Search Results (75)

Background: It has been demonstrated that levetiracetam can decrease absence epileptic activity in both human patients and different types of animal models of absence epilepsy, such as the genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. It was also suggested previously that exogenous ketone supplements (EKSs)-evoked ketosis not only decreases the number of spike-wave discharges (SWDs) but also enhances the anti-absence epileptic effect of pyrimidine nucleoside uridine in WAG/Rij rats. These findings suggest that EKSs may enhance the efficacy of clinically used anti-epileptic drugs, such as levetiracetam. Methods: We investigated the effect of not only levetiracetam (intraperitoneal/i.p. 200 mg/kg) alone and KEKS supplemented food (containing 10% ketone ester/KE and 10% ketone salt/KS in a normal rat chow) alone, but also the combination of levetiracetam and KEKS supplemented food on SWD number and SWD time for 5 days in WAG/Rij rats. For evaluation of SWDs, electroencephalographic (EEG) recordings were performed every day. Moreover, for the measurement of blood glucose and R-beta-hydroxybutyrate (R-βHB) levels, the blood was taken from the tail vein of rats after EEG registration. Results: It was demonstrated that the administration of both levetiracetam alone and KEKS food alone decreased the SWD number and time spent in SWD, compared to control. Moreover, after combined administration of levetiracetam with KEKS food, enhanced anti-absence epileptic effect was observed, compared to levetiracetam alone. Blood R-βHB level significantly increased after administration of both KEKS food alone and KEKS food in combination with levetiracetam. Nevertheless, these treatments did not significantly change the blood glucose levels. Conclusions: We can conclude that EKSs may be able to enhance the anti-epileptic effect of different drugs, and this combined treatment method may represent a promising new approach and effective therapy against epileptic seizures, especially in treatment-resistant patients. Full article

Tools for measuring the likelihood of relapse in infantile epileptic spasms syndrome (IESS) treatment could aid clinicians in making critical management decisions. High-frequency oscillations (HFOs), transient bursts of electroencephalography (EEG) activity with frequencies beyond 80 Hz, are a new and promising noninvasive biomarker. The present study aimed to investigate the association between the Burden of Amplitudes and Epileptiform Discharges (BASED) scores, an interictal EEG grading scale for IESS, and scalp HFOs in patients with IESS. The study enrolled 50 patients, 25 with a clinical diagnosis of IESS and 25 without epilepsy. The percentage of patients with at least one scalp HFO detected, stratified by BASED scores, differed significantly: for BASED scores ≤ 2, 7.7%; for 3, 16.7%; for 4, 87.5%; and for 5, 100% (p < 0.001). Compared with BASED scores ≤ 2, the median scalp HFO detection rate was significantly highest for BASED scores of 5 (median [IQR]: 6.24 [2.25–8.32], p < 0.001), followed by BASED scores of 4. The scalp HFO detection rates showed a better performance in estimating patients with BASED scores of 4 and 5. It is hoped that scalp HFOs can be used as an objective indicator to validate the results of BASED scores. Full article

Background/Objectives: Epilepsy is a common neurological disorder that not only severely impacts patients’ health but also imposes a significant burden on families and society. However, its pathogenesis remains unclear. Astrocytes play a crucial role in epileptic seizures and may serve as potential therapeutic targets. Establishing a network model of epileptic seizures based on the astrocyte–neuron cell coupling and the clinical electroencephalographic (EEG) characteristics of epilepsy can facilitate further research on refractory epilepsy and the development of treatment strategies. Methods: This study constructs a neuronal network dynamic model of epileptic seizures based on the Watts–Strogatz small-world network, with a particular emphasis on the biological mechanisms of astrocyte–neuron coupling. The phase-locking value (PLV) is used to quantify the degree of network synchronization and to identify the key nodes or connections influencing synchronous seizures, such that two epilepsy treatment strategies are proposed: seizure suppression through stimulation and surgical resection simulation therapy. The therapeutic effects are evaluated based on the PLV-quantified network synchronization. Results: The results indicate that the desynchronization effect of random noise and sinusoidal wave stimulation is limited, while square wave stimulation is the most effective. Among the four surgical resection strategies, the effectiveness is the highest when resecting nodes exhibiting epileptic discharges. These findings contribute to the development of rational seizure suppression strategies and provide insights into precise epileptic focus localization and personalized treatment approaches. Full article

Background/Objectives: In a patient suspected of having epilepsy, routine EEG primarily contributes to the recording of interictal epileptiform discharges (IEDs). Similarly, magnetic resonance imaging (MRI) has become the gold standard imaging technique for identifying epileptogenic structural brain abnormalities. Various EEG and MRI tools to improve epilepsy diagnosis will be presented. Methods: When the initial EEG fails to record IEDs, various EEG measures that can improve EEG performance are presented; a comprehensive epilepsy-targeted MRI protocol to identify, localize, and characterize an epileptogenic lesion will also be described. Results: Studies show that the initial routine EEG fails to record IEDs in approximately 47–50% of epileptic patients. To improve the yield of EEG, subsequent EEG recording should include sleep deprivation, sleep recording, prolonged hyperventilation, optimized light stimulation, addition of an inferior temporal electrode chain, extended EEG duration, and continuous video-EEG monitoring, all measures known to activate IEDs. Furthermore, MRI is interpreted as “normal” in many epilepsy patients, even when performed according to an epilepsy-specific protocol and evaluated by a specialized MRI reader. In such case, the use of the Harmonized Epilepsy Structural Sequence Imaging (HARNESS-MRI) protocol and other imaging tools will improve the detection of potential epileptic lesions, as described in this study. Conclusions: In a patient with a clinical diagnosis of epilepsy but a normal EEG and brain MRI, several options can improve the performance of subsequent EEG and MRI examinations, the subjects of this review. Full article

Background: Absence epilepsy is a non-convulsive form of genetic generalized epilepsy characterized by spontaneous bilateral spike-and-wave discharges (SWDs) in EEG. In contrast to grand-mal epilepsy, absence epilepsy without greatly expressed motor and interictal EEG abnormalities is difficult to detect, especially at the early stages. The WAG/Rij rat strain is a well-validated animal model of childhood absence epilepsy. At the early, preclinical stage, precursors or immature SWDs appear. Then, with age, immature discharges gradually turn into mature ones and mature SWDs prevail at the clinical stage. Mature SWDs, with an amplitude several times higher than the background EEG, can be easily distinguished visually. However, the amplitude of immature discharges is significantly lower than that of mature SWDs and is comparable to the amplitude of sleep spindles. Therefore, it is quite a difficult problem to distinguish immature discharges from sleep spindles. The task is further complicated by the fact that absence seizures mainly appear in a state of drowsiness and slow-wave (non-REM) sleep, when a lot of sleep spindles occur. The purpose of the present study was to develop a diagnostic method that allows us to precisely distinguish immature forms of epileptic seizures from background EEG and sleep spindles. Methods: The idea of analyzing wave-train electrical activity is to investigate the wavelet spectrum, find local peculiarities in this spectrum, and estimate generalized time-frequency peculiarities of the signal in terms of the found local peculiarities. Results: The criteria for diagnosis of the immature form of epileptic discharges and sleep spindles have been developed based on the analysis of wave-train activity with the construction of AUC diagrams (area under the curve diagrams). Conclusions: The method of wave-train analysis with the construction of AUC diagrams can be used for extracting the diagnostic features necessary for the diagnosis of absence epilepsy at the early stages of the disease in people with a genetic predisposition. Full article

Background/Objectives: To investigate the usefulness of an emergency electroencephalogram (emEEG) in the differential diagnosis of transient neurological deficits (TND) and acute confusional state (ACS). Methods: An analysis was performed on a subset of patients included in EMINENCE, a retrospective study of subjects admitted to the Emergency Department (ED) of our tertiary hospital over a 1-year period. The analysis was limited to patients with neurological symptoms/signs compatible with cerebral hemispheric origin or with an ACS of <24 h duration. We evaluated the usefulness of the emEEG in the diagnostic workup of TND and ACS. Results: Speech disorder (75.3%), hyposthenia (68.1%), and ACS (62.9%) were the signs/symptoms with the highest percentage of abnormal emEEGs, especially concerning epileptic discharges. Seizures (85.7%) and encephalopathy (74.3%) were the final diagnoses with the highest percentage of abnormal emEEGs, particularly epileptic discharges and focal slow waves in patients discharged with a diagnosis of seizures, and bilateral slow waves and generalized periodic discharges with triphasic morphology (GPDTM) in patients discharged with a diagnosis of encephalopathy. The presence/absence of epileptic discharges associated with focal slow waves could discriminate between seizures and vascular disease, especially in hyposthenia (100% of seizures when epileptic discharges were present, vs. 50% when absent). Migraine with aura (66%) and an unknown diagnosis (56%) were the final diagnoses with the most normal emEEG. The rapid timing of the emEEG recording compared to the patient’s admission allowed us to perform the test in 29.5% of patients who were still symptomatic, of whom 79% had an abnormal emEEG. Conclusions: The emEEG mainly contributed to the diagnosis when speech disorder, hyposthenia, and ACS were the admission signs/symptoms, especially for the final diagnosis of seizures and encephalopathy. Full article

Frmpd3 (FERM and PDZ Domain Containing 3), a scaffold protein potentially involved in excitatory synaptic function, has not been thoroughly characterized in terms of its expression and functional role in vivo. Here, we investigated the distribution of Frmpd3 in the central nervous system and its potential regulatory role in epilepsy, a neurological disorder characterized by disrupted excitatory–inhibitory balance. The distribution of Frmpd3 throughout the mouse brain was investigated by immunofluorescence. Western blotting was conducted to examine potential alterations in Frmpd3 protein expression in the hippocampus of a pentylenetetrazol (PTZ)-induced chronic epilepsy model. Using stereotaxic techniques, we delivered Frmpd3 siRNA-AAV9 into the hippocampal CA1 region to achieve targeted protein knockdown. Then, the functional consequences of Frmpd3 depletion were assessed through behavioral observations and electrophysiological recordings in PTZ-treated mice. Finally, protein–protein interactions were investigated using immunoprecipitation and Western blot analysis. Immunofluorescence analysis revealed Frmpd3 expression in cortical, hypothalamic, cerebellar, and hippocampal neurons of adult mice. Subcellular localization studies demonstrated predominant distribution of Frmpd3 in the excitatory postsynaptic density (PSD) of hippocampal CA1 neurons, with additional expression in inhibitory neurons. Quantitative analysis showed significantly elevated Frmpd3 protein levels in the hippocampus of PTZ-induced epileptic mice compared to controls. Frmpd3 knockdown in the CA1 region resulted in the following: (1) reduced seizure frequency, (2) prolonged seizure latency, and (3) decreased incidence of PTZ-induced generalized seizures. Local field potential (LFP) recordings demonstrated that seizure amplitude tended to be reduced, and epileptic discharge durations tended to be shorter in Frmpd3-depleted mice compared to controls. Furthermore, we observed decreased membrane expression of the AMPA receptor GluA2 subunit in the hippocampus of Frmpd3 knockdown mice. Molecular interaction studies revealed that Frmpd3 forms complexes with glutamate receptor-interacting protein (GRIP) and GluA2. Our findings identify Frmpd3 as a novel regulatory scaffold protein that modulates epileptic susceptibility through molecular interactions with GRIP and GluA2. The underlying mechanism appears to involve Frmpd3-mediated regulation of GluA2 trafficking from the cytoplasm to the membrane, ultimately enhancing neuronal excitability through increased membrane expression of GluA2-containing AMPA receptors. Full article

Background/Objectives: Polyphenols have been suggested to possess anticonvulsant properties, which can be exploited as tools in novel strategies against epilepsy. Along that line, the aim of this study was to investigate the effects of a polyphenol-rich extract of white grape juice (WGJe) in different rodent models of epilepsy, exploring its putative mechanism of action. Methods: In this study, we employed pentylenetetrazole (PTZ)-injected ICR-CD1 mice, audiogenic seizure (AGS)-susceptible DBA/2 mice and WAG/Rij rats. Seizures were monitored and scored, while absence was assessed by electroencephalogram. The open-field test was employed to assess the anxiolytic effects of WGJe. In order to assess the involvement of the GABA_A receptor, we used the antagonist flumazenil in AGS-susceptible DBA/2 mice. Computational analyses were employed to evaluate the interaction of the main polyphenols of WGJe and GABA_A receptors. Results: Our results showed that the intraperitoneal injection of WGJe hindered tonic seizures in PTZ-injected ICR-CD1 mice. In WAG/Rij rats, WGJe did not elicit any significant effects on spike-wave discharges compared to untreated rats. In AGS-susceptible DBA/2 mice, WGJe significantly hampered both clonic and tonic seizures, as well as induced anxiolytic effects. Interestingly, when administering WGJe with flumazenil to DBA/2 mice, we noted that the observed effects were mediated by the GABA_A receptor. Moreover, docking simulations confirmed that the main polyphenols of WGJe are able to interact with the benzodiazepine sites located in both extracellular and transmembrane domains in the GABA_A receptor. Conclusions: This study outlines the mechanism underlying the anti-epileptic activity of WGJe, thus supporting its potential role in the management of epilepsy. Full article

A generative adversarial network (GAN) makes it possible to map a data sample from one domain to another one. It has extensively been employed in image-to-image and text-to image translation. We propose an EEG-to-EEG translation model to map the scalp-mounted EEG (scEEG) sensor signals to intracranial EEG (iEEG) sensor signals recorded by foramen ovale sensors inserted into the brain. The model is based on a GAN structure in which a conditional GAN (cGAN) is combined with a variational autoencoder (VAE), named as VAE-cGAN. scEEG sensors are plagued by noise and suffer from low resolution. On the other hand, iEEG sensor recordings enjoy high resolution. Here, we consider the task of mapping the scEEG sensor information to iEEG sensors to enhance the scEEG resolution. In this study, our EEG data contain epileptic interictal epileptiform discharges (IEDs). The identification of IEDs is crucial in clinical practice. Here, the proposed VAE-cGAN is firstly employed to map the scEEG to iEEG. Then, the IEDs are detected from the resulting iEEG. Our model achieves a classification accuracy of 76%, an increase of, respectively, 11%, 8%, and 3% over the previously proposed least-square regression, asymmetric autoencoder, and asymmetric–symmetric autoencoder mapping models. Full article

Objective: Childhood epilepsy with centrotemporal spikes (CECTS) is associated with cognitive, behavioral, and language difficulties. These epileptic discharges predominantly occur in the temporal lobe, which is known to be involved in olfactory functions. This study aims to assess olfactory dysfunction in patients with CECTS. Methods: This study included patients diagnosed with CECTS who were attending follow-ups at the Department of Child Neurology between January 2022 and July 2023. Olfactory function was evaluated using the Sniffin’ Sticks (Burghart GmbH, Wedel, Germany) 12-point screening test, which was administered to 44 patients and 35 controls. The smell test and the final control EEGs were performed simultaneously. Results: A total of 44 patients and 35 control subjects were enrolled in this study. The smell scores were significantly lower in the patient group compared to the control group (p = 0.029). The patient group had a very high prevalence of anosmia compared to the control group. The normosmia rate in the control group was significantly higher. No significant difference was observed in the smell scores based on EEG findings or antiepileptic drug type. Conclusions: Olfactory dysfunction was identified in patients with CECTS compared to healthy controls, yielding results consistent with findings for other types of epilepsy. Olfactory dysfunction was detected in a greater frequency among the patients diagnosed with CECTS than among the healthy control group, and similar results were obtained with other types of epilepsy. It was deduced that these patients may experience problems with smell sensitivity throughout their lives. The most important result of this study is that this condition should be taken into account in regard to patients’ well-being and lives. Full article

Background and Objectives: Developmental and epileptic encephalopathy refers to a group of conditions where patients experience abnormal development due to various causes as well as frequent epileptiform discharges that ultimately contribute, in an independent and additive fashion, to cognitive and linguistic impairments. The language and cognition outcome of these patients in adulthood has been understudied. This paper aims to present a scoping review of linguistic abilities in adults with developmental and epileptic encephalopathy to determine the extent to which language outcomes in adulthood and their relation to cognitive outcomes have been studied. Design: Two online databases were searched and the methodological framework by Arksey & O’Malley (2005) was adopted. Results: Out of the 27 selected studies, only 13 exclusively examined adults, 15 were group studies, 5 were case studies and 7 were case series. A total of 9 out of the 15 group studies provided individual results for adults. Twenty-two studies included a follow-up examination. Twenty-three studies addressed the relationship between language and cognition. The selected studies indicate the presence of language impairments, which are nevertheless differentially manifested in the syndromes under investigation, whereas individual variability is also reported. Aspects of cognition seem to correlate with linguistic abilities. Conclusions: In sum, despite variability in linguistic abilities, language deficits constitute a significant aspect of the clinical profile of many adults with developmental and epileptic encephalopathy, a finding that should be taken into account for the treatment protocols of these individuals. Full article

Objectives: To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging (“MRI-negative” or “non-lesional MRI”). Methods: We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities. Results: We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32–100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52–89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28–75% of cases and altered the surgical plan in 5–33% of cases. Conclusions: MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy. Full article

Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities. However, acute metabolic adaptation during epileptic activity and its relationship to chronic epilepsy remains poorly understood. We elicited seizure-like events (SLEs) in an in vitro model of status epilepticus for eight hours. Electrophysiological recording and tissue oxygen partial pressure recordings were performed. After eight hours of ongoing SLEs, we used proteomics-based kinetic modeling to evaluate changes in metabolic capacities. We compared our findings regarding acute metabolic adaptation to published proteomic and transcriptomic data from chronic epilepsy patients. Epileptic tissue acutely responded to uninterrupted SLEs by upregulating ATP production capacity. This was achieved by a coordinated increase in the abundance of proteins from the respiratory chain and oxidative phosphorylation system. In contrast, chronic epileptic tissue shows a 25–40% decrease in ATP production capacity. In summary, our study reveals that epilepsy leads to dynamic metabolic changes. Acute epileptic activity boosts ATP production, while chronic epilepsy reduces it significantly. Full article

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by Polybia occidentalis venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202′s ED₅₀ did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically. Full article

Epilepsy is a neurological disease that affects approximately 50 million people worldwide. Despite an existing abundance of antiepileptic drugs, lifelong disease treatment is often required but could be improved with alternative drugs that have fewer side effects. Given that epileptic seizures stem from abnormal neuronal discharges predominately modulated by the human sodium channel Nav1.2, the quest for novel and potent Nav1.2 blockers holds promise for epilepsy management. Herein, an in vivo approach was used to detect new antiepileptic compounds using the maximum electroshock test on mice. Pre-treatment of mice with extracts from the Ficus religiosa plant ameliorated the tonic hind limb extensor phase of induced convulsions. Subsequently, an in silico approach identified potential Nav1.2 blocking compounds from F. religiosa using a combination of computational techniques, including molecular docking, prime molecular mechanics/generalized Born surface area (MM/GBSA) analysis, and molecular dynamics (MD) simulation studies. The molecular docking and MM/GBSA analysis indicated that out of 82 compounds known to be present in F. religiosa, seven exhibited relatively strong binding affinities to Nav1.2 that ranged from −6.555 to −13.476 kcal/mol; similar or with higher affinity than phenytoin (−6.660 kcal/mol), a known Na⁺-channel blocking antiepileptic drug. Furthermore, MD simulations revealed that two compounds: 6-C-glucosyl-8-C-arabinosyl apigenin and pelargonidin-3-rhamnoside could form stable complexes with Nav1.2 at 300 K, indicating their potential as lead antiepileptic agents. In summary, the combination of in vivo and in silico approaches supports the potential of F. religiosa phytochemicals as natural antiepileptic therapeutic agents. Full article