Rate Of Interictal Epileptiform Discharges Research Articles

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Acute Effects of High-Frequency Insular Stimulation on Interictal Epileptiform Discharge Rates in Patients with Refractory Epilepsy.

Rationale: Deep brain stimulation (DBS) of several sites, such as the thalamus, has been shown to reduce seizure frequency and interictal epileptiform activity in patients with refractory epilepsy. Recent findings have demonstrated that the insula is part of the 'rich club' of highly connected brain regions. This pilot study investigated short-term effects of high-frequency (HF) insular DBS on interictal epileptiform discharge (IED) rate in patients with refractory epilepsy. Methods: Six patients with drug-resistant epilepsy undergoing an intracranial electroencephalographic study received two sets of 10 min continuous 150 Hz HF-DBS of the insula. For each patient, epileptiform activity was analyzed for a total of 80 min, starting 20 min prior to stimulation set 1 (S1), and ending 20 min after stimulation set 2 (S2). All IEDs were identified and classified according to their anatomic localization by a board-certified epileptologist. The IED rate during the 20 min preceding S1 served as a baseline for comparison with IED rate during S1, S2 and post-stimulation periods. Results: HF-DBS of the anterior insula (aINS) was performed in a patient with an aINS epileptic focus (patient 1). HF-DBS of the posterior insula (pINS) was performed in two patients with a pINS epileptic focus (patients 2 and 4), in one patient with an aINS focus (patient 3), and in two non-insular patients (patients 5 and 6). The total IED (irrespective of their location) rate significantly decreased (p < 0.01) in two patients (patients 1 and 2) during the stimulation period, whereas it significantly increased (p < 0.01) in one patient (patient 6); there was no change in the other three patients. Looking at subsets of spike localization, HF-DBS of the aINS significantly reduced aINS and orbitofrontal IEDs in patient 1 (p < 0.01), while HF-DBS of the pINS had an effect on pINS IEDs (p < 0.01) in both patients with a pINS focus; there was no significant effect of HF-DBS of the insula on IEDs in temporal or other frontal regions. Conclusion: Short-term HF-DBS of the insula had heterogeneous effects on the IED rate. Further work is required to examine factors underlying these heterogeneous effects, such as stimulation frequency, location of IEDs and subregions of the insula stimulated.

Interictal epileptiform discharges show distinct spatiotemporal and morphological patterns across wake and sleep.

Presurgical evaluation of mesial temporal and neocortical focal pharmacoresistant epilepsy patients using intracranial EEG recordings has led to the generation of extensive data on interictal epileptiform discharges, located within or remotely from seizure onset zones. In this study, we used this data to investigate how interictal epileptiform discharges are modulated and how their spatial distribution changes during wake and sleep and analysed the relationship between these discharge events and seizure onset zones. Preoperative evaluation data from 11 adult patients with focal pharmacoresistant epilepsy were extracted from the Epilepsiae database. Interictal epileptiform discharges were automatically detected during wakefulness and over several hours of continuous seizure-free sleep (total duration of EEG recordings:106.7 h; mean per patient: 9.7 h), and analysed across four brain areas (mesial temporal, lateral neocortical, basal cortical and the temporal pole). Sleep stages were classified manually from scalp EEG. Discharge events were characterized according to their rate and morphology (amplitude, sharpness and duration). Eight patients had a seizure onset zone over mesial areas and three patients over lateral neocortical areas. Overall, discharge rates varied across brain areas during wakefulness and sleep [wake/sleep stages × brain areas interaction; Wald χ 2(df = 6) = 31.1, P < 0.0001]. N2-N3 non-rapid eye movement sleep increased interictal epileptiform discharges in mesial areas compared with wakefulness and rapid eye movement sleep (P < 0.0001), and to other areas (P < 0.0001 for all comparisons). This mesial pattern was observed both within and outside of seizure onset zones. During wakefulness, the rate of interictal epileptiform discharges was significantly higher than during N2-N3 non-rapid eye movement sleep (P = 0.04), and rapid eye movement sleep (P = 0.01) in lateral neocortical areas (referred to as lateral neocortical pattern), a finding that was more pronounced in seizures onset zones (P = 0.004). The morphological characteristics of the discharge events were modulated during wakefulness and sleep stages across brain areas. The effect of seizure onset zones on discharge morphology was conditioned by brain area and was particularly marked in temporal pole areas. Our analysis of discharge patterns in relation to cerebral localization, vigilance state and the anatomical affiliation of seizure onset zones revealed the global and local aspects of the complex relationship between interictal discharges, sleep and seizure onset zones. This novel approach may lead to a better understanding of cognitive decline and responses to therapy, as well as to adaptation of surgical interventions for epileptic patients.

Activation patterns of interictal epileptiform discharges in relation to sleep and seizures: An artificial intelligence driven data analysis

ObjectiveTo quantify effects of sleep and seizures on the rate of interictal epileptiform discharges (IED) and to classify patients with epilepsy based on IED activation patterns. MethodsWe analyzed long-term EEGs from 76 patients with at least one recorded epileptic seizure during monitoring. IEDs were detected with an AI-based algorithm and validated by visual inspection. We then used unsupervised clustering to characterize patient sub-cohorts with similar IED activation patterns regarding circadian rhythms, deep sleep activation, and seizure occurrence. ResultsFive sub-cohorts with similar IED activation patterns were found: “Sporadic” (14%, n = 10) without or few IEDs, “Continuous” (32%, n = 23) with weak circadian/deep sleep or seizure modulation, “Nighttime & seizure activation” (23%, n = 17) with high IED rates during normal sleep times and after seizures but without deep sleep modulation, “Deep sleep” (19%, n = 14) with strong IED modulation during deep sleep, and “Seizure deactivation” (12%, n = 9) with deactivation of IEDs after seizures. Patients showing “Deep sleep” IED pattern were diagnosed with temporal lobe epilepsy in 86%, while 80% of the “Sporadic” cluster were extratemporal. ConclusionsPatients with epilepsy can be characterized by using temporal relationships between rates of IEDs, circadian rhythms, deep sleep and seizures. SignificanceThis work presents the first approach to data-driven classification of epilepsy patients based on their fully validated temporal pattern of IEDs.

Continuous Intraoperative Monitoring of Temporal Lobe Epilepsy Surgery

Background/Aims: The monitoring of interictal epileptiform discharge rates (IEDRs) all along anterior temporal lobe resections (ATLRs) has never been reported. Here the effect of ATLR on continuous IEDR monitoring is described. Methods: IEDRs computed automatically during entire interventions were recorded in 34 patients (38.2%, 13/34 depth; 61.8%, 21/34 scalp electrodes only). Monitorings were invalidated when burst suppression occurred or if initial IEDRs were <5. Results: Monitoring was successful for 69.2% (9/13) of the patients with depth recordings and for 4.8% (1/21) of the patients with scalp recordings. Burst suppressions precluded it in 30.8% (4/13) of the depth and in 57.1% (12/21) of the scalp recordings. Initial IEDRs were <5 for 38.1% (8/21) of the scalp recordings. Significant IEDR decreases were observed in 8/10 patients with successful monitoring. These decreases started with resection of the superior temporal gyrus. IEDRs decreased further with amygdalohippocampectomy in 3/5 patients. At the 12-month follow-up, all patients with IEDR decreases remained seizure free; both patients without did not. Conclusion: IEDR monitoring was possible with depth, but not with scalp electrodes. IEDR decreases started with resection of the superior temporal gyrus. A larger patient cohort is necessary to confirm the high predictive values of IEDR monitoring that could become a tool for surgery customization.

Interictal epileptiform discharges in new‐onset epilepsy among older adults

AbstractBackgroundThe incidence of epilepsy is highest in older adults and exceeds that observed in children. Seizure disorders are also more common among older adults. However, there are few reports of interictal epileptiform discharges in new‐onset epilepsy among older adults.AimTo investigate the rate of interictal epileptiform discharges in elderly patients with new‐onset epilepsy.MethodsWe defined elderly patients with new‐onset epilepsy as those who developed epilepsy after the age of 65 years. We reviewed the interictal electroencephalographic characteristics of patients with new‐onset epilepsy treated between April 2005 and December 2011 at a tertiary referral center. Both outpatients and inpatients were included in this study. Epilepsy was diagnosed on the basis of clinical history, scalp‐recorded electroencephalography, physical findings, brain 3.0‐T magnetic resonance imaging/computed tomography, single‐photon emission tomography and neuropsychological evaluation. Epilepsy and seizure classifications, and age of onset were also reviewed.ResultsWe included 112 patients (58 men and 54 women) in this study. The mean age of seizure onset was 73.5 ± 6.7 years. Interictal epileptiform discharges were detected in 82 patients (73.2%). Temporal lobe epilepsy (odds ratio 6.3, P = 0.004) and complex partial seizures (odds ratio 8.0, P = 0.033) were associated with interictal epileptiform discharges.ConclusionInterictal epileptiform discharges were present in 73.2% of the elderly patients with new‐onset epilepsy in our cohort, which was higher than the previously reported rate. Temporal lobe epilepsy was the most frequent epilepsy diagnosis among the interictal epileptiform discharge‐positive patients.

Therapeutic Significance of Frequency of Deep Brain Stimulation in Intractable Epilepsy

In addition to the exact placement of electrodes in the target site, the successful outcome of DBS depends largely upon correct choice of its stimulation parameters (especially voltage, frequency, pulsewidth and mode of stimulation) and optimal stimulation parameters (SPs) are those that reduce seizures optimally with minimum side effects and minimum consumption of the device-battery. The DBS in the patients with IE is commonly delivered at initial SP settings of 5-6 voltage in the frequency range of 130-180 Hz and pulse width varying from 60-90 microseconds by a monopolar intermittent mode of stimulation (1-min ON and 5-min OFF). The frequency of stimulation (FOS) selected is invariably in the high range for reasons outlined below. In the authors’ opinion, the FOS is of utmost importance in the determination of success and efficacy of the DBS as changes in FOS can potentially exercise maximum impact on the seizure profile (frequency, duration, severity of seizures and interictal epileptiform discharge rates) of the patients. It is generally agreed that analogous to vagal nerve stimulation (VNS), DBS is also effective at highfrequency stimulation (HFS) in reducing seizures [1-3], whereas low-frequency stimulation (LFS) is generally ineffective and can even exacerbate existing seizures [2]. The main objectives of selection of SPs for a successful DBS that have been postulated earlier also [4] are induction of EEGdesynchronization with reduction (or even possibly abolishment) of interictal epileptiform discharges (IEDs). This is in keeping with the generally accepted electrophysiological concept that EEGdesynchronization is associated with seizure resistance and reduction in the occurrence of IEDs and seizures. It has been suggested that LFS induces EEG synchronization, whereas HFS is associated with desynchronization, which might have a therapeutic effect in epilepsy as it has been found to be effective in both animal models and patients with epilepsy [5,6]; LFS is assumed to have anti-epileptic properties but the efficacy is highly debated [5,6] and from their study [5], the researchers have concluded that HFS at 130Hz is more effective than LFS (5Hz) in affecting excitability in epileptic rats. In 2007, a study by Boex et al. [3] also identified that HFS, but not LFS, was associated with a reduction of the interictal discharges and seizures. In Parkinson’s disease also, another neurological disorder characterized by abnormal neuronal synchrony, the usual FOS of the subthalamic nucleus is in the range of 130-180 Hz [7] and in one study [8], FOS at 90 Hz or more yielded the best results, whereas, FOS at 10 Hz or even 50 Hz failed to yield the required clinical effect. From a previous study also [9], the researchers have suggested that the effects of hippocampal DBS depend upon the frequency and topography of stimulation and a patterned stimulation with LFS and HFS resulted in desynchronization and exhibited anti-kindling effects in animal models of epilepsy. Thus, in view of the above electrophysiological findings, we suggest that the FOS in DBS plays a crucial role in determining the clinical outcome of DBS therapy in IE and the selection of optimal FOS may be based on its ability to induce EEG-desynchronization that can be assessed with a simultaneous EEG monitoring. This is especially in view of the observations that the optimal FOS may vary from patient to patient and therefore require individual settings. Admittedly, larger well-designed prospective studies are recommended that may in the course of time validate the therapeutic significance of the FOS and the utility of EEG monitoring in determining the optimal FOS.

Effects of amygdala–hippocampal stimulation on synchronization

Changes in EEG synchronization, i.e., spatio-temporal correlation, with amygdala-hippocampal stimulation were studied in patients with temporal lobe epilepsy. Synchronization was evaluated for high frequency, 130 Hz, pseudo-monophasic or biphasic charge-balanced pulses. Desynchronization was most frequently induced by stimulation. There was no correlation between the changes in synchronization and the changes in interictal epileptiform discharge rates. Changes in synchronization do not appear yet to be a marker of stimulation efficiency in reducing seizures.

Magnetoencephalography and Magnetic Source Imaging in Epilepsy

Magnetoencephalograpy (MEG) and Electroencephalography (EEG) provide physicians with complementary data and should not be regarded as mutually exclusive evaluative methods of cerebral activity. Relevant to this edition, MEG applications related to the surgical treatment of epilepsy will be discussed exclusively. Combined MEG/EEG data collection and analysis should be a routine diagnostic practice for patients who are still suffering seizures due to the failure of drug therapy. Clinicians in the field of epilepsy agree that a greater number of patients would benefit from surgery than are currently referred for pre-surgical evaluation. Regardless of age or presumed epilepsy syndrome, all patients deserve the possibility of living seizure-free through surgery. Technological advances in superconducting elements as well as the digital revolution were necessary for the development of MEG into a clinically valuable diagnostic tool. Compared to the examination of electrical activity of the brain, investigation into its magnetic concomitant is a more recent development. In MEG, cerebral magnetic activity is recorded using magnetometer or gradiometer whole-head systems. MEG spikes usually have a shorter duration and a steeper ascending slope than EEG spikes, and variable phase relationships to EEG. When co-registered spikes are compared, it is apparent that EEG and MEG spikes differ. There is agreement among investigators that more interictal epileptiform spikes are seen in MEG than EEG. When MEG is co-registered with invasive intracranial EEG data, the detection rate of interictal epileptiform discharges depends on the number of electrocorticographic channels that record a spike. When patients have a non-localizing video-EEG recording, MEG pinpoints the resected area in 58-72% of the cases.

Metabotropic glutamate receptor activation modulates epileptiform activity in the hippocampus

Synchronous neuronal activity that resembles interictal epileptiform discharges occurs in hippocampal slices if there is an imbalance of inhibitory and excitatory synaptic activity. Antagonists of the GABA A receptor and agonists of the ionotropic glutamate receptors are convulsants that produce epileptiform discharges in hippocampal slices. We evaluated the effects of activation of the metabotropic class of glutamate receptors on epileptiform activity produced by convulsants. The metabotropic glutamate agonist (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid (ACPD, 30–100 μM) accelerated the rate of interictal epileptiform discharges produced by either bicuculline methiodide or 4-aminopyridine and had minimal effects on discharges produced by high [K +] o. The increase in rate was associated with a significant decrease in the amplitude and duration of the afterhyperpolarization that follows the paroxysmal depolarizing shift, the intracellular correlate of the interictal epileptiform discharge. A modest increase in input resistance (∼10%) accompanied the rate increase. β-adrenergic or muscarinic agonists, neurotransmitters that also decrease the afterhyperpolarization, acted synergistically with ACPD (100 μM) to increase the control rate of bicuculline-induced interictal discharges by more than eight-fold. Antagonists of β-adrenergic or muscarinic receptors reduced, but did not block, the acceleration of bicuculline-induced discharge rate produced by 30 μM ACPD. The results show that metabotropic glutamate receptors enhance the rate of interictal epileptiform discharges produced by bicuculline or 4-aminopyridine. ACPD had no effect on interictal epileptiform activity induced by high [K +] o, a finding that may indicate that in high [K +] o conditions the metabotropic receptor is activated or that the effects of high [K +] o already reduced the effect of depolarizing currents that are enhanced by ACPD. The acceleration in interictal discharge rate was associated with a reduction in the afterhyperpolarization that follows the paroxysmal depolarizing shift and this action appears to be important in determining the synchronization of neurons and the rate of interictal epileptiform discharges. Furthermore, interaction between mGluR activation and either muscarinic or β-adrenergic activation may be important for seizure generation.