Posttraumatic epilepsy in children

Posttraumatic epilepsy (PTE) after a traumatic brain injury occurs in 10%-20% of children.

Among children with moderate traumatic brain injury or severe traumatic brain injury, the presence of additional CT findings, other than skull fractures, seem to increase the risk of PTE. In the cohort of Keret et al, the occurrence of an early seizure did not confer an increased risk of PTE ¹⁾.

Mild traumatic brain injury (MTBI) was found to confer increased risk for the development of PTE and intractable PTE, of 4.5 and 8 times higher, respectively. As has been established in adults, these findings confirm that MTBI increases the risk for PTE in the pediatric population ²⁾.

There is a a need for biomarkers in children following traumatic brain injury to reliably evaluate the risk of post-traumatic epilepsy ³⁾.

Literature recognizes several posttraumatic seizure subtypes based on time of presentation and the underlying pathophysiology: impact, immediate, delayed early, and late/posttraumatic epilepsy. Appropriate classification of pediatric posttraumatic seizure subtypes can be helpful for appropriate management and prognosis.

A review of Arndt et al focused on early posttraumatic seizures, and the subtypes of early posttraumatic seizure. Incidence, risk factors, diagnosis, seizure semiology, status epilepticus, management, risk of recurrence, and prognosis were reviewed. The integration of continuous electroencephalographic (EEG) monitoring into pediatric traumatic brain injury management may hold the key to better characterizing and understanding pediatric early posttraumatic seizures ⁴⁾.

The aim of a rapid evidence review was to provide a synthesis of existing evidence on the effectiveness of treatment interventions for the prevention of PTE in people who have suffered a moderate/severe TBI to increase awareness and understanding among consumers. Electronic medical databases (n = 5) and gray literature published between January 2010 and April 2015 were searched for studies on the management of PTE. Twenty-two eligible studies were identified that met the inclusion criteria. No evidence was found for the effectiveness of any pharmacological treatments in the prevention or treatment of symptomatic seizures in adults with PTE. However, limited high-level evidence for the effectiveness of the antiepileptic drug levetiracetam was identified for PTE in children. Low-level evidence was identified for nonpharmacological interventions in significantly reducing seizures in patients with PTE, but only in a minority of cases, requiring further high-level studies to confirm the results ⁵⁾.

During a median follow-up period of 7.3 years, 9 (9%) of 95 children with moderate-to-severe TBI developed PTE; 4 developed intractable epilepsy. The odds for developing PTE was 2.9 in patients with severe compared to moderate TBI. CT findings showed fractures in 7/9 (78%) of patients with PTE, compared to 40/86 (47%) of those without PTE (p = 0.09). Of the patients with fractures, all those with PTE had additional features on CT (such as haemorrhage, contusion and mass effect), compared to 29/40 (73%) of those without PTE. One of nine (11%) PTE patients and 10 of 86 (12%) patients without PTE had immediate seizures. Two (22%) children with PTE had their first seizure more than 2 years after the TBI.

Among children with moderate or severe TBI, the presence of additional CT findings, other than skull fractures, seem to increase the risk of PTE. In this cohort, the occurrence of an early seizure did not confer an increased risk of PTE ⁶⁾.

Data were collected from electronic medical records of children 0-17 years of age, who were admitted to a single medical center between 2007 and 2009 with a diagnosis of MTBI. This prospective research consisted of a telephone survey between 2015 and 2016 of children or their caregivers, querying for information about epileptic episodes and current seizure and neurological status. The primary outcome measure was the incidence of epilepsy following TBI, which was defined as ≥ 2 unprovoked seizure episodes. Posttraumatic seizure (PTS) was defined as a single, nonrecurrent convulsive episode that occurred > 24 hours following injury. Seizures within 24 hours of the injury were defined as immediate PTS.

Of 290 children eligible for this study, 191 of them or their caregivers were reached by telephone survey and were included in the analysis. Most injuries (80.6%) were due to falls. Six children had immediate PTS. All children underwent CT imaging; of them, 72.8% demonstrated fractures and 10.5% did not demonstrate acute findings. The mean follow-up was 7.4 years. Seven children (3.7%) experienced PTS; of them, 6 (85.7%) developed epilepsy and 3 (42.9%) developed intractable epilepsy. The overall incidence of epilepsy and intractable epilepsy in this cohort was 3.1% and 1.6%, respectively. None of the children who had immediate PTS developed epilepsy. Children who developed epilepsy spent an average of 2 extra days in the hospital at the time of the injury. The mean time between trauma and onset of seizures was 3.1 years. Immediate PTS was not correlated with PTE.

In this analysis of data from medical records and long-term follow-up, MTBI was found to confer increased risk for the development of PTE and intractable PTE, of 4.5 and 8 times higher, respectively. As has been established in adults, these findings confirm that MTBI increases the risk for PTE in the pediatric population ⁷⁾.

Park et al. performed a retrospective electronic chart review of patients who had suffered traumatic brain injury and subsequently evaluated at Children's Hospital of Michigan from 2002 to 2012. Various epidemiologic and clinical variables were analyzed.

Patients who had severe traumatic brain injury and post-traumatic epilepsy had an abnormal acute head computed tomography. These patients had increased number of different seizure types, increased risk of intractability of epilepsy, and were on multiple antiepileptic drugs. Hypomotor seizure was the most common seizure type in these patients. There was a high prevalence of patients who suffered nonaccidental trauma, all of whom had severe traumatic brain injury.

This study demonstrates a need for biomarkers in children following traumatic brain injury to reliably evaluate the risk of post-traumatic epilepsy ⁸⁾.

Children ages 6-17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into a phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. The recruitment goal was 20 treated patients. Twenty patients who presented within 8-24 h post-TBI and otherwise met eligibility criteria were recruited for observation. Follow-up was for 2 years. Forty-five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm. The most common risk factor present for pediatric inclusion following TBI was an immediate seizure. Medication compliance was 95%. No patients died; 19 of 20 treatment patients were retained and one observation patient was lost to follow-up. The most common severe adverse events in treatment subjects were headache, fatigue, drowsiness, and irritability. There was no higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects. Only 1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7 days after trauma). This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at-risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at-risk population ⁹⁾.