Epilepsy Patients Research Articles

Một số đặc điểm về tuân thủ sử dụng thuốc kháng động kinh của người bệnh động kinh tại Trung tâm Thần kinh Bệnh viện Bạch Mai

Epilepsy is a common disease, affecting about 65 million people in the world, accounting for 1% of the global burden of disease. Many aspects are affected such as: Economic, social and especially the quality of life. Some researches have shown that the quality of life of people with epilepsy is much lower than that of healthy people. Treatment of epilepsy is necessary. However, epilepsy treatment is difficult with a high rate of seizure recurrence. One of the important causes of seizure recurrence is the medication non-adherence that even making the disease more difficult to control. Objective: Describe the characteristics of medication adherence in epilepsy patients at the Bach Mai neurology center and analyze some related factors. Subjects and methods: Cross-sectional descriptive study on patients who were diagnosed and treated for outpatient epilepsy, came for follow-up examination at the neurology center of Bạch Mai hospital. Patient classification based on medication adherence characteristics and patients beliefs about drug use, through MMAS-8 scale and BMQ scale. Results: Out of 193 patients, 80.5% of them often had difficulty remembering to take medication, 11.4% felt bothered when adhering to treatment. 0% of patients achieved a high level of compliance, 27.5% at average level and 72.5% at low level). Conclusion: The majority of patients have a moderate level of knowledge about epilepsy, with most of them understanding that epilepsy can be cured, the available treatment methods, and the necessity of adhering to medication. However, they also recognize the serious issue of using stimulants. Despite this, none of the patients achieved a high level of adherence, with most showing low adherence to treatment, primarily due to occasionally forgetting to take their medication.

Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.

Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

Reward recalibrates rule representations in human amygdala and hippocampus intracranial recordings

Adaptive behavior requires the ability to shift responding within (intra-dimensional) or between (extra-dimensional) stimulus dimensions when reward contingencies change. Studies of shifting in humans have focused mainly on the prefrontal cortex and/ or have been restricted to indirect measures of neural activity such as fMRI and lesions. Here, we demonstrate the importance of the amygdala and hippocampus by recording local field potentials directly from these regions intracranially in human epilepsy patients. Reward signals were coded in the high frequency gamma activity (HFG; 60-250 Hz) of both regions and synchronised via low frequency (3-5 Hz) phase-locking only after a shift when patients did not already know the rule and it signalled to stop shifting (“Win-Stay”). In contrast, HFG punishment signals were only seen in the amygdala when the rule then changed and it signalled to start shifting (“Lose-Shift”). During decision-making, hippocampal HFG was more inhibited on non-shift relative to shift trials, suggesting a role in preventing interference in rule representation and amygdala HFG was sensitive to stimulus novelty. The findings expand our understanding of human amygdala-hippocampal function and shifting processes, the disruption of which could contribute to shifting deficits in neuropsychiatric disorders.

GC-MS uncovers unique metabolic markers of drug-resistant epilepsy in capillary but not venous dried blood spots

This study compared the effectiveness of capillary dried blood spots (DBS) versus venous DBS in detecting metabolic changes related to drug-resistant epilepsy (DRE). DBS samples were collected from 142 epilepsy patients (58 drug-resistant, 84 drug-responsive) via venipuncture or fingerstick capillary sampling. Metabolomic analysis using gas chromatography-mass spectrometry compared DBS metabolite profiles between the two groups. While venous DBS profiles showed no distinct patterns, capillary DBS profiles revealed clustering patterns in principal components analysis, with the first two principal components explaining 14.5%, and 13.5% of the total variance, respectively. Orthogonal PLS-DA confirmed group discrimination (R2Y=0.989, Q2=0.742). Drug-resistant patients exhibited elevated capillary DBS levels of glutamine, pyruvic acid, and serine, and decreased palmitic acid compared to drug-responsive patients. Pathway analysis revealed disruptions in amino acid metabolism, neurotransmission, and cellular energy regulation. Elevated glutamine levels may contribute to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission, key factors in epileptogenesis and drug resistance. Capillary DBS, likely enriched with arterial blood supply to the brain, appears to better capture central nervous system metabolic disturbances compared to venous DBS containing systemic contributions. This minimally invasive capillary DBS approach offers effective metabolic profiling of brain conditions like DRE, for monitoring disease progression and treatment response, enhancing personalized patient management in epilepsy.

Cognitive deficits’ profiles of attention and executive functions in epilepsy versus psychogenic non-epileptic seizure patients: A preliminary cross-sectional study

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures (ES) but lack the associated brain electrical disruptions. Their underlying mechanism remains elusive, even though cognitive deficits are commonly reported in both ES and PNES patients. This preliminary cross-sectional study compared attention and executive functions in 20 patients with ES (ES group) and 18 with PNES or comorbid PNES and ES (PNES group) using the Stroop task and attentional network task (ANT). Both groups exhibited a significant Stroop effect, with no significant differences between them. In the ANT assessment, the ES group had significantly slower reaction times (RTs) in non-tone conditions compared to in-tone conditions (P &lt; 0.05). Meanwhile, the PNES group displayed no significant difference in RTs between these conditions, indicating a more pronounced alerting effect in the ES compared to PNES group. No significant disparities emerged in executive control and orientation between the groups. The findings underscore differences in attentional processing between these groups, emphasizing the clinical significance of understanding these cognitive deficits for accurate diagnosis and tailored neuropsychological rehabilitation.

Differential neural mechanisms underlie cortical gating of visual spatial attention mediated by alpha-band oscillations

Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval. Dorsal intraparietal areas contralateral to the attended hemifield primarily exhibited a delayed and sustained alpha desynchronization, while ventrolateral extrastriatal areas ipsilateral to the attended hemifield primarily exhibited an earlier and sustained alpha synchronization. Analyses of cross-frequency coupling between alpha phase and broadband high-frequency activity (HFA) further revealed cross-frequency interactions along the visual hierarchy contralateral to the attended locations. Directionality analyses indicate that alpha phase in early and extrastriatal visual areas modulated HFA power in downstream visual areas, thus potentially facilitating the feedforward processing of an upcoming, spatially predictable target. In contrast, in areas ipsilateral to the attended locations, HFA power modulated local alpha phase in early and extrastriatal visual areas, with suppressed interareal interactions, potentially attenuating the processing of distractors. Our findings reveal divergent alpha-mediated neural mechanisms underlying target enhancement and distractor suppression during the deployment of spatial attention, reflecting enhanced functional connectivity at attended locations, while suppressed functional connectivity at unattended locations. The collective dynamics of these alpha-mediated neural mechanisms play complementary roles in the efficient gating of sensory information.

Seizure Sources Can Be Imaged from Scalp EEG by Means of Biophysically Constrained Deep Neural Networks.

Seizure localization is important for managing drug-resistant focal epilepsy. Here, the capability of a novel deep learning-based source imaging framework (DeepSIF) for imaging seizure activities from electroencephalogram (EEG) recordings in drug-resistant focal epilepsy patients is investigated. The neural mass model of ictal oscillations is adopted to generate synthetic training data with spatio-temporal-spectra features similar to ictal dynamics. The trained DeepSIF model is rigorously validated using computer simulations and in a cohort of 33 drug-resistant focal epilepsy patients with high-density (76-channel) EEG seizure recordings, by comparing DeepSIF estimates with surgical resection outcome and seizure onset zone (SOZ) . These findings show that the trained DeepSIF model outperforms other methods in estimating the spatial and temporal information of origins of ictal activities. It achieves a high spatial specificity of 96% and a low spatial dispersion of 3.80±5.74mm when compared to the resection region. The source imaging results also demonstrate good coverage of SOZ, with an average distance of 10.89±10.14mm (from the SOZ to the reconstruction). These promising results suggest that DeepSIF has significant potential for advancing noninvasive imaging of the origins of ictal activities in patients with focal epilepsy, aiding management of intractable epilepsy.

[11C]Metoclopramide PET can detect a seizure-induced up-regulation of cerebral P-glycoprotein in epilepsy patients

BackgroundP-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [11C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [11C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.MethodsEight patients with drug-resistant (DRE) TLE, 5 seizure-free patients with drug-sensitive (DSE) focal epilepsy, and 15 healthy subjects underwent brain PET imaging with [11C]metoclopramide on a fully-integrated PET/MRI system. Concurrent with PET, arterial blood sampling was performed to generate a metabolite-corrected arterial plasma input function for kinetic modelling. The choroid plexus was outmasked on the PET images to remove signal contamination from the neighbouring hippocampus. Using a brain atlas, 10 temporal lobe sub-regions were defined and analysed with a 1-tissue-2-rate constant compartmental model to estimate the rate constants for radiotracer transfer from plasma to brain (K1) and from brain to plasma (k2), and the total volume of distribution (VT = K1/k2).ResultsDRE patients but not DSE patients showed significantly higher k2 values and a trend towards lower VT values in several temporal lobe sub-regions located ipsilateral to the epileptic focus as compared to healthy subjects (k2: hippocampus: +34%, anterior temporal lobe, medial part: +28%, superior temporal gyrus, posterior part: +21%).Conclusions[11C]Metoclopramide PET can detect a seizure-induced P-gp up-regulation in the epileptic brain. The efflux rate constant k2 seems to be the most sensitive parameter to measure increased P-gp function with [11C]metoclopramide. Our study provides evidence that disease-induced alterations in P-gp expression at the BBB can lead to changes in the distribution of a central nervous system-active drug to the human brain, which could affect the efficacy and/or safety of drugs. [11C]Metoclopramide PET may be used to assess or predict the contribution of increased P-gp function to drug resistance and disease pathophysiology in various brain diseases.Trial registrationEudraCT 2019-003137-42. Registered 28 February 2020.

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation.

Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, whichcontributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Progressive postoperative atrophy of ipsilateral thalamus, putamen, and globus pallidus in patients with temporal lobe epilepsy: A volumetric analysis.

Cortical atrophy close to medial temporal structures has been described consistently in patients with temporal lobe epilepsy (TLE). Successful TLE surgery may have a neuroprotective effect preventing further atrophy of temporal and extratemporal cortex. However, the effects of epilepsy surgery on subcortical structures demand additional enlightenment. This work aimed to determine how epilepsy surgery affects volumes of subcortical structures in medically refractory temporal lobe epilepsy patients. We compared MRI volumes of subcortical structures in 62 patients with TLE (36 left, 26 right) before and after anterior temporal lobectomy with 38 TLE patients (20 left, 18 right) who were considered to be good surgical candidates and had at least two brain MRIs. There were no volume differences in subcortical structures on preoperative and initial MRIs of non-operated TLE patients. At baseline, the ipsilateral thalamus and putamen in TLE patients were marginally smaller than contralateral structures. Operated patients showed a significant postoperative volume reduction in ipsilateral thalamus, putamen, and globus pallidus. In contrast, there were no significant volumetric reductions in non-operated patients longitudinally. There were no volumetric changes associated with different surgical outcomes or different postoperative cognitive outcomes. Our study demonstrated postoperative volume loss of thalamus, putamen and globus pallidus ipsilaterally to the side of resection. Our findings suggest surgery-related changes, likely Wallerian degeneration within subcortical networks not related to seizure or cognitive outcome. We studied 100 patients with epilepsy, comparing those who had surgery to those who did not. After surgery, the thalamus, putamen and globus pallidus on the same side as the surgery shrank significantly, but not in non-surgery patients. This suggests surgery-related changes in deeper brain structures, unrelated to seizure freedom or cognitive outcomes. This research sheds additional light on the response of the subcortical structure to epilepsy surgery, highlighting potential areas for further study.

Factors impacting time to genetic diagnosis for children with epilepsy.

Molecular diagnosis for pediatric epilepsy patients can impact treatment and health supervision recommendations. However, there is little known about factors affecting the time to receive a diagnosis. Our objective was to characterize factors affecting the time from first seizure to molecular diagnosis in children with epilepsy. A retrospective, population-based review was used to analyze data from pediatric patients with a genetic etiology for epilepsy over a 5 year period. A subgroup of patients with seizure onset after 2016 was evaluated for recent trends. We identified 119 patients in the main cohort and 62 in a more recent (contemporaneous) subgroup. Sex, race, and ethnicity were not significantly associated with time to molecular diagnosis. A greater number of hospitalizations was associated with a shorter time to diagnosis (p < 0.001). Developmental delay was associated with a longer time to diagnosis (p = 0.002). We found no association for time to diagnosis with a diagnosis of autism, utilization of free genetic testing, or epilepsy type. In the recent subgroup analysis, commercial insurance was associated with decreased time to diagnosis (p = 0.02). Developmental delay, public insurance, or patients in the outpatient setting had longer times to molecular diagnosis. These findings suggest that there may be opportunities to implement interventions aimed at accelerating the provision of genetic testing in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Genetic diagnosis for pediatric epilepsy patients can impact treatment and care. This study looked at factors that affect how long it takes a pediatric epilepsy patient to receive a genetic diagnosis. We found that sex, race and ethnicity, epilepsy type, and whether the patient had autism did not affect how long it took the patient to receive a diagnosis. However, we found that patients with developmental delay, fewer hospitalizations, and public insurance took a longer time to receive a diagnosis. Our findings suggest potential strategies for reducing the time to receive a genetic diagnosis.

CNN-Informer: A hybrid deep learning model for seizure detection on long-term EEG

Timely detecting epileptic seizures can significantly reduce accidental injuries of epilepsy patients and offer a novel intervention approach to improve their quality of life. Investigation on seizure detection based on deep learning models has achieved great success. However, there still remain challenging issues, such as the high computational complexity of the models and overfitting caused by the scarce availability of ictal electroencephalogram (EEG) signals for training. Therefore, we propose a novel end-to-end automatic seizure detection model named CNN-Informer, which leverages the capability of Convolutional Neural Network (CNN) to extract EEG local features of multi-channel EEGs, and the low computational complexity and memory usage ability of the Informer to capture the long-range dependencies. In view of the existence of various artifacts in long-term EEGs, we filter those raw EEGs using Discrete Wavelet Transform (DWT) before feeding them into the proposed CNN-Informer model for feature extraction and classification. Post-processing operations are further employed to achieve the final detection results. Our method is extensively evaluated on the CHB-MIT dataset and SH-SDU dataset with both segment-based and event-based criteria. The experimental outcomes demonstrate the superiority of the proposed CNN-Informer model and its strong generalization ability across two EEG datasets. In addition, the lightweight architecture of CNN-Informer makes it suitable for real-time implementation.

Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.

Effects of vagal nerve stimulation parameters on heart rate variability in epilepsy patients.

Vagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment. Our study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG. The mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9. In conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS.

Cost of epilepsy in the Russian Federation

Background. Epilepsy underdiagnosis in Russia, population aging, innovative drugs and expensive treatment regimens, the introduction of additional and alternative methods such as neurosurgery, annually increase the cost for treatment of epilepsy patients. In this regard, an issue of maximizing benefits for the largest number of the population becomes relevant. Pharmacoeconomical research within the assessment of healthcare technologies helps to choose the most economically and medically effective treatment strategy among numerous alternatives.Objective: analysis of epilepsy-associated costs in the Russian Federation, aimed at supporting decision-making processes in the field of health policy and financing.Material and methods. The empirical study was based on collecting the data on a continuous sampling of 384 epilepsy outpatient records from subjects aged 19 to 79 years for the period 2019–2022. The issues related to all costs of epilepsy were discussed. While planning, conducting and analyzing these studies, the principles of strengthening the reporting of observational studies in epidemiology (STROBE) were taken into account.Results. The total annual per-patient expenditure on epilepsy treatment comprised a fifth of gross domestic product per capita. Indirect costs exceed direct cost savings. It was found out that the economic damage caused to society, family, and individual related to epilepsy is three times higher than the direct costs.Conclusion. The results obtained are consistent with other publications in which unemployment among epilepsy patients is one of the major cost-determining factors and illustrates a critical need to maintain employment for such patients or to find suitable alternative work through professional retraining.

The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.

One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.

Sinapinic acid as a potential therapeutic agent for epilepsy through targeting NMDA receptors and nitrite level

Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P < 0.05). Additionally, in the receiving group of an ineffective dose of sinapinic acid alongside ketamine, the beginning of seizure time was significantly prolonged compared to the group that received the ineffective dose of sinapinic acid alone (P < 0.05). Serum and prefrontal cortex (PFC) nitrite levels were significantly lower in mice treated with sinapinic acid at doses of 1, 3, and 10 mg/kg compared to the saline-treated group (P < 0.05). The gene expression of the NMDAR NR2B subunit in the PFC was decreased in groups treated with sinapinic acid at 1 and 10 mg/kg compared to the saline-treated group. Furthermore, co-administration of sinapinic acid (10 mg/kg) with NMDA resulted in significantly lower NR2A gene expression than the group treated with 10 mg/kg of sinapinic acid alone. Conversely, co-administration of ketamine with sinapinic acid (1 mg/kg) significantly increased NR2B subunit gene expression compared to the group treated with sinapinic acid at 1 mg/kg alone. Sinapinic acid showed anticonvulsant effects through reduced serum and PFC nitrite and modulation of glutamatergic signaling.

Intracranial EEG-Based Directed Functional Connectivity in Alpha to Gamma Frequency Range Reflects Local Circuits of the Human Mesiotemporal Network.

To date, it is largely unknown how frequency range of neural oscillations measured with EEG is related to functional connectivity. To address this question, we investigated frequency-dependent directed functional connectivity among the structures of mesial and anterior temporal network including amygdala, hippocampus, temporal pole and parahippocampal gyrus in the living human brain. Intracranial EEG recording was obtained from 19 consecutive epilepsy patients with normal anterior mesial temporal MR imaging undergoing intracranial presurgical epilepsy diagnostics with multiple depth electrodes. We assessed intratemporal bidirectional functional connectivity using several causality measures such as Granger causality (GC), directed transfer function (DTF) and partial directed coherence (PDC) in a frequency-specific way. In order to verify the obtained results, we compared the spontaneous functional networks with intratemporal effective connectivity evaluated by means of SPES (single pulse electrical stimulation) method. The overlap with the evoked network was found for the functional connectivity assessed by the GC method, most prominent in the higher frequency bands (alpha, beta and low gamma), yet vanishing in the lower frequencies. Functional connectivity assessed by means of DTF and PCD obtained a similar directionality pattern with the exception of connectivity between hippocampus and parahippocampal gyrus which showed opposite directionality of predominant information flow. Whereas previous connectivity studies reported significant divergence between spontaneous and evoked networks, our data show the role of frequency bands for the consistency of functional and evoked intratemporal directed connectivity. This has implications for the suitability of functional connectivity methods in characterizing local brain circuits.

Terminology of medicines used to control seizure disorders: 2024 ILAE Recommendations and profile of real-world term use

Background. The International League Against Epilepsy (ILAE) has provided recommendations on the terminology of medicines for control of seizure disorders, which should be adapted into different languages.Objective: to evaluate the usage profile of terms describing the effects of medicines used in patients with epilepsy.Material and methods. The search query analysis systems Google Trends and Yandex Wordstat as well as PubMed/MEDLINE, Google Scholar and eLibrary databases were used to evaluate the general public and professional usage profile, respectively.The following terms in Russian and English were studied: “antiepileptic”, “antiepileptic drug”, “antiseizure”, “antiseizure drug”. In order to ascertain a prevailing opinion within professional and patient communities, a questionnaire survey was conducted on the public online resources of the non-profit partnership “The Association of Epileptologists and Patients” carried out via the cloud-based cross-platform social media as well as instant messaging service Telegram and the social media platform VK.Results. In the English-speaking internet segment, the term “antiepileptic” is used more than 5 times frequently than “antiseizure” by the general public. Conversely, in the Russian-language segment, the term “antiseizure” is almost 2.5 times more common. The term “antiepileptic” is more prevalent in scientific community in both segments. This finding aligns with the profile of terminology usage observed among epileptologists and epilepsy patients. The questionnaire survey results revealed that 56.42% of 179 respondents were in favor of the terms “antiepileptic drug”, “AED” and “antiepileptic therapy”, whereas as few as 17.32% of those endorsed the ILAE-proposed terminology.Conclusion. In light of the established practice of terminology use in both professional scientific community and among practicing epileptologists and epileptic patients, as well as the differences in the semantics of English- and Russian-language terms and the identified lack of precision in the ILAE definition of epilepsy, it can be concluded that for the Russian-speaking population, the terms “antiepileptic drug”, “AED” are more preferable rather than the terms “antiseizure medication”, “ASM”. Additionally, it is preferable to use the terms “convulsive ictus” and “epileptic ictus” due to negative connotation with term “seizure” in Russian. The terms “antiseizure” and “antiepileptic” should not be regarded as mutually exclusive in the context of treatment that has a direct impact on epilepsy course. Finally, it is necessary to further refine epilepsy definition and classification.

Value of Quantitative Intraoperative Electrocorticography During Anterior Temporal Lobectomy in Temporal Lobe Epilepsy Patients

Introduction: There is debate on the predictive usefulness of electrocorticography (ECoG) during anterior temporal lobectomy (ATL) in temporal lobe epilepsy (TLE) patients. The purpose of this study was to determine the usefulness of quantitative intraoperative ECoG monitoring for postoperative seizure outcomes after ATL in TLE patients. Methods: The study enrolled thirteen TLE patients who underwent ECoG-assisted ATL. Pre- and post-resection ECoG spike frequency (/min) and spike amplitude (μv/mm) were analyzed with histopathological and preoperative video-electroencephalography (EEG) data. After one year of follow-up, patients were classified as seizure-free (Engel Class I) or with residual seizure outcomes using the Engel Seizure Outcome Classification Scheme. Results: The pre-resection and post-resection ECoG showed significant differences in spike frequency (/min) and amplitude (μv/mm) (P-value &lt; 0.001). Patients with residual seizures (15.4%) showed significantly greater pre- and post-resection ECoG spike frequency and amplitude, as well as significantly higher seizure frequency before surgery, compared to patients with postoperative seizure freedom (84.6%). The pre-resection ECoG spike frequency was significantly greater in TLE patients with histopathology focal cortical dysplasia (FCD) than in those with non-FCD. The post-resection ECoG revealed a sensitivity of 100%, a specificity of 50%, a negative predictive value of 100%, and a positive predictive value of 91.67%. Conclusions: Pre-resection ECoG spike frequency and amplitude can be used as a predictive tool for postoperative seizure outcomes, particularly when video-EEG can't identify the epileptogenic zone (EZ) in TLE patients undergoing ATL.