What medications are used to manage seizures in encephalitis, both in mild and severe cases?

Medication Management for Seizures in Encephalitis

Benzodiazepines are the first-line treatment for seizures in encephalitis, followed by valproate or levetiracetam as second-line agents for both mild and severe cases. 1

Initial Management of Seizures in Encephalitis

First-Line Therapy

• Intravenous lorazepam or intramuscular midazolam are the most effective first-line treatments for acute seizures in encephalitis, controlling seizures in approximately 63-73% of patients 2
• In children or when IV access is not available, buccal midazolam is an effective alternative with similar efficacy to other benzodiazepines 3
• For status epilepticus, emergency physicians should administer benzodiazepines as first-line treatment 1

Second-Line Therapy

• For seizures that fail to respond to benzodiazepines, intravenous valproate, fosphenytoin, or phenytoin are recommended as second-line agents 1, 4
• Valproate has shown higher rates of seizure cessation (75.7%) compared to levetiracetam (68.5%) and phenytoin (50.2%) in established status epilepticus 3
• Levetiracetam is preferred in patients with hepatic dysfunction or those on multiple medications due to fewer drug interactions 4, 5

Medication Selection Based on Severity

Mild Cases

• For patients with mild encephalitis and isolated seizures, antiepileptic drugs may not be strictly needed if there is only one seizure and no temporal lobe involvement 4
• If treatment is required, oral levetiracetam (starting at 1500 mg loading dose) or valproate (15 mg/kg/day divided into 2 daily doses) are appropriate options 1, 4
• Monitor for at least three months after the acute phase, as this is the peak time for seizure relapse 4

Severe Cases

• For severe encephalitis with status epilepticus, a staged approach is necessary 1, 2:
  1. First stage: IV benzodiazepines (lorazepam or midazolam)
  2. Second stage: IV valproate (up to 30 mg/kg at max rate of 10 mg/kg/min), fosphenytoin (18 PE/kg), or levetiracetam (60 mg/kg) 1, 3
  3. Third stage (refractory status): Anesthetic agents such as propofol or barbiturates 1
• For refractory status epilepticus, emergency physicians may administer intravenous levetiracetam, propofol, or barbiturates 1

Special Considerations

Monitoring and Duration of Treatment

• EEG monitoring is recommended for patients with severe encephalitis and persistent altered mental status 1, 6
• Antiepileptic treatment should be continued for at least 3 months after the acute phase of encephalitis, as this is the peak time for seizure relapse 4
• Patients with risk factors for recurrent seizures (multiple seizures during acute phase or temporal lobe involvement) may require longer treatment 4

Medication-Specific Considerations

• Valproate therapeutic range is 50-100 μg/mL; monitor levels in patients with hepatic or renal disease as protein binding is reduced 7
• Common adverse effects of valproate include somnolence (27%), tremor (25%), dizziness (25%), nausea (48%), and vomiting (27%) 7
• Levetiracetam has fewer drug interactions but may worsen psychiatric symptoms in predisposed patients 5
• Phenytoin and fosphenytoin require careful monitoring due to risk of hypotension, cardiac arrhythmias, and need for blood level monitoring 1

Pitfalls and Caveats

• Avoid phenytoin in patients with cardiac conditions due to risk of hypotension and cardiac arrhythmias 1, 3
• Do not delay treatment of status epilepticus while waiting for laboratory results, as delays increase mortality and morbidity 1, 2
• Recognize that generalized myoclonus with epileptiform discharges may be manifestations of Lance-Adams syndrome, which is compatible with good outcomes; avoid overly aggressive treatment in these cases 1
• Be aware that high doses of antiepileptic drugs may confound neurological examination and lead to overly pessimistic prognostication 1
• Consider that sedatives commonly used in critically ill patients (propofol, benzodiazepines) have antiepileptic effects that may mask ongoing seizure activity 1