Frequent Interictal Epileptiform Discharges Research Articles

Confusing Transient Epileptic Amnesia versus Transient Global Amnesia: Unraveling the Diagnostic and Therapeutic Challenges

Transient global amnesia (TGA) and transient epileptic amnesia (TEA) are inherently challenging to diagnose and share many similarities, which can easily lead to confusion. In this report, we present a case of a 57-year-old female patient experienced recurrent transient amnesia with incidentally found chronic ischemic temporo-parietal lesion including hippocampus and also revealed frequent interictal epileptiform discharges in acute period which can be features of TEA. We aim to explore the differences between TEA and TGA through this confusing case and when further evaluation may be necessary.

Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.

Threshold-dependent association between non-rapid eye movement obstructive sleep apnea and interictal epileptiform discharges: A hospital study.

Obstructive sleep apnea frequently coexists with epilepsy, potentially influencing its pathophysiology. However, the effect of obstructive sleep apnea severity on interictal epileptiform discharges is not well understood. To explore this, we studied 108 Asian patients with epilepsy who underwent single-night polysomnography. We utilized generalized linear models, adjusting for age, sex, epilepsy type (focal versus generalized), antiepileptic medication use and disease duration, to analyse the relationship between obstructive sleep apnea severity, as measured by the apnea-hypopnea index, and interictal epileptiform discharge frequency during non-rapid eye movement and rapid eye movement sleep. Our analysis revealed that severe obstructive sleep apnea (apnea-hypopnea index ≥ 30) was associated with a higher frequency of interictal epileptiform discharges during non-rapid eye movement sleep (p = 0.04), but no such association was observed during rapid eye movement sleep. Additionally, the frequency of interictal epileptiform discharges in non-rapid eye movement sleep was positively correlated with the wake time between sleep onset and offset (p = 0.03). Further studies are warranted to validate our findings across diverse ethnicities, and over multiple nights of sleep and interictal epileptiform discharge recordings.

Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy. Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS. Active, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency. These findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Semiautomated electric source imaging determines epileptogenicity of encephaloceles in temporal lobe epilepsy.

We aimed to assess the ability of semiautomated electric source imaging (ESI) from long-term video-electroencephalographic (EEG) monitoring (LTM) to determine the epileptogenicity of temporopolar encephaloceles (TEs) in patients with temporal lobe epilepsy. We conducted a retrospective study involving 32 temporal lobe epilepsy patients with TEs as potentially epileptogenic lesions in structural magnetic resonance imaging scans. Findings were validated through invasive intracerebral stereo-EEG in six of 32 patients and postsurgical outcome after tailored resection of the TE in 17 of 32 patients. LTM (mean duration = 6 days) was performed using the 10/20 system with additional T1/T2 for all patients and sphenoidal electrodes in 23 of 32 patients. Semiautomated detection and clustering of interictal epileptiform discharges (IEDs) were carried out to create IED types. ESI was performed on the averages of the two most frequent IED types per patient, utilizing individual head models, and two independent inverse methods (sLORETA [standardized low-resolution brain electromagnetic tomography], MUSIC [multiple signal classification]). ESI maxima concordance and propagation in spatial relation to TEs were quantified for sources with good signal quality (signal-to-noise ratio > 2, explained signal > 60%). ESI maxima correctly colocalized with a TE in 20 of 32 patients (62.5%) either at the onset or half-rising flank of at least one IED type per patient. ESI maxima showed propagation from the temporal pole to other temporal or extratemporal regions in 14 of 32 patients (44%), confirming propagation originating in the area of the TE. The findings from both inverse methods validated each other in 14 of 20 patients (70%), and sphenoidal electrodes exhibited the highest signal amplitudes in 17 of 23 patients (74%). The concordance of ESI with the TE predicted a seizure-free postsurgical outcome (Engel I vs. >I) with a diagnostic odds ratio of 2.1. Semiautomated ESI from LTM often successfully identifies the epileptogenicity of TEs and the IED onset zone within the area of the TEs. Additionally, it shows potential predictive power for postsurgical outcomes in these patients.

Therapeutic Strategies in Children with Epilepsy: A Quality-of-Life-Related Perspective.

Back ground: Children with epilepsy are affected by several factors, including clinical and social variables. Among these variables, cognitive decline and behavioral disturbances, perceptions of stigma, and fatigue can lead to reductions in quality of life (QOL). Epileptic activities, including seizure severity, frequent seizures, and status epilepticus (SE), have been identified as important predictors of QOL. In addition, the frequency of interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) may also be an important predictor of QOL, because IEDs can lead to cognitive decline and behavioral disturbances. Moreover, frequent seizures and/or IEDs may play a role in emotional mediators, such as stigma and fatigue, in childhood epilepsy. Seizure severity and/or IEDs are, therefore, important QOL-related factors in childhood epilepsy. Seizure severity as a QOL-related factor: Frontal lobe dysfunctions, such as cognitive decline and behavioral disturbances, can result in reduced QOL for both the child and their family. Frontal and prefrontal lobe growth disturbances can be present during active-phase epilepsy in some children with neuropsychological impairments. Recovery from prefrontal lobe growth disturbances may depend on the active seizure period. Children with a shorter active seizure period can recover from disturbances in prefrontal lobe growth more rapidly. In contrast, recovery may be delayed in children with a longer active seizure period. Moreover, frequent seizures can lead to seizure-associated headaches, perceptions of self-stigma and parental stigma, and fatigue. Accordingly, severe seizures can lead to neuropsychological impairments in association with prefrontal lobe growth disturbances in children with epilepsy. EEG abnormalities as QOL-related factors: IEDs on EEG, representing persistent pathological neuronal discharges, may be associated with several pathological aspects. Frontal IEDs can be a risk factor for recurrent seizures, cognitive decline, and behavioral disturbances, and they may also play a role as emotional mediators similar to stigma. In addition, behavioral disturbances may result in the presence of secondary bilateral synchrony (SBS) on EEG. Behavioral disturbances can be improved in association with a reduction in IEDs in children with frontal IEDs and SBS. Therefore, EEG abnormalities, such as frontal IEDs and SBS, can also lead to neuropsychological impairments in children with epilepsy. Therapeutic strategies in children with epilepsy: Seizure severity and IEDs on EEG may be associated with neuropsychological impairments, leading to QOL reduction. Therapeutic management may be desirable to reduce seizures and EEG abnormalities, such as frontal IEDs and SBS, as early as possible to improve QOL in children with epilepsy. During antiseizure medication (ASM) selection and adjustment, physicians should strategize the therapeutic approach to controlling seizures and suppressing EEG abnormalities in children with epilepsy. Among various ASMs, novel ASMs, such as levetiracetam and perampanel, may suppress both clinical seizures and IEDs on EEG; thus, these novel ASMs may represent an important addition to the treatments available for epileptic children presenting with frontal IEDs and SBS.

Sleep and Epilepsy

The relationship between sleep and epilepsy is both intimate and bidirectional. The molecular mechanisms which control circadian rhythm and the sleep/wake cycle are dysregulated in epileptogenic tissue and are themselves effected by molecular pathways for epilepsy. Sleep affects the frequency of interictal epileptiform discharges and recent research has raised new questions regarding the impact of discharges on sleep function and cognition. Epileptiform discharges themselves affect sleep architecture and increase the risk of sleep disorders. Several sleep-related epilepsy syndromes have undergone changes in their classification which highlights their intimate relationship to sleep and novel screening tools have been developed to help clinicians better differentiate epileptic seizures from sleep-related paroxysmal events. Improving sleep and addressing sleep disorders has been associated with improved seizure control and increased well-being in people with epilepsy. These interactions are discussed in detail in this review.

Thermal neuromodulation using pulsed and continuous infrared illumination in a penicillin-induced acute epilepsy model

Infrared neuromodulation (INM) is a promising neuromodulation tool that utilizes pulsed or continuous-wave near-infrared (NIR) laser light to produce an elevation of the background temperature of the neural tissue. The INM-based cortical heating has been proven as an effective modality to induce changes in neuronal activities. In this paper, we investigate the effect of INM-based cortical heating on the characteristics of interictal epileptiform discharges (IEDs) induced by penicillin in anesthetized rats. Cortical heating was conducted using a NIR laser light guided through a needle-like silicon-based waveguide probe. We detected penicillin-induced cortical IEDs from preprocessed micro-electrocorticography (muECoG) recordings, then we assessed changes in various temporal and spectral features of IEDs due to INM. Our findings show that the fast cortical heating phase obtained with continuous-wave NIR light is highly associated with a reduction of IED amplitudes, small but significant changes in the negative amplitude of IEDs compared with the baseline, and a proportional increase in the power of frequency bands related to delta/theta (2–8 Hz) and gamma (28–80 Hz) oscillations. Furthermore, a low rate of cortical heating with pulsed NIR illumination has a more inhibitory impact on the sharp negative polarity of IEDs. Our findings do not indicate a clear reduction in the frequency of IEDs in anesthetized rodents. In contrast, 2–4 min of continuous laser illumination leads to a notable increase in IED frequency. This effect of INM could potentially restrict its use in therapeutic applications related to epilepsy. However, the thermal effect of INM on cortical neurons induces changes in other characteristics of IEDs, which could prove beneficial for future applications.

Disruption of EEG resting state functional connectivity in patients with focal epilepsy

BackgroundEpilepsy is a network disease and EEG could be used to evaluate dynamic inter-regional connectivity. The aim of the current study is to explore disruption of resting state EEG functional connectivity in focal epilepsy using coherence and phase lag degree. This cross-sectional study included 30 patients with focal epilepsy and 30 matched healthy controls. One to two minutes of EEG segmented into 2-s epochs during awake eye-closed state were analyzed using fast Fourier transform to yield four frequency bands: delta, theta, alpha and beta. Coherence and phase lag degree were computed between each pair of 19 EEG electrodes and were assessed at the intra-hemispheric (frontal–parietal and frontal–temporal) and inter-hemispheric (frontal, temporal and parietal) levels. The frequency of interictal epileptiform discharges (IEDs) was calculated from a 60-min EEG recording session.ResultsCompared to healthy controls, patients had lower theta coherence at left frontal–parietal (P = 0.017), lower delta coherence at inter-frontal (P = 0.045), higher theta phase lag at right frontal–parietal (P = 0.01) and lower delta phase lag at inter-temporal (P = 0.046) levels. Patients with left-sided epilepsy had lower theta coherence at left frontal–parietal (P = 0.026), higher theta phase lag at right frontal–parietal (P < 0.001), higher delta phase lag at right frontal–temporal (P = 0.036) and higher theta phase lag at inter-parietal (P = 0.028) levels. The frequency of IEDs correlated with phase lag of delta (P = 0.036, r = 0.406) and theta (P = 0.005, r = 0.513).ConclusionsPatients with focal epilepsy had significant interictal functional connectivity disruption detected by coherence and phase lag degree of delta and theta waves and correlated with frequency of IEDs.

0897 Sleep Architecture and Epileptiform Discharges in Rett Syndrome

Abstract Introduction Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting females and is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Sleep issues and frequent epileptiform discharges are common in RTT. Typical comorbidities in RTT include poor growth, feeding difficulties, hyperventilation and breath-holding, seizures, scoliosis, and disrupted sleep. Although polysomnographic studies indicate sleep disruption in patients with RTT, few evaluate if the epileptiform activity is associated with significantly greater changes in sleep. We analyzed if epileptiform discharges were associated with greater sleep changes than those seen without epileptiform discharges. Methods This retrospective case control of 10 RTT subjects (mean age, 11.19 years; ranged from 1 to 33 years) underwent standard in-lab polysomnography (PSG) recording. Subjects were compared to 10 age and gender matched controls with an AHI &amp;lt; 5 and no chronic medical problems. Rett children were divided into those with epileptiform discharges and those without. The two groups were compared using binomial cutoffs for each sleep parameter, and significance was determined by Fisher’s Exact Test. All studies were scored using the AASM criteria. Results Comparing our cohort of RTT patients to control subjects, the RTT patients have higher N3% of sleep, decreased N2%, and shorter sleep onset latency. 4 of the 10 PSGs are notable for frequent interictal epileptiform discharges. However, comparing those RTT patients with epileptiform discharges to those without, only REM latency trending shorter in those with epileptiform discharges (p= 0.057). No other significant differences were seen sleep staging, latency, total sleep time, efficiency, periodic limb movements nor respiratory parameters. Conclusion Our cohort did not find major differences in sleep features between those RTT patients with epileptiform discharges compared to those without. This may be related to a lack of influence of epileptiform discharges on these parameters or related to our small sample size. Although our cohort did not show major significant differences between those with epileptiform discharges, further study is required to delineate a more subtle relationship of these discharges to sleep. Support (if any)

Impact of two ketogenic diet types in refractory childhood epilepsy

BackgroundKetogenic diet (KD) refers to any diet in which food composition induces a ketogenic state of human metabolism.ObjectiveTo assess short- and long-term efficacy, safety, and tolerability of KD [classic KD and modified Atkins diet (MAD)] in childhood drug-resistant epilepsy (DRE) and to investigate the effect of KD on electroencephalographic (EEG) features of children with DRE.MethodsForty patients diagnosed with DRE according to International League Against Epilepsy were included and randomly assigned into classic KD or MAD groups. KD was initiated after clinical, lipid profile and EEG documentation, and regular follow-up was done for 24 months.ResultsOut of 40 patients with DRE, 30 completed this study. Both classic KD and MAD were effective in seizure control as 60% in classic KD group and 53.33% in MAD group became seizure free, and the remaining showed ≥50% seizure reduction. Lipid profile remained within acceptable levels throughout the study period in both groups. Adverse effects were mild and managed medically with an improvement of growth parameters and EEG during the study period.ConclusionsKD is an effective and safe non-pharmacologic, non-surgical therapy for the management of DRE with a positive impact on growth and EEG.ImpactBoth common types of KD (classic KD and MAD) are effective for DRE, but unfortunately, nonadherence and dropout rates are frequent.High serum lipid profile (cardiovascular AE) is often suspected in children following a high-fat diet, but lipid profile remained in the acceptable level up to 24 months. Therefore, KD constitutes a safe treatment.KD had a positive impact on growth, despite inconsistent results of the KD’s effect on growth.In addition to showing strong clinical effectiveness, KD also considerably decreased the frequency of interictal epileptiform discharges and enhanced the EEG background rhythm.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β±SE=49.91± 16.55 ms, p= .003) and number of IEDs (β±SE=49.84± 12.51 ms, p< .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p= .009) and improved task performance (β±SE=-107.43± 39.54 ms, p= .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

0519 Sleep Dysfunction in Rett Syndrome

Abstract Introduction Rett syndrome (RTT) is an X-linked neurodevelopmental disorder affecting females and is linked to mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. Typical comorbidities in RTT include poor growth, feeding difficulties, hyperventilation and breath-holding, seizures, scoliosis, and disrupted sleep. A few studies indicate sleep disruption in patients with RTT yet there is minimal data on polysomnographic findings in this population. We reviewed our cohort of Rett syndrome patients who underwent polysomnography. Methods This retrospective case control of 10 RTT subjects (mean age, 11.19 years; ranged from 1 to 33 years) underwent standard polysomnography (PSG) recording. Subjects were compared to 10 age and gender matched controls with an AHI &amp;lt;5 and no chronic medical problems using a student paired t test. All studies were scored using the AASM criteria. Results We found our cohort to have increased N3% sleep, decreased N2%, and shorter sleep onset latency (p&amp;lt; 0.05). Trends of lower BMI, lower oxygen saturation, and shorter REM latency (p &amp;lt; 0.10 but &amp;gt; 0.05). Review of PSGs shows the slow wave have morphological of typical slow waves and not that of the slowing seen on wake EEG nor the epileptiform activity. 4 of the 10 PSGs are notable for frequent interictal epileptiform discharges. 2 of the 10 subjects had a central apnea index &amp;gt;5, 2 had an AHI &amp;gt;5 and 1 demonstrated hypoventilation. There were central apneas associated with hyperventilation during awake and sleep-awake transition. Conclusion Our cohort of RTT patients demonstrates differences in sleep architecture, manifested most notably by a high percentage of SWS. This population has high amplitude rhythmic slow (theta) activity on wake EEG, primarily in the frontal-central regions. This slowing was distinct from the epileptiform activity seen in 40% of our cohort. Central apnea also appeared in older patients and the very young. Larger population studies are needed for future research. Support (If Any)

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

146 Human Interictal Epileptiform Discharges are Traveling Waves Reflecting Ictal Self-organization

INTRODUCTION: Interictal epileptiform discharges (IEDs), are large intermittent electrophysiological events observed between seizures in epileptic patients. While seizures are infrequent and unpredictable, IEDs are far more common, occurring several times per minute (0.67 IEDs per minute in this dataset). The relative frequency of IEDs makes them an alluring indicator of epileptogenic brain, especially when compared to more scarce and unpredictable seizures. Yet despite the relative abundance of IEDs, it remains unknown how they relate to seizures. METHODS: To better understand this relationship, we examined semi-chronic, multi-day recordings of 96-channel microelectrode arrays implanted in human epilepsy patients. These recordings—spanning single cell action potentials to local field potentials—allowed us to study the microscale spatiotemporal organization of over 45,000 IEDs across 10 patients. We used ordinary multivariate linear regression to estimiate IED speed and direction, and vonMises Mixture models to cluster bimodal IED directions in to sub-distributions. RESULTS: These recordings showed that the majority (66.4%) of IEDs propagate across neocortex as traveling waves with a dominant direction (Hermans-Rasson Tests, all p &lt; 10-3). IED traveling wave direction distributions were bimodal in 8 of the 10 subjects, with a median difference between sub-distributions of 178 degrees. Firing rates and voltages of IEDs in each sub distribution were not significantly different, however, the proportion of IEDs in each sub-distrbution and their speeds and directions were different among sub-distributions, and mimicked sub-distributions of ictal discharges. CONCLUSION: These results show that IEDs propagate across the surface of the brain as traveling waves, and the that their directions mimic those of discharges occuring during seizures. Furthermore, these results provide a new understanding of epileptic brian tissue, and suggest that spatial features of IEDs may be used to help diagnose and treat medically refractory epilepsy.

Therapeutic efficacy of seizure onset zone-targeting high-definition cathodal tDCS in patients with drug-resistant focal epilepsy

ObjectiveEpilepsy is a common neurological disease with recurrent seizures. Transcranial direct-current stimulation (tDCS) is a safe, non-invasive method used for neuromodulation. The aim of this study was to explore the efficacy of cathodal high-definition tDCS (HD-tDCS) as a noninvasive method for the treatment of patients with drug-resistant focal epilepsy (DRFE). MethodsThis study was conducted as a randomized parallel and double-blind clinical trial. Twenty patients with DRFE were randomly selected through the convenience sampling method and then were divided into two groups. Ten patients received 2 mA cathodal HD-tDCS targeting the seizure-onset zone for 30 min for 2 weeks (5 consecutive days in each week and 10 days in total). Ten patients were randomized to the sham group. Seizure frequency and Interictal Epileptiform Discharges (IEDs) frequency were the primary outcome measures of this study. Quality of Life in Epilepsy Inventory (QoLIE-89) and Montreal Cognitive Assessment (MoCA) scores were used as secondary outcome measures. ResultsSeizure frequency decreased significantly among the patients in the treatment group 2 weeks (P-value ≤ 0.05), 1 month (P-value ≤ 0.05), and 2 months (P-value ≤ 0.05) after the stimulation in comparison to the sham group. Patients in the treatment group showed a decrease in the frequency of IED 2 weeks (P-value ≤ 0.05), 1 month (P-value ≤ 0.05), and 2 months (P-value ≤ 0.05) after stimulation. This cathodal stimulation protocol also improved the overall QoLIE-89 score after the stimulation compared to the sham group. ConclusionsThe present study showed that cathodal HD-tDCS had a positive effect on seizure frequency and IED in patients with DRFE. More evidence is required to define the optimal stimulation parameters of HD-tDCS for the treatment of epilepsy. SignificanceCathodal HD-tDCS targeting the seizure-onset zone is a promising treatment modality for patients with drug-resistant focal epilepsy.

Factors predisposing patients with temporal lobe epilepsy to seizure cluster

Background: We aimed to identify the potential risk factors associated with seizure clusters in patients with temporal lobe epilepsy (TLE). Methods: This retrospective cross-sectional study was performed on all the consecutive patients with TLE, who were admitted to the Epilepsy Monitoring Unit (EMU), Loghman-Hakim Hospital, Tehran, Iran. Seizure cluster was defined as three or more habitual seizures occurring within 24 hours, in over 50% of ictal events, with inter-seizure interval of less than 8 hours. The patients’ demographic data, epilepsy duration, seizure frequency, frequency of interictal epileptiform discharges (IEDs), and brain magnetic resonance imaging (MRI) findings were collected. Results: Among a total number of 124 patients with TLE, 62 (50.0%) patients reported seizure clusters. In addition, 44 (37.9%), 42 (36.2%), and 30 (25.9%) patients had normal-appearing brain MRI, mesial temporal sclerosis (MTS), and other brain pathologies, respectively. In terms of IEDs frequency, 35 (29.4%), 43 (36.1%), 17 (14.3%), and 24 (20.2%) patients had respectively frequent, occasional, rare, and no spikes in one-hour of interictal scalp electroencephalography (EEG) recording. In our study, seizure clusters were not associated with the epilepsy duration (P = 0.100), the amount of IEDs (P = 0.764), or MRI findings (P = 0.112). Conclusion: In patients with TLE, seizure clustering had no correlation with the epilepsy duration, the amount of IEDs, or brain MRI findings.

Frequency of interictal epileptiform discharges in slow sleep with relapse of tonic-conical seizures in adults with generalized epilepsy after withdrawal of antiepileptic drugs

Frequency of interictal epileptiform discharges in slow sleep with relapse of tonic-conical seizures in adults with generalized epilepsy after withdrawal of antiepileptic drugs

Longitudinal impact of cannabidiol on EEG measures in subjects with treatment-resistant epilepsy

ObjectiveTo assess the longitudinal impact of highly purified cannabidiol (CBD) on the electroencephalogram (EEG) of children and adults. MethodsParticipants received an EEG prior to starting CBD, after approximately 12 weeks of CBD (FU1) and after approximately one year of CBD therapy (FU2). Longitudinal changes in five EEG measures (background frequency, focal slowing, reactivity, frequency of interictal, and ictal discharges) were examined following CBD exposure. Data were compared between pediatric and adult groups at two follow-up time points and within groups over time. Population-averaged models with generalized estimation equations or linear mixed effects models were used to analyze data where appropriate. Correlation analysis was used to assess any association between changes in seizure frequency and changes in EEG interictal discharge (IED) frequency. An alpha level of 5% was used to assess statistical significance. ResultsAt FU1, the adult group showed significant decrease in IED/minute (IDR 0.07, 95% CI [0.04, 0.14], P < 0.001); a nonsignificant decrease was observed among children (IDR 0.87, 95% CI [0.47, 0.64], P = 0.67). The difference in changes over time between participant groups was significant after adjusting for last CBD dose (IDR 11.8, 95% CI [4.86, 28.65], P < 0.0001). At FU2 both groups showed significant reduction from baseline after controlling for last CBD dose. This decrease was more pronounced in children (IDR 15.38, 95% CI [4.93, 47.99], P < 0.001). There was no significant correlation between changes in seizure frequency and EEG IED frequency at each timepoint (P = 0.542, 0.917 and 0.989 from baseline to FU1, FU1 to FU2 and baseline to FU2, respectively). SignificanceThis longitudinal EEG study shows that highly-purified plant-derived CBD has positive effects on interictal epileptiform discharge frequency but no effects on other EEG measures. The effect of CBD does not appear to be dose or treatment-duration dependent.