What is the management of seizures in patients with intracerebral and intraventricular hemorrhage?

Management of Seizures in Intracerebral and Intraventricular Hemorrhage

Prophylactic antiepileptic drugs (AEDs) are not recommended for routine use in patients with intracerebral hemorrhage (ICH) due to insufficient evidence of benefit and potential association with worse outcomes. 1

Epidemiology and Risk Factors

• The incidence of post-ICH seizures ranges from 3% to 17%, increasing to 42% when subclinical seizures are considered 1, 2
• Early seizures (within first 7 days) occur in approximately 14% of patients with ICH, with onset seizures occurring in about 8% 1
• Epilepsy develops in up to 10% of young patients (18-50 years) with ICH; the risk may be lower in older patients 1, 2
• Major risk factors for seizures include:
  • Cortical location of the hematoma 1, 2, 3
  • Presence of intraventricular hemorrhage 1, 3
  • Large hemorrhage volume 3
  • High clinical severity (high NIHSS score) 1, 4
  • History of alcohol abuse 3

Diagnostic Approach

• Continuous EEG monitoring should be considered in ICH patients with depressed mental status that is disproportionate to the degree of brain injury 1
• Electrographic seizures are detected in 28-31% of select ICH patients on continuous EEG monitoring, despite many having received prophylactic antiseizure medications 1, 3

Treatment Recommendations

Prophylactic AED Use

• Prophylactic antiepileptic drugs are not recommended for routine use in ICH patients 1
• Most studies suggest that prophylactic AEDs (primarily phenytoin) are associated with increased death and disability in ICH 1, 3
• A small randomized trial of 1-month prophylactic treatment with valproic acid showed no reduction in overall seizure incidence over 1-year follow-up (19.5% in treatment group vs. 22.2% in placebo group) 1, 5

Management of Clinical Seizures

• Clinical seizures or electrographic seizures in patients with altered mental status should be treated with antiseizure drugs 1
• For acute seizure management in status epilepticus:
  • Lorazepam 4 mg IV slowly (2 mg/min) is recommended as first-line treatment 6
  • If seizures continue after 10-15 minutes, an additional 4 mg IV dose may be administered 6
  • Phenytoin loading dose of 15-20 mg/kg IV at a rate not exceeding 50 mg/min should follow benzodiazepine treatment 7, 6
• For maintenance therapy after clinical seizures:
  • Levetiracetam is preferred over phenytoin due to better tolerability profile 1, 2
  • Treatment duration of ≤7 days is reasonable to reduce seizure-related complications in the acute period 1
• Long-term AED treatment is generally not indicated for patients without prior epilepsy who present with seizures, as it does not effectively reduce future ICH-associated seizure risk 1

Special Considerations

• Early seizures have not been consistently associated with worse neurological outcome or mortality in prospective studies 1, 2
• Phenytoin prophylaxis specifically has been associated with poor outcomes and should be avoided 1
• Recent studies suggest that newer generation AEDs like levetiracetam may have a better safety profile than phenytoin when treatment is necessary 8, 4
• Physicians most commonly consider lobar hematoma location (30%) and reduced level of consciousness (24%) when deciding to administer prophylactic AEDs 4

Monitoring and Follow-up

• Continuous EEG monitoring should be considered in patients with:
  • Depressed mental status disproportionate to brain injury 1
  • High-grade ICH 1
  • Cortical hemorrhage location 1, 2
• Therapeutic drug monitoring is recommended when using phenytoin, with target serum total concentrations between 10-20 mcg/mL (unbound phenytoin concentrations of 1-2 mcg/mL) 7