Onset Of Epilepsy Research Articles

Next-generation sequencing in pediatric-onset epilepsies: Analysis with target panels and personalized therapeutic approach.

The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments. In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy. We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., and unclassified epileptic syndromes. According to the results of the genetic screening, up to 33% of patients carrying class IV or V variants resulted potentially eligible for precision medicine treatments. The large-scale application of NGS multigene panels of analysis is a useful tool for the molecular diagnosis of patients with pediatric-onset epilepsies, allowing the identification of those who could benefit from a personalized therapeutic approach. The analysis of patients with pediatric-onset epilepsy using advanced technologies for the screening of all the implicated genes allows the identification of the cause of diseases in an ever-increasing number of cases. Understanding the pathogenic mechanisms could, in some cases, guide the selection and optimization of appropriate treatment approaches for patients.

Epilepsy and Myasthenia Gravis: A Case Series.

The association between epilepsy and myasthenia gravis has rarely been reported, and when it has been reported, it has only been in a small case series. The aim of the present study was to report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis and Epilepsy Unit of the Neurology Service, Hospital Universitari de Bellvitge. Five patients were included. The frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and the frequency of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered from focal epilepsy, mainly temporo-central, which was drug-resistant in 3/5 Myasthenia gravis, which was generalized and with exacerbations in 3/5. Three patients were thymectomized (anatomopathology: thymic hyperplasia). Other autoimmune diseases were found in two (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5, related to genetic predisposition due to altered innate immune system in 1/5, and due to chance or to treatment in 1/5. Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune etiology and coexists with other autoimmune conditions.

Events of children responsible for the development of epilepsy in patients with cerebral palsy

Background: Cerebral palsy (CP) is characterized by abnormal muscle tone, ‘posture, and movement’, thereby limiting the activity of the affected person. Epilepsy is said to occur in 15-90% of children with CP. The aim of this study was to evaluate the events of children responsible for the development of epilepsy considering natal, postnatal characteristics and associated impairment in patients with CP. Methods: This was a case-control study and was conducted in the Department of Pediatric Neurology at the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh during the period from January 2020 to December 2020. In total 150 children with cerebral palsy were enrolled in this study who were divided into two groups. In the ‘CP with epilepsy’ group, there were 50 patients, and in the CP without epilepsy group taken as a case group, there were 100 age-sex matched CP patients without epilepsy patients were taken as a control group. Informed written consent was taken from all the parents. Along with baseline characteristics, data regarding natal, postnatal events, general clinical findings, psychological assessment, computed tomography (CT) scan findings of the head, and electroencephalogram (EEG) findings in epilepsy cases were recorded in a predesigned questionnaire and analyzed. Results: In distributing the CP patients’ comparison regarding postnatal complications neonatal seizures were a strong predictor for epilepsy (p≤0.001). 1st seizure during 1st year of life and family history of epilepsy was also a significant event of epilepsy (p≤0.001). In the case of microcephaly, no significant difference was observed between groups (p=0.278). A significant difference was observed when the distribution of severity of intellectual disability of CP patients was compared between groups (p<0.001). Abnormal CT scan findings of the head were significantly higher in CP with epilepsy 42 (84.0%) than in CP without epilepsy 46 (46.0%) (p≤0.001). The total mean age at the onset of epilepsy was 13.58±14.47 months. Epilepsy was most common in spastic quadriplegic CP (54%). 38.0% had focal epileptiform activity on EEG. Clinically focal epilepsy was found in 36.0% of cases. Conclusions: This study demonstrates the presence of a history of neonatal seizure, 1st seizure during 1st year of life, a family history of epilepsy, CT scan abnormalities, severe intellectual disability, and spastic quadriplegic CP were the events responsible for the development of epilepsy in children with CP.

Optimizing ketogenic diet therapy for childhood epilepsy: Identifying key factors for seizure control and psychomotor enhancement.

To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.

Combined generalized and focal epilepsy with reflex features in Adaptor protein complex 4-associated hereditary spastic paraplegias: A cohort observational study

BackgroundPatients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far. PurposeWe aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency. MethodsObservational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications. ResultsPatients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %). ConclusionIn AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.

Nurture growth: Ketogenic diet therapy and growth velocity in infants under 12 months with epilepsy − A systematic review and infant data study

Ketogenic diet therapy (KDT) is well established for the treatment of early epileptic encephalopathies and specific aetiologies; however, the impact on growth in infancy remains controversial. Our aim was to examine the influence of early KDT on growth velocity and height percentiles completing two tasks. First, we systematically reviewed the literature on growth in infants younger than 12 months. Second, we analysed data from our prospective database, including infants <12 months (n = 63) treated with KDT. The literature review (n = 7) remains descriptive and includes growth percentiles and z-scores as growth velocity was not described. Studies up to 2010 used fasting, calorie restrictions, and ratios >3:1. In individual cases, significant growth delays were found; other authors did not find any changes in growth parameters. Study endpoints in our own cohort included z-scores of growth velocity, standard deviation (SD) of height, weight, BMI, deviation from individual height percentile, and daily macronutrient intake. The median z-score of growth velocity was 1.03 (first year of life). After three months, median daily intake of protein and energy was 1.68 g/kg and 85 kcal/kg. Until the age of one year, neither growth velocity nor individual growth percentiles decreased. Infants showed distinct growth improvements at three months, likely due to continuous nutritional monitoring and reduction in seizures. In the second year of life, z-scores of growth velocity decreased in patients still receiving KDT (from 1.03 at 12 months to −1.5 at 24 months). Furthermore, younger age at epilepsy onset and at KDT start correlated with slower growth velocities in the first year of life.With appropriate nutritional intake and monitoring, KDT does not reduce growth in the first year of life. Future directions might be to study the impact of KDT on growth velocity and growth hormones throughout childhood.

Frontal Disconnection for Treating Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) in the Frontal Lobe.

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

Presumed aetiologies and clinical outcomes of non-lesional late-onset epilepsy.

Our objective was to define phenotypes of non-lesional late-onset epilepsy (NLLOE) depending on its presumed aetiology and to determine their seizure and cognitive outcomes at 12 months. In all, 146 newly diagnosed NLLOE patients, >50 years old, were prospectively included and categorized by four presumed aetiological subtypes: neurodegenerative subtype (patients with a diagnosis of neurodegenerative disease) (n = 31), microvascular subtype (patients with three or more cardiovascular risk factors and two or more vascular lesions on MRI) (n = 39), inflammatory subtype (patient meeting international criteria for encephalitis) (n = 9) and unlabelled subtype (all individuals who did not meet the criteria for other subtypes) (n = 67). Cognitive outcome was determined by comparing for each patient the proportion of preserved/altered scores between initial and second neuropsychological assessment. The neurodegenerative subtype had the most severe cognitive profile at diagnosis with cognitive complaint dating back several years. The microvascular subtype was mainly evaluated through the neurovascular emergency pathway. Their seizures were characterized by transient phasic disorders. Inflammatory subtype patients were the youngest. They presented an acute epilepsy onset with high rate of focal status epilepticus. The unlabelled subtype presented fewer comorbidities with fewer lesions on brain imaging. The neurodegenerative subtype had the worst seizure and cognitive outcomes. In other groups, seizure control was good under antiseizure medication (94.7% seizure-free) and cognitive performance was stabilized or even improved. This new characterization of NLLOE phenotypes raises questions regarding the current International League Against Epilepsy aetiological classification which does not individualize neurodegenerative and microvascular aetiology per se.

Perampanel for the treatment of Asian people with epilepsy: Real-world evidence from the PERMIT extension study

This post-hoc analysis of the PERMIT Extension study compared the effectiveness and safety/tolerability of perampanel (PER) between Asian and non-Asian participants. Retention rates, adverse events (AEs), seizure frequency, responder rate (≥50% seizure frequency reduction), and seizure freedom rate (no seizures since at least the prior visit) were assessed. Retention was assessed after 3, 6 and 12 months. Effectiveness assessments were evaluated at 3, 6 and 12 months and the last visit by seizure type (total, focal and generalised). PERMIT Extension included 730 Asian and 1662 non-Asian individuals. Significant differences in demographic/baseline characteristics were reported for the Asian versus non-Asian subgroups including higher median age at epilepsy onset, longer median duration of epilepsy, higher mean number of previous and concomitant ASMs and lower mean monthly seizure frequency (total, focal and generalised). Retention rates were similar between the two subgroups at 3 and 12 months, but significantly lower in the Asian versus non-Asian subgroup at 6 months (65.6% vs. 71.8%; p = 0.004). At last visit, seizure freedom rate was significantly higher in the Asian versus non-Asian for total (35.9% vs. 25.4%; p = 0.001) and focal seizures (32.4% vs. 18.9%; p = 0.001) as was responder rate for both total (63.9% vs. 52.3%; p = 0.001) and focal seizures (62.2% vs. 44.7%; p < 0.001). Seizure freedom and responder rates for generalised seizures were similar between the two subgroups at the last visit. Rates of AEs were similar between the two subgroups (Asian, 47.6%; non-Asian, 45.4%). PER was effective and generally well-tolerated in Asian and non-Asian individuals.

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real-world study.

Dravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy-related hospital contacts administrated by pediatricians or epilepsy-trained nurses. A retrospective registry-based cohort study at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark, enrolled 30 pediatric patients with Dravet syndrome treated with fenfluramine between 2017 and 2023. Thirty patients with Dravet syndrome (aged 3-21 years, 12 females) with a verified pathogenic SCN1A variant were included. They were treated with fenfluramine at a mean duration of 29 months with a mean maintenance dose of 0.5 mg/kg/day. The number of patient-years on treatment was 75 years. At last follow-up, 6 patients had discontinued treatment due to lack of efficacy or adverse effects. In the remaining 24 patients, generalized tonic-clonic seizures were reduced by ≥30% in 83%, by ≥50% in 67%, and by 100% in 25%. Additionally, 71% of the patients were reduced in concomitant anti-seizure medication, and 75% experienced a reduction (mean reduction at 52%, range 11%-94%) in epilepsy-related hospital contacts from baseline to the end of the treatment period. Treatment with fenfluramine effectively reduced seizure frequency and concomitant antiseizure medication in patients with Dravet syndrome. Furthermore, a decrease in epilepsy-related contacts by 80% was observed over 6 years of treatment, which may indicate cost-effective benefits. Patients with Dravet syndrome suffer from severe epileptic seizures that are difficult to treat with medication. Earlier, treatment with fenfluramine (an anti-seizure medication) has been documented to decrease the total number of seizures in patients with Dravet syndrome. This publication summarizes the experiences with fenfluramine in children with Dravet syndrome at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark. Our publication also illustrates that treatment with fenfluramine may reduce the patients' number of yearly contacts with doctors and nurses specialized in epilepsy treatment, which may indicate cost-effectiveness.

Genetic Diagnostic Yield in Autism Spectrum Disorder (ASD) and Epilepsy Phenotypes in Children with Genetically Defined ASD.

We compared the epilepsy phenotypes in children with genetically defined versus undefined autism spectrum disorder (ASD). A single-center retrospective study was conducted to investigate diagnostic yields of different genetic testing for children with ASD. Patients with at least one testing modality were included and classified as having genetically defined ASD or not based on updated genotype-phenotype correlation. Of the 523 patients included, 79 (15.1%) had results explaining their ASD diagnosis. WES (whole exome sequencing) outperformed CMA (chromosomal microarray) on diagnostic yield (23.0% versus 8.3%). Compared to those with non-diagnostic test(s), children with genetically defined ASD were associated with higher rates for microcephaly, hypotonia, dysmorphic features, and developmental delay/regression. The prevalence of epilepsy was significantly higher in children with genetically defined ASD than those without a genetic diagnosis (35.4% versus 16.4%, p < 0.001, power = 0.97). Furthermore, children with genetically defined ASD had a younger age of epilepsy onset (median 2.2 versus 5.0years, p = 0.002, power = 0.90) and a higher rate of drug-resistant epilepsy although not reaching statistical significance (35.7% versus 21.9%, p = 0.20). Our study has provided further evidence to support WES as first-tier test for children with ASD and that an early genetic diagnosis has the potential to inform further surveillance and management for ASD comorbid conditions including epilepsy.

Hsp90aa1/JUN/Ccl2 regulatory axis mediates migration and differentiation of NSPCs, promoting the onset and progression of early post-ischemic stroke epilepsy

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

An efficient channel recurrent Criss-cross attention network for epileptic seizure prediction

Epilepsy is a chronic disease caused by repeated abnormal discharge of neurons in the brain. Accurately predicting the onset of epilepsy can effectively improve the quality of life for patients with the condition. While there are many methods for detecting epilepsy, EEG is currently considered one of the most effective analytical tools due to the abundant information it provides about brain activity. The aim of this study is to explore potential time-frequency and channel features from multi-channel epileptic EEG signals and to develop a patient-specific seizure prediction network. In this paper, an epilepsy EEG signal classification algorithm called Channel Recurrent Criss-cross Attention Network (CRCANet) is proposed. Firstly, the spectrograms processed by the short-time fourier transform is input into a Convolutional Neural Network (CNN). Then, the spectrogram feature map obtained in the previous step is input into the channel attention module to establish correlations between channels. Subsequently, the feature diagram containing channel attention characteristics is input into the recurrent criss-cross attention module to enhance the information content of each pixel. Finally, two fully connected layers are used for classification. We validated the method on 13 patients in the public CHB-MIT scalp EEG dataset, achieving an average accuracy of 93.8 %, sensitivity of 94.3 %, and specificity of 93.5 %. The experimental results indicate that CRCANet can effectively capture the time-frequency and channel characteristics of EEG signals while improving training efficiency.

Clinical features of unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy and seizure outcome with different treatment options.

To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long-term outcomes after surgical or nonsurgical (anti-seizure medications, ASMs) treatment. A total of 70 patients (49 surgical, 21 non-surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0-4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow-up (median 14.1 years), the rates of seizure-freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure-freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. We aim to summarize clinical characteristics and compare the long-term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)-related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

MicroRNA-33 regulates the synaptic plasticity-related gene ARC in temporal lobe epilepsy

This study aimed to elucidate the expression patterns of miR-33 and ARC in both a rat model of temporal lobe epilepsy (TLE) and human TLE patients, to explore the role of miR-33 in epilepsy onset through its regulation of ARC expression in the hippocampus. Our findings, supported by a Dual-Luciferase reporter assay, suggest that miR-33 can bind to the 3′ UTR region of ARC. We observed that miR-33 levels were reduced at 1 hour and 60 days post-seizure, while ARC expression notably increased at these time points. In the hippocampal CA1 and CA3 regions of post-seizure rats, ARC expression significantly exceeded that of control groups. Following the transfection of HEK cells with a miR-33 mimic, there was a decrease in both ARC mRNA and protein levels, whereas the group treated with a miR-33 inhibitor displayed the opposite effect. RNA sequencing in TLE patients revealed a similar miR-33 and ARC interaction. The regulation of Arc expression by miR-33 suggests that Arc may be a target gene of miR-33 in the context of epilepsy. Our findings indicate that miR-33 downregulation could contribute to the dysregulation of Arc expression observed in TLE, potentially influencing the disease process. Further studies are required to establish the exact role of miR-33-mediated Arc regulation in the development of epilepsy.

Mortality among veterans with epilepsy: Temporal significance of traumatic brain injury exposure.

Epilepsy is associated with significant mortality risk. There is limited research examining how traumatic brain injury (TBI) timing affects mortality in relation to the onset of epilepsy. We aimed to assess the temporal relationship between epilepsy and TBI regarding mortality in a cohort of post-9/11 veterans. This retrospective cohort study included veterans who received health care in the Defense Health Agency and the Veterans Health Administration between 2000 and 2019. For those diagnosed with epilepsy, the index date was the date of first antiseizure medication or first seizure; we simulated the index date for those without epilepsy. We created the study groups by the index date and first documented TBI: (1) controls (no TBI, no epilepsy), (2) TBI only, (3) epilepsy only, (4) TBI before epilepsy, (5) TBI within 6 months after epilepsy, and (6) TBI >6 months after epilepsy. Kaplan-Meier estimates of all-cause mortality were calculated, and log-rank tests were used to compare unadjusted cumulative mortality rates among groups compared to controls. Cox proportional hazard models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs). Among 938 890 veterans, 27 436 (2.92%) met epilepsy criteria, and 264 890 (28.22%) had a TBI diagnosis. Mortality was higher for veterans with epilepsy than controls (6.26% vs. 1.12%; p < .01). Veterans with TBI diagnosed ≤6 months after epilepsy had the highest mortality hazard (HR = 5.02, 95% CI = 4.21-5.99) compared to controls, followed by those with TBI before epilepsy (HR = 4.25, 95% CI = 3.89-4.58), epilepsy only (HR = 4.00, 95% CI = 3.67-4.36), and TBI >6 months after epilepsy (HR = 2.49, 95% CI = 2.17-2.85). These differences were significant across groups. TBI timing relative to epilepsy affects time to mortality; TBI within 6 months after epilepsy or before epilepsy diagnosis was associated with earlier time to death compared to those with epilepsy only or TBI >6 months after epilepsy.

Electroclinical characteristics and therapies of tonic spasms

BackgroudEpileptic spasms followed by a tonic component have been frequently observed in patients with late-onset spasms (LOS). However, there is a lack of comprehensive analysis and summary of clinical data related to tonic spasms (TS), including seizures, video-electroencephalogram (V-EEG), synchronous electromyography (EMG) and follow-up data.MethodsTo investigate the characteristics of TS, we prospectively collected the clinical data, including 24-h V-EEG and synchronous EMG data of 32 enrolled patients who suffered from epileptic spasms followed by a TS onset at least once during the 24-h V-EEG in the epilepsy center of Xijing Hospital between June 2015 and July 2020. The patients were prescribed anti-seizure medications (ASMs) and followed up for 2–7 years.ResultsThe average age of epilepsy onset was 48.06 ± 16.07 months (range: 25 to 88 months). Among the enrolled patients, 22 patients presented with mild intellectual deficits. During the 24-h video-EEG monitoring, an average of 6.94 TS events (range: 3 to 21) were recorded, and these TS seizures often occurred in clusters. In addition to TS, 26 patients experienced generalized tonic-clonic seizures (GTCS), atypical absence seizures, myoclonic seizure, and epileptic spasms. None of the 32 patients with TS displayed hypsarrhythmia during the 24-h video-EEG recording. A total of 28 patients showed normal EEG backgrounds. Interictal epileptic discharges, including slow waves (SW), spike/sharp slow waves (SSW), and spikes, often displayed multifocally. Notably, two patients achieved seizure freedom for more than 2 years through monotherapy with oxcarbazepine (OXC), which was associated with normalization of the EEG.ConclusionsIt is difficult to classify the patients with TS as any existing epileptic syndromes, which were distinct from West syndrome or Lennox-Gastaut syndrome. TS might be an underreported seizure type and further studies are needed to gain a more comprehensive understanding of the electro-clinical features and appropriate choice of ASMs for treating tonic spasms.

Epilepsy in inmate patients seen in a high complexity reference hospital in Colombia: A cross-sectional study.

To describe the sociodemographic and clinical characteristics of imprisoned patients with epilepsy seen at Samaritana University Hospital (HUS) in Bogotá D.C., between January 2017 and November 2020. Cross-sectional cohort study of inmate patients over 18 years of age seen at HUS between January 2017 and November 2020, with a discharge diagnosis of epilepsy. A descriptive univariate analysis of patient sociodemographic and clinical characteristics was carried out. Overall, 92 patients were included, 95.7% were males with a median age of 32 years (IQR: 26-44); 65% were assessed in the outpatient clinic; median hospital length of stay was 2 days (IQR: 0) and 7.6% required admission to the intensive care unit; 75% had focal onset epilepsy, 63.04% with undetermined etiology 31.52% with structural causes. Polytherapy was found in 53.3%, valproic acid being the most frequently used antiseizure medication in 59.78%; lack of adherence was reported in 15.22% and inadequate seizure control in 81.52%; status epilepticus occurred in 5.34%. A total of 31 EEG recordings and 53 brain images were performed, of which, 29% and 39.62%, respectively, were abnormal. Non-epileptic paroxysmal events were diagnosed in 5.34%, while organic or psychiatric comorbidities were found in 25%, and the use of psychoactive substances was documented in 17.39%. Upon discharge, 93.47% had no disability, and only 45.65% returned for outpatient follow-up. The clinical profile was of men in the fourth decade of life with focal onset epilepsy characterized by high seizure frequency, most of whom were receiving antiseizure medication, with a high proportion of polytherapy. The results are a point of departure for prospective studies designed to identify points to intervene and improve healthcare for inmates with epilepsy. Inmates are a vulnerable proportion of persons with epilepsy. In this group there are significant differences compared to the general population, especially with greater psychiatric comorbidity and worse control of epileptic seizures due to difficulties in accessing medical care, antiseizure medication and diagnostic tests. We found that the most characteristic population is made up of men in the fourth decade of life with a high frequency of seizures, most of whom were receiving multiple antiseizure medication This study is the first of its kind in Latin America and it is an initial approach to epilepsy in inmates.

Phenotypic and genotypic characteristics of children with PCDH19 clustering epilepsy in China

PurposePCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy. MethodsThis retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children's Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients. ResultsThe age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25–22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440–66.111)). ConclusionIn this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders

ObjectiveTo establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). Study designA single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule (ADOS) data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. ResultsAmong 151 patients, 17.2% (n=26) developed unprovoked seizures (Sz group), while 82.8% (n=125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs. 20.0%, p=0.01). The Sz group also exhibited a greater frequency of slowing (42.3% vs. 13.6%, p < 0.01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, p=0.01) or any slowing (HR 2.78, 95% CI 1.02-7.58, p=0.046 significantly increased the risk of developing unprovoked seizures. ConclusionLong-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.