Posttraumatic Seizures Research Articles

Epileptic seizures after the combat traumatic brain injury. The role and place of antiepileptic therapy

BACKGROUND: Taking into account the increasing number of armed conflicts, the number of combat head traumatic injuries and their consequences, which are faced not only by military doctors, but also by civilian healthcare, is thereof increasing. AIM: The purpose of this article is to focus the attention of practicing neurologists and neurosurgeons to the modern principles of diagnostic and treatment of post-traumatic epileptic seizures after high-energy combat traumatic brain injury of various severity. MATERIALS AND METHODS: The article presents the discussion of the clinical application of a number of theoretical concepts, definitions and recommendations used in cases to epileptic seizures after trauma and post-traumatic epilepsy. A prospective analysis of 224 patients with severe combat traumatic brain injury is presented. To evaluate different approaches to preventive therapy of epileptic seizures, the entire cohort of patients was divided into two groups: the first group (n = 122, 54.5% of patients) — without prophylactic use of antiepileptic drugs; the second group (n = 102, 45.5% of patients) — with prophylactic use of antiepileptic drugs. All patients underwent EEG, CT of the brain, and MRI of the brain in the absence of metal fragments in the body. The follow-up period was 12–18 months. Data from 79 patients with concussion in the structure of mine-blast injury were analyzed separately. RESULTS: The analysis of the incidence of early and late acute post-traumatic seizures is carried out, various approaches to their treatment are discussed, depending on the clinical and diagnostic findings. The historical aspect of comparing the incidence of post-traumatic epilepsy in major wars of the twentieth century and current armed conflicts is touched upon, taking into account the contemporary approaches — the availability of specialized medical care, the possibility of current methods of examination and therapy. CONCLUSION: The results obtained in the work provide grounds for revising the strategy of prophylactic administration of antiepileptic drugs to patients with severe head injury in modern conditions of providing specialized care.

Exploring the Connection Between Family History of Seizures and Post-traumatic Brain Injury Seizure Types: A Retrospective Study

Background: Traumatic brain injury (TBI) is one of the most common presentations to emergency departments and is associated with seizures carrying different significance at different stages following injury. The occurrence of seizures after head injury is a recognized complication of TBI and has been demonstrated to worsen functional outcomes significantly. Despite previous studies identifying various PTS risk factors, our understanding remains limited, particularly regarding familial seizure history. Materials and Methods: A retrospective study was conducted at King Abdullah University Hospital (KAUH), Jordan, examining 1934 TBI cases from 2017 to 2023, identifying 118 patients with confirmed post-traumatic seizures. Results: This study involved 118 TBI patients, aged between 2 and 86 years (median 21.5 years), with 74.6% male and 25.4% female. A family history of seizures was reported by 23.7% of patients. Intracerebral hemorrhage (ICH) (52.5%) and subarachnoid hemorrhage (SAH) (38.1%) were the predominant trauma types. Generalized tonicclonic (GTCs) seizures (69.5%) and focal seizures (30.5%) were observed post-TBI. Among 28 patients with a family history of seizures, no evidence of association was observed between the family history and post-traumatic seizure types (GTCs or focal seizures), this was confirmed by performing Chi-square tests (p = 0.9841) and logistic regression analysis (p = 0.79). Conclusion: Our findings suggest that there is no evidence of the association between family history and post-traumatic seizure types, implying that a specialized approach for patients with positive family histories may not be warranted. Larger studies are recommended for further validation.

Levetiracetam as an Alternative to Phenytoin for Prophylactic Use in Post-Traumatic Seizures: a Literature Review

Traumatic brain injury (TBI) is a common concern for the causes of disability and mortality and it can cause post-traumatic seizure (PTS). Currently, Brain Trauma Foundation (BTF) recommends phenytoin (PHY) as early PTS prophylaxis for patients with severe TBI. The two most common drugs prescribed for PTS are levetiracetam (LEV) and PHY. However, PHY displays a wide array of disadvantages. LEV appears as a better alternative to PHY because of its easier administration, the absence of need for drug level monitoring, lower drug-drug interaction, and better side-effects profile. It is due to the linear elimination kinetics LEV had in comparison to PHY that have zero order pharmacokinetics. Theoretically, LEV is better than PHY. But according to prior studies, LEV and PHY have comparable efficacy at preventing PTS in the early stages. Furthermore, the current evidence is insufficient to definitely recommend LEV over PHY in terms of effectiveness and adverse effects. This study aimed to analyze levetiracetam as an alternative to phenytoin for prophylactic use in post-traumatic seizure.

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.

Incidence of drug dependence and epilepsy in patients with PTC (Post Traumatic Contusions) manage conservatively. A prospective study.

Objective: To explore the presence of drug dependence and Epilepsy in patients with PTC (Post Truamatic Contusions) balanced cautiously. Study Design: Proposed Reviewed Research study. Setting: Hayatabad Medical Complex, Peshawar. Period: July 2020 to December 2020. Methods: About 90% of patients aged between fifteen to sixty-five years old identified with cerebral lesion and balanced cautiously were applied. Follow up sessions was provided to patients for 12to 18 months. Results: Among the enrolled patients, 23% established early PTS (Post Traumatic Seizures) and approximately established late PTS (Post Traumatic Seizures) from mild to moderate level of cerebral lesion. Patients having early signs of Post traumatic Seizure, about 6% utilized AEDs (Anti-epileptic Drugs) for about 3 months throughout the treatment period and about 7% of patients along with late Post Traumatic Seizures utilized AEDs. Moreover, approximately 8 percent patients established late post traumatic Seizure without considering any early signs of condition. Research findings indicated that only 3% of patients with early and late PTS actually required AEDs for at least 6 months. Although, about 44 percent of patients were utilizing Anti-epileptic drugs to control seizures. Sensible usage of Anti-epileptic drugs is familiar in our region, contributing to enhanced danger of medicine opposition and acquiring financial pressure on low-paid people in well-established state. Additionally, extreme usage of anti-epileptic and prophylactic drugs doesn’t impact the occurrence of PTE (Post Traumatic Epilepsy). Conclusion: The presence of late and early post-traumatic epilepsy observed within our study is contrast to that explored in another research. Sensible production of AEDs is occured in our state, that increases the danger of medicine opposition and attain financial issues for economically destruct people in well-established states. Extreme usage of AEDs and prophylactic drugs doesn’t have an important influence on stopping PTE.

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.

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.

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures

Traumatic Brain Injury (TBI) induces neuroinflammatory response that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist, used to treat drug addiction. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI seizures can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and/or seizures post-TBI. TBI was induced by a modified Marmarou Weight-Drop (WD) method on 4-week-old C57BL/6J male mice. Mice were placed in two groups: non-telemetry assessing the acute effects or in telemetry monitoring for interictal events and spontaneous seizures both following TBI and naltrexone. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation, neurodegeneration and fiber track integrity at 8 days and 3 months post-TBI. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. Our results show an increase in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. Video-EEG revealed increased interictal events in TBI mice, with 71% mice developing post-traumatic seizures (PTS). Naltrexone treatment ameliorated neuroinflammation, neurodegeneration, reduced interictal events and prevented seizures in all TBI mice, which makes naltrexone a promising candidate against PTS, TBI-associated neuroinflammation and epileptogenesis in a WD model of TBI.

A role of dentate gyrus mechanistic target of rapamycin activation in epileptogenesis in a mouse model of posttraumatic epilepsy.

The mechanistic target of rapamycin (mTOR) pathway has been implicated in promoting epileptogenesis in animal models of acquired epilepsy, such as posttraumatic epilepsy (PTE) following traumatic brain injury (TBI). However, the specific anatomical regions and neuronal populations mediating mTOR's role in epileptogenesis are not well defined. In this study, we tested the hypothesis that mTOR activation in dentate gyrus granule cells promotes neuronal death, mossy fiber sprouting, and PTE in the controlled cortical impact (CCI) model of TBI. An adeno-associated virus (AAV)-Cre viral vector was injected into the hippocampus of Rptorflox/flox (regulatory-associated protein of mTOR) mutant mice to inhibit mTOR activation in dentate gyrus granule cells. Four weeks after AAV-Cre or AAV-vehicle injection, mice underwent CCI injury and were subsequently assessed for mTOR pathway activation by Western blotting, neuronal death, and mossy fiber sprouting by immunopathological analysis, and posttraumatic seizures by video-electroencephalographic monitoring. AAV-Cre injection primarily affected the dentate gyrus and inhibited hippocampal mTOR activation following CCI injury. AAV-Cre-injected mice had reduced neuronal death in dentate gyrus detected by Fluoro-Jade B staining and decreased mossy fiber sprouting by ZnT3 immunostaining. Finally, AAV-Cre-injected mice exhibited a decrease in incidence of PTE. mTOR pathway activation in dentate gyrus granule cells may at least partly mediate pathological abnormalities and epileptogenesis in models of TBI and PTE. Targeted modulation of mTOR activity in this hippocampal network may represent a focused therapeutic approach for antiepileptogenesis and prevention of PTE.

Levetiracetam Dosing Based on Glasgow Coma Scale Scores in Pediatric Traumatic Brain Injury Patients.

Severe traumatic brain injury (TBI) increases the risk of early posttraumatic seizures (EPTS). Guidelines suggest the use of prophylactic antiseizure agents, including levetiracetam. This study aims to evaluate the feasibility of using levetiracetam dosing based on Glasgow Comas Scale (GCS) scores with higher doses used for more severe TBI. Patients 6 months to 18 years old admitted to Penn State Hershey Children's Hospital (PSHCH) with a TBI who received levetiracetam for EPTS prophylaxis with at least one documented GCS score were included. Patients were divided into two cohorts: before and after implementation of the pediatric TBI Cerner PowerPlan at PSHCH which standardized levetiracetam dosing based on GCS scores. Primary outcome was appropriate dosing of levetiracetam based on GCS. Secondary outcomes included seizure occurrence and adverse effects. Eighty-five patients were included: 42 in the pre-PowerPlan group and 43 in the post-PowerPlan group. Overall, 46 (54%) patients received the appropriate levetiracetam dose based on GCS (pre-PowerPlan, n = 19 [45%] vs. post-PowerPlan n = 27 [63%], p = 0.104). Sixty-four percent of severe TBI patients received appropriate levetiracetam dosing after implantation of the PowerPlan compared with 28% prior to the PowerPlan (p = 0.039). Three patients in each group experienced a seizure while on levetiracetam. Two patients experienced agitation and somnolence attributed to levetiracetam. Levetiracetam dosing based on GCS scores in pediatric TBI patients is a novel approach, and dosing accuracy may be increased with use of a PowerPlan. Additional large-scale studies are needed to evaluate efficacy and safety of this approach prior to widespread implementation.

Safety and Efficacy of Levetiracetam for Prevention of Epileptic Seizures in Acute Phase of Intracerebral Bleeding

Background: Epilepsy, characterized by recurrent, unprovoked seizures due to anomalous brain activity, is a significant complication for patients with intracerebral hemorrhage (ICH). The onset of epileptic convulsions during the acute phase of ICH can worsen the patient's prognosis and survival chances, making it crucial to identify a safe and effective method to prevent these seizures. Levetiracetam, a pyrrolidone derivative, is noted for its unique mechanism of action, exceptional tolerability, and advantageous pharmacokinetics, making it efficacious against various types of seizures. Objective: This study aims to evaluate the safety and efficacy of levetiracetam in preventing epileptic seizures during the acute phase of ICH and to determine its impact on neurological outcomes in this patient population. Methods: A cross-sectional investigation was conducted between October 2022 and June 2023 at Pak Emirates Military Hospital in Rawalpindi, Pakistan, involving 85 patients with spontaneous ICH confirmed by CT or MRI within 24 hours of symptom onset. Inclusion criteria included adult patients aged 18 or older, with various forms of ICH, excluding isolated subarachnoid hemorrhage, penetrating wound injury, depressed skull fracture, or early posttraumatic seizure. Patients with a Glasgow Coma Scale (GCS) score of less than 6, serum creatinine level &gt;1.7 mg/dL, history of psychosis, unprovoked seizures, cerebrovascular accidents, traumatic brain injuries, or encephalitis within the previous three years were excluded. Patients were administered an initial loading dose of levetiracetam (1,000 to 1,500 mg), followed by a maintenance dose (500 to 1,500 mg every 12 hours) based on renal function. Continuous electroencephalography (cEEG) monitoring was used to detect seizures for at least the first 72 hours of hospital admission. The primary outcome was the incidence of epileptic seizures during hospitalization, while the secondary outcome was the patient's neurological status at discharge, assessed using the Modified Rankin Scale (mRS). Data were analyzed using descriptive statistics and the Chi-square test, with a p-value of ≤0.05 considered statistically significant. Analyses were conducted using SPSS version 25. Results: The mean age of the patients was 47.89 years (SD=7.46), with 62.35% male and 37.65% female. The mean GCS score at admission was 10.52 (SD=2.13), and the mean volume of ICH was 17.5 ml (SD=3.4). At baseline, 2.35% of patients had GCS scores of 3-5, which improved to 0% after treatment. The percentage of patients with GCS scores of 13-15 increased from 65.88% to 83.52% (p=0.3730). Seizures within the first 7 days occurred in 10.58% of patients, and the overall seizure incidence during hospitalization was 20%. At discharge, 9.41% of patients had an mRS score of 0, and the percentage of patients with an mRS score of 2 increased significantly from 18.18% to 37.64% (p=0.4086*). The percentage of patients with severe disability (mRS score of 5) significantly decreased from 22.72% to 5.68% (p=0.0094*). Conclusion: Levetiracetam is effective in improving neurological outcomes and reducing the incidence of seizures in patients with acute intracerebral hemorrhage, with a manageable safety profile. These findings suggest that levetiracetam can be a valuable addition to therapeutic strategies for managing ICH-related seizures, potentially enhancing patient care and improving health outcomes.

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation, and Behavior in a Traumatic Brain Injury Animal Model.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute electroencephalograph (EEG) changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by magnetic resonance imaging (MRI). Then, TBI was induced in separate groups, (TBIH) and (TBIE), using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 h for the first 7 days after TBI for assessing the acute EEG seizure and gamma event coupling. The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared with the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p < 0.05). Similarly, EEG functional connectivity was lower in ShamE compared with ShamH rats. These results suggest that electrical versus hand-drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Advancing post-traumatic seizure classification and biomarker identification: Information decomposition based multimodal fusion and explainable machine learning with missing neuroimaging data

A late post-traumatic seizure (LPTS), a consequence of traumatic brain injury (TBI), can potentially evolve into a lifelong condition known as post-traumatic epilepsy (PTE). Presently, the mechanism that triggers epileptogenesis in TBI patients remains elusive, inspiring the epilepsy community to devise ways to predict which TBI patients will develop PTE and to identify potential biomarkers. In response to this need, our study collected comprehensive, longitudinal multimodal data from 48 TBI patients across multiple participating institutions. A supervised binary classification task was created, contrasting data from LPTS patients with those without LPTS. To accommodate missing modalities in some subjects, we took a two-pronged approach. Firstly, we extended a graphical model-based Bayesian estimator to directly classify subjects with incomplete modality. Secondly, we explored conventional imputation techniques. The imputed multimodal information was then combined, following several fusion and dimensionality reduction techniques found in the literature, and subsequently fitted to a kernel- or a tree-based classifier. For this fusion, we proposed two new algorithms: recursive elimination of correlated components (RECC) that filters information based on the correlation between the already selected features, and information decomposition and selective fusion (IDSF), which effectively recombines information from decomposed multimodal features. Our cross-validation findings showed that the proposed IDSF algorithm delivers superior performance based on the area under the curve (AUC) score. Ultimately, after rigorous statistical comparisons and interpretable machine learning examination using Shapley values of the most frequently selected features, we recommend the two following magnetic resonance imaging (MRI) abnormalities as potential biomarkers: the left anterior limb of internal capsule in diffusion MRI (dMRI), and the right middle temporal gyrus in functional MRI (fMRI).

Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury

Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

The Role of the Orexin System in Craniocerebral Trauma-Induced Epilepsy in Mice.

Following traumatic brain injury (TBI), an imbalance arises in the central nervous system within the hippocampus region, resulting in the proliferation of mossy cell fibers, causing abnormal membrane discharge. Moreover, disruptions in cellular neurotransmitter secretion induce post-traumatic epilepsy. Extensive experimental and clinical data indicate that the orexin system plays a regulatory role in the hippocampal central nervous system, but the specific regulatory effects are unclear. Therefore, further experimental evaluation of its relevance is needed. This study aims to investigate the effects of orexin receptor agonists (OXA) on the seizure threshold and intensity in controlled cortical impact (CCI) mice, and to understand the role of the orexin system in post-traumatic epilepsy (PTE). Male C57BL/6 mice weighing 18-22 g were randomly divided into three groups: Sham, CCI, and CCI+OXA. The three groups of mice were sequentially constructed with models, implanted with electrodes, and established drug-delivery cannulas. After a 30-day recovery, the Sham and CCI groups were injected with physiological saline through the administration cannulas, while the CCI+OXA group was injected with OXA. Subsequently, all mice underwent electrical stimulation every 30 minutes for a total of 15 times. Epileptic susceptibility, duration, intensity, and cognitive changes were observed. Concurrently, the expression levels and changes of GABAergic neurons in the hippocampus of each group were examined by immunofluorescence. Injecting OXA into hippocampal CA1 reduces the threshold of post-traumatic seizures, prolongs the post-discharge duration, prolongs seizure duration, reduces cognitive ability, and exacerbates the loss of GABAergic neurons in the hippocampal region. Based on the results, we can find that injecting OXA antagonists into the CA1 region of the hippocampus can treat or prevent the occurrence and progression of post-traumatic epilepsy.

239 The Influence of Apolipoproteins E Gene Polymorphism on Cognitive Outcome in Patients with Moderate Degree Diffuse Brain Injuries

INTRODUCTION: APO-lipoproteins have a primary role in solubilizing and transporting lipids across cell membranes. APO-lipoprotein E isoform 4 (among APOE ε 1,2,3,4) is least efficient in clearing Aβ protein from the brain and is considered as a risk factor for Alzheimer disease. METHODS: After institutional ethics committee clearance, a prospective cohort study was done from 2017 to 2021 on adult patients who sustained moderate degree diffuse brain injury. APOE gene analysis were carried out on them. Patients who went on to subsequently develop focal lesions, those who died or were lost to follow up were excluded. Fifty consecutive patients who fulfilled the criteria, subsequently participate in a Mini Mental State Examination at the end of 1 month and 3 months were analysed. RESULTS: In our study, the allele frequencies for APOE gene ɛ2, ɛ3, ɛ4 were 36%, 53%, 11%, respectively. Patients were categorized into group A (who had at least one APOE ɛ4 allele) and group B (who did not have any APOE ɛ4 allele). In our study patients in group A had a prolonged hospitalisation and increased risk of convulsion than group B. The lack of improvement in MMSE scores (language and praxis subdomains) in group A as compared to group B after 3 months was statistically significant. The difference between the two groups in the rest of subdomains (attention, calculation, memory, orientation) and total MMSE scores at 3 months compared to that at discharge were insignificant. CONCLUSIONS: The presence of the APOE ɛ4 allele affects language and praxis during recovery. It increases the risk of post-traumatic seizures and increases the length of hospital stay but does not have a significant outcome on overall cognition after a course of 3 months.

Effectiveness of Levetiracetam versus phenytoin in preventing seizure in traumatic brain injury patients: A systematic review and meta-analysis

ObjectiveTraumatic brain injury (TBI) and the subsequent Post-traumatic seizure (PTS) is a growing public health concern. Generally, anti-seizure drugs (ASDs) are recommended for PTS prophylaxis and treatment. This meta-analysis aimed to review the current state of knowledge and the evidence for the efficacy and safety of Levetiracetam (LEV) on the incidence of seizure in TBI patients compared to Phenytoin (PHT). MethodsA search was carried out based on PubMed, MEDLINE, Europe PMC database, and Cochrane Library up to November 2023. A total of 16 studies (3 randomized clinical trials, 10 retrospective cohort studies, and 3 prospective cohort studies) including 5821 TBI patients included in our meta-analysis. We included studies comparing LEV and PHT after brain injury in both adults and children. Risk of bias assessment was done for randomized controlled trials (RCTs) with a risk-of-bias tool (RoB-2) and the Newcastle–Ottawa Scale (NOS) was used to assess the quality of cohort studies. Two RCTs in our meta-analysis had a high risk of bias, therefore we applied sensitivity analysis to evaluate the robustness of our results. ResultsThe most commonly reported dosage for LEV was 500 mg twice daily and for PHT it was 5 mg/kg. There was no significant difference between LEV and PHT groups in reducing the early seizure incidence (OR = 0.85; 95% CI = [0.60, 1.21]; p = 0.375, fixed-effect, I2 = 21.75%). The result of sensitivity analysis for late seizure showed no significant difference between LEV and PHT in reducing the late seizure occurrence after TBI (OR = 0.87; 95% CI = [0.21, 3.67]; p = 0.853, fixed-effect, I2 = 0%). The mortality in TBI patients treated with LEV was not statistically significant compared to the PHT group (OR = 1.11; 95% CI = [0.92, 1.34], p = 0.266). The length of stay in the hospital was not significantly different between the LEV and PHT groups (MD = –1.33; 95% CI = [–4.55, 1.90]; p = 0.421). However, in comparison to PHT, LEV shortened the length of ICU stay (MD = –2.25; 95% CI = [–3.58, –0.91]; p =0.001). In terms of adverse effects, more patients in the PHT group have experienced adverse events compared to LEV but the difference was not significant (OR = 0.69; 95% CI = [0.44, 1.08]; p = 0. 11). ConclusionThe results of our meta-analysis showed LEV and PHT have similar effects on the occurrence of early and late seizures in TBI patients. Therefore, none of the drugs is superior to the other in reducing PTS. However, treating TBI patients with LEV did not shorten the length of hospital stay in comparison to PHT but reduced the length of ICU stay significantly. The analysis showed that patients in the LEV experienced fewer side effects than in the PHT group, while it was not sufficiently clear whether all reported side effects were related to the drug alone or other factors. The mortality was similar between the LEV and PHT groups. Finally, we recommend more high-quality randomized controlled trials to confirm the current findings before making any recommendations in practice.

Post-traumatic seizures and factors associated among adult patients with depressed skull fractures at Mulago National Referral hospital; cross-sectional study

IntroductionPost-traumatic seizures (PTS) are common among patients with depressed skull fractures (DSF). Understanding the burden of post traumatic seizures and the factors associated among adult patients with DSF is important to improve clinical care. ObjectiveTo determine the prevalence and factors associated with post-traumatic seizures among adult patients with DSF at Mulago National Referral hospital (MNRH). MethodsA cross-sectional study was conducted among 333 study participants between March 2021 and February 2022. Socio-demographic, clinical laboratory factors and anti-seizure medications were collected using a study questionnaire. Data was analysed to determine the prevalence of PTS and factors associated with occurrence of PTS among patients with DSF. ResultsThe mean age (±SD) of study participants was 31.2, (±10.5) years, with a male to female ratio of 10.4:1. Nearly half of the study participants had attained secondary level of education, while 31.6 % (105) were peasants (subsistence farmers). The overall prevalence of PTS among DSF study participants was 16.2 % (54participants). Late presentation of PTS was the highest at 9.0 % (30) followed by early PTS at 3.9 % [13] and immediate PTS at 3.3 % [11]. Moderate Glasgow coma score (GCS: 9–13), p < 0.015, severe traumatic brain injury (GCS: 3–8), p < 0.026 at the time of admission and midline brain shift (≥5mm), p < 0.009 were associated with PTS. Phenytoin (94.3 %) was the most commonly used ASM followed by phenobarbitone (1.4 %) and Valproate (1.1 %) among study participants. ConclusionPatients with moderate and severe traumatic brain injury and midline brain shift were associated with post traumatic seizures. Early identification and intervention may reduce the burden of posttraumatic seizures in this category of patients.

Evaluation of levetiracetam dosing for seizure prophylaxis in traumatic brain injury

Background Early post-traumatic seizures (PTSs) may occur within seven days of traumatic brain injury (TBI). Although levetiracetam is frequently used for early PTS prophylaxis, it is not recommended in current guidelines due to insufficient evidence. The objective of this study was to further evaluate levetiracetam dosing strategies for early PTS prophylaxis. Methods A single-center retrospective cohort study was conducted utilizing the electronic medical record and a trauma database. The primary outcome was an incidence of seizure within seven days of TBI, defined as any documentation of a seizure when utilizing low-dose levetiracetam (500 mg twice daily), compared to high-dose levetiracetam (&gt;500 mg twice daily). Subgroup analyses were performed based on mechanism of injury, trauma type, baseline Glasgow Coma Scale (GCS), injury severity score (ISS), and Augmented Renal Clearance in Trauma Intensive Care score, administration of a loading dose, and additional head injuries. Only patients who completed a full seven-day course of levetiracetam were included. Results Of the 203 patients included, 149 patients received low-dose levetiracetam and 54 patients received high-dose. The majority of patients had a GCS &lt; 8 (53.7%) and an ISS &gt; 15 on presentation (92.1%). Twelve of 203 patients (5.9%) experienced a seizure within seven days of TBI, which is similar to the rate seen in previous studies. Six patients in the low-dose group (4.0%) and six patients in the high-dose group (11.1%) experienced a seizure ( p = 0.059). There was no statistically significant difference in seizure rate when patients were stratified based on baseline GCS, ISS, or mechanism of injury. Conclusions There were no statistically significant differences in seizure rates when comparing low-dose to high-dose levetiracetam. Levetiracetam 500 mg twice daily may be as effective as levetiracetam doses &gt;500 mg twice daily for early onset post-traumatic seizure prophylaxis.