Neural dynamics and seizure correlations: Insights from neural mass models in a Tetanus Toxin rat model of epilepsy.

This study focuses on the use of a neural mass model to investigate potential relationships between functional connectivity and seizure frequency in epilepsy. We fitted a three-layer neural mass model of a cortical column to intracranial EEG (iEEG) data from a Tetanus Toxin rat model of epilepsy, which also included responses to periodic electrical stimulation. Our results show that some of the connectivity weights between different neural populations correlate significantly with the number of seizures each day, offering valuable insights into the dynamics of neural circuits during epileptogenesis. We also simulated single-pulse electrical stimulation of the neuronal populations to observe their responses after the connectivity weights were optimized to fit background (non-seizure) EEG data. The recovery time, defined as the time from stimulation until the membrane potential returns to baseline, was measured as a representation of the critical slowing down phenomenon observed in nonlinear systems operating near a bifurcation boundary. The results revealed that recovery times in the responses of the computational model fitted to the EEG data were longer during 5 min periods preceding seizures compared to 1 hr before seizures in four out of six rats. Analysis of the iEEG recorded in response to electrical stimulation revealed results similar to the computational model in four out of six rats. This study supports the potential use of this computational model as a model-based biomarker for seizure prediction when direct electrical stimulation to the brain is not feasible.

Seizure recurrence following the first unprovoked seizure: Risk factors among children in UAE.

In a retrospective study of paediatric and adolescent patients in Abu Dhabi, UAE, who experienced their first unprovoked seizure between March 2016 and March 2020, with a minimum one-year follow-up, we identified significant risk factors associated with seizure recurrence. Among 317 patients, 96.2% experienced seizure recurrence, with the majority (68.8%) occurring within the first 6-month follow-up period. Notable risk factors for recurrence included focal seizures, symptomatic seizure causes, abnormal initial electroencephalogram (EEG) findings, abnormal brain magnetic resonance imaging results, and the presence of neurological disorders. Interestingly, the type of epileptiform activity in the initial EEG did not predict recurrence risk. Over a 3-year period, the overall recurrence risk was 98.4%, particularly higher in cases with symptomatic seizures compared to idiopathic (genetic) ones. These findings underscore the importance of vigilant monitoring, particularly in the early post-seizure follow-up period, and advocate for initial EEG assessments, especially in cases of remote symptomatic first unprovoked seizures.

Seizure forecasting with ultra long-term EEG signals.

OBJECTIVE: The apparent randomness of seizure occurrence affects greatly the quality of life of persons with epilepsy. Since seizures are often phase-locked to multidien cycles of interictal epileptiform activity, a recent forecasting scheme, exploiting RNS data, is capable of forecasting seizures days in advance. METHODS: We tested the use of a bandpass filter to capture the universal mid-term dynamics enabling both patient-specific and cross-patient forecasting. In a retrospective study, we explored the feasibility of the scheme on three long-term recordings obtained by the NeuroPace RNS System, the NeuroVista intracranial, and the UNEEG subcutaneous devices, respectively. RESULTS: Better-than-chance forecasting was observed in 15 (83 %) of 18 patients, and in 16 (89 %) patients for daily and hourly forecast, respectively. Meaningful forecast up to 30 days could be achieved in 4 (22 %) patients for hourly forecast frequency. The cross-patient performance decreased only marginally and was patient-wise strongly correlated with the patient-specific one. Comparable performance was obtained for NeuroVista and UNEEG data sets. SIGNIFICANCE: The feasibility of cross-patient forecasting supports the universal importance of mid-term dynamics for seizure forecasting, demonstrates promising inter-subject-applicability of the scheme on ultra long-term EEG recordings, and highlights its huge potential for clinical use.

Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy.

Epilepsy and Alzheimer's disease share some common pathologies such as neurodegeneration, seizures and impaired cognition. However, the molecular mechanisms of these changes are still largely unknown. Fyn, a Src-family non-receptor tyrosine kinase (SFK), and its interaction with tau in mediating brain pathology in epilepsy and Alzheimer's disease can be a potential therapeutic target for disease modification. Although Fyn and tau pathology occurs in both Alzheimer's disease and epilepsy, the dynamics of Fyn-tau and PSD95-NR2B interactions affected by seizures and their impact on brain pathology in epilepsy have not been investigated. In this study, we demonstrate a significant increase of Fyn-tau interactions following seizure induction by kainate in both acute and chronic rodent models and in human epilepsy. In the early phase of epileptogenesis, we show increased Fyn/tau/NR2B/PSD95/neuronal nitric oxide synthase complexes after status epilepticus and a postsynaptic increase of phosphorylated tau (pY18 and AT8), Fyn (pSFK-Y416), NMDAR (pNR2B-Y1472) and neuronal nitric oxide synthase. Hippocampal proximity ligation assay and co-immunoprecipitation revealed a sustained increase of Fyn-tau and NR2B-PSD95 complexes/binding in rat chronic epilepsy at 3 months post-status epilepticus. Enhanced Fyn-tau complexes strongly correlated with the frequency of spontaneously recurring convulsive seizures and epileptiform spikes in the chronic epilepsy model. In human epileptic brains, we also identified increased Fyn-tau and NR2B-PSD95 complexes, tau phosphorylation (pY18 and AT8) and Fyn activation (pSFK-Y416), implying the translational and therapeutic potential of these molecular interactions. In tau knockout mice and in rats treated with a Fyn/SFK inhibitor saracatinib, we found a significant reduction of phosphorylated Fyn, tau (AT8 in saracatinib-treated), NR2B and neuronal nitric oxide synthase and their interactions (Fyn-tau and NR2B-PSD95 in saracatinib-treated group; NR2B-PSD95 in tau knockout group). The reduction of Fyn-tau and NR2B-PSD95 interactions in the saracatinib-treated group, in contrast to the vehicle-treated group, correlated with the modification in seizure progression in the rat chronic epilepsy model. These findings from animal models and human epilepsy provide evidence for the role of Fyn-tau and NR2B-PSD95 interactions in seizure-induced brain pathology and suggest that blocking such interactions could modify the progression of epilepsy.

Sudden death in epilepsy: the overlap between cardiac and neurological factors.

People with epilepsy are at risk of premature death, of which sudden unexpected death in epilepsy (SUDEP), sudden cardiac death (SCD) and sudden arrhythmic death syndrome (SADS) are the primary, partly overlapping, clinical scenarios. We discuss the epidemiologies, risk factors and pathophysiological mechanisms for these sudden death events. We reviewed the existing evidence on sudden death in epilepsy. Classification of sudden death depends on the presence of autopsy and expertise of the clinician determining aetiology. The definitions of SUDEP, SCD and SADS lead to substantial openings for overlap. Seizure-induced arrhythmias constitute a minority of SUDEP cases. Comorbid cardiovascular conditions are the primary determinants of increased SCD risk in chronic epilepsy. Genetic mutations overlap between the states, yet whether these are causative, associated or incidentally present is often unclear. Risk stratification for sudden death in people with epilepsy requires a multidisciplinary approach, including a review of clinical history, toxicological analysis and complete autopsy with histologic and, preferably, genetic examination. We recommend pursuing genetic testing of relatives of people with epilepsy who died suddenly, mainly if a post-mortem genetic test contained a Class IV/V (pathogenic/likely pathogenic) gene variant. Further research may allow more precise differentiation of SUDEP, SCD and SADS and the development of algorithms for risk stratification and preventative strategies.

Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition.

For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na+/K+ pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.

Management of non-lesional super-refractory status epilepticus: a rare case report.

Introduction and importance: Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the initiation of anesthetic therapy(continuum), a serious medical emergency with a potential for significant morbidity and mortality. Cortisectomy with invasive EEG recording electrocorticography (ECoG) can be a successful treatment option for super-refractory status epilepticus in selected cases after medical management has failed. Case presentation: The authors present a case of a young lady who suffered a super-refractory status epilepticus and failed five different anti-seizure medications, coma-producing agents, IVIG. After failure of multiple medical and sedative therapy cortisectomy was done with the use of invasive EEG recording electrocorticography (ECoG) to tailor and localize the epileptogenic zone. Clinical discussion: When dealing with status epilepticus (SE) that is refractory to treatment, early surgical intervention should be taken into consideration as a viable option. Although there are only a few published cases of SE treated with epilepsy surgery, these cases have shown positive outcomes. In fact, one study demonstrated a significant improvement in seizure control for patients with SE who underwent surgical treatment using these techniques. Conclusion: Cortisectomy, which is a rare and invasive procedure, could be considered as a potential treatment for patients who have not responded to multiple medical and sedative therapies.

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes.

Background: Drug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). Objective: This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. Materials and methods: This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. Results: We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. Conclusion: The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

The role of ketogenic diets in the treatment of status epilepticus.

Status epilepticus is a severe neurological condition, characterized by abnormally, prolonged seizures. Recent studies have explored the use of ketogenic diets (KDs) as a potential therapeutic approach for refractory status epilepticus. This article summarises the recent literature and discussions regarding the practicalities of implementing KDs in the critical care setting. This overview was presented at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in April 2024.

Epidemiology and real-world management of childhood epilepsy in Japan: A descriptive study using a health claim database.

INTRODUCTION: The purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning. MATERIALS AND METHODS: The study encompassed insured individuals aged 0-17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January-December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated. RESULTS: Among 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80-2.15) in the 0-2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98-9.72) in the 15-17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %-91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age. CONCLUSIONS: Our findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy.

Risk of recurrence after a first unprovoked seizure with different risk factors: A 10-year prospective cohort study.

OBJECTIVE: To evaluate the recurrence risk following a first unprovoked seizure using both single-factor and multiple-factor approaches, as well as to further analyze the potential risk factors associated with recurrence. METHODS: In a prospective cohort study, a total of 201 individuals who experienced their initial unprovoked seizure were recruited from January 2010 to December 2019. The cumulative recurrence rates were calculated by Kaplan-Meier survival curves. Multivariate analyses for recurrence risk were conducted utilizing the Cox regression model. Additionally, interaction effects were evaluated by quantifying the attributable proportion due to interaction (AP). RESULTS: The cumulative recurrence rates were as follows: 29.4 % at 6 months, 35.8 % at 1 year, 41.1 % at 2 years, 47.9 % at 5 years, and 57.5 % at 10 years. Notably, the majority of recurrences, specifically 61.2 %, manifested within the initial 6 months following the onset, with 74.4 % occurring within the first year, and 82.6 % within the initial 2 years. The recurrence risk of patients with epileptic abnormal discharges on VEEG, nocturnal seizure, abnormal MRI, prior brain insult and focal seizure was 71.9 %, 61.4 %, 61.5 %, 75.0 %, and 69.7 %, respectively. Epileptiform discharges (RR 2.5, 95 % CI 1.4-4.3, P=0.001) and prior brain insult (RR 2.1, 95 % CI 1.2-3.7, P=0.007) were predictors of recurrence. Interaction analysis showed the combination of epileptiform discharges and prior brain insult was associated with a 7-fold increased risk of recurrence (RR 7.0, 95 %CI 3.5-14.2)，with AP estimated at 0.34, the combination of epileptiform discharges and nocturnal seizure was associated with a 4-fold increased risk of recurrence(RR 4.3, 95 %CI 2.4-7.4), with AP estimated at -0.25,and the combination of prior brain insult and nocturnal seizures was associated with a 4-fold increased risk of recurrence(RR 4.1, 95 %CI 1.9-8.9), with AP estimated at -0.03. CONCLUSIONS: Patients with epileptiform discharges VEEG, nocturnal seizures, abnormal MRI findings, prior brain insult, or focal seizures exhibited a substantial recurrence rate. Specifically, the presence of epileptiform discharges in VEEG recordings, and a history of prior brain insult were identified as independent risk factors associated with recurrence following an initial unprovoked seizure. Notably, individuals with multiple risk factors exhibited a significantly higher recurrence risk compared to those with no or a single risk factor.

Individual and relational factors related to disclosure of epilepsy in the workplace.

BACKGROUND: The decision to disclose epilepsy in the workplace is complex, as it entails both advantages and disadvantages. In this study, we aimed to identify the factors associated with disclosure of epilepsy in the workplace based on the disclosure decision-making model for patients who required underwent comprehensive assessment in the Epilepsy Monitoring Unit (EMU). METHODS: This retrospective study included 193 patients with epilepsy (112 men, aged 18-66 years) who underwent comprehensive assessment, including long-term video-EEG monitoring, neuroimaging studies, and neuropsychological and psychosocial assessment in the Tohoku University Hospital EMU. Data were obtained from the medical records and self-reported questionnaires at our EMU. The outcome variable was disclosure of epilepsy. Predictive variables were selected based on the disclosure decision-making model: individual factors (i.e., age, sex, age at onset of epilepsy, seizure frequency, generalized tonic-clonic seizures or focal to bilateral tonic-clonic seizures in the last 2 years, experiences of viewing own seizure, and felt stigma), and relational factors (i.e., experiences of discrimination, enacted stigma, and social support). Data were analyzed using a logistic regression analysis model. RESULTS: Our results indicated that 43.5% of patients disclosed epilepsy to their employer. The factors that associated with disclosure of epilepsy were experiences of discrimination (odds ratio [OR], 7.78; 95% confidence interval [CI], 2.84-21.34, p < 0.01), experiences of viewing own seizure (OR, 3.51; 95% CI, 1.27-9.72, p < 0.05), and level of enacted stigma (OR, 0.69; 95% CI, 0.48-0.99, p < 0.05). CONCLUSION: This study indicated that the decision to disclose epilepsy was associated with both individual factors, such as experience of viewing own seizures, and relational factors, such as experience of discrimination and enacted stigma.

Machine learning models for predicting treatment response in infantile epilepsies.

Epilepsy stands as one of the prevalent and significant neurological disorders, representing a critical healthcare challenge. Recently, machine learning techniques have emerged as versatile tools across various healthcare domains, encompassing diagnostics, treatment assessment, and prognosis. We compared 11 machine learning model to find the best ML model to predict drug treatment outcomes for our cohort, which we previously evaluated using classical statistical methods. METHODS: In our study, we evaluated patients who presented to the pediatric neurology department of our university hospital with seizures at the age of 1 to 24 months and were diagnosed with epilepsy. We utilized 11 different machine learning techniques namely Decision Tree, Bagging, K-Nearest Neighbour, Linear Discriminant Analysis, Logistic Regression, Neural Networks, Deep Neural Networks, Support Vector Machine. Besides, we compared these techniques using various performance metrics to identify anti-seizure medicine response. We also utilized the chi-square feature selection methods to enhance performance in machine learning algorithms. RESULTS: Two hundred and twenty-nine patients (110 male and 119 female) who were diagnosed between the ages of 1-24 months were included in the study. Support Vector Machine algorithm was found to be effective in drug resistant epilepsy detection, with the highest aure under curve value (0.9934) and achieving a test accuracy of 97.06 %. CONCLUSION: This study can shed light on future studies by showing that the Support Vector Machine algorithm can effectively determine the drug resistant epilepsy. The pediatric neurologist and experts should be referred to non-medical treatment (epilepsy surgery, ketogenic diet) at the early stages and multidisciplinary approach should be provided.

Prediction begins with diagnosis: Estimating seizure recurrence risk in the First Seizure Clinic.

OBJECTIVES: To assess the feasibility of using a seizure recurrence prediction tool in a First Seizure Clinic, considering (1) the accuracy of initial clinical diagnoses and (2) performance of automated computational models in predicting seizure recurrence after first unprovoked seizure (FUS). METHODS: To assess diagnostic accuracy, we analysed all sustained and revised diagnoses in patients seen at a First Seizure Clinic over 5 years with 6+ months follow-up ('accuracy cohort', n = 487). To estimate prediction of 12-month seizure recurrence after FUS, we used a logistic regression of clinical factors on a multicentre FUS cohort ('prediction cohort', n = 181), and compared performance to a recently published seizure recurrence model. RESULTS: Initial diagnosis was sustained over 6+ months follow-up in 69% of patients in the 'accuracy cohort'. Misdiagnosis occurred in 5%, and determination of unclassified diagnosis in 9%. Progression to epilepsy occurred in 17%, either following FUS or initial acute symptomatic seizure. Within the 'prediction cohort' with FUS, 12-month seizure recurrence rate was 41% (95% CI [33.8%, 48.5%]). Nocturnal seizure, focal seizure semiology and developmental disability were predictive factors. Our model yielded an Area under the Receiver Operating Characteristic curve (AUC) of 0.60 (95% CI [0.59, 0.64]). CONCLUSIONS: High clinical accuracy can be achieved at the initial visit to a First Seizure Clinic. This shows that diagnosis will not limit the application of seizure recurrence prediction tools in this context. However, based on the modest performance of currently available seizure recurrence prediction tools using clinical factors, we conclude that data beyond clinical factors alone will be needed to improve predictive performance.

The value of electroencephalography features in the prognostic evaluation of large hemispheric infarction patients at different time intervals.

BACKGROUND: Large Hemispheric Infarction (LHI) is a devastating disease with high mortality. This study aimed to use electroencephalography (EEG) to evaluate the death risk of LHI patients and identify suitable evaluation time. METHODS: This study retrospectively collected clinical and EEG data from 73 LHI patients, dividing them into death and survival group at discharge. EEG data was classified as 1-5 days and 6-14 days after onset according to the time intervals of cerebral edema. Regression and receiver operator characteristic curve (ROC) analysis were applied to explore the impact of temporal changes in various EEG and clinical features on death. RESULTS: The areas under ROC curve (AUC) of death prediction for non-α frequency on non-infarct side at 6-14 days after onset was significantly higher than that at 1-5 days (p = 0.004). And there was no significant difference between the AUC of seizure activity for death prediction at 1-5 days and 6-14 days (p = 0.418). Multivariate regression analysis revealed that non-α frequency on non-infarct side and seizure activity at 6-14 days after onset were the independent risk factors for the death of LHI patients. Additionally, above two EEG features significantly improved the death predictive efficacy of clinical features in LHI patients with the integrated discrimination improvement index (IDI) of 0.174 (p = 0.015) and the net reclassification improvement (NRI) of 1.314 (p<0.001). CONCLUSIONS: Non-α frequency on non-infarct side and seizure activity were reliable indicators for death prediction. 6-14 days after onset was the better time window for death evaluation of LHI patients through EEG.

TBC1D15-regulated mitochondria-lysosome membrane contact exerts neuroprotective effects by alleviating mitochondrial calcium overload in seizure.

Mitochondrial calcium overload plays an important role in the neurological insults in seizure. The Rab7 GTPase-activating protein, Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15), is involved in the regulation of mitochondrial calcium dynamics by mediating mitochondria-lysosome membrane contact. However, whether TBC1D15-regulated mitochondria-lysosome membrane contact and mitochondrial calcium participate in neuronal injury in seizure is unclear. We aimed to investigate the effect of TBC1D15-regulated mitochondria-lysosome membrane contact on epileptiform discharge-induced neuronal damage and further explore the underlying mechanism. Lentiviral vectors (Lv) infection and stereotaxic adeno-associated virus (AAV) injection were used to regulate TBC1D15 expression before establishing in vitro epileptiform discharge and in vivo status epilepticus (SE) models. TBC1D15's effect on inter-organellar interactions, mitochondrial calcium levels and neuronal injury in seizure was evaluated. The results showed that abnormalities in mitochondria-lysosome membrane contact, mitochondrial calcium overload, mitochondrial dysfunction, increased levels of reactive oxygen species, and prominent neuronal damage were partly relieved by TBC1D15 overexpression, whereas TBC1D15 knockdown markedly deteriorated these phenomena. Further examination revealed that epileptiform discharge-induced mitochondrial calcium overload in primary hippocampal neurons was closely associated with abnormal mitochondria-lysosome membrane contact. This study highlights the crucial role played by TBC1D15-regulated mitochondria-lysosome membrane contact in epileptiform discharge-induced neuronal injury by alleviating mitochondrial calcium overload.

Clinical characteristics and serum 25-hydroxyvitamin D levels in children with febrile seizures in China.

The aim of this study was to evaluate the serum level of 25-hydroxyvitamin D (25(OH)D) in children with febrile seizures (FS) in Luzhou, Sichuan Province, China, and in particular its association with gender and age. This should inform possible strategies for supplementation with vitamin D, and hence for prevention of FS in the local pediatric population. The Febrile seizures group consisted of 747 children hospitalized with FS at the Southwest Medical University Affiliated Hospital from January 2020 to January 2024. The healthy control group was comprised of 750 children aged from 0 to 8 years who underwent health checkups during this period. The serum 25(OH)D level was analyzed in relation to gender and age to explore its association with FS. The median serum vitamin D level in the FS group (28.8 ng/mL; IQR 21.64, 33.64) was significantly lower than in the healthy control group (37.51 ng/mL; IQR 31.05, 37.51). The incidence of vitamin D deficiency in the FS group was 10.8%, which was significantly higher than in the healthy control group (P < 0.05). In addition, the serum vitamin D level in children with FS varied in different age groups, with significantly lower levels observed in older children (P < 0.05). ROC curve analysis revealed that a serum vitamin D level of 35.28 ng/mL showed 60.0% sensitivity and 84.7% specificity for predicting FS (P < 0.05). In this study cohort, the serum vitamin D level in children with FS was at the lower limit of the physiological range, and significantly lower than in healthy children. Furthermore, this level decreased with age in children with FS. Regular supplementation with vitamin D for 6 months after birth and outdoor sun exposure for more than 2 h per day can improve the serum vitamin D level in children with FS.

Generalized spike-waves in idiopathic generalized epilepsies: Does their frequency matter?

OBJECTIVES: We hypothesized that the frequency (in Hertz) of generalized spike-waves (GSWs) in patients with idiopathic generalized epilepsy (IGE) has associations with the syndromic diagnosis as well as with the prognosis of patients (their response to medical treatment). METHODS: This was a retrospective study of a prospectively developed database. All patients with a diagnosis of IGE were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Patients were classified into four IGE syndromes: childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and generalized tonic-clonic seizures alone. RESULTS: Five hundred and eighty-three patients were studied. GSWs were commonly observed in all four syndromes of IGE. Frequency of GSW (in Hertz) did not have a significant association with the syndromic diagnosis of the patients (p = .179). The presence of GSW did not have a significant association with the seizure outcome (becoming seizure free or not) of the patients (p = .416). Frequency of GSW did not have a significant association with the seizure outcome of the patients either (p = .574). CONCLUSION: GSWs are the hallmark electroencephalographic footprints of idiopathic generalized epilepsies; however, neither their presence nor their frequency has practical associations with the syndromic diagnosis of IGEs or their outcome (response to treatment).

Therapeutic potential of ketamine in management of epilepsy: Clinical implications and mechanistic insights.

Epilepsy, a widespread neurological disorder, affects approximately 50 million people worldwide. This disorder is typified by recurring seizures due to abnormal neuron communication in the brain. The seizures can lead to severe ischemia and hypoxia, potentially threatening patients' lives. However, with proper diagnosis and treatment, up to 70 % of patients can live without seizures. The causes of epilepsy are complex and multifactorial, encompassing genetic abnormalities, structural brain anomalies, ion channel dysfunctions, neurotransmitter imbalances, neuroinflammation, and immune system involvement. These factors collectively disrupt the crucial balance between excitation and inhibition within the brain, leading to epileptic seizures. The management of treatment-resistant epilepsy remains a considerable challenge, necessitating innovative therapeutic approaches. Among emerging potential treatments, ketamine-a drug traditionally employed for anesthesia and depression-has demonstrated efficacy in reducing seizures. It is noteworthy that, independent of its anti-epileptic effects, ketamine has been found to improve the balance between excitatory and inhibitory (E/I) activities in the brain. The balance is crucial for maintaining normal neural function, and its disruption is widely considered a key driver of epileptic seizures. By acting on N-methyl-D-aspartate (NMDA) receptors and other potential mechanisms, ketamine may regulate neuronal excitability, reduce excessive synchronized neural activity, and counteract epileptic seizures. This positive impact on E/I balance reinforces the potential of ketamine as a promising drug for treating epilepsy, especially in patients who are insensitive to traditional anti-epileptic drugs. This review aims to consolidate the current understanding of ketamine's therapeutic role in epilepsy. It will focus its impact on neuronal excitability and synaptic plasticity, its neuroprotective qualities, and elucidate the drug's potential mechanisms of action in treating epilepsy. By scrutinizing ketamine's impact and mechanisms in various types of epilepsy, we aspire to contribute to a more comprehensive and holistic approach to epilepsy management.