Risk Of Seizures Research Articles

Knowledge, attitudes and practices of psychiatrists in India regarding sudden unexpected death in epilepsy (SUDEP) and seizure-related harm

Sudden unexpected death in Epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy (PWE). Awareness and taking adequate preventive measures are pivotal to reducing SUDEP. Nearly 80% of PWE live in lower-middle-income countries (LMICs) such as India where for many, epilepsy management is by psychiatrists.To evaluate the knowledge, attitude and practices of Indian psychiatrists on SUDEP and seizure risk.A cross-sectional online survey of 12 Likert response questions using validated themes, was circulated among Indian Psychiatric Society members. Non-discriminatory exponential snowballing technique leading to convenience non-probability sampling was used. The inquiry involved SUDEP-related topics including the need for and importance of counselling. Descriptive statistics and the chi-square test were used for analysis.The psychiatrists responding (n = 134) were likely to be males (72.4 %), urban (94 %) and affiliated to academic institutions (76.1 %). Nearly all saw PWE monthly with over half (54 %) seeing more than 10. Nearly two-third (64.17 %) did not counsel PWE regarding SUDEP, due to fear of raising concerns in caregivers/family (33.3 %), patients (38.9 %) or lack of time (35.6 %), though 37 % had lost patients due to SUDEP. Over two-third (66.7 %) agreed risk counselling was important. Barriers included fear of raising concerns, limited time, and training. A strong need for national SUDEP guidelines (89 %) and suitable training (75.4 %) was expressed.Though epilepsy care is provided by a considerable number of psychiatrists, there is a poor understanding of SUDEP. Enhancing the awareness and understanding of SUDEP is likely to enhance epilepsy care.

Epileptic Seizure Detection Based on Path Signature and Bi-LSTM Network With Attention Mechanism.

Automatic seizure detection using electroen-cephalogram (EEG) can significantly expedite the diagnosis of epilepsy, thereby facilitating prompt treatment and reducing the risk of future seizures and associated complications. While most existing EEG-based epilepsy detection studies employ deep learning models, they often ignore the chronological relationships between different EEG channels. To tackle this limitation, a novel automatic epilepsy detection method is proposed, which leverages path signature and Bidirectional Long Short-Term Memory (Bi-LSTM) neural network with an attention mechanism. The path signature algorithm is used to extract discriminative features for capturing the dynamic dependencies between different channels of EEG, while Bi-LSTM with attention further analyzes the inherent temporal dependencies hidden in EEG signal features. Our method is evaluated on two public EEG databases with different sizes (CHB-MIT and TUEP) and a private database from a local hospital. Two experimental settings are used, i.e., five-fold cross-validation and leave-one-out cross-validation. Experimental results show that our method achieves 99.09%, 95.60%, and 99.87% average accuracies on CHB-MIT, TUEP with 250Hz, and TUEP with 256Hz, respectively. On the private dataset, our method also achieves 99.40% average accuracy, which outperforms other methods. Furthermore, our method exhibits robustness in patients, as demonstrated by the evaluation results of cross-patient experiments.

Ketamine: Pro or antiepileptic agent? A systematic review

Purposeof Review: This evidence-based systematic review evaluated the safety of ketamine as regard the potential to provoke epilepsy to help better guide anesthesiologists in their practice. Recent findingsKetamine, originally developed as a dissociative anesthetic, has gained attention for its potential therapeutic applications in various medical conditions, including epilepsy. Ketamine is generally well-tolerated and widely used in anesthesia, however, conflicting data are confusing the anesthesiologists regarding the potential risk of seizures associated with its use. The literature that claimed the proepileeptic property are inconsistent and the mechanism of action is unclear. Moreover, the case reports had been in same certain contexts, such as procedural sedation where ketamine was used as a single agent. On the other hand, the retrospective data analysis confirmed the positive role ketamine plays as antiepileptic agent. SummaryMany studies have shown promising results for the use of ketamine as antiepileptic agent. In case of epileptic patients, there is no contraindication for using ketamine, however, combining with benzodiazepine or propofol may enhance the safety.

Decoding the clinical effects of low-grade glioma-induced cortical excitability.

Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Relationship of SSVEP response between flash frequency conditions.

This study delves into the application of Brain-Computer Interfaces (BCIs), focusing on exploiting Steady-State Visual Evoked Potentials (SSVEPs) as communication tools for individuals facing mobility impairments. SSVEP-BCI systems can swiftly transmit substantial volumes of information, rendering them suitable for diverse applications. However, the efficacy of SSVEP responses can be influenced by variables such as the frequency and color of visual stimuli. Through experiments involving participants equipped with electrodes on the brain's visual cortex, visual stimuli were administered at 4, 17, 25, and 40Hz, using white, red, yellow, green, and blue light sources. The results reveal that white and green stimuli evoke higher SSVEP responses at lower frequencies, with color's impact diminishing at higher frequencies. At low light intensity (1W), white and green stimuli elicit significantly higher SSVEP responses, while at high intensity (3W), responses across colors tend to equalize. Notably, due to seizure risks, red and blue lights should be used cautiously, with white and green lights preferred for SSVEP-BCI systems. This underscores the critical consideration of color and frequency in the design of effective and safe SSVEP-BCI systems, necessitating further research to optimize designs for clinical applications.

Predictive capability of Cys112Arg single nucleotide polymorphisms of the apolipoprotein E gene in assessing the risk of immediate and early post-traumatic seizures

This study is aimed at investigating epileptic seizures, one of the consequences of traumatic brain injury (TBI). Immediate and early post-traumatic seizures, as well as late post-traumatic epileptic seizures or post-traumatic epilepsy, can have different pathogenetic bases. The following key risk factors associated with post-traumatic epilepsy are known: duration of unconsciousness, gunshot wounds, intracranial hemorrhage, diffuse axonal injury, prolonged (more than 3 days) post-traumatic amnesia, acute subdural hematoma with surgical evacuation, immediate and early post-traumatic epileptic seizures, fracture of the skull bones. The role of genetic factors in post-traumatic seizures is poorly understood due to the complexity and multiple causal mechanisms. This paper addresses the role of genetic factors in the occurrence and severity of epileptic events in patients with TBI. In particular, we investigated the role of the Cys112Arg single nucleotide polymorphism of the apolipoprotein E gene. Apolipoprotein E is known for its role in the transport and metabolism of lipids and, therefore, the development of cardiovascular diseases; it is also associated with Alzheimer's disease and has recently been studied in the context of association with epilepsy. The study shows an association between this polymorphism and the risk of immediate and early epileptic seizures in patients with severe TBI.

Multiple sclerosis and seizures: A retrospective observational study in a multiple sclerosis autoimmunity center of excellence

PurposeThe prevalence of epilepsy in patients with multiple sclerosis (MS) is three to six times the prevalence in the general population. Mechanisms resulting in increased seizure risk are not fully understood. Our objective is to characterize patients with MS and epilepsy regarding timing of diagnoses, MS and seizure (SZ) type, EEG findings suggesting cortical dysfunction, frequency of status epilepticus (SE), and seizure freedom. MethodsThis was a single center retrospective study. Cases were obtained via DataDirect via the University of Michigan electronic medical record from January 1, 2006 through October, 12, 2016. The University of Michigan Health System is a large academic institute with a tertiary referral center and an Autoimmunity Center of Excellence. Patients were included if chart listed one or more of the top 62 epilepsy, and one or more of the top 2 MS, most frequently entered ICD9 and ICD10 codes. Patients with alternative epilepsy etiology were excluded. 74 of 361 patients were included. We collected information regarding demographics, MS and SZ type, age at diagnosis, imaging, EEG, seizure freedom, medications, and SE. ResultsWe found a high percentage of patients with SE. Most patients with imaging had multiple lesions at seizure onset. 27/54 of patients with EEG data showed electrographic evidence of cortical dysfunction. 6/8 of EEGs in PPMS showed features consistent with cortical dysfunction, followed by 9/17 in SPMS and 11/23 in RRMS. 7/8 of patients with PPMS showed EEG evidence of temporal lobe dysfunction. ConclusionTime of seizure onset relative to MS diagnosis varied with MS type suggesting distinct pathophysiology. EEG results correspond with reports of increased cortical damage and temporal dysfunction in PPMS, but are unique as a functional modality (EEG) as indicator of gray matter dysfunction. EEG findings differed in RRMS and progressive MS suggesting possibility of supportive diagnostic marker. Our data suggests higher risk of SE in progressive MS and diminished rate of seizure freedom for MS patients with SE. We conclude that early treatment with antiseizure medication would be beneficial for MS patients with SE and with progressive MS forms and SZ, in agreement with previous studies.

Neurodevelopmental outcomes in a cohort of Australian families with self-limited familial epilepsy of neonatal/infantile onset

ObjectivesTo determine: i) seizure recurrence; ii) developmental disability; iii) co-morbidities and risk factors in self-limited familial neonatal and/or infantile epilepsy (SeLFE) in a multigenerational study. MethodsFamilies were retrospectively recruited from epilepsy databases (2021–2022) in 2 paediatric hospitals, Sydney, Australia. Eligible families had 2 first degree relatives with seizures and underwent genetic testing. Demographics/clinical data were collected from interviews and medical records. Vineland Adaptive Behaviour Scales-Third Edition measured adaptive function. ResultsFifteen families participated. Fourteen had a genetic diagnosis (93%): 11 pathogenic; PRRT2 (n=4), KCNQ2 (n=3), SCN2A (n=4), 3 likely pathogenic; KCNQ2 (n=1), SCN8A (n=2). Seizures affected 73 individuals (ages 1–76 years); 30 children and 20 adults had in-depth phenotyping. Ten of 50 individuals (20%) had seizure recurrence, aged 8–65 years. Median time from last neonatal/infantile seizure was 11.8/12.8 years. Predictors of recurrence were high seizure number (p=0.05) and longer treatment duration (p=0.03). Seven children had global developmental delay (GDD): mild (n=4), moderate (n=1) and severe (n=2). Vineland-3 identified 3 had low-average and 3 had mild-moderately impaired functioning. The majority (82%) were average. GDD was associated with older age at last seizure (p=0.03), longer epilepsy duration (p=0.02), and higher number of anti-seizure medications (p=0.05). Four children had speech delay, 5 (10%) had Autism Spectrum Disorder. Paroxysmal kinesiogenic dyskinesia (n=5) occurred in 4 families and hemiplegic migraine (n=8) in 3 families. ConclusionsIndividuals with SeLFE have a small risk of recurrent seizures (20%) and neurodevelopmental disability. Significant predictors are higher seizure number and longer epilepsy duration. Developmental surveillance is imperative.

Modified CAVE score for predicting late seizures after intracerebral hemorrhage

Background and purposeSeizures commonly occur in patients with intracerebral hemorrhage (ICH). Anticonvulsants are commonly used for preventing seizures in patients with ICH. Thus, patients with ICH at high risk of seizures must be identified. The study aims to elucidate whether double the score of cortex involvement in ICH patients can increase accuracy of CAVE score for predicting late seizures.MethodThis retrospective analysis of the medical records of surviving patients admitted between June 1, 2013, and December 31, 2019. Validated the CAVE score and modified it (CAVE2). The main outcome of patients with ICH was seizures. The first seizures occurring within 7 days after a stroke were defined as early seizures. Seizures occurring after 1 week of stroke onset, including patients who had experienced early seizures or patients who had not, were defined as late seizures. CAVE and CAVE2 scores were validated using the cohort. The accuracy and discrimination of those two scores were accessed by the area under the operating characteristic curve. Akaike information criterion, integrated discrimination improvement, and continuous net reclassification improvement were used to assess the performance of the CAVE and CAVE2 scores.ResultsIn the cohort showed that late seizures occurred in 12.7% (52/408) of patients with ICH. Male sex, age > 65 years, cortex involvement, and early seizures were associated with the occurrence of late seizures, with odds ratios of 2.09, 2.04, 4.12, and 3.78, respectively. The risk rate of late seizures was 6.66% (17/255), 14.8% (17/115), and 47.4% (18/38) for CAVE scores ≤ 1, 2, and ≥ 3, and 4.6% (12/258), 18.3% (13/71), and 54.4 (20/37) for CAVE2 scores ≤ 1, 2, and ≥ 3 respectively. The C-statistics for the CAVE and CAVE2 scores were 0.73 and 0.74 respectively.ConclusionThe CAVE score can identify patients with ICH and high risk for late seizures. The CAVE can be modified by changing the score of cortex involvement to 2 points to improve accuracy in predicting late seizures in patients with ICH.

Variation in seizure risk increases from antiseizure medication withdrawal among patients with well-controlled epilepsy: A pooled analysis.

Guidelines suggest considering antiseizure medication (ASM) discontinuation in seizure-free patients with epilepsy. Past work has poorly explored how discontinuation effects vary between patients. We evaluated (1) what factors modify the influence of discontinuation on seizure risk; and (2) the range of seizure risk increase due to discontinuation across low- versus high-risk patients. We pooled three datasets including seizure-free patients who did and did not discontinue ASMs. We conducted time-to-first-seizure analyses. First, we evaluated what individual patient factors modified the relative effect of ASM discontinuation on seizure risk via interaction terms. Then, we assessed the distribution of 2-year risk increase as predicted by our adjusted logistic regressions. We included 1626 patients, of whom 678 (42%) planned to discontinue all ASMs. The mean predicted 2-year seizure risk was 43% [95% confidence interval (CI) 39%-46%] for discontinuation versus 21% (95% CI 19%-24%) for continuation. The mean 2-year absolute seizure risk increase was 21% (95% CI 18%-26%). No individual interaction term was significant after correcting for multiple comparisons. The median [interquartile range (IQR)] risk increase across patients was 19% (IQR 14%-24%; range 7%-37%). Results were unchanged when restricting analyses to only the two RCTs. No single patient factor significantly modified the influence of discontinuation on seizure risk, although we captured how absolute risk increases change for patients that are at low versus high risk. Patients should likely continue ASMs if even a 7% 2-year increase in the chance of any more seizures would be too much and should likely discontinue ASMs if even a 37% risk increase would be too little. In between these extremes, individualized risk calculation and a careful understanding of patient preferences are critical. Future work will further develop a two-armed individualized seizure risk calculator and contextualize seizure risk thresholds below which to consider discontinuation. Understanding how much antiseizure medications (ASMs) decrease seizure risk is an important part of determining which patients with epilepsy should be treated, especially for patients who have not had a seizure in a while. We found that there was a wide range in the amount that ASM discontinuation increases seizure risk-between 7% and 37%. We found that no single patient factor modified that amount. Understanding what a patient's seizure risk might be if they discontinued versus continued ASM treatment is critical to making informed decisions about whether the benefit of treatment outweighs the downsides.

Temporal relationship between levetiracetam nonadherence and breakthrough seizures in a preclinical model of temporal lobe epilepsy.

Poor medication adherence remains a concern for individuals managing their epilepsy with antiseizure medicines (ASMs); however, ethical concerns around withholding medication make it impossible to study the causal relationship between missed doses and seizures in patients. Previous preclinical studies from our group suggest that mechanistically distinct ASMs have varying degrees of forgiveness when a dose is missed. However, with only a few ASMs studied in the context of nonadherence, we sought to expand on previous work to understand the relationship between levetiracetam (LEV) nonadherence and breakthrough seizures. Chronic oral dosing was initiated in rats with established epilepsy via our automated medication-in-food delivery system coupled to 24/7 video-electroencephalographic recording. Baseline seizure burden was established for 4 weeks before enrolling subjects into a 4-week treatment period with LEV in a 100% fully adherent (75 mg/kg four times daily) or 50% variably adherent paradigm. The temporal relationship between missed doses and breakthrough seizures was correlated with LEV plasma and brain concentrations in separate cohorts of animals. Full adherence to LEV significantly improved seizure control by 50% in half of the animals. Poor adherence worsened seizure frequency by 85%, with most rats having more severe seizures that formed in clusters following missed doses. LEV concentrations remained below therapeutic levels (<10 μg/mL) in nonadherent animals, with brain and plasma levels directly correlating with the degree of adherence in a 24-h period. Missed doses of LEV immediately increased the risk of breakthrough seizures; however, this risk was significantly reduced with improved adherence in a 24-h period. These findings enhance our understanding of ASM nonadherence in preclinical models, highlighting that the timing of missed doses and their impact on seizures may vary between different ASMs. Notably, LEV demonstrates a robust pharmacokinetic reliance on missed doses leading to breakthrough seizures.

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Up to date the brain tumors incidence keeps growing worldwide. Epilepsy and epileptic seizures are one of the most common clinical features of brain tumors. The aim of the study was to invent the algorithms antiepileptic treatment of patients with primary and metastatic brain tumors based on literature data. We searched eLIBRARY, PubMed databases by keywords. We concluded, that preventive antiepileptic drugs administration in patients with primary or metastatic brain lesions does not lower the risk of acute symptomatic postoperative seizures or epilepsy incidence, and therefore should not be recommended. Experts’ opinion states that in patients with brain tumors even one unprovoked seizure makes it feasible to initiate antiepileptic drugs therapy as soon as possible. In case of two or more unprovoked episodes (with over 24 hours difference) the diagnosis of “epilepsy” is legitimate and antiepileptic therapy should be started. The treating physician’s choice of antiepileptic therapy is based on type of seizures, age and sex of the patient, the comorbidity and potential antiepileptic drugs pharmacokinetic interactions with other drugs (including chemotherapy), in particular, one should avoid the use of liver microsomal-inducing antiepileptic drugs. The presented algorithms provide the decision-making guidelines in case of intraoperative focal seizures, acute symptomatic seizures and status epilepticus occurrence in early postoperative period.

Alcohol for seizure induction in the epilepsy monitoring unit

Rationale: Seizure induction techniques are used in the epilepsy monitoring unit (EMU) to increase diagnostic yield and reduce length of stay. There are insufficient data on the efficacy of alcohol as an induction technique. MethodsWe performed a retrospective cohort study using six years of EMU data at our institution. We compared cases who received alcohol for seizure induction to matched controls who did not. The groups were matched on the following variables: age, reason for admission, length of stay, number of antiseizure medications (ASM) at admission, whether ASMs were tapered during admission, and presence of interictal epileptiform discharges. We used both propensity score and exact matching strategies. We compared the likelihood of epileptic seizures and nonepileptic events in cases versus controls using Kaplan-Meier time-to-event analysis, as well as odds ratios for these outcomes occurring at any time during the admission. ResultsWe analyzed 256 cases who received alcohol (median dose 2.5 standard drinks) and 256 propensity score-matched controls. Cases who received alcohol were no more likely than controls to have an epileptic seizure (X2(1) = 0.01, p = 0.93) or nonepileptic event (X2(1) = 2.1, p = 0.14) in the first 48 h after alcohol administration. For the admission overall, cases were no more likely to have an epileptic seizure (OR 0.89, 95 % CI 0.61–1.28, p = 0.58), nonepileptic event (OR 0.97, CI 0.62–1.53, p = 1.00), nor require rescue benzodiazepine (OR 0.63, CI 0.35–1.12, p = 0.15). Stratified analyses revealed no increased risk of epileptic seizure in any subgroups. Sensitivity analysis using exact matching showed that results were robust to matching strategy. ConclusionsAlcohol was not an effective induction technique in the EMU. This finding has implications for counseling patients with epilepsy about the risks of drinking alcohol in moderation in their daily lives.

Association of a Remote Blood Pressure Monitoring Program With Postpartum Adverse Outcomes

(Abstracted from Obstet Gynecol 2023;141:1163–1170) A large percentage of maternal complications and deaths in the United States are due to hypertensive disorders of pregnancy; although these complications gradually improve after delivery, there are cases where it takes months for blood pressure to return to normal. Research has shown that blood pressure typically peaks 3 to 7 days postpartum, meaning that many individuals experience peaks in their blood pressure that put them at risk for stroke or seizure after discharge from the hospital.

ApoE variant associated with cognitive resilience alters AD associated hyperexcitability in dentate granule neurons

AbstractBackgroundCognitive decline in Alzheimer’s disease (AD) differs based on background genetics even with similar pathology. Using genetic linkage analysis, we identified a coding variant in the receptor binding domain of ApoE that leads to changes in cognitive performance across a genetically diverse population harboring familial (FAD) mutations known as the AD‐BXDs (Neuner et al., 2019). Using CRISPR‐based gene editing, we developed a C57BL/6J (B6) mouse carrying the ApoE allele from the DBA/2J (D2) strain (ApoEE163D) and determined that ApoEE163D mice with 5XFAD transgene (ApoEE163D‐5XFAD) are susceptible to cognitive decline compared to B6‐5XFAD mice (Kaczorowski, et al., 2022).Analysis of hippocampal RNA sequencing profiles from the hippocampus indicates robust transcriptomic changes in dentate gyrus (DG) granule cells associated with cognitive resilience to FAD mutations in the presence of the B6 ApoE genotype. Here we aim to evaluate the functional implications.MethodWe adapted the Patch‐Seq method (Cadwell et al., 2017) to investigate transcriptional and electrophysiological changes within the DG associated with both FAD mutations and ApoE genotype. Whole‐cell patch clamp was used to evaluate intrinsic excitability of granule cells from 14month old B6 mice carrying FAD mutations and ApoEE163D, compared to age matched controls. The cellular contents, including the nucleus, were collected after each recording to characterize the transcriptome, and the cells were filled and stained for downstream analysis of neuronal morphology.ResultWe observed a significant interaction of the 5XFAD and ApoE genotypes on DG granule cell excitability. Specifically, cells from ApoEE163D‐5XFAD required less current stimulus to both elicit a single action potential, and to fire in response to a current ramp (rheobase). Although input resistance was comparable across all 4 groups, the sag ratio of ApoEE163D‐5XFAD was also reduced.ConclusionEnhancement of DG excitability of ApoEE163D‐5XFAD mice may underlie increased seizure susceptibility that has been reported previously in FAD animal models on D2 genetic background and associated with increased risk of seizures in AD patients. Ongoing work will integrate DG excitability with single‐cell RNAseq, morphology, and behavior to dissect mechanisms underlying the modifier effect of ApoE genotype on susceptibility and resilience to cognitive deficits in FAD mutation carriers.

The Effectiveness of Prehospital Administration of Tranexamic Acid in Reducing Mortality in Trauma Patients: An Overview.

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces bleeding by inhibiting plasminogen activation and fibrin clot degradation. Its role in prehospital trauma management remains unclear. This article aims to systematically review the current evidence on the effect of prehospital TXA administration on mortality in adult and pediatric trauma patients. A literature search was conducted of PubMed, Web of Science, Scopus, and Cochrane databases from March 2023 to August 2023 for studies evaluating the impact of prehospital TXA use on trauma mortality. Inclusion criteria were articles published in the English language in the past 20 years focusing on clinical outcomes of prehospital TXA administration. Data on all-cause mortality, thromboembolic events, and time to TXA administration were extracted. In adult trauma, prehospital TXA appears to reduce early all-cause mortality when given within three hours of injury without increasing thromboembolic risks. Some studies found decreased delayed mortality, while others found no difference. In pediatric trauma, preliminary evidence suggests TXA may lower in-hospital mortality in hemodynamically unstable patients, though higher doses may increase seizure risk. Early prehospital administration of TXA within three hours of adult trauma may reduce mortality through improved hemorrhage control. Potential benefits in pediatric trauma warrant further investigation, balancing efficacy against safety risks such as seizures from high doses. Well-designed randomized trials are needed to validate optimal TXA dosing strategies across age groups and injury severity levels.

Ramifications of Sleep Deprivation and Stress on Juvenile Epilepsy

According to recent studies, there is a correlation between stress, sleep deprivation, and elevated levels of epileptic activity among the adult population. An increased presence of either sleep deprivation or stress within epileptic adults typically supports the correlation between stress and sleep deprivation and elevated levels of epileptic activity, showcasing them at an increased risk for experiencing an increase in epileptiform discharges, spike waves occurring in the form of a single discharge that is typically associated with epilepsy and seizures. Researchers have demonstrated that the presence of sleep deprivation and stress is a significant indicator for increased levels of epileptic activity in the adult population, however, they have yet to conclude whether the trend exists within adolescent populations diagnosed with epilepsy, specifically from the ages of 5 to 18. A qualitative study, an interview, and a questionnaire procedure with 47 respondents and 5 interviewees that were adolescents diagnosed with epilepsy and asked questions concerning three themes: (1) The presence of Stress in Juvenile Epilepsy, (2) REM Sleep Duration, (3) Academic and Societal Pressures. The results of the analyses concluded that I found the facilitation of increases in the epileptic activity to correlate with an increased presence of sleep deprivation and stress within adolescents with epilepsy, as it heightens the risk for seizures.

First unprovoked seizures among soldiers recruited to the Israeli Defense Forces during 10 consecutive years: A population-based study.

The management of patients after a first unprovoked seizure (FUS) can benefit from stratification of the average 50% risk for further seizures. We characterized subjects with FUSs, out of a large generally healthy homogenous population of soldiers recruited by law to the Israeli Defense Forces, to investigate the role of the type of service, as a trigger burden surrogate, in the risk for additional seizures. Soldiers recruited between 2005 and 2014, who experienced an FUS during their service, were identified from military records. Subjects with a history of epilepsy or lack of documentation of FUS characteristics were excluded from the study. Data on demographics and military service and medical details were extracted for the eligible soldiers. Of 816 252 newly recruited soldiers, representing 2 138 000 person-years, 346 had an FUS, indicating an incidence rate of 16.2 per 100 000 person-years. The FUS incidence rate was higher in combat versus noncombat male and female soldiers (p < .0001). Most subjects (75.7%) were prescribed antiseizure medications (ASMs), and 29.2% had additional seizures after the FUS. Service in combat units, abnormal magnetic resonance imaging, and being prescribed ASMs were correlated with a lower risk of having multiple seizures (95% confidence interval [CI] = .48-.97, .09-.86, .15-.28, respectively). On multivariate analysis, service in combat units (odds ratio [OR] = .48 for seizure recurrence, 95% CI = .26-.88) and taking medications (OR = .46, 95% CI = .24-.9) independently predicted not having additional seizures. FUS incidence rate was higher in combat soldiers, but they had a twofold lower risk of additional seizures than noncombat soldiers, emphasizing the value of strenuous triggers as negative predictors for developing epilepsy. This suggests a shift in the perception of epilepsy from a "yes or no" condition to a continuous trend of predisposition to seizures, warranting changes in the ways etiologies of epilepsy are weighted and treatments are delivered.

Delineating clinical and developmental outcomes in STXBP1-related disorders.

STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end points, have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1281 cumulative patient-years of seizure and developmental histories in 162 individuals with STXBP1-related disorders and established a natural history framework. STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions in STXBP1 (n = 39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n = 30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of end points revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range of trial success probabilities across the age span, with the highest probability in early childhood between 1 year and 3.5 years. In summary, we delineated epilepsy and developmental trajectories in STXBP1-related disorders using standardized measures, providing a foundation to interpret future therapeutic strategies and inform rational trial design.

The Impact of Vaccination against SARS-CoV-2 on Health Outcomes and Hospital Visits after Omicron Infection in Children and Adolescents Aged 5-18 Years: A Danish Nation-Wide Cohort Study.

This study investigates the impact of vaccination against SARS-CoV-2 on health outcomes and hospital contacts in children and adolescents aged 5-18 years infected with the SARS-CoV-2 Omicron variant, comparing previously vaccinated with unvaccinated. Using national register data, vaccinated and unvaccinated Danish children and adolescents with a positive SARS-CoV-2 test between 1 January and 31 March 2022 (Omicron dominance period) were included. The Prior Event Rate Ratio (PERR) was used to explore differences in hospital contacts (hospitalizations and emergency room (ER) visits), while Inverse Treatment Probability Weighted (IPW) risk ratios were used to explore the risk of severe health outcomes within six weeks following SARS-CoV-2 infection. Vaccinated 5-11-year-old girls had fewer visits to the ER compared to unvaccinated ones, PERR 0.92 (95% CI 0.84-1.00). Vaccinated 5-11-year-old boys had fewer hospitalizations (PERR 0.79 (0.64-0.99)) and more ER visits (PERR 1.13 (1.04-1.22)) compared to unvaccinated ones. An unadjusted and significant lower risk of febrile seizure among vaccinated 5-11-year-olds compared to unvaccinated ones was found (risk ratio 0.12 (0.04-0.39), p ≤ 0.01. No significant differences were found for severe conditions or for croup or pneumonia in either age group. The results indicate a modest protective effect of the vaccine in terms of hospital contacts, but no protective effect on health outcomes after SARS-CoV-2 Omicron infection in this population of Danish children and adolescents.