Multiple Seizures Research Articles

Virtual resection evaluation based on sEEG propagation network for drug-resistant epilepsy

Drug-resistant epilepsy with frequent seizures are considered to undergo surgery to become seizure-free, but seizure-free rates have not dramatically improved, partly due to imprecise intervention locations. To address this clinical need, we construct effective connectivity to reveal epilepsy brain dynamics. Based on the propagation path captured by the high order effective connectivity, calculate the control centrality evaluation scheme of the excised area. We used three datasets: simulation dataset, clinical dataset, and public dataset. The epileptogenic propagation network was quantified by calculating high-order effective connection to obtain accurate propagation path, based on this, combined with the outdegree index for virtual resection. By removing electrodes and recalculating control centrality, we quantify each electrode or region’s control centrality to evaluate the virtual resection scheme. Three datasets obtained consistent results. We track the accurate propagation path and find the obvious inflection points occurring during the excision process. The minimum intervention targets were obtained by comparing different schemes without recurrence. The clinical data with multiple seizures found that after resection, the brain reaches a stable state and is less likely to continue spreading. By quantitative analysis of control centrality to evaluate the possible excision scheme, finally we obtain the best intervention area for epilepsy, which assist in developing surgical plans.

Long-term phenobarbital treatment is effective in working-age patients with epilepsy in rural Northeast China: a 10-year follow-up study.

Effective management of epilepsy in working-age patients is essential to reduce the burden on individuals, families, and communities. This study aimed to assess the long-term efficacy of phenobarbital (PB) in working-age patients with epilepsy in rural Northeast China and identify the risk factors for seizures during treatment. Patients aged 18-65 years diagnosed with convulsive epilepsy in rural areas of Jilin Province between 2010 and 2024 were included, and demographic and clinical data were recorded. Seizure frequency, self-efficacy, adherence, and adverse events (AEs) were assessed monthly. Of the 3,568 participants, 288 (8.1%) withdrew from the study and 159 (4.5%) died. During the first year of treatment, 75.2% of patients experienced a ≥50% reduction in seizure frequency compared with baseline (considered as treatment effectiveness); 53.7% of patients were seizure-free. By the tenth year, 97.7% of patients showed treatment effectiveness, and 89.6% were seizure-free. Self-efficacy was improved in 37.8% of patients in the first year and in 72% of patients by the tenth year. The independent risk factors for seizures during treatment were higher baseline seizure frequency [odds ratio (OR) = 1.431, 95% confidence interval (CI): 1.122-1.824], presence of multiple seizure types (OR = 1.367, 95% CI: 1.023-1.826), and poor adherence (OR = 14.806, 95% CI: 3.495-62.725), with significant differences observed in the first, third, and fifth years. The most commonly reported AEs were drowsiness (43.3%), dizziness (25.0%), and headaches (17.0%), most of which were mild and decreased over time. Age at enrollment was the only factor influencing withdrawal (hazard ratio = 0.984, 95% CI: 0.973-0.996, p = 0.010), with a substantial number of patients who withdrew (32.6%) relocating for work. Cardiovascular disease was the primary cause of death, and age at enrollment was the only risk factor (hazard ratio = 1.026, 95% CI: 1.009-1.043, p = 0.002). Working-age adults with epilepsy demonstrated a favorable response and tolerability to PB monotherapy. Baseline seizure frequency, seizure type, and adherence consistently predicted prognosis throughout the treatment period. Withdrawal was mainly explained by work-related pressures in this age group. Therefore, it is essential to implement interventions that support patient adherence to therapy and maintain stable regimens.

8721 A Case of Congenital Hyperinsulinism Manifesting as Transient Hypoglycemia During Illness Due to Mosaic Variant of Unknown Significance in ABCC8

Abstract Disclosure: E.E. Bell-Sambataro: None. L. Mamilly: None. Background: Congenital hyperinsulinism (CHI) is characterized by inappropriate secretion of insulin during periods of low blood glucose. CHI can lead to significant complications such as seizures, developmental delays and neurologic damage. CHI can be caused by multiple genetic variants. The most common genetic etiologies are loss of function mutations in the genes ABCC8 and KCNJ11 encoding the pancreatic Beta (β)-cell ATP-sensitive potassium channel causing over secretion of insulin from the β-cells. We report a challenging pediatric case with a clinical presentation of CHI in an infant with a de novo mosaic ABCC8 gene variant of unknown significance manifesting only during times of illness. Clinical Case: A male infant born at 36 weeks gestational age was transferred to a tertiary center NICU secondary to seizure activity and hypoglycemia after the 24 hours of life with glucose levels as low as 32 mg/dL. His birth weight was normal and there was not maternal history of diabetes mellitus. The hypoglycemia persisted throughout the first week of life and required a glucose infusion rate of 11 mg/kg/min, without success in obtaining a critical sample. He had multiple seizures and MRI brain showed signs of hypoglycemic encephalopathy. Subsequently, he was weaned off IV dextrose and completed a 6 hour safety fast prior to discharge. Rapid genome testing resulted in a de novo, mosaic variant of unknown significance in ABCC8 (C.3622G>A resulting in amino acid substitution p.Glu1208Lys). His family reported significant but transient hypoglycemia during times of illness. At the age of 11 months, he was hospitalized for significant hypoglycemia during an episode of acute gastroenteritis and was treated with dextrose-containing fluids for 36 hours. A subsequent diagnostic fasting study resulted in hypoglycemia within 5.5 hours with capillary glucose of 49 mg/dL. At the time of hypoglycemia, beta hydroxybutyrate was inappropriately low at 0.78 mm, insulin level was suppressed <2 mcIU/mL. Glucagon (30 mcg/Kg) was administered after the initial sample was drawn with a significant increase in glucose from 49 mg/dL to 103 mg/dL. Based on the positive glucagon response and low serum ketone, the clinical diagnosis of CHI was made and diazoxide was initiated while awaiting other results. After the second dose of diazoxide, all glucose levels remained above 80 mg/dL. He was sent home on a continuous glucose monitor and diazoxide. Conclusion: CHI can occur due to autosomal recessive or autosomal dominant ABCC8 loss-of-function mutations of which more than half are not responsive to diazoxide. In this case report, we describe the diagnosis of hyperinsulinemic hypoglycemia in an infant with an ABCC8 variant classified with unknown significance. We describe a good initial response to diazoxide in normalizing blood glucose levels in this infant. Presentation: 6/2/2024

MNGA-02 MENINGIOMA WITH CONTROLATERAL SUB-DURAL HEMATOMA: CASE REPORT AND LITERATURE REVIEW

Abstract BACKGROUND Meningiomas account for around 20% of primary intracranial tumors. It is the most common benign brain tumor. The association of meningiomas with subdural hematoma is rare, and very few cases have been reported in the literature. The pathophysiological mechanisms are not yet fully understood. We therefore report a case of chronic subdural haematoma associated with a meningioma and review the relevant literature. CASE PRESENTATION A 72-year-old patient with known hypertension and a right basifrontal lesion discovered a few months previously. He was brought to emergency by his daughter for multiple comitial seizures and confusion. On clinical examination, the patient was conscious but confused, with anosmia and no sensory or motor deficits. A brain scan and MRI revealed a right parasagittal basifrontal meningioma associated with a chronic left subdural hematoma. The patient had no coagulation disorders. He underwent removal of the meningioma using a bifrontal approach, cranialisation of the sinuses, and drainage of the hematoma using an external subdural shunt. The postoperative course was favorable. Post-operative imaging showed satisfactory Simpson 1 resection and good drainage. The anatomopathological examination concluded that the meningioma had a meningothelial morphological subtype of doubtful invasiveness, suggesting a grade 2 invasive meningioma or a grade 1 meningothelial meningioma. No additional treatment was required. CONCLUSION The presence of a meningioma should always be suspected in the presence of an acute non-traumatic subdural hematoma. To obtain a more comprehensive pathophysiological explanation of the association, a meta-analysis involving a larger number of cases and a larger series would be necessary.

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.

Refractory Epilepsy in Adult Patient With COQ8A Variant Improves With CoQ10 Supplementation: A Case for Exome Sequencing in the ICU.

Describe a case of stroke-like episodes and refractory status epilepticus diagnosed with primary CoQ10 deficiency-4 (COQ10D4) using whole-exome sequencing in the intensive care unit (ICU), with treatment implications. A patient presented to the emergency department with 1 month of progressively worsening focal motor status epilepticus and stroke-like imaging abnormalities. Multiple seizure medications, ketogenic diet, and elective intubation for anesthetic drips failed to achieve sustained seizure freedom. Genetic testing was pursued for prognostic information and identified potential treatment. Whole-exome sequencing revealed compound heterozygous variants of COQ8A, including 1 allele not previously described as pathogenic. The patient's history, imaging, and genetic testing supported a diagnosis of COQ10D4. High-dose coenzyme Q10 supplementation was started with gradual clinical improvement. Whole-exome sequencing is a fast and cost-effective means to diagnose rare neurologic disease in critically ill patients and can uncover treatment options. While primarily used in the neonatal ICU, appropriately selected adult patients may also benefit.

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.

Lennox- Gastaut Syndrome (Childhood Epileptic Encephalopathy) – A Rare Case Report

Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is defined by generalized multiple type seizures, slowness of intellectual growth, and a specific EEG disturbance. Children affected may previously had infantile spasms or underlying brain disorder, but the aetiology can be idiopathic or symptomatic. The incidence of secondary epilepsy is higher in developed countries resulting in higher the incidence of disease. Lennox-Gastaut syndrome (LGS) 18 is characterized by multiple seizure types. An axial tonic seizure is the hallmark of LGS. Later on, atypical absence, atonic and myoclonic falls and recurrent status observed. Cognitive and behavioural abnormalities are common. Gastaut syndrome is usually between 2-7 years with a peak onset between 3 to 5 years. The awake EEG record shows 2-to2.5-Hz spike-and-wave and polyspike and wave discharges, which are usually diffuse and maximal bifrontal. The prognosis is unfavourable and only a minority of patients achieves seizure control. Newer antiepileptic drugs (AEDs) like felbamate lamotrigine and topiramate have been found to be useful. Anterior corpus callostomy may reduce seizure frequency in some patients. Astatic seizures preceded by a prominent tonic component are most improved by these procedures in some cases. LGS seizures are often treatment resistant and the long-term prognosis is poor.

Seizure burden and healthcare resource utilization among people living with drug-resistant focal epilepsy in the United States

Objective This study investigated clinical characteristics, burden of uncontrolled seizures, and seizure-related healthcare resource utilization (HRU) among individuals living with drug-resistant focal epilepsy (FE) in the United States (US). Methods Medical charts of adults with drug-resistant FE who initiated third-line (3 L) anti-seizure medication were extracted from clinical practices in the US (1/1/2013–1/31/2020). The index date, defined as the date of 3 L initiation, was used to indicate the emergence of drug resistance. Individuals on cenobamate were followed for any length of time from the index date. Demographic and clinical characteristics were analyzed descriptively. Primary clinical outcomes included seizure burden (i.e. change in seizure frequency and time to the first and second seizure events) and epilepsy-related HRU. Results Overall, 189 neurologists/epileptologists contributed 345 charts of individuals living with drug-resistant FE (66% male; average age 24 years at diagnosis and 32 years at index date). 66% had ≥1 neurologic/neuropsychiatric comorbidity at baseline. Average monthly seizure rate decreased from 6.1 at baseline to 3.8 at follow-up; however, nearly half of individuals experienced worse/no change or only some improvement (<50% reduction) in seizure frequency. Most individuals (91%) had ≥1 epilepsy-related outpatient visit during follow-up. Unplanned HRU included emergency department visits (43%) and hospitalizations (24%), primarily due to breakthrough seizure events. Conclusion Despite the availability of many anti-seizure medications in the US, people living with drug-resistant FE continue to experience multiple seizures per month and incur substantial healthcare resources. Novel pharmacotherapies may help individuals living with drug-resistant epilepsy achieve seizure freedom.

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.

Genotype and phenotype of WWOX gene related developmental and epileptic encephalopathy

Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Comprehensive scoping review of fenfluramine's role in managing generalized tonic-clonic seizures in developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmacoresistant seizures and developmental delay. Patients with DEEs experience multiple seizure types, including tonic-clonic seizures (TCS) that can be generalized tonic-clonic (GTCS) or focal evolving to bilateral tonic-clonic (FBTCS). Fenfluramine (FFA) has demonstrated efficacy in reduction of TCS in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs. Using the PRISMA-ScR (Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Review) guidelines, we performed a scoping review to describe changes in TCS in patients treated with FFA. A comprehensive search of five literature databases was conducted up to February 14, 2023. Studies were included if they reported change in GTCS or TCS (but not FBTCS) after treatment with FFA in patients with DEEs. Duplicate patients and studies with unclear efficacy data were excluded. Fourteen of 422 studies met the eligibility criteria. Data extracted and evaluated by expert clinicians identified 421 unique patients with DS (in nine studies), CDKL5 deficiency disorder, SCN8A-related disorder, LGS, SCN1B-related disorder, and other DEEs. The median percent reduction in GTCS or TCS from baseline was available in 10 studies (n = 328) and ranged from 47.2% to 100%. Following FFA treatment, 10 studies (n = 144) reported ≥50% reduction in GTCS or TCS from baseline in 72% of patients; in nine of those (n = 112), 54% and 29% of patients achieved ≥75% and 100% reduction in GTCS or TCS from baseline, respectively. Overall, this analysis highlighted improvements in GTCS or TCS frequency when patients were treated with FFA regardless of the DEE evaluated. Future studies may confirm the impact of FFA on TCS reduction and on decreased premature mortality risk (including sudden unexpected death in epilepsy), improvement in comorbidities and everyday executive function, decreased health care costs, and improvement in quality of life.

Have epilepsy outcomes changed for children with tuberous sclerosis complex in Queensland, Australia?

Historically, epilepsy has been the most frequently presenting feature of tuberous sclerosis complex (TSC). Advances in TSC health care have occurred over the past decade; thus, we studied whether TSC epilepsy outcomes have changed. A retrospective chart review was undertaken for all children with TSC in Queensland, Australia. Epilepsy outcome and TSC diagnosis data were extracted, and data were compared between children born before 2012 with those born in or after 2012. In this retrospective cohort, TSC diagnosis in children born in or after 2012 is now predominantly antenatal (51%, p < .05). Most patients with epilepsy are now known to have TSC before they develop epilepsy. Despite earlier TSC diagnosis, the frequency of epilepsy (85%) has not changed (p = .92), but diagnosis trends toward an earlier age (median = 3 months for patients born in or after 2012 vs. 5.5 months for those born before 2012, p = .23). Most (95%) patients had focal seizures as their initial clinical seizure type; it was rare (5%) for epileptic spasms (ES) to be the initial seizure type. The frequency of ES was lower in patients born in or after 2012 (36% vs. 50%, p = .27). Infantile (<24 months) onset ES was not associated with worse epilepsy outcome. Late onset ES was seen in 14%, and these patients hada lower rate of epilepsy remission. Lennox-Gastaut syndrome was seen in 7%. Febrile/illness-related status epilepticus occurred in 12% of patients, between 1 and 4 years of age. Despite many (78%) patients having multiple daily seizures at maximal seizure frequency, and 74% meeting criteria for treatment-refractory epilepsy, most patients achieved epilepsy remission (66%), either with epilepsy surgery (47%) or with age (53%). At the time of inclusion in this study, only 21% of patients had uncontrolled frequent (daily to 3 monthly) seizures and 14% had uncontrolled infrequent (3 monthly to <2 yearly) seizures. This study provides updated information that informs the counseling of parents of newly diagnosed pediatric TSC patients.

Clinical features and underlying etiology of children with Lennox-Gastaut syndrome.

Lennox-Gastaut Syndrome (LGS) is characterized by the presence of multiple seizure types and encompasses a heterogenous group of etiologies. The aim of our study was to evaluate the etiological profile of LGS and investigate seizure outcomes based on different clinical variables. The clinical features, neuroimaging findings, genetic testing and other testing results of LGS patients were systematically reviewed. The identifiable etiology was categorized as either acquired or nonacquired. Univariate and multivariate regression analyses were performed to explore the association between clinical variables and seizure outcome at the last follow-up. We enrolled 156 patients diagnosed with LGS, of whom 66% were male. The mean age of patients was 34.2months and the median follow-upduration was 29.5months (interquartile range = 14-56.25months). The initial seizure type was epileptic spasm in 61 patients, among which 33 of them met the criteria for infantile epileptic spasm syndrome. All patients underwent neuroimaging test, with 25% falling into the acquired structural category. Etiology could be identified in 84 individuals, including pathogenetic variants found in 34 out of 117 patients with nonacquired etiology. CHD2 mutations were most frequently observed among these pathogenetic variants. At the last follow-up, favorable outcomes were observed in 27 patients. The identification of etiology emerged as a significant determinant influencing LGS outcome; specifically, patients with unknown etiology had a higher likelihood of experiencing favorable outcomes compared to those with known cause (p = 0.041). Early onset age and longer epilepsy duration significantly increased the odds of an unfavorable outcome (p = 0.006 and 0.024). We present novel data on the clinical and etiological spectrum of LGS, with determined etiology observed in over half of the patients. Epileptic spasms were found to be more prevalent than tonic seizures as seizure onset types in LGS. The presence of a known etiology, earlier age at onset, and longer duration of epilepsy were associated with a poorer long-term epileptological outcome.

Clinical characteristics and multimodal imaging can help diagnosing and treating mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease. Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done. Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox-Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations. Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE.

Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria

A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. ClinicalTrials.gov Identifier: NCT03399318.

Clinical and genetic analysis of a child with West syndrome due to a de novo variant of NEXMIF gene

To investigate the clinical features and genetic variant of a child with West syndrome due to a variant of NEXMIF gene. A child who was admitted to the First Medical Center of Chinese PLA General Hospital in March 2021 was selected as the study subject. Clinical data of the patient was collected. The child and his parents were subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The child, a 4-month-old boy, had presented with spastic seizures with no obvious cause. Abnormal EEG, severe hypsarrhythmia, and multiple spastic seizures were discovered. Cranial MRI revealed widening of the extracerebral space at the top of the frontal lobe. Physical examination revealed that the child could not hold his head up, and could not respond to sounds or follow objects with his eyes. He also has microcephaly, with height < 1 s. The child was diagnosed with West syndrome at a local hospital, and was given prednisone orally for 3 months, with seizures under control. Topiramate tablets were taken orally for maintenance treatment, and he has been seizure-free for 7 months. DNA sequencing revealed that he has harbored a de novo nonsense variant of c.982_c.983delTT (p.L328Dfs*23) in the NEXMIF gene. For children with West syndrome with severe developmental delay or even regression as the first symptoms, uncontrollable seizures and abnormal facial appearance, mutations of the NEXMIF gene should be suspected, and genetic testing can facilitate early diagnosis and treatment.

DETERMINANTS OF MORTALITY AND COMPLICATIONS IN HYPERTENSIVE DISORDERS OF PREGNANCY : A SINGLE CENTER EXPERIENCE

Our retrospective cohort study set out to identify the determinants of adverse maternal and perinatal outcome in patients admitted to intensive care (ICU) with severe features of Hypertensive Disorders of Pregnancy(HDP).Case files of patients with severe pre-eclampsia and eclampsia (including HELLP syndrome) were analyzed.The prevalence of HDP was 6.01% and eclampsia 0.99%. Parity did not affect the severity of disease nor survival. The incidence of chronic hypertension was 15.38% and 12.5% in survivors and non-survivors respectively. There was a high number of patients who did not receive any antenatal care prior to admission in both the groups [69% and 87%]. Severe anemia was significantly higherin non-survivors (42%) than in survivors (13%). Symptoms such as blurred vision, respiratory distress, oliguria, altered sensorium and absent fetal movements were prognostic markers. Multiple seizures and a time lapse between the onset of symptoms and administration of magnesium sulfate produced an increased mortality. The stillbirth rate, as expected, was high is those who demised (62.5%).We conclude that complications due to hypertension in pregnancy should be considered as a failure to provide quality antenatal care and represent a missed opportunity to detect and treat raised blood pressure.

Dravet Syndrome: An Electroclinical, Genetic, Treatment, and Outcome Study of 35 Patients in Argentina

AbstractWe analyzed the electroclinical features, molecular findings, treatment, disease course, and outcomes of patients with Dravet syndrome (DS) with positive genetic markers seen at a public hospital in Argentina. A retrospective study was conducted assessing the clinical records of 44 patients who met the diagnostic criteria for DS according to the 2022 classification of epilepsy of the International League Against Epilepsy seen at our center between March 2018 and June 2023. Of 44 patients, 35 (18 males and 17 females), in whom genetic studies yielded positive results, were included. Median age was 9 years (range 4 to 16 years), and the median time of follow-up was 10 years (range 3 to 14 years). The mean age at onset was 7 months. The first seizure was associated with febrile illness in all patients, and in 11 (31.4%), seizures were immediately preceded by either infectious disease or vaccination. Heterozygous pathogenic/likely pathogenic SCN1A variants were detected in 32 of the original 44 patients (73%), of which 47% were novel. Variants in other genes related to DS (HCN1, STXB1, and SCN1B) were identified in three patients. Cognitive delay and motor impairment were found to be more severe in patients that had multiple and drug-resistant seizures and in those who had the complete phenotype with myoclonic seizures. Novel SCN1A gene variants were identified in nearly half of the patients. The prognosis for cognitive development is unfavorable. Seizures are not well controlled with antiseizure medications and early treatment with ketogenic dietary therapy as well as cannabidiol should be considered.

Deep learning‐based seizure prediction using EEG signals: A comparative analysis of classification methods on the CHB‐MIT dataset

AbstractEpilepsy is a brain disorder that causes patients to have multiple seizures. About 30% of patients with epilepsy are not treated with medication or surgery. The abnormal activity of brain before occurring of a seizure (about a few minutes before a seizure occurs) are known as the preictal area. Therefore, if we can predict this state, we can control possible seizures by using appropriate medications. In this study, we present a method for predicting epileptic seizures using electroencephalogram (EEG) signals. The method can identify the preictal region that occurs before the onset of seizures. In our proposed method, first the noise removal of EEG signals is performed, and then the necessary features are extracted using a convolution neural network. Finally, we use the feature vectors in order to train multiple classifiers, fully connected layer, random forest, and support vector machines with linear kernel. Additionally, we apply maximum voting, which is an ensemble method, to classify preictal segments from interictal ones. In this study, using EEG signals of patients from CHB‐MIT dataset, we were able to achieve sensitivity of 90.76%.