Interictal Epileptiform Discharges Research Articles

Comparison of Automated Spike Detection Software in Detecting Epileptiform Abnormalities on Scalp-EEG of Genetic Generalized Epilepsy Patients.

Despite availability of commercial EEG software for automated epileptiform detection, validation on real-world EEG datasets is lacking. Performance evaluation of two software packages on a large EEG dataset of patients with genetic generalized epilepsy was performed. Three epileptologists labelled IEDs manually of EEGs from three centres. All Interictal epileptiform discharge (IED) markings predicted by two commercial software (Encevis 1.11 and Persyst 14) were reviewed individually to assess for suspicious missed markings and were integrated into the reference standard if overlooked during manual annotation during a second phase. Sensitivity, precision, specificity, and F1-score were used to assess the performance of the software packages against the adjusted reference standard. One hundred and twenty-five routine scalp EEG recordings from different subjects were included (total recording time, 310.7 hours). The total epileptiform discharge reference count was 5,907 (including spikes and fragments). Encevis demonstrated a mean sensitivity for detection of IEDs of 0.46 (SD 0.32), mean precision of 0.37 (SD 0.31), and mean F1-score of 0.43 (SD 0.23). Using the default medium setting, the sensitivity of Persyst was 0.67 (SD 0.31), with a precision of 0.49 (SD 0.33) and F1-score of 0.51 (SD 0.25). Mean specificity representing non-IED window identification and classification was 0.973 (SD 0.08) for Encevis and 0.968 (SD 0.07) for Persyst. Automated software shows a high degree of specificity for detection of nonepileptiform background. Sensitivity and precision for IED detection is lower, but may be acceptable for initial screening in the clinical and research setting. Clinical caution and continuous expert human oversight are recommended with all EEG recordings before a diagnostic interpretation is provided based on the output of the software.

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes ( > 1 year), and 25 patients had enough recorded data ( > 6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Assessing 72 h vs. 24 h of long-term video-EEG monitoring to confirm the diagnosis of epilepsy: a retrospective observational study.

Paroxysmal seizure-like events can be a diagnostic challenge. Inpatient video-electroencephalography (EEG) monitoring (VEM) can be a valuable diagnostic tool, but recommendations for the minimal duration of VEM to confirm or rule out epilepsy are inconsistent. In this study, we aim to determine whether VEM of 48 or 72 h was superior to 24 h. In this monocentric, retrospective study, we included 111 patients with paroxysmal, seizure-like events who underwent at least 72 h of VEM. Inclusion criteria were as follows: (1) Preliminary workup was inconclusive; (2) VEM admission occurred to confirm a diagnosis; (3) At discharge, the diagnosis of epilepsy was conclusively established. We analyzed the VEM recordings to determine the exact time point of the first occurrence of epileptic abnormalities (EAs; defined as interictal epileptiform discharges or electrographic seizures). Subgroup analyses were performed for epilepsy types and treatment status. In our study population, 69.4% (77/111) of patients displayed EAs during VEM. In this group, the first occurrence of EAs was observed within 24 h in 92.2% (71/77) of patients and within 24-72 h in 7.8% (6/77). There was no statistically significant difference in the incidence of EA between medicated and non-medicated patients or between focal, generalized epilepsies and epilepsies of unknown type. Of the 19 recorded spontaneous electroclinical seizures, 6 (31.6%) occurred after 24 h. A VEM of 24 h may be sufficient in the diagnostic workup of paroxysmal seizure-like events under most circumstances. Considering the few cases of first EA in the timeframe between 24 and 72 h, a prolonged VEM may be useful in cases with a high probability of epilepsy or where other strategies like sleep-EEG or ambulatory EEG show inconclusive results. Prolonged VEM increases the chance of recording spontaneous seizures. Our study also highlights a high share of subjects with epilepsy that do not exhibit EAs during 72 h of VEM.

Altered Sleep Microarchitecture and Cognitive Impairment in Patients With Temporal Lobe Epilepsy.

To investigate the spatiotemporal characteristics of sleep waveforms in temporal lobe epilepsy (TLE) and examine their association with cognition. In this retrospective, cross-sectional study, we examined overnight EEG data from adult patients with TLE and nonepilepsy comparisons (NECs) admitted to the epilepsy monitoring unit at Mass General Brigham hospitals. Automated algorithms were used to characterize sleep macroarchitecture (sleep stages) and microarchitecture (spindles, slow oscillations [SOs]) on scalp EEG and to detect hippocampal interictal epileptiform discharges (hIEDs) from foramen ovale electrodes simultaneously recorded in a subset of patients with TLE. We examined the association of sleep features and hIEDs with memory and executive function from clinical neuropsychological evaluations. A total of 81 adult patients with TLE and 28 NEC adult patients were included with similar mean ages. There were no significant differences in sleep macroarchitecture between groups, including relative time spent in each sleep stage, sleep efficiency, and sleep fragmentation. By contrast, the spatiotemporal characteristics of sleep microarchitecture were altered in TLE compared with NEC and were associated with cognitive impairments. Specifically, we observed a ∼30% reduction in spindle density in patients with TLE compared with NEC, which was significantly associated with worse memory performance. Spindle-SO coupling strength was also reduced in TLE and, in contrast to spindles, was associated with diminished executive function. We found no significant association between sleep macroarchitectural and microarchitectural parameters and hIEDs. There is a fundamental alteration of sleep microarchitecture in TLE, characterized by a reduction in spindle density and spindle-SO coupling, and these changes may contribute to neurocognitive comorbidity in this disorder.

Interictal epileptiform discharges contribute to word-finding difficulty in epilepsy through multiple cognitive mechanisms.

Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word-finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word-finding difficulty in patients, and if so, through which cognitive mechanism(s). Twenty-three patients undergoing intracranial monitoring for drug-resistant epilepsy participated in multiple tasks involving word production (auditory naming, short-term verbal free recall, repetition) to probe word-finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed-effects models. We also evaluated for subjective word-finding difficulties through retrospective chart review. Subjective word-finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long-term lexicosemantic memory impairments as indexed by auditory naming (p = .009), in addition to their established impact on short-term verbal memory as indexed by free recall (p = .004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (p = .016 and p = .018), as well as phonological working memory impairments as indexed by repetition reaction time (p = .002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task. IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word-finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.

Rapid eye movement sleep affects interictal epileptic activity differently in mesiotemporal and neocortical areas.

Rapid eye movement (REM) sleep reduces the rate and extent of interictal epileptiform discharges (IEDs). Breakthrough epileptic activity during REM sleep is therefore thought to best localize the seizure-onset zone (SOZ). We utilized polysomnography combined with direct cortical recordings to investigate the influences of anatomical locations and the time of night on the suppressive effect of REM sleep on IEDs. Forty consecutive patients with drug-resistant focal epilepsy underwent combined polysomnography and stereo-electroencephalography during presurgical evaluation. Ten-minute interictal epochs were selected 2 h prior to sleep onset (wakefulness), and from the first and second half of the night during non-REM (NREM) sleep and REM sleep. IEDs were detected automatically across all channels. Anatomic localization, time of night, and channel type (within or outside the SOZ) were tested as modulating factors. Relative to wakefulness, there was a suppression of IEDs by REM sleep in neocortical regions (median=-27.6%), while mesiotemporal regions showed an increase in IEDs (19.1%) (p=0.01; d=0.39). This effect was reversed when comparing the regional suppression of IEDs by REM sleep relative to NREM sleep (-35.1% in neocortical; -58.7% in mesiotemporal) (p<0.001; d=0.39). Across all patients, no clinically relevant novel IED regions were observed in REM sleep versus NREM or wakefulness based on our predetermined thresholds (4 IEDs/min in REM, 0 IEDs/min in NREM and W). Finally, there was a reduction in IEDs in late (NREM: 1.08/min; REM: 0.61/min) compared to early sleep (NREM: 1.22/min; REM: 0.69/min) for both NREM (p<0.001; d=0.21) and REM (p=0.04; d=0.14). Our results demonstrate a spatiotemporal effect of IED suppression by REM sleep relative to wakefulness in neocortical, but not mesiotemporal regions, and in late versus early sleep. This suggests the importance of considering sleep stage interactions and the potential influences of anatomical locations when using IEDs to define the epileptic focus.

The differing effects of sleep on ictal and interictal network dynamics in drug-resistant epilepsy.

Sleep has important influences on focal interictal epileptiform discharges (IEDs), and the rates and spatial extent of IEDs are increased in non-rapid eye movement (NREM) sleep. In contrast, the influence of sleep on seizures is less clear and its effects on seizure topography are poorly documented. We evaluated the influences of NREM sleep on ictal spatiotemporal dynamics and contrasted these with interictal network dynamics. We included patients with drug-resistant focal epilepsy who underwent continuous intracranial EEG with depth electrodes. Patients were selected if they had 1-3 seizures from each vigilance state, wakefulness and NREM sleep, within a 48-hour window and under the same anti-seizure medication. A 10-min epoch of the interictal iEEG was selected per state, and IEDs were detected automatically. Twenty-five patients (13 females; 32.5±7.1 years) were included. The seizure onset pattern, duration, spatiotemporal propagation and latency of ictal high-frequency activity did not differ significantly between wakefulness and NREM sleep (all p>0.05). In contrast, IED rates and spatial distribution were increased in NREM compared to wakefulness (p<0.001, Cliff's d=0.48 and 0.49). The spatial overlap between vigilance states was higher for seizures (57.1±40.1%) than IEDs (41.7±46.2%) (p=0.001, Cliff's d=0.51). In contrast to its effects on IEDs, NREM sleep does not affect ictal spatiotemporal dynamics. This suggests that once the brain surpasses the seizure threshold, it will follow the underlying epileptic network irrespective of the vigilance state. These findings offer valuable insights into neural network dynamics in epilepsy and have important clinical implications for localizing seizure foci. This article is protected by copyright. All rights reserved.

The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.

Epilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy. The follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens. During a median follow-up time of 12.8 years [interquartile range (IQR): 10.8-17.3] in the AIS group and 12.5 years (IQR: 9.3-14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04-14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04-14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy. In children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.

Candidate Selection for Implantation: Noninvasive Predictors of Seizure Onset Zone Focality and Surgical Outcome in People with Drug-Resistant Epilepsy Evaluated by Intracranial Video-EEG Monitoring—A Retrospective Cohort Study

Objectives. People with drug-resistant epilepsy are potential candidates for epilepsy surgery, a subset of whom requires intracranial video-EEG monitoring (IVEM) to determine the seizure onset zone (SOZ). The purpose of this study is to investigate noninvasive predictors of SOZ focality and surgical outcome in order to optimise case selection for this procedure. Materials and Methods. We performed a retrospective cohort study of patients who underwent IVEM at our centre from January 2006 to July 2021. We applied a multivariate logistic regression model to estimate the effect of potential noninvasive data as influencing factors for both SOZ focality and surgical outcome. A focal SOZ included a sublobar onset on IVEM, and a good surgical outcome was defined as Engel class I. Results. A total of 783 underwent a presurgical evaluation, 102 of them with IVEM. Ninety-seven patients were included in the SOZ focality analysis, and 64 were included in the surgical outcome analysis. The presence of focal to bilateral tonic-clonic seizures ( p = 0.03 ) and generalised interictal epileptiform discharges (IEDs) during scalp EEG ( p = 0.02 ) predicted a nonfocal SOZ. A weekly ( p = 0.01 ) or daily seizure frequency ( p &lt; 0.01 ), focal to bilateral tonic-clonic seizures ( p = 0.01 ), nonlesional MRI ( p &lt; 0.01 ), and multifocal ( p = 0.02 ) or generalised IEDs ( p &lt; 0.01 ) were associated with a poor surgical outcome. Conclusions. A high seizure frequency, positive history of focal to bilateral tonic-clonic seizures, nonlesional MRI, and generalised and multifocal IEDs are noninvasive factors that may aid in selecting candidates for IVEM.

The Role of Long Monitoring EEG in Detection of Interictal Epileptiform Discharge in Idiopathic Epilepsy

The Role of Long Monitoring EEG in Detection of Interictal Epileptiform Discharge in Idiopathic Epilepsy

Electroencephalographic Patterns in Pediatric Patients With Multisystem Inflammatory Syndrome in Children and Coronavirus Disease 2019 Coinfection

BackgroundChildren with recent or acute coronavirus disease 2019 (COVID-19) infections are susceptible to a number of neurological complications, including encephalopathy and seizures. Within the phenomenon of multisystem inflammatory syndrome in children (MIS-C), patients may be encephalopathic or have other nervous system sequelae. The electroencephalographic (EEG) patterns accompanying neurological complications of COVID-19 infection have been reported but primarily in case reports or small case series. MethodsIn this study, we reviewed all reports of EEG patterns seen in pediatric patients with presentations attributed to COVID-19 infection. ResultsFifty patient reports were identified, drawn from 27 articles. We separately analyzed patients whose primary neurological concern was (1) encephalopathy, (2) seizures, or (3) other neurological abnormalities. Patients with acute encephalopathy tend to have EEG showing diffusely slow background, often in the delta range; however, the pattern of slowing is sometimes anterior or posterior predominant and may evolve over the course of illness. ConclusionsPatients with COVID-19 infection presenting with seizures may have focal or bilateral semiologies, but postictal EEG rarely shows interictal epileptiform discharges and is more likely to also show diffuse slowing. However, subclinical seizures and nonconvulsive status epilepticus have been reported, so prolonged EEG monitoring may still be indicated.

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.

Differences in generation and maintenance between ictal and interictal generalized spike-and-wave discharges in childhood absence epilepsy: A magnetoencephalography study

PurposeChildhood absence epilepsy (CAE) is characterized by impaired consciousness and distinct electroencephalogram (EEG) patterns. However, interictal epileptiform discharges (IEDs) do not lead to noticeable symptoms. This study examines the disparity between ictal and interictal generalized spike-and-wave discharges (GSWDs) to determine the mechanisms behind CAE and consciousness. MethodsWe enrolled 24 patients with ictal and interictal GSWDs in the study. The magnetoencephalography (MEG) data were recorded before and during GSWDs at a sampling rate of 6000 Hz and analyzed across six frequency bands. The absolute and relative spectral power were estimated with the Minimum Norm Estimate (MNE) combined with the Welch technique. All the statistical analyses were performed using paired-sample tests. ResultsDuring GSWDs, the right lateral occipital cortex indicated a significant difference in the theta band (5–7 Hz) with stronger power (P = 0.027). The interictal group possessed stronger spectral power in the delta band (P < 0.01) and weaker power in the alpha band (P < 0.01) as early as 10 s before GSWDs in absolute and relative spectral power. Additionally, the ictal group revealed enhanced spectral power inside the occipital cortex in the alpha band and stronger spectral power in the right frontal regions within beta (15–29 Hz), gamma 1 (30–59 Hz), and gamma 2 (60–90 Hz) bands. ConclusionsGSWDs seem to change gradually, with local neural activity changing even 10 s before discharge. During GSWDs, visual afferent stimulus insensitivity could be related to the impaired response state in CAE. The inhibitory signal in the low-frequency band can shorten GSWD duration, thereby achieving seizure control through inhibitory effect strengthening.

Interictal epileptiform discharges in Alzheimer's disease: prevalence, relevance, and controversies.

Alzheimer's disease (AD) is the most common type of dementia and remains an incurable, progressive disease with limited disease-modifying interventions available. In patients with AD, interictal epileptiform discharges (IEDs) have been identified in up to 54% of combined cohorts of mild cognitive impairment (MCI) or mild dementia and are a marker of a more aggressive disease course. Studies assessing the role of IEDs in AD are limited by the lack of standardization in the definition of IEDs or the different neurophysiologic techniques used to capture them. IEDs are an appealing treatment target given the availability of EEG and anti-seizure medications. There remains uncertainty regarding when to treat IEDs, the optimal drug and dose for treatment, and the impact of treatment on disease course. This review covers the state of knowledge of the field of IEDs in AD, and the steps needed to move the field forward.

Graph neural networks in EEG spike detection

Objective:This study develops new machine learning architectures that are more adept at detecting interictal epileptiform discharges (IEDs) in scalp EEG. A comparison of results using the average precision (AP) metric is made with the proposed models on two datasets obtained from Baptist Hospital of Miami and Temple University Hospital. Methods:Applying graph neural networks (GNNs) on functional connectivity (FC) maps of different frequency sub-bands to yield a novel architecture we call FC-GNN. Attention mechanism is applied on a complete graph to let the neural network select its important edges, hence bypassing the extraction of features, a model we refer to as CA-GNN. Results:On the Baptist Hospital dataset, the results were as follows: Vanilla Self-Attention →0.9029±0.0431, Hierarchical Attention →0.8546±0.0587, Vanilla Visual Geometry Group (VGG) →0.92±0.0618, Satelight →0.9219±0.046, FC-GNN →0.9731±0.0187, and CA-GNN →0.9788±0.0125. In the same order, the results on the Temple University Hospital dataset are 0.9692, 0.9113, 0.97, 0.9575, 0.963, and 0.9879. Conclusion:Based on the good results they yield, GNNs prove to have a strong potential in detecting epileptogenic activity. Significance:This study opens the door for the discovery of the powerful role played by GNNs in capturing IEDs, which is an essential step for identifying the epileptogenic networks of the affected brain and hence improving the prospects for more accurate 3D source localization.

P20.02.B ELECTRO-CLINICAL, NEUROIMAGING FEATURES AND NEUROPATHOLOGICAL CHARACTERIZATION OF POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG (PLNTY)

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) has been recently recognized by 2021 WHO Central nervous system classification. It is an epileptogenic tumor type, affecting mostly children and young adults, with peculiar radiological, and pathomolecular features. PLNTY is a very rare tumor, described in only 52 cases up to now. Herein, we describe 13 patients with electro-clinical and neuroimaging findings, associated to histopathological and molecular findings. MATERIAL AND METHODS We selected PLNTY patients from our Cancer Registry (Apr 2017-Dec 2022), and collected electro-clinical, radiological and histo-molecular data. Minimum follow-up was 6 months. Exams included EEG, long-term scalp video-EEG, pre-surgical brain computer tomography and Magnetic Brain Imaging (MRI). Immunohistochemistry included CD34, IDH1-R132H, GFAP, synaptophysin, ATRX, p53 and FGFR3. IDH1-2, BRAF (V600E) sequencing, Kiaa1549:BRAF, FGFR3:TACC3, FGFR2:kii1598 and FGFR2:CTNNA3 fusion analyses will be performed. RESULTS We describe 13 patients, median age 20.6 years (range 12.3-46.4). Most patients showed memory/executive impairment and had epilepsy, with an onset from 5 months-21 years before surgery. The main feature of seizures was a difficult localization and even lateralization, both semiologically and electrographically. Post-surgical seizure control was excellent.The tumors (n=11/13 temporal) presented as solid or solid-cystic cortical mass with no mass effect and unclear hedges. Calcifications were present in 4, and cysts in 6 cases. Microscopically the tumors showed infiltrative growth pattern, oligodendroglial-like cells, strong and often diffuse CD34 immunostaining, and frequent intra-tumoral calcifications. Malformation of cortical development, namely FCD type IIIB, was associated to PLNTY in 2 cases. Proliferation activity (MIB-1 LI) was very low (1%) in all cases except one (MIB-1 LI which reached 3%). CONCLUSION This study significantly extends the number of reported PLNTY associated to epilepsy, mostly characterized by bilateral interictal epileptiform discharges and difficult to lateralize seizures.The MRI features were heterogeneous and the differential diagnosis should include also dysplasia and glioneuronal tumors. PLNTY, despite its name, occurs also in adults, and electro-clinical and radiological diagnosis can be challenging. As recently described, PLNTY can show the MAPK pathway activating alterations, that are under investigation in our cohort to eventually clarify their role in the evolution of the disease. SUPPORT the study is partially supported by the Health Italian Minister (RC).

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.

Pharmacological inhibition of ictal and interictal epileptiform discharges

Background: Epilepsy is a brain disorder characterized by an enduring predisposition to generate epileptic seizures. Seizures are a transient occurrence of signs and/or symptoms due to abnormal excessive and synchronous neuronal activity in the brain. Electroencephalogram (EEG), a non-invasive instrumental test, has an important role in the diagnosis of epilepsy, as well as in monitoring the results and long-term treatment because it can detect interictal and ictal discharges that are crucial for confirmation and classification of seizures. Antiepileptic drugs are the first treatment option in patients with epilepsy, although the effectiveness of such drugs is limited only to symptom control and requires a regular intaking by the patient. These drugs exploit the cell membrane channels, modifying their permeability, allowing either an increase in the inhibitory neurotransmission or the reduction in the excitatory one, by hyperpolarizing neurons and avoiding the recurrence of the epileptic seizures without reversing or stopping the underlying mechanism of epileptogenesis. Materials and Methods: The internship took place in the Neurophysiopathology department of the Antonio, Biagio and Cesare Arrigo’s hospital in Alessandria, from October 2022 to March 2023. During this period, it was possible to attend the emergency treatment of prolonged and recurrent epileptic seizures during EEGrafic recording and the consequential amendments of the ictal discharges induced by the administration of antiepileptic drugs. Follow up EEG was also performed to investigate the modifications of interictal activity after a period of treatment with antiepileptic drugs. The patient who has been analyzed in this paper, underwent EEG recordings obtained by using bridge electrodes placed on the scalp according to the international 10-20 system. Objectives: The aim of this study is to analyze the mechanisms of action of the main antiepileptic drugs, in relation to the physiological cellular mechanisms regulating the neuronal excitability and their effect on the ictal and interictal epileptiform discharges in the EEG recordings.

Fast ripples reflect increased excitability that primes epileptiform spikes.

The neuronal circuit disturbances that drive inter-ictal and ictal epileptiform discharges remain elusive. Using a combination of extra-operative macro-electrode and micro-electrode inter-ictal recordings in six pre-surgical patients during non-rapid eye movement sleep, we found that, exclusively in the seizure onset zone, fast ripples (200-600 Hz), but not ripples (80-200 Hz), frequently occur <300 ms before an inter-ictal intra-cranial EEG spike with a probability exceeding chance (bootstrapping, P < 1e-5). Such fast ripple events are associated with higher spectral power (P < 1e-10) and correlated with more vigorous neuronal firing than solitary fast ripple (generalized linear mixed-effects model, P < 1e-9). During the intra-cranial EEG spike that follows a fast ripple, action potential firing is lower than during an intra-cranial EEG spike alone (generalized linear mixed-effects model, P < 0.05), reflecting an inhibitory restraint of intra-cranial EEG spike initiation. In contrast, ripples do not appear to prime epileptiform spikes. We next investigated the clinical significance of pre-spike fast ripple in a separate cohort of 23 patients implanted with stereo EEG electrodes, who underwent resections. In non-rapid eye movement sleep recordings, sites containing a high proportion of fast ripple preceding intra-cranial EEG spikes correlate with brain areas where seizures begin more than solitary fast ripple (P < 1e-5). Despite this correlation, removal of these sites does not guarantee seizure freedom. These results are consistent with the hypothesis that fast ripple preceding EEG spikes reflect an increase in local excitability that primes EEG spike discharges preferentially in the seizure onset zone and that epileptogenic brain regions are necessary, but not sufficient, for initiating inter-ictal epileptiform discharges.