Posttraumatic epilepsy in chronic disorders of consciousness due to severe traumatic brain injury after traffic accidents.

PURPOSE: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients. METHODS: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs). RESULTS: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations. CONCLUSION: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population.

Clinical characteristics and associated factors of posttraumatic epilepsy after traumatic brain injury in children: A retrospective case-control study.

BACKGROUND: Traumatic brain injury (TBI) affects approximately 69 million individuals annually, often resulting in well-documented complications such as epilepsy. Although numerous studies have been performed on posttraumatic epilepsy (PTE) in adults over the past decade, research on chronic consequences of TBI in children remains limited. Herein, we retrospectively assessed children who had experienced moderate to severe TBI to determine their clinical characteristics and identify associated factors associated with the development of PTE in the pediatric population. METHODS: The study population comprised children aged 0-18 years who had experienced moderate to severe TBI and underwent treatment at the Children's Hospital of Chongqing Medical University between 2011 and 2021. They were categorized into two groups: the PTE group, comprising individuals diagnosed with PTE within a one-year follow-up period, and the nPTE group, consisting of those who did not develop PTE during the same timeframe. The primary objective was to investigate the clinical characteristics and identify related associated factors. The relationship between various clinical factors and the incidence of PTE was assessed through univariate and multivariate logistic regression. RESULTS: A total of 132 patients were assessed. Most participants were male (65%) and the age distribution skewed towards younger children, with a median age of 41.0 months (interquartile range: 45.3). Upon their last clinical visit, 64 children (49%) were diagnosed with PTE. Notably, the first posttraumatic seizure predominantly occurred within the first week following the traumatic event. Further analyses revealed that increasing injury severity, as indicated by a lower Glasgow Coma Scale (GCS) score (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.54-1.12, p= 0.018), a contusion load ≥3 (OR: 8.1, 95% CI: 2.3-28.9, p= 0.001), immediate posttraumatic seizures (IPTS) (OR: 8.9, 95% CI: 2.5-31.2, p < 0.001), and early posttraumatic seizures (EPTS) (OR: 54, 95% CI: 11-276, p < 0.001), were all significantly associated with a higher risk of developing PTE. CONCLUSION: This study highlights that the onset of PTE was associated with the markers of injury severity or PTS and identified GCS scores, contusion loads of ≥3, IPTS, and EPTS as independent associated factors significantly associated with the development of PTE.

The Role of Decreased Levels of Neuronal Autophagy in Increased Susceptibility to Post-traumatic Epilepsy.

Post-traumatic epilepsy (PTE) caused by mild TBI (mild traumatic brain injury, mTBI) has a high incidence and poor prognosis, but its mechanisms are unclear. Herein, we investigated the role of reduced levels of neuronal autophagy during the latency period in the increased susceptibility to PTE. In the study, a gentle whole-body mechanical trauma rat model was prepared using Noble-Collip drums, and the extent of injury was observed by cranial CT and HE staining of hippocampal tissue. The incidence of epilepsy and its seizure form were observed 7-90 days after mTBI, and electroencephalography (EEG) was recorded during seizures in rats. Subcortical injection of non-epileptogenic dose of ferrous chloride (FeCl2) was used to observe the changes of PTE incidence after mTBI. Western blot and Real-time PCR were used to detect the level of autophagy in hippocampal cells at different time points during the latency period of PTE, and its incidence was observed after up-regulation of autophagy after administration of autophagy agonist-rapamycin. The results showed that mTBI was prepared by Noble-Collip drum, which could better simulate the clinical mTBI process. There was no intracerebral hemorrhage and necrosis in rats, no early-onset seizures, and the incidence of PTE after mTBI was 26.7%. The incidence of PTE was 56.7% in rats injected cortically with FeCl2 at a dose lower than the epileptogenic dose 48 h after mTBI, and the difference was significant compared with no FeCl2 injection, suggesting an increased susceptibility to PTE after mTBI. Further study of neuronal autophagy during PTE latency revealed that autophagy levels were reduced, and the incidence of PTE was significantly reduced after administration of rapamycin to upregulate autophagy. Taken together, the decreased level of neuronal autophagy during the latency period may be a possible mechanism for the increased susceptibility to PTE after mTBI.

Risk Factors and Incidence of Epilepsy after Severe Traumatic Brain Injury.

We determined the incidence of post-traumatic epilepsy after severe traumatic brain injury. Of 392 patients surviving to discharge, cumulative incidence of post-traumatic epilepsy was 25% at 5 years and 32% at 15 years, an increase compared with historical reports. Among patients with one late seizure (>7 days post-trauma), the risk of seizure recurrence was 62% after 1 year and 82% at 10 years. Competing hazards regression identified age, decompressive hemicraniectomy, and intracranial infection as independent predictors of post-traumatic epilepsy. Patients with severe traumatic brain injury and a single late post-traumatic seizure will likely require long-term antiseizure medicines. ANN NEUROL 2022;92:663-669.

Multimodal Quality of Life Assessment in Post-9/11 Veterans With Epilepsy: Impact of Drug Resistance, Traumatic Brain Injury, and Comorbidity.

BACKGROUND AND OBJECTIVES: Epilepsy is defined by the occurrence of multiple unprovoked seizures, but quality of life (QOL) in people with epilepsy is determined by multiple factors, in which psychiatric comorbid conditions play a pivotal role. Therefore, understanding the interplay between comorbid conditions and QOL across epilepsy phenotypes is an important step toward improved outcomes. Here, we report the impact of QOL across distinct epilepsy phenotypes in a cohort of post-9/11 veterans with high rates of traumatic brain injury (TBI). METHODS: This observational cohort study from the Veterans Health Administration included post-9/11 veterans with epilepsy. A process integrating an epilepsy identification algorithm, chart abstraction, and self-reported measures was used to classify patients into 1 of 4 groups: (1) epilepsy controlled with medications, (2) drug-resistant epilepsy (DRE), (3) posttraumatic epilepsy (PTE), or (4) drug-resistant PTE (PT-DRE). Summary scores for 6 QOL measures were compared across the groups after adjustment for age, sex, and number of comorbid conditions. RESULTS: A total of 529 survey respondents with epilepsy were included in the analysis: 249 controls (i.e., epilepsy without DRE or PTE), 124 with DRE, 86 with PTE, and 70 with PT-DRE. DRE was more common in those with PTE compared with those with nontraumatic epilepsy (45% vs 33%, odds ratio 1.6 [95% CI 1.1-2.4], p = 0.01). Patients with PTE and PT-DRE had significantly more comorbid conditions in health records than those with nontraumatic epilepsy. Those with both PTE and DRE reported the lowest QOL across all 6 measures, and this persisted after adjustment for comorbid conditions and in further linear analyses. DISCUSSION: Among those with PTE, DRE prevalence was significantly higher than prevalence of nontraumatic epilepsies. PTE was also associated with higher burden of comorbidity and worse overall QOL compared to nontraumatic epilepsies. People with PTE are distinctly vulnerable to the comorbid conditions associated with TBI and epilepsy. This at-risk group should be the focus of future studies aimed at elucidating the factors associated with adverse health outcomes and developing antiepileptogenic therapies.

Occurrence of early epilepsy in children with traumatic brain injury: a retrospective study.

BACKGROUND: Early post-traumatic seizures (EPTS) refer to epileptic seizures occurring within one week after brain injury. This study aimed to define the risk factors of EPTS and the protective factors that could prevent its occurrence. METHODS: This is a single-center retrospective study in the PICU, Beijing Children's Hospital. Patients diagnosed with traumatic brain injury (TBI), admitted with and without EPTS between January 2016 and December 2020 were included in the study. RESULTS: We included 108 patients diagnosed with TBI. The overall EPTS incidence was 33.98% (35/108). The correlation between EPTS and depressed fractures is positive (P = 0.023). Positive correlations between EPTS and intracranial hemorrhage and subarachnoid hemorrhage had been established (P = 0.011and P = 0.004, respectively). The detection rates of EPTS in the electroencephalogram (EEG) monitoring was 80.00%. There was a significant difference in the EEG monitoring rate between the two groups (P = 0.041). Forty-one (37.86%, 41/108) post-neurosurgical patients were treated with prophylactic antiepileptic drugs (AEDs), and eight (19.51%, 8/41) still had seizures. No statistical significance was noted between the two groups in terms of prophylactic AEDs use (P = 0.519). Logistic regression analysis revealed that open craniocerebral injury and fever on admission were risk factors for EPTS, whereas, surgical intervention and use of hypertonic saline were associated with not developing EPTS. CONCLUSIONS: Breakthrough EPTS occurred after severe TBI in 33.98% of pediatric cases in our cohort. This is a higher seizure incidence than that reported previously. Patients with fever on admission and open craniocerebral injuries are more likely to develop EPTS.

Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes.

PURPOSE: That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. METHODS: This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. RESULTS: Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22-2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event. CONCLUSIONS: Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury.

Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021. Exposure: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ). Main Outcomes and Measures: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI). Results: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months. Conclusions and Relevance: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

Incidence of post-traumatic epilepsy following paediatric traumatic brain injury: protocol for systematic review and meta-analysis.

INTRODUCTION: Post-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE. METHODS AND ANALYSIS: A systematic literature search of Embase (1947-2021), PubMed (1996-2021) and Web of Science (1900-2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion. PROSPERO REGISTRATION NUMBER: CRD42021245802.

Clinical characteristics of post-traumatic epilepsy and the factors affecting the latency of PTE.

OBJECTIVES: To summarize the clinical characteristics of post-traumatic epilepsy (PTE), and to identify the factors affecting the latency of PTE after traumatic brain injury (TBI). METHODS: We conducted a retrospective clinical analysis in patients with PTE who visited the outpatient Department of Epilepsy, Beijing Tiantan Hospital from January 2013 to December 2018. The clinical characteristics, including gender, age distribution, seizure type, and latency were summarized. Factors affecting the latency of PTE were evaluated using Kaplan-Meier curves and Cox proportional hazard regression analysis. RESULTS: Complete clinical information was available for 2862 subjects, of which 78.48% were males. The mean age at TBI was 21.4 ± 15.1 years and peaked in the 0 to 12-year-old and 15 to 27-year-old groups. Generalized onset seizure was the most frequent seizure type (72.82% of patients). Approximately 19.95% PTE patients developed drug-resistant epilepsy. The latency of PTE ranged from 8 days to 20 years, with a median of 24.0 (IQR, 5.0-84.0) months. The Kaplan-Meier curves demonstrated that gender, age at TBI, severity of TBI, multiple craniocerebral injuries, post-TBI treatments, acute seizures, and residual disability were associated with PTE latency. The Cox regression model indicated that age ≥ 18 years old, severe TBI with multiple surgical operations, acute seizures, and residual disability were risk factors for shorter PTE latency. CONCLUSIONS: PTE is more common in males than females, and peaked in the 0 to 12-year-old and 15 to 27-year-old groups. Generalized onset seizure was the most common seizure type and 19.95% of participants developed drug-resistant epilepsy. Patients aged ≥18 years old, who suffered severe TBI followed by multiple surgical operations, experienced acute seizures, or with residual disabilities had shorter PTE latency.

Animal models of post-traumatic epilepsy and their neurobehavioral comorbidities.

Traumatic brain injury (TBI) is defined as a disturbance in brain functioning caused by an external force. The development of post traumatic epilepsy (PTE) is a serious risk associated with TBI. Indeed, other neurological impairments are also common following TBI. In this review, we analyze and discuss the most widely used and best validated rodent models of TBI, with a particular focus on their contribution to the understanding of the PTE development. Furthermore, we explore the importance of these models for the study of other neurobehavioral comorbidities associated with brain injury. The efficient and accurate diagnosis of epilepsy and other neurological comorbidities as a consequence of brain trauma should improve the survival and quality of life of patients after TBI.

Risk factors for post-traumatic epilepsy.

PURPOSE: The aim of the current study was to investigate the risk factors for post-traumatic epilepsy (PTE) in a large cohort of patients after severe non-penetrating civilian traumatic brain injury (TBI). METHODS: This was a longitudinal study. All patients with a severe non-penetrating TBI, who were admitted at the neuro-intensive care unit of Shahid Rajaee Trauma Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran, from 2015 until 2019, were studied. Severe TBI was defined as a Glasgow Coma Scale-Motor score below six. Post-traumatic epilepsy was defined as any seizures that occurred after being discharged from the hospital. RESULTS: In total, 803 patients with severe non-penetrating TBI were studied; 82 patients (10.2%) reported any late post-traumatic seizures (PTSs). A higher Glasgow outcome scale (extended) at discharge was significantly inversely associated with PTE [Odds Ratio (OR)= 0.76, 95% Confidence Interval (CI): 0.65-0.87; p = 0.0001]. Depressed skull fracture (OR= 1.88, 95% CI: 0.92-3.80; p = 0.081), epi­dural hematoma (OR= 1.67, 95% CI: 0.93-2.97; p = 0.083), and sub-dural hematoma (OR= 1.64, 95% CI: 0.96-2.78; p = 0.068) were associated with PTE as trends. CONCLUSION: Our study adds to the literature on the risk of PTE after severe non-penetrating civilian TBI. Our large sample size and also the application of a logistic regression analysis model may suggest that other variables (e.g., depressed skull fracture and intracranial hematoma) are indeed associated with the Glasgow outcome scale (extended) at discharge and that is why they lost their significance in the model.

Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

BACKGROUND: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. DESIGN: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI). RESULTS: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy. CONCLUSIONS AND RELEVANCE: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid-percussion injury in rats.

OBJECTIVE: To identify postinjury physiologic, behavioral, and cognitive biomarkers for posttraumatic epilepsy to enrich study populations for long-term antiepileptogenesis studies. METHODS: The EPITARGET cohort with behavioral follow-up and 1-month 24/7 video-electroencephalography (vEEG) monitoring included 115 adult male Sprague-Dawley rats with lateral fluid-percussion-induced traumatic brain injury (TBI), 23 sham-operated controls, and 13 naive rats. Animals underwent assessment of somatomotor performance (composite neuroscore), anxiety-like behavior (elevated plus maze, open field), spatial memory (Morris water maze), and depression-like behavior (Porsolt forced swim, sucrose preference). Impact force, postimpact apnea time, postimpact seizure-like behavior, and body weight were monitored. RESULTS: TBI rats were impaired in the composite neuroscore (P < .001) on days (D) 2-14 and in the spatial memory test (P < .001) on D35-39 post-TBI. Differences in the elevated plus-maze (D28 and D126) and in the open field (D29 and D127) between TBI rats and controls were meager. No differences were observed in the Porsolt forced swim and sucrose preference tests as compared with sham-operated controls. Epilepsy developed in 27% of rats by the end of the sixth month. None of the behavioral or cognitive outcome measures discriminated rats with or without epilepsy. The receiver-operating characteristic analysis indicated that a decrease in body weight between D0 and D4 differentiated TBI rats with epilepsy from TBI rats without epilepsy (48% sensitivity, 83% specificity, area under the curve [AUC] 0.679, confidence interval [CI] 95% 0.56-0.80, P < .01). A 16% body weight decrease during D0-D4 could be used as a biomarker to enrich the study population from 27% (observed) to 50%. SIGNIFICANCE: Single behavioral and cognitive outcome measures showed no power as prognostic/diagnostic biomarkers for posttraumatic epilepsy. A reduction in body weight during the first postinjury week showed some prognostic value for posttraumatic epileptogenesis and could serve as a subacute measure for selectively enriching the study population for long-term preclinical biomarker and therapy discovery studies of posttraumatic epileptogenesis.

Epilepsy after severe traumatic brain injury: frequency and injury severity.

Objective: To estimate national frequency of posttraumatic epilepsy (PTE) after severe traumatic brain injury (TBI) and assess injury severity (Glasgow Coma Scale (GCS) and posttraumatic amnesia (PTA)) as prognostic factors for PTE. METHODS: Data on patients ≥18 years surviving severe TBI 2004-2016 were retrieved from the Danish Head Trauma Database (n = 1010). The cumulative incidence proportion (CIP) was estimated using death as competing event. The association between injury severity and PTE was assessed using multivariable competing risk regressions. RESULTS: CIP of PTE 28 days and one year post-TBI was 6.8% (95% confidence interval (CI) 5.4-8.5) and 18.5% (95% CI 16.1-21.1%), respectively. Injury severity was not associated with PTE within 28 days post-TBI but indicated higher PTE-rates in less severely injured patients. PTA-duration >70 days was associated with PTE 29-365 days post-TBI (Adjusted sub-hazard ratio 4.23 (95% CI 1.79-9.99)). GCS was not associated with PTE 29-365 days post-TBI. CONCLUSION: The PTE frequency was higher compared to previous estimates. Increasing injury severity was associated with PTE 29-365 days post-TBI when measured with PTA, but not with GCS. Though nonsignificant, the increased PTE-risk within 28 days in lower severity suggests an underdiagnosing of PTE.

A review of seizures and epilepsy following traumatic brain injury.

Traumatic brain injury (TBI) is one of the commonest presentations to emergency departments and is associated with seizures carrying different significance at different stages following injury. We describe the epidemiology of early and late seizures following TBI, the significance of intracranial haemorrhage of different types in the risk of later epilepsy and the gaps in current understanding of risk factors contributing to the risk of post-traumatic epilepsy (PTE). The delay from injury to epilepsy presents an opportunity to understand the mechanisms underlying changes in the brain and how they may reveal potential targets for anti-epileptogenic therapy. We review existing treatments, both medical and surgical and conclude that current research is not tailored to differentiate between PTE and other forms of focal epilepsy. Finally, we review the increasing understanding of the frequency and significance of dissociative seizures following mild TBI.

Epidemiology of traumatic brain injury-associated epilepsy in western China: An analysis of multicenter data.

OBJECTIVES: This study aims to explore the probability of developing posttraumatic epilepsy (PTE) in the following 8 years after traumatic brain injury (TBI), the risk factors associated with PTE and its cumulative prevalence. METHODS: This is a retrospective follow-up study of patients with traumatic brain injury (TBI) discharged from the West China Hospital between January 1, 2011 and December 31, 2017, Chengdu Shang Jin Nan Fu Hospital and Sichuan Provincial People's Hospital from January 1, 2013 to March 1, 2015. We used forward stepwise method to build the final multivariate cox proportional hazard regression model to obtain estimates of hazard ratio (HR) of PTE and 95% confidence intervals (CI). We also conducted Kaplan-Meier survival analysis to investigate the cumulative prevalence of PTE. RESULTS: The cumulative incidence of PTE rose from 6.2% in one year to 10.6% in eight years. There were more male patients in PTE group and generally older. Besides, patients with PTE tended to have abnormal CT scan results. The risk factors of PTE were male (HR = 1.6, 95% CI: 1.1-2.2, P = 0.009), early posttraumatic seizures (HR = 2.9, 95% CI: 2.2-4.1, P < 0.001), TBI severity (moderate TBI: HR = 3.0, 95% CI: 1.8-5.0, P = 0.001; severe TBI: HR = 4.3, 95% CI: 2.3-7.6, P < 0.029), loss of consciousness (LOC) more than 30 min (30 min-24 h: HR = 1.8, 95% CI: 1.02-3.1, P = 0.041; >24 h: HR = 2.4, 95% CI: 1.4-2.4, P = 0.001), subdural hematoma (SDH) (HR = 1.9, 95% CI: 1.4-2.5, P < 0.001), brain contusion sites (frontal-temporal lobe: HR = 2.7, 95% CI: 1.9-3.9, P < 0.001; other sites: HR = 1.5, 95% CI: 1.01-2.3, P = 0.042) and cranial surgery (HR = 1.7, 95% CI: 1.3-2.3, P < 0.001). SIGNIFICANCE: The probability of developing PTE increased during the study period. In addition, the risk of developing PTE was significantly associated with gender, EPTS, LOC time, SDH, brain contusion sites, surgery and TBI severity. However, further researches may be needed to predict the risk of PTE in combination with quantitative factors.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Posttraumatic epilepsy in intensive care unit-treated pediatric traumatic brain injury patients.

OBJECTIVE: Posttraumatic epilepsy (PTE) is a well-described complication of traumatic brain injury (TBI). The majority of the available data regarding PTE stem from the adult population. Our aim was to identify the clinical and radiological risk factors associated with PTE in a pediatric TBI population treated in an intensive care unit (ICU). METHODS: We used the Finnish Intensive Care Consortium database to identify pediatric (<18 years) TBI patients treated in four academic university hospital ICUs in Finland between 2003 and 2013. Our primary outcome was the development of PTE, defined as the need for oral antiepileptic medication in patients alive at 6 months. We assessed the risk factors associated with PTE using multivariable logistic regression modeling. RESULTS: Of the 290 patients included in the study, 59 (20%) developed PTE. Median age was 15 years (interquartile range [IQR] 13-17), and 80% had an admission Glasgow Coma Scale (GCS) score ≤12. Major risk factors for developing PTE were age (adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00-1.16), obliterated suprasellar cisterns (OR 6.53, 95% CI 1.95-21.81), and an admission GCS score of 9-12 in comparison to a GCS score of 13-15 (OR 2.88, 95% CI 1.24-6.69). SIGNIFICANCE: We showed that PTE is a common long-term complication after ICU-treated pediatric TBI. Higher age, moderate injury severity, obliterated suprasellar cisterns, seizures during ICU stay, and surgical treatment are associated with an increased risk of PTE. Further studies are needed to identify strategies to decrease the risk of PTE.