Risk Factors For Posttraumatic Epilepsy Research Articles

Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.

Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE). A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24 months follow-up. Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11-2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR = 0.20; 95% CI: 0.11-0.35, p < 0.001). These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted. Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.

Risk Factors for Post-traumatic Epilepsy in Patients with Traumatic Brain Injuries

Background: Post-traumatic epilepsy (PTE) is one of the types of epilepsy, which is a complication of traumatic brain injury (TBI) that occurs after TBI or 7 days later. Objectives: The present study aimed to determine the risk factors for PTE in patients with TBI. Methods: The computed tomography (CT)-scan results of all TBI patients were investigated in this retrospective study. At first, initial evaluation, including the examination of airways, vital signs, and breathing, was performed, and the level of consciousness was checked according to the Glasgow Coma Scale (GCS) for all traumatic patients. Then, the results of all CT scans were evaluated by a neurologist. If the patient had PTE, she/he was included in the study. Data analysis was carried out using descriptive statistics in SPSS software (version 16). Results: The results showed that mild, moderate, and severe GCS scores were reported in 8 (14.3%), 30 (52.5%), and 18 (32.2%) participants, respectively. Vehicle accidents were the main cause of TBI (n = 34, 60%), and the lowest TBI rate was due to other cases (n = 4, 7.2%). The most and least frequent CT-scan finding was epidural hemorrhage (EH) (n = 24, 42.3%) and midline shift and intracerebral hemorrhage (n = 6, 10.8%), respectively. A total of 24 patients (42.3%) had tonic epilepsy, and 10 patients (17.9%) had epilepsy duration of more than 10 minutes. Conclusions: The most frequent risk factors included vehicles, falling from a height, and strikes, respectively. Additionally, the most common CT scan findings included EH and subarachnoid hemorrhage (SH). Motor vehicle accidents account for the highest rate of TBI-related PTE. For this reason, it is necessary to take preventive measures in this regard.

Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy.

Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus-a structure that is highly susceptible to injury-has been implicated in the evolution of seizure development. Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by unbiased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching, and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-Seq were performed to determine differential gene expression in animals that developed post-traumatic epilepsy (PTE+) vs. those animals that did not (PTE-), which may be associated with epileptogenesis. CCI injury resulted in 37% PTE incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE+ hilus. These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

Risk factors for post-traumatic epilepsy

PurposeThe 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). MethodsThis 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. ResultsIn 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), epi‑dural 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. ConclusionOur 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.

Treatment options for posttraumatic epilepsy.

Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE) are common and debilitating consequences of traumatic brain injury (TBI). Early PTS result in secondary brain injury by raising intracranial pressure and worsening cerebral edema and metabolic crisis. PTE is a localization-related epilepsy strongly associated with TBI severity, but risk factors for PTE and epileptogenesis are incompletely understood and are active areas of research. Medical management of PTS in adults and children is reviewed. Surgical options for posttraumatic drug-resistant epilepsy are also discussed. Continuous electroencephalography is indicated for children and adults with TBI and coma because of the high incidence of nonconvulsive seizures, periodic discharges, and associated secondary brain injury in this population. Neuroinflammation is a central component of secondary brain injury and appears to play a key role in epileptogenesis. Levetiracetam is increasingly used for seizure prophylaxis in adults and children, but variability remains. PTS occur commonly after TBI and are associated with secondary brain injury and worse outcomes in adults and children. Current medical and surgical management options for PTS and PTE are reviewed.

Risk of post-traumatic epilepsy after severe head injury in patients with at least one seizure.

BackgroundTo explore the incidence and risk factors, including type of seizures for post-traumatic epilepsy (PTE) after severe traumatic brain injury (TBI).Subjects and methodsThis was a retrospective follow-up study of patients discharged from Liaocheng People’s Hospital between March 2011 and June 2015 with a diagnosis of post-traumatic seizures. Risk factors for PTE were evaluated in 68 inpatients by using Kaplan–Meier curves and the Cox model.ResultsComplete clinical information was available for 68 patients. A total of 54 cases (79.4%) were diagnosed as presenting with PTE, occurring from 10 days to 179 months after severe TBI. Nineteen out of 54 cases (35.2%) had been defined as PTE within the first 6 months after the trauma, 17 cases (31.5%) within 7–12 months, 8 cases (14.8%) within 13–24 months, 2 cases (3.7%) within 25–36 months, and 8 cases (14.8%) within 37–179 months after the TBI. The Kaplan–Meier curves demonstrated that simple partial seizures, surgical treatment, and onset of seizures occurring within 6 months after injury were associated with PTE.ConclusionsThe Cox model indicated that, for patients aged >34 years at the time of injury, the PTE risk was 2.55 times greater than for those aged ≤34 years. In addition, simple partial seizures, surgical treatment and onset of seizures occurring within 6 months after injury were significant risk factors for the development of PTE.

Risk factors for posttraumatic epilepsy: A systematic review and meta-analysis.

A systematic review and meta-analysis was performed to identify risk factors for posttraumatic epilepsy (PTE). Two electronic databases (Medline and Embase) were searched to identify studies with a cohort, case-control, or cross-sectional design reporting on epidemiologic evidence regarding risk factors for PTE. Men had a higher risk of developing PTE than women [relative ratio (RR), 1.32; 95% confidence interval (CI), 1.10-1.59]. A history of alcohol abuse (RR, 2.18; 95% CI, 1.26-3.79), posttraumatic amnesia (RR, 1.31; 95% CI, 1.12-1.53), focal neurologic signs (RR, 1.42; 95% CI, 1.16-1.74), and loss of consciousness at initial traumatic brain injury (TBI) (RR, 1.62; 95% CI, 1.13-2.32) were associated with a greater risk of PTE. TBI-related abnormal neuroimaging findings, including skull fracture (RR, 2.27; 95% CI, 1.49-3.44), midline shift (RR, 1.46; 95% CI, 1.14-1.87), brain contusion (RR, 2.35; 95% CI, 1.69-3.28), subdural hemorrhage (RR, 2.00; 95% CI, 1.33-3.01), and intracranial hemorrhage (RR, 2.65; 95% CI, 1.83-3.82) were strong risk factors for PTE. The risk of developing PTE after skull fracture, mild brain injury, and severe brain injury peaked within the first year after TBI, and then gradually decreased. However, a high risk of PTE was sustained for >10years. The current meta-analysis identified potential risk factors for PTE. The results may contribute to better prevention strategies and treatments for PTE.

Risk Factors for Post-Traumatic Epilepsy in Adults

Craniocerebral trauma (CCT) is the cause of 20% ofsymptomatic and 5% of all cases of epilepsy [23]. In Russia,CCT is the main cause (27.7%) of location-dependentepilepsy in adults [1, 18].Post-traumatic epilepsy (PTE) is one of the late and mostserious complications of CCT. CCT and, hence, the possiblerisk of PTE, is most common in the age range 15–34 years,where the number of cases is about 30% [30]. The mostimportant cause of CCT consists of transport accidents (most-ly traffic accidents), as well as domestic, sporting, and indus-trial accidents, as well as military injuries.Assessment of the morbidity of PTE involves use of var-ious definitions of CCT itself and PTE [17], as well as dif-ferent durations of studies. This is because the developmentof PTE requires a stably developed focus of epileptic activityresulting from organic brain injury [1, 29]. The mechanismsof epileptogenesis are tightly linked with the course of recov-ery processes after CCT or the occurrence of aberrant plas-ticity. The most important are changes in neurotransmitterprocesses, sprouting, the various mechanisms of neurondeath, changes in membrane and receptor properties, and theformation of hyperexcitable neuronal systems [19]. Whileepileptic activity during the acute phase of traumatic braininjuries results from cortical injury and the nonspecificresponse to intense physical actions (the mechanisms of pri-mary brain damage), in the later period of trauma, the harm-ful actions of free radicals and excitotoxicity due to gluta-mate accumulation (the mechanism of delayed secondarybrain damage) are probably more important [30]. An impor-tant role here is played by impairments to cellular andhumoral immunity and disintegration of the functions ofautonomic and humoral-endocrine regulation [1]. In allcases, genetic predisposition factors are of undoubted impor-tance, though they are complex and heterogeneous [17, 21].PTE should also be discriminated from post-traumaticseizures. PTE includes repeated, late (i.e., onset more thanone week after CCT) post-traumatic seizures [15, 23, 51].Post-traumatic epileptic seizures include any epilepticseizure developing as a result of CCT [21, 34, 35]. Epilepticseizures can develop at different times after CCT. In assess-ing the periods of onset of epileptic seizures, most authorsuse the Barolin et al. classification [5], initially developedfor epileptic seizures in cerebrovascular diseases. This clas-sification identifies the following types of epileptic seizures:immediate, developing within the first 24 h; early, develop-ing at 1–7 days from onset of illness; and late, starting atseven or more days.The time of onset and the frequency of development ofepileptic seizures depend on the type, location, and volumeof the focus of brain damage and the state of the premorbidbackground of the patient (presence of cerebrovascular dis-ease, repeated CCT in the history, genetic predisposition,chronic alcoholism, etc.) [1]. The incidence of early post-traumatic seizures is 3–5%, compared with an incidence of

Posttraumatic Epilepsy in Operation Enduring Freedom/Operation Iraqi Freedom Veterans

Penetrating traumatic brain injury (TBI) is a well-established risk factor for post-traumatic epilepsy (PTE). However, many veterans in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) who suffer from TBI do so from blast injury, and its consequences are not fully known. Two neurologists performed a chart review to describe patterns of injury and health care among all 16 OEF/OIF veterans at the VA Greater Los Angeles Healthcare System who were assigned an outpatient diagnosis of both epilepsy and TBI in 2008-2009. All Veterans were male, and the mean age was 30 years. Blast exposure was the most common mechanism of TBI (81%). Although all Veterans were assigned a diagnosis code of seizures, the diagnosis of PTE was clinically confirmed in only 3 veterans. On the other hand, the diagnosis of post-traumatic stress disorder was confirmed in 81% of the sample and a diagnosis of nonepileptic seizures was suspected in 44% of the sample. Researchers who study PTE among the OEF/OIF population using administrative data also should perform chart reviews to account for the prevalence of psychogenic nonepileptic seizures.

Localisation of War Craniocerebral Injury as Risk Factor for Posttraumatic Epilepsy

To evaluate localization of certain zones of craniocerebral trauma and determine their importance for genesis ofposttraumatic epilepsy. Study encompassed 50 war veterans, with craniocerebral trauma and posttraumatic epilepsy. Control group included 50 war veterans, with war craniocerebral injury who have not experienced epileptic seizures. The craniocerebral trauma zone in every patient was registered by computerized tomography (CT) of the brain at the Clinic for Radiology of the University Clinical Centre Tuzla. For statistical analysis it was used chi2 test. Average age in examinees' group was 29.92 (+/- 8.91); while in control group was 29.98 (+/- 9.97) (p > 0.05). Both, injury at several lobes and post-traumatic epilepsy were registered in 22 (44%) patients as well as in 8 (16%) patients in control group, which represents extra statistical significance (p < 0.05). Frontal lobe trauma in examinees' group had 7 (14%) patients and 15 (30%) patients in control group (p > 0.05). Temporal lobe trauma in examinees group had equal number of patients 6 in each (12%); parietal lobe injury was found in 14 (28%) patients with epilepsy and 11 (22%) patients without posttraumatic epilepsy (p > 0.05). Occipital lobe injury had one patient with posttraumatic epilepsy (2%) and 10 (20%) veterans in control group (p < 0.05). Trauma of several brain lobes at the same time increases the possibility of posttraumatic epilepsy. Trauma of certain brain lobes is not significant risk factor for posttraumatic epilepsy, but trauma of occipital lobe is significantly more represented in group of patients without posttraumatic epilepsy.

Posttraumatic epilepsy

The purpose of this study is to focus on recent advances in understanding of the genetic and epidemiologic risk factors, development, modeling, and prevention of epilepsy after traumatic brain injury (TBI). Epidemiologic data suggest that the epileptogenic period after TBI in humans may last longer than previously thought. Depression was found to be an important risk factor for posttraumatic epilepsy (PTE). Once PTE has developed, it remits less often than previously reported. Moreover, patients with PTE appear to have a higher mortality rate than patients with TBI without epilepsy. In animal models it was reported that in addition to rats, also mice develop PTE. Furthermore, the immature rat brain is sensitive to TBI-induced epileptogenesis. The development of a lowered seizure threshold after TBI can be alleviated by pharmacotherapy in rats. These observations provide small but encouraging steps towards a better understanding of the mechanisms of posttraumatic epileptogenesis, which is a key to developing a cure for this condition.

Predicting Posttraumatic Epilepsy with MRI: Prospective Longitudinal Morphologic Study in Adults

Evaluation of morphologic risk factors for posttraumatic epilepsy (PTE) by using brain magnetic resonance imaging (MRI) in serial assessments <or=2 years after traumatic brain injury (TBI). Brain MRI hyperintense (gliosis) or hypointense (hemosiderin) areas or both were assessed in the images of 135 adult TBI inpatients who completed a 2-year clinical, EEG, and MRI study protocol. Overall clinical follow-up for the development of PTE was 5-10 years (median, 102 months). Morphologic risk factors for PTE were evaluated by using Kaplan-Meier curves and Cox regression analysis. In 20 patients, PTE developed. Kaplan-Meier curves showed that gliomesenchymal sequelae of focal brain lesions (subdural hematomas/contusions) that required surgical treatment (sSDH-C) were a PTE risk factor (p<0.001), as were sequelae of nonsurgical hemorrhagic contusions with gliosis wall incompletely surrounding hemosiderin dregs (IW) (p=0.039) and mainly those with time-related changes from incomplete to complete gliosis wall around hemosiderin (I/CW) (p=0.005); those with early hemosiderin completely surrounded by gliosis (CW) were not (p=0.821). Cox regression analysis showed that for patients with sequelae of sSDH-C, the PTE risk was 4.38 (p=0.023) times higher than for those who did not require surgical treatment or underwent surgery because of purely extradural hematoma; for those with IW and I/CW lesions, considered pooled, it was 6.61 times higher (p=0.014) than for those with CW lesions. MRI follow-up examination in the early chronic stage can differentiate among low-, intermediate-, and high-risk sequelae of TBI. These findings yield new evidence for, but do not resolve, the debate on posttraumatic epileptogenesis.

Introduction

Traumatic brain injury affects over 700,000 people in the United States each year. Of this number, about 75,000 will die of the immediate injury and an additional 90,000 will suffer long-term consequences, including the 20,000 who can be expected to subsequently develop epilepsy. These numbers are particularly impressive when one considers that those at highest risk, the young adult, will lose many productive years due to consequences of the condition. Population-based studies of newly diagnosed epilepsy suggest that up to 10% of all new cases can be attributed to traumatic brain injury. Cases affected with epilepsy are predominantly in the young adult population. There have been consistent efforts to reduce the frequency of traumatic brain injury. Primary prevention efforts include mandatory use of motorcycle helmets, seat belts, and bicycle helmets. The success of such programs is unclear, although the incidence of traumatic brain injury has fallen in the last 10 years. Better understanding of the epidemiology of traumatic brain injury may lead to other efforts in primary prevention. There has also been considerable effort to reduce the consequences of traumatic brain injury. Most notable have been efforts to intervene in the occurrence of posttraumatic epilepsy through early therapeutic interventions. To date, attempts at prophylaxis have been unsuccessful in preventing epilepsy, although there are some interventions that reduce the proportion of people with severe traumatic brain injury who experience seizures in the immediate period following the injury. In this supplement, we review the epidemiology of traumatic brain injury, the epidemiology of posttraumatic epilepsy, risk factors for posttraumatic epilepsy, and the justification for and results of studies of attempts to prevent posttraumatic epilepsy. We also present experimental data suggesting alternative methods of drug administration for prevention. Since there is a potential down side to any therapeutic intervention, we also discuss the impact of some antiseizure drugs on non-neuronal brain structures. We hope this review will provide insights into characteristics of posttraumatic epilepsy and stimulate further interest in both primary prevention of traumatic brain injury as well as the identification of intervention that may reduce or prevent the consequences of traumatic brain injury.

Posttraumatic epilepsy risk factors: one-year prospective study after head injury.

Prospective evaluation of risk factors for posttraumatic epilepsy (PTE) by using clinical, EEG, and brain computed tomography (CT) data in four assessments from the head injury (HI) acute phase to 1 year later; and evaluation of the possible epileptogenic role of hemosiderin as shown by brain magnetic resonance imaging (MRI). Risk factors for PTE were evaluated by using Kaplan-Meier curves, log-rank test, and the Cox model in 137 consecutively enrolled adult inpatients. Percentage differences of patients with brain hyperintense and/or hemosiderin areas shown by MRI 1 year after HI were statistically evaluated by univariate tests considering two subgroups [e.g., patients with (PTE) and without (WLS) late seizures]. The PTE subgroup included 18 patients with at least two seizures between the second and twelfth months. Kaplan-Meier curves demonstrated that Glasgow Coma Scale low score, early seizures, and single brain CT lesions are PTE risk factors, as is the development of an EEG focus 1 month after HI. No significant percentage difference was found between PTE and WLS patients with hemosiderin spots shown by MRI 1 year after HI. the Cox model indicates that, for HI patients with early seizures and brain CT single temporal or frontal lesions in the acute phase, the PTE risk is 8.58 and 3.43 times higher, respectively, than for those without. An EEG focus 1 month after HI is a risk factor 3.49 times higher than for patients without such EEG changes. One year after HI, a higher percentage of PTE than WLS patients had cortical MRI hyper-intense areas including hemosiderin.

Points: Treating the discharging ear

Out of 233 patients admitted for head trauma during 1977-1978, 93 had a CT scan examination within the first 48 hours. Forty-nine of these had at least one clinical risk factor for post-traumatic epilepsy. Ten of this group developed post-traumatic epilepsy. In all cases early CT scan showed focal brain damage, which was related more significantly to post-traumatic epilepsy than to risk factors.

CT scan prediction of late post-traumatic epilepsy.

Out of 233 patients admitted for head trauma during 1977-1978, 93 had a CT scan examination within the first 48 hours. Forty-nine of these had at least one clinical risk factor for post-traumatic epilepsy. Ten of this group developed post-traumatic epilepsy. In all cases early CT scan showed focal brain damage, which was related more significantly to post-traumatic epilepsy than to risk factors.