Seizures prophylaxis in Traumatic Brain Injury

Neurocritical Care
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Sep 8, 2021
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  • Traumatic brain injury (TBI) presents frequently to the emergency departments visits and is associated with increase risks of seizures.
  • It requires effective prevention to improve the outcomes in patients recovering from traumatic brain injury.
  • However, late onset seizures increases the likelihood of progression to epilepsy.
  • Prophylactic administration of Anti-Seizure Medications (ASMs) is used as a measure to decrease the risks of post-traumatic seizures and progression into post-traumatic epilepsy (PTE).
  • PTE accounts for 10-20% of epilepsy cases in general population
Key Points
  • Short term (7-10 days) prophylaxis with ASM is recommended for Severe TBI
    • Severe TBI = With loss of consciousness or contusion on initial neuroimaging
  • Phenytoin or Levetiracetam: Most commonly used
  • Long-term treatment is recommended with ASMs after first onset late seizure.

Early Post-traumatic seizures:

  • Early seizures occurs within 7 days following traumatic brain injury

Factors associated with Early Post-traumatic seizures

  • Depressed skull fracture
  • Contusion
  • Surgery for Intra-cerebral hematoma
  • Subdural hematoma
  • Penetrating brain injury
  • Glasgow coma scale<10
  • Young children


  • Patients who had early seizures and at increased risk of developing PTE.


  • ASM is recommend for short term (7-10 Days) in patients with loss of awareness due to TBI
  • Phenytoin is the only recommended treatment for seizure prophylaxis.
  • IV Levetiracetam is also increasingly being used as a seizure prophylaxis because of favourable pharmacokinetics and pharmacodynamics.
  • A meta-analysis study by Yong et al failed to show superior safety and efficacy of Levetiracetam compared to phenytoin for early and late seizures prophylaxis.

Late Post-traumatic seizures/ Post-traumatic Epilepsy

Onset of seizures past seven days of traumatic brain injury.
Mechanism of progression of neuronal injury to late onset seizures is unknown.


Unfortunately, recurrence is common after first onset of late seizure.


Long-term treatment with AED drug is recommended after first late-onset seizure.
Development of novel medication to target molecular pathways to prevent progression into PTE is needed.

Guidelines on the management of seizures prophylaxis following TBI - Brain Trauma Foundation


  • There was insufficient evidence to support a Level I recommendation for seizures prophylaxis.


  • Prophylactic use of phenytoin/valproate is not recommended for preventing late post traumatic seizures (PTS).
  • Phenytoin is recommended to decrease the incidence of early PTS (within 7 days of injury), when the overall benefit is felt to outweigh the complications associated with such treatment.
  • However, early PTS have not been associated with worse outcomes.
  • At the present time there is insufficient evidence to recommend levetiracetam over phenytoin regarding efficacy in preventing early post-traumatic seizures/toxicity.

Further Reading


  • Chartrain, A. G., Yaeger, K., Feng, R., Themistocleous, M. S., Dangayach, N. S., Margetis, K., & Hickman, Z. L. (2017). Antiepileptics for Post-Traumatic Seizure Prophylaxis after Traumatic Brain Injury. Current pharmaceutical design, 23(42), 6428–6441.
  • Lucke-Wold, B. P., Nguyen, L., Turner, R. C., Logsdon, A. F., Chen, Y. W., Smith, K. E., Huber, J. D., Matsumoto, R., Rosen, C. L., Tucker, E. S., & Richter, E. (2015). Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure. Seizure, 33, 13–23.
  • Yang, Y., Zheng, F., Xu, X., & Wang, X. (2016). Levetiracetam Versus Phenytoin for Seizure Prophylaxis Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis. CNS drugs, 30(8), 677–688.
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