What medications are used to manage seizures in encephalitis?

Management of Seizures in Encephalitis

For patients with encephalitis presenting with seizures, initiate immediate treatment with acyclovir (10 mg/kg IV every 8 hours in adults) alongside benzodiazepines as first-line antiepileptic therapy, followed by second-line agents such as valproate, levetiracetam, or phenytoin/fosphenytoin for refractory seizures. 1

Immediate Management Approach

First-Line Treatment

• Administer acyclovir immediately for all suspected encephalitis cases with seizures at 10 mg/kg IV every 8 hours in adults and children with normal renal function, or 20 mg/kg IV every 8 hours in neonates 1
• Benzodiazepines (lorazepam) are the first-line antiepileptic treatment for active seizures in encephalitis, regardless of other antiepileptic medications the patient may already be taking 2
• Patients require urgent neurological specialist assessment within 24 hours and should be managed where clinical neurological review is immediately available 1

Critical Care Considerations

• Patients with declining consciousness require immediate ICU assessment for airway protection, ventilatory support, and management of raised intracranial pressure 1
• Ensure access to neuroimaging (MRI) and neurophysiology (EEG) for proper diagnosis and ongoing management 1
• Consider continuous EEG monitoring for refractory status epilepticus with escalation to anesthetic agents under ICU care 1

Second-Line Antiepileptic Medications

For Refractory Seizures After Benzodiazepines

Valproate (Preferred Option)

• IV valproate at 20-30 mg/kg loading dose is highly effective for refractory seizures in encephalitis 3
• Valproate demonstrated 88% seizure cessation within 20 minutes in status epilepticus refractory to benzodiazepines, with no associated hypotension 3
• For ongoing control, infuse at 1-2 mg/kg per hour after loading 3
• Therapeutic range is 50-100 μg/mL total valproate, though some patients require higher concentrations 4

Levetiracetam (Alternative Option)

• Levetiracetam 30-60 mg/kg/day (or 30 mg/kg IV load at 5 mg/kg per minute) is equally effective to valproate for refractory seizures 3, 5
• Demonstrated 73% seizure cessation rate in refractory status epilepticus after lorazepam and phenytoin failure 3
• Particularly effective in acute encephalitis with refractory, repetitive partial seizures (AERRPS), enabling withdrawal from barbiturate-induced coma 5
• Well-tolerated with minimal drug interactions, making it advantageous in the complex medication regimens typical of encephalitis management 6

Phenytoin/Fosphenytoin (Traditional Option)

• Phenytoin 18-20 mg/kg IV or fosphenytoin equivalent can be used, though efficacy is only 56% when following benzodiazepines 3
• Associated with hypotension in 12% of cases, compared to 0% with valproate 3
• Less preferred due to lower efficacy and higher adverse effect profile 3

Etiology-Specific Considerations

Herpes Simplex Virus Encephalitis

• Continue acyclovir 10 mg/kg IV every 8 hours for 14-21 days in adults and children 1
• Higher-dose acyclovir (20 mg/kg IV every 8 hours for 21 days) is required in neonates 1
• Adjunctive corticosteroids remain controversial but one retrospective study showed better outcomes when used 1
• Seizures during acute HSE are the main risk factor for developing postencephalitic epilepsy 7

Varicella-Zoster Virus Encephalitis

• Acyclovir 10-15 mg/kg IV three times daily 1
• Consider short course of corticosteroids, particularly if vasculitic component is present 1

Cytomegalovirus Encephalitis

• Combination therapy with ganciclovir (5 mg/kg IV every 12 hours) and foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) for 3 weeks 1

Autoimmune/Antibody-Mediated Encephalitis

• Consider antibody-mediated encephalitis in all patients with intractable seizures, particularly with subacute presentation, orofacial dyskinesia, choreoathetosis, or hyponatraemia 3
• For VGKC-complex or NMDA receptor antibody-associated encephalitis, immunosuppression with high-dose steroids (0.5 mg/kg/day) often leads to rapid improvement in seizures 3
• IVIg (0.4 g/kg/day) or plasma exchange can be added for acutely unwell patients 3
• Early immune suppression and tumor removal (if present) results in improved outcomes 3

Duration of Antiepileptic Therapy

Risk Stratification for Continued AED Use

• For patients with only one seizure and no temporal lobe involvement, the risk of seizure relapse is low (similar with or without AED continuation), and AEDs may not be strictly needed 8
• For patients with more than one seizure OR temporal lobe involvement, continue AEDs as these are independent predictors of seizure relapse (OR 2.80 and 5.34 respectively) 8
• The first three months after the acute phase is the peak time for seizure relapse (overall 5-year relapse risk is 43.6%), so AEDs should be maintained during this critical period 8

Chronic Phase Management

• Both sodium valproate and levetiracetam are equally effective for chronic seizure control after encephalitis 8
• Levetiracetam 750-1500 mg/day reduced seizure frequency by >75% for 5-18 months in chronic AERRPS patients 5
• Monitor for drug interactions between antimicrobials and antiepileptic medications 1

Critical Pitfalls to Avoid

• Do not withhold benzodiazepines due to concerns about polypharmacy in patients already on antiepileptics—this increases risk of status epilepticus progression with associated morbidity and mortality 2
• Do not use phenytoin or fosphenytoin as first-line therapy before benzodiazepines, as this approach has limited success 2
• Monitor for carbapenem antibiotic interactions with valproate, as carbapenems (ertapenem, imipenem, meropenem) can reduce valproate to subtherapeutic levels, resulting in loss of seizure control 4
• In elderly patients, increase valproate doses slowly with regular monitoring for somnolence, dehydration, and reduced nutritional intake 4
• Check antiepileptic drug serum levels after seizure cessation to ensure therapeutic ranges 2
• Screen for neoplasm in all patients with VGKC complex or NMDA receptor antibody-associated encephalitis 3
• Assess for rehabilitation needs as sequelae may not be immediately apparent at discharge 1