Post-traumatic seizure prophylaxis in severe traumatic brain injury: a risk-benefit analysis.

M. Ardissino¹, S. Muttoni¹, A. Tang¹, A. Faraj¹, K. Tsang². ¹Imperial College London, London, United Kingdom, ²Department of Neurosurgery, Imperial College NHS Trust, Hammersmith, United Kingdom.

Introduction: Post traumatic seizures (PTS) are a common long-term complication of traumatic brain injury (TBI) (1) and constitute a large cause of short and long-term morbidity and mortality for patients. Strong controversy exists surrounding the use of anti epileptic drugs (AEDs) to prevent PTS, both regarding their efficacy and effect on long term outcomes. Currently, guidelines recommend the use of PTS prophylaxis in severe TBI, conditional to a thorough risk-benefit analysis being carried out on a case by case basis. (2) But what are the risks and benefits to be considered? Which patients are most likely to benefit from treatment, and which ones are not?

Methods: An extensive literature search was carried out, using MEDLINE and EMBASE. We analysed data to determine the overall short- and long-term benefits associated with the use of early AEDs for PTS prophylaxis. Overall, a total of 2029 studies were found of which 7 were included. This totalled 8146 patients. We qualitatively analysed further epidemiological data to determine the patients at highest risk of developing PTS, and therefore those most likely to benefit from intervention.

Results: The use of AEDs was correlated with a decrease in early PTS in only one study. Only one study found a reduction in late PTS. There was no overall difference in mortality. We identified the most at-risk groups for early PTS to be those undergoing surgical interventions, and that risk of early PTS increased with injury severity.

Conclusion: Overall, there currently is very weak evidence to support routine PTS prophylaxis in all severe TBI patients. The findings, when combined with the cost, side effect profile and pharmacokinetic burden of the most commonly used anti-epileptic drugs, call for a thorough consideration of risks and benefits. We identified subgroups at highest risk, on whom PTS prophylaxis may confer the largest benefit, to help guide clinical decision-making in the field.

References:

(1) Ferguson PL et.al. (2010) Epilepsia. 51(5): 891-898.

(2) Carney N et.al (2016). Neurosurgery. 0:1-10.