Neurosurgery notes/Trauma/Management of trauma/Non surgical/Seizure management

Seizure management

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Non surgical
Seizure (See seizures)
See MAST trial-ongoing

Epidemiology of post-traumatic seizures

  • Two large population based studies
    • Annegaers et al 1998
      • N=4541 TBI patients
      • Between 1935 to 1984 in Minnesota
      • Risk of PTS increases with TBI severity and varies according to time since injury
    • Christensen et al., 2009
      • 78,572 people with TBI over 25 yrs.
      • In Denmark (1977-2002)
      • Traumatic head injury is long lasting risk factor for epilepsy and there is a window for prevention of prevention post traumatic epilepsy

Post-traumatic seizures (PTS)

Classification

  • Early: < 7 days of injury
    • Early PTS have not been associated with worse outcomes.
  • Late: > 7 days following injury
    • True Post traumatic epilepsy

Numbers

  • Overall average risk of PTS after HI=2% in 10 yrs
  • Mild TBI
    • Clinical PTS: similar to without HI
  • Moderate TBI
    • Clinical PTS: 5%
  • Severe TBI, the rate of
    • Clinical PTS: 12%,
    • Subclinical seizures (via EEG): 20% to 25%.

The risk factors for early PTS include:

  • Acute subdural, epidural. or intracerebral hematoma (SDH, EDH or ICH)
    • Risk of seizure >20%
  • Open-depressed skull fracture with parenchymal injury
  • Seizure within the first 24 hrs after injury
    • Risk of seizure >20%
  • Glasgow Coma Scale score< 10
    • Risk of seizure after Severe TBI (GCS <8): 15%
  • Penetrating brain injury
    • Risk of seizure >20%
  • History of significant alcohol abuse
  • ± cortical (hemorrhagic) contusion on CT

Management

  • Recommendation
    • Give 7 days of keppra 1g BD
  • Seizure prophylaxis for PTS
    • Prophylactic phenytoin, carbamazepine, phenobarbital, or valproate do not prevent late PTS
    • AEDs (e.g. phenytoin, valproate, or carbamazepine) may be used to decrease the incidence of early PTS (within 7 days of TBI) in patients at high risk of seizures after TBI
    • AEDs does not improve outcome
    • Advantage
      • A relatively high incidence of PTS in severe TBI patients
      • Potential benefits to preventing seizures following TBI (e.g., limiting derangement in acute physiology, preventing the development of chronic epilepsy, and preventing herniation and death).
    • Disadvantage
      • Side effect of antiepileptics (neurobehavioral)
  • Phenytoin
    • Recommended to decrease the incidence of early PTS (within 7 days of injury),
      • Temkin, 1990:
        • N=404
        • Single centre double blind RCT
        • Primary endpoint
          • Occurrence of seizures
            • Early (<1 week)
            • Late (>1 week)
          • Diagnosis of seizure by experienced clinician with use of EEG
        • Cumulative seizure rate phenytoin 3.6% vs placebo 14.2%
          • Results
              • Phenytoin treatment reduced risk of seizures by 73% in the first week.
              • Additional secondary analysis revealed no difference in the cumulative probability of all seizures (early or late) in both groups.
              Outcome
              Phenytoin group
              Placebo group
              Statistical significance
              Early seizure rate (cumulative)
              3.6 ± 1.3%
              14.2 ± 2.6%
              p < 0.001
              Late seizure rate (2 years)
              27.5 ± 4.0%
              21.1 ± 3.7%
              None
          • Conclusions
            • Phenytoin has a beneficial effect in reducing the incidence of post-traumatic seizures only in the first week following severe head injury.
        • PTS critique
          • Good:
            • 1st RCTs with sufficient numbers to analyse efficacy of phenytoin for PTS prophylaxis
            • Meta-analysis of all published trials support findings of this study
              • Schierhout and Roberts, 2001 Cochrane review
                • 6 published RCTs
                • Use of AEDs would keep 1 in 10 patients seizure free in post injury but no evidence for efficacy against late seizures
    • Prophylactic use of phenytoin or valproate is not recommended for preventing late PTS.
      • Temkin, 1990:
        • At 2 years 27.5% Phenytoin vs. 21.1% Placebo, p>0.2.
  • Levetiracetam (known by the brand name Keppra) appears to be increasing in use for seizure prophylaxis for various pathologies, including TBI.
    • The available comparative studies are insufficient to support a recommendation for or against the use of levetiracetam over another agent.
    • At the present time there is insufficient evidence to recommend levetiracetam over phenytoin regarding efficacy in preventing early post-traumatic seizures and toxicity.
      • Best study shows no difference (seizure rate, adverse drug reaction, mortality) between levetiracetam vs phenytoin: Inaba 2013
  • Duration of drug
    • Temkin 1990: phenytoin 12 months
    • Inaba 2013: 7 days Keppra 1000mg BD phenytoin 7 days
  • Claassen et al., 2013
    • EEG to exclude seizures in TBI patients with unexplained and persistent altered consciousness

Post-traumatic epilepsy (PTE)

  • Defined as recurrent seizures more than 7 days following injury.
  • A 2010 population-based study showed that rates of PTE are substantially higher than the risk of developing epilepsy in the general population.
  • Risk for PTE
    • Severe TBI and early PTS prior to discharge;
    • Acute intracerebral hematoma or cortical contusion;
    • Posttraumatic amnesia lasting longer than 24 hours;
    • Age >65 years;
    • Premorbid history of depression.