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Epilepsy is a chronic clinical disorder and does not have a rational treatment, which basically aims to prevent seizure activity. Therefore, developing new treatment strategies that can intervene in epileptogenesis will make important contribution to epilepsy treatment. In order to find new compounds and develop new treatment strategies, here, we explored the potential antiepileptic effects of Allium schoenoprasum L. commonly known as chives. Two different epilepsy models were used to study the potential antiepileptic effects of A. schoenoprasum L. The first epilepsy model was induced by intracortical injection of 500 IU penicillin. The second epilepsy model was induced by injecting pentylenetetrazol (PTZ) at the dose of 60 mg intraperitoneally (i.p.). In the penicillin model, the animals were given A. schoenoprasum L. extract (200 or 400 mg/kg i.p.) after penicillin was applied and electrocortical activity was recorded for 120 min. In the PTZ model, the animals were given A. schoenoprasum L. extract at doses of 200 or 400 mg/kg orally for 7 days, after which the PTZ was applied, and tonic-clonic seizures were video recorded. A. schoenoprasum L. did not significantly change either the spike frequency or amplitude in the penicillin epilepsy model. Although it did not change the seizure score in the PTZ epilepsy model it reduced the death rate and significantly decreased the tonic-clonic seizure duration. The result suggests that A. schoenoprasum L. may have antiepileptic effects when applied chronically. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anticonvulsant mechanisms of bile acid monomer compounds cholic acid (CA) and deoxycholic acid (DCA). Methods: Male SD rats were randomly divided into a control group, a model group, a sodium valproate or valproic acid (VPA), (189 mg/kg), a CA group (60 mg/kg), and a DCA group (60 mg/kg), with nine rats in each group. The rats in the control group and model group were given placebo, and the mice in each treatment group was pre⁃treated 1 h before modeling, and continuously treated for 16 d. A seizure rat model was established using a water bath at (45.0±0.5) ℃, with a bath given every other day for a total of eight times. The seizure onset time, seizure termination time, and the severity of seizure behavior of rats were observed and recorded. Meanwhile, the levels of interleukin 1β (IL⁃1β), interleukin 6 (IL⁃6), and tumor necrosis factor α (TNF⁃α) in rat serum and hippocampal tissues, as well as the contents of glutamate (Glu) and γ-aminobutyric acid (GABA) in hippocampal tissues were detected. Hematoxylin⁃eosin (HE) staining was used to observe the pathological damage of hippocampal neurons. Metabolomic analysis of rat serum was performed using the ultra-high performance liquid chromatography ⁃tandem mass spectrometry (UHPLC ⁃MS/MS). Results: Compared with the model group, all treatment groups significantly prolonged the latency of seizures but significantly reduced the duration of seizures (P < 0.001); both the VPA group and DCA group significantly reduced the severity of seizures (P < 0.001, P < 0.01), while there was no significant difference in the CA group. Compared with the control group, the contents of IL⁃1β TNF⁃α, and IL⁃6 in serum and hippocampal tissues of the model group were significantly increased (P < 0.001), and the contents of Glu and GABA in hippocampus were also significantly increased (P < 0.001). Compared with the model group, the effects produced by the DCA group and the VPA group were similar, both of which reduced the levels of various biochemical indicators (P < 0.001), while the CA group significantly reduced all indicators except the TNF⁃α level in serum and the IL⁃6 level in the hippocampus (P < 0.01). HE staining results of hippocampal tissues showed that compared with the control group, the pyramidal cells in the hippocampus of rats in the model group were contracted, with a smaller volume, a darker staining, an enhanced alkalinity, and the unclear cytoplasmic nuclear boundaries; compared with the model group, the morphology of hippocampal neurons in each treatment group was significantly improved. Among them, the morphology of hippocampal neurons in the DCA group was similar to that in the VPA group. A total of 312 differential compounds were identified in serum metabolomics analysis. Through principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS⁃DA) analysis, nine differential compounds were selected. The results of metabolic pathway enrichment showed that the anticonvulsant effects of CA and DCA were mainly involved the citric acid cycle, amino acid metabolism, and butyric acid metabolism pathways. Conclusion: CA and DCA have certain improvement effects on behavioral and biochemical indicators of rats with febrile seizures, and their mechanisms of action may be correlated with energy metabolism, amino acid metabolism, and short⁃chain fatty acid metabolism during seizures. [ABSTRACT FROM AUTHOR]

The clinical presentations of abusive head trauma can abruptly worsen, so the occurrence of seizures and changes of EEG can be variable according to patients' conditions. Since the changes of EEG background waves reflect the cortical function of children, we aimed to find out whether the timing of EEG background, epileptiform discharges and seizure patterns were associated with the outcomes of patients with AHT. Using seizure type and acute stage electroencephalographic (EEG) characteristics to assess adverse neurological outcomes in children with seizures secondary to abusive head trauma (AHT). Children who were hospitalized with AHT at a tertiary referral hospital from October 2000 to April 2010 were evaluated retrospectively. A total of 50 children below 6 years of age admitted due to AHT were included. KOSCHI outcome scale was used to evaluate the primary outcome and neurological impairment was used as secondary outcome after 6 months discharge. Children with apnea, cardiac arrest, reverse blood flow and skull fracture in clinic had a higher mortality rate even in the no-seizure group (3/5 [60%] vs. 3/45 [6.7%], odds ratio [OR] = 11; 95% CI = 2.3–52; p = 0.025). Seizure occurrence reduced mostly at the second day after admission in seizure groups; but children with persistent seizures for 1 week showed poor neurological outcomes. The occurrence of initial seizure was frequency associated with younger age; focal seizure, diffuse cortical dysfunction in acute-stage EEG, and low Glasgow Coma Scale (GCS) score were significantly related to poor outcomes after 6 months. Diffuse cortical dysfunction was also associated with motor, speech, and cognitive dysfunction. Diffuse cortical dysfunction in acute-stage EEG combined with low GCS score and focal seizure may related to poor outcomes and neurological dysfunctions in children with AHT. • Ages of the children in the repetitive seizures and status epilepticus groups were younger than in the single seizure group in abusive head trauma. • No significant differences in outcome between the seizure groups. • EEG findings of diffuse cortical dysfunction, focal seizures and severe Glasgow Coma Scale were significantly related to poor outcomes. • Acute-stage background EEG of diffuse cortical dysfunction could predict poor outcomes with the development of multiple neurological dysfunctions. [ABSTRACT FROM AUTHOR]

• Epileptic seizures have been described in some operas. • Generalized seizures are described as descending chromatic scales. • Seizures often occur in a dramatic turning point of the opera. Epilepsy or epileptic seizures have only rarely been described in the classical opera. Four operas were detected, in which epileptic seizures are described also by musical means. Three of them ("Der Golem" by Eugen d'Albert; "Idiot" by Mieczyslaw Weinberg; "Otello" by Giuseppe Verdi) describe a generalized tonic-clonic epileptic seizure by a descending chromatic scale. One opera ("The turn of the screw" by Benjamin Britten) describes temporal lobe seizures by overtone music played by the instrument celesta. [ABSTRACT FROM AUTHOR]

• Aim: Find feasible alternative for adults with epilepsy presenting to ambulances. • Workshops with n = 27 stakeholders (paramedics, specialists, commissioners, users). • Discrete choice evidence on users' preferences considered; judged mostly feasible. • Optimal alternative care configuration specified by workshop participants. • Workshop specified configuration should now be implemented and evaluated. Adults presenting to the ambulance service for diagnosed epilepsy are often transported to emergency departments (EDs) despite no clinical need. An alternative care pathway (CP) could allow paramedics to divert them from ED and instigate ambulatory care improvements. To identify the most promising CP configuration for subsequent testing, the COLLABORATE project surveyed people with epilepsy and family/friends who had recently used the English ambulance service to elicit preferences for 288 CP configurations for different seizures. This allowed CPs to be ranked according to alignment with service users' preferences. However, as well as being acceptable to users, a CP must be feasible. We thus engaged with paramedics, epilepsy specialists and commissioners to identify the optimal configuration. Three Knowledge Exchange workshops completed. Participants considered COLLABORATE's evidence on service users' preferences for the different configurations. Nominal group techniques elicited views on the feasibility of users' preferences according to APEASE criteria. Workshop groups specified the configuration/s considered optimum. Qualitative data was analysed thematically. Utility to users of the specified CP configurations estimated using the COLLABORATE preference survey data. Twenty-seven participants found service users' preferences broadly feasible and outlined delivery recommendations. They identified enough commonality in preferences for different seizures to propose a single CP. Its configuration comprised: 1) patients staying where they were; 2) paramedics having access to medical records; 3) care episodes lasting <6 h; 4) paramedics receiving specialist advice on the day; 5) patient's GP being notified; and 6) a follow-up appointment being arranged with an epilepsy specialist. Preference data indicated higher utility for this configuration compared to current care. Stakeholders are of the view that the CP configuration favoured by service users could be NHS feasible. It should be developed and evaluated. [ABSTRACT FROM AUTHOR]

• Alternatives for adults with epilepsy presenting to ambulances – user preferences. • Discrete choice experiments with n = 427 people with epilepsy and n = 167 friends/family. • Experiments captured their care preferences for 3 different seizure scenarios. • Users' preferences are similar for the scenarios but diverge from current practice. • People with epilepsy prefer to avoid conveyance to an emergency department. To identify service users' preferences for an alternative care pathway for adults with epilepsy presenting to the ambulance service. Extensive formative work (qualitative, survey and knowledge exchange) informed the design of a stated preference discrete choice experiment (DCE). This hypothetical survey was hosted online and consisted of 12 binary choices of alternative care pathways described in terms of: the paramedic's access to medical records/ 'care plan', what happens next (described in terms of conveyance), time, availability of epilepsy specialists today, general practitioner (GP) notification and future contact with epilepsy specialists. DCE scenarios were described as: (i) typical seizure at home. (ii) typical seizure in public, (iii) atypical seizure. Respondents were recruited by a regional English ambulance service and by national public adverts. Participants were randomised to complete 2 of the 3 DCEs. People with epilepsy (PWE; n = 427) and friends/family (n = 167) who completed the survey were representative of the target population. PWE preferred paramedics to have access to medical records, non-conveyance, to avoid lengthy episodes of care, availability of epilepsy specialists today, GP notification, and contact with epilepsy specialists within 2–3 weeks. Significant others (close family members or friends) preferred PWE experiencing an atypical seizure to be conveyed to an Urgent Treatment Centre and preferred shorter times. Optimal configuration of services from service users' perspective far out ranked current practice (rank 230/288 possible configurations). Preferences differ to current practice but have minimal variation by seizure type or stakeholder. Further work on feasibility of these pathways in England, and potentially beyond, is required. [Display omitted] [ABSTRACT FROM AUTHOR]

• Despite emerging evidence, oral benzodiazepines with unsuitable pharmacokinetics for treatment of prolonged seizures remain widely used. • A substantial proportion of patients (28.0 %, n = 35) reports inappropriate use, administering medication after every seizure. • Almost half (46.0 %) of patients with continuing seizures have no access to rescue medication, this might indicate a lack of adequate therapy of seizure emergencies. • On average, rescue medication prescription occurred 7.1 years after epilepsy diagnosis. Seizure clusters, prolonged seizures, and status epilepticus are life-threatening neurological emergencies leading to irreversible neuronal damage. Benzodiazepines are current evidence-based rescue therapy options; however, recent investigations indicated the prescription of mainly unsuitable benzodiazepines and inappropriate use of rescue medication. To examine current use, satisfaction, and adverse events concerning rescue medication in patients with epilepsy in Germany. The study was conducted at epilepsy centres in Frankfurt am Main, Greifswald, Marburg, and Münster between 10/2020 and 12/2020. Patients with an epilepsy diagnosis were assessed based on a questionnaire examining a 12-month period. In total, 486 patients (mean age: 40.5, range 18–83, 58.2 % female) participated in this study, of which 125 (25.7 %) reported the use of rescue medication. The most frequently prescribed rescue medications were lorazepam tablets (56.8 %, n = 71 out of 125), buccal midazolam (19.2 %, n = 24), and rectal diazepam (10.4 %, n = 13). Seizures continuing for over several minutes (43.2 %, n = 54), seizure clusters (28.0 %, n = 35), and epileptic auras (28.0 %, n = 35) were named as indications, while 28.0 % (n = 35) stated they administered the rescue medication for every seizure. Of those continuing to have seizures, 46.0 % did not receive rescue medication. On average, rescue medication prescription occurred 7.1 years (SD 12.7, range 0–66) after an epilepsy diagnosis. Unsuitable oral benzodiazepines remain widely prescribed for epilepsy patients as rescue medication. Patients also reported inappropriate use of medication. A substantial proportion of patients who were not seizure-free did not receive rescue medication prescriptions. Offering each patient at risk for prolonged seizures or clusters of seizures an individual rescue treatment with instructions on using it may decrease mortality and morbidity and increase quality of life.. [ABSTRACT FROM AUTHOR]

Background: Infant, junior, and adult patients with neuronal intranuclear inclusion disease (NIID) present with various types of seizures. We aimed to conduct a systematic literature review on the clinical characteristics of NIID with seizures to provide novel insight for early diagnosis and treatment and to improve prognosis of these patients. Methods: We used KEYWORDS: to screen articles related to NIID and seizures, and data concerning the clinical characteristics of patients, including demographic features, disease characteristics of the seizures, treatment responses, imaging examinations, and other auxiliary examination results were extracted. Results: The included studies comprised 21 patients with NIID with seizures. The most common clinical phenotypes were cognitive impairment (76.20%) and impaired consciousness (57.14%), and generalized onset motor seizures (46.15%) represented the most common type. Compared with infantile and juvenile cases, the use of antiepileptic drugs in adults led to significant seizure control and symptom improvement, in addition to providing a better prognosis. The number of GGC sequence repeats in the NOTCH2NLC gene in six NIID patients with seizures who underwent genetic testing ranged 72-134. Conclusion: The most common clinical phenotypes in patients with NIID with seizures were cognitive impairment and consciousness disorders. Patients with NIID presented with various types of seizures, with the most common being generalized onset motor seizures. Adult patients had a better prognosis and were relatively stable. The early diagnosis of NIID with seizures is of great significance for treatment and to improve prognosis. [ABSTRACT FROM AUTHOR]

Abstract:Introduction: Epilepsy, affecting 1% of the global population, is a neuropsychiatric disease often co-occurring with psychiatric disorders. It is characterized by recurrent "epileptic seizures" caused by abnormal electrical activity in the brain, which poses risks during exercise and damages athletic identity. In Japan, psychiatrists perform essential roles in the treatment of patients with epilepsy. Methods: This review examines and addresses the challenges and opportunities for individuals with epilepsy in athletic endeavors. Results: Historically, misconceptions regarding seizure triggers, societal stigma, and overprotective attitudes have limited physical activity among individuals with epilepsy, resulting in obesity and reduced wellbeing. However, exercise does not typically induce seizures. Recent research suggests that exercise benefits seizure control, quality of life, and comorbidities among individuals with epilepsy. Sports participation risks were categorized into three groups using tailored guidelines provided by the International League Against Epilepsy (ILAE). Water-based sports require controlled environments, monitoring, and distinctive attire due to the risk of drowning. In contact sports, precautions are required to address seizures prior to physical contact. Guidelines for children with epilepsy in school events emphasize inclusion, as restrictions may lead to social and developmental challenges. Few prominent athletes who openly disclosed their epilepsy diagnoses. Conclusion: Physical activity offers benefits to individuals with epilepsy, necessitating a re-evaluation of exercise restrictions. Guidelines and seizure type considerations are essential. Athletes' openness about epilepsy enhances awareness and support, contributing to the overall well-being of this population. Dipruption of epilepsy on competitive mindset might extend to Athletic Identity (AI). [ABSTRACT FROM AUTHOR]

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Background Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent pacing should be avoided whenever possible. Cardioneuroablation may obviate the need for a pacemaker in well-selected patients. Case summary A previously healthy 24-year-old woman was referred to the emergency department after recurrent episodes of transient loss of consciousness (TLOC). The electrocardiogram (ECG) and the echocardiogram were normal. An electroencephalogram (EEG) showed intermittent, generalized pathological activity. During EEG under photostimulation, the patient developed a short-term TLOC followed by brachial myocloni, while the concurrent ECG registered a progressive bradycardia, which turned into a complete atrioventricular block and sinus arrest with asystole for 14 s. Immediately after, the patient regained consciousness without sequelae. The episode was interpreted as cardioinhibitory convulsive syncope. However, due to the pathological EEG findings, an underlying epilepsy with ictal asystole could not be fully excluded. Therefore, an antiseizure therapy was also started. After discussing the consequences of pacemaker implantation, the patient agreed to undergo a cardioneuroablation and after 72 h without complications, she was discharged home. At 10 months, the patient autonomously discontinued the antiepileptics. The follow-up EEG displayed unspecific activities without clinical correlations. An implantable loop recorder didn't show any relevant bradyarrhythmia. At 1-year follow-up, the patient remained asymptomatic and without syncopal episodes. Discussion Reflex syncope must be considered in the differential diagnosis of seizures. The cardioneuroablation obviated the need for a pacemaker and allowed for the withdrawal of anticonvulsants, originally started on the premise of seizure. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30–40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients' lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment. [ABSTRACT FROM AUTHOR]

The law distinguishes between the concepts of "thing" and "money." While the concept of "thing" refers to the object of a right, whether physical or moral, money is considered every right that possesses a monetary value. The Tunisian legislator defines money in the first article of the real rights code as: "Everything that is not outside the transaction by nature or by law and can be the subject of a right with a monetary value." The second article of the same code adds that "Money is divided into real estate and movable property." The importance of studying the differences between real estate and movable property in the Tunisian Civil law, lies in analyzing the differences between the rules governing them, whether substantively or procedurally. The research aims to enrich legal knowledge by providing researchers with a study of the provisions of Tunisian law and its applications, which may serve as a starting point for comparative studies. [ABSTRACT FROM AUTHOR]

It has been known for a long time that epileptic seizures provoke brain neuroinflammation involving the activation of microglial cells. However, the role of these cells in this disease context and the consequences of their inflammatory activation on subsequent neuron network activity remain poorly understood so far. To fill this gap of knowledge and gain a better understanding of the role of microglia in the pathophysiology of epilepsy, we used an established zebrafish Dravet syndrome epilepsy model based on Scn1Lab sodium channel loss-of-function, combined with live microglia and neuronal Ca2+ imaging, local field potential (LFP) recording, and genetic microglia ablation. Data showed that microglial cells in scn1Lab-deficient larvae experiencing epileptiform seizures displayed morphological and biochemical changes characteristic of M1-like pro-inflammatory activation; i.e., reduced branching, amoeboid-like morphology, and marked increase in the number of microglia expressing pro-inflammatory cytokine Il1β. More importantly, LFP recording, Ca2+ imaging, and swimming behavior analysis showed that microglia-depleted scn1Lab-KD larvae displayed an increase in epileptiform seizure-like neuron activation when compared to that seen in scn1Lab-KD individuals with microglia. These findings strongly suggest that despite microglia activation and the synthesis of pro-inflammatory cytokines, these cells provide neuroprotective activities to epileptic neuronal networks, making these cells a promising therapeutic target in epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Phenobarbital (PB) and levetiracetam (LEV) are the first-line therapies for neonates with diagnosed seizures, however, a growing body of evidence shows that these drugs given during critical developmental windows trigger lasting molecular changes in the brain. While the targets and mechanism of action of these drugs are well understood-what is not known is how these drugs alter the transcriptomic landscape, and therefore molecular profile/gene expression during these critical windows of neurodevelopment. PB is associated with a range of neurotoxic effects in developing animals, from cell death to altered synaptic development to lasting behavioral impairment. LEV does not produce these effects. Methods: Here we evaluated the effects of PB and Lev on the hippocampal transcriptome by RNA sequencing. Neonatal rat pups were given a single dose of PB, Lev or vehicle and sacrificed 72 h later-at time at which drug is expected to be cleared. Results: We found PB induces broad changes in the transcriptomic profile (124 differentially expressed transcripts), as compared to relatively small changes in LEV-treated animals (15 transcripts). PB exposure decreased GABAergic and oligodendrocyte markers pvalb and opalin, and increased the marker of activated microglia, cd68 and the astrocyte-associated gene vegfa. These data are consistent with the existing literature showing developmental neurotoxicity associated with PB, but not LEV. Discussion: The widespread change in gene expression after PB, which affected transcripts reflective of multiple cell types, may provide a link between acute drug administration and lasting drug toxicity. [ABSTRACT FROM AUTHOR]

A missense mutation in the transcription repressor Nucleus accumbens-associated 1 (NACC1) gene at c.892C>T (p.Arg298Trp) on chromosome 19 causes severe neurodevelopmental delay (Schoch et al., 2017). To model this disorder, we engineered the first mouse model with the homologous mutation (Nacc1+/R284W) and examined mice from E17.5 to 8 months. Both genders had delayed weight gain, epileptiform discharges and altered power spectral distribution in cortical electroencephalogram, behavioral seizures, and marked hindlimb clasping; females displayed thigmotaxis in an open field. In the cortex, NACC1 long isoform, which harbors the mutation, increased from 3 to 6 months, whereas the short isoform, which is not present in humans and lacks aaR284 in mice, rose steadily from postnatal day (P) 7. Nuclear NACC1 immunoreactivity increased in cortical pyramidal neurons and parvalbumin containing interneurons but not in nuclei of astrocytes or oligodendroglia. Glial fibrillary acidic protein staining in astrocytic processes was diminished. RNA-seq of P14 mutant mice cortex revealed over 1,000 differentially expressed genes (DEGs). Glial transcripts were downregulated and synaptic genes upregulated. Top gene ontology terms from upregulated DEGs relate to postsynapse and ion channel function, while downregulated DEGs enriched for terms relating to metabolic function, mitochondria, and ribosomes. Levels of synaptic proteins were changed, but number and length of synaptic contacts were unaltered at 3 months. Homozygosity worsened some phenotypes including postnatal survival, weight gain delay, and increase in nuclear NACC1. This mouse model simulates a rare form of autism and will be indispensable for assessing pathophysiology and targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionsEpilepsy is a neurological disorder characterized by recurrent seizures. We aimed to investigate the association between the percentage of dietary carbohydrate intake (DCI) and epilepsy prevalence among American adults.We analyzed the data from 9,584 adults aged 20–80 years who participated in the National Health and Nutrition Examination Survey from 2013 to 2018. Logistic regression was applied to explore the association between the percentage of DCI and epilepsy prevalence.A total of 146 (1.5%) individuals with epilepsy were enrolled in this study. The average age of the participants was 56.4 years, and 5,454 (56.9%) individuals were female. A high DCI was associated with an increased prevalence of epilepsy (odds ratio [OR], 4.56; 95% confidence interval [CI], 1.11–18.69; P = 0.035) after adjusting for age, sex, marital status, race/ethnicity, educational level, family income, body mass index, smoking status, drinking status, hypertension, diabetes, and cardiovascular disease. Stratified analyses indicated a positive correlation between DCI and epilepsy prevalence in adults with different characteristics. Compared with individuals in quartile 1 of DCI (<40.5%), those in quartile 4 (>55.4%) had an adjusted OR for epilepsy of 1.72 (95% CI, 1.09–2.73, P = 0.02, P for trend = 0.012).A high percentage of DCI was associated with an increased prevalence of epilepsy. The risk of epilepsy increased 3.5-fold with a 1% increase in DCI. These results suggest an important role of DCI in the dietary management of epilepsy. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurological disorders globally, affecting about 50 million people, with nearly 80% of those affected residing in low- and middle-income countries. It is characterized by recurrent seizures that result from abnormal electrical brain activity, with seizures varying widely in manifestation. The exploration of the biomechanical effects that seizures have on brain dynamics and stress levels is relevant for the development of more effective treatments and protective strategies. This study uses a blend of experimental data and computational simulations to assess the brain's physical response during seizures, particularly focusing on the behavior of cerebrospinal fluid and the resulting mechanical stresses on different brain regions. Notable findings show increases in stress, predominantly in the posterior gyri and brainstem, during seizures and an evidence of brain displacement relative to the skull. These observations suggest a dynamic and complex interaction between the brain and skull, with maximum shear stress regions demonstrating the limited yet essential protective role of the CSF. By providing a deeper understanding of the mechanical changes occurring during seizures, this research supports the goal of advancing diagnostic tools, informing more targeted treatment interventions, and guiding the creation of customized therapeutic strategies to enhance neurological care and protect against the adverse effects of seizures. [ABSTRACT FROM AUTHOR]

Background: Continuous infusion ketamine has demonstrated efficacy in the management of refractory seizures yet does not suppress respiratory drive like other continuous infusion anesthetics (CIAs) used for this indication. The aim of this study is to describe the safety and efficacy of ketamine infusions in patients with refractory seizure without intubation. Methods: We analyzed a retrospective cohort of adult patients who were not intubated at the time of initiation of a ketamine infusion for refractory seizures. Seizure onset was determined to be the first clinical seizure or nonconvulsive seizure reported on electroencephalography (EEG) or the start time of EEG for patients with seizures at EEG initiation. Responders were defined as patients with resolution of seizures within 24 h of initiation without the need for intubation or an additional CIA. Results: A total of 28 patients were analyzed (median age 62 years, 64.3% female, 82.1% African American, 82.1% with structural seizure etiology, and 85.7% focal seizures). Of patients, 78.5% received an initial bolus averaging 0.9 mg/kg, and the majority (89.3%) were initiated on an infusion at 10 μg/kg/minute; median duration was 39.8 h. Maximum infusion rates were 10 μg/kg/minute in 16 patients, 20 μg/kg/minute in seven patients, and 30 μg/kg/minute in five patients. Of patients, 71.4% were assessed to be ketamine responders; six of the eight nonresponders required intubation and an additional CIA. Responders were 80% more likely to have received ketamine 5 or more hours earlier than nonresponders. Hypotension (systolic blood pressure < 90 mmHg) occurred in 31.8% of patients receiving only ketamine, which did not correlate with duration or maximum dose of ketamine; hypertension (systolic blood pressure > 180 mmHg) occurred in 39.3%. Conclusions: Ketamine represents a safe and effective treatment option for refractory seizures and has potential to reduce morbidity associated with intubation in a carefully selected patient population. Early initiation may increase the likelihood of success. [ABSTRACT FROM AUTHOR]

Introduction: Epileptic seizures are thought to be caused by the impaired balance between excitatory (glutamate) and inhibitor [gamma amino butyric acid (GABA)] neurotransmitters in the brain. Neuropeptides have potent modulator properties on these neurotransmitters.Objective: Ghrelin exerts anticonvulsant effects in an acute pentylenetetrazole (PTZ) model. However, the effect of repeated ghrelin injections in chronic pentylenetetrazole kindling model is not known. In this study, the effects of repeated ghrelin administration on seizure scores, working memory, locomotor activity, oxidative biomarkers, and neurochemical parameters in PTZ kindling in rats was examined.Methods: For this purpose, 35 mg/kg of PTZ was administered intraperitoneally to the experimental groups. The rats also received physiological saline/diazepam or ghrelin before each PTZ injection. After behavioural analysis (Y-maze, rotarod, and locomotor activity tests), biochemical and neurochemical analyses were conducted using ELISA.Results: PTZ administration induced progression in the seizure scores and all of the rats in the PS + PTZ group were kindled with the 20th injection. Ghrelin treatment significantly reduced the seizure scores. The difference among the groups in terms of the Y-maze, locomotor activity, and rotarod tests was nonsignificant. PTZ administration significantly decreased the brain GABA, CAT, and AChE levels, and increased the MDA, NO, and protein carbonyl levels. Repeated ghrelin treatment ameliorated the GABA, AChE, CAT, MDA, NO, and protein carbonyl levels.Conclusion: Taken together, the results indicated that repeated ghrelin treatment had antioxidant, and anticonvulsant activity on PTZ kindling in rats. [ABSTRACT FROM AUTHOR]

Objective: Electroconvulsive therapy (ECT) is used to treat several mental illnesses. Seizure duration is used to determine if the administered stimulus was adequate. Duration is estimated by electroencephalogram (EEG) interpretation and/or observed motor response (OMR). Neither method is considered the gold standard. This study investigated the relationship between the 2 methods. The hypothesis was that both EEG and OMR would be significantly positively correlated. Previous researchers have suggested that the 2 methods resulted in different estimates. Methods: A case series was conducted using recorded estimates obtained prospectively from 102 ECTs on adult psychiatric inpatients. Results: A strong positive association was not observed in this study, correlation coefficient 0.510 (p < 0.001). Conclusions: This study suggests that the 2 methods differ, and further research is needed to determine the best indicator of adequate treatment. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and increases the risk of cognitive impairment, negatively impacting the quality of life of affected individuals. Objectives: This study aimed to investigate cognitive function in patients with low socioeconomic status affected by TLE and identify factors influencing such function. Methods: This case-control study, conducted between July 2021 and August 2022, compared the cognitive function of 40 patients affected by TLE to 92 healthy controls. The Montreal cognitive assessment (MoCA) was used for neurocognitive evaluation. Data analysis was performed using SPSS 25.0 for Windows. Results: The mean age of the patient group was 33.35 years, compared to 35.37 years in the control group. Moreover, 70% of patients affected by TLE displayed cognitive impairment and demonstrated lower performance in cognitive functions than the control group (P < 0.05). Significant correlations were identified between overall MoCA scores and several factors, including seizure frequency, educational level, polytherapy, disease duration, and self-esteem scores (P < 0.05). Multivariate analysis revealed that seizure control and higher educational level were statistically significant predictors of overall MoCA scores in patients affected by TLE. Conclusions: In low-income patients affected by TLE, seizure control and a higher educational level emerged as predictors of cognitive performance. These findings underscore the importance of identifying and managing comorbidities and the need for tailored cognitive rehabilitation programs for this population. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic brain disease with a global prevalence of 70 million people. According to the World Health Organization, roughly 5 million new cases are diagnosed every year. Anti-seizure drugs are the treatment of choice. However, in roughly one third of the patients, these drugs fail to produce the desired effect. As a result, finding novel treatments for epilepsy becomes inevitable. Recently, angiotensin receptor blockers have been proposed as a treatment to reduce the over-excitation of neurons in epilepsy. For this purpose, we conducted a review using Medline/PubMed and Google Scholar using the relevant search terms and extracted the relevant data in a table. Our review suggests that this novel approach has a very high potential to treat epilepsy, especially in those patients who fail to respond to conventional treatment options. However, more extensive and human-based trials should be conducted to reach a decisive conclusion. Nevertheless, the use of ARBs in patients with epilepsy should be carefully monitored keeping the adverse effects in mind. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) is an indispensable part of the healthcare system since it creates a link between the doctor and the patient for remote medical consultations. IoT-based seizure prediction detects seizures and monitors the health of patients remotely. The disease seizure is classified as the sudden and repeated malfunction of the neurons of the brain. To protect patients' lives, it's critical to recognise the risk of an epileptic seizure. In this research, a hybrid cuckoo finch optimisation is proposed using a tuned Deep-CNN (Deep-Convolutional Neural Network) classifier to recognise and predict the occurrence of epileptic seizures using electroencephalogram (EEG) signal data obtained through IoT. Initially, the gathered data is pre-processed and subjected to frequency band generation. Then there are the notable characteristics, such as statistical features, wavelet features, entropy-based features, spectral features, CPR (common spatial patterns), and logarithmic band power, which are extracted and concatenated. The optimal electrode selection is done by using the proposed hybrid cuckoo finch optimisation that inherits the characteristics of intrusive and attentive search agents. The data is finally normalised and fed to the proposed hybrid cuckoo finch optimisation tuned to Deep-CNN to classify the seizure disease. The specificity, accuracy, and sensitivity of the proposed model are 92.5212%, 97.7648%, and 95.6324%, which demonstrate the efficient performance of the proposed seizure prediction model. [ABSTRACT FROM AUTHOR]

Background: Altered concentrations of cerebrospinal fluid (CSF) and blood amino acids may be related to epilepsy or the severity of the seizure. In the present study, we assessed the concentrations of amino acids in CSF and plasma in neonates with refractory seizures. Methods: In this prospective cohort study, 27 neonates aged 1 to 56 days with refractory seizures were included. Blood and CSF samples were collected from each neonate within 24 hours after receiving 2nd antiseizure medications. All plasma and CSF samples were sent to the laboratory to measure amino acid concentrations. The associations between CSF and plasma amino acid levels with different variables were evaluated. Results: Except for leucine (P=0.15) and isoleucine (P=0.07), the levels of all amino acids were significantly higher in plasma than CSF. Significant associations were observed between types of seizure and plasma citrulline (P=0.008) and leucine concentrations (P=0.04). The mean of CSF glutamic acid was also statistically different among neonates with different EEG results (P=0.02). Conclusion: Our findings indicate that several plasma and CSF amino acids could be candidate biomarkers for neonatal refractory seizures. Further studies with larger sample size are to confirm our findings. [ABSTRACT FROM AUTHOR]

Aim: To investigate the evolution of clinical symptoms of COVID‐19 in children throughout the pandemic. Methods: In this national prospective surveillance study, symptoms in children hospitalised with COVID‐19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS‐CoV‐2 variant: T1 (wild‐type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group. Results: The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild‐type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school‐aged children presented with neurological symptoms more often than other age groups. Conclusion: Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID‐19. [ABSTRACT FROM AUTHOR]

Objectives Shigellosis is one of the common causes of bacterial diarrhea in children. Seizures are common in shigellosis. It is essential to identify the risk factors of seizure in this disease. Materials & Methods This study was conducted on 224 children with shigellosis. The patients were divided into: With (case groups = 63 cases) and without seizures (control group = 161 cases). Groups were compared regarding different variables such as age, gender, clinical symptoms, and laboratory findings. Data analysis was done using statistical tests and SPSS software. Logistic regression analysis was used to determine the risk factors of seizures. Results Out of 224 cases of children with shigellosis, 107 (47.8%) were male and 117 (52.2%) female. Significant differences were observed between the two groups in terms of age, history of febrile convulsions, frequency of bloody diarrhea, frequency of fever, duration of diarrhea before hospitalization, abdominal pain, increase in BUN, hyponatremia, hypocalcemia, and red blood cell count in stool (P<0.05). Logistic regression analysis showed that a history of febrile seizure, fever, and hyponatremia are the risk factors for seizures in shigellosis. Conclusion This study concluded that a history of febrile seizure, fever, and hyponatremia are risk factors for seizure in childhood shigellosis, thus rapid diagnosis and treatment of childhood shigellosis with risk factors is very important. [ABSTRACT FROM AUTHOR]

• The ILAE 2022 diagnostic criteria for epilepsy syndromes were easily applied among 858 children in a resource-limited setting. • 11.5 % children were newly classified under an epilepsy syndrome who had previously remained unclassified. • 1.3 % children who were previously classified into an epilepsy syndrome could not be classified using the new diagnostic criteria. • 0.9 % were shifted to a new syndromic category. Recently, the ILAE Nosology and Definitions Task Force defined diagnostic criteria for epilepsy syndromes. There is paucity of data on the use of these new diagnostic criteria in children with epilepsy, and how these criteria may lead to changes from previous practice. This was a retrospective chart review of data of children attending the epilepsy clinic in a tertiary care children's hospital from January 2011 to January 2023. The clinical details such as age at onset, types of seizures, co-morbidities, and results of EEG, MRI and genetic testing were reviewed. Epilepsy syndrome diagnosis was made as per the ILAE 2022 criteria, and compared with the previous syndrome diagnosis as per records. Data from 1550 children (63 % boys) with epilepsy were analysed, and 55.4 % children were classified to have epilepsy syndromes as per the new ILAE 2022 diagnostic criteria. Application of the new 2022 ILAE diagnostic criteria was associated with a change in name alone in 676 (77.8 %) children. Hundred (11.5 %) children were newly classified under an epilepsy syndrome who had previously remained unclassified. Eleven (1.3 %) children who were previously classified into an epilepsy syndrome could not be classified using the new diagnostic criteria. Eight (0.9 %) were shifted to a new syndromic category. Overall, change in diagnosis occurred in 13.7 (11.5 + 1.3 + 0.9)%. No change in epilepsy syndrome classification/nomenclature occurred in 74 (8.5 %) children. The new diagnostic criteria led to an overall change in diagnosis in 13.7 % of children with epilepsy. These criteria will hopefully lead to uniformity in diagnosis of epilepsy syndromes across diverse settings. [ABSTRACT FROM AUTHOR]

• Continuous EEG monitoring (CEEG) requires extensive staff and equipment resources. • A machine learning-based multi-stage model to guide CEEG utilization in critically ill children in the pediatric intensive care unit was developed. • Application of this model has the potential to reduce CEEG utilization for patients at low risk of electrographic seizures. • A developed web application (EEGLE) enables straightforward implementation of the model. Strategies are needed to optimally deploy continuous EEG monitoring (CEEG) for electroencephalographic seizure (ES) identification and management due to resource limitations. We aimed to construct an efficient multi-stage prediction model guiding CEEG utilization to identify ES in critically ill children using clinical and EEG covariates. The largest prospective single-center cohort of 1399 consecutive children undergoing CEEG was analyzed. A four-stage model was developed and trained to predict whether a subject required additional CEEG at the conclusion of each stage given their risk of ES. Logistic regression, elastic net, random forest, and CatBoost served as candidate methods for each stage and were evaluated using cross validation. An optimal multi-stage model consisting of the top-performing stage-specific models was constructed. When evaluated on a test set, the optimal multi-stage model achieved a cumulative specificity of 0.197 and cumulative F1 score of 0.326 while maintaining a high minimum cumulative sensitivity of 0.938. Overall, 11 % of test subjects with ES were removed from the model due to a predicted low risk of ES (falsely negative subjects). CEEG utilization would be reduced by 32 % and 47 % compared to performing 24 and 48 h of CEEG in all test subjects, respectively. We developed a web application called EEGLE (EEG L ength E stimator) that enables straightforward implementation of the model. Application of the optimal multi-stage ES prediction model could either reduce CEEG utilization for patients at lower risk of ES or promote CEEG resource reallocation to patients at higher risk for ES. [ABSTRACT FROM AUTHOR]

• We undertook a systematic review and meta-analysis in order to clarify the potential impact of a low glycemic index (LGI) diet on the frequency of seizures in the pediatric population. • Our findings indicated that pooled efficacy rate for < 50 %, ≥ 50 %, > 90 % seizure reduction in epilepsy patients receiving a low glycemic index diet was 39 %, 34 %, and 19 %, respectively. • It also seems that the efficacy of this ketogenic diet to reduce seizures is greater during the intervention of less than 12 weeks. • It seems that according to the results of the subgroup, the length of the intervention period is one of the sources of high heterogeneity. Despite extensive research examining the effect of a low glycemic index (LGI) diet on the frequency of seizures in patients with epilepsy, the findings are inconclusive. Hence, we performed a systematic review and meta-analysis in order to clarify the potential effect of a low glycemic index (LGI) diet on the frequency of seizures in children. A systematic review and meta-analysis written in accordance with the PRISMA checklist was realized using a comprehensive systematic search in four electronic databases until October 2023 without time or language restrictions. A random effects model was employed to combine the data. The main outcomes were analyzed using weight mean difference (WMD) and 95 % confidence interval (95 % CI). In total, 13 studies met the eligible criteria and were included. The publications included in this study were published between 2005 and 2021. The duration of the interventions in the studies included in this analysis ranged from 6 to 58 weeks. Our findings indicated that the pooled efficacy rate for < 50 %, ≥ 50 %, > 90 % seizure reduction in patients with epilepsy receiving a low glycemic index diet was 39 % (95 % CI: 26, 52), 34 % (95 % CI: 23, 45), and 19 % (95 % CI: 13, 25), respectively. It seems that the efficacy of this ketogenic diet in reducing seizures is greater during a shorter intervention period than 12 weeks. This systematic review and meta-analysis suggests that the low glycemia index diet can be beneficial as a treatment for epilepsy in pediatric patients. [ABSTRACT FROM AUTHOR]

• PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. • The aim of this present study is to elucidate the phenotypic presentations and molecular genetic characteristics of PAFAH1B1-related epilepsy in a Chinese cohort. • Notably, the clinical presentation in patients with PAFAH1B1 gene variants exhibits heterogeneity, and this heterogeneity is associated with the specific type of variant. PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy. We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children's Hospital from June 2017 to November 2022. The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant. The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations. [ABSTRACT FROM AUTHOR]

• Women with generalized epilepsy have a higher likelihood of seizure freedom during pregnancy. • Non-compliance with antiseizure medications contributes to the worsening of seizure control. • Women with epilepsy have a higher risk of preterm birth and delivery by cesarean section. • Maternal seizures are associated with a higher risk of cesarean section and perinatal hypoxia. • The epilepsy type is not significantly associated with adverse delivery outcomes. To prospectively investigate the course of epilepsy and assess seizure control during pregnancy in women with focal epilepsy (FE) compared with generalized epilepsy (GE), to ascertain the effects of epilepsy and its types on delivery and neonatal outcomes, and to compare adverse outcomes between pregnancies complicated by epilepsy and normal pregnancies. 124 pregnant women with epilepsy (WWE) were enrolled in a prospective study. Obstetric and neonatal outcomes were compared with those of 277 healthy women in the control group. Occurrence of seizures during pregnancy was more often in FE (77.1 %) compared with GE (50.0 %) (Odds ratio [OR] 2.08; 95 % confidence interval [CI] 0.97–4.46, p = 0.06); the overall seizure freedom was significantly higher in women with GE compared with women with FE (p = 0.0038). Poor seizure control one year prior to the pregnancy and nonadherence to treatment were significantly associated with presence of seizures during pregnancy (p < 0.0001). Compared with pregnancies of women without epilepsy, WWE were at increased risk of cesarean section (CS) (p < 0.0001) and preterm birth (p = 0.03). Offspring of mothers with epilepsy were at higher risks of Apgar scores at 5 min ≤7 (p < 0.0001) and perinatal hypoxia (p = 0.03) compared with infants of unaffected women. Seizures during pregnancy were significantly correlated with the higher rate of CS, Apgar scores at 5 min ≤7, and perinatal hypoxia (p = 0.0069; p = 0.0098; and p = 0.0045, respectively). The risks of adverse outcomes were not significantly increased in women with FE compared to women with GE. Epileptic seizures in pregnancy are associated with increased risks of adverse delivery and neonatal outcomes. Hence, early assessment of seizure disorder, adequate seizure control prior to and during pregnancy, and effective treatment are required to prevent potential seizure-related complications and improve maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Objective: Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population. Methods: This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017. Results: The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001). Conclusions: SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors. [ABSTRACT FROM AUTHOR]

Structural epilepsies display complex immune activation signatures. However, it is unclear which neuroinflammatory pathways drive pathobiology. Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor β, interferon α/β, and nuclear factor erythroid 2-related factor 2 pathways. Since these pathways are regulated by ubiquitin-specific proteases (USP), in particular USP15, we hypothesized that USP15 blockade may provide therapeutic relief in treatment-resistant epilepsies. For validation, transgenic mice which either constitutively or inducibly lack Usp15 gene expression underwent intrahippocampal kainate injections to induce mTLE. We show that the severity of status epilepticus is unaltered in mice constitutively lacking Usp15 compared to wild types. Cell death, reactive gliosis, and changes in the inflammatory transcriptome were pronounced at 4 days after kainate injection. However, these brain inflammation signatures did not differ between genotypes. Likewise, induced deletion of Usp15 in chronic epilepsy did not affect seizure generation, cell death, gliosis, or the transcriptome. Concordantly, siRNA-mediated knockdown of Usp15 in a microglial cell line did not impact inflammatory responses in the form of cytokine release. Our data show that a lack of USP15 is insufficient to modulate the expression of relevant neuroinflammatory pathways in an mTLE mouse model and do not support targeting USP15 as a therapeutic approach for pharmacoresistant epilepsy. [ABSTRACT FROM AUTHOR]

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects. [ABSTRACT FROM AUTHOR]

Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy. A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone. The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference −1.45 (95% CI: −3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo. Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile. CRD42023434883 [ABSTRACT FROM AUTHOR]

Epilepsy is a complex genetic disorder that affects about 2% of the global population. Although the frequency and severity of epileptic seizures can be reduced by a range of pharmacological interventions, there are no disease-modifying treatments for epilepsy. The development of new and more effective drugs is hindered by a lack of suitable animal models. Available rodent models may not recapitulate all key aspects of the disease. Spontaneous epileptic convulsions were observed in few Göttingen Minipigs (GMPs), which may provide a valuable alternative animal model for the characterisation of epilepsy-type diseases and for testing new treatments. We have characterised affected GMPs at the genome level and have taken advantage of primary fibroblast cultures to validate the functional impact of fixed genetic variants on the transcriptome level. We found numerous genes connected to calcium metabolism that have not been associated with epilepsy before, such as ADORA2B, CAMK1D, ITPKB, MCOLN2, MYLK, NFATC3, PDGFD, and PHKB. Our results have identified two transcription factor genes, EGR3 and HOXB6, as potential key regulators of CACNA1H, which was previously linked to epilepsy-type disorders in humans. Our findings provide the first set of conclusive results to support the use of affected subsets of GMPs as an alternative and more reliable model system to study human epilepsy. Further neurological and pharmacological validation of the suitability of GMPs as an epilepsy model is therefore warranted. [ABSTRACT FROM AUTHOR]

Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long‐term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs‐foods (‐drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4–5 folds with concomitant intake of fat‐rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well‐designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. Plain Language Summary: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy. [ABSTRACT FROM AUTHOR]

The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.

Despite new antiseizure medications, the development of cholinergic-induced refractory status epilepticus (RSE) continues to be a therapeutic challenge as pharmacoresistance to benzodiazepines and other antiseizure medications quickly develops. Studies conducted by Epilepsia. 2005;46:142 demonstrated that the initiation and maintenance of cholinergic-induced RSE are associated with trafficking and inactivation of gamma-aminobutyric acid A receptors (GABAA R) thought to contribute to the development of benzodiazepine pharmacoresistance. In addition, Dr. Wasterlain's laboratory reported that increased N-methyl-d-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) contribute to enhanced glutamatergic excitation (Neurobiol Dis. 2013;54:225; Epilepsia. 2013;54:78). Thus, Dr. Wasterlain postulated that targeting both maladaptive responses of reduced inhibition and increased excitation that is associated with cholinergic-induced RSE should improve therapeutic outcome. We currently review studies in several animal models of cholinergic-induced RSE that demonstrate that benzodiazepine monotherapy has reduced efficacy when treatment is delayed and that polytherapy with drugs that include a benzodiazepine (eg midazolam and diazepam) to counter loss of inhibition, concurrent with an NMDA antagonist (eg ketamine) to reduce excitation provide improved efficacy. Improved efficacy with polytherapy against cholinergic-induced seizure is demonstrated by reduction in (1) seizure severity, (2) epileptogenesis, and (3) neurodegeneration compared with monotherapy. Animal models reviewed include pilocarpine-induced seizure in rats, organophosphorus nerve agent (OPNA)-induced seizure in rats, and OPNA-induced seizure in two mouse models: (1) carboxylesterase knockout (Es1-/- ) mice which, similarly to humans, lack plasma carboxylesterase and (2) human acetylcholinesterase knock-in carboxylesterase knockout (KIKO) mice. We also review studies showing that supplementing midazolam and ketamine with a third antiseizure medication (valproate or phenobarbital) that targets a nonbenzodiazepine site rapidly terminates RSE and provides further protection against cholinergic-induced SE. Finally, we review studies on the benefits of simultaneous compared with sequential drug treatments and the clinical implications that lead us to predict improved efficacy of early combination drug therapies. The data generated from seminal rodent studies of efficacious treatment of cholinergic-induced RSE conducted under Dr. Wasterlain's guidance suggest that future clinical trials should treat the inadequate inhibition and temper the excess excitation that characterize RSE and that early combination therapies may provide improved outcome over benzodiazepine monotherapy.

OBJECTIVE: Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations. METHODS: We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1 Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates. RESULTS: We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ. SIGNIFICANCE: These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1 Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.

Epilepsy is a common chronic neurological disease. People with epilepsy (PWE) and their caregivers face several challenges related to their epilepsy management, including quality of care, care coordination, side effects, and stigma management. The sociotechnical issues of the information management contexts and challenges for epilepsy care may be mitigated through effective information management. We conducted 4 focus groups with 5 PWE and 7 caregivers to explore how they manage epilepsy-related information and the challenges they encountered. Primary issues include challenges of finding the right information, complexities of tracking and monitoring data, and limited information sharing. We provide a framework that encompasses three attributes - individual epilepsy symptoms and health conditions, information complexity, and circumstantial constraints. We suggest future design implications to mitigate these challenges and improve epilepsy information management and care coordination.

BackgroundDrug-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).ObjectiveThis study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs.Materials and methodsThis 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.ResultsWe 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.ConclusionThe 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.

Abstract This case report details the clinical presentation, diagnosis, management and prognosis of paroxysmal dyskinesia (PD) in four small‐breed dogs, each weighing under 6 kg: A 7‐year‐old spayed female Pomeranian, an 8‐year‐old female mixed breed, a 1‐year‐old female Pomeranian and a 9‐year‐old castrated male Poodle. These dogs were referred to our hospital due to movement disorders. Diagnosis was facilitated by video recordings of the episodes, assessing motor activity, consciousness, episode duration, any pre‐ or post‐episodic behaviour as well as the presence of autonomic signs. Magnetic resonance imaging conducted on two of the dogs returned unremarkable results. Treatment trials included a gluten‐free diet for all four dogs, with two also receiving acetazolamide. This intervention led to a decrease in the frequency of abnormal movement in all patients. Our findings suggest that PD in dogs can be effectively diagnosed through detailed symptom description using videos and questionnaires. Furthermore, once diagnosed, a combination of nutritional and medical management can be beneficial.

Clinical studies have reported that increased epileptiform and subclinical epileptiform activity can be detected in many patients with an Alzheimer's disease (AD) diagnosis using electroencephalogram (EEG) and this may correlate with poorer cognition. Ascorbate may have a specific role as a neuromodulator in AD as it is released concomitantly with glutamate reuptake following excitatory neurotransmission. Insufficiency may therefore result in an exacerbated excitatory/inhibitory imbalance in neuronal signaling. Using a mouse model of AD that requires dietary ascorbate (Gulo−/-APPswe/PSEN1dE9), EEG was recorded at baseline and during 4 weeks of ascorbate depletion in young (5-month-old) and aged (20-month-old) animals. Data were scored for changes in quantity of spike trains, individual spikes, sleep-wake rhythms, sleep fragmentation, and brainwave power bands during light periods each week. We found an early increase in neuronal spike discharges with age and following ascorbate depletion in AD model mice and not controls, which did not correlate with brain amyloid load. Our data also show more sleep fragmentation with age and with ascorbate depletion. Additionally, changes in brain wave activity were observed within different vigilance states in both young and aged mice, where Gulo−/-APPswe/PSEN1dE9 mice had shifts towards higher frequency bands (alpha, beta, and gamma) and ascorbate depletion resulted in shifts towards lower frequency bands (delta and theta). Microarray data supported ascorbate insufficiency altering glutamatergic transmission through the decreased expression of glutamate related genes, however no changes in protein expression of glutamate reuptake transporters were observed. These data suggest that maintaining optimal brain ascorbate levels may support normal brain electrical activity and sleep patterns, particularly in AD patient populations where disruptions are observed.

Seizures occur when there is a hyper-excitation of the outer layer of the brain, with subsequent excessive synchrony in a group of neurons. According to the World Health Organization (WHO), an estimated 50 million people are affected by this disease, a third of whom are resistant to the treatments available on the market. Caffeine (1,3,7-trimethylxanthine), which belongs to the purine alkaloid family, is the most widely consumed psychoactive drug in the world. It is ingested by people through drinks containing this substance, such as coffee, and as an adjuvant in analgesic therapy with non-steroidal antiflammatory drugs. The present study evaluated the electrocorticographic changes observed in the hippocampus of Wistar rats subjected to acute doses of caffeine (150 mg/kg i.p), which represents a toxic dose of caffeine corresponding to an estimated acute intake of more than 12 cups of coffee to record its convulsant activity. Our results showed, for the first time, that the administration of high doses of caffeine (150 mg/kg i.p.) in rats caused an increase in the spectral distribution of power in all frequency bands and suggested the appearance of periods of ictal and interictal peaks in the electrocorticogram (ECog). We have also shown that the anticonvulsants phenytoin, diazepam and phenobarbital have a satisfactory response when associated with caffeine.

IntroductionThe prevalence of vitamin D deficiency and vitamin D levels in patients with epilepsy (PWE) were systematically evaluated, and the differences between subgroups were analyzed.MethodWe identified all articles investigating the prevalence of vitamin D deficiency in patients with epilepsy from the database established in March 2024 from PubMed, Web of Science, and Embase. We divided them into anti-seizure medication (ASM) interventions and non-ASM interventions according to whether or not someone used ASM.ResultsA total of 68 articles were included. The prevalence of newly diagnosed epilepsy was 50.2% (95% CI: 38.7–61.7%), and the prevalence after ASM intervention was 47.9% (95% CI: 40–55.9%), including 7,070 patients with epilepsy. Subgroup and meta-regression analyses were performed according to the diagnostic criteria, economic development level, region, age, ASM treatment, and other factors. The results showed that the differences were not significant. In addition, the vitamin D content of epilepsy patients (18.719 ng/mL) was lower than that of healthy people (20.295 ng/mL).ConclusionThe prevalence of vitamin D deficiency in patients with epilepsy is very high. Still, the related factors have little effect on the high prevalence of vitamin D in epilepsy, and ASM intervention can reduce the vitamin D content in patients with epilepsy. Therefore, it is emphasized that monitoring vitamin D levels is part of the routine management of patients with epilepsy.Systematic review registrationThe protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). (registration number CRD42023493896). https://www.crd.york.ac.uk/PROSPERO/ # myprospero.

Despite an abundance of pharmacologic and surgical epilepsy treatments, there remain millions of patients suffering from poorly controlled seizures. One approach to closing this treatment gap may be found through a deeper mechanistic understanding of the network alterations that underly this aberrant activity. Functional optical imaging in vertebrate models provides powerful advantages to this end, enabling the spatiotemporal acquisition of individual neuron activity patterns across multiple seizures. This coupled with the advent of genetically encoded indicators, be them for specific ions, neurotransmitters or voltage, grants researchers unparalleled access to the intact nervous system. Here, we will review how in vivo functional optical imaging in various vertebrate seizure models has advanced our knowledge of seizure dynamics, principally seizure initiation, propagation and termination.

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis.

ObjectivePreclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish.MethodsLocal field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin (H&E) staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis.ResultsAcute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains.SignificanceHere, we comprehensively investigated a new model of PILO-induced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes.