Early Seizures Research Articles

GLIOMA-RELATED EPILEPSY

Diffuse low-grade gliomas (LGGs), originating from glial tissue, have a propensity to progress to higher-grade tumors over time, presenting a complex challenge in clinical management. Glioma-associated epilepsy is a significant clinical indicator influencing both treatment strategies and prognostication. This study aims to assess the impact of glioma-related epilepsy on treatment outcomes and explore the current management guidelines. Material and Methods A retrospective analysis was conducted on 38 patients diagnosed with LGGs (WHO grades 2 and 3) treated in our neurosurgical department from 2013 to 2023. The focus was on glioma-related epileptic seizures, with outcomes evaluated using the Engel classification six months post-surgery. Additionally, anti-seizure medication (ASM) regimens were reviewed, and current National Institute for Health and Care Excellence (NICE) guidelines on low-grade gliomas were synthesized. Results Of the 38 patients, 30 had diffuse astrocytoma and 8 had oligodendroglioma. Among those with glioma-related epilepsy (n=25), management strategies included biopsy only (8%), gross total resection (GTR) (40%), subtotal resection (StR) (32%), and partial resection (PaR) (20%). No significant correlation was found between seizures and tumor volume, growth rate, or histological findings. However, a positive correlation between the extent of surgical resection and improved Engel outcomes was observed. Discussion Existing research suggests that early seizures may be a favorable prognostic indicator for malignant progression-free and overall survival. Epilepsy significantly impacts the quality of life for glioma patients. Exploring targeted epilepsy surgery for glioma-related seizures could potentially enhance patient outcomes and quality of life posttreatment. Conclusion Advancing approaches in epilepsy surgery for glioma-related seizures holds promise for improving patient quality of life and treatment efficacy. Further investigation into these strategies is warranted.

Local field potential-based brain-machine interface to inhibit epileptic seizures by spinal cord electrical stimulation.

This study proposes a closed-loop brain-machine interface (BMI) based on spinal cord stimulation to inhibit epileptic seizures, applying a semi-supervised machine learning approach that learns from Local Field Potential (LFP) patterns acquired on the pre-ictal (preceding the seizure) condition.
 
Approach. LFP epochs from the hippocampus and motor cortex are band-pass filtered from 1 to 13 Hz, to obtain the time-frequency representation using the continuous Wavelet transform, and successively calculate the phase lock values (PLV). As a novelty, the Z-score-based PLV normalization using both modified k-means and Davies-Bouldin's measure for clustering is proposed here. Consequently, a generic seizure's detector is calibrated for detecting seizures on the normalized PLV, and enables the spinal cord stimulation for periods of 30 s in a closed-loop, while the BMI system detects seizure events. To calibrate the proposed BMI, a dataset with LFP signals recorded on five Wistar rats during basal state and epileptic crisis was used. The epileptic crisis was induced by injecting pentylenetetrazol (PTZ). Afterwards, two experiments without/with our BMI were carried out, inducing epileptic crisis by PTZ in Wistar rats. 

Main Results. Stronger seizure events of high LFP amplitudes and long time periods were observed in the rat, when the BMI system was not used. In contrast, short-time seizure events of relative low intensity were observed in the rat, using the proposed BMI. The proposed system detected on unseen data the synchronized seizure activity in the hippocampus and motor cortex, provided stimulation appropriately, and consequently decreased seizure symptoms. 

Significance. Low-frequency LFP signals from the hippocampus and motor cortex, and cord spinal stimulation can be used to develop accurate closed-loop BMIs for early epileptic seizures inhibition, as an alternative treatment.

Agomelatine Is Unable to Attenuate Kainic Acid-Induced Deficits in Early Life Communicative Behavior.

Early life seizures are associated with a variety of behavioral comorbidities. Among the most prevalent of these are deficits in communication. Auditory communicative behaviors in mice, known as ultrasonic vocalizations (USVs), can be used to assess potential treatments. Agomelatine is a melatonin agonist that effectively reduces behavioral comorbidities of seizures in adults; however, its ability to attenuate seizure-induced communicative deficits in neonates is unknown. To address this, we administered C57 mice either saline or kainic acid (KA) on postnatal day (PD) 10. The mice then received either agomelatine or saline 1-h post-status epilepticus. On PD 11, we assessed the quantity of USVs produced, the duration, peak frequency, fundamental frequency, and amplitude of the vocalizations, as well as the call type utilization. We found that KA increased vocal production and reduced USV variability relative to controls. KA also increased USV duration and amplitude and significantly altered the types of calls produced. Agomelatine did not attenuate any of the deficits. Our study is the first to assess agomelatine's efficacy to correct USVs and thus provides an important point of context to the literature, indicating that despite its high therapeutic efficacy to attenuate other behavioral comorbidities of seizures, agomelatine's ability to correct neonatal communicative deficits is limited.

Accumulated seizure burden predicts neurodevelopmental outcome at 36 months of age in patients with tuberous sclerosis complex.

Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear. Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of candidate biomarkers to predict 36-month neurodevelopmental subgroup using univariable and multivariable logistic regression. Candidate biomarkers included age at seizure onset, accumulated seizure burden, tuber volume, sex, and earlier neurodevelopmental test scores. Patients clustered into two neurodevelopmental subgroups at 36 months of age, higher and lower scoring. Subgroup was mostly (75%) the same at 12 months. Significant univariable effects on subgroup were seen only for accumulated seizure burden (largest effect), earlier test scores, and tuber volume. Neither age at seizure onset nor sex significantly distinguished 36-month subgroups, although for girls but not boys there was a significant effect of age at seizure onset. In the multivariable model, accumulated seizure burden and earlier test scores together predicted 36-month neurodevelopmental group with 82% accuracy and an area under the curve of .86. These results untangle the contributions of age at seizure onset and accumulated seizure burden to neurodevelopmental outcomes in young children with TSC. Accumulated seizure burden, rather than the age at seizure onset, most accurately predicts neurodevelopmental outcome at 36 months of age. These results emphasize the need to manage seizures aggressively during the first 3 years of life for patients with TSC, not only to promote seizure control but to optimize cognitive function.

Mouse models of Slc35a2 brain mosaicism reveal mechanisms of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy.

Brain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of SLC35A2 in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored. Here, we generated a novel Slc35a2 floxed allele, which we used to develop two Slc35a2 conditional knockout mouse lines targeting (1) the Emx1 dorsal telencephalic lineage (excitatory neurons and glia) and (2) the Olig2 lineage (oligodendrocytes). We examined brain structure, behavior, and seizure activity. Knockout of Slc35a2 from the Emx1 lineage, which targets both cortical neurons and oligodendrocytes, resulted in early lethality and caused abnormal cortical development, increased oligodendroglial cell density, early onset seizures, and developmental delays akin to what is observed in patients with MOGHE. By tracing neuronal development with 5-Ethynyl-2'-deoxyuridine (EdU) birthdating experiments, we found that Slc35a2 deficiency disrupts corticogenesis by delaying radial migration of neurons from the subventricular zone. To discern the contributions of oligodendrocytes to these phenotypes, we knocked out Slc35a2 from the Olig2 lineage. This recapitulated the increased oligodendroglial cell density and resulted in abnormal electroencephalographic activity, but without a clear seizure phenotype, suggesting Slc35a2 deficiency in neurons is required for epileptogenesis. This study presents two novel Slc35a2 conditional knockout mouse models and characterizes the effects on brain development, behavior, and epileptogenesis. Together, these results demonstrate a direct causal role for SLC35A2 in MOGHE-like phenotypes, including a critical role in neuronal migration during brain development, and identify neurons as key contributors to SLC35A2-related epileptogenesis.

MENINGIOMA OEDEMA AND SEIZURES – A META-ANALYSIS

Abstract AIMS Meningiomas are primary intracranial neoplasms. Oedema and seizures can occur in the pre and postoperative period and oedema is commonly cited as a risk factor for seizures. A meta-analysis of eight studies published in 2016 identified preoperative oedema as a risk factor for preoperative seizures. Our aim is to perform an updated review. The literature base has grown and there are studies presenting data on postoperative seizures. METHOD The meta-analysis protocol is uploaded to INPLASY (DOI: 10.37766/inplasy2023.7.0101). Existing literature from seven databases was collected and Cochrane guidance was followed. Data was analysed using packages within R programming software. Part of this work was presented in draft form at ILAE 2023 and here we present updated work. RESULTS Our search identified 44 unique studies for meta-analysis. Many studies were biased by subjective oedema measurement or lack of seizure definition. Preoperative oedema increased the odds of preoperative seizures; odds ratio (OR) 3.41, 95% confidence interval (CI) 3.00 to 3.87, p <.001, studies (k) 24, participants (n) 6,917, low heterogeneity (I2) 0%. There were no subgroup differences by oedema measurement or use of seizure definition. Preoperative oedema was associated with increased odds of early postoperative seizure (within one week of surgery) but the difference was not significant; OR 1.39, CI 0.97-1.99, p =.063, k = 6, n = 2,445, I2 = 0% (low). Preoperative oedema increased the odds of late postoperative seizures; OR 1.95, CI 1.55-2.45, p <.001, k = 7, n = 1,722, I2 = 0% (low). Oedema was associated with seizures following stereotactic radiosurgery in two studies. CONCLUSION Preoperative oedema is associated with seizures prior to and following treatment. While there is a positive association between preoperative oedema and early postoperative seizure it is not statistically significant.

Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts.

Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery. We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.0%). The surgical strategy utilized "anatomy-guided resection," targeting specific anatomical compartments infiltrated by the tumor (e.g., temporal pole, anterior temporo-mesial region = uncus and hippocampal head, posterior temporo-mesial, insula) rather than treating the tumor as a single mass. The most frequent histologies were ganglioglioma CNS WHO grade 1 (55 patients, 35.0%) and IDH1 wildtype glioblastoma (36 patients, 22.9%). Tumor infiltration was most commonly found in the anterior temporo-mesial compartment (145 patients, 92.4%). An anterior temporal lobectomy was part of the surgical strategy in 131 cases (83.4%). Seventy-six patients (48.4%) with drug-resistant epilepsy underwent a formal presurgical epilepsy work-up, including depth electrode placement in three cases. Complete resections were achieved in 117 patients (74.5%), with supramarginal resections performed in 89 cases (56.7%). Four patients experienced non-temporary neurological complications (CTCAE grade 3-5). At 6 months, 127 of 147 assessable patients (86.4%) were free from seizures or auras (ILAE class 1), excluding early postoperative seizures (<30 days). At 24 months, 122 of 144 assessable cases (84.7%) remained seizure-free (ILAE class 1). Kaplan-Meier estimates for 5-year overall survival were 98.5% for non-recurrent glioneuronal tumors. The 2-year overall survival estimates were 96.0% for 24 primary diffuse CNS WHO grade 2 and 3 gliomas and 55.2% for 30 patients undergoing first surgeries for glioblastomas/astrocytomas CNS WHO grade 4. Combining both epilepsy and tumor surgery concepts in the surgical treatment of intrinsic brain tumors involving the mesial temporal lobe, often extending into the insula, led to more extensive resections, improved seizure outcomes, and potentially even better patient survival outcomes.

Subdural Electroencephalogram Monitoring for Early Seizure Detection in Patients With Subdural Hematoma: Considering It in the Real World.

Subdural Electroencephalogram Monitoring for Early Seizure Detection in Patients With Subdural Hematoma: Considering It in the Real World.

Regulating the NMDA/NR2B signaling pathway mediates anticonvulsant, antineuroinflammation, and anti-oxidative stress effects of 1,3,benzothiazole derivative 1M in pentylenetetrazole-induced kindling in mice.

Periodic epileptic episodes are the hallmark of epilepsy, a prevalent neurological disorder. Research suggests a significant correlation between neuroinflammation and oxidative stress in a variety of neurological diseases, such as epilepsy. A substantial amount of evidence supports the role of N-methyl-D-aspartate receptors (NMDARs) in the progression of epilepsy. Although several lines of research have disclosed numerous biochemical effects of early seizures, its connection with disturbed NMDAR/NR2B subunit expression remains unclear. 2-Mercaptobenzothiazole (MBT) is a vital scaffold with several biological activities, and its various substitutes show promising anti-inflammatory potential. The current study aimed to investigate the newly synthesized 1,3-(benzothiazole-2-sulfanyl)-1-(morpholine-4-yl)ethan-1-one (1M), a substituted MBT, for its neuroprotective potential in a mice model of pentylenetetrazole-induced epilepsy (PTZ), by modulating NMDA/NR2B pathway. The compound was tested for docking and simulation analysis, demonstrating a solid and stable bond with the NR2B subunit of NMDA. To ascertain the effects of 1M, as well as to further illustrate its mechanism of neuroprotection via NMDA/NR2B in PTZ-induced kindling model, mice of either sex were given two doses of test compound, 1M (10mg/kg and 20mg/kg). The behavioral assessments were evaluated using open-field, Y-maze, and elevated-plus maze tests, which indicated improved behavioral alterations caused by PTZ after 1M treatment. The antioxidant profiling was done by estimating glutathione-S-transferase (GST), catalase (CAT), reduced glutathione (GSH), and LPO (lipid peroxidation) in hippocampal tissues, where the test compound 1M significantly restored the depleted antioxidants, showcasing its antioxidant potential. Moreover, the cellular morphological damages induced by PTZ were detected by H&E staining, which was rescued after 1M administration. Furthermore, the activation of the inflammatory pathway was confirmed by quantitative analysis of inflammatory mediators tumor necrotic factor (TNF-α), nuclear factor kappa B (NF-κB), and cylooxegenase2 (COX-2) by enzyme-linked immunosorbent assay (ELISA), where 1M administration significantly ameliorated their expression. Furthermore, to demonstrate the involvement of the NR2B pathway, NR2B-antagonist ifenprodil was employed, and results were further confirmed through RT-PCR analysis. Our results, when considered collectively, indicate that 1M may act by inhibiting the NR2B subunit of the NMDA receptor, subsequently mitigating downstream oxidative stress and inflammatory mediators through various pathways.

Acute Symptomatic Epileptic Seizures After Microsurgical Removal of Supratentorial Meningiomas

RELEVANCE. One of the problems complicating the early postoperative period in patients with supratentorial meningiomas is epileptic seizures, which in 9-16% of cases first develop within the first 7 days after tumor removal (acute symptomatic epileptic seizures).AIM OF THE STUDY. To identify risk factors for the occurrence of acute symptomatic epileptic seizures in the early postoperative period in patients with supratentorial meningiomas and to evaluate the effectiveness of prophylactic antiepileptic therapy.MATERIAL AND METHODS. A prospective, single-blind, randomized, placebo-controlled study was conducted using the sequential, alternate-arm randomization method. The treatment of 102 patients with supratentorial meningiomas was analyzed, in whom the tumor was removed between 01.01.2021 and 30.09.2023 at the N.V. Sklifosovsky Research Institute for Emergency Medicine. To identify risk factors for the development of acute symptomatic epileptic seizures in patients, we assessed the data of the anamnesis, examination of the patient, electroencephalography before surgery, neuroimaging before and after tumor resection, as well as the characteristics of the intraoperative period, duration and outcomes of hospitalization. To evaluate the effectiveness of the prophylactic use of antiepileptic drugs, patients were divided into two groups. The first group consisted of 49 patients who took an antiepileptic drug as a prophylaxis of early epileptic seizures. The second group consisted of 53 patients who took a placebo drug. Both groups were divided into two subgroups each depending on the development of an epileptic seizure or its absence after surgery. In the first group, patients with epileptic seizures were considered the main subgroup, the patients without seizures were considered the control. We assessed the placebo group similarly.RESULTS. In the placebo group, a risk factor for the development of acute symptomatic epileptic seizures was the transection of one or more veins, which was necessary to achieve sufficient surgical access, leading to a change in cerebral venous blood flow (p=0.013, odds ratio (OR)=11.43; 95% CI [1.75–74.73]). In both the antiepileptic drug group and the placebo group, risk factors included an increase in the volume of cerebral edema according to postoperative CT scan data compared with preoperative (p=0.05, OR=18.8; 95% CI [2.0–182.7] and p=0.01, OR=12.6; 95% CI [2.36–68.0], respectively), as well as hemorrhagic transformation of the perifocal edema zone (p=0.03, OR=8.75; 95% CI [1.36–56.4] and p=0.02, OR=9.7; 95% CI [2.1–44.6], respectively). The efficacy of prophylactic use of antiepileptic drugs in reducing the incidence of acute symptomatic epileptic seizures in the first 7 days after surgery was not established (p=0.295, OR=0.533; 95% CI [0.181–1.572]).CONCLUSION. We have identified the following risk factors for the development of acute symptomatic epileptic seizures: an increase in the volume of cerebral edema compared to the preoperative level according to postoperative computed tomography, the development of hemorrhagic transformation of cerebral edema in both groups, and the intersection of one or more veins during surgery (in the placebo group). Confirmation of the efficacy of routine use of antiepileptic drugs for the prevention of acute symptomatic epileptic seizures not received.

Explaining slow seizure propagation with white matter tractography.

Epileptic seizures recorded with stereo-EEG can take a fraction of a second or several seconds to propagate from one region to another. What explains such propagation patterns? We combine tractography and stereo-EEG to determine the relationship between seizure propagation and the white matter architecture and to describe seizure propagation mechanisms. Patient-specific spatiotemporal seizure propagation maps were combined with tractography from diffusion imaging of matched subjects from the Human Connectome Project. The onset of seizure activity was marked on a channel-by-channel basis by two board-certified neurologists for all channels involved in the seizure. We measured the tract connectivity (number of tracts) between regions-of-interest pairs among the seizure onset zone, regions of seizure spread and non-involved regions. We also investigated how tract-connected the seizure onset zone is to regions of early seizure spread compared with regions of late spread. Comparisons were made after correcting for differences in distance. Sixty-nine seizures were marked across 26 patients with drug-resistant epilepsy; 11 were seizure free after surgery (Engel IA) and 15 were not (Engel IB-Engel IV). The seizure onset zone was more tract-connected to regions of seizure spread than to non-involved regions (P < 0.0001); however, regions of seizure spread were not differentially tract-connected to other regions of seizure spread compared with non-involved regions. In seizure-free patients only, regions of seizure spread were more tract-connected to the seizure onset zone than to other regions of spread (P < 0.0001). Over the temporal evolution of a seizure, the seizure onset zone was significantly more tract-connected to regions of early spread compared with regions of late spread in seizure-free patients only (P < 0.0001). By integrating information on structure, we demonstrate that seizure propagation is likely to be mediated by white matter tracts. The pattern of connectivity between seizure onset zone, regions of spread and non-involved regions demonstrates that the onset zone might be largely responsible for seizures propagating throughout the brain, rather than seizures propagating to intermediate points, from which further propagation takes place. Our findings also suggest that seizure propagation over seconds might be the result of a continuous bombardment of action potentials from the seizure onset zone to regions of spread. In non-seizure-free patients, the paucity of tracts from the presumed seizure onset zone to regions of spread suggests that the onset zone was missed. Fully understanding the structure-propagation relationship might eventually provide insight into selecting the correct targets for epilepsy surgery.

Early life seizures and olfactory communication in rats.

Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats. KA-induced seizures or saline was administered. Rats were then exposed to a series of biologically relevant scents including male scent, female scent, nest scent, and phenylethylamine during the juvenile period and again during adulthood. Alterations in sensory modalities were expected to be expressed via abnormal preference for certain scents and/or production of abnormal ultrasonic vocalizations in response to scents. The olfactory bulbs were also assessed for the biologically relevant markers glial fibrillary acidic protein (GFAP) and calcium/calmodulin-dependent protein kinase II (CAMKII). Our findings resulted in no significant differences in olfactory preference following ELS for juveniles or adults compared to controls. Similarly, there were no differences in GFAP expression or the ratio of phosphorylated CAMKII to CAMKII in either olfactory bulb. Interestingly, despite a lack of treatment differences, different scents were shown to elicit different responses in juvenile rats, yet these differences subsided in adulthood. Overall, the results of this study suggest that olfaction does not contribute to socialization deficit following ELS within the KA model.

Prevalence of Early Seizures in Acute Stroke Patients

A stroke is defined as a sudden neurological deficit of cerebrovascular cause that persists beyond 24 hours. Stroke is associated with a whole spectrum of complications, especially post-stroke seizures. These seizures may adversely affect the outcome of stroke in terms of mortality and morbidity. This study was designed to find out the frequency of early post-stroke seizures. Objective: To determine the frequency of early-onset seizures after stroke among patients presenting to tertiary care hospitals. Methods: Two hundred and forty patients, presenting on the Medical floor of Jinnah Hospital Lahore with acute stroke and fulfilling the selection criteria, were approached after informed consent. The patients were followed for 14 days for the development of early seizures after the stroke. Results: Among 240 stroke patients, there were 123 (51.3%) male patients and 117 (48.8%) female patients. The minimum age observed was 30 years and the maximum was noted as 77 years. In 45% of patients, hemorrhagic stroke was detected and 55% of patients had ischemic stroke. From 108 cases of hemorrhagic stroke, there were 10.4% cases in which an episode of seizure occurred within 14 days of stroke. On the other hand, in 132 patients with ischemic stroke, 15.9% of patients developed seizure episodes. Conclusions: It was concluded that ischemic stroke was more common in frequency than hemorrhagic stroke in our population and the occurrence of episode early seizure within 14 days of stroke was more prevalent in ischemic stroke patients.

Comparison of Risk Factors for Early Seizures Between Angiogram-Negative and Aneurysmal Subarachnoid Hemorrhage.

Early-onset seizures are common in aneurysmal subarachnoid hemorrhage (aSAH), with risk factors that have been explored. However, early-onset seizures in patients with angiogram-negative nonperimesencephalic SAH (an-SAH) are less understood. We sought to compare the incidence and risk factors of early-onset seizures between these groups. We conducted a retrospective study of a cohort of consecutive patients admitted to an academic center between July 2016 and July 2023. Patients were categorized into aSAH or an-SAH based on imaging findings. Clinical data and electroencephalogram findings were retrieved and analyzed. Multivariable logistic regression analysis was used to determine risk factors for clinical or electrographic seizures, as well as other epileptic features. We included 473 patients (63% female) in the final analysis, of whom 79 had an-SAH and 394 had aSAH. Patients with an-SAH were older (mean age 61.9years [standard deviation 15.9] vs. 56.7 [standard deviation 13.4]; p = 0.02). The rate of clinical or electrographic seizures was similar between the two groups (13% in aSAH vs. 11% in an-SAH; p = 0.62). Highly epileptic features (electrographic seizures, ictal-interictal continuum, and periodic epileptic discharges) occurred more frequently in the aSAH group compared with the an-SAH group, although this difference was not significant (15% vs. 8%; p = 0.09). Risk factors for seizures in aSAH were Hunt and Hess grade (odds ratio [OR] 1.25 per grade increase, 95% confidence interval [CI] 1.05-1.49; p = 0.011), modified Fisher score (OR 1.64 per point increase, 95% CI 1.25-2.15; p < 0.001), cerebral infarct (OR 3.64, 95% CI 2.13-6.23; p < 0.001), and intracerebral hemorrhage (OR 10, 95% CI 1.35-76.9; p = 0.017). However, none of these factors were associated with seizures in an-SAH. Early-onset seizures occur at similar rates in patients with an-SAH and aSAH. However, seizure risk factors appear to differ between these groups. Larger prospective studies are needed to identify predictors of seizures in patients with an-SAH.

Comment on – “Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis”

Comment on – “Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis”

The role of genetic testing in adult patients with unexplained epilepsy.

Genetic causes are often overlooked in patients with epilepsy of unknown etiology, particularly in adults. We aimed to evaluate clinical features of genetic epilepsy and the utility of genetic testing. We retrospectively screened consecutive unrelated adult epilepsy patients at an epilepsy clinic from April 2022 to May 2023. Patients with unknown etiology or special brain lesions were classified as unexplained epilepsy. In them, patients with young-onset seizures or family history of seizures who were recommended for and ultimately underwent genetic testing using either panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were enrolled. A definite or probable genetic diagnosis was established through genotype-phenotype correlation. We compared the demographic characteristics between genetic epilepsy and other etiologies. Of the 374 adult epilepsy patients, 258 were classified as unexplained epilepsy, 129 were suspected of having genetic epilepsy due to young-onset seizures or a positive family history, 33 underwent genetic testing; 13 harbored variants classified as pathogenic, and 6 reached a definite genetic diagnosis, resulting in a yield of 18%. Among the 27 patients without a definite genetic diagnosis, 7 had a nongenetic structural etiology. Patients with genetic etiology exhibited greater multisystem involvement particularly multiple structural anomalies and early childhood-onset seizures, but wasn't directly correlated with young-onset seizures or a positive family history. The diagnostic yield was comparable between panel NGS and WES. In adult patients with unexplained epilepsy, genetic epilepsy is more associated with multisystem involvement and multiple structural anomalies but not family history of seizures or young-onset seizures.

Development of Seizures Following Traumatic Brain Injury: A Retrospective Study.

Objectives: The multifaceted impact of Traumatic brain injury (TBI) encompasses complex healthcare costs and diverse health complications, including the emergence of Post-Traumatic Seizures (PTS). In this study, our goal was to discern and elucidate the incidence and risk factors implicated in the pathogenesis of PTS. We hypothesize that the development of PTS following TBI varies based on the type and severity of TBI. Methods: Our study leveraged the Nationwide Inpatient Sample (NIS) to review primary TBI cases spanning 2016-2020 in the United States. Admissions featuring the concurrent development of seizures during the admission were queried. The demographic variables, concomitant diagnoses, TBI subtypes, hospital charges, hospital length of stay (LOS), and mortality were analyzed. Results: The aggregate profile of TBI patients delineated a mean age of 61.75 (±23.8) years, a male preponderance (60%), and a predominantly White demographic (71%). Intriguingly, patients who encountered PTS showcased extended LOS (7.5 ± 9.99 vs. 6.87 ± 10.98 days, p < 0.001). Paradoxically, PTS exhibited a reduced overall in-hospital mortality (6% vs. 8.1%, p < 0.001). Notably, among various TBI subtypes, traumatic subdural hematoma (SDH) emerged as a predictive factor for heightened seizure development (OR 1.38 [1.32-1.43], p < 0.001). Conclusions: This rigorous investigation employing an extensive national database unveils a 4.95% incidence of PTS, with SDH accentuating odds of seizure risk by OR: 1.38 ([1.32-1.43], p < 0.001). The paradoxical correlation between lower mortality and PTS is expected to be multifactorial and necessitates further exploration. Early seizure prophylaxis, prompt monitoring, and equitable healthcare provision remain pivotal avenues for curbing seizure incidence and comprehending intricate mortality trends.

Comparison of Effectiveness of Brivaracetam and Levetiracetam for Prophylaxis of Early Post-Traumatic Seizures: A Prospective Comparative Interventional Study

Abstract Introduction Early posttraumatic seizures (EPTS) are a major complication after a head injury, defined as seizures developing within the first 7 days of trauma. Levetiracetam has become a popular drug for the prevention of posttraumatic seizures in institutions worldwide. However, it has been reportedly associated with adverse effects like behavioral changes and somnolence. This study aimed to compare the efficacy of a newer drug, brivaracetam, which is reported to have a better pharmacokinetic profile. These findings may be significant in providing a safer yet efficacious alternative to levetiracetam. Objective The aim of this study was to evaluate the efficacy of brivaracetam for prophylaxis of EPTS and to compare it with levetiracetam. Materials and Methods A prospective, single-blind, parallel-group (alternate allocation) controlled trial over 100 patients admitted with traumatic brain injury in the Department of Neurosurgery, Goa Medical College, Panaji, Goa, India. The data was analyzed using IBM SPSS Statistics 29.0. Results Twenty patients developed EPTS in the study group: 8 from the group receiving brivaracetam and 12 from the group receiving levetiracetam. Although the brivaracetam group had a lower incidence of EPTS, the difference was not statistically significant. Eleven patients from the levetiracetam group developed side effects, while six patients from the brivaracetam group had side effects. There was no significant difference in the incidence of side effects. Conclusion Brivaracetam has efficacy equal to that of levetiracetam for prophylaxis of EPTS.

A single exposure to brivaracetam or perampanel does not cause cell death in neonatal rats.

Exposure to a range of anti-seizure medications (ASMs) during early brain development adversely impacts neurodevelopmental outcomes in both animal models and in clinical studies. Many ASMs, including phenobarbital, phenytoin, valproate (VPA), and benzodiazepines, are associated with acute neurotoxicity (cell death), impaired synaptic development, and long-term behavioral changes following gestational or neonatal exposure in animals. This is mirrored in clinical studies which show lasting neurodevelopmental deficits following early-life or gestational exposure to these drugs. Brivaracetam (BRV) and perampanel (PER) are two newer generation anti-seizure medications and are of interest based on their mechanisms of action (SV2A modulator, AMPA antagonist, respectively), as other drugs with these mechanisms of action do not trigger acute neurotoxicity. Both BRV and PER show anti-seizure efficacy in developing animals, but potential neurotoxicity of these drugs is unexplored. To address this gap, we treated postnatal day (P)7 Sprague-Dawley rats with BRV (20, 40, 80 mg/kg) and PER (0.1, 0.9, 2.7 mg/kg), and assessed the induction of cell death across a range of vulnerable brain regions 24 h after exposure. Cell death was assessed using pathogreen staining. In each of the regions examined (dorsal striatum, nucleus accumbens, motor cortex, cingulate cortex, lateral thalamus, septum, hippocampus), VPA, which served as a positive control, significantly increased cell death as measured by the numer of pathogreen positive cells. By contrast, neither BRV nor PER increased the number of pathogreen positive cells in any region examined. Our results suggest that BRV and PER may have a positive safety profile-at least with respect to acute induction of cell death - and therefore may offer a safer option for the treatment of early life seizures.

Early alterations of thalami- and hippocampi-cortical functional connectivity as biomarkers of seizures after traumatic brain injury

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx, project 3) is a prospective multicenter clinical observational study to identify early biomarkers of epileptogenesis after moderate-to-severe traumatic brain injury (TBI). We used a seed-based approach applied to acute (i.e., ≤14 days) fMRI imaging data, directly testing the hypothesis that the presence of seizures up to two years following brain trauma is associated with functional changes within hippocampi and thalami-cortical networks. Additionally, we hypothesized that the network connectivity involving thalami and hippocampi circuits underlying early and late-onset seizures would differ. Approximately 30% of the initial dataset was deemed unusable due to MRI issues. Approximately 50% of the enrolled sample was lost to a 2-year follow-up. After preprocessing the fMRI data, approximately 40% of the follow-up sample had to be excluded from the analysis due to excessive in-scanner movements, as assessed by state-of-the-art quality control protocols. Only 37 patients provided data that was suitable for the seed-based analysis. Despite these challenges, the remaining, high-quality data returned noteworthy findings. We identified specific hippocampi and thalami biomarkers associated with both early and late seizures following TBI (p < .05, FWE-corrected at the cluster level). The predictive capability for the development of late seizures after TBI, when adding fMRI data to demographic and clinical data, provided 88% accuracy — an additional 8% improvement compared to using demographic and clinical data alone. Our findings highlight the potential of fMRI for uncovering, in hippocampal and thalamic cortical networks, biomarkers of early and late seizures following TBI. However, they also highlight the important challenges that need to be overcome in order for fMRI to become an effective biomarker and prognostic tool in the intensive care context.