Beyond the Norm: A Report of a Rare Case of Sodium Channel 8 Alpha (SCN8A) Gene-Related Epilepsy Unveiled in a Nine-Year-Old Child.

Sodium channel 8 alpha (SCN8A) mutations encompass a spectrum of epilepsy phenotypes with diverse clinical manifestations, posing diagnostic challenges. We present a case of a nine-year-old male with SCN8A gene-associated developmental and epileptic encephalopathies (DEEs), characterized by generalized tonic-clonic seizures (GTCS) since infancy. Despite treatment with multiple antiepileptic drugs (AEDs), including phenytoin, valproate, levetiracetam, carbamazepine, and clobazam, seizure control remained elusive, prompting genetic testing. Whole exome sequencing confirmed a heterozygous mutation (p.Phe210Ser) in SCN8A exon 6, indicative of DEE-13. Functional studies revealed a gain-of-function mechanism in SCN8A variants, resulting in heightened ion channel activity and altered voltage dependence of activation. Despite treatment adjustments, the patient's seizures persisted until topiramate was introduced, offering partial relief. SCN8A, encoding Nav1.6 sodium channels, modulates neuronal excitability, with mutations leading to increased persistent currents and hyperexcitability. Early seizure onset and developmental delays are hallmarks of SCN8A-related DEE. This case highlights the significance of genetic testing in refractory epilepsy management, guiding personalized treatment strategies. Sodium channel blockers like phenytoin and carbamazepine are often first-line therapies, while topiramate presents as a potential adjunctive option in SCN8A-related DEE. Overall, this case underscores the diagnostic and therapeutic complexities of managing SCN8A-related epileptic encephalopathy, emphasizing the importance of long-term monitoring and personalized treatment approaches for optimizing outcomes in refractory epilepsy.

Optimizing automated detection of high frequency oscillations using visual markings does not improve SOZ localization.

OBJECTIVE: High frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithm's parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. METHODS: We detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. RESULTS: SOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization. CONCLUSIONS: SOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization. SIGNIFICANCE: Visual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.

Cortico-cortical evoked potential and language mapping: A meta-analysis.

PURPOSE: The purpose of this meta-analysis was to determine the best available evidence for the use of cortico-cortical evoked potential (CCEP) for language mapping. METHODS: PubMed/Medline/Google Scholar/Cochrane and Scopus electronic databases were searched for articles using CCEP for language mapping. CCEP data was obtained including the area of the cortex generating CCEP, resection data, and post-resection language outcomes. Inclusion criteria were clinical articles reporting the use of CCEP in language regions of the brain, reporting language outcomes and whether there was final resection of the cortex, studies with more than five patients, and studies in either English or Spanish. Review articles, systematic reviews, meta-analyses, or case series with less than five patients were excluded. RESULTS: Seven studies with a total of 59 patients were included in this meta-analysis. The presence of CCEPs from stimulation of Broca's area or posterior perisylvian region in the resection predicts language deficits after surgery. The diagnostic odds ratio shows values greater than 0 perioperatively (0.69-5.82) and after six months (1.38-11), supporting a high likelihood of a language deficit if the presence of CCEPs from stimulation of Broca's area or posterior perisylvian region are included in the resection and vice versa. The True Positive rate varied between 0.38 and 0.87. This effect decreases after six months to 0.61 (0.30-0.86). However, the True Negative rate increased from 0.53 (0.32-0.79) to 0.71 (0.55-0.88). CONCLUSION: This meta-analysis supports the utility of CCEP to predict the probability of having long-term language deficits after surgery. .

Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review.

Objectives: Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading to higher mortality rates than the general population. Drug-refractory epilepsy, resistant to conventional treatments, affects a range of 7-20% of pediatric patients. The search for alternative therapies has led to exploring the therapeutic potential of Cannabis sativa L. compounds, particularly cannabidiol (CBD). Examine the use of CBD for treating drug-refractory epilepsy in children and young adults, summarizing existing evidence on its efficacy. Materials and Methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, assessed studies from 2018 to 2023, focusing on CBD's efficacy and safety for treatment-resistant epilepsy in pediatric and juvenile populations. The search spanned seven databases, and the studies underwent rigorous screening and data extraction. Results: Out of 6351 identified articles, eight were selected for review. The included studies reported positive outcomes, with CBD leading to a reduction in seizure frequency ranging from 50% to complete seizure freedom. Adverse effects were mostly mild and reversible, including drowsiness, diarrhea, and loss of appetite. Conclusion: The CBD emerges as a promising tool for refractory epilepsy in pediatric patients, showing efficacy in reducing seizure frequency and improving overall quality of life. Despite mild and reversible adverse effects, CBD's benefits outweigh the risks. However, more research on long-term effects is needed to fully understand its implications.

Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort.

PURPOSE: This study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). METHODS: This prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. RESULTS: CEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. CONCLUSION: This is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

Decimocuarta lección Jesús Culebras. Dieta cetogénica, un tratamiento a medio descubrir / Fourteenth Jesús Culebras Lecture. Ketogenic diet, a half-discovered treatment

La dieta cetogénica constituyó desde su inicio un planteamiento sorprendente para el tratamiento de la epilepsia. Someter al organismo a un cambio en la obtención de energía, pasando de depender de los carbohidratos a hacerlo de las grasas, pone en marcha toda una serie de rutas bioquímicas que, de forma independiente pero también complementaria, dan lugar a un conjunto de efectos que benefician al paciente. Esta búsqueda de su mecanismo de acción, de idear cómo mejorar el cumplimiento y de aprovecharla para otras enfermedades ha marcado su trayectoria. En este artículo se revisan someramente estos aspectos, haciendo hincapié en la importancia de seguir realizando investigación básica y clínica para que este tratamiento pueda aplicarse con bases científicas sólidas.(AU)

The ketogenic diet was an amazing approach to treating epilepsy from its beginning. The body undergoes a change in obtaining energy, going from depending on carbohydrates to depending on fats, and then a whole series of biochemical routes are launched that, independently but also complementary, give rise to a set of effects that benefit the patient. This search for its mechanism of action, of devising how to improve compliance and take advantage of it for other diseases has marked its trajectory. This article briefl y reviews these aspects, emphasizing the importance of continuing to carry out basic and clinical research so that this treatment can be applied with solid scientific bases.(AU)

The impact of social determinants of health on utilization of pediatric epilepsy surgery: a systematic review.

OBJECTIVE: A minority of pediatric patients who may benefit from epilepsy surgery receive it. The reasons for this utilization gap are complex and not completely understood. Patient and caregiver social determinants of health (SDOH) may impact which patients undergo surgery and when. The authors conducted a systematic review examining SDOH and surgical intervention in children with drug-resistant epilepsy (DRE). They aimed to understand which factors influenced time to surgical program referral or receipt of epilepsy surgery among children with DRE, as well as identify areas to characterize the SDOH impacting epilepsy surgery in children and guide efforts aimed to promote health equity in epilepsy. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases in January 2022. Studies were analyzed by title and abstract, then full text, to identify all studies examining the impact of SDOH on utilization of epilepsy surgery. Studies meeting inclusion criteria were analyzed for SDOH examined, outcomes, and key findings. Quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Of 4545 resultant articles, 18 were included. Studies examined social, cultural, and environmental factors that contributed to SDOH impacting epilepsy surgery. Patients who underwent surgical evaluation were found to be most commonly White and privately insured and have college-educated caregivers. Five studies found differences in time to referral/surgery or rates of surgery by racial group, with most finding an increased time to referral/surgery or lower rates of surgery for those who were Hispanic and/or non-White. Four studies found that private insurance was associated with higher surgical utilization. Three studies found higher household income was related to surgical utilization. No studies examined biological, psychological, or behavioral factors that contributed to SDOH impacting epilepsy surgery. CONCLUSIONS: The authors conducted a systematic review exploring the impact of SDOH in DRE surgery utilization. They found that race, ethnicity, insurance type, caregiver educational attainment, and household income demonstrate relationships with pediatric epilepsy surgery. Further study is necessary to understand how these factors, and others not identified in this study, contribute to the low rates of utilization of epilepsy surgery and potential target areas for interventions aiming to increase equity in access to epilepsy surgery in children.

Telemedicine for Ketogenic Dietary Treatment in Refractory Epilepsy and Inherited Metabolic Disease: State of Play and Future Perspectives.

Ketogenic dietary therapies (KDT) are diets that induce a metabolic condition comparable to fasting. All types of KDT comprise a reduction in carbohydrates whilst dietary fat is increased up to 90% of daily energy expenditure. The amount of protein is normal or slightly increased. KDT are effective, well studied and established as non-pharmacological treatments for pediatric patients with refractory epilepsy and specific inherited metabolic diseases such as Glucose Transporter Type 1 Deficiency Syndrome. Patients and caregivers have to contribute actively to their day-to-day care especially in terms of (self-) calculation and (self-) provision of dietary treatment as well as (self-) measurement of blood glucose and ketones for therapy monitoring. In addition, patients often have to deal with ever-changing drug treatment plans and need to document occurring seizures on a regular basis. With this review, we aim to identify existing tools and features of telemedicine used in the KDT context and further aim to derive implications for further research and development.

Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

Design and validation of a diagnostic suspicion checklist to differentiate epileptic from psychogenic nonepileptic seizures (PNES-DSC).

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. METHODS: A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. RESULTS: The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. CONCLUSION: The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.

Evaluation of Commercially Available Seizure Detection Wearables in Canada: Current Evidence.

Wearable-based seizure detection devices hold promise in reducing seizure-related adverse events and relieving the daily stress experienced by people with epilepsy. In this work, we present the latest evidence regarding the performance of three seizure detection wearables (eight studies) commercially available in Canada to provide guidance to clinicians. Overall, their ability to detect focal-to-bilateral and/or generalized tonic-clonic seizures ranges between 21.0% and 98.15% in sensitivity, with the 24h false alarm rates ranging from 0 to 1.28. While performance in epilepsy monitoring units show promise, the lack of evidence in outpatient settings precludes strong recommendations for their use in daily life.

Assessing short-term and long-term security and efficacy of anterior nucleus of the thalamus deep brain stimulation for treating drug-resistant epilepsy: A systematic review and single-arm meta-analysis.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.

Leukodystrophy with Macrocephaly, Refractory Epilepsy, and Severe Hyponatremia-The Neonatal Type of Alexander Disease.

INTRODUCTION: Alexander disease (AxD) is a rare neurodegenerative condition that represents the group of leukodystrophies. The disease is caused by GFAP mutation. Symptoms usually occur in the infantile age with macrocephaly, developmental deterioration, progressive quadriparesis, and seizures as the most characteristic features. In this case report, we provide a detailed clinical description of the neonatal type of AxD. METHOD: Next-Generation Sequencing (NGS), including a panel of 49 genes related to Early Infantile Epileptic Encephalopathy (EIEE), was carried out, and then Whole Exome Sequencing (WES) was performed on the proband's DNA extracted from blood. CASE DESCRIPTION: In the first weeks of life, the child presented with signs of increased intracranial pressure, which led to ventriculoperitoneal shunt implementation. Recurrent focal-onset motor seizures with secondary generalization occurred despite phenobarbital treatment. Therapy was modified with multiple anti-seizure medications. In MRI contrast-enhanced lesions in basal ganglia, midbrain and cortico-spinal tracts were observed. During the diagnostic process, GLUT-1 deficiency, lysosomal storage disorders, organic acidurias, and fatty acid oxidation defects were excluded. The NGS panel of EIEE revealed no abnormalities. In WES analysis, GFAP missense heterozygous variant NM_002055.5: c.1187C>T, p.(Thr396Ile) was detected, confirming the diagnosis of AxD. CONCLUSION: AxD should be considered in the differential diagnosis in all neonates with progressive, intractable seizures accompanied by macrocephaly.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

OBJECTIVE: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). METHODS: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. RESULTS: Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. SIGNIFICANCE: This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. PLAIN LANGUAGE SUMMARY: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization.

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

Complete Heart Block and Ventricular Asystole Caused by Vagus Nerve Stimulation Therapy.

Left vagus nerve stimulation (VNS) is an advanced therapeutic option for refractory, drug-resistant epilepsy. A 45-year-old woman with a history of refractory catamenial focal epilepsy since age 16, treated with a five-drug antiepileptic regimen and VNS (implanted eight and one-half years prior), presented with dyspnea, chest discomfort, and lightheadedness. During observation, symptoms recurred and were associated with bradycardia (<20 bpm) and a complete atrioventricular node (AVN) block. Following admission, she continued to experience recurrent symptomatic AVN block and transient ventricular asystole, temporally correlated with her baseline seizure activity and resultant activation of her VNS. Deactivation of VNS resolved her bradyarrhythmia, and she experienced no recurrence over 14 months of follow-up. This case highlights a therapeutic dilemma in cases of refractory epilepsy, with limited therapeutic options if seizure activity requires VNS to be controlled.

Drug resistant epilepsy and ketogenic diet: A narrative review of mechanisms of action.

Drug-resistant epilepsy (DRE) poses a significant global challenge, impacting the well-being of patients. Anti-epileptic drugs often fail to effectively control seizures in individuals with DRE. This condition not only leads to persistent seizures but also induces neurochemical imbalances, elevating the risk of sudden unexpected death in epilepsy and comorbidities. Moreover, patients experience mood and personality alterations, educational and vocational setbacks, social isolation, and cognitive impairments. Ketogenic diet has emerged as a valuable therapeutic approach for DRE, having been utilized since 1920. Various types of ketogenic diets have demonstrated efficacy in controlling seizures. By having a multimodal mechanism of action, the ketogenic diet reduces neuronal excitability and the frequency of seizure episodes. In our narrative review, we have initially provided a concise overview of the factors contributing to drug resistance in epilepsy. Subsequently, we have discussed the different available ketogenic diets. We have reviewed the underlying mechanisms through which the ketogenic diet operates. These mechanisms encompass decreased neuronal excitability, enhanced mitochondrial function, alterations in sleep patterns, and modulation of the gut microbiome. Understanding the complex mechanisms by which this diet acts is essential as it is a rigorous diet and requires good compliance. Hence knowledge of the mechanisms may help to advance research on achieving similar therapeutic effects through other less stringent approaches.

Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients.

The aim of this study was to determine the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) in patients with refractory epilepsy. Serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were determined using the spectrophotometer method. Refractory epilepsy patients' serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were statistically significant compared to the healthy control group (p < 0.05). In conclusion, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels may play an important role in the etiopathogenesis of refractory epilepsy. This study was the first to investigate some parameters in refractory epilepsy disease.

Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach.

OBJECTIVES: Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. METHODS: High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. RESULTS: The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. CONCLUSION: This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. CRITICAL RELEVANCE STATEMENT: Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. KEY POINTS: • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions.