality or even on the existence of such a relation. We set to investigate this relation taking in consideration seizure severity and spatial extent of spike rate. We developed a novel automated spike detection algorithm based on morphological filtering techniques and then tested the hypothesis that there is a pre-ictal increase and post-ictal decrease of the spatial extent of spike rate. Peri-ictal (around seizures) spikes were detected from intracranial EEG recordings in 5 patients with temporal lobe epilepsy. The 94 recorded seizures were classified into two classes, based on the percentage of brain sites having higher or lower rate of spikes in the pre-ictal compared to post-ictal periods, with a classification accuracy of 87.4%. This seizure classification showed that seizures with inc...
Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy
Epileptic disorders : international epilepsy journal with videotape, 2005
We wanted to investigate factors that are associated with frequency of interictal epileptiform discharges by investigating 303 patients with temporal lobe epilepsy (TLE). We included all patients who consecutively underwent the adult presurgical evaluation program at our center and who had intractable, medial TLE with complex partial seizures due to unilateral medial temporal lobe lesions. The interictal EEG samples were automatically recorded and stored on computer. The location and frequency of interictal epileptiform discharges were assessed by visual analysis of interictal EEG samples of 2-minute duration every hour. There were 303 patients (aged 16-63) who met the inclusion criteria. The median interictal epileptiform discharge frequency was 15 IED/h, the median seizure frequency was 4 seizures/month. According to univariate analyses, we found that age at monitoring, epilepsy duration, and higher seizure frequency were associated with higher interictal epileptiform discharge fr...
Time-domain features of epileptic spikes as potential bio-markers of the epileptogenesis process
2010 Annual International Conference of the IEEE Engineering in Medicine and Biology, 2010
Epilepsy is a neurological disorder characterized by recurrent seizures which affects about 1 people worldwide. During the past % decades, some mechanisms involved in ictogenesis (generation of seizures) have been identified and, to some extent, partially understood. However, regarding epileptogenesis (process by which a neuronal system becomes epileptic), underlying mechanisms remain elusive. This difficulty is mostly related to the fact that epileptogenesis can only be addressed using experimental models. In this study, we have analyzed the shape of a specific electrophysiological pattern, referred to as epileptic spike , encountered during " " the epileptogenesis process in an model of temporal lobe epilepsy (mouse, kainate). Results show that the features of these in vivo transient events (duration and amplitude) change as a function of time as the brain evolves towards the chronic epileptic state characterized by the appearance of spontaneous seizures. Using a detailed computational model of the hippocampus (CA1 sub-field), an interpretation of observed modifications is provided, in relationship with possible alterations that take place in underlying neuronal circuits.
Nature Precedings
A fine balance between neuronal excitation and inhibition governs the physiological state of the brain. It has been hypothesized that when this balance is lost as a result of excessive excitation or reduced inhibition, pathological states such as epilepsy emerge. Decades of investigation have shown this to be true in vitro. However, in vivo evidence of the emerging imbalance during the "latent period" between the initiation of injury and the expression of the first spontaneous behavioral seizure has not been demonstrated. Here, we provide the first demonstration of this emerging imbalance between excitation and inhibition in vivo by employing long term, high temporal resolution, and continuous local field recordings from microelectrode arrays implanted in an animal model of limbic epilepsy. We were able to track both the inhibitory and excitatory postsynaptic field activity during the entire latent period, from the time of injury to the occurrence of the first spontaneous epileptic seizure. During this latent period we observe a sustained increase in the firing rate of the excitatory postsynaptic field activity, paired with a subsequent decrease in the firing rate of the inhibitory postsynaptic field activity within the CA1 region of the hippocampus. Firing rates of both excitatory and inhibitory CA1 field activities followed a circadian-like rhythm, which is locked near in-phase in controls and near anti-phase during the latent period. We think that these observed changes are implicated in the occurrence of spontaneous seizure onset following injury. Epilepsy is the propensity to have seizures and is one of the most common serious neurological conditions, affecting 0.4% to 1.0% of the world population 1. EEG recordings usually demonstrate interictal discharges (population spikes, sharp waves) over the hippocampal formation 2. Brief synchronous activity of a group of neurons leading to a population spike shares some mechanisms with seizure generation; spikes should, however, be recognized as a distinct phenomenon 3. Since spikes corresponding to both excitatory and inhibitory synaptic activities are significant features of network changes during epileptogenesis 4,5,6 , it is imperative to understand their evolution leading up to spontaneous seizures. If one could observe and characterize the evolution of these spikes over the entire period from the time of injury up to the onset of
eneuro, 2019
Hypersynchronous network activity is the defining hallmark of epilepsy and manifests in a wide spectrum of phenomena, of which electrographic activity during seizures is only one extreme. The aim of this study was to differentiate between different types of epileptiform activity (EA) patterns and investigate their temporal succession and interactions. We analyzed local field potentials (LFPs) from freely behaving male mice that had received an intrahippocampal kainate injection to model mesial temporal lobe epilepsy (MTLE). Epileptiform spikes occurred in distinct bursts. Using machine learning, we derived a scale reflecting the spike load of bursts and three main burst categories that we labeled high-load, medium-load, and low-load bursts. We found that bursts of these categories were non-randomly distributed in time. High-load bursts formed clusters and were typically Significance Statement It is a major challenge in epilepsy research to understand how different types of epileptiform activity (EA) interact and whether epileptiform spikes prevent or promote major epileptic events. In our mouse model for mesial temporal lobe epilepsy (MTLE), epileptiform spikes occurred in bursts. Increased rates of bursts with low spike load were clearly associated with extended phases lacking high-load bursts, which is in line with the view that low-level activity could promote network stability in epilepsy. Low-load bursts, however, also occurred during transition phases to clusters of high-load bursts. Both findings are consistent with the hypothesis that low-level EA could reduce the excitability of the network but that its impact depends on the current state of the network. New Research September/October 2019, 6(5) ENEURO.0299-18.2019 1-14 surrounded by transition phases with increased rates of medium-load and low-load bursts. In apparent contradiction to this, increased rates of low-load bursts were also associated with longer background phases, i.e., periods lacking high-load bursting. Furthermore, the rate of low-load bursts was more strongly correlated with the duration of background phases than the overall rate of epileptiform spikes. Our findings are consistent with the hypothesis that low-level EA could promote network stability but could also participate in transitions towards major epileptiform events, depending on the current state of the network.
Changes in interictal spike features precede the onset of temporal lobe epilepsy
Annals of Neurology, 2012
Objective: One cornerstone event during epileptogenesis is the occurrence of the first spontaneous seizure (SZ1). It is therefore important to identify biomarkers of the network alterations leading to SZ1. In experimental models of temporal lobe epilepsy (TLE), interictal-like activity (ILA) precedes SZ1 by several days. The goal of this study was to determine whether ILA dynamics bore electrophysiological features signaling the impeding transition to SZ1. Methods: Experimental TLE was triggered by pilocarpine-or kainic acid-induced status epilepticus (SE). Continuous electroencephalographic recordings were performed 7 days before and up to 40 days after SE. The amplitude and duration of the spike and wave components of interictal spikes were analyzed. Results: Two types of interictal spikes were distinguished: type 1, with a spike followed by a long-lasting wave, and type 2, with a spike without wave. The number, amplitude, and duration of type 1 spikes started to decrease, whereas the number of type 2 spikes increased, several days before SZ1, reaching their minimum/maximum values just before SZ1. Interpretation: The change in ILA pattern could constitute a predictive biomarker of SZ1. The mechanisms underlying these dynamic modifications and their functional impact are discussed in the context of the construction of an epileptogenic network.
Interictal spikes on intracranial recording: Behavior, physiology, and implications
Epilepsia, 2008
Purpose: The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes.Methods: Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24-h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24-h intervals.Results: Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24 h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase.Conclusions: These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.
Neurobiology of Disease, 2014
Mesial temporal lobe epilepsy (MTLE) is characterized in humans and in animal models by a seizure-free latent phase that follows an initial brain insult; this period is presumably associated to plastic changes in temporal lobe excitability and connectivity. Here, we analyzed the occurrence of interictal spikes and high frequency oscillations (HFOs; ripples: 80-200 Hz and fast ripples: 250-500 Hz) from 48 h before to 96 h after the first seizure in the rat pilocarpine model of MTLE. Interictal spikes recorded with depth EEG electrodes from the hippocampus CA3 area and entorhinal cortex (EC) were classified as type 1 (characterized by a spike followed by a wave) or type 2 (characterized by a spike with no wave). We found that: (i) there was a switch in the distribution of both types of interictal spikes before and after the occurrence of the first seizure; during the latent phase both types of interictal spikes predominated in the EC whereas during the chronic phase both types of spikes predominated in CA3; (ii) type 2 spike duration decreased in both regions from the latent to the chronic phase; (iii) type 2 spikes associated to fast ripples occurred at higher rates in EC compared to CA3 during the latent phase while they occurred at similar rates in both regions in the chronic phase; and (iv) rates of fast ripples outside of spikes were higher in EC compared to CA3 during the latent phase. Our findings demonstrate that the transition from the latent to the chronic phase is paralleled by dynamic changes in interictal spike and HFO expression in EC and CA3. We propose that these changes may represent biomarkers of epileptogenicity in MTLE.
Distinct EEG seizure patterns reflect different seizure generation mechanisms
Journal of Neurophysiology, 2015
Low-voltage fast-(LVF) and hypersynchronous-(HYP) seizure onset patterns can be recognized 34 in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples 35 and fast ripples (250-500 Hz) have been linked to each pattern, with ripples predominating 36 during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine 37 model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the 38 contribution of neural networks with distinct transmitter signaling characteristics. Here, we 39 tested this hypothesis by analysing the seizure activity induced with the K + channel blocker 4-40 aminopyridine (4AP, 4-5 mg/kg, i.p.) -which enhances both glutamatergic and GABAergic 41 transmission -or the GABA A receptor antagonist picrotoxin (3-5 mg/kg, i.p.); rats were 42 implanted with electrodes in the hippocampus, the entorhinal cortex and the subiculum. We 43 found that LVF-onset occurred in 82% of 4AP-induced seizures while seizures following 44 picrotoxin were always HYP. In addition, HFO analysis revealed that 4AP-induced LVF seizures 45 were associated to higher ripple rates compared to fast ripples (p<0.05), whereas picrotoxin-46 induced seizures contained higher rates of fast ripples compared to ripples (p<0.05). These 47 results support the hypothesis that two distinct patterns of seizure onset result from different 48 pathophysiological mechanisms.