Keppra for Subdurals

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Motivation: As a medicine intern last year, I often scoffed at the algorithmic recommendation by neurosurgery of Keppra for seven days after every small subdural hemorrhage.  Two nights ago, I self-consciously found myself writing the same recommendation while consulting as neurology for a patient after a fall.  What is the data?

Turns out that there is no high quality randomized trial testing anti-epileptics in acute sub-dural hematomas.  The practice is drawn from literature in traumatic brain injury.

Paper: Chang, B.S. and Lowenstein, D.H.  "Practice Parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury." Neurology (2003); 60: 10-16.

Method: A meta-analysis of prospective placebo controlled trials testing anti-epileptic drugs in traumatic brain injury.  Literature search revealed that data existed only for severe TBI - typically with loss of consciousness or amnesia for 12 to 24 hours, depressed skull fracture, or brain contusion on CT scan.  No constraint was placed on the choice of AED.  Authors separated analysis by prevention of early or late seizures.

Results:
Prevention of Early Seizures: Four randomized trials examined early (less than 7 days) prevention of seizure from TBI.  Three studies used phenytoin and one used carbamazepine.   The pooled RR for seizure on AED compared to placebo was 0.37 (CI: 0.18-0.74).  Of the four studies, one did not find any benefit with AED though that study was hindered by low event rate.  There was no significant increase in frequency of adverse effects in group taking AED.

Prevention of Late Seizures: Five high quality trials tested long-term AED for prevention of seizures.  The treatment duration was 6 months to 2 years (most trials were 1-2 years) with median follow-up of 2 years (five trials) with range of 18 months to 2 years.  Trials used phenytoin, carbamazepine, or valproic acid.  The pooled RR for seizure on AED compared to placebo was 1.05 (CI: 0.82-1.35) demonstrating no benefit - none of the individual studies showed benefit.  Some unblinded studies (not included in pooled analysis) showed benefit.  Adverse effects (particularly rash) was significantly higher in the intervention group than placebo group.

Discussion: In severe TBI, anti-epileptic drugs appear beneficial in preventing seizures in the short term (7 days) but ineffective in the long-term.  This landmark meta-analysis, though, has been commonly extended to justify prescribing anti-epileptics for many minor to mild TBI without changes in consciousness or brain contusions.  Although probably beneficial, the practice is still more opinion based rather than evidence based.    Also, the trials used mostly phenytoin as the anti-epileptic of choice while current practice is more heavily biased towards levetiracetam (Keppra).  While I do not plan to rebel against the seven day course of Keppra for subdurals, there is need for data in this common clinical situation.