Seizure Types Research Articles

Variants loci and phenotype correlation of TRIM8-related neuro-renal syndrome: three cases reports and literature review.

TRIM8-related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of TIRM8-related NRS. A retrospective analysis was conducted for three Chinese children with NRS due to TRIM8 variants identified through whole-exome sequencing (WES). Previous reports of patients with TRIM8-related NRS were reviewed systematically. Demographic and clinical data were collected from these patients. Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p.Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. This study expands the number of individuals with confirmed NRS due to pathogenic variants in TRIM8. Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants.

Effectiveness of add-on acetazolamide in children with drug-resistant CHD2-related epilepsy and in a zebrafish CHD2 model.

CHD2-related epilepsy is characterized by early-onset photosensitive myoclonic epilepsy with developmental delay and a high rate of pharmacoresistance. We sought to evaluate the efficacy of acetazolamide (ACZ) in CHD2-related epilepsy, due to ACZ's unexpected efficacy in our first patient harboring a pathogenic CHD2 variant. We collected patients from different Eastern European countries with drug-resistant CHD2-related epilepsy who were then treated with ACZ. Patients underwent video EEG before and during ACZ treatment. In a zebrafish model of CHD2-related epilepsy, ictal-like events were recorded 5 days post-fertilization after overnight ACZ exposure. Developmental delay preceded the onset of seizures in 10 of the 12 patients. Four had ataxia, and 6 exhibited autistic features. Seizures, primarily myoclonic, began at an average age of 3.4 years and were photosensitive in all 12 patients. Add-on ACZ treatment controlled photosensitive seizures in all patients: 6 became seizure-free, and in the remaining 6, seizure frequency decreased by over 75%. Four patients transitioned to ACZ monotherapy. The median follow-up was 13 months. In the zebrafish model, ACZ exposure reduced ictal-like events by 72%. ACZ, a well-tolerated and cost-effective medication, could be a good option for CHD2-related epilepsy, predominantly manifesting with myoclonic seizures and photosensitivity. PLAIN LANGUAGE SUMMARY: Epilepsy associated with CHD2 mutations is often pharmacoresistant and associated with developmental delay and eventually ataxia. There are several generalized seizure types, including generalized tonic-clonic seizures, but the most characteristic are jerks triggered by light stimulation. We collected 12 patients who received acetazolamide, a drug usually given as a diuretic and registered as a mild antiseizure medication. All jerks triggered by light disappeared while the frequency of spontaneous seizures decreased by over 75%. Further studies are needed to confirm this promising finding and identify the mechanism by which an old compound seems to have such a specific antiseizure effect.

Predictors of drug-resistant epilepsy in childhood epilepsy syndromes: A subgroup analysis from a prospective cohort study.

Previous studies assessing factors associated with drug-resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies. This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self-limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group. Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified. This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course.

Ketogenic Diet as a Therapeutic Intervention for Doose Syndrome: A Case Report and Review of Current Evidence

Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome or myoclonic–astatic epilepsy (MAE), represents a challenging pediatric epilepsy syndrome, initially described by Doose et al. in 1970. MAE accounts for 1%–2.2% of juvenile-onset epilepsy cases, characterized by normal early development, followed by seizure onset between 7 months and 6 years. Seizure types include myoclonic, myoclonic-atonic, generalized tonic–clonic, and atypical absences, often accompanied by nonconvulsive status epilepticus. Electroencephalogram typically shows parietal-dominant rhythmic theta activity or a posterior 4 Hz pattern. While conventional antiseizure medications (ASMs) offer some efficacy, outcomes vary widely, and up to 50% of patients may experience refractory seizures and poor intellectual outcomes. The ketogenic diet (KD), a high-fat, low-carbohydrate diet inducing ketosis, has shown promise in reducing seizure frequency and severity in refractory epilepsy, including MAE. This case report describes a successful outcome with a South Indian style KD in a 3-year-old boy with Doose syndrome presenting with 20–25 daily head drop seizures despite multiple ASMs and steroid therapy. Initiation of a home-based KD utilizing traditional household ingredients significantly reduced seizure frequency by 60% within 1 month and 80% within 2 months and was 100% seizure-free in 3rd month following KD, alongside developmental improvements. The KD was well-tolerated, with improved nutritional status. This case underscores KD’s potential as a viable complementary therapy for MAE, emphasizing the need for ongoing parental support and supervision to ensure dietary adherence and optimize outcomes. It is commonly believed that the KD is challenging for the South Indian population to follow due to the high carbohydrate content in South Indian cuisine. However, this case demonstrates that a KD can indeed be tailored around South Indian dishes, highlighting the uniqueness of this approach. When the diet is customized to consider a child’s dietary habits, culture, and cuisine, it becomes easier to follow over the long term, leading to effective seizure control. Further research is necessary to refine dietary protocols and evaluate long-term efficacy in MAE management.

Vitamin D Supplementation for Children with Epilepsy on Antiseizure Medications: A Randomized Controlled Trial.

Antiseizure medications (ASMs) are crucial for managing epilepsy in children. However, a well-documented side effect of ASMs is their impact on bone health, often due to interference with vitamin D metabolism. This can lead to vitamin D deficiency in children with epilepsy. This study aimed to determine if a daily dose of 400 IU or 1000 IU would maintain adequate vitamin D levels in children with epilepsy. A phase IV randomized controlled trial enrolled children aged 2-16 years with epilepsy and receiving antiseizure medications. Children were divided into two groups: the monotherapy group, which was defined as children on one antiseizure medication (ASM), and the polytherapy group, which was defined as children receiving two or more ASMs. Eligible children with levels above 75 nmol/L were randomized to receive a maintenance dose of either 400 IU/day or 1000 IU/day of cholecalciferol. Baseline and 6-month assessments included demographic data, anthropometric measurements, seizure type, medications, seizure control, and 25(OH)D level. Out of 163 children, 90 were on monotherapy and 25 on polytherapy. After 6 months of vitamin D maintenance, the proportion of children with 25(OH)D concentration below 75 nmol/L was 75.0% in the 400 IU group and 54.8% in the 1000 IU group. In the monotherapy group, baseline seizure-free children increased from 69% to 83.6% after treating vitamin D deficiency. Daily vitamin D supplementation with 1000 IU may be beneficial for children with epilepsy, particularly those receiving monotherapy, to maintain sufficiency and potentially improve seizure control.

Impaired excitability of fast-spiking neurons in a novel mouse model of KCNC1 epileptic encephalopathy.

The recurrent pathogenic variant KCNC1-p.Ala421Val (A421V) is a cause of developmental and epileptic encephalopathy characterized by moderate-to-severe developmental delay/intellectual disability, and infantile-onset treatment-resistant epilepsy with multiple seizure types including myoclonic seizures. Yet, the mechanistic basis of disease is unclear. KCNC1 encodes Kv3.1, a voltage-gated potassium channel subunit that is highly and selectively expressed in neurons capable of generating action potentials at high frequency, including parvalbumin-positive fast-spiking GABAergic inhibitory interneurons in cerebral cortex (PV-INs) known to be important for cognitive function and plasticity as well as control of network excitation to prevent seizures. In this study, we generate a novel transgenic mouse model with conditional expression of the Ala421Val pathogenic missense variant (Kcnc1-A421V/+ mice) to explore the physiological mechanisms of KCNC1 developmental and epileptic encephalopathy. Our results indicate that global heterozygous expression of the A421V variant leads to epilepsy and premature lethality. We observe decreased PV-IN cell surface expression of Kv3.1 via immunohistochemistry, decreased voltage-gated potassium current density in PV-INs using outside-out nucleated macropatch recordings in brain slice, and profound impairments in the intrinsic excitability of cerebral cortex PV-INs but not excitatory neurons in current-clamp electrophysiology. In vivo two-photon calcium imaging revealed hypersynchronous discharges correlated with brief paroxysmal movements, subsequently shown to be myoclonic seizures on electroencephalography. We found alterations in PV-IN-mediated inhibitory neurotransmission in young adult but not juvenile Kcnc1-A421V/+ mice relative to wild-type controls. Together, these results establish the impact of the recurrent Kv3.1-A421V variant on neuronal excitability and synaptic physiology across development to drive network dysfunction underlying KCNC1 epileptic encephalopathy.

Functional seizure semiology and classification in a public and private hospital

PurposeOur understanding of potential differences in seizure semiology among patients with functional seizures (FS), also known as psychogenic non-epileptic seizures (PNES), across socioeconomic contexts is currently limited. By examining the differences in seizure manifestations between different socioeconomic groups, we aim to enhance the understanding of how socioeconomic factors may influence FS presentation. This study aimed to describe FS semiology in patients from a private and public epilepsy monitoring units (EMUs) in Cape Town, South Africa. MethodsThe study included patients with FS confirmed through video-electroencephalography (video-EEG) and without comorbid epilepsy. For this retrospective case-control study, data on seizure semiology was gathered from digital patient records, beginning with the earliest available record for each hospital. ResultsA total of 305 patients from a private hospital and 67 patients from a public hospital were eligible for the study (N = 372). The private hospital tended to report more akinetic and subjective seizure types when compared to the public hospital. Additionally, patients at the public hospital had higher odds of reporting emotional seizure triggers (aOR=2.57, 95% CI [1.03, 6.37]), loss of consciousness or awareness (aOR=2.58, 95% CI [1.07, 6.24]), and rapid post-event recovery (aOR=6.01, 95% CI [2.52, 14.34]). At the same time, they were less likely to report both short (<30 s) (aOR=0.21, 95% CI [0.08, 0.55]) and long (>5 min) seizures (aOR=0.73, 95% CI [0.13, 0.56]), amnesia for the event (aOR=0.19, 95% CI [0.09, 0.43]), ictal aphasia (aOR=0.33, 95% CI [0.14, 0.76]) or falls and drop attacks (aOR=0.43, 95% CI [0.18, 0.996]), when compared to the private hospital patients. ConclusionWhile the seizure manifestations were largely consistent across the two socioeconomic cohorts of patients with FS, some subtle differences were observed and warrant further investigation.

Awake Craniotomy in Epilepsy Surgery: A Case Series and Proposal for Three Different Scenarios.

Awake craniotomy (AWC) allows intraoperative evaluation of functions involving the cortical surface and subcortical fibers. In epilepsy surgery, indications for and the role of AWC have not been established because evaluation with intracranial electrodes is considered the gold standard. We report herein our case series of patients who underwent AWC in epilepsy surgery and propose the scenarios for and roles of AWC. Patients who underwent AWC in epilepsy surgery at our institutions between 2014 and 2023 were included. Information about age, sex, etiology, location of epileptogenicity, seizure type, use of intracranial electrode placement, surgical complications, neurological deficits, additional surgery, and seizure outcomes was reviewed. Following a diagnostic and treatment flow for epilepsy surgery, we clarified three different scenarios and roles for AWC. Ten patients underwent AWC. Three patients underwent AWC after non-invasive evaluations. Two patients underwent AWC after intracranial evaluation with stereotactic electroencephalography (SEEG). Five patients underwent AWC after intracranial evaluation with subdural grid electrodes (SDG). Among these, two patients were initially evaluated with SEEG and with SDG thereafter. One patient reported slight numbness in the hand, and one patient showed slight cognitive decline. Seizure outcomes according to the Engel outcome scale were class 1A in three patients, IIA in two patients, IIIA in four patients, and IVA in one patient. AWC can be used for purposes of epilepsy surgery in different situations, either immediately after non-invasive studies or as an additional invasive step after invasive monitoring with either SEEG or SDG. The application of AWC should be individualized according to each patient's specific characteristics.

Influenza Infection During Pregnancy and Risk of Seizures in Offspring

Seizure is a common neurological problem among infants and children up to age 6 years. Prenatal exposure to maternal influenza infection has been reported to be associated with childhood seizures. To evaluate the association between maternal influenza infection and risk of childhood seizures. This cohort study identified mother-offspring pairs from January 1, 2004, to December 31, 2013, using records in Taiwan's Maternal and Child Health Database. Mothers who had influenza infection during pregnancy and their first offspring were identified and assigned to the influenza group. Mothers in the control group were those without influenza during pregnancy and were matched 1:4 with mothers in the influenza group by maternal age, offspring sex, and date of delivery. Offspring were followed up until December 31, 2020. Data were analyzed between March 2023 and July 2024. Diagnosis of influenza infection during pregnancy defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes 487.0, 487.1, and 487.8, or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes J09, J10, and J11. The primary outcome was the association between maternal influenza infection during pregnancy and risk of any type of seizures during childhood, including both epilepsy and febrile seizures. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression models. Pregnancy-related complications were collected as covariates. A total of 1 316 107 mother-offspring pairs were enrolled, of whom 75 835 mothers (predominant maternal age, 25-29 years; 39 324 male offspring [51.9%]) were assigned to the influenza group and 1 240 272 were matched and assigned to the control group (n = 303 340; predominant maternal age, 30-34 years; 157 296 male offspring [51.9%]). In the influenza group, there was a slightly higher prevalence of placenta previa or abruption compared with the control group (1.6% [1241] vs 1.4% [4350]; P < .001). The cumulative risk of seizures was higher among offspring whose mothers had influenza infection. After controlling for potential confounders, the AHRs were 1.09 (95% CI, 1.05-1.14) for seizures, 1.11 (95% CI, 1.06-1.17) for febrile convulsions, and 1.04 (95% CI, 0.97-1.13) for epilepsy. In the subgroup analysis, no statistically significant differences were observed between the trimesters regarding the timing of influenza infection. Results of this cohort study suggest that maternal influenza infection during pregnancy was associated with an increased risk of childhood seizures, especially febrile seizures, but not epilepsy. Further studies are needed to elucidate the mechanisms underlying childhood neurological development.

Clinical efficacy and safety of perampanel monotherapy as primary anti-seizure medication in the treatment of pediatric epilepsy: A single-center, prospective, observational study.

To assess the efficacy and safety of perampanel (PER) as primary monotherapy in patients aged 4-18 years old with epilepsy. A single-center, prospective, observational study was conducted from October 2021 to October 2023, to evaluate PER monotherapy's efficacy and safety as initial therapy for pediatric epilepsy. Changes in seizure frequency, safety, and retention rate were observed at 3, 6, 9, and 12 months after initiating PER primary monotherapy. A total of 124 children aged 4-15 years (mean age = 8.25 ± 2.50 years) were included in the Analysis Sets. The retention rates at 3, 6, 9, and 12 months were 88.71% (110/124), 84.68% (105/124), 78.26% (90/115), and 71.58% (68/95), respectively. Seizure freedom rates at 3, 6, 9, and 12 months were 85.45%, 79.09%, 76.24%, and 75.31%, respectively. The responder rates (≥50% but <100%) at the same endpoints were 9.09%, 14.55%, 12.87%, and 7.41%, respectively. Seizure freedom rate of PER was independent of age at PER initiation, seizure onset age, gender, baseline frequency, seizure types, and family history of epilepsy (p > 0.05) but associated with duration of treatment (p = 0.001) and maintenance dose (p = 0.022). Additionally, 124 patients were included in the safety analysis set. The overall adverse event rate was 38.71% (48/124), with irritability (19 cases, 15.32%) and dizziness (18 cases, 14.52%) being the most common adverse effects. One patient discontinued PER monotherapy within 1 month due to unbearable itching of the skin. PER monotherapy as the primary anti-seizure medication (ASM) for pediatric epilepsy demonstrates high efficacy and safety in real-world clinical treatment. Patients who respond well to this drug and adhere to long-term treatment can achieve favorable seizure control. Furthermore, patients achieving seizure freedom with a relatively lower dose can opt for the same dose as the maintenance dose. This study provided the efficacy and safety of PER monotherapy as the primary ASM for Chinese pediatric epilepsy. In total, 124 patients took part. The seizure freedom rates were over 70% at different observation points (OPs), along with a retention rate of 71.58% at the 12-month OP. Most of adverse effects observed were mild to moderate.

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy-specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti-seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient-reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs. PLAIN LANGUAGE SUMMARY: Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic-clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic-clonic seizures on patients was rarely reported, and future research is needed.

Patients carrying pathogenic SCN8A variants with loss‐ and gain‐of‐function effects can be classified into five subgroups exhibiting varying developmental and epileptic components of encephalopathy

AbstractObjectivePhenotypic heterogeneity presents challenges in providing clinical care to patients with pathogenic SCN8A variants, which underly a wide disease spectrum ranging from neurodevelopmental delays without seizures to a continuum of mild to severe developmental and epileptic encephalopathies (DEEs). An important unanswered question is whether there are clinically important subgroups within this wide spectrum. Using both supervised and unsupervised machine learning (ML) approaches, we previously found statistical support for two and three subgroups associated with loss‐ and gain‐ of‐ function vari‐ants, respectively. Here, we test the hypothesis that the unsupervised subgroups (U1–U3) are distinguished by differential contributions of developmental and epileptic components.MethodsWe predicted that patients in the U1 and U2 subgroups would differ in timing of developmental delay and seizure onset, with earlier and concurrent onset of both features for the U3 subgroup. Standard statistical procedures were used to test these predictions, as well as to investigate clinically relevant associations among all five subgroups.ResultsTwo‐population proportion and Kruskal–Wallis tests supported the hypothesis of a reversed order of developmental delay and seizure onset for patients in U1 and U2, and nearly synchronous developmental delay/seizure onset for the U3 (termed DEE) subgroup. Association testing identified subgroup variation in treatment response, frequency of initial seizure type, and comorbidities, as well as different median ages of developmental delay onset for all five subgroups.SignificanceUnsupervised ML approaches discern differential developmental and epileptic components among patients with SCN8A‐related epilepsy. Patients in U1 (termed developmental encephalopathy) typically gain seizure control yet rarely experience improvements in development, whereas those in U2 (termed epileptic encephalopathy) have fewer if any developmental impairments despite difficulty in achieving seizure control. This understanding improves prognosis and clinical management and provides a framework to discover mechanisms underlying variability in clinical outcome of patients with SCN8A‐related disorders.

Statistical characteristics of large-scale objective tonic-clonic seizure records from medical smartwatches used in daily life.

This study aimed to assess whether population-level patterns in seizure occurrence previously observed in self-reported diaries, medical records, and electroencephalographic recordings were also present in tonic-clonic seizure (TCS) diaries produced via the combined input of a US Food and Drug Administration-cleared wristband with an artificial intelligence detection algorithm and patient self-reports. We also investigated the characteristics of patient interactions with wearable seizure alerts. We analyzed wristband data from patients with TCSs who had at least three reported TCSs over a minimum of 90 days. We quantified TCS frequency and cycles, and the relationship between the mean and variability of monthly TCS counts. We also assessed interaction metrics such as false alarm dismissal and seizure confirmation rates. Applying strict criteria for usable data, we reviewed 137 490 TCSs from 3012 patients, with a median length of TCS alert records of 445 days (range = 90-1806). Analyses showed consistency between prior diary studies and the present data concerning (1) the distribution of monthly TCS frequency (median = 3.1, range = .08-26); (2) the linear relationship (slope = .79, R2 = .83) between the logarithm of the mean and the logarithm of the SD of monthly TCS frequency (L-relationship); and (iii) the prevalence of multiple coexisting seizure cycles, including circadian (84.0%), weekly (24.6%), and long-term cycles (31.1%). Key population-level patterns in seizure occurrence are recapitulated in wrist-worn device recordings, supporting their validity for tracking TCS burden. Compared to other approaches, wearables can provide noninvasive, objective, long-term data, revealing cycles in seizure risk. However, improved patient engagement with wristband alerts and further validation of detection accuracy in ambulatory settings are needed. Together, these findings suggest that data from smart wristbands may be used to derive features of TCS records and, ultimately, facilitate remote monitoring and the development of personalized forecasting tools for TCS management. Our findings may not generalize to other types of seizures.

Unveiling the disease progression in developmental and epileptic encephalopathies: Insights from EEG and neuropsychology.

Developmental and epileptic encephalopathies (DEEs) are neurological disorders characterized by developmental impairment and epilepsy. Our study aims to assess disease progression by comparing clinical findings, electroencephalography (EEG), and neuropsychological data from seizure onset to the last follow-up evaluation. We retrospectively reviewed patients with genetic DEEs who were followed-up at the epilepsy unit of Bambino Gesù Children's Hospital, Rome. We collected information regarding gender, family history, genetic variant, age at onset and at last follow-up, neurological examination, type of seizure, drug resistance, occurrence of status epilepticus, and movement and cognitive and behavioral disorders. We compared EEG background activity, epileptiform abnormalities, and cognitive functions between seizure onset and the last follow-up evaluation using the McNemar-Bowker test (α = 5%). A total of 160 patients (94 female) were included. Genetic analysis revealed a spectrum of pathogenic variants, with SCN1A being the most prevalent (25%). The median age at seizure onset and at the last follow-up was 0.37 (interquartile range [IQR]: 0.09-0.75) and 8.54 years (IQR: 4.32-14.55), respectively. We documented a statistically significant difference in EEG background activity (p = .017) and cognitive impairment (p = .01) from seizure onset to the last follow-up evaluation. No significant differences were detected for epileptiform abnormalities (p = .2). In addition, high prevalence rates were observed for drug resistance (81.9%), movement disorders (60.6%), behavioral and autism spectrum disorders (45%), neurological deficits (31.3%), and occurrence of status epilepticus (23.1%). Our study provides evidence that a clinical progression may appear in genetic DEEs, manifesting as development or worsening of cognitive impairment and disruption of EEG background activity. These results highlight the challenging clinical course and the importance of early intervention and personalized care in the management of patients with DEEs.

Characteristics of motion signal profiles of tonic-clonic, tonic, hyperkinetic, and motor seizures extracted from nocturnal video recordings.

In this study, characteristics of signal profiles formed by motion, oscillation, and sound signals were analyzed to evaluate generalizability and variability in a single patient setting (intra-patient variability) and between patients (inter-patient variability). As a secondary objective, the effect of brivaracetam intervention on signal profiles was explored. Patient data included 13 hyperkinetic seizures, 65 tonic seizures, 13 tonic-clonic seizures, and 138 motor seizures from 11 patients. All patients underwent an 8-week monitoring, and after a 3-week baseline, brivaracetam was initiated. Motion, oscillation, and sound features extracted from the video were used to form signal profiles. Variance of signals was calculated, and combined median and quartile visualizations were used to visualize the results. Similarly, the effect of intervention was visualized. Hyperkinetic motion signals showed a rapid increase in motion and sound signals without oscillations and achieved low intra-patient variance. Tonic component created a recognizable peak in motion signal typical for tonic and tonic-clonic seizures. For tonic seizures, inter-patient variance was low. Motor signal profiles were varying, and they did not form a generalizable signal profile. Visually recognizable changes were observed in the signal profiles of two patients. Video-based motion signal analysis enabled the extraction of motion features characteristic for different motor seizure types which might be useful in further development of this system. Tonic component formed a recognizable seizure signature in the motion signal. Hyperkinetic and motor seizures may have not only significantly different motion signal amplitude but also overlapping signal profile characteristics which might hamper their automatic differentiation. Motion signals might be useful in the assessment of movement intensity changes to evaluate the treatment effect. Further research is needed to test generalizability and to increase reliability of the results.

Utility of Various Activation Procedures in Provoking Ictal and Interictal Patterns, during Routine Electroencephalogram (rEEG) Recording.

Activation procedures (APs) are adopted during routine electroencephalography (rEEG) to provoke interictal epileptiform abnormalities (EAs). This study aimed to observe interictal and ictal (EAs) of different EEG patterns, provoked by various APs. This cross-sectional study was performed in the neurology department of King Fahd hospital of university, Saudi Arabia. The EEGs and medical records of patients who presented for EEG recordings were screened initially, then 146 EEGs provoked EAs due to utilization of APs, were included for analysis. Among all EEGs with provoked EAs, Non-rapid eye movement sleep (NREM) provoked EAs in 93 (63.7%) patients with following patterns, focal spike wave discharges (FSWDs) 45 (P= 0.01), focal spike wave discharges with bilateral synchrony (FSWDBS) 27 (P=0.03) and generalized spike wave discharges (GSWDs) 46 (P=0.01). Intermittent photic stimulation (IPS) most significantly provoked FSWDs in 07 patient (P =0.01) and GSWDs in 30 patients (P=<0.001) 7 patients (P = 0.01) and GSWDs in 30 patients (P < 0.001). Hyperventilation (HV) was associated with a higher occurrence of GSWDs in 37 patients (P =0.01). Female sex 7 (P = 0.02), provoked GSWDs 3 (P = 0.03), NREM sleep 8 (P = 0.04), prolonged EEG record 3 (P = 0.02), clinical events during recording 5 (P ≤ 0.01), diagnosis of genetic 05 (P = 0.03), and immune-mediated epilepsies 2 (P = 0.001) were associated with the provocation of ictal EAs; however, in multiple logistic regression analysis, no statistically significant association of these variables (P ≥ 0.05 each) was noted. The provocation of EAs in rEEG with different APs varies according to circumstances, including seizure types, epilepsy etiology, and the type of AP applied. These clinical and procedural parameters affect the diagnostic yield of rEEG and need careful consideration during rEEG recordings. APs adopted during rEEG recording can induce FSWDs, FSWDBS, and GSWDs in the form of either interictal or ictal EAs in various etiologies of epilepsy. Ictal EAs may appear in the form of GSWDs, during NREM sleep, in prolonged EEG records; however, their independent association needs to be evaluated in larger sample studies. Further, prospective cohort studies with adequate sample sizes are warranted.

Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.

The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes. At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting. LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure. Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

Evaluation of Risk Factors, Clinical Spectrum and Management of New Onset Seizure

A seizure is a brief deviation from the brain's regular electrical activity that alters awareness and behavior. Seizures are brief burst so fun controllable movement that can affect either a piece of the body (partial) or the full body (generalized) and are frequently followed by a loss of awareness and control over bowel or bladder function. Epilepsy is distinguished by recurring seizures. Epilepsy is a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, associated with abnormal electrical activity in the brain. The goal of the study is to find out risk factors and prescribing pattern of antiseizure drugs in different types of seizure disorder. An educational observational study was carried out among 42 samples in the In-patient Department of General Medicine, ESI MC- PGIMSR, and Rajajinagar. The data was collected using self-designed data collection form. All information’s were processed and analyzed by using Microsoft excel. It was observed that a majority of the subjects involved in the study was prescribed with Levetiracetam (69.81%). A high prevalence of New onset seizure with risk factor of CVS causes (36.92%) and Alcohol withdrawal (20%) was observed. In CVS cause, stroke was prominent. From this study, generalized tonic clonic seizure was most commonly observed type of seizure and Levetiracetam was most frequently prescribed drug to them. Majority of patients were given mono therapy to achieve seizure control.

AGR – 2 The Multi-Dimensional Role of Neuropsychology in Diagnostically Complex Epilepsy Patients: Refining the Surgical Plan and Post-Operative Expectations

Abstract Objective We present a case highlighting the importance of neuropsychological involvement at all phases of a pre-surgical epilepsy work-up, including clinical interview, neuropsychological evaluation, Wada testing, extra-operative electrical stimulation mapping (ESM), and psychoeducation. Method A 24-year-old, right-handed, Caucasian female presented with non-lesional, intractable left-hemisphere localization-related epilepsy characterized by frequent experiences of déjà vu and autonomic sensations. Results Neuropsychological evaluation revealed weaknesses in processing speed and verbal memory implicating left hippocampal involvement. Wada testing suggested minimal contralateral memory support, indicating poor candidacy for resective surgery. The patient underwent prolonged sEEG monitoring to refine a plan for device implantation (i.e., responsive neurostimulation; RNS). No typical events were captured during extended study. Episodic somatosensory changes were captured, which had no electrographic correlate and were presumed to be non-epileptic. ESM evoked the patient’s classic semiology, elucidating nuanced information about her seizure onset zone and network. Barriers to extended monitoring and consistent, reliable engagement during ESM included depression, anxiety, and trauma; considerable neuropsychologist-led emotional support was required. Typical seizure semiology was elicited during stimulation of entorhinal cortices, posterior and anterior hippocampi, amygdala, cingulate and insula. RNS placement included a depth electrode targeting the medial structures (via a posterior approach) with a sub-temporal strip. Conclusions Involvement of neocortical and mesial temporal structures, coupled with a clear neuropsychiatric component, were believed to be poly-etiological factors to the patient’s presentation. Neuropsychological input at all phases of pre-surgical assessment was instrumental in systematically identifying and addressing her complex needs. Psychotherapeutic intervention was suggested to be equally as important to clinical, long-term patient outcome.

Intravenous lacosamide for acute repetitive seizures and convulsive status epilepticus in critically ill children.

Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in critically ill children. The aim of the study was to evaluate the effectiveness and safety of intravenous lacosamide in critically ill children with acute repetitive seizures and convulsive status epilepticus. This retrospective study included children who received intravenous lacosamide for acute repetitive seizures or convulsive status epilepticus from October 2017 to September 2022 and were admitted to the pediatric intensive care unit at a tertiary medical center. Children who were newly started on intravenous lacosamide were included and divided into two groups: (a) previously healthy, and (b) history of epilepsy and receiving antiseizure medications. Efficacy was defined as the cessation of seizures within 72 h of administering lacosamide. Adverse effects were defined using predefined criteria, and most were evaluated during the first 7 days. Sixty-seven children were enrolled, including 25 (37.3%) girls and 42 (62.7%) boys with a mean age of 7.20 ± 5.66 years. Among them, 30 (44.8%) had acute repetitive seizures, and 37 (55.2%) had convulsive status epilepticus. The seizure types were focal onset (n = 34, 50.7%), generalized onset (n = 27, 40.3%), and mixed type (n = 6, 9.0%). In the previously healthy group, 9 patients had acute repetitive seizures and 23 had convulsive status epilepticus, and the rates of seizure cessation when lacosamide was used as the first to fourth choice of antiseizure medication were 100.0%, 85.7%, 40.0%, and 50.0%, respectively, compared to 73.7%, 54.5%, 100.0%, and 0.0% in the patients with epilepsy (21 had acute repetitive seizures and 14 had convulsive status epilepticus). Sixteen (23.9%) patients developed bradycardia and 1 (1.5%) patient developed a rash. The early use of intravenous lacosamide was effective with acceptable side effects in treating acute repetitive seizures and convulsive status epilepticus in critically ill children, including young infants and children less than 4 years old and those with different etiologies. Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in pediatric intensive care units (PICUs), traditional intravenous antiseizure medications (ASMs) include phenytoin, valproic acid, levetiracetam, and phenobarbital. In this study, we categorized patients based on their epilepsy history and different etiologies. We observed that early use of lacosamide, even in young infants, demonstrated good efficacy and safety.