An end-to-end deep learning pipeline to derive blood input with partial volume corrections for automated parametric brain PET mapping.

Dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (dFDG-PET) for human brain imaging has considerable clinical potential, yet its utilization remains limited. A key challenge in the quantitative analysis of dFDG-PET is characterizing a patient-specific blood input function, traditionally reliant on invasive arterial blood sampling. This research introduces a novel approach employing non-invasive deep learning model-based computations from the internal carotid arteries (ICA) with partial volume (PV) corrections, thereby eliminating the need for invasive arterial sampling. We present an end-to-end pipeline incorporating a 3D U-Net based ICA-net for ICA segmentation, alongside a Recurrent Neural Network (RNN) based MCIF-net for the derivation of a model-corrected blood input function (MCIF) with PV corrections. The developed 3D U-Net and RNN was trained and validated using a 5-fold cross-validation approach on 50 human brain FDG PET datasets. The ICA-net achieved an average Dice score of 82.18% and an Intersection over Union of 68.54% across all tested scans. Furthermore, the MCIF-net exhibited a minimal root mean squared error of 0.0052. The application of this pipeline to ground truth data for dFDG-PET brain scans resulted in the precise localization of seizure onset regions, which contributed to a successful clinical outcome, with the patient achieving a seizure-free state after treatment. These results underscore the efficacy of the ICA-net and MCIF-net deep learning pipeline in learning the ICA structure's distribution and automating MCIF computation with PV corrections. This advancement marks a significant leap in non-invasive neuroimaging.

Treating Seizures and Improving Newborn Outcomes for Infants with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Continuous electroencephalographic monitoring is recommended given high rates of subclinical seizures. Prompt diagnosis and treatment of seizures may improve neurodevelopmental outcomes. International League Against Epilepsy guidelines indicate that (1) phenobarbital remains the first-line treatment of neonatal seizures and (2) early discontinuation of antiseizure medications following resolution of acute provoked seizures, and prior to discharge home, is recommended. Long-term follow-up of these infants is necessary to screen for postneonatal epilepsy and support neurodevelopment.

Investigating current clinical opinions in stereoelectroencephalography-informed epilepsy surgery.

OBJECTIVE: Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions. METHODS: We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders. RESULTS: A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis. SIGNIFICANCE: This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.

Vagus nerve stimulation in lesional and Non-Lesional Drug-Resistant focal onset epilepsies.

PURPOSE: Drug-resistant epilepsy (DRE) affects one-third of patients with focal epilepsy. A large portion of patients are not candidates for epilepsy surgery, thus alternative options, such as vagus nerve stimulation (VNS), are proposed. Our objective is to study the effect of vagus nerve stimulation on lesional versus non-lesional epilepsies. METHODS: This is a retrospective cohort study in a single center in London, Ontario, which includes patients with DRE implanted with VNS, implanted between 1997-2018 and the date of analysis is December 2023. PARTICIPANTS: Patients implanted with VNS were classified by lesional (VNS-L) and non-lesional (VNS-NL) based on their MRI head findings. We further subdivided the VNS groups into patients with VNS alone versus those who also had additional epilepsy surgeries. RESULTS: A total of 29 patients were enrolled in the VNS-L, compared to 29 in the VNS-NL. The median age of the patients in the study was 31.8 years, 29.31 % were men (N = 17). 41.4 % (n = 12) of the patients were VNS responders (≥50 % seizure reduction) in the VNS-L group compared to 62.0 % (n = 18) in the VNS-NL group (p = 0.03). When other epilepsy surgeries were combined with VNS in the VNS-L group, the median rate of seizure reduction was greater (72.4 (IQR 97.17-45.88) than the VNS-NL group 53.9 (IQR 92.22-27.92); p = 0.27). CONCLUSIONS: VNS is a therapeutic option for patients with lesional epilepsy, with slightly inferior results compared to patients with non-lesional epilepsy. Patients implanted with VNS showed higher seizure reduction rates if they had previous epilepsy surgeries. This study demonstrates that VNS in lesional epilepsies can be an effective treatment.

Dexamethasone attenuates low-frequency brainwave disturbances following acute seizures induced by pentylenetetrazol in Wistar rats.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Two-year mortality and seizure recurrence following status epilepticus in Auckland, New Zealand: A prospective cohort study.

PURPOSE: To document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE). METHODS: Patients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes. RESULTS: We identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence. CONCLUSIONS: All-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life.

Can intravenous lorazepam prevent postictal generalized EEG suppression? A case report.

Background: Postictal generalized electrographic suppression (PGES) may be considered an electrophysiological marker associated with an increased risk of sudden unexplained death in epilepsy (SUDEP). Case Presentation: A case study is presented whereby a young man with focal to bilateral tonic-clonic seizures exhibited PGES after two spontaneously-aborted seizures; yet, after a third benzodiazepine-aborted seizure, PGES was absent. Conclusion: This suggests that acutely administered benzodiazepines may offer direct anti-suppressive effects to prevent PGES, potentially reducing SUDEP risk.

Prevalence of COVID-19 neurological manifestations in patients referred to the Golestan Hospital in Ahvaz between March 2020 to the March 2023.

Due to the abundance of ACE2 receptors in nervous system cells, the SARS-CoV-2 virus can cause damage to this system. This study aims to examine the prevalence of neurological symptoms in COVID-19 patients. In this cross-sectional observational study, 75 COVID-19 positive patients admitted to Golestan Hospital's neurology department in Ahvaz, Iran, from March 2020 to March 2023, were investigated. Neurological clinical symptoms were categorized into three groups: central nervous system, peripheral, and muscular symptoms. The relevant information was collected from patient files, including medical history, imaging data, and laboratory test results. Statistical analysis was performed using SPSS software, employing the rank-biserial correlation coefficient (r), Mann-Whitney U tests, Phi correlation, Cramer's V, and Kendall's Tau to evaluate the prevalence and significance of neurological symptoms. The most common clinical symptoms observed were hemiparesis, dysarthria, Central Facial Palsy (CFP), ataxia, and nausea, respectively. Among these symptoms, headaches (p = 0.001), seizures (p = 0.024), and nausea (p = 0.046) were found to be more prevalent in younger patients. Additionally, a significant relationship was identified between the level of serum Creatine phosphokinase (CPK) and seizures (p = 0.024), with lower levels observed in individuals with vomiting (p = 0.024), and higher levels observed in individuals with CFP (p = 0.040). This study highlights that patients with COVID-19 may experience serious neurological symptoms. The clinical spectrum and range of neurological symptoms associated with COVID-19 were found to be diverse and extensive, emphasizing the importance of considering this infection as a potential cause of neurological disorders.

SaE-GBLS: an effective self-adaptive evolutionary optimized graph-broad model for EEG-based automatic epileptic seizure detection.

Introduction: Epilepsy is a common neurological condition that affects a large number of individuals worldwide. One of the primary challenges in epilepsy is the accurate and timely detection of seizure. Recently, the graph regularized broad learning system (GBLS) has achieved superior performance improvement with its flat structure and less time-consuming training process compared to deep neural networks. Nevertheless, the number of feature and enhancement nodes in GBLS is predetermined. These node settings are also randomly selected and remain unchanged throughout the training process. The characteristic of randomness is thus more easier to make non-optimal nodes generate, which cannot contribute significantly to solving the optimization problem. Methods: To obtain more optimal nodes for optimization and achieve superior automatic detection performance, we propose a novel broad neural network named self-adaptive evolutionary graph regularized broad learning system (SaE-GBLS). Self-adaptive evolutionary algorithm, which can construct mutation strategies in the strategy pool based on the experience of producing solutions for selecting network parameters, is incorporated into SaE-GBLS model for optimizing the node parameters. The epilepsy seizure is automatic detected by our proposed SaE-GBLS model based on three publicly available EEG datasets and one private clinical EEG dataset. Results and discussion: The experimental results indicate that our suggested strategy has the potential to perform as well as current machine learning approaches.

A scheme combining feature fusion and hybrid deep learning models for epileptic seizure detection and prediction.

Epilepsy is one of the most well-known neurological disorders globally, leading to individuals experiencing sudden seizures and significantly impacting their quality of life. Hence, there is an urgent necessity for an efficient method to detect and predict seizures in order to mitigate the risks faced by epilepsy patients. In this paper, a new method for seizure detection and prediction is proposed, which is based on multi-class feature fusion and the convolutional neural network-gated recurrent unit-attention mechanism (CNN-GRU-AM) model. Initially, the Electroencephalography (EEG) signal undergoes wavelet decomposition through the Discrete Wavelet Transform (DWT), resulting in six subbands. Subsequently, time-frequency domain and nonlinear features are extracted from each subband. Finally, the CNN-GRU-AM further extracts features and performs classification. The CHB-MIT dataset is used to validate the proposed approach. The results of tenfold cross validation show that our method achieved a sensitivity of 99.24% and 95.47%, specificity of 99.51% and 94.93%, accuracy of 99.35% and 95.16%, and an AUC of 99.34% and 95.15% in seizure detection and prediction tasks, respectively. The results show that the method proposed in this paper can effectively achieve high-precision detection and prediction of seizures, so as to remind patients and doctors to take timely protective measures.

Intranasal Versus Buccal Versus Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Patients: A Randomized Controlled Trial.

BACKGROUND: Benzodiazepines are the recommended first-line treatment of acute seizures. We wished to compare the efficacy, side effects, and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children at homes and in emergency room (ER). METHODS: A prospective, randomized, controlled trial was performed in children aged one month to 17 years with acute seizures lasting longer than five minutes. The primary end point was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. RESULTS: In the home group, 67 patients received midazolam via buccal route, 60 via intranasal route, and 69 via intramuscular route, whereas in the ER group, 37 patients received buccal, 34 received intranasal, and 34 received intramuscular midazolam. The primary end point was achieved in 94.2% and 85.3% after intramuscular midazolam in the home and ER groups, respectively. The intranasal midazolam was successful in stopping seizures in 93.3% in the home group and 88.2% in the ER group. The buccal route was effective in 91% in the home group and 78.4% in the ER group. There were no significant differences in efficacy between all groups (P = 0.763 and P = 0.509) among the home and ER groups, respectively. There were no significant cardiorespiratory events in all groups. CONCLUSIONS: Intramuscular, intranasal, and buccal doses of midazolam resolved most seizures in prehospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of midazolam. Intranasal route showed the highest satisfaction rate among caregivers.

Non epileptiform abnormal neurologic signs in newborns following in-utero psychotropic medication exposure.

BACKGROUND: Post natal adaptation syndrome is well reported but early presentation of neurological symptoms severe enough to warrant detailed neurological work up is rare. Our aim was to evaluate and describe abnormal early neurological symptoms in infants following in-utero exposure to a varying combination of selective serotonin uptake inhibitor medication and other psychotropic medications, with negative seizure work-up. METHOD: Descriptive case series of infant exposed to selective serotonin uptake inhibitor medication and other psychotropic medications, presenting with early neurologic signs and symptoms within the first 24 hours of life concerning for seizures, who underwent an extensive neurologic evaluation. RESULTS: Five infants met criteria. Infant #1 : 39-weeks gestational age (GA), with escitalopram, clonazepam, gabapentin, methadone exposure, presented with generalized hypertonia and intermittent back-arching. #2 : 40-weeks GA with escitalopram and hydroxyzine exposure, with bilateral arm stiffening and sucking mouth movements. #3 : 34-weeks GA with fluoxetine, quetiapine and clonazepam exposure, presented with decerebrate posturing. #4 : 38-weeks GA with fluoxetine, clonazepam, clonidine, quetiapine and gabapentin exposure, presented with asynchronous tremoring of all extremities. #5 : 35-weeks GA with citalopram, quetiapine exposure, presented with increased tone and posturing of upper extremities. Electroencephalogram was negative for seizures in all infants. CONCLUSION: In-utero exposure to selective serotonin uptake inhibitor medication, especially in combination with other psychotropic medications, may be associated with significant abnormal neurological symptoms, which may not represent true seizures.

Efficacy and safety of 12-hour versus 24-hour magnesium sulfate in management of patients with pre-eclampsia and eclampsia: a systematic review and meta-analysis.

INTRODUCTION: Magnesium sulfate is the most utilized anticonvulsant for treating patients with eclampsia and pre-eclampsia. The purpose of this study is to determine whether the 12-h regimen of magnesium sulfate outweighs the 24-h regimen in both efficacy and safety in the management of patients with mild or severe pre-eclampsia and eclampsia. METHODS: We searched six electronic databases: PubMed, Scopus, Web of Science, Cochrane Library, Ovid, and Google Scholar. This search was conducted to yield any studies that were published until 15 January 2023. We did the statistical analysis plan by Review Manager Software version 5.4. RESULTS: We included 13 randomized control trials with 2813 patients in this systematic review. Our meta-analysis revealed that there were no statistically significant differences between the 12-h regimen of the magnesium sulfate group and the 24-h regimen of the magnesium sulfate group in our outcome of interest: occurrence of seizure (RD: -0.00, 95% CI [-0.01, 0.00], P = 0.56), diminished deep tendon reflexes (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.80), respiratory depression (RD: -0.00, 95% CI [-0.02, 0.01], P = 0.57), and pulmonary edema (RD: -0.00, 95% CI [-0.01, 0.01], P = 0.85). CONCLUSION: Our study showed no statistically significant difference in effectiveness and toxicity risk between the 12-h and 24-h regimens.

EEG-fMRI in awake rat and whole-brain simulations show decreased brain responsiveness to sensory stimulations during absence seizures.

In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and-wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures. This study aimed to investigate responsiveness to visual and somatosensory stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established rat model for absence epilepsy. Animals were imaged under non-curarized awake state using a quiet, zero echo time, functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole-brain hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to explain the changes of neural responsiveness to visual stimulation between states. During a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In the cortex, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The mean-field simulation revealed restricted propagation of activity due to stimulation and agreed well with fMRI findings. Results suggest that sensory processing is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.

Successful Diagnosis of Neuroleptic Malignant Syndrome in an Unconscious Patient Using Amplitude-Integrated Electroencephalography: A Case Report.

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening medical condition often characterized by altered consciousness and clinical features resembling seizures. This case report presents a unique and successful diagnosis of NMS in an unconscious patient with an unknown medical history. We demonstrate the potential utility of amplitude-integrated electroencephalography (aEEG) as a valuable tool for the differential diagnosis of seizure-like medical conditions, including NMS. The application of aEEG allowed for early diagnosis and prompt initiation of appropriate treatment, potentially contributing to improved patient outcomes.

Foramen ovale electrode investigation in the era of SEEG: Results and a reappraisal.

INTRODUCTION: Patients with medication-resistant disabling epilepsy should be considered for potential epilepsy surgery. If noninvasive techniques are unable to identify the location of the seizure onset zone (SOZ), it becomes necessary to consider intracranial investigations. Stereo-electroencephalography (SEEG) is currently the preferred method for such monitoring, however foramen ovale (FO) electrodes offer a less invasive alternative that may be suitable in certain situations. Previous studies have demonstrated the effectiveness of FO electrodes in suspected mesial temporal epilepsy, nevertheless, increased experience with FO electrode use could further enhance their safety and efficacy. Therefore, we conducted an analysis of recent FO electrode investigations to assess their utility in surgical decision making, post resection outcomes, and complication rates. METHODS: We conducted a retrospective analysis of 61 patients who underwent FO placement at Mass General Brigham between 2009 and 2020. Patient and seizure characteristics, preoperative investigation data, and seizures outcomes were collected. In addition, identified predictors of FO utility using logistic regression. RESULTS: A total of 61 patients were identified. FO evaluation localized the SOZ in 56 % of patients. Complications were encountered in 1.6 % of patients. Subsequent surgical resection was pursued by 49 % of patients, with 56 % becoming seizure free, and 67 % having favorable seizure outcomes at last follow-up. Multivariate analysis identified younger patients with a higher number of preoperative ASMs as more likely to undergo subsequent treatment, however, these features were not predictive features of SOZ localization, seizure freedom, or favorable seizure outcomes. In patients with bitemporal or cross-over onsets on scalp EEG, FO was able to identify the SOZ in 79 %, whereas in patients with discordant or unclear onset, the rates were 71 % and 45 %, respectively. CONCLUSION: In a contemporary cohort, FO electrode placement had a low complication rate and a high utility primarily in cases of unclear laterality of mesial temporal onsets or discordance between scalp EEG and other pre-FO investigation data in cases of suspected mesial temporal onsets.

Resolution of anti-LGI1-associated autoimmune encephalitis in a patient after treatment with efgartigimod.

BACKGROUND: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. CASE DESCRIPTION: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. CONCLUSIONS: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Arbidol, an antiviral drug, identified as a sodium channel blocker with anticonvulsant activity.

BACKGROUND AND PURPOSE: Sodium channel blockers (SCBs) have traditionally been utilized as anti-seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models. EXPERIMENTAL APPROACH: Patch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice. KEY RESULTS: Arbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain-of-function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine-induced status epilepticus model. CONCLUSIONS AND IMPLICATIONS: Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs.

Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.