What is the role of Levetiracetam (antiepileptic medication) and Diazepam (benzodiazepine) in the management of seizures in a patient with Herpes Simplex Virus (HSV) encephalitis?

Management of Seizures in HSV Encephalitis with Levetiracetam and Diazepam

Seizures in HSV encephalitis should be treated with benzodiazepines (diazepam or lorazepam) for acute seizure termination, followed by levetiracetam as the preferred antiepileptic drug for ongoing seizure management, while simultaneously initiating intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days. 1, 2, 3

Acute Seizure Management

For active seizures or status epilepticus:

• Administer intravenous benzodiazepines (diazepam or lorazepam) immediately to terminate the acute seizure event, following standard status epilepticus protocols 4
• Approximately one-third of HSV encephalitis patients present with seizures, making this a common and critical complication requiring prompt intervention 1
• Seizures during the acute phase are the main risk factor for developing postencephalitic epilepsy, which is frequently refractory to medical treatment 5

Antiepileptic Drug Selection

Levetiracetam is the preferred first-line antiepileptic drug for HSV encephalitis:

• Levetiracetam offers favorable tolerability and predictable pharmacokinetics, making it an optimal choice for seizure prophylaxis and management 4
• It can be administered for refractory status epilepticus if seizures persist despite benzodiazepine administration 4
• One documented case successfully used levetiracetam alongside acyclovir and corticosteroids in a COVID-19 patient with encephalitis and status epilepticus 1

Critical Treatment Pitfalls to Avoid

Do not delay antiviral therapy while managing seizures:

• Intravenous acyclovir must be initiated within 6 hours of admission if diagnostic results are not immediately available, as early treatment is associated with reduced mortality and morbidity 2, 3
• The mortality rate reaches 70% without antiviral therapy, compared to significantly improved outcomes with prompt acyclovir treatment 6, 3
• Antiviral therapy should never be withheld while awaiting serological confirmation, as false-negative HSV PCR results can occur, especially if CSF is sampled within 72 hours of symptom onset 1, 2, 7

Duration of Antiepileptic Therapy

The optimal duration of antiepileptic treatment remains controversial:

• No randomized controlled trials exist for the ideal duration of antiepileptic treatment in acute HSV encephalitis 5
• Seizures during the acute phase significantly increase the risk of postencephalitic epilepsy, which develops in a substantial proportion of survivors 5
• Clinical judgment should guide whether to continue antiepileptic drugs beyond the acute phase, particularly in patients with ongoing seizure activity, temporal lobe involvement on imaging, or EEG abnormalities 5

Monitoring Considerations

Electroencephalogram monitoring is essential:

• EEG should be performed in all patients with suspected encephalitis and altered consciousness to detect subtle seizure activity or non-convulsive status epilepticus 1
• Temporal lobe spike-and-wave activity and periodic lateralized epileptiform discharges (PLEDs) occur frequently in HSV encephalitis, reflecting the characteristic temporal lobe involvement 2
• Subtle motor status epilepticus can follow overt convulsive seizures and requires EEG diagnosis 1

Concurrent Antiviral Treatment Protocol

Acyclovir dosing must be precise:

• Administer intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days in all confirmed or suspected HSV encephalitis cases 2, 3
• Treatment duration of 14-21 days is recommended, with PCR testing of CSF after completion to confirm viral clearance 3
• Renal function monitoring is essential during acyclovir therapy to adjust dosing appropriately 1

Special Circumstances

Refractory seizures warrant additional investigation:

• Persistent seizures despite adequate antiviral and antiepileptic therapy may indicate relapsing HSE or post-infectious autoimmune conditions requiring immunomodulatory treatment 5
• Intracranial hemorrhage, though rare (2.7% of cases), can complicate HSV encephalitis and cause neurological deterioration despite appropriate treatment 6
• Repeat neuroimaging should be considered if clinical improvement does not occur with standard therapy 6