Epileptiform Activity Research Articles

The Importance of Epileptiform Activities in Breach Rhythms

The Importance of Epileptiform Activities in Breach Rhythms

Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring.

Congenital cytomegalovirus (CMV) infections represent one leading cause of human neurodevelopmental disorders. Despite their high prevalence and severity, no satisfactory therapy is available and pathophysiology remains elusive. The pathogenic involvement of immune processes occurring in infected developing brains has been increasingly documented. Here, we have used our previously validated rat model of CMV infection of the fetal brain in utero to test whether the maternal administration of four different drugs with immunomodulatory properties would have an impact on the detrimental postnatal outcome of CMV infection. CMV infection of the rat fetal brain was done intracerebroventricularly. Each of the drugs, including acetylsalicylic acid (aspirin, ASA), a classical inhibitor of cyclooxygenases Cox-1 and Cox-2, the two key rate-limiting enzymes of the arachidonic acid-to-prostaglandins (PG) synthesis pathway, was administered to pregnant dams until delivery. ASA was selected for subsequent analyses based on the improvement in postnatal survival. A combination of qRT-PCR, mass spectrometry-based targeted lipidomics, immunohistochemistry experiments, monitoring of neurologic phenotypes and electrophysiological recordings was used to assess the impact of ASA in CMV-infected samples and pups. The postnatal consequences of CMV infection were also analyzed in rats knocked-out (KO) for Cox-1. Increased PGE2 levels and increased proportions of Cox-1+ and Cox-2+ microglia were detected in CMV-infected developing brains. Maternal intake of ASA led to decreased proportion of Cox-1+ fetal, but not neonatal, microglia, while leaving the proportions of Cox-2+ microglia unchanged. Maternal intake of ASA also improved the key postnatal in vivo phenotypes caused by CMV infection and dramatically prevented against the spontaneous epileptiform activity recorded in neocortical slices from CMV-infected pups. In contrast with maternal intake of ASA, Cox-1 KO pups displayed no improvement in the in vivo phenotypes after CMV infection. However, as with ASA administration, the spontaneous epileptiform activity was dramatically inhibited in neocortical slices from CMV-infected, Cox-1 KO pups. Overall, our data indicate that, in the context of CMV infection of the fetal brain, maternal intake of ASA during pregnancy improved CMV-related neurodevelopmental alterations in the offspring, likely via both Cox-1 dependent and Cox-1 independent mechanisms, and provide proof-of-principle for the use of ASA against the detrimental outcomes of congenital CMV infections.

Epileptiform activity in brain organoids derived from patient with Glucose Transporter 1 Deficiency Syndrome

IntroductionGlucose Transporter 1-Deficiency Syndrome (GLUT1-DS) is a rare genetic disorder caused by mutations in the gene encoding for GLUT1 and characterized by impaired glucose uptake in the brain. This leads to brain hypometabolism and the development of symptoms that include epilepsy, motor dysfunctions and cognitive impairment. The development of patient-specific in vitro models is a valuable tool for understanding the pathophysiology of rare genetic disorders and testing new therapeutic interventions.MethodsIn this study, we generated brain organoids from induced pluripotent stem cells (iPSCs) derived either from a GLUT1-DS patient or a healthy individual. The functional organoids were analyzed for cellular composition, maturity, and electrophysiological activity using a custom-made microelectrode array (MEA) platform, which allowed for the detection of spikes, burst patterns, and epileptiform discharges.ResultsImmunostaining revealed a similar distribution of neurons and astrocytes in both healthy and GLUT1-DS brain organoids, though GLUT1-DS brain organoids exhibited reduced cellular density and smaller overall size. Electrophysiological recordings demonstrated functional spike profiles in both organoid types. Notably, our study demonstrates that brain organoids derived from a GLUT1-DS patient exhibit distinct epileptiform activity and heightened sensitivity to glucose deprivation, reflecting key features of the disorder.DiscussionThese findings validate the use of brain organoids as a model for studying GLUT1-DS and highlight their potential for testing novel therapeutic strategies aimed at improving glucose metabolism and managing epilepsy in patients.

3D bioprinted in vitro epilepsy models for pharmacological evaluation in temporal lobe epilepsy

This study introduces a novelin vitromodel for intractable temporal lobe epilepsy (TLE) utilizing 3D bioprinting technology, aiming to replicate the complex neurobiological characteristics of TLE more accurately. Primary neural cell constructs were fabricated and subjected to epileptiform-inducing conditions, fostering synaptic proliferation and neuronal loss. Systematically electrophysiological and immunofluorescent analyses indicated that significant synaptic connectivity and sustained epileptiform activities within the constructs akin to those observed in human epilepsy models. Notably, the model responded to treatments with phenytoin and tetrodotoxin, illustrating its potential utility in drug response kinetics studies. Furthermore, we performed drug permeability simulations using COMSOL Multiphysics to analyze the diffusion characteristics of these drugs within the constructs. These results confirm that our 3D bioprinted neural model provides a physiologically relevant and ethically sustainable platform, which is beneficial for studying TLE mechanisms and developing therapeutic strategies with high accuracy and clinical relevance.

Evaluation of simplified wireless EEG recordings in the neurological emergency room.

In the neurological emergency room (nER), timely electroencephalography (EEG) diagnostic is often crucial in patients with altered state of consciousness as well as in patients presenting with a first seizure. Yet, routine-EEG (rEEG) is often not available, especially during off-hours. We analyzed the value of a commercially available, simplified wireless eight-channel EEG recording (swEEG, CerebAir® EEG headset, Nihon Kohden), applied by non-EEG-specialized medical students, in patients presenting in our nER with (suspicion of) epileptic seizures and/or loss of or altered state of consciousness between 08/2019 and 08/2022. We evaluated the feasibility and validity compared to a standard rEEG (21 electrodes according to the international 10/20 system) and also included the clinical follow-up of the patients. 100 patients were included in our analysis (mean age 57.6 ± 20.4 years; 61 male). Median time of electrode application was 7 minutes (range 4-20 minutes), with significantly longer duration in patients with altered level of consciousness (median 8 minutes, p = 0.035). Electrode impedances also differed according to state of consciousness (p = 0.032), and were higher in females (p<0.001). 55 patients received additional rEEG, either during their acute nER stay (25) and/or during the next days (38). Considering normal EEG findings vs. pathological slowing vs. epileptiform activity, swEEG matched first rEEG results in 48/55 cases (87.3%). Overall, swEEG detected the same or additional pathological EEG patterns in 52/55 cases (94.5%). In 7/75 patients (9.3%) who did not receive rEEG, or had their rEEG scheduled to a later time point during their hospital stay, swEEG revealed important additional pathological findings (e.g. status epilepticus, interictal epileptiform discharges), which would have triggered acute therapeutic consequences or led to further diagnostics and investigations. The introduced swEEG represents a practicable, valuable technique to be quickly applied by non-EEG-specialized ER staff to initiate timely diagnostic and guide further investigations and treatment in the nER. Moreover, it may help to avoid under-diagnostic with potentially harmful consequences caused by skipped or postponed regular 10/20 EEG examinations, and ultimately improve the outcome of patients.

Latent periodicity in epilepsy

AbstractEvidence collected from trials of chronic electroencephalographic (EEG) recordings has shown that a cyclical organization of seizures and interictal epileptiform activity is widespread among patients with focal epilepsy. Yet, seizures reported by patients themselves or their family do not always exhibit such regularity. In this review, we discuss various reasons explaining the apparent discrepancy between continuous EEG data and patient-reported seizures.

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.

Clinical and Radiological Parameters Affecting the Yield of Routine Electroencephalography in Various Indications.

To highlight the significance of various clinical and radiological parameters in association with specific electroencephalographic (EEG) patterns in order to prioritize EEG referrals. This retrospective, cross-sectional study was conducted in the neurology department of King Fahad University Hospital, Alkhobar, and involved a review and analysis of EEG and medical records pertaining to 604 patients referred for routine EEG. The data were analyzed using SPSS version 22. An association between various parameters and EEG yield was established. Factors associated with the yield of abnormal EEG patterns were diverse, like generalized tonic-clonic seizures (GTCs) (P =.05), status epilepticus (SE) (P =.05), altered level of consciousness (ALC) (P =.00), abnormal movement (P =.00), cardiac arrest (P =.00), prior history of epilepsy (P =.04), chronic renal disease (CRD) (P =.03), abnormal neurological exam (P =.00), and cortical lesions on brain imaging (P =.00). Among the abnormal EEG patterns, epileptiform activity (EA) in EEG was associated with focal seizures (P =.03), GTCs (P =.00), falls (P =.05), cardiac arrest (P =.00), a history of epilepsy (P =.00), and hypoxic ischemic injury (P =.03). Encephalopathy in EEG was also associated with focal sz (P =.02), GTCs (P =.00), SE (P =.01), ALC (P =.00), cardiac arrest (P =.00), history of stroke (P =.01), and epilepsy (P =.00). Among the studied parameters, patient level of consciousness, neurological exam findings, and neuroimaging findings, with some discrepancies, were found to be the most consistent in predicting the EEG yield. The study demonstrated the value of a proper neurological exam and careful selection of patients to gain the optimum benefit from the routine EEG.

Electroencephalographic monitoring in detection and prediction of delayed cerebral ischemia due to non-traumatic subarachnoid hemorrhage

Intensive care of patients with acute non-traumatic subarachnoid hemorrhage primarily relies on diagnostics of delayed cerebral ischemia (DCI). The major difficulty in detecting DCI emerges upon suppression of wakefulness, when clinical assessment of growing neurological deficit becomes complicated. Widely used transcranial dopplerography allows solely to verify a vasospasm development not always leading to DCI exhibiting a multifactorial underlying mechanism. Electroencephalography (EEG) is the only broadly available instrumental tool ensuring a continuous monitoring of cerebral functional status including in subjects at intensive care unit. To date, non-specific EEG parameters pointing at development of acute cerebral injury were identified that provide varying diagnostic and predictive informative value in DCI. We reviewed publications aimed at assessing the data on visual and quantitative EEG parameters such as regional slowing, alpha rhythm spectral power and relative variability, alpha-to-delta power ratio, and detection of epileptiform activity. Having searched international and Russia-wide medical databases, we found only 7 publications quantitatively assessing diagnostic value of EEG monitoring, which showed that for DCI diagnosis its sensitivity ranged from 76% to 100%, and specificity – from 54% to 100%. We also present a clinical case with a 70-year-old female patient who underwent surgery for non-traumatic subarachnoid hemorrhage due to a ruptured aneurysm of the communicating segment of the right internal carotid artery. During the continuous videoEEG monitoring 2 days before clinical deterioration and appearance of ischemic changes in the right cerebral hemisphere on computed tomography scans, an ictal-interictal continuum pattern was noted to emerge. Future studies should be aimed at clarifying and validating the most informative DCI biomarkers including while recording EEG with intracranial electrodes that may contribute to development of automated algorithms for DCI detection.

Results of surgical treatment for drug-resistant temporal epilepsy and related predictors of negative post-surgery outcome

Objective: to evaluate the results of surgical treatment and identify related predictors of unfavorable outcome in patients with temporal drug-resistant epilepsy (DRE) in long-term postoperative period.Material and methods. Fifty-one patients with temporal lobe DRE were examined using clinical, neuroimaging, electro- physiological, and laboratory research methods from June 2020 to June 2023. Anteromedial temporal lobectomy (AMLE) and selective amygdalohippocampectomy (SAHE) were performed in 38 (74.5%) and 13 (25.5%) cases, respectively. Postsurgery outcomes were evaluated in 51 patients 6 months later, continued in 43 and 20 patients 1 year and 2 years, respectively, afterwards.Results. The percentage of patients with significant improvement (Engel I/II) 6 months, 1 year and 2 years post-surgery was 82.4%, 72.1%, and 55.0%, respectively. After AMLE vs. SAHE, patients had a more favorable outcome while assessing seizure control. The predictors of unfavorable post-surgery outcome included a prolonged epilepsy course before surgery, the presence of electroencephalography-verified epileptiform activity in postoperative period, and repeated surgical intervention. Patient age, the presence of focal seizures evolving into bilateral tonic-clonic seizures as well as more frequent seizures before surgery were considered as potential predictors.Conclusion. The study results show that quite high effectiveness of seizure control in postoperative period in temporal DRE is quite high that may be accounted for by probability of removing epileptogenic foci and suppression of the mechanisms ensuring emergence and irritation of epileptic discharges. Nevertheless, effectiveness of surgical treatment fades off with time, which requires to further investigate the negative factors countering long-term post-surgery effect. In connection with this, a special attention should be paid to factors such as the presence of electroencephalography-verified epileptiform activity in postoperative period, repeated surgical intervention as well as prolonged epilepsy before surgery.

Low-frequency stimulation of corpus callosum suppresses epileptiform activity in the cortex through γ-aminobutyric acid type B receptor and slow afterhyperpolarization-mediated reduction in tissue excitability.

Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear. This study investigates the mechanisms underlying the antiepileptic effect in the cortex of LFS of the CC in coronal rodent brain slices. An invitro 4-aminopyridine (4-AP) seizure model of cortical seizures was generated. LFS stimulation parameters were optimized to provide the largest antiepileptic effect in the cortex when applied to the CC. Changes to tissue excitability and percent time spent seizing were measured due to LFS in artificial cerebrospinal fluid, 4-AP, and in the presence of various specific and nonspecific γ-aminobutyric acid type B (GABAB) and slow afterhyperpolarization (sAHP) antagonists. LFS significantly suppressed seizure activity in the cortex, with an optimal frequency of 5 Hz (76.5%). Tissue excitability during LFS reduces across a wide range of interstimulus intervals, with a maximum reduction at 200 ms. Notably, the tissue excitability remains depressed at 1000 ms. LFS, in the presence of GABAB antagonists, had diminished seizure reduction (<15%) and failed to reduce tissue excitability in the 50-400-ms range. Tissue excitability measured with paired pulses in the 600-1000-ms range was depressed in the presence of GABAB antagonists, suggesting a different antiepileptic mechanism was active. Upon administering sAHP antagonists, seizure reduction was once again diminished (<15%). Upon administration of both sAHP and GABAB antagonists, LFS failed to provide any meaningful seizure reduction (<5%). LFS of the CC provides an antiepileptic effect in the cortex with well-understood mechanisms and could be an alternative to surgical intervention for patients suffering from DRE.

WONOEP appraisal: The role of glial cells in focal malformations associated with early onset epilepsies.

Epilepsy represents a common neurological disorder in patients with developmental brain lesions, particularly in association with malformations of cortical development and low-grade glioneuronal tumors. In these diseases, genetic and molecular alterations in neurons are increasingly discovered that can trigger abnormalities in the neuronal network, leading to higher neuronal excitability levels. However, the mechanisms underlying epilepsy cannot rely solely on assessing the neuronal component. Growing evidence has revealed the high degree of complexity underlying epileptogenic processes, in which glial cells emerge as potential modulators of neuronal activity. Understanding the role of glial cells in developmental brain lesions such as malformations of cortical development and low-grade glioneuronal tumors is crucial due to the high degree of pharmacoresistance characteristic of these lesions. This has prompted research to investigate the role of glial and immune cells in epileptiform activity to find new therapeutic targets that could be used as combinatorial drug therapy. In a special session of the XVI Workshop of the Neurobiology of Epilepsy (WONOEP, Talloires, France, July 2022) organized by the Neurobiology Commission of the International League Against Epilepsy, we discussed the evidence exploring the genetic and molecular mechanisms of glial cells and immune response and their implications in the pathogenesis of neurodevelopmental pathologies associated with early life epilepsies.

A Clinical-Electrographic Profile of Neonatal Seizures and Their Etiologies in a Single Level III Neonatal Intensive Care Unit

Background: Seizures are the most frequent neurological emergency in neonatal period and can be associated with significant mortality and subsequent neuro-developmental disability if not recognized and managed early. Repaid identification of neonatal seizures and evaluation is critically required to identify and treat the underlying etiology. Clinicians face a major challenge in diagnosing and treating neonatal seizure because of inconspicuous clinical presentation, variable electro-clinical correlation. Assessing the combination of clinical presentation, etiological factors, different diagnostic tools, and treatments, can broaden the knowledge and understanding towards neonatal seizure providing better management and outcome. Objective: To study the characteristics of clinical and electrographic profile of neonatal seizure and the relations to their etiologies in neonatal intensive care unit. Methods: This is a descriptive cross sectional retrospective study of electronic health records with ICD- 10 diagnosis of neonatal seizure from birth to 28 days, who were admitted to neonatal intensive care unit at Sheikh Shakhbout Medical City between January 2020 to December 2021. Clinical data obtained including basic demographics: gender, gestational age, mode of delivery, birth weight, and Apgar score. Onset and type seizure, type of antiepileptic drugs administered, EEG findings, brain imaging, results of relevant laboratory tests and etiology of seizure were collected. Results: Total 31 neonates included in the study. Majority were male (71%), term (87%), and birth weight &gt;2,5 kg (90%). Seizure within 24 hours was 58% and semiology was focal clonic in 32% of patient. No events in EEG in 81% and 6% had electrographic seizure (n=2). 94 % were treated with anti-convulsant, 86% of them before EEG. The majority (86%) received phenobarbitone as 1st line treatment and 83% received monotherapy. Leading causes of seizure were HIE (48%) followed by Vascular causes (16%). Seizure within 24 hours caused mainly by HIE (61%) and 60% of neonates with vascular and all infectious and genetic causes had seizure after 24 hours. In vascular causes, (60%) presented with focal clonic seizure. 60% of Multifocal epileptiform activity seen in HIE whereas focal presented more in vascular patient (36%). In HIE cases, 53% had normal brain MRI and 47% were abnormal. All cases with vascular causes had diagnostic abnormal MRI. The majority of HIE cases (87%) and all vascular cases received monotherapy. Conclusion: In this descriptive study of neonatal seizure, certain demographic data, clinical and electrographic characteristics had established links to their etiologies. Clinical events captured during EEG with no electrographic seizure are classified as non-epileptic clinical phenomenon. Diagnostic utility of EEG is required in diagnosis of involuntary movements and avoid unnecessary anti-seizure medications. Understanding the clinical-electrographic profile of neonatal seizure helps in the early recognition of specific etiologies, allowing an early diagnosis by organized diagnostic approach and management.

Uncovering etiologic genes through whole exome sequencing in pediatric epilepsy: A case series from Thailand

Introduction Developmental and epileptic encephalopathy (DEE) is characterized by seizures that are difficult to control for a long time and affect development in children who are previously normal or delayed. Therefore, children with DEE should be diagnosed promptly because certain types of the disease respond well to specific medications. In developing countries with limited universal coverage for whole exome sequencing (WES), identifying key clinical features in this patient group will help us make more accurate selections for investigations. The purpose of this study was to determine the prevalence of WES and its common clinical features in children with epileptic encephalopathy. Methods Ten volunteers aged 0-15 years were diagnosed with epilepsy with two or more symptoms of drug-resistant epilepsy, developmental delays, and abnormal nervous system/or dysmorphic features, and their electroencephalogram (EEG) showed abnormal background or specific patterns of epileptiform discharges. These were subjected to WES for the standard &gt; 400 genes in the epilepsy panel. Results The established diagnosis was 4/10. Two known pathogenic variants, SCN2A and PCDH19. Two novel pathological variants, CHD2 and SCN1A. These are drug-resistant epilepsy, which is initially difficult to control and cannot stop antiseizure medications. Out of the 2/4 had moderate to severe intellectual disability. 3/4 had generalized epileptiform discharge activities. Conclusions This study showed a similar detection rate to that of a previous WES study. All the patients had difficult-to-treat epilepsy. For those who have not found abnormalities with the same clinical symptoms, further examinations using other methods should be conducted.

A spike is a spike: On the universality of spike features in four epilepsy models.

Frequency properties of the EEG characteristics of different seizure types including absence seizures have been described for various rodent models of epilepsy. However, little attention has been paid to the frequency properties of individual spike-wave complexes (SWCs), the constituting elements characterizing the different generalized seizure types. Knowledge of their properties is not only important for understanding the mechanisms underlying seizure generation but also for the identification of epileptiform activity in various seizure types. Here, we compared the frequency properties of SWCs in different epilepsy models. A software package was designed and used for the extraction and frequency analysis of SWCs from long-term EEG of four spontaneously seizing, chronic epilepsy models: a post-status epilepticus model of temporal lobe epilepsy, a lateral fluid percussion injury model of post-traumatic epilepsy, and two genetic models of absence epilepsy-GAERS and rats of the WAG/Rij strain. The SWCs within the generalized seizures were separated into fast (three-phasic spike) and slow (mostly containing the wave) components. Eight animals from each model were used (32 recordings, 104 510 SWCs in total). A limitation of our study is that the recordings were hardware-filtered (high-pass), which could affect the frequency composition of the EEG. We found that the three-phasic spike component was similar in all animal models both in time and frequency domains, their amplitude spectra showed a single expressed peak at 18-20 Hz. The slow component showed a much larger variability across the rat models. Despite differences in the morphology of the epileptiform activity in different models, the frequency composition of the spike component of single SWCs is identical and does not depend on the particular epilepsy model. This fact may be used for the development of universal algorithms for seizure detection applicable to different rat models of epilepsy. There is a large variety between people with epilepsy regarding the clinical manifestations and the electroencephalographic (EEG) phenomena accompanying the epileptic seizures. Here, we show that one of the EEG signs of epilepsy, an epileptic spike, is universal, since it has the same shape and frequency characteristics in different animal models of generalized epilepsies, despite differences in recording sites and location.

Exploration of epileptic networks in temporal lobe encephaloceles with stereotactic EEG: Electroclinical characteristics and surgical outcomes.

Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network. A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up. Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15-41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy-surgical outcomes were favorable, with 5/7 achieving Engel I outcomes. Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options. Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. Invasive monitoring with SEEG may help characterize the epileptogenic network and result in more optimal surgical outcomes.

Seizure recurrence following the first unprovoked seizure: Risk factors among children in UAE.

In a retrospective study of paediatric and adolescent patients in Abu Dhabi, UAE, who experienced their first unprovoked seizure between March 2016 and March 2020, with a minimum one-year follow-up, we identified significant risk factors associated with seizure recurrence. Among 317 patients, 96.2% experienced seizure recurrence, with the majority (68.8%) occurring within the first 6-month follow-up period. Notable risk factors for recurrence included focal seizures, symptomatic seizure causes, abnormal initial electroencephalogram (EEG) findings, abnormal brain magnetic resonance imaging results, and the presence of neurological disorders. Interestingly, the type of epileptiform activity in the initial EEG did not predict recurrence risk. Over a 3-year period, the overall recurrence risk was 98.4%, particularly higher in cases with symptomatic seizures compared to idiopathic (genetic) ones. These findings underscore the importance of vigilant monitoring, particularly in the early post-seizure follow-up period, and advocate for initial EEG assessments, especially in cases of remote symptomatic first unprovoked seizures.

Temporal Lobe Epilepsy with Bitemporal Interictal Epileptiform Discharges: Effects of Sleep and Wakefulness

Introduction. Independent bitemporal interictal discharges are often found in patients with temporal lobe epilepsy. The likelihood of registering epileptiform activity (EA) is higher during sleep. Assessment of bitemporal interictal epileptiform discharges (BIEDs) with various discharge predominance ratio is used for presurgical evaluation of epilepsy patients and prediction of surgical outcomes. Our objective was to determine the predominant side (PS) in patients with bitemporal epilepsy using the incidence of epileptiform discharges for each sleep stage. Materials and methods. We analyzed 45 recordings of 10–24 h long-term video-EEG monitoring (LTM) in patients with bitemporal EA. For each recording, the total incidence of EA (IEA) and EA incidence for wakefulness and for each sleep stage were calculated individually. We also assessed the discharge predominance index (DPI) as a ratio of IEA in the predominant and contralateral sides for the entire recording and for each sleep stage. Results. We observed an IEA increase with sleep deepening, with maximum values observed during N2 and N3 sleep stages. The minimum IEA values were recorded during REM sleep; nevertheless, most of the REM sleep discharges were detected on the PS. DPI values were the highest and the most stable during N2 and N3 stages. Conclusion. The findings of our study demonstrate an increase in DPI values with non-rapid eye movement (NREM) sleep deepening in patients with bitemporal localization of EA. Despite the protective effects of REM sleep (i.e., reducing the likelihood of EA), it may be pivotal in lateralization of EA in patients with BIEDs. The PS is generally determined by a higher DPI during N2 and N3 stages.

Chronobiological Spatial Clusters of Cortical Regions in the Human Brain.

We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs). High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us. We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2). This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.

Sensitivity of detecting interictal epileptiform activity using rapid reduced montage EEG

ObjectiveRapid EEG devices (REDs) have demonstrated substantial benefit regarding reduced time to performance of study and diagnosis in cases where urgent EEG is needed to evaluate patients for potentially revealing nonconvulsive status epilepticus and seizures. However, urgent EEG is also important in identifying cases regarding the need for initiation of antiseizure medication as well as triaging the use of continuous EEG monitoring. Some forms of REDs have a reduced montage (RRME) with electrode derivations that are one-half of standard recordings. This could impact spatial resolution and therefore potentially limit recovery of epileptiform abnormalities. MethodsIn this study we evaluated the use of the Ceribell® rapid response EEG system and compared it to conventional video EEG (CvEEG). After applying inclusion and exclusion criteria, a total of 20 subjects were included in our analysis. ResultsRRME was highly sensitive in detecting abundant and periodic discharges (p = 0.013) as well as discharges with a broad spatial distribution on CvEEG (p = 0.039). Sensitivity for detecting less prevalent discharges or those with more restricted spatial distribution was lower. SignificanceGiven the possibility of less frequent and more restricted epileptiform discharges eluding detection on RRME, we propose a protocol for the approach of using RRME and when to consider CvEEG when RRME is negative for epileptiform activity and highlight that urgent CvEEG may still be warranted following RRME.