Is anti-epileptic (AED) prophylaxis required in patients with cortical stroke?

Anti-Epileptic Prophylaxis in Cortical Stroke

Routine prophylactic anti-epileptic drugs (AEDs) are NOT recommended for patients with cortical stroke, whether ischemic or hemorrhagic, as they do not prevent seizures and may be associated with worse functional outcomes. 1, 2

Evidence Against Prophylaxis

The strongest guideline evidence consistently opposes routine seizure prophylaxis:

• Multiple major guidelines explicitly recommend against prophylactic AEDs in both ischemic stroke and intracerebral hemorrhage (ICH), including the 2022 AHA/ASA ICH guidelines, 2016 AHA/ASA stroke rehabilitation guidelines, and 2015 ICH management guidelines 1

• Meta-analyses demonstrate no benefit: Prophylactic AEDs do not prevent early seizures (within 14 days) or late seizures in stroke patients 1, 3

• Potential harm from prophylaxis: Most studies suggest prophylactic AEDs (particularly phenytoin) are associated with increased death and disability, though this may reflect confounding by indication 1, 3

• Interference with recovery: Many traditional seizure medications (phenytoin, benzodiazepines) dampen neural plasticity mechanisms essential for behavioral recovery after stroke 1, 2

When to Treat Seizures (Not Prophylaxis)

AEDs should only be initiated when seizures actually occur:

• Treat documented seizures: Any patient with clinical or electrographic seizures should receive standard seizure management, including investigation for reversible causes 1, 2, 3

• Single self-limiting seizure within 24 hours: Does NOT require long-term AED treatment 2, 4

• Recurrent seizures: Should be treated according to standard epilepsy management protocols 2, 4

• Altered consciousness disproportionate to injury: Consider continuous EEG monitoring for 24-48 hours to detect subclinical seizures, as 28% of electrographic seizures are detected after 24 hours 1, 3

Medication Selection When Treatment Is Needed

If AEDs are required for documented seizures:

• Prefer levetiracetam over phenytoin/fosphenytoin due to better tolerability, fewer drug interactions, and less impact on recovery 3

• Avoid phenytoin: Associated with worse outcomes in ICH and may impair neural plasticity 1, 3

Risk Context (Why Prophylaxis Seems Tempting But Isn't Indicated)

Understanding seizure risk helps explain why prophylaxis is still not warranted:

• Actual seizure incidence is low: Early seizures occur in 2-16% of stroke patients (true risk toward lower end), with cortical involvement being the strongest risk factor 1, 4

• Cortical location increases risk: Particularly lobar ICH and cortical ischemic strokes involving middle temporal, post-central, supramarginal, or superior temporal gyri 1, 4

• Hemorrhagic transformation and pre-existing dementia also increase risk 4

• Even with these risk factors, prophylaxis remains unjustified as the number needed to treat would be excessive given low baseline risk and potential harms 1

Common Pitfalls to Avoid

• Do not use risk scores (like CAVE score) to justify continuing prophylactic AEDs beyond 7 days, as there is no evidence they prevent late seizures 1, 3

• Do not assume early seizures worsen outcomes: Prospective studies show early seizures are not independently associated with worse neurological outcomes or mortality 1, 3

• Do not continue AEDs started empirically: If AEDs were initiated without documented seizures, they should be discontinued promptly 2, 5

• Recognize that subclinical EEG seizures (detected in 28-31% of select ICH cohorts) have unclear clinical significance and do not justify prophylaxis 1

Monitoring Approach

For patients with cortical stroke but no seizures:

• Monitor neurological status routinely during vital sign checks 2, 4

• Reserve continuous EEG for patients with unexplained altered consciousness disproportionate to brain injury 1, 3

• Investigate reversible causes if seizures occur (metabolic derangements, medications, infection) 1, 2