Recurrent Seizures Research Articles

DEPDC5 mutations in familial epilepsy syndrome: genetic insights and therapeutic approaches

Background. DEPDC5 (disheveled, Egl-10 and pleckstrin domain-containing protein 5) familial epilepsy syndrome is a group of epilepsy disorders caused by mutations in DEPDC5 gene, which is a part of the gap activity towards rag 1 (GATOR1) complex involved in regulating the mechanism target of rapamycin (mTOR) pathway. These mutations lead to hyperactivation of the mTOR pathway, disrupting the shaping of neurons and resulting in increased excitatory transmission and the development of epilepsy. The incidence and prevalence of DEPDC5 familial epilepsy syndrome are not well established, but studies suggest it may account for up to 10% of familial focal epilepsy cases. Genetic testing, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) are important in diagnosing the disorder, although normal MRI results are common.Objective: to explain the rare sporadic mutation in DEPDC5 gene with p.R389H, a variant of unknown significance.Case report. A 6-year-old South-Asian girl was born at 34-weeks from non-consanguineous marriage without any prenatal events. She had hyperbilirubinemia by week-1, which was successfully treated with phototherapy. Her initial seizure occurred when she was three months old, just 2 days after the fever from the vaccination had subsided. It was considered a simple-febrile seizure and no treatment was given. At 3.5-months, she started having recurrent seizures. Workup including MRI/ infectious/metabolic panel was non-conclusive. EEG during the initial presentation showed epileptiform activity from the left temporal region. Despite being on multiple anti-epileptic drugs, the child was diagnosed with refractory epilepsy. Subsequently, EEG at 2.5-years showed inter-ictal bi-hemispheric epileptiform activity. EEG at 5-years showed inter-ictal spikes and wave discharges from bilateral fronto-temporal region with secondary generalization. By 3-years, MRI showed mildly deformed corpus callosum with inadequate thickening of splenium. DNA analysis confirmed heterozygous missense mutation in exon 16 of DEPDC5 gene, without chromosomal abnormalities. Mother was heterozygous for the same mutation but no mutations in the father was found. The child has grossly delayed milestones. Corrected age is approximately 1-year for fine motor and language, 1.5-years for gross motor, 2.5-years for cognition, social skills. She had developed autistic features as well with significant impaired auditory/visual processing. She had hypotonia (Right>Left), wide-based gait, and extrapyramidal movements.Conclusion. DEPDC5 gene mutation results in amino acid substitution of Histidine for Arginine at codon 389. This mutation has shown to be inherited in familial pattern. This R389H variant is not present in the 1000 genomes database and is predicted to be benign. However, It rather appears to be a sporadic mutation, which is a very rarely observed phenomena. Such patients may respond well to mTOR inhibitors such as rapamycin, making prompt diagnosis and treatment crucial.

Effects of Klotho in epilepsy: An umbrella review of observational and mendelian randomization studies.

Klotho is a geroprotective protein which has been recognized for its anti-aging properties. Pre-clinical evidence suggested that boosting Klotho might hold therapeutic potential in ageing and disease. Epilepsy is a neurological disorder characterized by its recurrent seizures. The complex interplay between Klotho and epilepsy has not been elucidated. The main objective was to investigate the role of Klotho in epilepsy with combination of observational and mendelian randomization (MR) studies. The observational data set comprised 13,766 adults who were aged 20-80years from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. We used weighted multivariable-adjusted logistic regression models to examine the association between Klotho and epilepsy. We also applied MR to discern if a causal link is present between Klotho and epilepsy. In NHANES study, the incidence of epilepsy tended to decline with an increase of Klotho levels after covariate adjustments. Klotho was identified to have causal effects on epilepsy. MR analyses revealed that higher transformed Klotho (by rank-based inverse normal transformation) levels were correlated with a higher likelihood of developing generalized epilepsy, lesion-negative focal epilepsy, and focal epilepsy, indicating that higher Klotho concentrations were associated with reduced risks of epilepsy. The sensitivity analyses upheld these consistent relationships. Our research, encompassing comprehensive NHANSE analysis and MR methods, revealed that an increase in Klotho levels was associated with a reduced risk of epilepsy, suggesting that increasing or restoring Klotho might play a protective role and offer new anti-aging therapeutic potential in epilepsy.

Early-Onset Seizures After Orthotopic Liver Transplantation: A Single-Center Retrospective Study.

After encephalopathy, epileptic seizures (ES) are the second most common neurologic complication after orthotopic liver transplantation (OLT) and may announce a disabling/fatal neurologic disease. In this retrospective study, we collected clinical information from patients who underwent OLT at our institution and analyzed outcomes and potential risk factors for developing ES after OLT. Fourteen of our 376 patients (3.72%) who underwent OLT had ES. After excluding 2 patients with already known epilepsy, among the other 12 patients, 2 were diagnosed with nonanoxic cerebral edema, 2 with anoxic damage, 1 with intracranial hemorrhage, 1 with metabolic derangement, and 4 with neurotoxicity; 2 did not receive a diagnosis of certainty. 9 of 12 patients had structural abnormalities on neuroimaging exams. Patients with ES had lower body mass index, higher rate of pretransplant portal thrombosis, and lower pre-transplant plasma concentration of albumin than patients without ES. Multiple post-transplantation systemic complications, postoperative infections, and graft rejection were correlated with a significantly higher risk of ES. Compared with patients without seizures, patients with ES had longer in-hospital and intensive care unit (ICU) length of stay, higher probability of ICU readmission, in-hospital death, and need for rehabilitation. Just 3 of the 12 patients with ES had a good prognosis, while the other 9 had at least mild neurologic sequelae, 5 of whom died because of the underlying neurologic disease. ES after OLT may announce detrimental neurologic disease. When an underlying neurologic disease is excluded, prognosis in terms of seizure recurrence and long-term antiseizure medication need is warranted.

Case Report: Diagnosis and treatment of incontinentia pigmenti with central nervous system anomalies in one patient

IntroductionThis article reports a detailed case of a patient with incontinentia pigmenti who exhibited epileptic status and dermatologic symptoms.Case presentationA 5-month-old female patient was brought to our hospital due to status epilepticus, with erythematous vesicular skin lesions on her trunk and extremities. Routine magnetic resonance imaging revealed infarction, ischemia, and encephalomalacia. Skin biopsy pathology indicated pigmentation disorder. Molecular genetic testing was conducted to identify IKBKG mutations, and the case was finally diagnosed with incontinentia pigmenti complicated by central nervous system anomalies. She was treated with oral levetiracetam (10 mg/kg/day, administered every 12 h) to control her recurrent seizures, and prednisone (1 mg/kg/day, once a day) for anti-inflammatory effects.ConclusionAfter nine months, her skin lesions have resolved, with only a few newly developed erythematous papules and areas of hyperpigmentation being evident. There were no recurrent epilepsy symptoms, developmental impairments, or other associated symptoms.

NORSE secondary to anti-GAD65 antibody-positive encephalitis treated with novel adjunctive rapid titrationVNS protocol.

New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by refractory seizures in individuals without a prior history of epilepsy. This case report describes a 37-year-old woman diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-positive encephalitis-related NORSE. Her seizures were refractory to multiple interventions, including anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, after 32 days of treatment, the seizures were successfully controlled. To maintain seizure control and facilitate the weaning of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted using a novel rapid titration protocol. This allowed for the successful tapering of anesthetics by day 50, with no recurrence of seizures. At her 9-month follow-up, the patient remained seizure-free and had an improved quality of life. This case highlights that early initiation of immunosuppressive treatment may lead to a favorable prognosis. The novel application of VNS therapy assisted seizure control in NORSE, thus encouraging further research investigating the potential role of VNS in this condition. PLAIN LANGUAGE SUMMARY: New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by relentless seizures in individuals without a prior epilepsy history. This report shares the case of a 37-year-old woman with NORSE, associated with a high anti-glutamic acid decarboxylase 65 antibody titer. Her seizures were super-refractory, requiring multiple anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, by hospital day 32, the seizures were successfully controlled with these interventions. To further stabilize seizure control and enable the successful discontinuation of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted. The patient had no further seizures and gradually recovered back to her pre-disease baseline. This case suggests that a novel rapid VNS titration protocol could be a promising treatment option for NORSE, warranting further investigation.

Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.

Developmental and epileptic encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, FGF13 were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because FGF13 is expressed in both excitatory and inhibitory neurons, FGF13 undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell-type-specific conditional knockout mice. Interneuron-targeted deletion of Fgf13 led to perinatal mortality associated with extensive seizures and impaired the hippocampal inhibitory/excitatory balance while excitatory neuron-targeted deletion of Fgf13 caused no detectable seizures and no survival deficits. While best studied as a voltage-gated sodium channel (Nav) regulator, we observed no effect of Fgf13 ablation in interneurons on Navs but rather a marked reduction in K+ channel currents. Re-expressing different Fgf13 splice isoforms could partially rescue deficits in interneuron excitability and restore K+ channel current amplitude. These results enhance our understanding of the molecular mechanisms that drive the pathogenesis of Fgf13-related seizures and expand our understanding of FGF13 functions in different neuron subsets.

Congenital goiter in an alpaca (Vicugna pacos) fetus concomitant with brain pathology in the dam: composing the puzzle.

This study describes the congenital goiter in an alpaca (Vicugna pacos) fetus aborted in November 2021 with the clinical and pathological findings in the dam that was found dead on the farm three weeks after a miscarriage. The dam was a black coat alpaca bred in the Netherlands, imported in Italy in January 2021, and housed in a farm of central Italy for breeding purposes. Signalment and clinical data on dam and fetus were collected from the farmer and referring veterinarian. Necropsies and histopathological investigations on mother and conceptus were conducted at the Department of Veterinary Medicine, University of Perugia. The fetus was aborted at the 5th gestational month and at necropsy revealed bilateral thyroid gland enlargement. Microscopically the thyroid gland presented follicular cell hypertrophy and hyperplasia, follicles greatly varying in size, with macrofollicles lined by attenuated to atrophic epithelium and distended by eosinophilic colloid (colloid goiter). The dam presented a history of anorexia, wasting, dullness, severe weakness, incoordination, recurrent seizures, and, most recently, abortion. At necropsy, a cerebral focal loss of substance was found at the right parietal cortex, which histologically corresponded to laminar ischemic neuronal necrosis; most importantly, histological examination of cerebellum showed multifocal necrosis of the Purkinje cells associated with severe depletion of the granular layer neurons. These cerebellar findings in the dam combined with goiter in the conceptus suggest organomercurial poisoning as the likely cause of abortion followed by mother's death. Mercury poisoning is hypothesized as the possible link between mother's and fetus' lesions.

Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy

Recurrent spontaneous seizures with an extended epileptic discharge are the hallmarks of epilepsy. At present, there are several available anti-epileptic drugs (AEDs) in the market. Still no adequate treatment for epilepsy treatment is available. The main disadvantages of AEDs are their associated adverse effects. It is a challenge to develop new therapies that can reduce seizures by modulating the underlying mechanisms with no adverse effects. In the last decade, the neuromodulatory potential of phytoconstituents has sparked their usage in the treatment of central nervous system disorders. Curcumin is an active polyphenolic component that interacts at cellular and molecular levels. Curcumin’s neuroprotective properties have been discovered in recent preclinical and clinical studies due to its immunomodulatory effects. Curcumin has the propensity to modulate signaling pathways involved in cell survival and manage oxidative stress, apoptosis, and inflammatory mechanisms. Further, curcumin can persuade epigenetic alterations, including histone modifications (acetylation/deacetylation), which are the changes responsible for the altered expression of genes facilitating the process of epileptogenesis. The bioavailability of curcumin in the brain is a concern that needs to be tackled. Therefore, nanonization has emerged as a novel drug delivery system to enhance the pharmacokinetics of curcumin. In the present review, we reviewed curcumin’s modulatory effects on potential biomarkers involved in epileptogenesis including dendritic cells, T cell subsets, cytokines, chemokines, apoptosis mediators, antioxidant mechanisms, and cognition impairment. Also, we have discussed the nanocarrier systems for encapsulating curcumin, offering a promising approach to enhance bioavailability of curcumin.

Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses.

One of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression omnibus series (GSE) 33,000 and GSE63808 datasets were used to search for differentially expressed disulfidptosis-related molecules (DE-DRMs). A correlation between the DE-DRMs was discovered. Individuals with epilepsy were then used to investigate molecular clusters based on the expression of DE-DRMs. Following that, the best machine learning model which is validated by GSE143272 dataset and predictor molecules were identified. The correlation between predictive molecules and clinical traits was determined. Based on the in vitro and in vivo seizures models, experimental analyses were applied to verify the DE-DRMs expressions and the correlation between them. Nine molecules were identified as DE-DRMs: glycogen synthase 1 (GYS1), solute carrier family 3 member 2 (SLC3A2), solute carrier family 7 member 11 (SLC7A11), NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), 3-oxoacyl-ACP synthase, mitochondrial (OXSM), leucine rich pentatricopeptide repeat containing (LRPPRC), NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), NUBP iron‑sulfur cluster assembly factor, mitochondrial (NUBPL), and NCK associated protein 1 (NCKAP1). NDUFS1 interacted with NDUFA11, NUBPL, and LRPPRC, while SLC3A2 interacted with SLC7A11. The optimal machine learning model was revealed to be the random forest (RF) model. G protein guanine nucleotide-binding protein alpha subunit q (GNAQ) was linked to sodium valproate resistance. The experimental analyses suggested an upregulated SLC7A11 expression, an increased number of formed SLC3A2 and SLC7A11 complexes, and a decreased number of formed NDUFS1 and NDUFA11 complexes. This study provides previously undocumented evidence of the relationship between disulfidptosis and EP. In addition to suggesting that SLC7A11 may be a specific DRM for EP, this research demonstrates the alterations in two disulfidptosis-related protein complexes: SLC7A11-SLC3A2 and NDUFS1-NDUFA11.

A Review of the Association between Infections, Seizures, and Drugs.

Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs. The aim of this study was to present a systematic review of the association between infections, seizures, and drugs. Through February 18, 2024, according to the PRISMA guidelines and based on the PICO standard format, relevant, in-depth consequent guide approach and evidence-based options were selected associated with a knowledgeable collection of current, high-quality manuscripts. Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring. Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.

Pharmacological Investigation of Anticonvulsant Effect of Artemisia Vulgaris on Pentylenetetrazole-Induced Epileptic Seizures in Zebrafish Experimental Model

Background: Epilepsy is the most common neurological disorder, characterized by abnormal, unpredictable, and recurrent seizures. In the alternative medicine system, Artemisia vulgaris has been used to treat epileptic symptoms since its inception. However, scientific evidence concerning its effect on the treatment of epileptic seizures is not available. Objective: The objective of the study is to evaluate the anti-convulsant potential of Artemisia vulgaris in zebrafish experimental models. Methods: Zebrafish larvae and adult zebrafish were used as experimental models. Briefly, larvae and adult zebrafish were exposed to 0.5% of the test medicine Artemisia vulgaris mother tincture (ϕ) and its potencies (6 CH, 30 CH), and valproic acid for 1 hour. After 1 hour of exposure, they were exposed to pentylenetetrazole to record different seizure scores from 1 to 5 using ANY maze video tracking software. Results: Artemisia vulgaris 30CH in zebrafish larvae and Artemisia vulgaris 6 CH and 30 CH in adult zebrafish delayed the latency score from score 1 to score 5 and were found effective against PTZinduced locomotor activity and seizure duration and intensity. Conclusion: In conclusion, Artemisia vulgaris (6 CH and 30 CH) has the potential to be a novel treatment for symptomatic epileptic seizures and could be a potential alternative drug candidate for symptomatic treatment of epilepsy.

The potential therapeutic role of berberine in treating epilepsy focusing on temporal lobe epilepsy: State of art and ongoing perspective.

Epilepsy is a neurological disease characterized by unprovoked recurrent epileptic seizures. Temporal lobe epilepsy (TLE) is the commonest type of focal epilepsy in adults that resist to the conventional anti-seizure medications (ASMs). Interestingly, ASMs do not affect the epileptogenesis and progression of disease. Therefore, repurposing of natural products with anti-inflammatory, anti-oxidant and anti-seizure effects such as berberine (BRB) may be logical in treating refractory epilepsy and TLE. However, the molecular mechanism of BRB against the development of epilepsy and progression of epileptic seizure mainly in TLE was not fully elucidated. Therefore, we attempt in this review to discuss the potential underlying molecular mechanism of BRB against the development and progression of epilepsy mainly the TLE.

A Revolutionary Approach for Combating Efflux Transporter-mediated Resistant Epilepsy: Advanced Drug Delivery Systems.

Epilepsy is a persistent neurological condition that affects 60 million individuals globally, with recurrent spontaneous seizures affecting 80% of patients. Antiepileptic drugs (AEDs) are the main course of therapy for approximately 65% of epileptic patients, and the remaining 35% develop resistance to medication, which leads to Drug-Resistant Epilepsy (DRE). DRE continues to be an important challenge in clinical epileptology. There are several theories that attempt to explain the neurological causes of pharmacoresistance in epilepsy. The theory that has been studied the most is the transporter hypothesis. Therefore, it is believed that upregulation of multidrug efflux transporters at the blood-brain barrier (BBB), such as P-glycoprotein (P-gp), which extrudes AEDs from their target location, is the major cause, leading to pharmacoresistance in epilepsy. The most effective strategies for managing this DRE are peripheral and central inhibition of P-gp and maintaining an effective concentration of the drug in the brain parenchyma. Presently, no medicinal product that inhibits P-gp is being used in clinical practice. In this review, several innovative and promising treatment methods, including gene therapy, intracranial injections, Pgp inhibitors, nanocarriers, and precision medicine, are discussed. The primary goal of this work is to review the P-gp transporter, its substrates, and the latest novel treatment methods for the management of DRE.

A New Perspective in Epileptic Seizure Classification: Applying the Taxonomy of Seizure Dynamotypes to Noninvasive EEG and Examining Dynamical Changes across Sleep Stages.

Epilepsy, a neurological disorder characterized by recurrent unprovoked seizures, significantly impacts patient quality of life. Current classification methods focus primarily on clinical observations and electroencephalography (EEG) analysis, often overlooking the underlying dynamics driving seizures. This study uses surface EEG data to identify seizure transitions using a dynamical systems-based framework-the taxonomy of seizure dynamotypes-previously examined only in invasive data. We applied principal component and independent component (IC) analysis to surface EEG recordings from 1,177 seizures in 158 patients with focal epilepsy, decomposing the signals into ICs. The ICs were visually labeled for clear seizure transitions and bifurcation morphologies (BifMs), which were then examined using Bayesian multilevel modeling in the context of clinical factors. Our analysis reveals that certain onset bifurcations (saddle node on invariant circle and supercritical Hopf) are more prevalent during wakefulness compared with their reduced rate during nonrapid eye movement (NREM) sleep, particularly NREM3. We discuss the possible implications of our results in the context of modeling approaches and suggest additional avenues to continue this exploration. Furthermore, we demonstrate the feasibility of automating this classification process using machine learning, achieving high performance in identifying seizure-related ICs and classifying interspike interval changes. Our findings suggest that the noise in surface EEG may obscure certain BifMs, and we suggest technical improvements that could enhance detection accuracy. Expanding the dataset and incorporating long-term biological rhythms, such as circadian and multiday cycles, may provide a more comprehensive understanding of seizure dynamics and improve clinical decision-making.

The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.

Epilepsy is one of the common chronic neurological diseases, affecting more than 70 million people worldwide. The brains of people with epilepsy exhibit a pathological and persistent propensity for recurrent seizures. Epilepsy often coexists with cardiovascular disease, cognitive dysfunction, depression, etc., which seriously affects the patient's quality of life. Although our understanding of epilepsy has advanced, the pathophysiological mechanisms leading to epileptogenesis, drug resistance, and associated comorbidities remain largely unknown. The use of newer antiepileptic drugs has increased, but this has not improved overall outcomes. We need to deeply study the pathogenesis of epilepsy and find drugs that can not only prevent the epileptogenesis and interfere with the process of epileptogenesis but also treat epilepsy comorbidities. Sphingosine-1-phosphate (S1P) is an important lipid molecule. It not only forms the basis of cell membranes but is also an important bioactive mediator. It can not only act as a second messenger in cells to activate downstream signaling pathways but can also exert biological effects by being secreted outside cells and binding to S1P receptors on the cell membrane. Fingolimod (FTY720) is the first S1P receptor modulator developed and approved for the treatment of multiple sclerosis. More and more studies have proven that the S1P signaling pathway is closely related to epilepsy, drug-resistant epilepsy, epilepsy comorbidities, or other epilepsy-causing diseases. However, there is much controversy over the role of certain natural molecules in the pathway and receptor modulators (such as FTY720) in epilepsy. Here, we summarize and analyze the role of the S1P signaling pathway in epilepsy, provide a basis for finding potential therapeutic targets and/or epileptogenic biomarkers, analyze the reasons for these controversies, and put forward our opinions. PLAIN LANGUAGE SUMMARY: This article combines the latest research literature at home and abroad to review the sphingosine 1-phosphate signaling pathway and epileptogenesis, drug-resistant epilepsy, epilepsy comorbidities, other diseases that can cause epilepsy, as well as the sphingosine-1-phosphate signaling pathway regulators and epilepsy, with the expectation of providing a certain theoretical basis for finding potential epilepsy treatment targets and/or epileptogenic biomarkers in the sphingosine-1-phosphate signaling pathway.

Cortical hemodynamics of electrographic status epilepticus in the critically ill.

The pathophysiological mechanisms of status epilepticus (SE) underlying potential brain injury remain largely unclear. This study aims to employ functional near-infrared spectroscopy (fNIRS) combined with video-electroencephalography (vEEG) to monitor brain hemodynamics continuously and non-invasively in critically ill adult patients experiencing electrographic SE. Our primary focus is to investigate neurovascular coupling and cerebrovascular changes associated with seizures, particularly during recurring and/or prolonged episodes. Eleven critically ill adult patients underwent simultaneous vEEG-fNIRS with large cortical coverage. Data from seven patients with identified electrographic SE were analyzed. The timing of recorded seizures was marked using standardized critical care EEG terminology. A general linear model was employed to extract the hemodynamic response to seizures from the fNIRS recordings. Linear mixed-effects models were utilized to correlate hemodynamic responses with seizure characteristics. A total of >200 h of monitoring and >1000 seizures were recorded. In most patients, an increase in oxyhemoglobin (HbO) and a decrease in deoxyhemoglobin (HbR) were observed during shorter-duration seizures. Although a similar response could also be seen initially for longer-duration seizures, this hemodynamic change was often followed by a progressive decline in HbO concentration and an increase in HbR. At the systemic level, no significant difference in peripheral oxygenation occurred during seizures, and only small changes in mean arterial blood pressure and heart rate occurred in four and two patients, respectively. We demonstrate the feasibility of using multichannel vEEG-fNIRS to measure the hemodynamic changes associated with electrographic seizures in critically ill adult patients. Our findings suggest that disrupted neurovascular coupling is more prevalent during prolonged seizures compared to recurrent short-duration seizures. This research provides valuable insights into the dynamic interplay between neuronal activity and hemodynamics during critical care seizures.

Age differences in organophosphorus nerve agent-induced seizure, blood brain barrier integrity, and neurodegeneration in midazolam-treated rats.

Exposure to organophosphorus nerve agents irreversibly inhibits acetylcholinesterase and may lead to cholinergic crisis and seizures. Although benzodiazepines are the standard of care after nerve agent-induced status epilepticus, when treatment is delayed for up to 30 min or more, refractory status epilepticus can develop. Adult male rodents are often utilized for evaluation of therapeutic efficacy against nerve agent exposure. However, there may be age and sex differences in toxicity and in therapeutic response. We previously reported that juvenile rats are less susceptible to the lethal effects of soman compared to adults, while pups are the most susceptible. Here, we report on age and sex differences in delayed midazolam treatment efficacy on survival, seizures and brain pathology. Male and female pups, juvenile and adult rats were exposed to an equitoxic dose of soman and treated with atropine sulfate and the oxime asoxime chloride (HI-6 dimethanesulphonate) 1 min after exposure and with midazolam 40 min after seizure onset, determined by EEG in juvenile and adult rats, and by behavior in pups. Survival, seizure data, and spontaneous recurrent seizures were evaluated. Brains were processed to assess neurodegeneration, neuroinflammation, and blood brain barrier (BBB) integrity. Juvenile and adult rats exposed to soman and treated with midazolam had BBB disruption, epileptogenesis, neurodegeneration, microglial activation, and astrogliosis; adult rats had poorer outcomes. Pups and juvenile rats exposed to soman had poor survival prior to midazolam treatment but most survived once treated; overall, neurodegeneration or disrupted BBB integrity was not detected in midazolam-treated pups. We found that age is a determinant factor in soman-induced toxicity and response to standard medical countermeasures. In addition, we observed sex differences in response to soman in juveniles and males with respect to body weight growth curves and in neuronal loss in juveniles and adults. Adjunct therapies to midazolam are warranted and it is important to evaluate both age and sex as factors in therapeutic response.

ESR Essentials: Image evaluation of patients with seizures and epilepsy-practice recommendations by the European Society of Neuroradiology.

Epilepsy, a neurological disorder characterised by recurrent seizures, poses significant challenges in diagnosis, treatment, and management. Understanding the underlying causes and identifying precise anatomical locations of epileptogenic foci are critical for effective management strategies, particularly in drug-resistant patients. Neuroimaging techniques, particularly magnetic resonance (MR), play a pivotal role in the evaluation of epilepsy patients, offering insights into structural abnormalities, epileptogenic lesions, and functional alterations within the brain. Diverse clinical scenarios that warrant neuroimaging in epilepsy patients, ranging from first-onset seizures to drug-resistant epilepsy, will be presented, elucidating the considerations and recommendations for imaging modalities. The dedicated MR protocol for epilepsy patients will be discussed, justifying the rationale behind sequence selection and optimisation strategies and providing clues about how to read these magnetic resonance imaging (MRI) exams. Finally, MR findings associated with common epileptogenic lesions, such as hippocampal sclerosis, focal cortical dysplasia, and long-term epilepsy-associated tumours, will be described. This article reviews essential concepts, including definitions, classification, imaging indications, protocols, and neuroradiological findings, aiming to understand how neuroimaging contributes to diagnosing and managing epilepsy comprehensively. KEY POINTS: MR should be performed in adults and children with a recent diagnosis of epilepsy of unknown aetiology, a first seizure, and a negative CT. Performing a dedicated MR protocol in focal epilepsy is essential for increasing the detection of potentially epileptogenic lesions. For presurgical evaluations, MR abnormalities should correlate with the electric pattern, semiology data, or other neuroimaging examination to be considered the epileptogenic lesion.

Optimisasi Model Backpropagation untuk Meningkatkan Deteksi Kejang Epilepsi pada Sinyal Electroencephalogram

Epilepsy is a chronic neurological disorder characterized by recurrent seizures caused by abnormal electrical activity in the brain. Fast and accurate seizure detection is crucial to support medical intervention and improve patients' quality of life. Currently, Electroencephalogram (EEG) signals are widely used to diagnose epilepsy as they record brain electrical activity in real-time. However, manual analysis of EEG signals requires time and precision, necessitating a more effective automated solution. This study aims to optimize the Backpropagation model for detecting epileptic seizures using EEG data. The research involved collaboration between Telkom University, Sumber Waras Hospital, and the University of Bonn. The EEG data collected was processed through Discrete Cosine Transform (DCT) to extract important features before being used to train the artificial neural network (ANN) model. The model was trained and tested using varying numbers of epochs to measure its accuracy. The results show that the Backpropagation model achieved optimal accuracy of 91.15% at 100 epochs and increased to 93.05% at 200 epochs. Although accuracy improved with more epochs, the longer computational time posed a risk of overfitting. This research demonstrates that the Backpropagation algorithm can be optimized to detect epileptic seizures accurately and efficiently. The implication for Sumber Waras Hospital is that this model can be implemented in EEG monitoring systems to detect seizures in real-time, supporting faster medical intervention and reducing reliance on manual analysis. Thus, this study contributes to providing a more efficient diagnostic solution and enhancing healthcare services for epilepsy patients.

The role of the endocannabinoid system in the pathogenesis and treatment of epilepsy.

Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5-1 % of thepopulation, epilepsy remains a serious public health concern. Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to asubstantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important. In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy. Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research inthis area. This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.