Partial Seizures Research Articles

Customized GPT model largely increases surgery decision accuracy for pharmaco-resistant epilepsy

BackgroundTo develop an enhanced epilepsy diagnosis system by integrating an expert-informed ontology with a custom generative pre-trained transformer (GPT), validated by inferring possible seizure lateralization and localization using retrospective textual data from the pre-surgical assessments of patients with pharmaco-resistant epilepsy (PRE). MethodsWe developed an AI system for epilepsy diagnosis using Protégé with OWL/SWRL, integrating a knowledge base with seizure semiology, seizure types EEG descriptors, expert insights, and literature to pinpoint seizure locations. A customized GPT model was then tailored for specific diagnostic needs. Validated through 16 surgical cases, the system’s accuracy in seizure localization and the JSON (JavaScript Object Notation) Epilepsy Matcher’s term matching capabilities were confirmed against a Protégé-based knowledge base. ResultsA total of 117 patients with PRE underwent video-EEG monitoring at a single institution. However, only 16 of these patients received epilepsy surgery. The Protégé system achieved 75 % accuracy in diagnosing epilepsy from 16 cases using semiology, which increased to 87.5 % with EEG data. The Json Epilepsy Matcher further improved accuracy to 87.5 % with symptoms alone and 93.8 % when including EEG data, highlighting the benefits of applying GPT techniques. ConclusionsThis study highlights the efficacy of the JSON Epilepsy Matcher in improving seizure diagnosis accuracy. When combined with EEG data, it achieves a 93.8 % accuracy rate, suggesting a potential improvement in the practicality and generalizability of the original ontology expert system, boosting physicians’ confidence in confirming surgery and potentially sparing many children from prolonged suffering. This innovative approach not only improves diagnostic accuracy but also sets a precedent for future applications of AI in neurology

A universal method for seizure onset zone localization in focal epilepsy using standard deviation of spike amplitude

BackgroundPrecisely localizing the seizure onset zone (SOZ) is critical for focal epilepsy surgery. Existing methods mainly focus on high-frequency activities in stereo-electroencephalography, but often fail when seizures are not driven by high-frequency activities. Recognized as biomarkers of epileptic seizures, ictal spikes in SOZ induce epileptiform discharges in other brain regions. Based on this understanding, we aim to develop a universal algorithm to localize SOZ and investigate how ictal spikes within the SOZ induce seizures. MethodsWe proposed a novel metric called standard deviation of spike amplitude (SDSA) and utilized channel-averaged SDSA to describe seizure processes and detect seizures. By integrating SDSA values in specific intervals, the score for each channel located within SOZ was calculated. Channels with high SOZ scores were clustered as SOZ. The localization accuracy was asserted using area under the receiver operating characteristic (ROC) curve. Further, we analyzed early ictal signals from SOZ channels and investigated factors influencing their duration to reveal the seizure inducing conditions. ResultsWe analyzed data from 15 patients with focal epilepsy. The channel-averaged SDSA successfully detected all 28 seizures without false alarms. Using SDSA integration, we achieved precise SOZ localization with an average area under ROC curve (AUC) of 0.96, significantly outperforming previous methods based on high-frequency activities. Further, we discovered that energy of ictal spikes in SOZ was concentrated at a specific frequency distributed in [6, 12Hz]. Additionally, we found that the higher the energy per second in this frequency band, the faster ictal spikes could induce seizures. ConclusionThe SDSA metric offered precise SOZ localization with robustness and low computational cost, making it suitable for clinical practice. By studying the propagation patterns of ictal spikes between the SOZ and non-SOZ, we suggest that ictal spikes from SOZ need to accumulate energy at a specific central frequency to induce epileptic spikes in non-SOZ, which may have significant implications for understanding the seizure onset pattern.

Investigation of Clinical Features, EEG Findings, and Brain Imaging in Psychiatric Patients With Epilepsy at Razi Psychiatric Hospital

Objectives: This study aimed to assess the clinical features, Electroencephalography (EEG) findings, and brain imaging results in psychiatric patients diagnosed with epilepsy at Razi Psychiatric Hospital. Methods: This retrospective descriptive-analytical study was carried out on patients with epilepsy and psychiatric disorders admitted to Razi Psychiatric Hospital over two years. A total of 94 patient files seizure and epilepsy comorbidity, recorded in the hospital’s health information system (HIS), were reviewed. Data collection involved a demographic checklist and an epilepsy scale; the latter, developed by DiIorio, Colleen, et al., encompassed personal characteristics, mental disorders, epilepsy, and seizures. The Kruskal-Wallis and Mann-Whitney non-parametric tests were utilized to compare the mean scores of variables, with SPSS software, version 21 facilitating the analysis. Results: Out of 94 patients with seizure and epilepsy, 9.6% had focal seizure, 26.6% had generalized epilepsy, 36.1% had focal-generalized seizure, and 26.8% had unknown seizure. About 12% had a structural etiology, while the remaining 88% had an etiology that remained unidentified. Conclusion: The findings indicate that epilepsy, affecting individuals from adolescence through to old age, can lead to psychiatric disorders. For many patients, the etiology of their condition remains elusive, and EEG findings and brain imaging appear normal in the majority of cases.

Diaphragm relaxation causes seizure-related apnoeas in chronic and acute seizure models in rats.

Ictal central apnoea is a feature of focal temporal seizures. It is implicated as a risk factor for sudden unexpected death in epilepsy (SUDEP). Here we study seizure-related apnoeas in two different models of experimental seizures, one chronic and one acute, in adult genetically-unmodified rats, to determine mechanisms of seizure-related apnoeas. Under general anaesthesia rats receive sensors for nasal temperature, hippocampal and/or neocortical potentials, and ECG or EMG for subsequent tethered video-telemetry. Tetanus neurotoxin (TeNT), injected into hippocampus during surgery, induces a chronic epileptic focus. Other implanted rats receive intraperitoneal pentylenetetrazol (PTZ) to evoke acute seizures. In chronically epileptic rats, convulsive seizures cause apnoeas (9.9±5.3s; 331 of 730 convulsive seizures in 15 rats), associated with bradyarrhythmias. Absence of EEG and ECG biomarkers exclude obstructive apnoeas. All eight TeNT-rats with diaphragm EMG have apnoeas with no evidence of obstruction, and have apnoea EMGs significantly closer to expiratory relaxation than inspiratory contraction during pre-apnoeic respiration, which we term "atonic diaphragm". Consistent with atonic diaphragm is that the pre-apnoeic nasal airflow is expiration, as it is in human ictal central apnoea. Two cases of rat sudden death occur. One, with telemetry to the end, reveals a lethal apnoea, the other only has video during the final days, which reveals cessation of breathing shortly after the last clonic epileptic movement. Telemetry following acute systemic PTZ reveals repeated seizures and seizure-related apnoeas, culminating in lethal apnoeas; ictal apnoeas are central - in 8 of 35 cases diaphragms initially contract tonically for 8.5±15.0s before relaxing, in the 27 remaining cases diaphragms are atonic throughout apnoeas. All terminal apnoeas are atonic. Differences in types of apnoea due to systemic PTZ in rats (mainly atonic) and mice (tonic) are likely species-specific. Certain genetic mouse models have apnoeas caused by tonic contraction, potentially due to expression of epileptogenic mutations throughout the brain, including in respiratory centres, in contrast with acquired focal epilepsies. We conclude that ictal apnoeas in the rat TeNT model result from atonic diaphragms. Relaxed diaphragms could be particularly helpful for therapeutic stimulation of the diaphragm to help restore respiration.

Serum MicroRNAs as Predictors of Diagnosis and Drug-resistance in Temporal Lobe Epilepsy: A Preliminary Study.

Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy, and the current clinical diagnosis is based on EEG, clinical neurological history and neuroimaging findings. So far, there are no blood-based molecular biomarkers of TLE to support clinical diagnosis, despite the pathogenic mechanisms underlying TLE involving defects in the regulation of gene expression. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression. Recent studies show the feasibility of detecting miRNAs in body fluids; circulating miRNAs have emerged as potential clinical biomarkers in epilepsy, although the TLE miRNA profile needs to be addressed. Here, we analysed the diagnostic potential of 8 circulating miRNAs in sera of 52 TLE patients and 40 age- and sex-matched donor controls by RT-qPCR analyses. We found that miR-34a-5p, -106b-5p, -130a-3p, -146a-5p, and -19a-3p are differently expressed in TLE compared to control subjects, suggesting a diagnostic role. Furthermore, we found that miR-34a-5p, -106b-5p, -146a-5p and miR-451a could become prognostic biomarkers, being differentially expressed between drug-resistant and drug-responsive TLE subjects. Therefore, serum miRNAs are diagnostic and drug-resistance predictive molecules of TLE.

Epilepsy in children and anesthesia

Epilepsy, also called seizure disorder, is the most common childhood brain disorder in the United States. The aetiology of epilepsy in children is multifactorial with congenital, metabolic, infective, and problems associated with prematurity being common causes. Nearly 3 million Americans have epilepsy. About 450,000 of them are under 17 years old. About 1 in 200 children (0.5%) have epilepsy, a neurological condition where children have a predisposition to recurrent, unprovoked seizures. There are many different types of epilepsy, especially in infancy, childhood and adolescence. Epilepsy can be thought of in terms of either: the site of seizure origin in the brain (generalised or focal seizures), or the underlying cause. Genetic epilepsies (formerly called idiopathic or primary epilepsies) occur in an otherwise normal person and are due to a genetic predisposition to seizures. Some epilepsies are due to an underlying abnormality of the brain structure or chemistry (formerly called symptomatic or secondary epilepsies). Other epilepsies have no known cause. Epilepsy is commonly diagnosed in children and can be confused with other conditions. An accurate diagnosis is essential. A seizure is an excessive surge of electrical activity in the brain that can cause a variety of symptoms, depending on which parts of the brain are involved. Seizures can be provoked or unprovoked. Provoked seizures, caused by fever in a young child or severe hypoglycemia, are not considered to be forms of epilepsy. Unprovoked seizures have no clear cause but can be related to genetics or brain injury. When a child has two or more unprovoked seizures, epilepsy is often the diagnosis. Despite advances in antiepileptic medication therapy, a significant number of pediatric patients with epilepsy have seizures that are not well controlled. Antiepileptic medications interact with anesthetic agents, and common anesthetics can precipitate or suppress seizure activity. There are important pharmacokinetic and pharmacodynamic interactions between AEDs and drugs commonly used in anaesthesia. These affect both drug efficacy and the risk of seizure activity intraoperatively.

Person-Directed Ictal Pointing Gesture During a Focal Seizure: Intracranial EEG Correlation.

Person-Directed Ictal Pointing Gesture During a Focal Seizure: Intracranial EEG Correlation.

Determinants of health-related quality of life of patients with focal epilepsy: A systematic literature review.

Focal epilepsy can have significant negative impacts on a person's health-related quality of life (HRQoL). Although studies have been published on HRQoL in persons with focal epilepsy (PWFE), determinants of HRQoL have not been comprehensively examined. This systematic literature review (SLR) queried existing literature to identify aspects associated with HRQoL in PWFE without focus on resective epilepsy surgery, with an interest in identifying modifiable determinants for medical/nonmedical interventions. This SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches were conducted in PubMed and Google Scholar for articles published from January 1, 1900, to February 19, 2023, reporting on the association between HRQoL or employability and a range of demographic, psychosocial, or epilepsy-related factors and comorbidities in PWFE. A total of 879 abstracts were identified, with 126 manuscripts reviewed and 37 studies selected for inclusion that quantified the relationship between HRQoL and the variable of interest by multivariate (N = 21) or univariate only (N = 15) methods; 10 multivariate models also included univariate data. In adjusted models, the most commonly examined determinants of HRQoL included depression (n = 15/21), number of antiseizure medications (ASMs; n = 13/21), seizure frequency (continuous seizure count, n = 11/21; seizure freedom, n = 5/21), anxiety (n = 10/21), duration of disease (n = 9/21), and cognition (n = 9/21). Depression, anxiety, and cognition were frequently seen as significant contributors to HRQoL when studied (14/15 [93%], 9/10 [90%], and 7/9 [78%], respectively). Among concepts studied less frequently, ASM severity/adverse event burden was significant each time examined (in 5/19 studies). Attainment of seizure freedom and employability was significant 75% (n = 3/4) and 72% (n = 5/7) of the time, respectively. Poor HRQoL in PWFE can be attributed to a multitude of factors, including depression, anxiety, factors in disease management, and employability. An unmet need remains in addressing elements associated with poor HRQoL in this population.

Diagnostic and Therapeutic Challenges of Focal Cortical Dysplasia in Mali: A Case Report

Focal Cortical Dysplasias (FCDs) are a common cause of pharmaco-resistant epilepsy. FCDs are rare conditions, and their pathogenesis remains poorly understood. We report a 12-year-old patient seen in our clinic for focal onset epileptic seizures. Neurological examination and brain CT-scan were nearly normal. However, an electroencephalogram (EEG) revealed a slightly slow background rhythm with slow spikes in the medial and right parietal regions and a brain magnetic resonance imaging (MRI) showed a focal cortical thickening in the right parietal lobe with FLAIR hypersignal, indicating a focal cortical dysplasia. Ongoing seizures marked the disease course under antiepileptic polytherapy after 15 months of treatment. Keywords: Focal cortical dysplasia, pharmaco-resistant epilepsy, Mali, Africa.

Emergent responsive neurostimulation in pediatric super-refractory epilepsia partialis continua.

Focal status epilepticus, particularly the motor variant of epilepsia partialis continua (EPC), is a rare condition characterized by near-continuous, chronic focal motor seizures, and associated with poor outcomes. Medications, including anesthetics, are often unsuccessful. Surgical resection can result in motor deficits. We report a medically complex pediatric case of super-refractory EPC that was successfully managed with combined focal resection and responsive neuromodulation. This case introduces neuromodulation as a treatment modality for this challenging condition.

A multicenter, cross-sectional analysis to assess the safety and usage pattern of brivaracetam in the management of partial-onset seizure with BAEs-BREEZE study: A post-hoc analysis.

Brivaracetam (BRV), a third-generation anti-seizure medication (ASM) offers strong conformational receptor domain binding, faster blood brain barrier (BBB) permeability and better tolerability making it potential therapeutic option as an initial line or initial line add-on strategy for focal onset seizure (FoS). The following study was planned to further understand the role and relevance of BRV in the real world settings of India. This was a multicentric, cross-sectional, and non-interventional study conducted in patients with FoS across India. The study was approved by central independent ethics committee. Descriptive and analytical statistics employed using SPSS version 29.0.1.0. Per protocol (PP) analysis included 8479 eligible patients from 1069 sites, gender; 5771 (68.06%) male and 2708 (31.94%) female with mean age 41.21 ± 12.74 years. Total 8019 (94.57%) patients had FoS and 460 (5.43%) patients had focal to bilateral tonic-clonic seizures (FBTCs). In FoS, 4105 (51.19%) patients switched from LEV to BRV whereas 3914 (48.81%) switched from other ASMs to BRV. BAEs accounted for 2059 (50.16%) patients in LEV to BRV switch versus 133 (3.39%) in other ASM to BRV switch. Post switch, LEV-associated BAEs reduced irrespective of being used as monotherapy 85.65% (p < 0.001) or as an adjuvant therapy 83.71% (p < 0.001) at BRV dosage of 50 to 100 mg BID. This RWE showed the utility of BRV as mono component as an initial add-on strategy in FoS cases. BRV remains a pertinent therapeutic choice for FoS for the treatment naïve and/or BAE cases. Exposure of LEV leads to considerable BAEs compared to patients without LEV exposure. Patients who switched to BRV due to LEV-induced BAEs significantly improved tolerability with BRV irrespective being used as monotherapy or as adjuvant therapy. Current study was planned to understand the clinical role and relevance of third-generation anti-seizure medication (ASM), brivaracetam (BRV) in the real world settings of India. Outcome of the study highlighted that BRV is an emerging, potential and safe ASM treatment option for epilepsy in Indian context. Many patients with epilepsy who are not able to tolerate the other ASM including levetiracetam (LEV) primarily due to behavioral side effects improves tolerability post switch to BRV, additionally results are consistent either BRV being used as an adjuvant therapy or as monotherapy therapy.

High-resolution multimodal profiling of human epileptic brain activity via explanted depth electrodes.

The availability and integration of electrophysiological and molecular data from the living brain is critical to understand and diagnose complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus on epilepsy patients could enable the integration of such multimodal data. Here, we report MoPEDE (Multimodal Profiling of Epileptic Brain Activity via Explanted Depth Electrodes), a method that recovers extensive protein-coding transcripts, including cell-type markers, DNA methylation and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function. We find gene expression gradients that correspond with the neurophysiology-assigned epileptogenicity index but also outlier molecular fingerprints in some electrodes, potentially indicating seizure generation or propagation zones not detected during electroclinical assessments. Additionally, we identify DNA methylation profiles indicative of transcriptionally permissive or restrictive chromatin states and SEEG-adherent differentially expressed and methylated genes not previously associated with epilepsy. Together, these findings validate that RNA profiles and genome-wide epigenetic data from explanted SEEG electrodes offer high-resolution surrogate molecular landscapes of brain activity. The MoPEDE approach has the potential to enhance diagnostic decisions and deepen our understanding of epileptogenic network processes in the human brain.

Anxiety and depression in people with epilepsy during andone year after the COVID-19 pandemic.

Compare the prevalence and severity of anxiety and depression among people with epilepsy (PWE) evaluated by telemedicine during the initial stages of the COVID-19 pandemic and follow up on their status 15 months later. We conducted a prospective, observational, and analytical study at the Epilepsy Clinic of the National Institute of Neurology and Neurosurgery (NINN) in Mexico City during the COVID-19 pandemic. HADS-A and HADS-D instruments were administered to adult patients diagnosed with epilepsy, initially through telemedicine and later through in-person visits or phone calls after one year. A sample of 115 patients was obtained, with 62.5% being women. The mean age of the patients was 33.6 years (± 12), and the mean age of epilepsy onset was 16.82 years (± 13.82). The majority of patients had focal epilepsy (78.3%), and only 42% reported being seizure-free. The results from the HADS-A scale showed that 48.69% of the patients had anxiety. On the HADS-D scale, 29.56% of the patients were found to have depression. At follow-up, the HADS-A results indicated that 50.64% of the patients had anxiety, and the HADS-D results showed that 36.36% had depression. An analysis of associations between sociodemographic or clinical variables and the presence of anxiety and/or depression in PWE revealed no statistically significant results, except for the clinical variable of patients taking anxiolytic or antidepressant medications during the assessment. These patients had lower HADS-A and HADS-D scores, with a statistically significant p-value of 0.0001. Comparing these findings with a previously published paper by our group showed a significant increase in both depression and anxiety, which were already prevalent in the earlier study. In conclusion, PWE exhibited high levels of anxiety and depression during and one year after the pandemic, despite receiving appropriate treatment. These symptoms, present before the pandemic, have been further exacerbated and continue to persist. This study examined anxiety and depression in patients with epilepsy (PWE) during the COVID-19 pandemic at the National Institute of Neurology and Neurosurgery in Mexico. Using the HADS-A and HADS-D scales, 115 patients were assessed over a year. Results showed that 48.69% had anxiety and 29.56% had depression, with both increasing to 50.64% and 36.36%, respectively, after one year. The only significant finding was that patients on anxiolytic or antidepressant medication had lower scores for anxiety and depression. The study concludes that anxiety and depression in PWE worsened during the pandemic and persisted despite treatment.

Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures.

Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere. In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp). The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp. Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.

Level 4 seizure monitoring unit admissions are associated with reduced long-term health care costs.

This study was undertaken to determine whether admission to dedicated seizure monitoring units (SMUs) result in reduced health care use (HCU). This was a retrospective open cohort study covering the years 2010-2018 of patients residing in Alberta, Canada, who were referred to the Calgary Comprehensive Epilepsy Program and admitted to a level 4 SMU. Patients were required to have ≥3 years pre- and postadmission follow-up. The outcome was the change in trajectory of composite HCU (primary care, specialist outpatient visits, emergency department visits, and hospitalizations) for the 3 years prior to and 3 years following SMU admission using the point of admission as the "index date." Secondary outcomes were HCU limited to specific settings. We excluded the first 30 days following the point of admission to mitigate the confounding admission would have on the postadmission HCU trajectory. We used adjusted restricted maximum likelihood linear and nonlinear effects models to determine trajectories expressed as Canadian dollars. A total of 315 of 600 (53%) patients met eligibility criteria. Mean age was 40 years (SD = 17.4), 176 (56%) were female, 220 (70%) had focal epilepsy, and 60 (19%) had functional seizures or physiologic seizure mimics without epilepsy as adjudicated by the attending physician at the point of discharge. Mean per person health care costs increased by CAD$341.28 (95% confidence interval [CI] = -25.17 to 707.74) for each successive 6-month interval prior to SMU admission (p = .07). Following admission, mean per person costs decreased by CAD$802.34 (95% CI = 699.62-905.06, p < .001) for each successive 6-month interval up to 3 years postdischarge. Similar trends were noted for primary and specialist care, emergency department, admitted care, and when nonlinear models were applied. Admission to an SMU is associated with significant and enduring declines in HCU. Each 6-months following discharge overall HCU declined by a mean of CAD$802.34 and acute inpatient, emergency department, and outpatient physician interactions declined by 25%, 26%, and 18% respectively. Comprehensive epilepsy care not only reduces morbidity and mortality but also reduces cost.

Interictal EEG spikes increase perfusion in low-grade epilepsy-associated tumors: a pediatric arterial spin labeling study.

Arterial spin labeling (ASL), a noninvasive magnetic resonance (MRI) perfusion sequence, holds promise in the presurgical evaluation of pediatric lesional epilepsy patients, including those with low-grade epilepsy-associated tumors (LEATs). The interpretation of ASL-derived perfusion patterns, however, presents challenges. Our study aims to elucidate these perfusion changes in children with LEATs, exploring their correlations with clinical, electroencephalography (EEG), and anatomical MRI findings. Our cohort included 15 children with LEAT-associated focal lesional epilepsy who underwent single-delay pseudo-continuous ASL imaging; eight were imaged under sedation. We assessed perfusion images both qualitatively and quantitatively, focusing on LEAT-related perfusion changes, as indicated by the asymmetry index (AI) and regional cerebral blood flow (rCBF). ASL revealed LEAT-related perfusion changes in all but two patients: 12 LEATs were hypoperfused and one was hyperperfused relative to the contralateral brain parenchyma (CBP). LEATs showed significantly lower perfusion compared to CBP (median: 38.7 vs. 59.1mL/100g/min for LEAT and CBP, respectively; p value = 0.004, Wilcoxon-Mann-Whitney), regardless of sedation. Notably, elevated AI and rCBF values correlated with interictal spikes on EEG (median: -0.008 and 0.84 vs -0.27 and 0.58, respectively), but not to other clinical, EEG, or MRI variables (p value = 0.036, Wilcoxon-Mann-Whitney). By highlighting the connection between LEAT and brain perfusion, and by correlating perfusion characteristics and epileptogenicity, our research enhanced our understanding of pediatric epilepsy associated with LEATs. Also, by proving the robustness of these findings to sedation we confirmed the importance of adding ASL to epilepsy protocols to as a valuable tool to supplement anatomical imaging.

Multicentre analysis of seizure outcome predicted by removal of high frequency oscillations.

In drug-resistant focal epilepsy, planning surgical resection may involve presurgical intracranial EEG recordings (iEEG) to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. Eight international epilepsy centres recorded iEEG during the patients' pre-surgical evaluation. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis we applied a fully automated definition of HFO which was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the "HFO area". After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990). We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with completely resected HFO area were more likely to achieve seizure freedom compared to those without (OR 2.61 CI [1.15-5.91], P = 0.02). Among seizure free patients, the HFO area was completely resected in 31 and was not completely resected in 43. Among patients with recurrent seizures, the HFO area was completely resected in 14 and was not completely resected in 58. When predicting seizure freedom, the negative predictive value of the HFO area (68% CI [52-81]) was higher than that for the resected volume as predictor by itself (51% CI [42-59], P = 4e-5). The sensitivity and specificity for complete HFO area resection were 0.88 CI [0.72-0.98] and 0.39 CI [0.25-0.54] and the area under the curve was 0.83 CI [0.58-0.97], indicating good predictive performance. In a blinded cohort study from independent epilepsy centres, applying a previously validated algorithm for HFO marking without the need of adjusting to new datasets allowed us to validate the clinical relevance of HFOs to plan the surgical resection.

Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Rasmussen encephalitis (RE) is a rare and progressive form of chronic encephalitis that typically affects one hemisphere of the brain and primarily occurs in pediatric individuals. The current study aims to narratively review the literature about RE, including historical information, pathophysiology, and management of this condition. RE often occurs in individuals with normal development, and it is estimated that only a few new cases are identified each year in epilepsy centers. Approximately 10% of cases also occur in adolescents and adults. The hallmark feature of RE is drug-resistant focal seizures that can manifest as epilepsia partialis continua. Also, patients with RE usually develop motor and cognitive impairment throughout the years. Neuroimaging studies show progressive damage to the affected hemisphere, while histopathological examination reveals T-cell-dominated encephalitis with activated microglial cells and reactive astrogliosis. The current therapy guidelines suggest cerebral hemispherotomy is the most recommended treatment for seizures in RE, although significant neurological dysfunction can occur. Another option is pharmacological management with antiseizure medications and immunomodulatory agents. No significant progress has been made in understanding the pathophysiology of this condition in the last decades, especially regarding genetics. Notably, RE diagnosis still depends on the criteria established by Bien et al., and the accuracy can be limited and include genetically different individuals, leading to unexpected responses to management.

Deciphering temporal gene expression dynamics during epilepsy development using a rat model of focal neocortical epilepsy.

Epilepsy involves significant changes in neural cells during epileptogenesis. Although the molecular mechanism of epileptogenesis remains obscure, changes in gene regulation play a crucial role in the evolution of epilepsy. This study aimed to compare changes in a subset of specific genes during epilepsy development, focusing on the period after the first spontaneous seizure, to identify critical time windows for targeting different regulators. Using a rat model of acquired focal neocortical epilepsy induced by tetanus toxin, we characterized gene expression at acute, subacute, and chronic stages (48-72 h, 2 weeks, and 30 days after first spontaneous seizure, respectively), focusing on genes' potential contribution to epilepsy progression. We observed dynamic changes in the expression of these genes throughout the period after the first spontaneous seizure. Astrocytic reactions primarily occur early, before epilepsy is well established. Changes in Mtor (mammalian target of rapamycin) and Rest (repressor element 1 silencing transcription factor) signaling pathways are highly dynamic and correlated with the progression of epilepsy development. Ccl2 (chemokine C-C-motif ligand) is upregulated at the chronic stage, indicating activation of the neuroinflammatory pathway. Finally, Gabra5 (γ-aminobutyric acidergic signaling) is downregulated at the late stage after epilepsy is established. Surprisingly, changes in the expression of specific genes are linked to the time since the first seizure, rather than seizure frequency or duration. These results suggest that the regulation of specific genes is essentially stage-dependent during the development of epilepsy, highlighting the importance of targeting specific genes at appropriate stages of epilepsy development.

Peri-ictal yawning: A potential lateralizing sign in temporal lobe epilepsy.

The primary objective of this retrospective analysis was to evaluate the incidence and lateralization value of peri-ictal yawning (PY) in people with temporal lobe epilepsy (TLE). PY has only occasionally been reported as a manifestation of focal epilepsy. We aimed to determine whether PY could serve as an indicator to help lateralize seizure onset during epileptic seizures. Among 236 consecutive TLE patients admitted for video-EEG monitoring, we analyzed the clinical characteristics, along with scalp video-EEG, magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), Wada test, and stereo EEG (SEEG) in patients with PY. Among the 236 patients, 26 (11.0%) exhibited PY, and 36 of 1018 recorded seizures (3.5%) were associated with PY. Of the 26 patients with PY, 19 (73.1%) had non-dominant TLE, while 7 (26.9%) had dominant TLE. The majority of these patients presented with staring, arrest, and automatisms during their seizures with accompanying vegetative signs. PY occurred either during the ictal or postictal phase in all patients. Exception for 10 seizures (10/36, 27.8%) at the early stage (less than 25% total duration), PY was primarily linked to the late ictal and postictal phases. Surgical intervention was performed in 12 patients, 9 of whom (75%) achieved seizure freedom (Engel class I), with 7 of these 9 (77.8%) having non-dominant TLE. Yawning is a physiological phenomenon typically not associated with epilepsy. The present series suggests that PY is relatively uncommon in TLE, but may represent a rare vegetative sign, particularly in cases with non-dominant TLE. Further investigation with a larger cohort of surgically confirmed cases and using intracranial EEG is essential to deepen our understanding of this phenomenon. Yawning is a typical physiological response that is generally not linked to epilepsy. However, it can occasionally indicate seizure activity, particularly in TLE. PY happens more often observed in non-dominant TLE and usually occurs in the later stages of a seizure or just after it. It may hold potential as a lateralizing marker in TLE.