What is the treatment for subclinical seizures, including electroencephalogram (EEG) monitoring and antiepileptic drugs (AEDs) such as Levetiracetam (Keppra) or Lamotrigine (Lamictal)?

Treatment of Subclinical Seizures

Subclinical seizures should be treated with antiepileptic drugs only when accompanied by changes in mental status, with levetiracetam being the preferred first-line agent due to its favorable side effect profile and rapid onset of action. 1, 2

Definition and Diagnosis

Subclinical seizures are electrographic seizures without clinically apparent symptoms. They are detected through EEG monitoring and can be categorized as:

• Electrographic seizure: EEG pattern with repetitive discharges evolving in frequency, location, or morphology, lasting at least 10 seconds 1
• Electrographic status epilepticus: Electrographic seizure lasting ≥10 continuous minutes or a total duration of ≥20% of any 60-minute recording period 1

Diagnostic Approach

• Continuous EEG monitoring is recommended for patients with:
  • Unexplained altered mental status disproportionate to the degree of brain injury 1
  • Comatose patients after cardiac arrest 1
  • Critically ill patients with risk factors for subclinical seizures 3, 4

Treatment Algorithm

Step 1: Determine Need for Treatment

• Treat if:

  • Electrographic seizures with changes in mental status 1
  • Electrographic status epilepticus 1

• Do not treat prophylactically as evidence shows prophylactic antiepileptic drugs without documented seizures may be associated with worse outcomes 1

Step 2: First-Line Treatment

• Levetiracetam (Keppra):
  • Initial dose: 1000 mg/day (500 mg twice daily) 5
  • Titration: Increase by 1000 mg/day every 2 weeks 5
  • Maximum dose: 3000 mg/day 5
  • Advantages: Rapid onset of action, minimal drug interactions, can be administered intravenously 6, 7

Step 3: Alternative or Add-on Treatments

• Lamotrigine (Lamictal): Consider for focal epilepsy when levetiracetam is ineffective or not tolerated 8
• Valproate: Consider for generalized epilepsy patterns 8
• For refractory cases: Consider adding benzodiazepines or propofol, especially for status epilepticus 1

Monitoring and Duration of Treatment

Monitoring

• Continue EEG monitoring to assess treatment response 3, 4
• Regular clinical assessments for breakthrough seizures and adverse effects

Treatment Duration

• Short-term treatment (days to weeks) for acute situations (post-cardiac arrest, ICH) 2
• Discontinue after the acute phase if no recurrent seizures 2
• Taper gradually when discontinuing: reduce dose by 250-500 mg every 2-4 weeks 2

Special Considerations

Post-Cardiac Arrest Patients

• Continuous EEG monitoring is recommended to detect subclinical seizures 1
• Treatment of electrographic seizures may improve outcomes in this population 1
• Sedatives like propofol may effectively suppress both clinical and electrographic seizures 1

Intracerebral Hemorrhage (ICH) Patients

• 28-31% of ICH patients may have electrographic seizures despite prophylactic treatment 1
• Continuous EEG monitoring should be considered in ICH patients with depressed mental status 1
• Cortical involvement is the most important risk factor for seizures after ICH 1

Pitfalls and Caveats

• Avoid prophylactic use of antiepileptic drugs without documented seizures, as this may be associated with worse outcomes 1
• Beware of misdiagnosis: Some EEG patterns (ictal-interictal continuum) may not represent true seizures and may not require treatment 1
• Avoid phenytoin as it has been associated with worse outcomes in ICH patients 1
• Consider drug interactions when selecting antiepileptic medications for critically ill patients on multiple medications
• Monitor for adverse effects: Levetiracetam may cause psychiatric symptoms, especially during discontinuation 2

By following this algorithm and considering the special circumstances of each patient, clinicians can effectively manage subclinical seizures while minimizing risks associated with unnecessary treatment.