Post-traumatic seizures, their prevention and management

The College had asked about this in Question 28from the second paper of 2011.
Specifically, they wanted the risk factors for post-traumatic seizures.

The best resource for such things is the Brain Trauma Organisation Guidelines for Management Traumatic Brain Injury. In fact, the College examiners pillage their guidelines liberally, cutting and pasting whole blocks of text into the model answers.

Risk factors for post-traumatic seizures

  • Glasgow Coma Scale (GCS) Score < 10
  • Cortical contusion
  • Depressed skull fracture
  • Subdural hematoma
  • Epidural hematoma
  • Intracerebral hematoma
  • Penetrating head wound
  • Seizure within 24 h of injury

The below-linked review article on post-traumatic seizure prophylaxis presents an even more extensive table, which is perhaps more than is expected of a 2-mark SAQ answer.

It is reproduced below, more for completeness than educational value.

Risk Factors for Early and Late Post-Traumatic Seizures

Risk factors for early seizures

  • Glasgow Coma Scale score of ≤10
  • Immediate seizures
  • Cortical contusion
  • Linear fracture
  • No or brief unconsciousness
  • Penetrating head injury
  • Depressed skull fracture
  • Age ≤ 65 yr
  • Increased severity of injury
  • Chronic alcoholism
  • Postraumatic amnesia lasting longer than 30 min
  • Subdural, epidural, or intracerebral hematoma

Risk factors for late seizures

  • Early post-traumatic seizures
  • Acute intracerebral hematoma
  • Cortical contusion
  • Increased severity of injury
  • Posttraumatic amnesia lating longer than 24 hr
  • Loss of consciousness
  • Age > 65 yr

Rationale for antiepileptic prophylaxis

A good 2013 review article is available for the time-rich exam candidate to scrutinise.

For the rest of us, here are the salient points:

  • Approximately 5-7% of TBI patients experience post-traumatic seizures.
  • Neurotoxicity from such seizures represents a preventable morbidity
  • Seizure activity (even when non-convulsive, and in the context of a protected airway) is a cause for increased cereberal metabolic demand, and may cause secondary brain injury.
  • Antiepileptic therapy is not without its risks, but uncontrolled seizures in TBI represent an even greater risk
  • However, there does not seem to be any evidence that reduction in post-traumatic seizures within the first week decreases long term mortality in any way.

Choice of agents and duration of therapy

  • The 2003 AAN guidelines recommend a one-week course of therapy.
  • There is no evidence to support prophylaxis for longer than seven days after TBI, even if risk factors are present.
  • Phenytoin has been the drug of choice. BTF were unable to find any evidence to recommend levitiracetam over phenytoin.
    • Advantages include:
    • Disadvantages include:
      • It requires monitoring
      • The exact therapeutic level to aim for in TBI is not well established
      • It has extensive interactions
      • It has unusual nonlinear elimination kinetics
      • It may have a negative effect on long-term cognitive function
  • Levitiracetam is becoming the drug of choice.
    • Advantages include:
    • Disadvantages include:
      • Its expensive
      • There are no studies to convincingly demonstrate its superiority over phenytoin. A survey of epilepsy specialists conducted in 2015 has demonstrated that there is genuine equipoise among senior medical experts, to the point where one major neurotrauma center might use exclusively phenytoin, and the other might use only levitiracetam.

References

Chang, Bernard S., and Daniel H. Lowenstein. "Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury Report of the Quality Standards Subcommittee of the American Academy of Neurology."Neurology 60.1 (2003): 10-16.

Torbic, Heather, et al. "Use of antiepileptics for seizure prophylaxis after traumatic brain injury." Am J Health Syst Pharm 70.9 (2013): 759-66.

Brain Trauma Organisation Guidelines for Management Traumatic Brain Injury is the definitive source.

Oh's Intensive Care manual:

Chapter 43 (pp. 563) Cerebral protection by Victoria Heaviside and Michelle Hayes, and

Chapter 67 (pp. 765) Severe head injury by John A Myburgh.

Haltiner, Alan M., et al. "Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis." Journal of neurosurgery91.4 (1999): 588-592.

Temkin, Nancy R., et al. "A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures." New England Journal of Medicine 323.8 (1990): 497-502.

Zafar, Syed N., et al. "Phenytoin versus leviteracetam for seizure prophylaxis after brain injury–a meta analysis." BMC neurology 12.1 (2012): 30.

Gabriel, Wendy M., and A. Shaun Rowe. "Long-Term Comparison of GOS-E Scores in Patients Treated With Phenytoin or Levetiracetam for Posttraumatic Seizure Prophylaxis After Traumatic Brain Injury." Annals of Pharmacotherapy48.11 (2014): 1440-1444.

Szaflarski, Jerzy P. "Is There Equipoise Between Phenytoin and Levetiracetam for Seizure Prevention in Traumatic Brain Injury?." Epilepsy Currents 15.2 (2015): 94-97.