Ictal Events Research Articles

Epilepsy adverse events post vaccination

Aim: Seizure and epilepsy adverse events (AEs) can occur following vaccination. For epilepsy AEs, they are generally expected to only occur at background population frequencies without associations with immunizations. The Vaccine AEs Reporting System (VAERS) collects a subset of AEs experienced by vaccinees, including multiple epilepsy related AEs. This study examines the possibility of immunization associated epilepsy AEs in VAERS occurring above background rates. Methods: Herein, VAERS is retrospectively examined for epilepsy and seizure AEs following immunizations (AEFIs). Reported AEFIs are normalized by total AEFIs for each vaccine. VAERS data is examined by vaccine type, vaccine source, vaccinee gender, and age-stratified for infants. Results: Association signals for examined epilepsy and seizure AEFIs are identified for multiple vaccines when compared to other vaccines with normalized frequencies above expected population background frequencies. Normalized epilepsy AEFI frequencies for children less than 1 year are higher than children aged 1 year for several vaccines. For pairs of matched vaccines from different manufacturers, statistically different epilepsy AEFI normalized frequencies were observed. These matched pairs for multiple vaccines implicate likely vaccine contaminations (e.g., endotoxins) as likely candidates for causing elevated epilepsy and seizure AEFIs. Conclusions: Based on the reported results, delaying some immunizations of a small set of vaccines until children are 1 year of age is predicted to reduce epilepsy AEFI occurrences for these vaccines. For several vaccines, statistically significant differences in epilepsy AEFI normalized frequencies were detected for the same (or similar) vaccine from different manufacturers; this suggests that possible manufacturing contaminant(s) (e.g., endotoxins) as the likely causative agent(s) for observed epilepsy AEFIs above background rates. Eliminating or reducing these possible contaminants is predicted to reduce the observed associations closer to background population levels observed for other vaccines with very low epilepsy AEFI normalized frequencies.

Overdose as a complex contagion: modelling the community spread of overdose events following law enforcement efforts to disrupt the drug market

BackgroundThe opioid overdose mortality crisis in the USA is an ongoing public health epidemic. Ongoing law enforcement strategies to disrupt local unregulated drug markets can have an iatrogenic effect of...

Analysis of Psychotropic Substance Seizures Occurring in 2017–2022 in Tamaulipas, a Mexican Border State with USA

The trafficking of illegal substances is a global issue. Tamaulipas, a northeastern state in Mexico, is strategically located for drug trafficking to the United States by organized crime. In this study, drug seizure events conducted by the Mexican government in the main cities of Tamaulipas between 2017 and 2022 are analyzed. It was noticed that there was a decrease in events from 2017 to 2020, followed by a slight increase in 2021. Marijuana was the most seized drug, with cocaine and amphetamines following behind. The frequency of drug seizure events was higher in the border cities of Nuevo Laredo, Reynosa, and Matamoros due to their international commercial bridges with the USA. Nuevo Laredo and Reynosa showed a high amount of marijuana seized. In Matamoros, a coastal city, the quantity of cocaine seized was the highest. Results suggest that substances seized were intended to be illegally transported to the USA through Mexican border cities.

Ictal and Postictal Central Apnea in DEPDC5-Related Epilepsy.

DEPDC5-related epilepsy carries an increased risk of sudden unexpected death in epilepsy. We evaluated the occurrence and features of ictal central apnea (ICA) in patients with pathogenic sequence variant in DEPDC5. We reviewed data of 108 patients collected in 2 independent cohorts of patients with focal epilepsy who prospectively underwent long-term video-EEG monitoring (LTVM) with cardiorespiratory polygraphy. All patients underwent (1) at least an overnight polysomnography, (2) a high-field (3T) brain MRI study, and (3) CSF analysis when clinically indicated. Genetic testing (next-generation sequencing [NGS]) was offered for diagnostic purposes to patients with focal epilepsy of unknown etiology. In this cohort, NGS was finally performed in 29 patients, resulting in DEPDC5 pathogenic mutations in 5 patients. According to the presence of ictal apnea events, 5 of 14 patients with ICA showed pathogenic DEPDC5 variants (35%) while none of the 15 patients without ICA showed pathogenic mutation. Notably, DEPDC5 patients showed ICA in all recorded seizures (n = 15) with apnea duration ranging from 20 seconds to more than 1 minute. All seizures were characterized by motor arrest without overt automatic behaviors during ictal apnea. Scalp EEG showed the involvement of temporal lobe leads in all events. Severe oxygen desaturation was observed in 2 cases. In our cohort, ictal central apnea was a common finding in DEPDC5. These results support (1) the need for respiratory polygraphy during LTVM in DEPDC5-related epilepsy and (2) the potential relevance of genetic testing in patients with focal epilepsy of unknown etiology and ictal apnea.

Pro-Ictal EEG Scheduling Improves the Yield of Epilepsy Monitoring: Validating the Use of Multiday Seizure Cycles to Optimize Video-EEG Timing.

A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. In this study, we introduce and validate "pro-ictal EEG scheduling", a method to schedule vEEG monitoring to coincide with periods of increased seizure likelihood as a low-risk approach to enhance the diagnostic yield. A database of long-term ambulatory vEEG monitoring sessions (n = 5,038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events) to generate cycle-based estimates of seizure risk. In adults, vEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (n = 305) and compared to remaining studies (baseline: n = 3,586). Test of proportions and risk-ratios (RR) were applied to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure, and diary event) during monitoring. The impact of clinical and demographic factors (age, sex, epilepsy-type, and medication) was also explored. During vEEG monitoring, the high-risk group was significantly more likely to have an abnormal vEEG report (190/305:62% vs 1,790/3,586:50% [%change = 12%], RR = 1.25, 95% confidence interval [CI] = [1.137-1.370], p < 0.001), present with a confirmed seizure (56/305:18% vs 424/3,586:11% [%change = 7%], RR = 1.63, 95% CI = [1.265-2.101], p < 0.001) and report an event (153/305:50% vs 1,267/3,586:35% (%change = 15%), RR = 1.420, 95% CI = [1.259:1.602], p < 0.001). Similar effects were observed across clinical and demographic features. This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management. ANN NEUROL 2024.

Anxiolytic and Anticonvulsant Potential of Biosynthetic Limonene Derivatives in Adult Zebrafish.

This study investigated the anxiolytic and anticonvulsant effects and safety profile of limonene enantiomers and their oxidized derivatives.The toxicity test was performed by monitoring the animals for 96 hours, with no deaths or significant toxicity observed up to the highest dose, which allowed the determination of the LD50. Doses of 4, 20 and 40 mg/kg were tested, with no toxicity observed up to 96h (LD50 > 40 mg/kg). Anxiolytic activity was measured in a preference test for light and dark areas, and the effect of the compounds was evaluated in the presence of serotonergic antagonists. The (S)-(-)-LIM and (R)-(+)-LIM enantiomers showed anxiolytic effects, with (S)-(-)-LIM being effective at all doses. In the anticonvulsant test, the oxidized derivatives, such as perilyl acid (PAC), significantly delayed PTZ-induced seizures, an effect blocked by flumazenil (FMZ). The oxidized derivatives, especially perilyl acid (PAC), showed anxiolytic effects at all doses and significantly delayed the three PTZ-induced seizure events. This effect was blocked by FMZ, suggesting a relationship between PAC and the GABAergic pathway. PAC, being the most oxidized derivative, was the most effective for both anxiety and delaying seizure progression, suggesting that oxidation of limonene compounds may increase their therapeutic efficacy.

Seizure prophylaxis in pneumococcal meningitis, cohort study.

Our aim was to assess seizure development as a complication of pneumococcal meningitis and its possible prevention with antiseizure medication prophylaxis. Antiseizure medication (ASM) prophylaxis has been practiced for a long time at our center. We assessed all cases of community-acquired pneumococcal meningitis admitted from January 2010 to April 2021 recorded in our prospective database and conducted further retrospective studies. Of the 86 cases recorded, 21 (24.4%) developed acute symptomatic seizures, more than half of which (11/21; 52.4%) before admission. Seizure development increased the need for orotracheal intubation and intensive care unit admission, while also lengthening hospital stays and suggesting more risk of death and disability at discharge [adjusted odds ratio (aOR), 3.13; 95% confidence interval (CI): 1-9.8]. Of the 74 patients eligible for ASM prophylaxis, 64 received it and 10 did not. ASM prophylaxis seemed effective in preventing seizure development, as only six seizure events were recorded in 64 patients with ASM prophylaxis (9.4%) compared with four in the 10 patients without prophylaxis (40%). Its preventive capacity was especially notable when administered within 4 h of admission. Differences in mortality did not reach statistical significance. Adverse effects were rare. Seizure development is a common complication in pneumococcal meningitis and is associated with increased risks of Intensive Care Unit admission, orotracheal intubation, and longer hospital stays. ASM prophylaxis may be effective in blocking seizure development in patients with preventable seizures and may be associated with better prognosis. Further studies are now warranted. Infection of the meninges (the covering of the brain) due to the common bacteria S pneumoniae, used to be a fatal disease before the introduction of antibiotics and corticoids. Thanks to these drugs, more people survive this disease but, due to the frequent complications, they may have several sequelae. Seizures are a common complication. Our study suggests that they might be prevented by using antiseizure drugs which may reduce both severity and hospital stay.

Association of dietary fiber intake with epileptic seizures in U.S. adults: A Population-base study of 13,277 participants

ObjectiveEpilepsy, a neurological disorder, is identified by the presence of recurrent seizures. We aimed to detect dietary fiber intake and its association with epilepsy prevalence in U.S. adults. MethodsThis cross-sectional study obtained data from the 2013–2018 National Health and Nutrition Examination Survey database. Univariate and multivariate logistic regression models were employed to estimate the association between dietary fiber intake and epilepsy prevalence. The restricted cubic spline (RCS) model was also applied to investigate the dose-response relationships between dietary fiber intake and epileptic seizure events(ESEs). ResultsOur final sample included 13,277 NHANES participants, with the average prevalence of ESEs being 1.09 % (145/13277). After adjusting for all confounding factors, the third quartile of dietary fiber intake levels remained significantly associated with a decreased risk of ESEs[odds ratios (OR) 0.54,95 % confidence interval (CI) 0.33–0.88, P = 0.014)] compared to the first quartile. Higher fiber intake indicated a stable negative association with ESEs in the multivariate logistic regression analysis, weighted generalized additive model. A nonlinear dose-response relationship was observed between dietary fiber intake levels and decreased ESEs risk (P for overall=0.017, P for nonlinear=0.155). Interaction tests showed no significant effect of demographic and disease status on the association between dietary fiber intake and ESEs. ConclusionIn this cross-sectional study, people with a high dietary fiber intake were at a reduced risk of ESEs. However, further prospective studies are needed to investigate the effect of dietary fiber intake in epilepsy events and to determine causality.

First-Generation Antihistamines and Seizures in Young Children

The widespread use of antihistamines in children for treatment of common cold symptoms and their central nervous system effects, like drowsiness, underscore the importance of being aware of the associated risks. To assess associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset. This cohort study used a self-controlled case-crossover design. Data were obtained from the National Health Insurance Service database in Korea. Children born between January 1, 2002, and December 31, 2005, who visited the emergency department for seizure events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes R56.8, G40, and G41) during the follow-up period were included. Follow-up was completed on December 31, 2019, and data were analyzed from June 3, 2023, to January 30, 2024. First-generation antihistamine prescription. Primary outcome consisted of an index seizure event. Odds ratios (ORs) for seizure events were estimated using a conditional logistic regression model, comparing first-generation antihistamine prescription 1 to 15 days before seizure (hazard period) against control period 1 (31-45 days before the event) and control period 2 (61-75 days before the event) using the same period windows. Stratified analyses were conducted to examine the association with individual participant characteristics. Of 11 729 children who had a seizure event, 3178 (1776 [55.9%] boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both. Seizure events were predominantly observed in children aged 6 to 24 months (985 [31.0%]) and 25 months to 6 years (1445 [45.5%]). During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively. After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) than children aged 25 months to 6 years (AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction). Furthermore, sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk. In this cohort study, prescriptions for first-generation antihistamines were associated with a 22.0% higher seizure risk in children, especially in those aged 6 to 24 months. These findings emphasize the need for careful and judicious prescription of first-generation antihistamines in young children and underline the need for further research to elucidate associations between antihistamine prescriptions and seizure risk.

Seizure burden and healthcare resource utilization among people living with drug-resistant focal epilepsy in the United States

Objective This study investigated clinical characteristics, burden of uncontrolled seizures, and seizure-related healthcare resource utilization (HRU) among individuals living with drug-resistant focal epilepsy (FE) in the United States (US). Methods Medical charts of adults with drug-resistant FE who initiated third-line (3 L) anti-seizure medication were extracted from clinical practices in the US (1/1/2013–1/31/2020). The index date, defined as the date of 3 L initiation, was used to indicate the emergence of drug resistance. Individuals on cenobamate were followed for any length of time from the index date. Demographic and clinical characteristics were analyzed descriptively. Primary clinical outcomes included seizure burden (i.e. change in seizure frequency and time to the first and second seizure events) and epilepsy-related HRU. Results Overall, 189 neurologists/epileptologists contributed 345 charts of individuals living with drug-resistant FE (66% male; average age 24 years at diagnosis and 32 years at index date). 66% had ≥1 neurologic/neuropsychiatric comorbidity at baseline. Average monthly seizure rate decreased from 6.1 at baseline to 3.8 at follow-up; however, nearly half of individuals experienced worse/no change or only some improvement (<50% reduction) in seizure frequency. Most individuals (91%) had ≥1 epilepsy-related outpatient visit during follow-up. Unplanned HRU included emergency department visits (43%) and hospitalizations (24%), primarily due to breakthrough seizure events. Conclusion Despite the availability of many anti-seizure medications in the US, people living with drug-resistant FE continue to experience multiple seizures per month and incur substantial healthcare resources. Novel pharmacotherapies may help individuals living with drug-resistant epilepsy achieve seizure freedom.

Preclinical efficacy profiles of the sigma-1 modulator E1R and of fenfluramine in two chronic mouse epilepsy models.

Given its key homeostatic role affecting mitochondria, ionotropic and metabotropic receptors, and voltage-gated ion channels, sigma-1 receptor (Sig1R) represents an interesting target for epilepsy management. Antiseizure effects of the positive allosteric modulator E1R have already been reported in acute seizure models. Although modulation of serotonergic neurotransmission is considered the main mechanism of action of fenfluramine, its interaction with Sig1R may be of additional relevance. To further explore the potential of Sig1R as a target, we assessed the efficacy and tolerability of E1R and fenfluramine in two chronic mouse models, including an amygdala kindling paradigm and the intrahippocampal kainate model. The relative contribution of the interaction with Sig1R was analyzed using combination experiments with the Sig1R antagonist NE-100. Whereas E1R exerted pronounced dose-dependent antiseizure effects at well-tolerated doses in fully kindled mice, only limited effects were observed in response to fenfluramine, without a clear dose dependency. In the intrahippocampal kainate model, E1R failed to influence electrographic seizure activity. In contrast, fenfluramine significantly reduced the frequency of electrographic seizure events and their cumulative duration. Pretreatment with NE-100 reduced the effects of E1R and fenfluramine in the kindling model. Surprisingly, pre-exposure to NE-100 in the intrahippocampal kainate model rather enhanced and prolonged fenfluramine's antiseizure effects. In conclusion, the kindling data further support Sig1R as an interesting target for novel antiseizure medications. However, it is necessary to further explore the preclinical profile of E1R in chronic epilepsy models with spontaneous seizures. Despite the rather limited effects in the kindling paradigm, the findings from the intrahippocampal kainate model suggest that it is of interest to further assess a possible broad-spectrum potential of fenfluramine.

Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events

A diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 700k Finns and Estonians. We found that a high genetic generalized epilepsy PRS (PRSGGE) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRSGGE standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRSGGE was significantly larger on idiopathic generalized epilepsies, in females and for earlier epilepsy onset. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). Here, we outline the potential of epilepsy specific PRSs to serve as biomarkers after a first seizure event.

On the performance of seizure prediction machine learning methods across different databases: the sample and alarm-based perspectives.

Epilepsy affects 1% of the global population, with approximately one-third of patients resistant to anti-seizure medications (ASMs), posing risks of physical injuries and psychological issues. Seizure prediction algorithms aim to enhance the quality of life for these individuals by providing timely alerts. This study presents a patient-specific seizure prediction algorithm applied to diverse databases (EPILEPSIAE, CHB-MIT, AES, and Epilepsy Ecosystem). The proposed algorithm undergoes a standardized framework, including data preprocessing, feature extraction, training, testing, and postprocessing. Various databases necessitate adaptations in the algorithm, considering differences in data availability and characteristics. The algorithm exhibited variable performance across databases, taking into account sensitivity, FPR/h, specificity, and AUC score. This study distinguishes between sample-based approaches, which often yield better results by disregarding the temporal aspect of seizures, and alarm-based approaches, which aim to simulate real-life conditions but produce less favorable outcomes. Statistical assessment reveals challenges in surpassing chance levels, emphasizing the rarity of seizure events. Comparative analyses with existing studies highlight the complexity of standardized assessments, given diverse methodologies and dataset variations. Rigorous methodologies aiming to simulate real-life conditions produce less favorable outcomes, emphasizing the importance of realistic assumptions and comprehensive, long-term, and systematically structured datasets for future research.

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Impaired brain-heart axis in focal epilepsy: Alterations in information flow and implications for seizure dynamics.

This study delves into functional brain-heart interplay (BHI) dynamics during interictal periods before and after seizure events in focal epilepsy. Our analysis focuses on elucidating the causal interaction between cortical and autonomic nervous system (ANS) oscillations, employing electroencephalography and heart rate variability series. The dataset for this investigation comprises 47 seizure events from 14 independent subjects, obtained from the publicly available Siena Dataset. Our findings reveal an impaired brain-heart axis especially in the heart-to-brain functional direction. This is particularly evident in bottom-up oscillations originating from sympathovagal activity during the transition between preictal and postictal periods. These results indicate a pivotal role of the ANS in epilepsy dynamics. Notably, the brain-to-heart information flow targeting cardiac oscillations in the low-frequency band does not display significant changes. However, there are noteworthy changes in cortical oscillations, primarily originating in central regions, influencing heartbeat oscillations in the high-frequency band. Our study conceptualizes seizures as a state of hyperexcitability and a network disease affecting both cortical and peripheral neural dynamics. Our results pave the way for a deeper understanding of BHI in epilepsy, which holds promise for the development of advanced diagnostic and therapeutic approaches also based on bodily neural activity for individuals living with epilepsy.

EEG Ictal Power Dynamics, Function-Structure Associations, and Epilepsy Surgical Outcomes.

Postoperative seizure control in drug-resistant temporal lobe epilepsy (TLE) remains variable, and the causes for this variability are not well understood. One contributing factor could be the extensive spread of synchronized ictal activity across networks. Our study used novel quantifiable assessments from intracranial EEG (iEEG) to test this hypothesis and investigated how the spread of seizures is determined by underlying structural network topological properties. We evaluated iEEG data from 157 seizures in 27 patients with TLE: 100 seizures from 17 patients with postoperative seizure control (Engel score I) vs 57 seizures from 10 patients with unfavorable surgical outcomes (Engel score II-IV). We introduced a quantifiable method to measure seizure power dynamics within anatomical regions, refining existing seizure imaging frameworks and minimizing reliance on subjective human decision-making. Time-frequency power representations were obtained in 6 frequency bands ranging from theta to gamma. Ictal power spectrums were normalized against a baseline clip taken at least 6 hours away from ictal events. Electrodes' time-frequency power spectrums were then mapped onto individual T1-weighted MRIs and grouped based on a standard brain atlas. We compared spatiotemporal dynamics for seizures between groups with favorable and unfavorable surgical outcomes. This comparison included examining the range of activated brain regions and the spreading rate of ictal activities. We then evaluated whether regional iEEG power values were a function of fractional anisotropy (FA) from diffusion tensor imaging across regions over time. Seizures from patients with unfavorable outcomes exhibited significantly higher maximum activation sizes in various frequency bands. Notably, we provided quantifiable evidence that in seizures associated with unfavorable surgical outcomes, the spread of beta-band power across brain regions is significantly faster, detectable as early as the first second after seizure onset. There was a significant correlation between beta power during seizures and FA in the corresponding areas, particularly in the unfavorable outcome group. Our findings further suggest that integrating structural and functional features could improve the prediction of epilepsy surgical outcomes. Our findings suggest that ictal iEEG power dynamics and the structural-functional relationship are mechanistic factors associated with surgical outcomes in TLE.

Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials

BackgroundSeizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies...

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Development of a novel, concentric micro-ECoG array enabling simultaneous detection of a single location by multiple electrode sizes

Objective. Detection of the epileptogenic zone is critical, especially for patients with drug-resistant epilepsy. Accurately mapping cortical regions exhibiting high activity during spontaneous seizure events while detecting neural activity up to 500 Hz can assist clinicians’ surgical decisions and improve patient outcomes. Approach. We designed, fabricated, and tested a novel hybrid, multi-scale micro-electrocorticography (micro-ECoG) array with a unique embedded configuration. This array was compared to a commercially available microelectrode array (Neuronexus) for recording neural activity in rodent sensory cortex elicited by somatosensory evoked potentials and pilocarpine-induced seizures. Main results. Evoked potentials and spatial maps recorded by the multi-scale array (‘micros’, ‘mesos’, and ‘macros’ refering to the relative electrode sizes, 40 micron, 1 mm, and 4 mm respectively) were comparable to the Neuronexus array. The SSEPs recorded with the micros had higher peak amplitudes and greater signal power than those recorded by the larger mesos and macro. Seizure onset events and high-frequency oscillations (∼450 Hz) were detected on the multi-scale, similar to the commercially available array. The micros had greater SNR than the mesos and macro over the 5-1000 Hz frequency range during seizure monitoring. During cortical stimulation experimentation, the mesos successfully elicited motor effects. Significance. Previous studies have compared macro- and microelectrodes for localizing seizure activity in adjacent regions. The multi-scale design validated here is the first to simultaneously measure macro- and microelectrode signals from the same overlapping cortical area. This enables direct comparison of microelectrode recordings to the macroelectrode recordings used in standard neurosurgical practice. Previous studies have also shown that cortical regions generating high-frequency oscillations are at an increased risk for becoming epileptogenic zones. More accurate mapping of these micro seizures may improve surgical outcomes for epilepsy patients.

Reducing False Alarms in Wearable Seizure Detection With EEGformer: A Compact Transformer Model for MCUs.

The long-term, continuous analysis of electroencephalography (EEG) signals on wearable devices to automatically detect seizures in epileptic patients is a high-potential application field for deep neural networks, and specifically for transformers, which are highly suited for end-to-end time series processing without handcrafted feature extraction. In this work, we propose a small-scale transformer detector, the EEGformer, compatible with unobtrusive acquisition setups that use only the temporal channels. EEGformer is the result of a hardware-oriented design exploration, aiming for efficient execution on tiny low-power micro-controller units (MCUs) and low latency and false alarm rate to increase patient and caregiver acceptance.Tests conducted on the CHB-MIT dataset show a 20% reduction of the onset detection latency with respect to the state-of-the-art model for temporal acquisition, with a competitive 73% seizure detection probability and 0.15 false-positive-per-hour (FP/h). Further investigations on a novel and challenging scalp EEG dataset result in the successful detection of 88% of the annotated seizure events, with 0.45 FP/h.We evaluate the deployment of the EEGformer on three commercial low-power computing platforms: the single-core Apollo4 MCU and the GAP8 and GAP9 parallel MCUs. The most efficient implementation (on GAP9) results in as low as 13.7 ms and 0.31 mJ per inference, demonstrating the feasibility of deploying the EEGformer on wearable seizure detection systems with reduced channel count and multi-day battery duration.