It is not understood why children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of seizures, including infantile spasms and tonic-clonic seizures. Using a novel humanized mouse model of DS (TcMAC21), we recently showed that TcMAC21 mice express an increased propensity to infantile spasms and demonstrate an increased neocortical synaptic excitation-to-inhibition ratio. To understand the pathophysiology of DS that may predispose animals to increased seizure susceptibility, we investigated 1) kainic-acid receptor (KAR)-mediated excitation, 2) gamma-aminobutyric acid receptors A and B (GABAR and GABAR)-mediated inhibition, and 3) synaptojanin 1 (SYNJ1) function in TcMAC21 mice, as genes encoding KAR, GABAR and SYNJ1 are among those triplicated in DS. Layer V neocortical neurons were recorded using whole-cell patch-clamp recordings to test KAR, GABAR, GABAR, and SYNJ functions. TcMAC21 neurons responded to focal KA application with significantly larger currents than control euploid neurons. GABAR-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) were less frequent in TcMAC21 than in euploid neurons while sIPSC amplitudes remained unchanged. Bath application of a GABAR agonist, baclofen, caused similar hyperpolarization in TcMAC21 and euploid neurons. During repetitive synaptic stimulation, excitatory postsynaptic currents (EPSCs) in TcMAC21 neurons decayed slower and to a lesser extent than control euploid neurons, indicating less transmitter depletion (i.e., enhanced synaptic vesicle trafficking). These data provide the first physiological evidence for gain-of-function of KAR and SYNJ1, and altered GABA-mediated synaptic function in TcMAC21 mice, and may represent some important DS-specific mechanisms of seizure pathogenesis.

Anhedonia, characterized by reduced pleasure or interest, is linked to various neurological disorders, including genetic epilepsies. Previous studies in genetic rat models of absence epilepsy, such as WAG/Rij rats, have reported anhedonia-like behaviors. Here, we hypothesize that these behaviors depend on experimental factors rather than epilepsy itself. To test this, we conducted sucrose preference tests in WAG/Rij rats using different concentrations (2 % and 20 %), fasting durations (0 and 23 h), and test lengths (1 and 48 h). Rats underwent non-invasive electroencephalographic examination, which revealed typical 8-10 Hz spike-wave discharges (SWD) and a hallmark of absence epilepsy. In Experiment 1 (2 % sucrose), 59 symptomatic and 31 asymptomatic rats were tested at 6 and 12 months. In Experiment 2 (20 % sucrose), 34 rats were tested at 6 months. Surprisingly, there were no significant differences in sucrose preference or consumption between symptomatic and asymptomatic rats, indicating that absence epilepsy in WAG/Rij rats does not cause anhedonia. After a 23-h fast, female rats showed a lower preference for 20 % sucrose than males, suggesting that fasting conditions might introduce stress and metabolic differences that affect males and females differently. Both the 2 % and 20 % sucrose preference tests showed that symptomatic WAG/Rij rats did not exhibit anhedonia and had similar preferences to asymptomatic rats, regardless of concentration or fasting conditions. These findings challenge previous assumptions and emphasize the importance of considering methodological factors when interpreting rodent behavior.

To compare the effectiveness and safety of perampanel as first add-on vs. late add-on therapy in children with focal or generalized epilepsy.

Epilepsy represents a significant global burden, with antiseizure drugs (ASDs) essential for treatment. This study examines past and recent trends in ASD consumption in 11 European countries, forecasts future developments, analyses Anatomical Therapeutic Chemical Classification (ATC) subgroup use, and offers an initial assessment of treatment sufficiency.

This study aims to evaluate seizure outcomes and identify predisposing factors for epilepsy in patients diagnosed with B-cell acute lymphoblastic leukemia (B-ALL).

To evaluate the safety and potential efficacy of fenfluramine (FFA) in patients with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS).

An imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters is a key mechanism in epilepsy. Astrocytic glutamate transporter-1 (GLT-1) helps reuptake glutamate in the synaptic cleft to maintain glutamate concentration and prevent neuronal hyperactivity. Sulbactam (SUL), a β-lactam drug, increases GLT-1 expression. Valproate (VPA) is a first-line antiepileptic drug. The current study evaluated the effects of SUL and VPA on histology and electroencephalography in a pentylenetetrazol (PTZ)-induced epilepsy rat model. Male Wistar rats received intraperitoneal injection of PTZ (20-35 mg/kg, every other day) for 25 days (13 injections in total) to establish an epilepsy model. From day 26, saline, SUL (50 or 150 mg/kg), VPA (50 mg/kg), or a combination of SUL and VPA was intraperitoneally administered daily for 25 days. Electroencephalography recordings were taken on day 46 or 47. Brains were used for histological analyses. Electrophysiological results indicated that during the PTZ challenge session, the epilepsy group had significantly more spikes and seizures and higher delta, theta, and beta power compared with the control group. SUL at 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly reduced the numbers of spikes and seizures. SUL at both 50 and 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly inhibited the increase in delta, theta, and beta power. In terms of histology, the epilepsy group exhibited lower neuronal density in the hippocampus, lower GLT-1 expression in astrocytes, lower GABAergic density, and hyperactivity in the subthalamic nucleus. These neurophysiological impairments were restored by treatment with SUL and a combination of SUL and VPA. The results suggest that SUL increases GLT-1 expression in astrocytes and the number of GABAergic neurons, indicating it holds potential as an antiepileptic treatment.

Patients with epilepsy (PWE) taking antiseizure medications (ASMs) exhibit altered autonomic nervous system (ANS) parameters. ANS signals may monitor ASM applications and effectiveness non-invasively. Due to limited research, we reviewed the effects of ASMs on the pediatric ANS. We followed PRISMA guidelines and searched PubMed, Web of Science, and Embase for publications until 12/2024. These studies investigated the impact of ASMs on ANS, including heart rate (HR), heart rate variability (HRV), temperature, and sweat. We used Covidence software for screening processes and data extraction. After screening 9837 studies, 23 were included. Zonisamide and topiramate showed reduced sweating and increased temperature. In polytherapy patients, HRV decreased, with reductions in high-frequency (HF) values on valproic acid and low-frequency values on phenobarbital. Higher ASM doses reduced HRV but did not affect HR or sweat glands. One study reported altered cardiac ventricle functioning in PWE on ASMs. Two studies reviewing the effect of levetiracetam found minimal short-term ANS effects within the ECG but improved parasympathetic control and restored balance in HRV parameters over time. Sympathetic and parasympathetic dysfunctions were prominent in some patients, with polytherapy increasing HR and reducing HF values of HRV. In one study, higher ASM concentrations lowered HRV. Overall, ASMs may influence HR, sweat, and temperature, though many studies lacked analysis of specific ASM types. A better understanding of how ASMs affect ANS is essential for assessing medication efficacy, side effects, and their role as confounders in seizure prediction. These biosignal data can support device-based neuromodulation, seizure detection, and prediction algorithms.

To evaluate the relationship between multimodal diagnostic concordance and postoperative seizure outcomes in patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG)-guided volumetric radiofrequency thermocoagulation (RFTC).

To investigate whether Tailored Provocation (TP) can result in habitual seizures during electroencephalogram (EEG) recording in patients with a probable diagnosis of functional seizures (FS) and if future research is feasible.

We systematically reviewed the existing literature on the efficacy of the ketogenic diet (KD) in patients with epileptic spasms (ES) and analyzed predictors of seizure outcomes.

This study investigates structural changes in the hippocampus, fornix, and mammillary bodies in patients with mesial temporal sclerosis (MTS), examining their relationship to clinical characteristics and association with memory performance. We conducted a retrospective study involving 104 patients with unilateral MTS and 47 age-matched healthy controls. Automatic segmentation of MRI scans was performed to calculate volumes, and atrophy was assessed relative to average values in the control group. Volume differences between patients and controls as well as associations of circuit atrophy with clinical features and memory impairment were examined. In the left MTS group, all three structures showed significantly lower normalized volumes compared to healthy controls whereas atrophy was confined to the hippocampus and fornix in the right MTS group. No significant correlations were found between atrophy and disease duration or age at seizure onset for any structure, though age at MRI was significantly correlated with hippocampal atrophy. Volume reductions in each of the circuit endpoints (hippocampus and mammillary bodies) were correlated with the degree of atrophy in the bridging white matter structure, the fornix. Lastly, comparisons between subgroups with hippocampal atrophy only versus those with greater circuit damage revealed no significant differences in memory scores, age of onset, or duration. Our findings support the view that MTS involves network-level degeneration affecting multiple memory-related structures beyond the hippocampus. Unexpectedly, no significant associations were found between atrophy and clinical or memory measures, suggesting structural damage in this portion of the Papez circuit may be of limited clinical relevance in this population.

We investigated effects of long-term and acute administration of EQU-001 (ivermectin) against NMDA-triggered spasms in immature rats prenatally exposed to betamethasone and in the model of infantile epilepsy spasms syndrome (IESS). Pregnant rats were injected with betamethasone on gestational day 15 (2 ×0.4 mg/kg, i.p.). Offspring were injected with ivermectin once daily (1-4 mg/kg, i.p.) from postnatal day (P) 10 through P15. Spasms were triggered on P15 with NMDA (17 mg/kg, i.p.). Other rats received a single dose of ivermectin (1-8 mg/kg, i.p.) on P15 prior to NMDA to test acute anticonvulsant activity. Also, a randomized model was used: The spasms were triggered on P12 and ivermectin treatment (4 mg/kg) was initiated after this bout of spasms on P12, P13 and P14, with additional spasms elicited on P13 and P15. A nicotinic cholinergic α7 agonist was used to mimic effects of ivermectin, and α7 antagonist was used together with ivermectin to prevent its effects. P10-P15 administration of 4 mg/kg of ivermectin significantly suppressed occurrence of spasms on P15, an effect comparable to that of ACTH (positive control). Conversely, an acute P15 administration of ivermectin had no effects on spasms. Ivermectin in the randomized trial suppressed occurrence of spasms as well P15/P12 ratio of spasms. Ivermectin also decreased body weight gain in those animals. None of the nicotinic cholinergic α7 drugs mimicked or prevented effects of ivermectin. Our data indicate that ivermectin may become a powerful tool in the armamentarium for treatment of IESS, however the mechanisms of this action remain to be determined.

While epilepsy secondary to vascular insults represents a well-documented cause of drug-resistant epilepsy that requires surgical intervention for optimal management, the prognostic factors for postoperative seizure-freedom among this patient population have not been well-established. This individual-patient data (IPD) meta-analysis aimed to 1) determine prognostic factors associated with seizure-freedom postoperatively and 2) factors associated with postoperative complications.

Brain tumor-related epilepsy (BTRE) is a common and disabling complication of primary brain tumors. While older antiseizure medications (ASMs) are limited by adverse effects and drug interactions, newer ASMs such as levetiracetam (LEV), lamotrigine (LTG), and lacosamide (LCS) may offer better tolerability and seizure control. This study aimed to evaluate the efficacy and safety of these newer ASMs in patients with BTRE.

Frontal lobe epilepsy (FLE) is the second most common type of focal epilepsy and among the most challenging to diagnose and treat. Although surgical resection offers potential seizure freedom, outcomes vary, and high-quality data from low- and middle-income countries are scarce. This study aimed to describe a cohort of patients with FLE undergoing epilepsy surgery and identify clinical, imaging, and pathological factors associated with favorable outcomes.

Neurosurgery is a viable treatment option for patients with drug-resistant epilepsy (DRE), where accurate localization of the epileptogenic zone (EZ) is crucial for surgical success. This study aims to develop an interpretable machine learning (ML) framework that integrates electrophysiological features to enhance EZ localization.

Human temporal lobe epilepsy (TLE), particularly drug-resistant TLE, is associated with chronic peripheral immune activation. Here, we determined whether a similar association was detectable in a genetic mouse model of TLE with spontaneous recurrent seizures (SRS), Kcna1-null mice. Flow cytometry was used with fluorescence-activated cell sorting to determine the presence of lymphocytes, macrophages and granulocytes in isolated brain and spleen of wildtype (WT) and Kcna1-null mice. Splenic analysis revealed uniformly elevated Mac-1MHC-II macrophages across all epileptic mice, whereas CD8 cytotoxic T-cells increased proportionally with severe seizure frequency and burden, resulting in reduced CD4/CD8 ratios-an immune risk phenotype. Brain tissue showed increased infiltration of both CD4 and CD8 T-cells. Importantly, Kv1.1 was not expressed on T-cells of WT mice. Using an allostatic interpretative framework, our results indicate that the immune system anticipates ongoing challenges (SRS) and maintains elevated readiness with an allostatic shift towards chronic adaptation (macrophages), but in doing so potentially damaging dynamic allostatic loads (CD8 T-cells) are accumulated. The Kcna1-null model provides a valuable tool for investigating epilepsy immunopathogenesis without chemoconvulsant confounds. These findings support the notion that TLE has a significant immunological component which may participate in pathology and be a target for intervention.

Epilepsy(ICD-10 G40-G41) and stroke-including hemorrhagic stroke (HS: I60-I62) and ischemic stroke (IS: I63))-are major neurological disorders. Although epilepsy has been proposed as a risk factor for stroke, large-scale evidence from Asian populations and analyses of time-dependent risk remain limited. This study investigated long-term risks of HS and IS after epilepsy using a nationwide cohort in South Korea.

To evaluate the effectiveness and safety of lacosamide (LCM) in children with epilepsy aged 1 month to 2 years, including those with developmental epileptic encephalopathy (DEE), and to identify risk factors influencing effectiveness.

Predicting the postoperative outcome of stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) remains challenging despite its increasing use in epilepsy treatment. Although SEEG-guided RF-TC has attracted extensive clinical interest, reliable biomarkers for treatment efficacy are still lacking. This study aims to address this gap by analyzing the altered brain network to predict postoperative outcome. Thirty-one focal cortical dysplasia epileptic patients who underwent RF-TC based on SEEG were enrolled in this study. They were included in the favorable outcome and poor outcome groups according to the follow-up. Partial Directed Coherence and Directed Transfer Function were applied to construct SEEG brain networks, and then brain network features were extracted. Subsequently, the differences in the presurgical and postsurgical brain network features were compared using the Wilcoxon test in the favorable and poor outcome groups, respectively. Finally, four machine learning models were applied to predict the outcome of RF-TC. After RF-TC surgery, the Characteristic Path Length (L) and average Betweenness Centrality (BC) increased while the average Clustering Coefficient (C) and Assortativity Coefficient (R1, R2) decreased in the favorable outcomes group. In contrast, there were no significant changes in the patient group with poor outcomes. The Support Vector Machine (SVM) model achieved the highest performance, with accuracy, sensitivity, specificity, and ROC values of 0.887, 0.821, 0.920, and 0.879, respectively. This study sheds light on the mechanisms of epilepsy from the perspective of brain networks and introduces a novel therapeutic strategy by altering network features. These feature alterations can also support machine learning models in effectively distinguishing favorable from poor outcomes.