Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT)).

BACKGROUND: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid-base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment. METHODS: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality. DISCUSSION: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff. TRIAL REGISTRATION: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

Ascorbic acid mitigates the impact of oxidative stress in a human model of febrile seizure and mesial temporal lobe epilepsy.

Prolonged febrile seizures (FS) in children are linked to the development of temporal lobe epilepsy (MTLE). The association between these two pathologies may be ascribed to the long-term effects that FS exert on neural stem cells, negatively affecting the generation of new neurons. Among the insults associated with FS, oxidative stress is noteworthy. Here, we investigated the consequences of exposure to hydrogen peroxide (H2O2) in an induced pluripotent stem cell-derived neural stem cells (iNSCs) model of a patient affected by FS and MTLE. In our study, we compare the findings from the MTLE patient with those derived from iNSCs of a sibling exhibiting a milder phenotype defined only by FS, as well as a healthy individual. In response to H2O2 treatment, iNSCs derived from MTLE patients demonstrated an elevated production of reactive oxygen species and increased apoptosis, despite the higher expression levels of antioxidant genes and proteins compared to other cell lines analysed. Among the potential causative mechanisms of enhanced vulnerability of MTLE patient iNSCs to oxidative stress, we found that these cells express low levels of the heat shock protein HSPB1 and of the autophagy adaptor SQSTM1/p62. Pre-treatment of diseased iNSCs with the antioxidant molecule ascorbic acid restored HSBP1 and p62 expression and simultaneously reduced the levels of ROS and apoptosis. Our findings suggest the potential for rescuing the impaired oxidative stress response in diseased iNSCs through antioxidant treatment, offering a promising mechanism to prevent FS degeneration in MTLE.

Feeding metformin during pregnancy and lactation periods improved learning and memory impairment in the rat offspring exposed to febrile seizure: Role of oxidative stress and inflammatory response.

BACKGROUND: Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti-oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure. METHOD AND MATERIALS: Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3-5) FS-Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis. RESULTS: According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test. CONCLUSION: Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti-oxidant effect of metformin is strongly supported.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

Suppressive Effects of Docosahexaenoic Acid Intake on Increased Seizure Susceptibility after Growth Due to Febrile Seizures in Infancy.

Febrile seizures are seizures accompanied by a fever and frequently occur in children six months to five years of age. Febrile seizures are classified as simple or complex, and complex febrile seizures increase the risk of temporal lobe epilepsy after growth. Therefore, it is important to interfere with epileptogenesis after febrile seizures to prevent post-growth epilepsy. The present study challenged nutritional intervention using docosahexaenoic acid (DHA). Febrile seizures were induced in mice at the age of 10 d using a heat chamber, and seizure sensitivity was examined using pentylenetetrazol (PTZ) administration after growth. PTZ increased the seizure score and shortened the latency in the complex febrile seizure group compared to the control, hyperthermia and simple febrile seizure groups. Mice in the complex febrile seizure group showed abnormal electroencephalograms pre- and post-PTZ administration. Therefore, seizure susceptibility increases the episodes of complex febrile seizures. DHA supplementation after febrile seizures clearly suppressed the increased seizure susceptibility due to complex febrile seizures experienced in infancy. DHA also attenuated microglial activation after complex febrile seizures. Taken together, DHA suppressed microglial activation following complex febrile seizures, which may contribute to protecting the brain from post-growth seizures. The intake of DHA in infancy may protect children from high fever-induced developmental abnormalities.

Heterozygous deletion of Gpr55 does not affect a hyperthermia-induced seizure, spontaneous seizures or survival in the Scn1a+/- mouse model of Dravet syndrome.

A purified preparation of cannabidiol (CBD), a cannabis constituent, has been approved for the treatment of intractable childhood epilepsies such as Dravet syndrome. Extensive pharmacological characterization of CBD shows activity at numerous molecular targets but its anticonvulsant mechanism(s) of action is yet to be delineated. Many suggest that the anticonvulsant action of CBD is the result of G protein-coupled receptor 55 (GPR55) inhibition. Here we assessed whether Gpr55 contributes to the strain-dependent seizure phenotypes of the Scn1a+/- mouse model of Dravet syndrome. The Scn1a+/- mice on a 129S6/SvEvTac (129) genetic background have no overt phenotype, while those on a [129 x C57BL/6J] F1 background exhibit a severe phenotype that includes hyperthermia-induced seizures, spontaneous seizures and reduced survival. We observed greater Gpr55 transcript expression in the cortex and hippocampus of mice on the seizure-susceptible F1 background compared to those on the seizure-resistant 129 genetic background, suggesting that Gpr55 might be a genetic modifier of Scn1a+/- mice. We examined the effect of heterozygous genetic deletion of Gpr55 and pharmacological inhibition of GPR55 on the seizure phenotypes of F1.Scn1a+/- mice. Heterozygous Gpr55 deletion and inhibition of GPR55 with CID2921524 did not affect the temperature threshold of a thermally-induced seizure in F1.Scn1a+/- mice. Neither was there an effect of heterozygous Gpr55 deletion observed on spontaneous seizure frequency or survival of F1.Scn1a+/- mice. Our results suggest that GPR55 antagonism may not be a suitable anticonvulsant target for Dravet syndrome drug development programs, although future research is needed to provide more definitive conclusions.

Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Febrile seizure is a common neurologic disorder with limited treatment occurring in infants and children under the age of five. Jujuboside B (JuB) is a main bioactive saponin component isolated from the Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen (ZSS), seed of Ziziphus jujuba Mill, which has been proved to exhibit neuroprotective effects recently. AIM OF THE STUDY: In this study, we aimed at elucidating the effect of JuB on suppressing febrile seizure and the potential mechanisms. METHODS: Electroencephalogram (EEG) recording was used to monitor the severity of febrile seizures. The JuB in the brain was identified by mass spectrometry. Neuronal excitability was investigated using patch clamp. RESULTS: JuB (30 mg/kg) significantly prolonged seizure latency and reduced the severity in hyperthermia-induced seizures model mice. Hippocampal neuronal excitability was significantly decreased by JuB. And JuB significantly reduced the excitatory synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR), including evoked excitatory postsynaptic currents (eEPSCs), and miniature EPSCs (mEPSCs) in hippocampal neurons. Furthermore, JuB also significantly inhibited recombinant GluA1 and GluA2 mediated AMPA current in HEK293 cell and decreased the upregulation of [Ca2+]i induced by AMPA in primary cultured cortex neurons. CONCLUSIONS: JuB suppressed the excitability of hippocampal neurons by inhibiting the activity of AMPAR and reducing the intracellular free calcium, thereby relieving febrile seizures.

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure.

BACKGROUND: Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. OBJECTIVE: To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. METHODS: Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. RESULTS: The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p < 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p < 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). CONCLUSIONS: Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

ANTECEDENTES: Embora a convulsão febril (CF) seja geralmente considerada benigna e autolimitada, existem diferenças nos fatores de risco, prognóstico e desenvolvimento de epilepsia. OBJETIVO: O objetivo foi examinar as características clínicas e sociodemográficas de pacientes diagnosticados com CF e determinar os riscos de recorrência e desenvolvimento de epilepsia. MéTODOS: Trezentos pacientes com CF, acompanhados por pelo menos 24 meses, foram avaliados retrospectivamente entre 2015 e 2020. RESULTADOS: A primeira CF foi simples em 72,7% dos pacientes e complexa em 27,3%. CS foi recorrente em 40% dos pacientes. Encontrou-se que a idade da primeira CF inferior a 12 meses, CF complexa e atraso no neurodesenvolvimento aumentaram estatisticamente o risco de recorrência (p < 0,05). Epilepsia se desenvolveu em 7% dos pacientes. A epilepsia foi maior em pacientes com atraso no desenvolvimento neurológico e uso prolongado de drogas antiepilépticas (p < 0,001). A epilepsia se desenvolveu em 77,8% dos pacientes com eletroencefalograma (EEG) anormal. Uma diferença estatisticamente significativa foi determinada em pacientes com EEG anormal em risco de epilepsia (p < 0,001). CONCLUSõES: O atraso no neurodesenvolvimento foi um importante fator de risco para recorrência de CF e epilepsia. A anormalidade do EEG é um importante fator de risco para o desenvolvimento de epilepsia. O tratamento de profilaxia a longo prazo não diminuiu a recorrência de CS e o desenvolvimento de epilepsia.

Risk factors for acute encephalitis and early seizure recurrence in complex febrile seizures.

The purpose of this study is to elucidate risk factors for central nervous system infection and early seizure recurrence in children with febrile seizures (FSs) and thus facilitate outpatient management of complex FS. This single-center, retrospective cohort study investigated 688 children (6-60 months old) with FSs in Japan during 2011-2021. We investigated the incidence and clinical manifestations of children with acute encephalitis or bacterial meningitis. Logistic regression modeling was used to examine risk factors for seizure recurrence within 24 h. Among children with recurrent FSs, the distribution of intervals between first and second FS was assessed. Among 145 children with complex FSs, 2 patients (1.4%) had acute viral encephalitis and none had bacterial meningitis. Acute encephalitis was found in 2 of 8 patients (25%) with FSs prolonged ≥30 min and 2 of 3 patients (67%) requiring ≥2 intravenous anticonvulsants to stop seizures. Seizure recurrence within 24 h was observed in 16% of participants and was independently associated with preceding use of diazepam and family history of FS. In 82% of patients with FS recurrence within 24 h, early recurrences occurred within 8 h of the first seizure.      Conclusion: Patients with prolonged or refractory FSs are still indicated for hospital admission due to the risk of acute encephalitis. FS patients with a family history of FS may be managed safely by 8-h observation or single-dose rectal diazepam as prophylaxis against early recurrent seizure. What is Known: • Hospitalization has been recommended for children with complex febrile seizures due to the increased risk of central nervous infections. • Recent studies showed low incidences of bacterial meningitis (<1%) in children with complex febrile seizures in the presence of routine immunization. What is New: • Acute encephalitis was identified in 1.4% of children with complex febrile seizures, characterized by prolonged seizures ≥30 min and refractory seizures. • Early recurrent seizures may be safely managed by prophylactic diazepam or 8-h expectant observation.

Liraglutide Is Protective against Brain Injury in Mice with Febrile Seizures by Inhibiting Inflammatory Factors.

The febrile seizure (FS) is a common disease in emergency pediatrics, and about 30% of patients are children aged between 6 months and 5 years. Therefore, we aim to observe the protective impact of liraglutide (LIR) on brain injury in mice with FS and to explore its relevant mechanisms. Male SD mice were selected, and the FS model was established by heat bath method. The behavioral score was performed on mice with Racine grading, and nerve cells in apoptosis in the hippocampus were determined by TUNEL. The content of glutamate was determined by ELISA. mRNA levels and protein expression of GLP-1, GLP-1R, IL-1ß, IL-6, TNF-α, and cleaved-caspase 3 were examined in mice by q-PCR and WB. Protein expression of γ-aminobutyric acid was influenced by WB as well. LIR prolonged the seizure latency and seizure duration in mice with FS. The GLP-1 and GLP-1R in the mouse hippocampus with FS expressed highly and also inhibited the number of nerve cells in apoptosis, decreased glutamate content, and increased γ-aminobutyric acid expression in the mouse hippocampus with FS. In addition, The IL-1ß, IL-6, and TNF-α, in the mouse hippocampus with FS expressed to reduce with LIR. LIR is protective against brain injury in mice with FS and protects brain injury by inhibiting inflammatory factors in mice with FS. Our finding provides a reference for mitigating and delaying the development of FS as well as the prevention and treatment of brain injury caused by FS.

Febrile seizures: perceptions and knowledge of parents of affected and unaffected children.

Febrile seizures (FS) in children are common, but little is known about parents' perceptions and knowledge of FS. We interviewed parents of children aged 6 months to 6 years affected by FS (FS group, 65 parents) or unaffected (control group, 54 parents). In the FS group, 32% said they knew their child had an FS when the first event occurred, and 89% described fear when the child had a seizure, with a median intensity of 10/10 (Q25/Q75: 9/10). Related to follow-up, 77% in the FS group (will) observe their child more carefully after the first seizure happened, and 63% (will) give antipyretics earlier at a median temperature of 38.2 °C (100.8 °F). In the FS group, 62% were unaware of FS before the first event (54% of control group did not know about FS thus far, n.s.). In the FS group, 20% would put a solid object in the mouth of a child having a seizure (control group, 39%, p = 0.030), and 92% would administer an available anti-seizure rescue medication (control group, 78%, p = 0.019). In the FS group, 71% feared that children with FS might suffocate (control group, 70%, n.s.). CONCLUSION: Information about FS and their management should be more available to improve parents' coping and patient safety. WHAT IS KNOWN: • Febrile seizures in children are common. • The prognosis of children suffering from febrile seizures is usually rather good. WHAT IS NEW: • Over half of parents had not informed themselves about febrile seizures so far; and only 32% of parents realized their child had a febrile seizure when it occurred. • Most parents described own fear with a median intensity of 10/10; and 63% (will) give antipyretics earlier at a median temperature of 38.2 °C (100.8 °F).

Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.

BACKGROUND: Febrile Seizures (FS) are the most common seizures in children younger than 5 years. In the last decade, various coding and noncoding sequence variations of voltage-gated sodium channels SCN2A have been identified in patients with seizures, implying their genetic base. We aimed to evaluate the association between SCN2A c. G/A genetic polymorphism among Egyptian children with febrile seizure plus. METHODS: The present cross-sectional study was carried out on 100 epileptic infants and children, attendants of the Neurology Unit, pediatric department, Menoufia University Hospitals (Group Ι). The patients were sub-classified into two groups, according to response to anti-epileptic treatment; Group Ι a (drug responder) and Group Ι b (drug-resistant). Evenly divided number of apparently healthy, age and gender-matched children were selected as controls (Group II). A complete history, throughout the systemic examination and radiological & metabolic assessment, whenever needed was provided, all participants were genotyped for SCN2A rs17183814 polymorphism by Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Both of A allele and AA, GA genotypes of SCN2A c. 56 G/A were detected more in patients with febrile seizure plus comparison to the control group with a statistically significant difference at frequencies of 17% and 11% and 12% respectively; OR (CI95%): 10.04 (3.49-28.87) and p <0.001. On classifying epileptic patients into 2 subgroups, carriers of SCN2A rs17183814 AA genotype tended to respond poorly to Anti-epileptic Drugs (AEDs). Moreover, multivariate analysis revealed that rs17183814 A allele and positive family history of epilepsy were considered the highest predicted risk factors for the development of epilepsy; p<0.05. CONCLUSION: SCN2A rs17183814 (A) allele was specifically associated with developing febrile seizure plus and could modulate the patient's response to anti-epileptic medications.

Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice.

OBJECTIVE: Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) most often caused by de novo pathogenic variants in SCN1A. Individuals with Dravet syndrome rarely achieve seizure control and have significantly elevated risk for sudden unexplained death in epilepsy (SUDEP). Heterozygous deletion of Scn1a in mice (Scn1a+/- ) recapitulates several core phenotypes, including temperature-dependent and spontaneous seizures, SUDEP, and behavioral abnormalities. Furthermore, Scn1a+/- mice exhibit a similar clinical response to standard anticonvulsants. Cholesterol 24-hydroxlase (CH24H) is a brain-specific enzyme responsible for cholesterol catabolism. Recent research has indicated the therapeutic potential of CH24H inhibition for diseases associated with neural excitation, including seizures. METHODS: In this study, the novel compound soticlestat, a CH24H inhibitor, was administered to Scn1a+/- mice to investigate its ability to improve Dravet-like phenotypes in this preclinical model. RESULTS: Soticlestat treatment reduced seizure burden, protected against hyperthermia-induced seizures, and completely prevented SUDEP in Scn1a+/- mice. Video-electroencephalography (EEG) analysis confirmed the ability of soticlestat to reduce occurrence of electroclinical seizures. SIGNIFICANCE: This study demonstrates that soticlestat-mediated inhibition of CH24H provides therapeutic benefit for the treatment of Dravet syndrome in mice and has the potential for treatment of DEEs.

Zinc Supplementation for Prevention of Febrile Seizures Recurrences in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have documented lower serum zinc levels in patients with febrile seizures in comparison to febrile patients without seizure. However, there is limited evidence comparing the effects of zinc supplementation with placebo on recurrence of febrile seizures in children. OBJECTIVES: To study the effects of zinc supplementation on recurrence rate of febrile seizures in children less than 60 months of age. DESIGN: Systematic review and meta-analysis of randomized and quasi-randomized controlled trials. DATA SOURCE AND SELECTION CRITERIA: We searched PubMed, EMBASE and CENTRAL databases for articles reporting randomized or quasi-randomized controlled trials comparing the effects of zinc supplementation with placebo on recurrence of febrile seizures in children aged less than 60 months. We performed a fixed effect meta-analysis to provide pooled odds ratio of febrile seizure recurrence. Quality of evidence was assessed using GRADE approach. PARTICIPANTS: Children aged less than 60 months. INTERVENTION: Zinc supplementation. OUTCOME MEASURES: Odds of febrile seizure recurrence. RESULTS: Four clinical trials with a total of 350 children were included in the review. There was no statistically significant difference between odds of febrile seizure recurrence during one year follow up, in children on zinc supplementation compared to those on placebo (OR 0.70; 95% CI 0.41 - 1.18, I2 = 0%). CONCLUSIONS: Available evidence is very low quality and thus inadequate to make practice recommendations.

Acute encephalopathy with biphasic seizures and late reduced diffusion; posterior frontal hyperperfusion before late seizures revealed by arterial spin labeling: A case report.

BACKGROUND: Arterial spin labeling, a magnetic resonance imaging modality that can evaluate cerebral perfusion without using a contrast material or ionizing radiation, is becoming increasingly accessible. However, only a few reports have used this method to assess the perfusion abnormalities observed in acute encephalopathy with biphasic seizures and late reduced diffusion. PATIENT DESCRIPTION: A 10-month-old Japanese girl presented with febrile status epilepticus (early seizures). Her convulsions ceased after the administration of intravenous phenobarbital, although her impaired consciousness was protracted. Five days later, diffusion-weighted imaging revealed slightly high signal intensity lesions in the bilateral posterior frontal areas. Arterial spin labeling revealed bilateral frontal-dominant hypoperfusion and posterior frontal hyperperfusion. On day 6, she had three convulsions (late seizures) and was diagnosed with acute encephalopathy with biphasic seizures and late reduced diffusion. She received treatment accordingly and recovered eventually. DISCUSSION: Based on previous reports, hypoperfusion within 1-2 days of early seizures and hyperperfusion accompanied by bright tree appearance on diffusion-weighted imaging within 1-2 days of late seizures are typical in acute encephalopathy with biphasic seizures and late reduced diffusion. In our patient, the first magnetic resonance imaging scan was performed one day prior to the onset of late seizures. We observed posterior frontal hyperperfusion accompanied by high signals on diffusion-weighted imaging, which leads us to speculate that this could be a predictive marker of late seizures.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology.

OBJECTIVE: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription that can be effective in treating febrile seizures (FS) and there are few research works conducted on its mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. MATERIALS AND METHODS: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS is obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software, the potential core compounds and targets of FS were obtained. The R language and ClusterProfiler software package are adopted to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets are also revealed. RESULTS: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened, which were involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS in regulating FS in the pathogenesis and the therapeutic mechanism of FS were discussed and clarified. CONCLUSION: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS were preliminarily screened through the analysis of network pharmacology data, which are consistent with the principle of multi-compounds' compatibility with TCM prescriptions and a unified treatment of diseases from multiple aspects, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Use of antipyretics for preventing febrile seizure recurrence in children: a systematic review and meta-analysis.

The efficacy of antipyretics for preventing febrile seizure recurrence has been reported by a recent study, and the results might overturn previous evidence. We systematically reviewed the efficacy of antipyretics in the prevention of febrile seizure recurrence in children focused on the timing of its administration. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases for randomized and quasi-randomized trials and prospective non-randomized studies of aged up to 60 months, diagnosed with febrile seizure, who were treated with antipyretics. Data were extracted from eight studies. Only one study reported that antipyretics prevented the recurrence of febrile seizures within the same fever episode (9.1% in the acetaminophen group vs. 23.5% in the control group, p < 0.01). Four studies found no evidence for the efficacy of antipyretics in preventing febrile seizure recurrence in distant fever episodes (odds ratio, 0.92; 95% confidence interval, 0.57-1.48, for two randomized controlled studies).Conclusion: This review provides very limited support for the use of antipyretics in preventing febrile seizure recurrence within the same fever episode and no evidence for its use in distant fever episodes. New studies are required to evaluate this topic further and determine whether the effectiveness of antipyretics is based on intervention timing. What is Known: • Reviews of prophylactic drug management among febrile seizure children found that antipyretics had no significant benefits. • Recent data suggest that antipyretics are effective in preventing febrile seizures. What is New: • Weak evidence suggests a possible role in preventing febrile seizure recurrence within the same fever episode. • There is clearly no role for antipyretic prophylaxis in preventing febrile seizures during distant fever episodes.

Anti-convulsant effects of cultures bear bile powder in febrile seizure via regulation of neurotransmission and inhibition of neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural bear bile powder (NBBP) has been used to treat seizures for thousands of years, but its application is greatly restricted due to ethical reasons. Cultured bear bile powder (CBBP), which is produced by biotransformation, may be an appropriate substitute for NBBP. However, the anti-convulsant effects of CBBP and its mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate the anti-convulsant effects and possible mechanisms of CBBP in a febrile seizure (FS) rat model. MATERIALS AND METHODS: FS was induced by placing the rats in a warm water bath (45.5 °C). The incidence rate and latency of FS, and hematoxylin-eosin staining (HE) were conducted for neurological damage. The levels of 4 bile acids and 8 main neurotransmitters in vivo were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The expression of bile acid related transports, neurotransmitter receptors, inflammatory factors, neurotrophic factors and glial fibrillary acidic protein (GFAP) in hippocampal tissues were detected by real-time PCR, western blotting, and immunohistochemistry. RESULTS: Pre-treatments with CBBP and similarly, NBBP, significantly reduced the incidence rate and prolonged the latency of FS. Additionally, CBBP alleviated the histological injury induced by FS in the rat hippocampus tissue. LC-MS/MS analyses revealed that CBBP markedly increased the levels of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) in FS rats. Furthermore, the content of gamma-aminobutyric acid (GABA) was up-regulated in rats pre-treated with CBBP whereas GFAP was down-regulated. CBBP also significantly suppressed the expression of interleukin -1ß (IL-1ß), tumor necrosis factor α (TNF-α), nuclear factor kappa B (NF-κB), and brain-derived neurotrophic factor (BDNF) and its TrkB receptors, and improved the expression of GABA type A receptors (GABAAR) and farnesoid X receptors (FXR). CONCLUSIONS: The present study demonstrated that CBBP had anti-convulsant effects in a FS rat model. CBBP may protect rats against FS, probably by up-regulating FXR, which was activated by increasing brain bile acids, up-regulating GABAergic transmission by inhibiting BDNF-TrkB signaling, and suppressing neuroinflammation by inhibiting the NF-κB pathway.