Letter to the Editor: Early seizure prophylaxis in pediatric severe traumatic brain injury: still a long way to go

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TO THE EDITOR: It was with great interest that I read the article by Ostahowski et al.5 (Ostahowski PJ, Kannan N, Wainwright MS, et al: Variation in seizure prophylaxis in severe pediatric traumatic brain injury. J Neurosurg Pediatr 18:499–506, October 2016). The authors wanted to demonstrate the variation in seizure prophylaxis in a retrospective cohort study of 5 pediatric trauma centers. Overall, 79% of 236 patients received seizure prophylaxis (mostly with fosphenytoin), and in only 63% of these patients was this prophylaxis introduced in the first 24 hours after trauma.

Posttraumatic seizures (PTSs) are defined as those occurring early, within 7 days of injury, or late, beyond 8 days of recovery.7 It is estimated that early PTSs occur in about 10% of children after a traumatic brain injury (TBI). Risk factors associated with the occurrence of PTS have been examined in previous studies and include location of the lesion (mainly nonfrontal traumas), cerebral contusions, retained bone and metal fragments, depressed skull fracture, focal neurological deficits, loss of consciousness, Glasgow Coma Scale (GCS) score < 10 at admission, duration of posttraumatic amnesia, subdural or epidural hematoma, and penetrating injury.3

It is already known that PTS increases the risk of childhood-onset epilepsy, although this association remains unclear. A recent study published by Camfield and Camfield1 consisted of a survey of 472 adults who had developed epilepsy in childhood, and 11% reported a serious injury before the onset of epilepsy. In that paper, most injuries occurred years after the initial diagnosis of seizure (range 1.5–30 years), and the authors concluded that early seizure prophylaxis could be useful to reduce the incidence of PTS.

Although PTS remains a significant concern among pediatricians, neurologists, and neurosurgeons, there is little evidence that antiepileptic drugs really reduce the incidence of these seizures in a TBI setting. In the last set of guidelines for the management of severe TBI in children and adolescents, published by Kochanek et al. in 2012,3 only 1 study conducted by Lewis et al.4 was included in the analysis of the possible benefits of seizure prophylaxis. In that retrospective cohort study, 194 children with TBI were analyzed. For children with a GCS score of 3–8, treatment with prophylactic phenytoin was associated with a reduced rate of seizures (15%) compared with the rate among patients not treated with prophylactic medication (p = 0.04). In the guidelines' conclusions,3 Kochanek and colleagues state that there are only Level III (weak) recommendations that prophylactic treatment with phenytoin can be considered to reduce the incidence of early PTS in pediatric patients with severe TBI.

Another point of interest is which anticonvulsant drug should be used. Some recent studies have included levetiracetam as a drug of choice to prevent PTS. In a prospective observational study by Chung and O'Brien,2 34 patients with moderate to severe TBI received either levetiracetam or phenytoin. The authors concluded that early clinical PTS occurred frequently in children with moderate to severe TBI despite seizure prophylaxis with levetiracetam and that younger children and those with abusive head trauma were at an increased risk for seizures. Tanaka and Litofsky6 also pointed out that levetiracetam may not be a better choice for PTS prophylaxis if compared to phenytoin or fosphenytoin.

Given this, the article by Ostahowski et al.5 brings useful and important information about how PTS prophylaxis is conducted in trauma centers among all those uncertain conclusions about when to start it or which drug to use. Some interesting points to be elucidated include the efficacy and safety of drugs required for the prevention of early PTS, the mechanisms of epileptogenesis after TBI, and improvements in the classification of PTS, including the use of electroencephalography in the emergency department to detect and classify PTS. Although one would think that PTS prophylaxis is almost universal in the initial prescriptions for children with moderate to severe TBI, the paper by Ostahowski and colleagues showed that this practice is variable and that the outcomes are unclear. It is clear that larger studies with proper allocation and randomization should be performed to find the real place for PTS prophylaxis in this scenario.

References

  • 1

    Camfield CCamfield P: Injuries from seizures are a serious, persistent problem in childhood onset epilepsy: a population-based study. Seizure 27:80832015

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  • 2

    Chung MGO'Brien NF: Prevalence of early posttraumatic seizures in children with moderate to severe traumatic brain injury despite levetiracetam prophylaxis. Pediatr Crit Care Med 17:1501562016

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  • 3

    Kochanek PMCarney NAdelson PDAshwal SBell MJBratton S: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents—second edition. Pediatr Crit Care Med 13:Suppl 1S1S822012. (Erratum in Pediatr Crit Care Med 13: 252 2012)

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  • 4

    Lewis RJYee LInkelis SHGilmore D: Clinical predictors of posttraumatic seizures in children with head trauma. Ann Emerg Med 22:111411181993

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  • 5

    Ostahowski PJKannan NWainwright MSQiu QMink RBGroner JI: Variation in seizure prophylaxis in severe pediatric traumatic brain injury. J Neurosurg Pediatr 18:4995062016

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  • 6

    Tanaka TLitofsky NS: Anti-epileptic drugs in pediatric traumatic brain injury. Expert Rev Neurother 16:122912342016

  • 7

    Yablon SA: Posttraumatic seizures. Arch Phys Med Rehabil 74:98310011993

Disclosures

The author reports no conflict of interest.

Response

We thank Dr. Filho for a thorough discussion of the evidence leading to recommendations regarding antiepileptic drug use in pediatric TBI. We also thank him for taking an interest in our paper. One goal of our study was to examine practices between and within centers, and a second goal was to try to understand whether this variability is a reason why previously published studies regarding antiepileptic use were negative. In fact, the Brain Trauma Foundation Guidelines, which have outlined evidence-based treatment for children with TBI, have very few studies from which to glean information regarding PTS prophylaxis.1 While we expected between-center variability in antiepileptic drug use, we were surprised by the within-center use. This finding suggests that we must first come to consensus on medication choices and include their use in different treatment locations in all analyses. Although our research outlines the general use of antiseizure medication as prophylaxis in this pediatric population, we agree that more research is needed to provide higher-level evidence for the use of seizure prophylaxis in TBI. Higher-level studies are needed to determine best practices, including the specific medication to use for seizure prophylaxis, the efficacy of seizure prophylaxis in preventing seizures, and methods to identify PTS earlier after TBI.

References

1

Kochanek PCarney NAdelson PAshwal SBell MBratton S: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents—second edition. Pediatr Crit Care Med 13:Suppl 1S1S822012. (Erratum in Pediatr Crit Care Med 13: 252 2012)

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Article Information

INCLUDE WHEN CITING Published online January 6, 2017; DOI: 10.3171/2016.7.PEDS16384.

© AANS, except where prohibited by US copyright law.

Headings

References

  • 1

    Camfield CCamfield P: Injuries from seizures are a serious, persistent problem in childhood onset epilepsy: a population-based study. Seizure 27:80832015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Chung MGO'Brien NF: Prevalence of early posttraumatic seizures in children with moderate to severe traumatic brain injury despite levetiracetam prophylaxis. Pediatr Crit Care Med 17:1501562016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Kochanek PMCarney NAdelson PDAshwal SBell MJBratton S: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents—second edition. Pediatr Crit Care Med 13:Suppl 1S1S822012. (Erratum in Pediatr Crit Care Med 13: 252 2012)

    • Search Google Scholar
    • Export Citation
  • 4

    Lewis RJYee LInkelis SHGilmore D: Clinical predictors of posttraumatic seizures in children with head trauma. Ann Emerg Med 22:111411181993

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Ostahowski PJKannan NWainwright MSQiu QMink RBGroner JI: Variation in seizure prophylaxis in severe pediatric traumatic brain injury. J Neurosurg Pediatr 18:4995062016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Tanaka TLitofsky NS: Anti-epileptic drugs in pediatric traumatic brain injury. Expert Rev Neurother 16:122912342016

  • 7

    Yablon SA: Posttraumatic seizures. Arch Phys Med Rehabil 74:98310011993

  • 1

    Kochanek PCarney NAdelson PAshwal SBell MBratton S: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents—second edition. Pediatr Crit Care Med 13:Suppl 1S1S822012. (Erratum in Pediatr Crit Care Med 13: 252 2012)

    • Search Google Scholar
    • Export Citation

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