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There is currently no efficacious intervention for preventing post-traumatic epilepsy (PTE). Preclinical studies support the potential use of anticholinergics for this condition. The purpose of this study was to evaluate the effects of biperiden as an intervention for preventing PTE. A randomized, double-blinded clinical trial was conducted at HC/FMUSP between 2018–2022. Adults with acute traumatic brain injury (TBI) were randomly assigned to receive biperiden or placebo, for 10 days. The primary outcome was the incidence of PTE while the secondary outcomes included the frequency of seizures, the frequency of any adverse events and mortality after 24 months. The study was powered at a planned enrolment of 132 patients. The trial began in January 2018 and was halted by researchers on March 2020 (and terminated in December 2022) in the face of the global COVID-19 pandemic. Overall, 123 participants were randomized and 112 contributed with data for modified mITT analysis, being that 61 (49.5%) participants completed the 24-month follow-up consult. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65–10.57; p = 0.170) or the mortality rate (1.57, 95%CI, 0.73–3.38; p = 0.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912–3.1597; p

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological disease with an unknown incidence. The manifestations of DDMS are variable, while typical symptoms are seizures, hemiparesis, and mental retardation. Here, we present a case involving a 19-year-old male patient who presents with headaches, mood changes, and a history of seizures during childhood. Based on the neuroimages, a diagnosis of DDMS was established. The application of sertraline hydrochloride as a therapeutic intervention has alleviated the symptoms. This case report illustrates the importance of understanding the clinical features of DDMS based on imaging.

The metabotropic glutamate receptor 7 (mGluR7) is a presynaptic G-protein-coupled glutamate receptor that modulates neurotransmitter release and synaptic plasticity at presynaptic terminals. It is encoded by GRM7, and recently variants have been identified in patients with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay (DD), intellectual disability (ID), and brain malformations. To gain updated insights into the function of GRM7 and the phenotypic spectrum of genetic variations within this gene, we conducted a systematic review of relevant literature utilizing PubMed, Web of Science, and Scopus databases. Among the 14 articles meeting the inclusion criteria, a total of 42 patients (from 28 families) harboring confirmed mutations in the GRM7 gene have been documented. Specifically, there were 17 patients with heterozygous mutations, 20 patients with homozygous mutations, and 5 patients with compound heterozygous mutations. Common clinical features included intellectual behavioral disability, seizure/epilepsy, microcephaly, developmental delay, peripheral hypertonia and hypomyelination. Genotype-phenotype correlation was not clear and each variant had unique characteristics including gene dosage, mutant protein surface expression, and degradation pathway that result with a spectrum of phenotype manifestations through ASD or ADHD to severe DD/ID with brain malformations. Neuroinflammation may play a role in the development and/or progression of GRM7-related neurodegeneration along with excitotoxicity. The clinical and functional data presented here demonstrate that both autosomal dominant and recessive inheritance of GRM7 mutation can cause disease spectrum phenotypes through ASD or ADHD to severe DD/ID and seizure with brain malformations.

Introduction: Epilepsy is a widespread disease requiring long-term drug treatment. The aim of this study was to collect information on reported suspected adverse drug reactions (sADRs) of antiseizure medications (ASMs) and study their seriousness and outcomes in various system organ classifications (SOCs). We intended to compare old and new ASMs’ ADRs.Methods: Using EudraVigilance (EV) database, we extracted line listings of reported sADRs with different ASMs over the period from January 2012 to December 2021. The list of ASMs was compiled according to the Anatomical therapeutic chemical classification system. The Medical Dictionary for Regulatory Activities version 24.0 was used for determining the SOCs of individual reported preferred terms (PTs) sADRs. In addition, we calculated the Reporting Odds Ratio (ROR), 95% confidence interval (95% CI), p-value (statistically significant if p< 0.05) and chi-square statistics.Results: A total of 276,694 reports were contained in the exported line listings which included 1,051,142 individual sADRs reported as PTs such as seizure (3.49%), drug ineffective (2.46%), somnolence (1.32%), dizziness (1.29%) and represented four SOCs: nervous system disorders (19.26%), general disorders and administration site conditions (14.39%), psychiatric disorders (11.29%) and injury, poisoning and procedural complications (9.79). Among patients, the age group between 18 and 64 years had the highest percentage (52.40%), followed by those aged over 64 years (18.75%). Of all the reported PTs, 882,706 (83.98%) had reported seriousness. Old ASMs had a significant positive association with “caused/prolonged hospitalisation”, “congenital anomaly”, “disabling”, “life threatening” and “results in death”, while new ASMS with ‘other medically important condition’. There were 386 (0.04%) PTs related to Sudden Unexpected Death in Epilepsy (SUDEP).Conclusion: In our study, we examined 10 years’ reported sADRs of ASMs in the EV international database. The majority of PTs were serious. Old ASMs were generally more commonly associated with undesired outcomes and seriousness. Considering their expected seriousness and outcomes, the safety profile of the different ASMs, can play a cardinal role in the selection of ASMs.

Introduction: Posterior Reversible Encephalopathy Syndrome (PRES) is conventionally defined as a clinical and imaging syndrome marked by symptoms such as headaches, encephalopathy, visual disturbances, and seizures. Although psychiatric symptoms might be present. Clinical case: A 29-year-old female patient hospitalized after a hypovolemic cardiac arrest due to ectopic pregnancy rupture, previously healthy, after a two-week hospitalization started with suicidal ideas, visual hallucinations, headache, and seizures. She presented two episodes of tonic-clonic generalized seizures, depressive symptoms, and hypertension. A brain CT scan showing parieto-occipital edema compatible with PRES findings. After the diagnosis of PRES, antiepileptic medication, antihypertensive therapy, and second-generation antipsychotic drugs were started. After stabilization, there was clinical improvement, and following 40 days she was discharged with no neurological deficit. Discussion: Patients with PRES have distinct symptoms like seizures, headaches, and visual disturbances, often mimicking other conditions, highlighting the importance of its accurate diagnosis for timely intervention. Moreover, the psychiatry manifestations also should be considered as a part of the clinical features. Conclusions: Awareness of factors such as hypertension, pregnancy-related complications, and psychiatric manifestations associated with PRES is crucial for personalized and appropriate management to reduce potential risks of this disease.

Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and in vitro seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.

Due to the abundance of ACE2 receptors in nervous system cells, the SARS-CoV-2 virus can cause damage to this system. This study aims to examine the prevalence of neurological symptoms in COVID-19 patients. In this cross-sectional observational study, 75 COVID-19 positive patients admitted to Golestan Hospital’s neurology department in Ahvaz, Iran, from March 2020 to March 2023, were investigated. Neurological clinical symptoms were categorized into three groups: central nervous system, peripheral, and muscular symptoms. The relevant information was collected from patient files, including medical history, imaging data, and laboratory test results. Statistical analysis was performed using SPSS software, employing the rank-biserial correlation coefficient (r), Mann–Whitney U tests, Phi correlation, Cramer’s V, and Kendall’s Tau to evaluate the prevalence and significance of neurological symptoms. The most common clinical symptoms observed were hemiparesis, dysarthria, Central Facial Palsy (CFP), ataxia, and nausea, respectively. Among these symptoms, headaches (p = 0.001), seizures (p = 0.024), and nausea (p = 0.046) were found to be more prevalent in younger patients. Additionally, a significant relationship was identified between the level of serum Creatine phosphokinase (CPK) and seizures (p = 0.024), with lower levels observed in individuals with vomiting (p = 0.024), and higher levels observed in individuals with CFP (p = 0.040). This study highlights that patients with COVID-19 may experience serious neurological symptoms. The clinical spectrum and range of neurological symptoms associated with COVID-19 were found to be diverse and extensive, emphasizing the importance of considering this infection as a potential cause of neurological disorders.

Magnetic resonance imaging (MRI) in an integral part of the diagnostic workup in canines with idiopathic epilepsy (IE). While highly sensitive and specific in identifying structural lesions, conventional MRI is unable to detect changes at the microscopic level. Utilizing more advanced neuroimaging techniques may provide further information on changes at the neuronal level in the brain of canines with IE, thus providing crucial information on the pathogenesis of canine epilepsy. Additionally, earlier detection of these changes may aid clinicians in the development of improved and targeted therapies. Advances in MRI techniques are being developed which can assess metabolic, cellular, architectural, and functional alterations; as well alterations in neuronal tissue mechanical properties, some of which are currently being applied in research on canine IE. This mini-review focuses on novel MRI techniques being utilized to better understand canine epilepsy, which include magnetic resonance spectroscopy, diffusion-weighted imaging, diffusion tensor imaging, perfusion-weighted imaging, voxel based morphometry, and functional MRI; as well as techniques applied in human medicine and their potential use in veterinary species.

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. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Pharmacology titled "Recent advances in the treatment of epilepsy." It discusses the complexities of epilepsy and the different treatment options available. The editorial highlights the use of anti-seizure medications as the first line of treatment, but acknowledges that some patients are resistant to these medications. It explores new pharmacological and non-pharmacological approaches, such as specific drugs, neurostimulation techniques, and the ketogenic diet. The editorial also mentions the potential role of the gut microbiota and natural compounds in epilepsy treatment. It provides valuable insights for clinicians and researchers in the field of neuroscience. The article titled "Nutrients" published in Frontiers in Pharmacology emphasizes the importance of nutrients in maintaining good health. It discusses the role of various nutrients in supporting bodily functions and preventing diseases. The article provides a comprehensive overview of different types of nutrients, their sources, and their impact on specific health conditions. It is a valuable resource for library patrons interested in understanding the significance of nutrients in their diet and overall well-being. [Extracted from the article]

Stimulus-induced epilepsy is termed reflex epilepsy. It is an uncommon entity. It can be induced due to exposure to stimuli such as flashes of light, music, hot water, or while eating, running, brushing teeth, or micturating. In reflex epilepsy, the patient can have any kind of seizure semiology. Treatment of these entities in many cases is difficult. Counseling of the patient and antiepileptic drugs are the mainstay of treatment. We present here a case of reflex epilepsy who developed it every time he had a prolonged cough.

Introduction: Neuroimaging is recommended for patients with seizures to identify intracranial pathology. However, emergency physicians should consider the risks and benefits of neuroimaging in pediatric patients because of their need for sedation and greater sensitivity to radiation than adults. The purpose of this study was to identify associated factors of neuroimaging abnormalities in pediatric patients experiencing their first afebrile seizure.Methods: This was a retrospective, multicenter study that included children who presented to the emergency departments (ED) of three hospitals due to afebrile seizures between January 2018–December 2020. We excluded children with a history of seizure or acute trauma and those with incomplete medical records. A single protocol was followed in the three EDs for all pediatric patients experiencing their first afebrile seizure. We performed multivariable logistic regression analysis to identify factors associated with neuroimaging abnormalities.Results: In total, 323 pediatric patients fulfilled the study criteria, and neuroimaging abnormalities were observed in 95 patients (29.4%). Multivariable logistic regression analysis showed that Todd’s paralysis (odds ratio [OR] 3.72, 95% confidence interval [CI] 1.03-13.36; P=0.04), absence of poor oral intake (POI) (OR 0.21, 95% CI 0.05-0.98; P=0.05), lactic acidosis (OR 1.16, 95% CI 1.04-1.30; P=0.01), and higher level of bilirubin (OR 3.33, 95% CI 1.11-9.95; P=0.03) were significantly associated with neuroimaging abnormalities. Based on these results, we constructed a nomogram to predict the probability of brain imaging abnormalities.Conclusion: Todd’s paralysis, absence of POI, and higher levels of lactic acid and bilirubin were associated factors of neuroimaging abnormalities in pediatric patients with afebrile seizure.

Exercising the jurisdiction of states in different maritime areas is a subject that has always been a source of controversy throughout the history of the international law of the seas. The efforts that have been made to increase these qualifications and the restrictions that have been applied to regulate them. However, on what basis such an increase and limitation of jurisdiction is done, it has caused many disputes. On the one hand, states emphasize the unquestionable principle of freedom of navigation contained in the UNCLOS, and on the other hand, by entering into some agreements to inspect and seize ships, they limit and, as a result, interfere with navigation. Today, in addition to the traditional interventions and restrictions on navigation that are stated in article110 of UNCLOS, we are facing emerging issues in the field of seas, which can be the reason for the intervention of ships in order to maintain international peace and security, interests and internal laws of states. Providing and implementing sanctions is an important part of this position. The main question is how to justify the intervention of international navigation in the implementation of cross border sanctions? In the present article, which is written with a descriptive analytical method and using library sources, by examining the legal bases of intervention in shipping and the implementation of economic sanctions in this regard, it can be concluded that today the acceptance and implementation of international agreements that it is considered as one of the main policies of governments, it it has been able to remove the interventions towards the ships from the framework of the Convention on the Law of the Sea and puts the implementation of unilateral policies of the governments such as the application of cross border sanctions, which is a sign of deviation from important principles such as the principle of freedom of navigation.

Neuropsychiatric systemic lupus erythematosus (NPSLE) affects the brain, spinal cord, or other nerves and leads to neurological and psychiatric symptoms directly related to SLE. We report a series of four female patients with NPSLE as the first presentation for SLE. None of them were previously diagnosed with SLE. The first case involved a 50-yearold patient who presented with back pain and lower limb weakness for three weeks associated with numbness. A lumbar puncture was done, and CSF analysis showed high WBC and normal glucose levels with negative CSF cultures for bacteria. The patient was diagnosed with aseptic meningitis and treated with antibiotics and antiviral medication without improvement. So she was treated as a case of SLE aseptic meningitis with steroids. In the second case, a 20-yearold patient had a generalized tonic-clonic seizure with the acute manifestation of hypertensive urgency. Magnetic resonance imaging (MRI) was done and suggested posterior reversible encephalopathy syndrome (PRES). The third case was for a 38-year-old patient who complained of dizziness, general weakness, and convulsion. On review of the systems, the patients had positive symptoms of SLE. Anti-nuclear antibody (ANA) and double-stranded ds-DNA were positive. Computed tomography (CT) scans were done and showed a thymoma. The patient was diagnosed with SLE in association with focal seizures and thymoma. In the last case, a 44-year-old patient presented with tongue heaviness and right-side weakness. MRI revealed small acute lacunar infarction scattered at both cerebral hemispheres and the right side of the cerebellum, and chest CT showed pulmonary embolism (PE). The patient was diagnosed with an acute ischemic stroke and PE related to SLE. In conclusion, the neurological manifestations of SLE are a significant issue for both patients and clinicians. Here we report a unique case series and describe the prognosis and outcome of the treatment in these cases.

Purpose. This study investigated the relationship between serum immunoglobulin A (IgA) concentration and epileptic seizures in children. Methods. Pediatric patients with epilepsy were included in this cross-sectional investigation. Serum IgA levels were analyzed using a biochemical analyzer during admission for initial diagnosis before any medical treatment was administered. Results. Among the 94 patients, 19.1% had decreased serum IgA levels, with a median value of 0.57 g/L. No significant relationship existed between serum IgA concentration and gender, age, epilepsy type, seizure duration or epilepsy waves. Children with low IgA levels experienced more spastic episodes and had a higher seizure frequency compared to those without decreased IgA levels. Changes in serum IgA levels were significantly associated with seizure frequency after three months of treatment. Initially, the occurrence of seizures in the low IgA group was 10.5 times lower than in the non-low IgA group, but, after three months, the low IgA group had a significantly higher seizure rate (72.2%) compared to the non-low IgA group (19.7%). After six months, the low IgA group had a higher proportion of children without seizures (100% versus 84.8%), although the difference was not statistically significant. Conclusion. Serum IgA concentration plays a crucial role in diagnosing and predicting outcomes for pediatric epilepsy.

Background Epilepsy is defined as a neurologic condition caused by a pathological brain condition. Epilepsy patients who have stopped treatment and are seizure-free for two years are considered to have achieved complete remission. Relapse occurs when seizures return after anti-epileptic drug (AED) withdrawal. Several studies reported that frequent seizures, prolonged duration to control seizures, number of AEDs consumed, and abnormal electroencephalography (EEG) found during AEDs tapered, were reported as predictors of relapse. Methods This retrospective, case-control study was carried out from 2012 – 2016 using multisite medical record evaluation, followed by interviews and EEG examinations. The case group included children with epilepsy who had seizure relapse, while the control group included children with complete remission of epilepsy. Bivariate and multivariate analyses were performed to identify predictors of relapse. Results Relapse predictors in bivariate analysis were symptomatic etiology epilepsy (OR 5.000; 95%CI 2.345 to 10.660; P

Abstract Background High concentrations of complement factors are presented in serum of animal epilepsy models and human patients with epilepsy. Objectives To determine whether complement dysregulation occurs in dogs with idiopathic epilepsy (IE). Animals The study included 49 dogs with IE subgrouped into treatment (n = 19), and nontreatment (n = 30), and 29 healthy dogs. Methods In this case‐control study, the serum concentrations of the third (C3) and fourth (C4) components of the complement system were measured using a canine‐specific ELISA kit. Results Serum C3 and C4 concentrations were significantly higher in dogs with IE (C3, median; 4.901 [IQR; 3.915‐6.673] mg/mL, P 3 times/month had significantly higher serum C3 (6.461 [4.695‐8.735] mg/mL; P

Abstract Background Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy. Methods The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case–control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights. Results We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96–1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13–1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83–1.56). Conclusions While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy. Systematic review registration CRD42022342510.

Background: In the presurgical evaluation of patients with drug-resistant epilepsy, magnetic resonance imaging (MRI) and ictal brain perfusion SPECT with the chemical microspheres 99mTc-HMPAO are widely used for diagnosing the seizure onset zone (SOZ). For both modalities, there is theoretical controversy over favoring one over the other. This study aimed to compare the performance of 99mTc-HMPAO SPECT with MRI for SOZ identification in EEG-proved epileptic Saudi patients. Methods and Results: For this observational retrospective study, the database of the nuclear medicine departments at the Prince Sultan Military Medical City (PSMMC) and King Abdullah bin Abdulaziz University Hospital (KAAUH) were searched for male and female patients with suspected unifocal epilepsy in whom ictal brain perfusion SPECT and MRI had been performed for presurgical evaluation. A total of 14 adult epileptic patients above 18 years were included who have undergone SPECT scans using 99mTc-HMPAO and MRI between Jan 2014 and Dec 2021. 99mTc-HMPAO SPECT and MRI scans were performed simultaneously for each patient, and there was almost general agreement that 99mTc-HMPAO SPECT accurately localized and detected the SOZ in 12/14 patients (sensitivity 85.71%). It was superior to MRI, which detected and localized the SOZ in only 7/14 patients (sensitivity 50.0%). Unfortunately, the specificity of ictal brain perfusion SPECT, by using 99mTc-HMPAO in seizure localization in epileptic patients, was not detected due to the shortage of data that led to all the EEG findings being 100% positive. Conclusion: This study reported that ictal SPECT using 99mTc-HMPAO provides more valuable information about SOZ localization than MRI. However, future studies with a larger sample size are needed to assess the specificity of 99mTc-HMPAO SPECT in detecting the SOZ.

Abstract Background Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. Methods A case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search. Results Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases. Conclusions Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations. Key points We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4–7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.

Abstract Background There are wide-ranging differential diagnoses for the myriad of neurological symptoms associated with non-ketotic hyperglycemia. Similarly, various secondary complications of diabetic ketoacidosis present with nonspecific clinical symptoms. These are inadvertently misdiagnosed as epilepsies and strokes with associated hyperglycemia. Direct association between these nonspecific symptoms and hyperglycemia has been proved by demonstrating their resolution with correction of the latter. This case series portrays the spectrum of few rare neuroimaging findings of uncontrolled hyperglycemia, which helps in proper and prompt diagnoses. Case presentation Five diabetic patients with uncontrolled hyperglycemia were observed. Striatal hyperdensity on computed tomography or striatal T1 hyperintensity on magnetic resonance imaging was observed in three patients who presented with movement disorders. The abnormality was bilateral in one case. These observations were consistent with hyperglycemia-induced hemichorea–hemiballismus syndrome. In another patient who had presented with focal seizures, magnetic resonance imaging revealed subcortical T2/FLAIR hypointensity in bilateral occipital regions, which has been described to be characteristic for non-ketotic hyperglycemia-related seizures. Yet another patient who had been treated for diabetic ketoacidosis had developed bilateral lower-limb weakness. In correlation with a background of rapid correction of hyponatremia, magnetic resonance imaging revealed symmetric areas of altered signal intensity in the bilateral perirolandic region showing an open ring pattern of diffusion restriction, suggesting extrapontine myelinolysis. Conclusions In all the cases, the clinical differentials were wide. Neuroimaging was mandatory in establishing hyperglycemia as the underlying cause for the movement disorders and seizures. Also, neuroimaging aided in timely identification of extra-pontine myelinolysis, which might have prevented further central pontine involvement in the patient with diabetic ketoacidosis.

Introduction: The postictal state is a temporary condition that occurs after seizures, often characterized by EEG slowing or suppression, and can last from minutes to days. Seizures can be accompanied by various postictal complications, including headache, automatism, delirium, psychosis, functional deficits, neuropsychological deficits, and abnormal behavioral manifestations. Effective management of postictal states requires identification of associated comorbidities and underlying neurological and systemic disorders. However, there is limited information regarding the causes, prevalence, and optimal treatment of postictal complications following status epilepticus. This study aimed to determine the different types of postictal complications and comorbidities. Materials and Methods: Patients with status epilepticus were observed after their seizure episode subsided, and their medical history and comorbidities were recorded. It was a cross sectional observation study. 100 participants were selected for the study at MLB Medical College, Jhansi, between March 2020 and November 2021. Written informed consent was obtained from all participants after explaining the study's objectives and procedures. Results: The most common postictal complication observed in our study was headache, experienced by 51% of patients after the seizure subsided. Delirium was observed in approximately 28% of patients, while psychosis and automatism were reported by 9% and 8% of patients, respectively. Conclusions: The results of our study indicate that individuals with seizures have significantly higher odds of experiencing various comorbid conditions compared to those without seizures. The strongest association was found between seizures and stroke.

The precise and automated detection of epileptic seizures has become a focal point of research due to its potential to alleviate the severe consequences experienced by patients. Recent advancements in deep learning-based detection techniques utilizing electroencephalogram (EEG) signals have yielded state-of-the-art performance. However, these methods typically require a large number of training samples to effectively train the deep neural networks. Consequently, their performance can be compromised in scenarios where only a limited number of samples are available. This paper presents two novel approaches that aim to improve seizure detection accuracy in situations with a scarcity of data by harnessing the power of empirical mode decomposition (EMD) applied to EEG signals. Specifically, in both methods, the EMD of EEG signals and the power spectral density (PSD) of the resulting EMD components are employed as inputs for subsequent neural networks. Multiple convolutional neural networks (CNNs) are purposefully designed to perform seizure detection using these inputs. Experimental results demonstrate that our proposed methods achieve superior detection accuracy compared to traditional deep learning-based detection methods that do not incorporate EMD in few-shot scenarios. In particular, when the number of training samples is reduced to 10%, our method shows an improvement of 23%, 19%, and 26% in accuracy, sensitivity, and specificity, respectively, compared to the original EEG input across different networks.

Introduction: Phenytoin is one of the commonly used anti-seizure medications in nontraumatic seizures. However, its utility and safety in young patients with traumatic brain injury (TBI) for the prevention of early-onset seizures (EOS) are debatable. We sought to explore the use of phenytoin as a seizure prophylaxis following TBI. We hypothesized that administering phenytoin is not effective in preventing EOS after TBI. Methods: This was a retrospective observational study conducted on adult TBI patients. EOS was defined as a witnessed seizure within a week postinjury. Data were compared as phenytoin versus no-phenytoin use, EOS versus no-EOS, and among TBI severity groups. Results: During 1 year, 639 TBI patients were included with a mean age of 32 years; of them, 183 received phenytoin as seizure prophylaxis, and 453 received no prophylaxis medication. EOS was documented in 13 (2.0%) patients who received phenytoin, and none had EOS among the nonphenytoin group. The phenytoin group was more likely to have a higher Marshall Score (P = 0.001), lower Glasgow Coma Scale (GCS) (P = 0.001), EOS (P = 0.001), and higher mortality (P = 0.001). Phenytoin was administrated for 15.2%, 43.2%, and 64.5% of mild, moderate, and severe TBI patients, respectively. EOS and no-EOS groups were comparable for age, gender, mechanism of injury, GCS, Marshall Score, serum phenytoin levels, liver function levels, hospital stay, and mortality. Multivariable logistic regression analysis showed that low serum albumin (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.676–0.962) and toxic phenytoin level (OR 43; 95% CI 2.420–780.7) were independent predictors of EOS. Conclusions: In this study, the prophylactic use of phenytoin in TBI was ineffective in preventing EOS. Large-scale matched studies and well-defined hospital protocols are needed for the proper utility of phenytoin post-TBI.

Objective: This study aimed to investigate the incidence and pattern of tramadol-induced seizures and injuriesin patients admitted to the hospital.Methods: The cross-sectional study included 300 patients with alleged tramadol intoxication. Demographicinformation, tramadol dosage and duration of abuse, co-existing illicit drug abuse, hospital stay length, andoccurrence of seizures and trauma (type and site of injuries) were collected. Different statistical tests, includingthe Mann-Whitney U-test, Pearson’s Chi-square test, and Student’s t-test, were conducted to compare thepatients with and without seizures, trauma, and co-ingestion of illicit drugs. The analysis was performed usingSPSS software (version 21.0). A p value of less than 0.05 was considered statistically significant.Results: The average patient’s age was 24.66±5.64 years, with males comprising 84.3% of the sample. Themean tramadol dose and duration of abuse were 1339.3±1310.2 mg and 2.43±1.35 years, respectively. Seizureswere observed in 66% of patients, with men having a higher incidence (69.6% vs. 46.8%; p=0.004). Trauma wasreported in 23% of patients, accounting for 35.4% of seizure cases. All trauma patients had experienced seizures,with the head and neck being the most prevalent injury sites (55.1%), typically presenting as abrasions (55.9%).Patients with seizures and trauma had an average hospital stay of 1.73±0.94 days, which was significantlylonger.Conclusion: Trauma occurs in more than one-third of tramadol-induced seizures, highlighting the needto perform physical examinations to detect and localize injuries. Tramadol-associated traumas prolongedhospitalization times and thus required prompt attention to prevent further injuries during pre-hospital handlingand transferring to hospitals.

Epilepsy remains a significant non-communicable disease with global health relevance. The World Health Organization (WHO) estimates that between 4 and 10 per 1000 people worldwide suffer from active epilepsy, with the African population having the highest associated morbidity and mortality.This review highlights the prevalence of epilepsy in sub-Saharan Africa using data collected via online resources, including Google Scholar and PubMed. It aims to highlight the various harmful traditional practices used in this part of the world to abort seizure attacks, as well as the common clinical examination and investigative findings noticed at the presentation after such traditional interventions have been applied, to better guide clinicians towards a more thorough management of such dynamic presentations.Harmful cultural beliefs and practices on the interventions of epileptic conditions are common in many developing countries across Africa, many of which have been found to cause more harm than good. Healthcare providers must be aware of these interventions and provide tailored and individualized care in their management.

Abstract Background SCN8A-related disorders are a group of variable conditions caused by pathogenic variations in SCN8A. Online Mendelian Inheritance in Man (OMIM) terms them as developmental and epileptic encephalopathy 13, benign familial infantile seizures 5 or cognitive impairment with or without cerebellar ataxia. Methods In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing. Results Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4. Conclusions This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.

Yun Yang,1,2 Chao Zhang,1 Chen Cao,3 Wenhua Su,1 Na Zhao,1 Wei Yue1,4 1Department of Neurology, Clinical College of Neurology, Neurosurgery, and Neurorehabilitation, Tianjin Medical University, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China; 2Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Medical Imageology, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China; 4Department of Biomedical Engineering, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Wei Yue, Department of Neurology, Tianjin Huanhu Hospital, 6 Jizhao Road, Tianjin, 300350, People’s Republic of China, Fax +862259065662, Email hhyuewei2021@163.comBackground: Myelin oligodendrocyte glycoprotein (MOG) antibody–associated encephalitis is a new clinical phenotype of inflammatory demyelinating diseases. Some MOG antibody–positive patients with central nervous system demyelinating events present with isolated seizures. However, there are gaps in the epidemiological knowledge regarding seizures with MOG antibody–associated encephalitis in adults. This study characterized the clinical features and treatment of MOG antibody–positive patients with isolated seizures.Methods: We reviewed all the patients admitted to Tianjin Huanhu Hospital between Jan. 1st 2017 and Jan. 1st 2022, to screen the MOG antibody–positive patients with isolated seizures, and collected the concerned patients’ information regarding epidemiology, clinical presentations, laboratory and radiological characteristics, electroencephalogram (EEG), treatments, and prognoses.Results: We collected six MOG antibody–positive adult patients who had isolated symptomatic seizures. The mean age of the patients was 33 years (range, 29– 40 years), and five (83.3%) were men. All patients presented with motor seizures, five (83.3%) had cognitive dysfunction, and only one (16.7%) had status epilepticus. Five (83.3%) patients had a good response to immunotherapy and antiseizure medications; only one had a sequela. The cerebrospinal fluid or serum anti-MOG antibody test turned negative over time.Discussion: The most common seizure type in patients with MOG antibody–associated encephalitis with isolated seizures was focal to bilateral tonic-clonic seizures, and most patients had a good prognosis. Adding antiseizure medications were beneficial for MOG antibody–positive patients with seizures. Relapses and sequelae were associated with low-dose, short-time, or delayed therapy, and wide-range demyelinating brain damage.Plain Language Summary: We reported six adult patients with seizures (as the isolated symptom without any ophthalmoneuromyelitis symptom) associated with MOG antibodies. Focal to bilateral tonic-clonic seizures are the common seizure type in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Antiseizure medications and immunotherapy are beneficial for treating MOG antibody–associated encephalitis with seizures. Many patients had good or complete recovery; low-dose, short-time, or delayed therapy is associated with relapses and sequelae. Emphasized the MOG antibodies testing should be relevant in patients with isolated seizures, particularly occurred in clusters, to guarantee the acute management timely.Keywords: myelin oligodendrocyte glycoprotein, antibody-associated disease, seizure, clinical features, antiseizure medications

Abstract Background The muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here. Methods One hundred ninety-three patients (18–60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness. Results Six thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p

Abstract Background The brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate extra- and intracellular proteases, which implies an altered brain secretome. Thus, we applied a 4-aminopyridine (4-AP) epilepsy model to study the hippocampal ECF peptidome alterations upon treatment in rats. Methods We performed in vivo microdialysis in the hippocampus for 3–3 h of control and 4-AP treatment phase in parallel with electrophysiology measurement. Then, we analyzed the microdialysate peptidome of control and treated samples from the same subject by liquid chromatography-coupled tandem mass spectrometry. We analyzed electrophysiological and peptidomic alterations upon epileptic seizure induction by two-tailed, paired t-test. Results We detected 2540 peptides in microdialysate samples by mass spectrometry analysis; and 866 peptides—derived from 229 proteins—were found in more than half of the samples. In addition, the abundance of 322 peptides significantly altered upon epileptic seizure induction. Several proteins of significantly altered peptides are neuropeptides (Chgb) or have synapse- or brain-related functions such as the regulation of synaptic vesicle cycle (Atp6v1a, Napa), astrocyte morphology (Vim), and glutamate homeostasis (Slc3a2). Conclusions We have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis.

Background: With the outbreak of COVID-19, school closures and quarantines following social distancing have brought significant changes to children's lifestyles. Therefore, we aimed to compare the population-adjusted incidence of febrile seizures(FS) and epilepsy before and after the COVID-19 outbreak in Korea and to assess the effects of the COVID-19 outbreak on the incidence by region and age group. Methods: A retrospective cohort study was conducted using nationwide claims data and covid data from January 2019 to December 2020. The incidence of diseases and difference in incidence before (Jan 20 to Dec 30, 2019) and after (Jan 20 to Dec 30, 2020) the COVID-19 outbreak was measured using rate ratio. An Interrupted time series analysis was used to identify the effect of COVID-19 on trends of FS and epilepsy. Subgroup analysis by age, sex, insurance, and risk of coronavirus by area were conducted. Results: Following the onset of the pandemic, the number of newly diagnosed FS cases decreased sharply by 69 % (24,182 to 7238), whereas the incidence of epilepsy, increased to 1.02 times (30,286−29,312), when adjusted in proportion to the population. Notably, a greater decrease in the incidence of FS were found in the regions with high-risk of coronavirus. A result of segmented regression analysis proved the decrease was significant and made immediately after the pandemic started(p

Despite being protected under the law, illegal trade in tortoises and freshwater turtles is common in India, with different species being trafficked for different markets. Indian species of tortoises and hard-shell turtles are predominantly trafficked for the pet trade and soft-shell turtles for the meat trade. Given their distinct markets, the operation of trade may vary between these different groups of tortoises and freshwater turtles, thereby necessitating different types of interventions. However, a systematic examination of illegal trade in tortoises and freshwater turtles that takes into account the differences between these markets is currently lacking. Here we compare the supply networks of tortoises/hard-shell turtles (in demand for pet trade) vs soft-shell turtles (meat trade), using information from 78 and 64 seizures, respectively, that were reported in the media during 2013–2019. We used social network analysis to compare the two networks and the role of individual nodes (defined as locations at the district or city scale) within these networks. We found that the tortoise/hard-shell turtle network had a larger geographical scale, with more international trafficking links, than the soft-shell turtle network. We recorded convoluted smuggling routes in tortoise/hard-shell turtle trafficking, whereas soft-shell turtle trafficking was uni-directional from source to destination. Within both networks, we found that a few nodes played disproportionately important roles as key exporting, importing or transit nodes. Our study provides insights into the similarities and differences in the illegal supply networks of different groups of tortoises and freshwater turtles, in demand for different markets. We highlight the need for intervention strategies tailored to address the illegal trade in each of these groups.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Neuronal hyperexcitability and excitotoxicity lies at the core of debilitating brain disorders such as epilepsy and traumatic brain injury, culminating in neuronal death and compromised brain function. Overcoming this challenge requires a unique approach that selectively restores normal neuronal activity and rescues neurons from impending damage. However, delivering drugs selectively to hyperexcitable neurons has been a challenge, even upon local administration. Here, we demonstrate the remarkable ability of a novel, scalable, generation‐two glucose‐dendrimer (GD2) made primarily of glucose and ethylene glycol building blocks, to specifically target hyperexcitable neurons in primary culture, ex vivo acute brain slices, and in vivo mouse models of acute seizures. Pharmacology experiments in ex vivo brain slices suggest GD2 uptake in neurons is mediated through glucose transporters (GLUT and SGLT). Inspired by these findings, we conjugated GD2 with a potent anti‐epileptic drug, valproic acid (GD2–VPA), for efficacy studies in the pilocarpine‐mouse model of seizure. When delivered intranasally, GD2–VPA significantly decreased the seizure‐severity. In summary, our findings demonstrate the unique selectivity of glucose dendrimers in targeting hyperexcitable neurons, even upon intranasal delivery, laying the foundation for neuron‐specific therapies for the precise protection and restoration of neuronal function, for targeted neuroprotection. [ABSTRACT FROM AUTHOR]

Background: Ictal bradycardia (IB) and asystole (IA) represent a rare but potentially harmful feature of epileptic seizures. The aim of this study was to study IB/IA in patients with sleep-related hypermotor epilepsy (SHE). Methods: We retrospectively included cases with video-EEG-confirmed SHE who attended our Institute up to January 2021. We reviewed the ictal polysomnography recordings focusing on ECG and identified cases with IB (R-R interval ≥ 2 s or a ≥10% decrease of baseline heart rate) and IA (R-R interval ≥ 4 s). Results: We included 200 patients (123 males, 61.5%), with a mean age of 42 ± 16 years. Twenty patients (20%) had focal cortical dysplasia (FCD) on brain MRI. Eighteen (out of 104 tested, 17.3%) carried pathogenic variants (mTOR pathway, n = 10, nAchR subunits, n = 4, KCNT1, n = 4). We identified IB/IA in four cases (2%): three had IA (mean 10 s) and one had IB. Three patients had FCD (left fronto-insular region, left amygdala, right mid-temporal gyrus) and two had pathogenic variants in DEPDC5; both features were more prevalent in patients with IB/IA than those without (p = 0.003 and p = 0.037, respectively). Conclusions: We identified IB/IA in 2% of patients with SHE and showed that this subgroup more frequently had FCD on brain MRI and pathogenic variants in genes related to the mTOR pathway. [ABSTRACT FROM AUTHOR]

Epilepsy ranks as the second-most prevalent neurological disease, and is characterized by seizures resulting in neurobiological and behavioral impairment. Naturally occurring in coffee beans or tea leaves, the alkaloid caffeine (CAF) is the most prevalent global stimulant. Caffeine has been observed to influence epileptic seizures and the efficacy of antiepileptic medications, with a notable impact on topiramate (TPM). This study aimed to explore the influence of CAF on TPM's anticonvulsant effects in zebrafish larvae within a PTZ-induced seizure model, concurrently determining TPM concentrations through a sophisticated analytical approach based on ultrahigh-performance liquid chromatography and subsequent mass spectrometric detection. Zebrafish larvae four days post-fertilization were incubated for 18 h with varying doses of TPM or combinations of CAF + TPM, and locomotor activity was then assessed. Seizures were induced by introducing a PTZ solution to achieve a final concentration of 20 mM. Utilizing liquid chromatography–mass spectrometry (LC–MS/MS), TPM levels in the larvae were quantified. CAF co-administration (especially in higher doses) with TPM caused a decrease in the average locomotor activity in the larvae compared to TPM alone. Moreover, CAF decreased TPM levels in the larvae at all investigated doses. In conclusion, these findings offer a novel perspective on the interplay between CAF and TPM, shedding light on previously unexplored facets. The potential impact of CAF consumption in assisting with epileptic seizure control, unless proven otherwise, suggests a noteworthy consideration for future research and clinical practices. [ABSTRACT FROM AUTHOR]

Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23kg/m², donor age ≥45years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome. [ABSTRACT FROM AUTHOR]

Accumulation of amyloid-beta (Aβ) can lead to the formation of aggregates that contribute to neurodegeneration in Alzheimer's disease (AD). Despite globally reduced neural activity during AD onset, recent studies have suggested that Aβ induces hyperexcitability and seizure-like activity during the early stages of the disease that ultimately exacerbate cognitive decline. However, the underlying mechanism is unknown. Here, we reveal an Aβ-induced elevation of postsynaptic density protein 95 (PSD-95) in cultured neurons in vitro and in an in vivo AD model using APP/PS1 mice at 8 weeks of age. Elevation of PSD-95 occurs as a result of reduced ubiquitination caused by Akt-dependent phosphorylation of E3 ubiquitin ligase murine-double-minute 2 (Mdm2). The elevation of PSD-95 is consistent with the facilitation of excitatory synapses and the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induced by Aβ. Inhibition of PSD-95 corrects these Aβ-induced synaptic defects and reduces seizure activity in APP/PS1 mice. Our results demonstrate a mechanism underlying elevated seizure activity during early-stage Aβ pathology and suggest that PSD-95 could be an early biomarker and novel therapeutic target for AD. Synopsis: Neuronal hyperactivity and elevated susceptibility to seizures have been observed in early stage of Alzheimer's disease. Accumulation of Aβ leads to an elevation of excitatory synapse numbers and seizure susceptibility, which can be ameliorated by inhibition of PSD-95. Post-synaptic density protein 95 (PSD-95) is elevated in young APP/PS1 mice as well as cultured cortical neurons treated with synthetic Aβ peptides. Elevated PSD-95 is caused by its reduced ubiquitination resulting from Akt-dependent phosphorylation of E3 ubiquitin ligase Mdm2. Genetically inhibiting PSD-95 reduces Aβ-induced elevation of excitatory synapse numbers. Genetically inhibiting PSD-95 ameliorates seizure response in APP/PS1 mice as well as wildtype mice injected with synthetic Aβ peptides. Neuronal hyperactivity and elevated susceptibility to seizures have been observed in early stage of Alzheimer's disease. Accumulation of Aβ leads to an elevation of excitatory synapse numbers and seizure susceptibility, which can be ameliorated by inhibition of PSD-95. [ABSTRACT FROM AUTHOR]

Background: Epilepsy's pathogenesis and progression are significantly influenced by neuroinflammation, blood-brain barrier function, and synaptic remodeling function. Matrix metalloproteinase 9 (MMP-9), as a critical factor, may contribute to the development of epilepsy through one or more of the above-mentioned pathways. This study aims to evaluate and quantify the correlation between MMP-9 levels and epilepsy. Methods: We conducted a comprehensive search of Embase, Web of Science, PubMed, Cochrane Library, WanFang DATA, VIP, and the CNKI to identify studies that investigate the potential association between MMP-9 and epilepsy. The data were independently extracted by two researchers and assessed for quality using the Cochrane Collaboration tool. The extracted data were analyzed using Stata 15 and Review Manager 5.4. The study protocol was registered prospectively at PROSPERO, ID: CRD42023468493. Results: Thirteen studies with a total of 756 patients and 611 matched controls met the inclusion criteria. Eight of these studies reported total serum MMP-9 levels, and the other five studies were used for a further subgroup analysis. The metaanalysis indicated that the serum MMP-9 level was higher in epilepsy patients (SMD = 4.18, 95% confidence interval = 2.18-6.17, p<0.00001) compared with that in the control group. Publication bias was not detected according to Begg's test. The subgroup analysis of country indicated that the epilepsy patients in China, Poland, and Egypt had higher levels of serum MMP-9 than the control group, with the increase being more pronounced in Egypt. The subgroup analysis of the age category demonstrated that the serum MMP-9 levels of the adult patients with epilepsy were significantly higher than those of the matched controls. However, the serum MMP-9 levels did not significantly differ in children with epilepsy. The subgroup analysis of the seizure types demonstrated substantial difference in the MMP-9 levels between patients of seizure-free epilepsy (patients who have been seizure-free for at least 7 days) and the control group. Meanwhile, the serum MMP-9 level in patients with epileptic seizures was significantly higher than that in the control group. The subgroup analysis based on seizure duration in patients showed that the serum MMP-9 levels at 1-3, 24, and 72 h after seizure did not exhibit significant differences between female and male patients with epilepsy when compared with the control group. The serum MMP-9 levels at 1-3 and 24 h were significantly higher than those of the matched controls. Nevertheless, the serum MMP-9 level at 72 h was not significantly different from that in the control group. Conclusion: This meta-analysis presents the first comprehensive summary of the connection between serum MMP-9 level and epilepsy. The MMP-9 levels in epilepsy patients are elevated. Large-scale studies with a high level of evidence are necessary to determine the exact relationship between MMP-9 and epilepsy. [ABSTRACT FROM AUTHOR]

Hypothalamic hamartomas (HHs) are congenital developmental malformations located in the hypothalamus. They are associated with a characteristic clinical manifestation known as gelastic seizures (GS). However, the traditional understanding of HHs has been limited, resulting in insufficient treatment options and high recurrence rates of seizures after surgery. This is consistent with the network hypothesis of focal epilepsy that the epileptogenic zone is not only limited to HH but may also involve the distant cerebral cortex external to the HH mass. The epilepsy network theory, on the other hand, provides a new perspective. In this study, we aim to explore HH-related epilepsy as a network disease, challenging the conventional notion of being a focal lesional disease. We analyze various aspects of HHs, including genes and signaling pathways, local circuits, the whole-brain level, phenotypical expression in terms of seizure semiology, and comorbidities. By examining HHs through the lens of network theory, we can enhance our understanding of the condition and potentially identify novel approaches for more effective management and treatment of epilepsy associated with HHs. Plain language summary: Hypothalamic hamartomas (HHs) are unusual brain malformations present from birth in the hypothalamus region. They often lead to a distinctive type of seizures known as GSs. However, our current understanding of HHs is limited, and this has made it challenging to treat them effectively. Many patients continue to experience seizures even after surgery. We've typically considered HH-related epilepsy as a localized problem, but a new theory suggests that it may involve a network of brain areas. In our study, we aim to change the way we view HH-related epilepsy. Instead of thinking of it as a single lesion in the brain, we explore the idea that it's a network disease. To do this, we'll investigate various aspects of HHs, such as the genes and pathways involved, how different parts of the brain interact, the impact on the whole brain, the types of seizures experienced, and any related health issues. By looking at HHs through this network theory, we hope to gain a deeper understanding of the condition and potentially discover new ways to manage and treat epilepsy associated with HHs. This shift in perspective could offer hope to those living with HH-related epilepsy and lead to more effective treatments, ultimately improving their quality of life. [ABSTRACT FROM AUTHOR]