Recurrent Seizures Research Articles

Early versus late switch over of antiseizure medications from intravenous to the oral route in children with seizures: Single-blinded, randomized controlled trial (ELAIO trial)

IntroductionEarly switch-over of anti-seizure medications (ASMs) from intravenous to oral route may reduce the duration of hospitalization, drug acquisition costs, and behavioral upset in hospitalized children with seizures. ObjectiveThe primary objective was to compare short-term seizure recurrence within 1 week in hospitalized children aged 1 month to 18 years with new-onset/breakthrough seizures after an early versus late switch-over from intravenous to the oral route of ASMs. Secondary objectives were to compare the incidence of status epilepticus, duration of hospital stay, drug acquisition costs, and caregiver-reported satisfaction scores in both groups. MethodsIn this single-blind randomized controlled trial, patients with seizures were categorized based on the number of ASMs required and the history of status epilepticus. Patients in each category were randomized in a 1:1 ratio into either early or late switch-over (ES or LS) groups. In the ES groups, ASMs were tapered one-by-one between 0 and 24 hours of seizure freedom, while in the LS groups, they were tapered one-by-one between 24 and 48 hours of seizure freedom. ResultsA total of 112 children were enrolled in the study, with 56 in each arm. Seizure recurrence at 1 week and 12 weeks was comparable in ES and LS groups (3/55 vs. 1/54 at 1 week, p=0.61; 7/49 vs. 6/49 at 12 weeks, p=0.98). Drug acquisition costs were significantly lower in the ES group (393±274 vs. 658±568 INR, p=0.002). Thrombophlebitis and dysphoria were significantly more common in the LS group (p=0.008 and 0.03, respectively). ConclusionThe early switch-over of ASMs from intravenous to oral route is safe without any significant increased risk of short-term seizure recurrence and also associated with a reduction in the incidence of thrombophlebitis and ASM acquisition costs. Trial registration NoCTRI/2021/03/032145

Investigating the Effects of Perampanel on Autophagy-mediated Regulation of GluA2 and PSD95 in Epilepsy.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite various treatment approaches, a significant number of patients continue to experience uncontrolled seizures, leading to refractory epilepsy. The emergence of novel anti-epileptic drugs, such as perampanel (PER), has provided promising options for effective epilepsy treatment. However, the specific mechanisms underlying the therapeutic effects of PER remain unclear. This study aimed to investigate the intrinsic molecular regulatory mechanisms involved in the downregulation of GluA2, a key subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, following epileptic seizures. Primary mouse hippocampal neurons were cultured and subjected to an epilepsy cell model. The expression levels of GluA2 and autophagy-related proteins were assessed using Western blotting and real-time fluorescent quantitative PCR. Immunofluorescence and immunohistochemistry techniques were employed to investigate the nuclear translocation of CREB-regulated transcriptional coactivator 1 (CRTC1). Additionally, status epilepticus animal models were established to further validate the findings. The epilepsy cell model exhibited a significant decrease in GluA2 expression, accompanied by elevated levels of autophagy-related proteins. Immunofluorescence analysis revealed the nuclear translocation of CRTC1, which correlated with the expression of autophagy-related genes. Treatment with an autophagy inhibitor reversed the decreased expression of GluA2 in the epilepsy cell model. Furthermore, the calcium/calmodulin-dependent protein phosphatase inhibitor FK506 and CaN overexpression affected the dephosphorylation and nuclear translocation of CRTC1, consequently influencing GluA2 expression. Animal model results further supported the involvement of these molecular mechanisms in epilepsy. Our findings suggest that the downregulation of GluA2 following epileptic seizures involves the activation of autophagy and the regulation of CRTC1 nuclear translocation. These intrinsic molecular regulatory mechanisms provide potential targets for developing novel therapeutic strategies to alleviate refractory epilepsy and preserve cognitive functions in patients.

Biochemical, structural, and computational analyses of two new clinically identified missense mutations of ALDH7A1

Aldehyde dehydrogenase 7A1 (ALDH7A1) catalyzes a step of lysine catabolism. Certain missense mutations in the ALDH7A1 gene cause pyridoxine dependent epilepsy (PDE), a rare autosomal neurometabolic disorder with recessive inheritance that affects almost 1:65,000 live births and is classically characterized by recurrent seizures from the neonatal period. We report a biochemical, structural, and computational study of two novel ALDH7A1 missense mutations that were identified in a child with rare recurrent seizures from the third month of life. The mutations affect two residues in the oligomer interfaces of ALDH7A1, Arg134 and Arg441 (Arg162 and Arg469 in the HGVS nomenclature). The corresponding enzyme variants R134S and R441C (p.Arg162Ser and p.Arg469Cys in the HGVS nomenclature) were expressed in Escherichia coli and purified. R134S and R441C have 10,000- and 50-fold lower catalytic efficiency than wild-type ALDH7A1, respectively. Sedimentation velocity analytical ultracentrifugation shows that R134S is defective in tetramerization, remaining locked in a dimeric state even in the presence of the tetramer-inducing coenzyme NAD+. Because the tetramer is the active form of ALDH7A1, the defect in oligomerization explains the very low catalytic activity of R134S. In contrast, R441C exhibits wild-type oligomerization behavior, and the 2.0 Å resolution crystal structure of R441C complexed with NAD+ revealed no obvious structural perturbations when compared to the wild-type enzyme structure. Molecular dynamics simulations suggest that the mutation of Arg441 to Cys may increase intersubunit ion pairs and alter the dynamics of the active site gate. Our biochemical, structural, and computational data on two novel clinical variants of ALDH7A1 add to the complexity of the molecular determinants underlying pyridoxine dependent epilepsy.

Are Recurrent Focal Seizures or Focal Status Epilepticus in Older Adults a Risk Factor for Early Mortality? (P4-1.013)

Are Recurrent Focal Seizures or Focal Status Epilepticus in Older Adults a Risk Factor for Early Mortality? (P4-1.013)

Lack of Direct Effects of Neurotrophic Factors in an In Vitro Model of Neuroinflammation.

Neuroinflammation is associated with several neurological disorders including temporal lobe epilepsy. Seizures themselves can induce neuroinflammation. In an in vivo model of epilepsy, the supplementation of brain-derived neurotropic factor (BDNF) and fibroblast growth factor-2 (FGF-2) using a Herpes-based vector reduced epileptogenesis-associated neuroinflammation. The aim of this study was to test whether the attenuation of the neuroinflammation obtained in vivo with BDNF and FGF-2 was direct or secondary to other effects, for example, the reduction in the severity and frequency of spontaneous recurrent seizures. An in vitro model of neuroinflammation induced by lipopolysaccharide (LPS, 100 ng/mL) in a mouse primary mixed glial culture was used. The releases of cytokines and NO were analyzed via ELISA and Griess assay, respectively. The effects of LPS and neurotrophic factors on cell viability were determined by performing an MTT assay. BDNF and FGF-2 were tested alone and co-administered. LPS induced a significant increase in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NO. BDNF, FGF-2, and their co-administration did not counteract these LPS effects. Our study suggests that the anti-inflammatory effect of BDNF and FGF-2 in vivo in the epilepsy model was indirect and likely due to a reduction in seizure frequency and severity.

Assessing the outcome of drug therapy in adult patients with epilepsy who have experienced seizure recurrence after remission

Background. Remission in general sense means disappearance of signs and symptoms of the disease. The risk of recurrence of seizures is usually evaluated only in terms of the risk of a second unprovoked seizure after the first one or the risk of recurrence of seizures after discontinuation of therapy. There are no studies that assess the probability of achieving a second remission in patients with recurrent seizures.Aim. To develop a tool for assessing the probability of favorable and unfavorable treatment outcomes after recurrent seizures in adult patients with different forms of epilepsy.Materials and methods. We analyzed data from 215 patients with recurrent seizures after achieving remission, followed up for 12 or more months, and analyzed disease outcomes.Results and conclusion. At the end of the study, repeat remission was observed in 67 patients, improvement in 48, and no effect in 100. Patients with remission and improvement were combined into a “favorable outcome” group (n = 115), while patients with no effect from therapy formed an “unfavorable outcome” group (n = 100).Patients with an unfavorable outcome were statistically significantly more likely to have factors such as longer disease duration, coexisting serious somatic diseases, structural etiology of epilepsy, bilateral tonic-clonic seizures with focal onset, focal forms of epilepsy, daily seizures, epileptogenic changes on neuroimaging, and regional epileptiform activity on EEG (p <0.05). In turn, patients with a favorable outcome were statistically significantly more likely to have factors such as genetic etiology of epilepsy, generalized tonic-clonic seizures, absences, myoclonic seizures, generalized forms of epilepsy, no pathology on neuroimaging, diffuse epileptiform activity on electroencephalogram, and no pathology on electroencephalogram (p <0.05).Based on the obtained data using the results of constructing contingency tables, a scale for assessing the probability of achieving repeat remission in patients with recurrent epileptic seizures was developed, consisting of 9 sections. To assess the effectiveness of the model, ROC analysis was performed, confirming statistically significant sensitivity and specificity of the obtained scale.Further research is needed to develop more accurate predictors of epilepsy outcomes to understand the peculiarities of the disease pathogenesis.

Latarjet operation carries three times the risk of failure in seizure versus non-seizure recurrent anterior dislocation of the shoulder joint: outcome of a systematic review with meta-analysis.

Recurrent anterior shoulder dislocation (RASD) in cases of seizure disorders (SDs) total 50%-80% of all SD-associated shoulder instabilities. Based on the extent of bone loss, treatment options include bony and soft-tissue reconstructions, arthroplasty, and arthrodesis. The primary objective of this paper was to review the treatment options for RASD in SDs. Several bibliographic databases were searched for RASD treatment options in SD patients. The demographic outcome measures, the failure rate (defined as the relative risk of recurrence of dislocation postoperation), and the postoperative seizure recurrence rate were recorded. We pooled 171 cases (187 shoulders) from 11 studies. Of these, one, five, two, two, and one reports studied Bankart's operation with remplissage (27 cases/29 shoulders), the Latarjet procedure (106/118), bone block operation (21/23), arthroplasty (11/11), and arthrodesis (6/6), respectively, in treating SD-associated RASD. The relative risk of failure between SD and non-SD patients was 3.76 (1.3610.38) after the Latarjet operation. The failure rates were 17% and 13% for Bankart's operation with remplissage and the Latarjet procedure in SD patients, respectively, but 0% each for bone block operation, arthroplasty, and arthrodesis. The total rate of seizure recurrence after operation was 33% of the pooled cases. SD recurrence in the postoperative period, the size of the bone block, and the muscular attachments to a small coracoid autograft are the determinants of failure among various reconstructive operations in SD-associated RASD. Level of evidence: III.

Case Study Application of Warm Compresses to Reduce Hyperthermia in Children with Febrile Seizures

Children are more susceptible to infectious diseases, which often cause high fever. When the fever experiences a continuous increase in temperature above 380C, it will result in febrile seizures in children. Recurrent and untreated febrile seizures can have long-term impacts, such as neurological and behavioral disorders, and can increase the mortality rate in children. This research contributed to applying warm compresses to reduce hyperthermia. The research design uses a descriptive method with a case study approach with one research sample. This research uses a bleeding maintenance process approach starting from assessment, diagnosis, intervention, implementation, and evaluation. The research results showed a case study of a child patient with febrile seizures who had problems with hyperthermia on the first day. An assessment was carried out on the first day; the body temperature was measured at 38.50C (the skin looked reddish and felt warm), and I had one seizure. The interventions and implementation provided to children are based on SIKI standards (Indonesian Nursing Intervention Standards). The nursing implementation in this case study was planned to overcome the problem of hyperthermia by applying warm compresses. Warm compresses are applied for three days, lasting 30 minutes and 2 hours before administering the drug. Implementation was carried out on February 20–22, 2023. After hyperthermia management, temperature regulation, and warm compresses on the third day of evaluation, the results showed a temperature of 36.5 °C with no recurrent seizures occurring. The conclusion is that there is a significant change due to the effect of warm compresses on reducing body temperature in pediatric patients with hyperthermia in cases of febrile seizures.

Insights into epileptogenesis from post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies.

Association between dietary carbohydrate intake percentage and epilepsy prevalence in the NHANES 2013–2018: a cross-sectional study

ABSTRACT Background Epilepsy 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. Methods 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. Results 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). Conclusions 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.

Evaluation of Anti-epileptic Activity of Leaves of Leucas Cephalotes

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting millions of people worldwide. Despite advancements in therapeutic interventions, there remains a need for novel and effective treatments with fewer side effects. This study aimed to evaluate the anti-epileptic potential of Leucas cephalotes leaves through experimental models. The leaves of Leucas cephalotes were collected, dried, and subjected to extraction using suitable solvents. The obtained extract was then evaluated for acute toxicity using standard guidelines. Subsequently, anti-epileptic activity was assessed using chemically induced seizure models in rodents. Behavioral observations, seizure latency, duration, and severity were recorded to determine the extract's efficacy. Preliminary phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, terpenoids, and phenolic compounds, which are known for their neurological effects. Acute toxicity testing indicated the safety of the extract at tested doses. In seizure models, the extract demonstrated a significant increase in seizure latency, reduction in seizure duration, and alleviation of seizure severity compared to control groups. These findings suggest that the leaves of Leucas cephalotes possess anti-epileptic properties, possibly attributed to the presence of bioactive compounds. Further studies are warranted to elucidate the underlying mechanisms and optimize dosage regimens for clinical application. Leucas cephalotes could emerge as a promising natural source for developing anti-epileptic agents with improved safety profiles.

Literature review and protocol for a prospective multicentre cohort study on multimodal prediction of seizure recurrence after unprovoked first seizure

IntroductionEpilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive...

Hashimoto's encephalitis - A case report

A 50 year-old woman with a background of focal epilepsy presented to Emergency Department (ED) in convulsive status epilepticus.After 1 year seizure-free on levetiracetam,she initially presented with headache, tremor, fatigue and general malaise. She was discharged, then re-presented to ED several days later in status epilepticus. Two doses of diazepam administered pre-hospital failed to terminate the seizure. She was loaded with phenytoin,intubated and ventilated and commenced on a midazolam infusion. She spent 7 days in neuro-intensive care and was discharged home on levetiracetam 1.5 g twice daily and phyentoin 250 mg twice daily.One month later, she re-presented to ED with 4 days of worsening tremors and reduced mobility. Physical examination revealed multifocal myoclonus. She had experienced significant cognitive decline and neuropsychiatric symptoms including severe anxiety, delusions and paranoia.InvestigationsImagingInitial MRI head with gadolinium showed marked symmetric abnormality within the white matter of both hemispheres extending into subcorticol regions, most predominant at the vertex and involving U fibres. The neuro-radiologist commented that the differential for these changes was broad, including an encephalitis, PML, meningitis or a leukoencephalopathy.Repeat MRI head 1 month later showed complete resolution of the white matter changes leaving no sequelae.Blood testsHer past medical history included subclinical hypothyroidism. Thyroid function tests showed an elevated TSH of 21.33 and thyroid peroxidase(TPO) antibody level of 188.0 IU/mL, with FT4 levels within normal range.Extensive relevant blood screen, including the following was all negative• NMDA, glycine receptor and anti-cardiolipin antibody• Connective tissue screen, anti-MPO and anti-PR3• Serum electrophoresis• Paraneoplastic antibody screen including Cerebellum IIF, MA2, MA1, amphiphysin, CV2(CRMP5), Anti-Ri (ANNA 2) Ab, Anti Yo Ab and Anti Hu Ab• HIV and syphilis serology• JC virus• Plasma amino acid, urine organic acid and ammoniaLumbar punctureCSF WCC 1/mm3CSF protein- 816 mg/LCSF viral PCR (including JC virus) and oligoclonal bands negativeEEG- normal background activity with no clear focal or diagnostic epileptiform abnormalities.Treatment and follow-upThe clinical picture, elevated TPO antibodies and absence of other relevant investigation abnormality raised Hashimoto's encephalitis as a potential unifying diagnosis. She had a good response to inpatient treatment with steroids, her neuropsychiatric features resolved and she has remained seizure-free since discharge. She remains under neurology outpatient follow-up.Discussion:It can be challenging to make a diagnosis of Hashimoto encephalitis, and other potential causes such as infection, metabolic or paraneoplastic processes must be rigorously ruled out (1). In this case, high titres of TPO alongside the clinical presentation with recurrent seizures and cognitive decline were key in making the diagnosis (2,3). Due to an overlap of features, including myoclonus and rapid cognitive decline, it was important to consider Creutzfeldt-Jakob disease (CJD) in the differential. We ruled out CJD due to the rapid response to steroid therapy and lack of typical EEG and MRI findings (4). Overall, due to low prevalence and non-specific MRI and EEG features, this diagnosis can be difficult to make and requires thorough systemic clinical assessment.

Clinical characteristics and impact of comorbidities on the prognosis of senile epilepsy in Southwest China: a retrospective cohort study

BackgroundSenile epilepsy and its comorbidities pose a tremendous burden on patients and the society. This study was aimed to investigate the clinical characteristics and comorbidities of senile epilepsy, as well as the impact of comorbidities on the prognosis of senile epilepsy.MethodsInformation of patients with senile epilepsy was retrospectively collected from three tertiary hospitals in Southwest China between December 2014 and December 2022. A total of 154 patients met the inclusion criteria and were divided into two groups based on the presence or absence of comorbidities. The prevalence, type, characteristics, and impacts of the comorbidities were investigated. The characteristics of patients with and without comorbidities were also compared.ResultsEighty-one percent of patients with senile epilepsy had at least one comorbidity, and 36% had three or more comorbidities. Eighteen different types of comorbidities were identified. The most common comorbidities were neurological (61%), followed by cardiovascular (45%) and psychiatric (26%) comorbidities. More than one-third of patients had bidirectional comorbidities, whereas more than half of the patients had additional causal comorbidities. Among all types of comorbidities, neurological and psychiatric comorbidities were found to be associated with an increased risk of recurrent seizures. Compared to patients without bidirectional comorbidities, those with at least one bidirectional comorbidity had a lower rate of achieving seizure freedom. The higher the number of bidirectional comorbidities, the lower the seizure-free rate. Survival analysis revealed that patients with neurological comorbidities had a higher risk of death.ConclusionsThis study revealed a high comorbidity rate and a low seizure-freedom rate among patients with senile epilepsy. In particular, neuropsychiatric comorbidities can increase the risk of seizures and affect the survival rate of patients with senile epilepsy. Therefore, preventing and managing these comorbidities may improve seizure outcomes and reduce mortality in this special population.

Public Awareness of Epilepsy and Social Attitude Toward Persons With Epilepsy Among the General Population in Makkah, Saudi Arabia.

Epilepsy is a common neurological disorder characterized by an ongoing propensity to experience recurrent seizures. Public awareness varies significantly across different countries. The lack of awareness may lead to misconceptions, which in turn may affect the quality of care for these patients. This study aims to assess public awareness and social attitudes toward patients with epilepsy among the general population in Makkah, Saudi Arabia. A questionnaire-based cross-sectional study was conducted, targeting the general population of Makkah, Saudi Arabia. Data were collected anonymously fromparticipants who met our inclusion criteria via electronic data collection Google Forms distributed through social media platforms. Questionnaires included participants' demographic data and details about their awareness regarding epilepsy, attitude, and anticipated behaviors. The eligible persons were asked to fill out the study questionnaire completely. A total of 1,126 eligible participants completed the study questionnaire. The participants' ages ranged from 18 to over 60, with a mean age of 32.1 ± 13.9 years. Of these participants, 849 (75.4%) were female. Interestingly, 97% of the participants reported that they had heard about epilepsy. A total of 96.7% do not think epilepsy is contiguous. Exactly 350 (31.1%) had an overall good knowledge and awareness regarding epilepsy. The most reported sources included relatives/friends (46.8%), internet (38.5%), and personal experience (27.9%). A total of 337 (29.9%) reported that they know how to deal with a seizure. Our study revealed that the sampled population of Makkah is aware of epilepsy on a superficial level, but approximately one out each three participants in Makkah were knowledgeable regarding epilepsy and related causes overall. The overall attitude is positive. A well-targeted educational campaign, designed by physicians as trustful sources, is recommended.

COMPARISON OF INTRAVENOUS DIAZEPAM AND INTRAVENOUS MIDAZOLAM FOR TREATMENT OF RECURRENT FEBRILE SEIZURES

Background: Recurrent febrile seizures are seizures in children less than 5 years of age which reoccur within 24 hours. Benzodiazepines such as midazolam and diazepam are used to stop and decrease the recurrent rate of febrile seizures. The objective of study was to compare the efficacy of intravenous midazolam with intravenous diazepam for treatment of recurrent febrile seizures in paediatric patients. Methods: This observational cross-sectional study observed 60 children aged 6 to 59 months with recurrent febrile seizures who presented at paediatric clinic in Combined Military Hospital Kharian and THQ Hospital, Kharian from Sep to Nov 2023. The response time was noted for children who received intravenous midazolam 0.2 mg/Kg only and IV diazepam 0.2 mg/Kg only. The children were randomly allocated into group A (midazolam group) and Group B (diazepam group.) Study was done after taking informed consent from the parents. Both drugs were given during the fits. Results: The time interval from drug administration to cessation of febrile seizures was 2.50±0.94 minutes in the midazolam group and 2.4±1.12 minutes in the diazepam group. There was no significant difference between the two groups (p=0.567). Minor dizziness and sedation were the only main effects reported. Conclusion: Both diazepam and midazolam have same efficacy in the treatment of recurrent febrile seizures. Pak J Physiol 2024;20(1):12?4

A Rare Case of Pial Arteriovenous Fistula in an Infant – A Case Report

Introduction: Pial arteriovenous fistula (PAVF) is a rare intracranial vascular malformation with diverse clinical presentations. Early diagnosis and intervention are crucial due to its poor natural history. Endovascular treatment has emerged as a preferred option with promising results. Case Report: We report a case of an 8-month-old infant who presented with recurrent focal seizures and acute intraparenchymal hematoma. Further investigation with magnetic resonance angiography and digital subtraction angiography confirmed the presence of a PAVF. Results: Endovascular embolization successfully obliterated the PAVF with no postprocedural complications. Clinical follow-up demonstrated a favorable outcome. Conclusion: This case highlights the significance of early detection through suitable imaging modalities and timely intervention in preventing life-threatening complications associated with PAVFs. Endovascular embolization offers an effective and safe treatment option for pediatric PAVFs, leading to positive outcomes in this rare entity.

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy.

Epilepsy is a multifaceted neurological syndrome characterized by recurrent, spontaneous, and synchronous seizures. The pathogenesis of epilepsy, known as epileptogenesis, involves intricate changes in neurons, neuroglia, and endothelium, leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy. Although current research on epilepsy treatments primarily centers around anti-seizure drugs, it is imperative to seek effective interventions capable of disrupting epileptogenesis. To this end, a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets. Emphasizing early diagnosis and timely intervention is paramount, as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden. In this review, we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

Sorbs2 regulates seizure activity by influencing AMPAR-mediated excitatory synaptic transmission in temporal lobe epilepsy

Temporal lobe epilepsy (TLE), the most common type of drug-resistant epilepsy, severely affects quality of life. However, the underlying mechanism of TLE remains unclear and deserves further exploration. Sorbs2, a key synaptic regulatory protein, plays an important role in the regulation of synaptic transmission in the mammalian brain. In this study, we aimed to investigate the expression pattern of Sorbs2 in a kainic acid (KA)-induced TLE mouse model and in patients with TLE to further determine whether Sorbs2 is involved in seizure activity and to explore the potential mechanism by which Sorbs2 affects seizures in this TLE mouse model. First, we found that the expression of Sorbs2 was obviously increased in the hippocampus and cortex of a TLE mouse model and in the temporal cortex of TLE patients, indicating an abnormal expression pattern of Sorbs2 in TLE. Importantly, subsequent behavioral analyses and local field potential (LFP) analyses of a TLE mouse model demonstrated that the downregulation of hippocampal Sorbs2 could prolong the latency to spontaneous recurrent seizures (SRSs) and protect against SRSs. We also found that the knockdown of Sorbs2 in the hippocampus could decrease excitatory synaptic transmission in pyramidal neurons (PNs) in the hippocampal CA1 region and reduce the expression levels of the AMPAR subunits GluA1 and GluA2. Thus, we speculated that Sorbs2 may promote epileptogenesis and the development of TLE by affecting AMPAR-mediated excitatory synaptic transmission in PNs in the CA1 region. Therefore, reducing the expression of hippocampal Sorbs2 could restrain epileptogenesis and the development of TLE.

First seizure in elderly patients: Need to treat? Evidence from a retrospective study

BackgroundThe risk of seizure recurrence after a first unprovoked epileptic seizure is reported to be approximately 40%. Little is known about the recurrence risk after a first seizure in elderly patients, who may be at higher risk due to an increased rate of structural lesions, encephalopathy, subcortical arteriosclerotic encephalopathy or brain atrophy.MethodsIn a retrospective approach, the recurrence rate in 304 patients aged 60 years and above who presented with a first seizure between 2004 and 2017 was analyzed. Hierarchical Cox regression was used to investigate the impact of EEG and neuroimaging results, age or the prescription of anti-seizure medication (ASM) on seizure recurrence.ResultsSeizure recurrence rates were 24.5% and 34.4% after one and two years, respectively. Anti-seizure medication was started in 87.8% of patients, in 28.8% despite the absence of clear epileptogenic lesions on neuroimaging or epileptiform potentials in the EEG. Medical treatment significantly reduced the risk of recurrence (hazard ratio = 0.47). Epileptiform potentials in the EEG, epileptogenic lesions in neuroimaging and age had no significant effect on seizure recurrence. Age and the presence of neurodegenerative and psychiatric comorbidities showed a significant association with ASM prescription.ConclusionsThe present data show a strong protective effect of ASM on seizure recurrence in patients above the age of 60, even in the absence of pathologic neuroimaging or EEG results needed for the diagnosis of epilepsy. Treatment with ASM therefore seems beneficial for reducing the recurrence risk in elderly patients. The lack of a significant association between seizure recurrence and epileptogenic lesions might be related to other confounding factors like encephalopathy, subcortical arteriosclerotic encephalopathy, neurodegenerative diseases or brain atrophy.