Risk Of Seizures Research Articles

Antiseizure medication practices in the adult traumatic brain injury patient population

BackgroundAntiseizure medication (ASM) use in traumatic brain injuries (TBI) reduces the risk of early post-traumatic seizure (PTS). Agent selection and dosing strategies remain inconsistent among trauma centers in the United States. ObjectiveThe purpose of this study was to identify and characterize the most common PTS prophylaxis regimens among adult trauma centers in brain injured patients throughout the United States. MethodsA survey assessing PTS prophylaxis practices of trauma centers was created and distributed in March 2023. Data was then evaluated based on practice site demographics and various sub-group analyses including academic vs. non-academic centers, trauma center designation, geographic practice location, and total number of TBI activations annually. ResultsA total of 84 different trauma centers responded of which, 82 (97.6 %) respondents reporting levetiracetam (LEV) as their ASM of choice for PTS prophylaxis. The most reported dosing regimen included an initial dose of 1000 mg (n = 24, 46.2 %) followed by a maintenance dose of 500 mg BID (n = 39, 48.8 %). There were no statistically significant differences in practice between sub-group analyses evaluated. Conclusion and relevanceThis multicenter, survey study, identified variances in practice for PTS prophylaxis for brain injured patients throughout the U.S. Interestingly, the overwhelming majority of trauma centers do not conform to the Brain Trauma Foundation guidelines and utilize LEV as their agent of choice. Further studies should evaluate ideal patient selection for PTS prophylaxis, optimal agent, and dosing schemes within this cohort.

Association between tumor location and toxicity outcomes after stereotactic radiosurgery for brain metastases.

Toxicities associated with stereotactic radiosurgery (SRS) are important when considering treatment and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and risk of toxicity after SRS. We conducted a retrospective institutional review of patients treated with SRS for brain metastases between 2008 and 2023. Outcomes included radiation necrosis, seizure, local failure, and overall survival (OS). We reviewed 215 patients treated to 605 metastases (median diameter 10mm, IQR 5-17 mm), in the frontal (34%), cerebellar (19%), parietal (16%), temporal (13%), and occipital (13%) regions. Median follow-up was 16 months (IQR 7-36). New-onset seizures developed in 11% (19/174) of patients without prior seizure and was higher in patients with motor or sensory cortex lesions (12/48, 25%) on multivariate analysis (MVA, P = 0.02). SRS-related grade ≥ 2 symptomatic radionecrosis occurred in 6% (33/605) of lesions and correlated with larger metastasis volume (P < 0.001) and renal cell carcinoma histology (P < 0.05), while supratentorial location was nearly significant (MVA, P = 0.06). Median OS across all patients was 16 months (95% CI 12-20). Patients with symptomatic radiation necrosis had a longer median survival compared to those who did not (43 vs. 14 months, P = 0.002), which remained significant alongside Karnofsky performance status and extracranial disease on MVA. Brain metastasis location in the motor or sensory cortex is associated with increased risk of new-onset seizure following SRS and may warrant consideration of steroid and/or anti-epileptic prophylaxis. Symptomatic radiation necrosis is uncommon in the cerebellum and may be increasing with improvements in survival.

Seizure Burden and Clinical Risk Factors in Glioma-Related Epilepsy: Insights From MRI Voxel-Based Lesion-Symptom Mapping.

Epilepsy is the most common preoperative symptom in patients with supratentorial gliomas. Identifying tumor locations and clinical factors associated with preoperative epilepsy is important for understanding seizure risk. To investigate the key brain areas and risk factors associated with preoperative seizures in glioma patients. Retrospective. A total of 735 patients with primary diffuse supratentorial gliomas (372 low grade; 363 high grade) with preoperative MRI and pathology data. Axial T2-weighted fast spin-echo sequence at 3.0 T. Seizure burden was defined as the number of preoperative seizures within 6 months. Tumor and high-signal edema areas on T2 images were considered involved regions. A voxel-based lesion-symptom mapping analysis was used to identify voxels associated with seizure burden. The involvement of peak voxels (those most associated with seizure burden) and clinical factors were assessed as risk factors for preoperative seizure. Univariable and multivariable binary and ordinal logistic regression analyses and chi-square tests were performed, with results reported as odds ratios (ORs) and 95% confidence intervals. A P-value <0.05 was considered significant. A total of 448 patients experienced preoperative seizures. Significant seizure burden-related voxels were located in the right hippocampus and left insular cortex (based on 1000 permutation tests), with significant differences observed in both low- and high-grade tumors. Tumor involvement in the peak voxel region was an independent risk factor for an increased burden of preoperative seizures (OR = 6.98). Additionally, multivariable binary logistic regression results indicated that 1p/19q codeletion (OR = 1.51), intermediate tumor volume (24.299-97.066 cm3), and involvement of the peak voxel (OR = 6.06) were independent risk factors for preoperative glioma-related epilepsy. Voxel areas identified through voxel-based lesion-symptom mapping analysis, along with clinical factors, show associations with clinical seizure burden, offering insights for assessing seizure burden for glioma patients. 4 TECHNICAL EFFICACY: Stage 1.

Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force.

To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden. The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), amplitude-integrated EEG (aEEG), or clinical features. The scoping review yielded 44 articles containing a definition of neonatal SE. Studies mainly included infants with hypoxic-ischemic encephalopathy or neonates considered at risk for seizures. SE identification and classification most often relied on cEEG. The majority of studies based the definition of SE on seizure duration, including summed duration of seizures comprising ≥50% of any 1-h epoch, recurrent seizures for >50% of the total recording time, or either electrographic seizures lasting >30 min and/or repeated electrographic seizures totaling >50% in any 1-h period. Seizure burden was reported in 20 studies, and the most commonly used approach assessed total seizure burden, defined as total duration of EEG seizures in minutes. Sixteen studies assessed the relationship between seizure burden and outcomes, and most identified a significant association between higher seizure burden and unfavorable outcomes. This scoping review demonstrates a substantial variation in neonatal SE definitions across the literature. The most common definitions were based around a 30-min seizure duration criterion, but evidence was insufficient to support that 30 min was a cutoff defining prolonged seizures or that seizures exceeding this burden were more likely to be pharmacoresistant or associated with worse outcomes. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE. Prolonged seizures are a neurologic emergency, if untreated, can lead to permanent injury or death. In adults and children, seizures lasting longer than 30 min are believed to cause brain damage. However, it is not clear if this definition can be applied to neonates. The International League Against Epilepsy Neonatal Taskforce performed a scoping literature review which identified 44 articles containing a definition of neonatal status epilepticus. In this article, the authors reviewed the current used definitions for prolonged seizures in neonates to establish a relationship between seizure duration and neurological outcome. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE.

DECISION MAKING IN EPILEPTIC AVMS

While there is no doubt about the need for surgical treatment of a ruptured arteriovenous malformation (AVM), the decision to surgically treat a patient presenting solely with seizures is more controversial. Arteriovenous malformations (AVMs) arise from an abnormal connection between high-flow arterial vessels and low-flow venous vessels, resulting in a dysplastic vascular nidus within the brain tissue. The inherent flow irregularities within AVMs make them prone to rupture, which occurs in approximately half of patients. Additionally, seizures represent the second most common clinical manifestation of AVMs, presenting in 20%–45% of individuals with these lesions. This paper investigates the angiographic and MRI features of arteriovenous malformations that present with epilepsy, and discusses the surgical considerations in managing these patients and integration of multimodal approach focusing on the standard microsurgical techniques utilized. Patients presenting with seizures as the primary symptom of an arteriovenous malformation carry a higher surgical risk compared to those presenting with haemorrhage. Several factors have been associated with an increased risk of seizures in patients with arteriovenous malformations (AVMs). These include male gender, younger patient age, AVMs located in the frontal or temporal lobes, AVMs situated in the brain cortex, superficial venous drainage, a superficial temporal lobe AVM nidus, fistulous AVMs, and AVMs with venous stenosis. Surgical treatment is the recommended approach for patients with Spetzler-Martin grade I–III arteriovenous malformations. Resecting an unruptured brain arteriovenous malformation in a patient presenting only with epilepsy is a complex decision that requires a thorough understanding of the lesion’s anatomy, the patient’s history, and the neurosurgeon’s skills.

Risk factors of seizure and complex seizure in febrile children: a clinical study.

There is some evidence that trace element and mineral deficiencies may promote the occurrence of febrile seizures. However, the role of these elements in the occurrence of complex seizures in children with FS has not been comprehensively investigated. The present study was conducted to evaluate this issue. In a cross-sectional study, 220 patients including 110 febrile and 110 FS children aged 6-60 months were studied. Blood samples were taken and serum zinc, potassium, sodium, magnesium and calcium levels were measured. Demographic and clinical characteristics were also recorded. The patients were similar in age and sex. Higher serum zinc levels decreased the risk of seizure (RR = 0.95, p-value = 0.0001) and complex seizure (OR = 0.96, p-value = 0.03). Higher serum sodium levels decreased the risk of complex seizures (OR = 0.85, p-value = 0.023). Higher serum potassium levels were associated with a lower risk of seizure (OR = 0.55, p-value = 0.035). Serum calcium and magnesium levels were not associated with the risk of seizure and complex seizure. A BMI at the upper end of the normal range decreased the risk of complex seizures (OR = 0.83, p-value = 0.05). Male sex increased the risk of complex seizure (OR = 4.14, p-value = 0.016). Low serum levels of zinc, potassium and sodium are risk factors for seizure and complex seizure in febrile children. Male sex is also a risk factor for complex seizures. The time from fever to seizure was shorter in younger children. Children with a BMI at the upper end of the normal range have a lower risk of having a complex seizure.

SURG-07. QUANTIFYING THE RISK OF SHORT TERM SEIZURES FOLLOWING LASER INTERSTITIAL THERMAL THERAPY

Abstract BACKGROUND Tumor-related epilepsy is a common sequela of both primary and metastatic brain tumors, as well as radiation necrosis (RN). Laser interstitial thermal therapy (LITT) is an effective option for lesional cytoreduction but induces transient peritumoral edema that typically resolves within 3 months of the procedure. Accordingly, we quantified the risk of seizure development early post-LITT in patients with tumors or RN of diverse histologies. METHODS Patients treated with LITT for brain tumors or radiation necrosis at a high-volume center from 2015 – 2021 with at least 3 months of clinical follow-up were evaluated for seizure risk and time to discontinuation of anti-epileptic drugs (AEDs) for at least 4 weeks, with censoring at death or last follow-up. RESULTS One-hundred and seventeen patients met inclusion criteria, and 22 (19%) experienced a post-LITT seizure within 3 months of surgery. Those with pre-LITT seizures (P = 0.03), prior whole-brain radiation (WBRT) (P = 0.0099), or lower pre-operative KPS (P = 0.04) were more likely to have a post-LITT seizure. Frontal lobe tumors appeared to be more frequently associated with seizures (68% vs 45%, P = 0.06). Prior WBRT, odds ratio (OR) 4.27 (95% CI 1.01 – 18.55), P = 0.047 and pre-LITT seizure, OR 5.39 (95% CI 1.87 – 16.31), P = 0.002 remained predictive on multivariate analyses. Successful AED weaning occurred at a median of 1.68 months (no seizure within 3-months group) versus undefined for patients experiencing seizures (P = 0.015). Post-LITT seizures within 3 months were associated with worsened post-LITT overall survival, 5.95 vs 17.2 months, P &amp;lt; 0.0001. DISCUSSION Prior seizure history or previous WBRT pose a risk of breakthrough seizures following laser ablation. Neurosurgeons should consider extended AED treatment or referral for management of tumor-related epilepsy in patients with these neurologic risk factors.

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal: A focussed literature review.

There is an increasing awareness of the link between chronic alcohol consumption and the development of cognitive, behavioural and functional deficits. Currently, preventative strategies are limited and require engagement in dedicated long-term rehabilitation and sobriety services, the availability of which is low. The acute alcohol withdrawal syndrome is an episode of neurochemical imbalance leading to autonomic dysregulation, increased seizure risk and cognitive disorientation. In addition to harm from symptoms of alcohol withdrawal (e.g. seizures), the underpinning neurochemical changes may also lead to cytotoxicity through various cellular mechanisms, which long-term, may translate to some of the cognitive impairments observed in Alcohol-Related Brain Damage (ARBD). Here we review some of the pharmacological and neurochemical mechanisms underpinning alcohol withdrawal. We discuss the cellular and pharmacological basis of various potential neuroprotective strategies that warrant further exploration in clinical populations with a view to preventing the development of ARBD. Such strategies, when integrated into the clinical management of acute alcohol withdrawal, may impact large populations of individuals, who currently face limited dedicated service delivery and healthcare resource.

Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.

This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features. We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions. The UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power. This study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.

Newer glucose-lowering drugs reduce the risk of late-onset seizure and epilepsy: A meta-analysis.

Newer glucose-lowering drugs (GLDs) protect against cerebrovascular, neurodegenerative, and neuroinflammatory pathologies. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) comparing newer GLDs to placebo that assessed long-term cardiovascular and renal outcomes to analyze their potential to prevent late-onset seizures and epilepsy, separately and as a combined outcome. A comprehensive MEDLINE and CENTRAL databases search for DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitor RCTs, which reported adverse effects, including seizures and epilepsy on clinicaltrials.gov, yielded 413 studies. Of them, 27 studies with almost 200 000 patients (mean age 64.9 years, 65.6% males) were included. We calculated relative risk (RR) and odds ratio (OR) using the Mantel-Haenszel method and Peto's method. Patients taking newer GLDs had a 24% lower risk of late-onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62-0.95) and 22% lower risk of late-onset seizures only (RR = 0.78; 95% CI = 0.60-1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP-1 receptor agonists. Stroke incidence was comparable between newer GLDs and placebo group. GLP-1 receptor agonists like Semaglutide significantly reduce late-onset seizures and epilepsy, and their anti-epileptogenic potential in older adults needs further exploration. PLAIN LANGUAGE SUMMARY: Our analysis 27 clinical trials and nearly 200 000 patients evaluated the potential of newer glucose-lowering drugs (GLDs) to prevent late-onset seizures and epilepsy in older adults. The study found that newer GLDs, especially GLP-1 receptor agonists like Semaglutide, reduced the combined risk of seizures and epilepsy by 24% compared to placebo. These findings suggest that newer GLDs may offer prevention against the development of seizures and epilepsy in older adults. However, further research is needed to confirm their anti-epileptogenic effects.

The causal relationship of DTI phenotypes and epilepsy: A two sample mendelian randomization study.

Clinical studies indicated a link between DTI imaging characteristics and epilepsy, but the causality of this connection had not been established. Therefore, we employed the Mendelian randomization analysis method to determine the causal relationship between DTI imaging characteristics and epilepsy. We used Mendelian randomization analysis to identify the causal relationship between brain structure and the risk of epilepsy. GWAS data of DTI phenotypes, focal epilepsy, and genetic generalized epilepsy (GGE) were utilized in the analysis. Our study found that DTI imaging phenotypes had a causal risk relationship with epilepsy. These phenotypes had a statistical impact on the risk of epilepsy seizures. There were differences in DTI phenotype causality between GGE and focal epilepsy, which were associated with the clinical phenotype differences of the two types of epilepsy. Our study demonstrated that the diagnosis of subtypes could be assisted by comparing the differences in DTI phenotypes of specific brain regions. This meant that by studying the changes in brain regions before the onset of epilepsy, we might be able to intervene in epilepsy at an earlier stage. Our study used Mendelian randomization to explore the causal relationship between brain structure, as seen in DTI imaging, and epilepsy. We found that specific DTI phenotypes are linked to an increased risk of epilepsy seizures, with notable differences between genetic generalized epilepsy and focal epilepsy. This suggested that analyzing DTI phenotypes could help in diagnosing and potentially intervening in epilepsy earlier by finding brain changes before seizures begin.

Enhanced behavioral impact of optimized bupropion-encapsulated bilosomes over traditional niosomes treating depression.

Bupropion (Bpn), an FDA-approved NDRI (norepinephrine-dopamine reuptake inhibitor), poses risks of seizures and liver failure due to its stimulant properties, necessitating the development of alternative formulations. This research aims to develop a Bpn nanoformulation within bilosomal vesicles to enhance therapeutic efficacy at lower doses, using three bile salts, span 20 surfactants, and cholesterol via thin-film hydration. Optimization of bilosomal stability is achieved by trialing various ingredient concentrations, identifying a surfactant-to-cholesterol-to-bile salt ratio of 1.5:1:0.17µM, with sodium cholate (B.SCF) yielding the most stable system. Bpn encapsulated in the optimized bilosomal vesicle (Bpn@B.SC F) demonstrated high encapsulation efficiency of 78.142 ± 11.07% and drug-retaining capacity compared to the niosomal system. The in vitro and in vivo toxicity profile of the product is superior to the niosomal system and shows negligible toxicity with a viability rate of not less than 95%, with a sustained release profile in artificial cerebrospinal fluid (ACSF). In vivo, behavioral analysis on zebrafish revealed that Bpn@B.SC F treatment more effectively improved depressive behavior compared to free Bpn and other treatments, evidenced by increased exploration rates and reduced irregular movements, as shown through statistical and trajectory data. Hence, it is concluded that the bilosomal structure, compared to the niosomal system, is a better carrier of drugs to achieve brain delivery and improve mood.

Clinical characteristics of severe influenza as a risk factor for febrile seizures in children: a retrospective analysis.

To retrospectively analyze the clinical characteristics and independent risk factors of severe influenza combined with febrile seizures, and to provide more basis for early clinical intervention. A total of 161 children with severe influenza were collected as study subjects and divided into convulsive (FC) group (40 cases) and non-convulsive (NFC) group (121 cases) according to whether they had febrile seizures. The demographic characteristics and clinical data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of severe influenza combined with febrile seizures. The predictive efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. (1) Multiple logistic regression analysis revealed that C-reactive protein (CRP) levels, Serum interleukin 6 (IL-6) levels, Days from onset of Flu symptoms to hospitalization, cerebrospinal fluid protein (CSF-TP) levels and the influenza virus type A (FluA) infection rate were found to be independent risk factors for severe influenza combined with febrile seizures in children. (2) ROC curve analysis showed that the cut-off value of CRP, Serum IL-6, Days from onset of Flu symptoms to hospitalization and CSF-TP were 7.57 mg/L, 9.84 pg/ml, 4.5 days and 194.8 mg/L, respectively. Children with severe influenza with CRP ≥ 7.57 mg/L, Serum IL-6 ≥ 9.84 pg/ml, Days from onset of Flu symptoms to hospitalization ≤4.5 days, CSF-TP ≥ 194.8 mg/L and FluA had a significantly increased risk of febrile seizures. It is useful for clinicians to determine the risk of severe influenza combined with febrile seizures, to adjust the early treatment plan, and to reduce the incidence of critically ill patients.

Utility of Clinical Features in Identifying Electrographic Seizures in Hospitalized Patients Admitted for Non-Neurological Diagnoses.

Electrographic seizures (ESz) are seizures without prominent motor activity diagnosed with electroencephalogram and are a common complication in critically ill patients with alterations of consciousness. Previous studies suggested clinical signs, including ocular movement abnormalities, facial/periorbital twitching, or remote seizure risk factors, are sensitive for presence of ESz. To assess the utility of clinical features in identifying ESz in critically ill patients with alterations of consciousness. This is a retrospective case-control study of 50 patients admitted to the University of North Carolina (UNC) Medical Center and UNC Rex Hospital. Inpatients older than 18 years old undergoing continuous video electroencephalogram (cEEG) were included. Patients admitted for neurologic diagnoses were excluded. A total of 25 patients with ESz (Sz-EEG) were matched with 25 controls by electroencephalogram duration ± 12 hours (No-Sz-EEG). Elements of patient's history and physical findings previously shown to be sensitive for presence of ESz were collected. Descriptive statistical analyses were used. Most patients were admitted to medical ICUs (72%; n = 36). There was no difference between groups in clinical findings previously shown to be sensitive for ESz. Positive and negative likelihood ratios for these findings generally fell between 1-2 and 0.5-1, respectively, indicating they are inaccurate predictors for ESz. Patients with ESz had significantly higher mortality (p = 0.012). Our matched case-control study showed that in the critically ill patient population hospitalized in tertiary care centers and admitted for non-neurologic primary diagnoses, incidence of ocular movement abnormalities, facial/periorbital twitching, and presence of remote risk factors for seizures had low predictive accuracy for ESz. However, these findings are not generalizable to patients with neurologic diseases or to other practice settings with different levels of access to cEEG. We concluded that in this exploratory analysis of hospitalized critically ill patients with non-neurologic diagnoses, these clinical signs did not reliably stratify risk for ESz on cEEG. However, further prospective studies are needed to better evaluate these conclusions.

Common Causes of Neonatal Seizure among Neonates Admitted to Neonatal Care Unit at Al Ramadi Teaching Hospital for Maternity and Children

Neonatal seizures are the transient occurrence of signs and symptoms due to an abnormal excessive or synchronous neuronal activity in the neural cells causing paroxysmal electro clinical changes. Neonates are at high risk for seizures as compared to other age groups. The aim of this study was to identify the common causes that lead to neonatal seizure during the period from first of October 2020 to the end of July 2021using history, physical examination, and investigations in Al Ramadi teaching hospital for maternity and children. The total number of neonates diagnosed as neonatal seizure during the period of study in Al Ramadi teaching hospital for maternity and childhood was 64 cases. Total number of admissions to neonatal care unit was 4102 so the prevalence in neonatal care unit was 15.6 per 1000 live births. 30 (47.1 %) cases were diagnosed as perinatal asphyxia, 18 (28 %) cases were diagnosed as metabolic, 6 (9.4 %) cases were diagnosed as infections, seizures, 4 (6.3%) cases were diagnosed as intracranial hemorrhage, 3(4.6%) cases were diagnosed as CNS malformation, while 3 cases (4.6 %) were Unknown etiology. 38 (59.3%) of studied neonatal seizures were male, while 26 (40.7%) were female. Male to female ratio was (1.4:1). 37 (57.8%) were term babies (≥37 gestational age), while 27 (42.2%) were preterm babies (&lt;37 gestational age). 41 (64%) of studied neonatal seizure cases were born by normal vaginal delivery, while 23 (36%) of cases were born by caesarian section delivery. The most common cause of neonatal seizure was perinatal asphyxia followed by metabolic causes then infection, intracranial hemorrhage, CNS malformations and unknown causes. Male are more common than female. In term neonates more common than preterm and in normal vaginal delivery more than cesarean section.

P18.39.A SEIZURE PROPHYLAXIS IN GLIOMA SURGERY (SPRING): A MULTI-CENTRE, UNBLINDED, RANDOMISED TRIAL

Abstract BACKGROUND 50-80% of all glioma patients will suffer from seizures during their lifetime. Over half of these patients will have drug resistant seizures. Seizure risk is increased peri-operatively, at tumour progression, and shortly before death. Current guidelines do not support routine use of prophylactic peri-operative anti-epileptic drugs (AED) in seizure naïve patients; despite this, levetiracetam is frequently prescribed for this indication. The aim of this trial was to determine the clinical and cost effectiveness of prophylactic levetiracetam in seizure naïve patients undergoing surgery for a glioma at reducing the risk of seizures. MATERIAL AND METHODS Seizure naïve patients with newly diagnosed glioma undergoing surgery (biopsy or resection) were randomised (1:1) to receive 12 months prophylactic levetiracetam or no prophylaxis at 14 neurosurgery and neuro-oncology units in the UK. Participants received standard of care neurosurgery and neuro-oncology treatment and were followed until death or for a maximum of one year. The primary outcome was one year risk of first seizure analyzed using a logistic regression model and intention to treat analysis. Outcomes were analyzed by intention-to-treat. The target accrual was 804 participants. This trial was registered with ISRCTN 49474281. RESULTS Between Oct 10, 2019 and Aug 30, 2022, we randomised 96 patients, from 24 to 79 years of age, to levetiracetam (n=49) or no prophylaxis (n=47). Due to slow accrual during the Covid-19 pandemic the trial closed early. In the levetiracetam group there were 43 high grade glioma (HGG) and 6 low grade glioma (LGG), and in the no prophylaxis group there were 43 HGG and 4 LGG. Seventeen (35%) of 49 patients randomised to levetiracetam had a seizure, compared to 15 (32%) of 47 patients randomised to no prophylaxis (OR 1.25, 95%CI 0.49-3.21, p=0.64). Median time to first seizure was 4.8 months in the levetiracetam group and 3.0 months in the no prophylaxis group. In the levetiracetam group 20 (41%) of 49 patients died within 12 months (median overall survival 6.8 months; range 0.2-11.9), and in the no prophylaxis group 15 (32%) of 47 patients died within 12 months (median 4.7 months; range 0.1-12.0). There were no serious adverse events or suspected unexpected serious adverse events related to levetiracetam. CONCLUSION Due to poor accrual caused by the Covid-19 pandemic the SPRING trial closed early and is therefore underpowered. Based on the limited data there was no difference in the 12 month seizure risk in the prophylaxis and no prophylaxis patients undergoing surgery for newly diagnosed glioma. The role of prophylactic anti-epileptic drugs remains undefined.

Giant cell arteritis (GCA) as a risk factor for seizures: a cohort study

ABSTRACT Objectives The objective of this study was to assess the risk of seizures in Giant Cell Arteritis (GCA) patients in a large cohort of Israeli subjects, in comparison to matched controls. Methods Patients diagnosed with GCA between 2002 and 2017 were included. Controls were matched based on sex, age, socioeconomic status, country of birth, diabetes mellitus, and hypertension in a 4:1 ratio. Patients with seizure records prior to the study period were excluded. Hazard ratios for seizures was obtained by cox regression models. Results The study cohort was composed by 8,103 GCA patients and 32,412 matched controls. The GCA group included 5,535 women (68%), 2,644 patients born in Israel (33%), and 2,888 patients with low socioeconomic status (36%). The median age of this group was 71. During the followed cumulative person-years of 54,641 and 222,537 in the GCA and control group, respectively, 15.92 cases per 10,000 person-years was found in the GCA group, compared to 9.62 per 10,000 person-years in the controls. GCA was associated with seizures in the unadjusted (HR = 1.66, 95% CI [1.29 to 2.13]) and adjusted (HR = 1.67, 95% CI [1.3 to 2.14]) models. GCA was also associated with seizures after controlling for strokes (HR = 1.55, 95% CI [1.16 to 2.07]). Conclusion According to this study, individuals with GCA are at a higher risk of developing seizures when compared to the general population. This increased risk is independent of their predisposition for stroke. One proposed mechanism is that the GCA pro-inflammatory state may decrease the neuronal threshold for depolarization.

Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine activity in aged mice.

Alzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults; these seizures, left untreated, may worsen functional decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled mouse model of acquired chronic secondarily generalized focal seizures allows for precisely timed drug administration studies to quantify the efficacy and tolerability of ASMs in an AD-associated genetic model. We hypothesized that mechanistically distinct ASMs would exert differential anticonvulsant activity and tolerability in aged AD mice (8-15 months) to define whether rational ASM selection may benefit specific AD genotypes. Aged male and female PSEN2-N141I versus age-matched non-transgenic control (PSEN2 control) C57Bl/6J mice, and APP swe /PS1 dE9 versus transgene negative (APP control) littermates underwent corneal kindling to quantify latency to fully kindled criterion. Dose-related ASM efficacy was then compared in each AD model versus matched control over 1-2 months using ASMs commonly prescribed in older adults with epilepsy: valproic acid, levetiracetam, lamotrigine, phenobarbital, and gabapentin. Sex and AD genotype differentially impacted seizure susceptibility. Male PSEN2-N141I mice required more stimulations to attain kindling criterion (X 2 =5.521; p<0.05). Male APP/PS1 mice did not differ in kindling rate versus APP control mice, but they did have more severe seizures. There were significant ASM class-specific differences in acute seizure control and dose-related tolerability. APP/PS1 mice were more sensitive than APP controls to valproic acid, levetiracetam, and gabapentin. PSEN2-N141I mice were more sensitive than PSEN2 controls to valproic acid and lamotrigine. AD genotypes may differentially impact ASMs activity and tolerability in vivo with advanced biological age. These findings highlight the heterogeneity of seizure risk in AD and suggest that precisely selected ASMs may beneficially control seizures in AD, thus reducing functional decline.

Seizure forecasting based on AI-supported analysis of multidien and circadian cycles in EEG and non-EEG long-term datasets

AbstractLong-term datasets in epilepsy encompassing weeks to months of continuous physiological signal recordings along with novel data analysis techniques have recently advanced the understanding of epilepsy in several aspects. Patterns of seizures, interictal discharges, and autonomous nervous system activity were observed to often exhibit long, multidien cycles that are often correlated with each other. These observations have provided the basis for new approaches to forecast seizure risk from electroencephalographic (EEG) and non-EEG data.

In a child with ADHD and a history of seizure, can stimulants safely be prescribed without significantly increasing the risk of recurrent seizure?

In a child with ADHD and a history of seizure, can stimulants safely be prescribed without significantly increasing the risk of recurrent seizure?