Seizure Prophylaxis

Traumatic Brain Injury:

  • (BTF Guidelines March 2016) Prophylactic use of phenytoin or valproate is not recommended for preventing late PTS.
  • Phenytoin is recommended to decrease the incidence of early PTS (within 7 d of injury), when the overall benefit is thought 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 compared with phenytoin regarding efficacy in preventing early post-traumatic seizures and toxicity.
  • Use antiepileptic drugs short-term for the prevention of early seizures in patients who are at high risk and in whom seizures present a threat because of elevated intracranial pressure, systemic injury, or other reasons.
  • Use AEDs long-term after first late post-traumatic seizure because of high rate of recurrence.
  • Do not use AEDs to prevent late seizures or post-traumatic epilepsy in patients who have NOT had a late-post-traumatic seizure.
  • Post-trauma seizures can be early (within 7d) vs late (after 7d)
  • Early post-trauma seizure correlates with severity of injury (penetrating TBI with highest incidence ~50%, also high risk are depressed skkull fractures, SDH, ICH, GCS <10 or cortical contusions incidence 20-25%)
  • pivotal 1990 study PHT vs placebo in TBI with 404 patients – early seizures lower (3.6% vs 14.2%) but no decrease in late seizures, high % of rash withdrawal from PHT group, and decreased function at f/u in 1 month; same findings for valproate but trend toward increased mortality; same findings for CMZ as well
  • current BTF recommendations: give prophylactic AEDs only for first 7d after injury (Level II)
  • AAN: prophylactic phenytoin is effective for prevention of early PTS
  • keppra may be a reasonable alternative (both guidelines published before levetiracetam trials)

ENLS 2017 – Use of prophylactic AEDs is indicated if seizures accompany the presentation, patient has severe TBI (GCS<9) and/or patient has an abnormal CT scan. AEDs should be stopped after 7d if there is no clinical or EEG seizure activity.


Metastatic Brain Tumors:

  • Start prophylactic AEDs perioperatively in patients without history of seizures who undergo brain tumor resection.  Taper AEDs post-operatively if patient remains seizure-free.  Long-term seizure prophylaxis is not required.
  • Do not use prophylactic AEDs for patients without history of seizures who have not undergone a neurosurgical procedure. (2010 systematic review [3])
  • seizures more likely with primary vs metastatic brain tumors
  • seizures more likely with low-grade glioma than high-grade glioma
  • seizures more likely with specific tumor types (dysembryoplastic neuroepithelial tumors than meningiomas)

Intracerebral Hemorrhage:

  • Do not start prophylactic AEDs in patients with ICH.  (Some experts suggest brief period of AED prophylaxis in patients with lobar hemorrhages but 2010 guidelines recommend against this.)

Cerebral Venous Thrombosis:

  • May be reasonable to continue AED treatment for 1 year in patients with early seizures and hemorrhagic lesionson admission brain scan (2010 EFNS guidelines for CVT)
  • AED prophylaxis associated with reduced risk of early seizures in patients with CVT (especially supratentorial lesions and seizure at presentation).  Start seizure prophylaxis only for patients with both seizures at presentation and supratentorial lesions s.a. edema, infarction or hemorrhage on admission head CT or brain MRI.
  • Prophylaxis is not required for single early symptomatic seizure with CVT in the absence of a supratentorial lesion.  Seizure prophylaxis is not required for patients who have focal cerebral lesions without seizures.
  • Some advocate prophylaxis for all patients with CVT because of moderately high incidence of seizures during acute phase of the disease.

Subarachnoid Hemorrhage:

  • Seizure prophylaxis in the setting of unsecured aneurysm is reasonable, given low risk associated with AED vs potential deleterious effects of seizures on an already dysautoregulated brain.
  • Evidence from large case series suggest that AED exposure to phenytoin may be associated with worse neurologic and cognitive outcome after SAH.
  • Based on location of blood, lower impetus to start AEDS in perimesencephalic bleed without cortical layering, but higher in patients with poor neurologic grade, unsecured aneurysm and associated ICH.
  • AED not necessary to continue after clipping, especially those without acute seizures who present with a good grade.
  • incidence of seizures after aSAH ~20%4
  • ISAT: higher incidence of post-treatment seizures after clipping compared to coiling (13.6% vs 8.3%)
  • phenytoin has a drug-drug interaction with nimodipine due to cytochrome P450 enzyme-inducing nature, patients chronically taking phenytoin had a >70% decrease in nimodipine AUC
  • 2011 NCS guidelines and 2012 AHA/ASA guidelines – recommends against use of phenytoin; may consider prophylaxis in immediate post-hemorrhagic period x 3-7days, consider longer duration if prior seizure, ICH, infarct, or MCA aneurysm; extend duration for patients with seizure after presentation


  • Do not start AED after a single seizure after stroke, especially if provoked by factors that resolve.
  • Start AED therapy for patients at significant risk for recurrent seizures s.a. remote symptomatic seizures.
  • AED generally started after 2 or more unprovoked seizures.
  • AED therapy is not necessarily lifelong.
  • early seizures are due to edema and cytotoxicity from ischemia, late seizures are due to scar tissue formed after anoxia and deformation of dendrites
  • no consensus on size of infarct or subtype of stroke that has tendency to causes seizures more
  • in general, ischemic is less epileptogenic than hemorrhagic stroke
  • AHA/ASA Guideline for Early Mx of Adults with AIS recommends 
    • prophylaxis not recommended (III/C)
    • recurrent seizures should be treated (I/B)

Post Craniotomy

  • De novo seizure following craniotomy (DNC) rate 1.26% (keppra prophylaxis) and 6.60% phenytoin); keppra is superior to phenytoin in seizure prophylaxis. [5]
  • The incidence of postoperative seizures varies widely depending on procedure performed and underlying pathology
  • use after direct surgical, endovascular or radiosurgical management of AVMs – new onset seizure is presenting symptom in 20-25%
  • ASA guidelines for anagement of AVM does not give specific recommendations
  • recent study evaluated seizure risk from cavernous malformation (0.9%) or AVM (2%) – supports recommendation to NOT start seizure prophylaxis in these patients

Examples of seizure prophylaxis regimen: *used in some trials

  • levetiracetam 1000mg perioperative loading dose followed by second 1000mg dose that day, then 1000mg BID tapered to 500mg BID by post-op day 5
  • phenytoin 750mg loading dose then continue x 24 hours as infusion 30mg/hour then conversion to PO tapering from 300mg/day to 50mg/day on post op day 5
  • phenytoin 900-1100 mg loading dose followed by 300mg/day through hospital discharge vs x 3 days
  • phenytoin loading 250mg BID immediately post-op then 100mg TID continued x 12 months


[1] Rowe, A. Shaun et al. “Seizure Prophylaxis In Neurocritical Care: A Review Of Evidence-Based Support”. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 34.4 (2013): 396-409.

[2] Uptodate.

[3] Mikkelsen, Tom et al. “The Role Of Prophylactic Anticonvulsants In The Management Of Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline”. J Neurooncol96.1 (2009): 97-102.

[4] Carney, Nancy et al. “Guidelines For The Management Of Severe Traumatic Brain Injury, Fourth Edition”. Neurosurgery (2016): 1.

[5] Lee, C., Koo, H., Han, S., Choi, C., Sohn, M. and Lee, C. (2018). Phenytoin versus levetiracetam as prophylaxis for postcraniotomy seizure in patients with no history of seizures: systematic review and meta-analysis. Journal of Neurosurgery, pp.1-8.