Abstracts

Rationale: Traumatic brain injury is a known risk factor for developing epilepsy. [i][ii]However, the factors that are predictive of development of post-traumatic epilepsy (PTE) have not been well defined, especially in children. Children who suffer traumatic brain injury (TBI) are felt to be at high risk for seizures in the first 72 hours after injury.[iii] Studies on pharmacologic treatment post-TBI in children have been equivocal. While several studies have addressed the safety and feasibility of treatment with levetiracetam (LEV) after pediatric TBI, none have been able to show a statistically significant trend for treatment with LEV in reducing post-traumatic epilepsy years after injury.[iv][v][vi] At the University of Wisconsin, a TBI protocol has been in place since 2011. All children 24 months of age or less with TBI with a GCS of 12 or less receive a loading dose of LEV and are placed on continuous EEG monitoring for 72 hours. Through retrospective review of patients treated both before and after initiation of our protocol, we aimed to determine whether early administration of LEV decreases the incidence of early post-traumatic seizures and development of PTE. In addition, we aim to identify other factors that are associated with increased incidence of PTE and poor neurologic outcomes. [i]Piccenna L, Shears G, O'Brien T. Management of post-traumatic epilepsy: An evidence review over the last 5 years and future directions. Epilepsia Open 2017; 2(2): 123-144.[ii]Lee S et al. Prediction of Outcome after Traumatic Brain Injury Using Clinical and Neuroimaging Variables.J Clin Neurol 2012; 8: 224 - 229.[iii]Arndt D, Learner J et al.Subclinical Early Posttraumatic Seizures detected by continuous EEG monitoring in a consecutive pediatric cohort. Epilepsia 2013; 54: 1780-1788.[iv]Pearl PL, McCarter R, McGavin CL, et al. Results of phase II levetiracetam trial following acute head injury in children at risk for post-traumatic epilepsy. Epilepsia 2013: 54e135-e137.[v]Klein R, Herr D, Pearl PL, et al. Results of Phase 2 safety and feasibility study of treatment with levetiracetam for prevention of post-traumatic epilepsy. Arch Neurol 2012; 69:1290-1295.[vi]Pieracci FM, Moore EE, Beauchamp K, et al. A cost-minimization analysis of phenytoin versus levetiracetam for early seizure pharmaco-prophylaxis after traumatic brain injury. J Trauma Acute Care Surg 2012; 72: 276-281.  Methods: Pediatric patients with acute TBI requiring PICU admission at the University of Wisconsin were identified through a search of the electronic medical record using diagnosis codes of non-accidental trauma, TBI, or Closed Head Injury. Additional charts were abstracted from the historical list of all EEGs completed in the PICU from 2001-2017. The charts were separated into two separate cohorts from 2001-2011 (414 charts) prior to the initiation of the TBI protocol and 2011-2017 (225 charts) after the TBI protocol was established. Data on age at presentation, past medical history, GCS at presentation, mechanism of injury, imaging findings, antiepileptic medication administration, post-traumatic seizures, and neurologic outcomes were collected.  Results: Of the 639 available records, 250 charts were initially reviewed including 125 records from each cohort. Records were eliminated for lack of adequate data, inaccurate diagnoses, or duplicate entries, leaving 115 records in the 2001-11 cohort and 124 records from 2011-2017 in this initial analysis. The average age of pediatric patients in this review was 7 years, 8 months and average GCS score was 10.3. Post-injury images were reviewed and scored with a score of '1' for the presence of each imaging finding including subdural hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, skull fracture, intraparenchymal injury, hypoxic-ischemic injury, diffuse axonal injury, T2 changes, or diffusion-weighted abnormalities. The average total imaging score was 1.9. Thirty-seven (30%) of patients in the 2011-17 cohort received a 20-40 mg/kg load of LEV in the first 24 hours after injury. None of the patients in the 2001-2011 cohort received LEV, while 38 (33%) of these patients received an alternative antiepileptic medication, most often (73%) phenytoin. There was a statistically significant decrease in the incidence of post-traumatic seizures 24 hours after injury in patients treated with early load of LEV (8%) versus patients treated with early bolus of another AED (31%) (p=0.011). Neurologic outcomes were measured on a scale of 1 - 4 with 0=normal or pre-injury baseline, 1=mild but independent, 2=needs help, 3=totally dependent, 4=death. The incidence of death after traumatic brain injury was 10% in both cohorts. There was a statistically significant increase in neurologic sequelae score 2 - 4 in patients with 2 or greater findings on brain imaging (p<0.001).  Conclusions: The institution of a TBI protocol requiring loading of LEV in children 24 months of age or younger and with GCS 12 or less has resulted in an increase in use of LEV in the acute management of traumatic brain injury in children with no worsening of outcomes. Preliminary analysis shows a decrease in early post-traumatic seizures (p = 0.011) but not PTE (p = 0.24). The presence of more than one pathologic imaging finding was associated with poorer neurologic outcome (p<0.001). Funding: No funding