Different Types Of Epilepsy Research Articles

Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.

Approximately 30% of patients with epilepsy are drug-refractory. There is an urgent need to elucidate the exact pathophysiology of different types of epilepsies and the mechanisms of action of both antiseizure medication and metabolic therapies to treat patients more effectively and safely. For example, it has been demonstrated that exogenous ketone supplement (EKS)-generated therapeutic ketosis, as a metabolic therapy, may decrease epileptic activity in both animal models and humans, but its exact mechanism of action is unknown. However, it was demonstrated that therapeutic ketosis, among others, can increase adenosine level, which may enhance activity of A1 adenosine receptors (A1Rs) in the brain. It has also been demonstrated previously that adenosine has anti-epileptic effect through A1Rs in different models of epilepsies. Thus, it is possible that (i) therapeutic ketosis generated by the administration of EKSs may exert its anti-epileptic effect through, among other mechanisms, increased adenosine level and A1R activity and that (ii) the enhanced activity of A1Rs may be a necessary anti-epileptic mechanism evoked by EKS administration-generated ketosis. Moreover, EKSs can evoke and maintain ketosis without severe side effects. These results also suggest that the therapeutic application of EKS-generated ketosis may be a promising opportunity to treat different types of epilepsies. In this literature review, we specifically focus on the putative role of A1Rs in the anti-epileptic effect of EKS-induced ketosis.

Study of Inflammatory Markers in Patients with Uncontrolled Generalized Motor Tonic–Clonic Seizures

Abstract Background Epilepsy is a multifaceted chronic neurological disease characterized by recurrent spontaneous seizures. It affects almost 70 million patients around the globe, making it one of the most common chronic causes of neurological morbidities. Aim of the Work detect an association between some inflammatory markers {C-reactive protein (CRP), Neutrophil-lymphocyte ratio (NLR), and Platelet-lymphocyte ratio (PLR)}and epilepsy in order to detect a pathogenic relation that in turn can influence the course and management of epilepsy. Patients and Methods the current body of evidence recognizes the association between inflammation and epilepsy. Several inflammatory markers have been investigated in relation to different types of epilepsy. This study chose CRP as a convenient and widely used inflammatory marker, together with NLR and PLR, the two novel, readily available indices of inflammation that are yet to be fully investigated in relation to epilepsy. We included 50 patients with uncontrolled generalized motor tonic–clonic seizures. Ages ranged from 18 – 45 years and both genders were represented. Patients were compared with 50 controls of same age and gender. Strict inclusion and exclusion criteria were applied to all volunteers. Results In this study, levels of CRP, NLR and PLR in 50 patients with epilepsy were significantly higher than controls. These results add to the pool of evidence that support the association between epilepsy and inflammatory processes. This study managed to investigate the correlation between inflammatory markers and specific independent variables such as frequency of seizures, time interval between last seizure and presentation, number of status epilepticus per year, number of anti-epileptic medications, duration of postictal confusion, age of onset of seizures, duration of illness, and EEG findings, in addition to age and gender differences. This study found increased levels of CRP, NLR, and PLR in patients with high frequency seizures compared to those with intermittent seizures. Similar results were obtained with increased number of episodes of status epilepticus, number of anti-epileptic medications and shorter time interval between last reported seizure and sample withdrawal. Longer duration of postictal confusion was associated with high values of NLR and PLR. Conclusion systemic inflammatory response has been detected in patients with uncontrolled generalized motor tonic–clonic seizures, which confirms the association between inflammation and epilepsy. This association is specifically correlated to higher seizure frequency, shorter duration between last seizure and blood sample withdrawal, higher number of status epilepticus in the last 12 months, higher number of anti-epileptic medications, longer duration of post-ictal confusion and female gender.

Analysis of the expression patterns of AVP, IGF-1, and TNF-α, APP, CD44, IFN-β IFN A β-6, α-syn, and NFL and CLU genes in generalized and focal seizures

ObjectiveThe aim of our study was to investigate the relationship between clinical indicators and gene dysregulation in different types of epilepsy, while also seeking to identify a diagnostic model capable of distinguishing between focal and generalized seizures. This highlights the critical importance of understanding clinical indicators and gene dysregulation for targeted therapeutic interventions to effectively address the specific seizure types effectively. Materials and methodsIn this study, we conducted a comprehensive analysis of the peripheral blood of epilepsy patients (n = 100) and a control group (n = 51) to determine the differential gene expression. Our analysis involved a range of statistical approaches, including correlation analysis to establish the association between clinical indicators and gene dysregulation, and principal component analysis to highlight distinct disease group from control group. Furthermore, we developed diagnostic models using logistic regression to aid in the accurate diagnosis of epilepsy. ResultsAmong several selected genes in this study such as AVP (AUC = 0.832, p < 0.0001), IGF-1 (AUC = 0.658, p = 0.0015), TNF-α (AUC = 0.8970, p < 0.0001), APP (AUC = 0.742, p < 0.0001), CD44 (AUC = 0.614, p = 0.021) and NfL (AUC = 0.937, p < 0.0001), and CLU (AUC = 0.923, p < 0.0001) have shown the outstanding discrimination. In addition to this, when all genes were included in the model, the overall diagnostic power increased significantly (AUC = 0.9968). A differential diagnostic model for focal and generalized seizures was established which discloses AUC = 0.7027, (95 % CL, 0.5765 to 0.8289, p = 0.0019). ConclusionThe conclusions drawn from these findings represented that this is the first study to highlight the distinctive gene patterns of both focal and generalized seizures, implying that peripheral blood can serve as a diagnostic source to distinguish between these seizures types, aiding in the accurate classification of epilepsy. The findings from this study indicate a promising direction for investigating more targeted pharmacological interventions directed to address the distinct needs of both focal and generalized epilepsy, which offers advancements in treatment strategies for distinctive seizure types.

Tailoring epilepsy treatment: personalized micro physiological systems illuminate individual drug responses

Introduction: Approximately 50 million people worldwide have epilepsy, with many not achieving seizure freedom. Organ-on-chip technology, which mimics organ-level physiology, could revolutionize drug development for epilepsy by replacing animal models in preclinical studies. Our goal is to determine if customized micro-physiological systems can lead to tailored drug treatments for epileptic patients. Materials and methods: A comprehensive literature search was conducted utilizing various databases, including PubMed, Ebscohost, Medline, and the National Library of Medicine, using a predetermined search strategy. We focused on articles that addressed the role of personalized micro-physiological systems in individual drug responses and articles that discussed different types of epilepsy, diagnosis, and current treatment options. Additionally, articles that explored the components and design considerations of micro-physiological systems were reviewed to identify challenges and opportunities in drug development for challenging epilepsy cases. Results: The micro-physiological system offers a more accurate and cost-effective alternative to traditional models for assessing drug effects, toxicities, and disease mechanisms. Nevertheless, designing patient-specific models presents critical considerations, including the integration of analytical biosensors and patient-derived cells, while addressing regulatory, material, and biological complexities. Material selection, standardization, integration of vascular systems, cost efficiency, real-time monitoring, and ethical considerations are also crucial to the successful use of this technology in drug development. Conclusion: The future of organ-on-chip technology holds great promise, with the potential to integrate artificial intelligence and machine learning for personalized treatment for epileptic patients.

Research Status, Synthesis and Clinical Application of Antiepileptic Drugs.

According to the 2017 ILAE's official definition, epilepsy is a slow brain disease state characterized by recurrent episodes. Due to information released by ILAE in 2017, it can be divided into four types, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and unknown epilepsy. Since 1989, 24 new antiepileptic drugs have been approved to treat different types of epilepsy. Besides, there are a variety of antiepileptic medications under clinical monitoring. These novel antiepileptic drugs have plenty of advantages. Over the past 33 years, there have been many antiepileptic drugs on the mearket, but no one has been found that can completely cure epilepsy. In this paper, the mentioned drugs were classified according to their targets, and the essential information, and clinical studies of each drug were described. The structure-activity relationship of different chemical structures was summarized. This paper provides help for the follow-up research on epilepsy drugs.

A PROSPECTIVE OBSERVATIONAL STUDY ON PRESCRIPTION ANALYSIS OF ANTIEPILEPTIC DRUGS AT TERTIARY CARE HOSPITAL

The present study was aimed to analyze the prescription patterns of various uses of antiepileptic drugs (AEDs)in the strategic treatment of different types of epilepsy in a tertiary care hospital in the northern Telangana of India. A total of 157 patients were included in this study and patients with epilepsy of specific group are included. The demographic data shows a greater number of males 99 (63%) and female 58 (37%). The majority of patients were 44 (28%) belonged to 20-30 years of age group, 43 (27%) patients belonged to 30-40 years of age group. Generalized tonic clonic seizures (GTCS) were the most commonly diagnosed epilepsy (46%) and monotherapy (75%) were prescribed. Levetiracetam was the most common monotherapy (54%). Levetiracetam with clobazam was commonly prescribed two drug combinations (6%). Among polytherapy levetiracetam with sodium valproate and clobazam (2%). Levetiracetam was commonest prescribed AED as monotherapy and in combinational as well as polytherapy. The study concluded that educating patients regarding the antiepileptic drugs is necessary to avoid the medications related problems which helps in improving patient for better care.

Altered static and dynamic functional connectivity of the default mode network across epilepsy subtypes in children: A resting-state fMRI study

BackgroundEpilepsy is a chronic neurologic disorder characterized by abnormal functioning of brain networks, making it a complex research topic. Recent advancements in neuroimaging technology offer an effective approach to unraveling the intricacies of the human brain. Within different types of epilepsy, there is growing recognition regarding ongoing changes in the default mode network (DMN). However, little is known about the shared and distinct alterations of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in DMN among epileptic subtypes, especially in children with epilepsy. MethodsHere, 110 children with epilepsy at a single center, including idiopathic generalized epilepsy (IGE), frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), and parietal lobe epilepsy (PLE), as well as 84 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scan. We investigated both sFC and dFC between groups of the DMN. ResultsDecreased static and dynamic connectivity within the DMN subsystem were shared by all subtypes. In each epilepsy subtype, children with epilepsy displayed significant and distinct patterns of DMN connectivity compared to the control group: the IGE group showed reduced interhemispheric connectivity, the FLE group consistently demonstrated disturbances in frontal region connectivity, the TLE group exhibited significant disruptions in hippocampal connectivity, and the PLE group displayed a notable decrease in parietal-temporal connectivity within the DMN. Some state-specific FC disruptions (decreased dFC) were observed in each epilepsy subtype that cannot detect by sFC. To determine their uniqueness within specific subtypes, bootstrapping methods were employed and found the significant results (IGE: between PCC and bilateral precuneus, FLE: between right middle frontal gyrus and bilateral middle temporal gyrus, TLE: between left Hippocampus and right fusiform, PLE: between left angular and cingulate cortex). Furthermore, only children with IGE exhibited dynamic features associated with clinical variables. ConclusionsOur findings highlight both shared and distinct FC alterations within the DMN in children with different types of epilepsy. Furthermore, our work provides a novel perspective on the functional alterations in the DMN of pediatric patients, suggesting that combined sFC and dFC analysis can provide valuable insights for deepening our understanding of the neuronal mechanism underlying epilepsy in children.

Expert Opinion on the Prescription Practice of Levetiracetam for Different Types of Epilepsy in Indian Clinical Settings

Despite some studies assessing antiepileptic drug usage patterns in single-centre settings, there was a lack of consensus regarding usage patterns, drug choices for various seizure types, and the sociodemographic and clinical factors that influence treatment decisions in India. So, this current survey-based study was intended to gather expert opinions regarding the clinical use of anti-epileptic drugs with a special focus on levetiracetam for the management of epilepsy in Indian settings. A questionnaire-based cross-sectional study involving 25 questions collected perspectives of experts across India regarding the prescription practice of anti-epileptic drugs for epilepsy management. It was noted that majority of the responders (85.93% of 192 experts) stated levetiracetam as a preferred therapeutic option for patients with newly diagnosed epilepsy. Levetiracetam 1000 mg/day was the frequently recommended dosage for such patients in clinical practice (66%). Approximately 76% of the experts suggested that patients receiving the drug might experience behavioural changes. About 49% and 82% of responders recommended levetiracetam for treating resistant epilepsy and pregnant epilepsy respectively. Nearly 62% of the clinicians recommended levetiracetam for paediatric patients with partial seizures over other antiepileptic drugs. Levetiracetam and brivaracetam were both rated as beneficial for treating epileptic patients by 50% of clinicians. Levetiracetam was rated as being more effective than brivaracetam by 28% of clinicians, while brivaracetam was rated as being more effective by 14% of clinicians. Hence, this consensus among clinician’s highlights levetiracetam as the preferred antiepileptic medication for the management of patients with recently diagnosed epilepsy. This recommendation extends patients with refractory epilepsy, pregnant subjects with epilepsy, and young children experiencing partial seizures, where the majority of the clinicians endorse levetiracetam over alternative antiepileptic medications. Both levetiracetam and brivaracetam offer comparable treatment benefits for patients with epilepsy.

Association of GABRG2 rs211037 Gene Polymorphism With Epilepsies and Pharmacoresistance to Anti-Epileptic Drugs; A Meta-Analysis

GABRG2 protein which is a crucial part of GABA receptor encoded by the gamma-aminobutyric acid A receptor, gamma 2 (GABRG2) gene. The exonic GABRG2 rs211037 gene polymorphism has been commonly explore with respect to variable association to different types of epilepsies (all types, IGE and FS) and AEDs response. The current meta-analysis study was designed to explore whether the GABARG2 C588 T (rs211037) genetic variant predicts susceptibility to different types epilepsy and pharmacoresistance to AEDs. Twenty studies were included, contained 3351 epileptic patients and 3649 controls in meta-analysis, for the association GABRG2 rs211037 polymorphism with susceptibility to different types of epilepsy. Similarly, five studies comprised of 632 responder patients and 401 non-responder patients in meta-analysis, were selected for the evaluation of the GABRG2 rs211037 polymorphism to pharmacoresistance to AEDs. Meta-analysis was performed separately for FS and IGE in Asian and Caucasian population for association to epilepsies and pharmacoresistance to AEDs but pharmacoresistance to AEDs in FS and IGE was not performed in Asian and Caucasian due to limited number of studies. Meta-analysis showed a significant link between GABRG2 rs211037 polymorphism and susceptibility to all types of epilepsies in total Population in (CC vs CT, OR 1.03, 95% CI 0.0–1.2, p = 0.0006 and CC vs TT, OR 0.03, 95% CI 0.8–1.2, p = 0.01) genetic models. Similarly, a significant association of this polymorphisms with all types of epilepsy was found with Asian population in genetic models of CC vs CT( OR 0.86 (0.7-1.0,p=0.11), CC vs TT (OR 0.67 (0.5-0.9, p=0.000), but CC vs CT+TT genetic model shows the association of all types of epilepsies in Asian as well Caucasian population ( OR 0.6 (0.5-0.7), p=0.001 and OR 1.05 (0.9-1.2), p=0.000). Similarly, CC vs CT, CC vs TT and CC vs CT+TT genetic models were also associated with IGE and FS epilepsies in total population, Asian and Caucasian population. The alleles also showed a significant association with epilepsy. Genetic models of CC vs CT, CC vs TT and CC vs CT+TT were also associated with pharmacoresistance to AEDs (P&lt;0.05) in total population, Asian and Caucasian population. The publication bias was not significant (P&lt;0.05) but the heterogenicity (I2%) was mostly more than 50%. FS, caused by two studies with small sample sizes, however the possibility of false positive results because of significant studies for FS cannot be excluded. This study showed a significant association of GABRG2 rs211037 polymorphism with susceptibility to different types of epilepsies and pharmacoresistance to AEDs in all population. Future studies with larger sample sizes from different population are suggested to verify the results.

An Integrated Multi-Channel Deep Neural Network for Mesial Temporal Lobe Epilepsy Identification Using Multi-Modal Medical Data.

Epilepsy is a chronic brain disease with recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is the most common pathological cause of epilepsy. With the development of computer-aided diagnosis technology, there are many auxiliary diagnostic approaches based on deep learning algorithms. However, the causes of epilepsy are complex, and distinguishing different types of epilepsy accurately is challenging with a single mode of examination. In this study, our aim is to assess the combination of multi-modal epilepsy medical information from structural MRI, PET image, typical clinical symptoms and personal demographic and cognitive data (PDC) by adopting a multi-channel 3D deep convolutional neural network and pre-training PET images. The results show better diagnosis accuracy than using one single type of medical data alone. These findings reveal the potential of a deep neural network in multi-modal medical data fusion.

Review of the Epilepsy, Including Its Causes, Symptoms, Biomarkers, and Management

Epilepsy is a long-term medical disorder that frequently causes unpredictable, unprovoked repeated seizures that have an impact on both physical and mental abilities. It is among the most prevalent neurological conditions. Greek term epilambanein, which is the root of the English word epilepsy, means "to be seized." Both the sickness and the one-time attack were meant by this. The word refers to the magical beliefs of the time, which led to the stigma associated with epilepsy because people with epilepsy were seen to be dirty or bad. A recent study found that nearly 90% of the 70 million epileptics worldwide live in developing countries. Genetic testing has expanded the possibility of figuring out the aetiology of different types of epilepsies. It needs some prior clinical application knowledge to complete this challenging endeavour. Genetic testing techniques include chromosome microarray analysis, karyotyping, single-gene testing, gene panel testing, whole exome sequencing, and whole genome sequencing. The allegedly first documented account of epilepsy, as it was then perceived and understood, may be found in one of the earliest Babylonian medical manuals, Sakikku (English translation: "All Diseases"), which dates from around 1050 BC. The pathogenesis, aetiology, treatment, biomarkers, and risk factors for epilepsy are reviewed in this review article.

Automated analysis of a large-scale paediatric dataset illustrates the interdependent relationship between epilepsy and sleep

Slow waves are an electrophysiological characteristic of non-rapid eye movement sleep and a marker of the restorative function of sleep. In certain pathological conditions, such as different types of epilepsy, slow-wave sleep is affected by epileptiform discharges forming so-called “spike-waves”. Previous evidence shows that the overnight change in slope of slow waves during sleep is impaired under these conditions. However, these past studies were performed in a small number of patients, considering only short segments of the recording night. Here, we screened a clinical data set of 39′179 pediatric EEG recordings acquired in the past 25 years (1994–2019) at the University Children’s Hospital Zurich and identified 413 recordings of interest. We applied an automated approach based on machine learning to investigate the relationship between sleep and epileptic spikes in this large-scale data set. Our findings show that the overnight change in the slope of slow waves was correlated with the spike-wave index, indicating that the impairment of the net reduction in synaptic strength during sleep is spike dependent.

Reliable HPLC-UV method for therapeutic levetiracetam monitoring in serum and cerebrospinal fluid of patients with epilepsy

The present study was to develop and validate a rapid analytical method of high-performance liquid chromatography with UV (HPLC/UV) detection for the determination of levetiracetam (LEV) concentration in human serum and cerebrospinal fluid (CSF) samples. The newly developed method was used to measure LEV concentration in the serum/CSF of 29 patients with different types of epilepsy; 52% (group I, n = 15) were treated with LEV in monotherapy, 48% (group II, n = 14) were co-administered with other AEDs. Serum and CSF levels of LEV were correlated with patients dosage, concomitant AEDs, therapeutic effect, and adverse drug reactions (ADRs). The calibration curves for serum and CSF were linear in the range 0.5-100 and 0.5-50 mg/L, respectively, with a coefficient correlation (R) value &gt; 0.998 in each case. The quantitation limit was 0.5 mg/L in serum and CSF. The validated method was found to be selective, precise, and accurate. Optimal Cssmin values according to International League Against Epilepsy (12-46 mg/L) were achieved in 40 and 50% of patients in group I and II, and did not correlate with treatment efficacy in 27 and 21% patients, respectively. The ratio of serum LEV to CSF concentration (Kp) after 2 h administration LEV ranged in group I from 0.31 to 0.92 and in group II from 0.18 to 0.65. These findings indicate that the developed simple and rapid HPLC/UV method may be useful for monitoring serum/CSF LEV concentrations in patients receiving standard doses.

Heterogeneity in INF-γ Levels Among Children with Different Types of Epilepsy

Heterogeneity in INF-γ Levels Among Children with Different Types of Epilepsy

Prematurity and Neurological Sequelae

Any birth that takes place three weeks or more before the baby’s due date is a premature birth. Prematurity is a public health problem worldwide. Every year, 15 million infants are born premature, accounting for a prevalence of 11% in 84 surveyed countries. Premature births alone account for a quarter of all neonatal deaths. Survivors of premature births have high rates of postnatal morbidities. With the development technologies and medical procedures, the morbidities are increasing due to improving survival of borderline viable cases. The prevalence of cerebral palsy, intellectual and cognitive dysfunction, retinopathy, hearing loss, epilepsy, ADHD and autistic disorder are more in babies born preterm. The risk of cerebral palsy is 8- 10 times higher in preterm infants and nearly 30 times higher in infants born &lt;32 weeks. Children born preterm have an average 12.9 IQ points lower than term born controls and these children face difficulty in making communication, executive functioning and cognition. ADHD and autism spectrum disorders are frequently diagnosed (OR 3.3) in children born preterm. ROP associated blindness is 10% in high income countries and 40% in middle and low income countries. As many as 10% children born preterm have hearing loss and 35% suffer from different types of epilepsy. Adequate antenatal check-up and immediate postnatal care are key issues to reduce or prevent neurological sequelae in survivors of premature birth. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 212

The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.

Observational studies have shown an association between 25-hydroxyvitamin D (25(OH)D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25(OH)D levels and epilepsy. We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25(OH)D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25(OH)D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity. MR analyzed the relationship between 25(OH)D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25(OH)D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval (CI): 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy. Higher serum levels of 25(OH)D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.

Efficacy of brivacetam as an anti-epileptic in patients with epilepsy, with special reference to previous exposure to levetiractam

Brivaracetam (BRV) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. It is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with much higher affinity than Levetiracetam (LEV). It has a high lipid solubility and rapid brain penetration, and has been shown to have potent broad-spectrum antiepileptic activity in animal models. The aim of the study was to evaluate the efficacy and tolerability of BRV in everyday clinical practice. This observational study included 35 participants, suffering from different types of epilepsy. Patients were observed over a period of 1 year and data was collected using an interview design model. After the initial interview, a final interview took place after 1 year. Various parameters studied included demographic parameters, seizure frequency and duration, any side effects such as behavioral issues. This study included total 35 patients. The mean age of the participants was 33 years (range 3 – 90 years). Approximately 63% patients demonstrated a decrease in seizure frequency after switching to Brivacetam. Out of these patients, 76% patients were those patients, who were earlier treated with Levetiracetam, and it was discontinued either due to inadequate control of seizures or prominent side-effects. Brivaracetam also improved emotional balance in the treated patients (treatment naïve or Levetiracteam associated behavioral issues).Brivaracetam seems to be an effective and safe antiepileptic drug in the routine clinical setting.

Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.

The course of sleep habits in newly diagnosed epilepsy in children: A prospective study

BackgroundEpilepsy and sleep have a close, complex, and reciprocal relationship. Sleep may also be adversely affected by epilepsy and anti-seizure medication (ASM). This study sought to determine sleep-related problems before and after six months of treatment with ASMs follow-up in children with epilepsy, to reveal changes in sleep habits, and to determine the effect of ASMs on sleep in different types of epilepsy. MethodsThis is a prospective study that included 61 children, aged 4–18 years with newly diagnosed epilepsy, who regularly had follow-up checks and used ASM for six months, and completed the Children's Sleep Habits Questionnaire (CSHQ). Children's Sleep Habits Questionnaire was completed before and after six months of ASM, allowing for assessments based on treatment group and type of epilepsy. ResultsThe mean ages of 61 children were 10.6 ± 3.9 years. The participants’ post-treatment total scores on the CSHQ decreased by 2.9 ± 7.8 units on average compared to their pretreatment scores (p = 0.008; p < 0.01). In the levetiracetam group, post-treatment CSHQ subscale scores showed a mean decrease for bedtime resistance (p = 0.001), sleep duration (p = 0.005), sleep anxiety (p = 0.030), and total scores (p = 0.012) (p < 0.05). In the valproic acid group, post-treatment CSHQ subscale scores showed a mean decrease in sleep duration (p = 0.007) and a mean increase in daytime sleepiness (p = 0.03) (p < 0.05). ConclusionOur study found that children diagnosed with epilepsy had significantly higher rates of pretreatment sleep problems, which significantly decreased in patients who regularly attended follow-up examinations and received treatment. Except for the daytime sleepiness factor, our study found that sleep-related problems improved with treatment. It was observed that the initiation of epilepsy treatment had a positive effect on the patient’s sleep, regardless of the type of treatment or epilepsy.

Different relationships between epilepsy syndromes and autoimmune diseases.

Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analysed. Adult patients with IGEs and MTLE-HS at a tertiary epilepsy centre were consecutively enrolled between January 2016 and December 2020. A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p<0.001). The frequency of autoimmune diseases was 5.5% (n=23) and 4.5% (n=11), in patients with IGEs and MTLE-HS, respectively (p=0.716). The mean age of autoimmune disease onset was 20±15.6 years in patients with IGEs and 36.7±16.5 years in patients with MTLE-HS (p<0.05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset, from adolescence onwards. Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.