Search Results (148)

About 70 million people globally have been diagnosed with epilepsy. Electroencephalogram (EEG) devices are the primary method for identifying and monitoring seizures. The use of EEG expands the preclinical research involving the long-term recording of neuro-activities in rodent models of epilepsy targeted towards the efficient testing of prospective antiseizure medications. Typically, trained epileptologists visually analyse long-term EEG recordings, which is time-consuming and subject to expert variability. Automated epileptiform discharge detection using machine learning or deep learning methods is an effective approach to tackling these challenges. This systematic review examined and summarised the last 30 years of research on detecting epileptiform discharge in rodent models of epilepsy using machine learning and deep learning methods. A comprehensive literature search was conducted on two databases, PubMed and Google Scholar. Following the PRISMA protocol, the 3021 retrieved articles were filtered to 21 based on inclusion and exclusion criteria. An additional article was obtained through the reference list. Hence, 22 articles were selected for critical analysis in this review. These articles revealed the seizure type, features and feature engineering, machine learning and deep learning methods, training methodologies, evaluation metrics so far explored, and models deployed for real-world validation. Although these studies have advanced the field of epilepsy research, the majority of the models are experimental. Further studies are required to fill in the identified gaps and expedite preclinical research in epilepsy, ultimately leading to translational research. Full article

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013–2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent. Full article

Moyamoya disease is a cerebrovascular pathology characterized by progressive stenosis of the internal carotid arteries and their branches, leading to ischemic and/or hemorrhagic disorders of the cerebral circulation, primarily affecting children and young adults. We present a case of a 23-year-old woman with a history of recurrent cerebrovascular accidents since childhood. Despite experiencing focal motor seizures and transient ischemic attacks, her condition remained undiagnosed until 2006, when, at the age of 7, a digital subtraction angiography revealed characteristic bilateral internal carotid artery occlusions. Subsequent diagnostic challenges and treatments preceded a worsening of symptoms in adulthood, including generalized tonic–clonic seizures. Upon presentation to our clinic, the patient exhibited upper motor neuron syndrome and occipital lobe syndrome, consistent with the disease’s pathophysiology, neuroimaging, and clinical manifestations. Imaging studies confirmed multiple ischemic lesions throughout the cerebral vasculature. Treatment adjustments were made due to the increased incidence of seizures, and the dose of her anti-seizure medication—divalproex sodium—was increased. This case underscores the diagnostic complexities and challenges in managing moyamoya disease, emphasizing the importance of early recognition and prompt intervention. Full article

Background and Objectives: Oxidative stress resulting from a disturbance of the endogenous redox system is suspected in numerous diseases of the central nervous system, including epilepsy. In addition, antiseizure medications (ASMs), especially those of the old generation, may further increase oxidative stress. To evaluate the effects of ASM generation on oxidative stress, we conducted a cross-sectional study in patients with epilepsy treated with old, new, and polytherapy. Materials and Methods: The antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as the concentrations of malondialdehyde, protein carbonyl, nitrate, nitrite, and glutathione in reduced and oxidized forms, were measured in 49 patients with epilepsy and 14 healthy controls. In addition, the plasma concentrations of ASMs and metabolites of carbamazepine and valproic acid were measured in the patients. Results: Patients with epilepsy showed increased activities of superoxide dismutase and catalase (p < 0.001), concentrations of glutathione disulfide and markers of nitric oxide metabolism (p < 0.001), and decreased activities of glutathione peroxidase, glutathione reductase, glutathione, and nitrite concentrations (p ≤ 0.005) compared to healthy controls. A comparison of ASM generations revealed increased levels of superoxide dismutase and catalase (p ≤ 0.007) and decreased levels of glutathione peroxidase and glutathione reductase (p ≤ 0.01) in patients treated with old ASMs compared to those treated with new generation ASMs. In addition, an increase in protein carbonyl and nitric oxide metabolites (p ≤ 0.002) was observed in patients treated with old generation ASMs compared to those treated with new generation ASMs. Most oxidative stress parameters in patients receiving polytherapy with ASMs were intermediate between the results of patients treated with the old and new generations of ASMs. Conclusions: An increase in oxidative stress markers and modulation of antioxidant enzyme activities was observed in patients with epilepsy compared to controls. The results of our study showed significantly higher oxidative stress in patients treated with old ASMs compared to those treated with new generation ASMs. Full article

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.2 (NaV1.2), a validated target for antiseizure medications. Four of the resulting in silico hits were submitted for experimental confirmation using in vitro patch clamp experiments, and their protective role was evaluated in an acute mice seizure model, the Maximal Electroshock seizure model. These four compounds were found to protect mice against seizures. Two of them exhibited blocking effects on NaV1.2, CaV2.2, and CaV3.1. Full article

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed. Full article

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration. Full article

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)–drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs. Full article

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities. Full article

Background and Objectives: The investigation of the psychosomatic symptoms in women residing in developing countries is still emerging. To be precise, the prevalence and correlates of severe fibromyalgia, depression, anxiety, and insomnia are understudied in Arab women, as these symptoms could relate to improper self-medication. This study mainly investigated the association between self-medication with analgesics and fibromyalgia, depression, anxiety, and insomnia symptoms among a community-based cohort of females in Jordan. Materials and Methods: We used a web-based cross-sectional study design. Fibromyalgia, depression, anxiety, and insomnia were assessed using validated scales. The used over-the-counter (OTC) painkillers were recorded. Results: Data were analyzed from 741 women, and fibromyalgia was screened in 16.4%, depression in 37.4%, anxiety in 27.8%, and insomnia in 38.3%. Fibromyalgia was associated with “married” (OR = 1.5, 95% CI = 1.017–2.305), “using OTC acetaminophen” (OR = 1.75, 95% CI = 1.15–2.69), “using herbal remedies” (OR = 2.02, 95% CI = 1.33–3.07), and “using antiseizure medications” (OR = 2.43, 95% CI = 1.38–4.28). Severe depression was significantly associated with “age” (OR = 0.97, 95% CI = 0.96–0.99), “high school education” (OR = 1.90, 95% CI = 1.21–2.98), “smoking” (OR = 1.72, 95% CI = 1.15–2.56), “OTC acetaminophen” (OR = 1.40, 95% CI = 1.02–1.92), “OTC non-steroidal anti-inflammatory drugs” (OR = 1.75, 95% CI = 1.15–2.65), and “antiseizures” (OR = 2.19, 95% CI = 1.30–3.70). Severe anxiety was significantly associated with “smoking” (OR = 2.08, 95% CI = 1.40–3.12), “OTC acetaminophen” (OR = 1.48, 95% CI = 1.06–2.06), and “antiseizure medications” (OR = 2.04, 95% CI = 1.22–3.41). Severe insomnia was significantly associated with “age” (OR = 0.98, 95% CI = 0.96–0.99), “high school education” (OR = 1.58, 95% CI = 1.01–2.47), “smoking” (OR = 1.51, 95% CI = 1.01–2.25), “OTC non-steroidal anti-inflammatory drugs” (OR = 1.74, 95% CI = 1.13–2.64), “antiseizure medications” (OR = 1.84, 95% CI = 1.09–3.11), and “No analgesics” (OR = 0.48, 95% CI = 0.32–0.71). Conclusions: Self-medication with analgesics is associated with a high burden of psychosomatic symptoms in Arab women, and awareness campaigns are required to guide self-medication behavior. Full article

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life. Full article

Epilepsy is one of the most common neurological diseases worldwide. Anti-seizure medications (ASMs) with anticonvulsants remain the mainstay of epilepsy treatment. Currently used ASMs are, however, ineffective to suppress seizures in about one third of all patients. Moreover, ASMs show no significant impact on the pathogenic mechanisms involved in epilepsy development or disease progression and may cause serious side-effects, highlighting the need for the identification of new drug targets for a more causal therapy. Compelling evidence has demonstrated a role for purinergic signalling, including the nucleotide adenosine 5′-triphosphate (ATP) during the generation of seizures and epilepsy. Consequently, drugs targeting specific ATP-gated purinergic receptors have been suggested as promising treatment options for epilepsy including the cationic P2X7 receptor (P27XR). P2X7R protein levels have been shown to be increased in the brain of experimental models of epilepsy and in the resected brain tissue of patients with epilepsy. Animal studies have provided evidence that P2X7R blocking can reduce the severity of acute seizures and the epileptic phenotype. The current review will provide a brief summary of recent key findings on P2X7R signalling during seizures and epilepsy focusing on the potential clinical use of treatments based on the P2X7R as an adjunctive therapeutic strategy for drug-refractory seizures and epilepsy. Full article

Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy. Full article

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy. Full article

Background and Objectives: Ketogenic diet therapy (KDT) has been used as a non-pharmacological treatment for childhood refractory epilepsy. Its efficacy and safety have been described in numerous studies and reviews. However, there have been fewer studies evaluating the challenges experienced by patients and their family members when starting KDT. When implementing a new treatment method, challenges arise for both the healthcare professionals and patients, making it important to summarize the initial results and compare them with the experiences of other centers. To analyze and evaluate the efficacy and safety of KDT in children with epilepsy, as well as to consider the challenges faced by their parents/caregivers. Materials and Methods: A retrospective analysis of patients’ data (N = 30) and an analysis of the completed questionnaires of the parents/caregivers (N = 22) occurred. Results: In the study group, 66.7% of the patients had a >50% decrease in seizure frequency, and 2/3 of them had a >90% decrease in seizure frequency or were seizure-free, which enabled reducing the anti-seizure medications in 36.4% of the patients, as well as reducing the hospital visits. Cognitive improvement and better alertness were subjectively reported by 59.1% of the parents/caregivers. No dangerous long-term adverse effects of KDT have been observed in the study group. The patients with generalized epilepsy experienced significantly more adverse events. Most of the adverse effects of KDT were related to the digestive system, but usually they were temporary and controllable. The challenges of the parents/caregivers were mostly related to social life issues and financial difficulties; the medical-related challenges were minimal. Conclusions: KDT is an effective and safe treatment option for children with drug-resistant epilepsy, and the challenges faced by families are resolvable. In order to ensure effective KDT, a multidisciplinary team is required. This would ensure smooth and comprehensive care and the timely resolution of emerging problems. The cooperation of the families undergoing KDT is also important, enabling them to share their experiences. Full article