Herpes Simplex Encephalitis Prognosis
Even with optimal acyclovir treatment, herpes simplex encephalitis carries a 20-30% mortality rate and leaves 70% of survivors with persistent neurological deficits, making it a devastating disease where early treatment initiation within 48 hours of hospital admission is the single most critical modifiable factor determining outcome. 1
Mortality Outcomes
- Untreated HSE has a mortality rate exceeding 70%, which decreases to 20-30% with acyclovir treatment. 1
- Mortality at 18 months remains 25-28% even with appropriate antiviral therapy. 2
- Starting acyclovir within the first 4 days of symptom onset reduces mortality from 28% to 8%. 1
- Case fatality rates in contemporary series range from 8-15% with prompt treatment. 2, 3
Functional Recovery and Neurological Sequelae
The majority of survivors (65-70%) regain independence in daily activities, but most continue to experience persistent neurological symptoms or signs. 1, 4
Common Long-Term Sequelae (occurring in survivors):
- Memory impairment affects 69-70% of survivors, representing the most common persistent deficit. 4
- Personality and behavioral abnormalities occur in 45% of patients, reflecting damage to limbic structures. 2, 4
- Epilepsy develops in 24% of survivors as a consequence of temporal lobe injury. 2, 4
- Anosmia affects 65% of patients due to involvement of olfactory pathways. 4
- Dysphasia occurs in 41% of survivors, particularly with dominant hemisphere involvement. 4
Functional Outcome Distribution:
- Approximately 48% of patients return to their pre-illness level of functioning in everyday activities. 4
- 21% live independently but function at a lower level than before the illness. 4
- 12-20% have severe neurological disability requiring ongoing care. 1, 4
- 35% overall have poor outcomes (death or severe disability). 5
Critical Prognostic Factors
Most Important Modifiable Factor:
Delaying acyclovir initiation beyond 2 days after hospital admission is independently associated with poor prognosis and represents the only modifiable parameter that can improve outcomes. 1, 5
- Treatment within 6 hours of hospital admission is the recommended target. 1
- Delay beyond 48 hours significantly worsens prognosis across all outcome measures. 1, 6
- Duration of symptoms before hospital admission also correlates with worse outcomes (OR=1.24 per day). 3
Non-Modifiable Prognostic Factors:
- Advanced age (≥30 years) is associated with poor outcomes. 1
- Simplified Acute Physiology Score II (SAPS II) ≥27 at admission independently predicts poor prognosis. 5
- Glasgow Coma Score <6 at presentation correlates with worse outcomes. 1
- Extent of brain involvement on MRI at admission is a strong predictor (OR=37.22 for poor outcome). 3
Pediatric Considerations
- Children with HSE have a 65% rate of good outcomes, which is comparable to adults. 7
- No mortality was reported in one pediatric series, though 35% still had poor functional outcomes. 7
- Delayed acyclovir initiation (≥3 days) was more prevalent in children with poor outcomes (92% vs 71%). 7
Treatment Duration and Monitoring
- Treatment should continue for 14-21 days with PCR control at completion to ensure viral clearance. 1, 2
- Weekly PCR monitoring should continue until negativity is achieved to prevent relapse. 1
- Relapse rates reach 5-8% with inadequate treatment duration. 6
- Immunocompromised patients require longer treatment durations and closer monitoring. 1
Common Pitfalls in Prognostication
- Do not assume a good outcome based solely on survival—70% of survivors have persistent neurological symptoms despite regaining independence. 4
- Viral load does not determine prognosis; timing of treatment, age, and clinical condition at presentation are the key determinants. 1
- A single negative CSF PCR does not rule out HSE, especially if obtained <72 hours after symptom onset. 2, 8
- Even patients who appear to recover initially may develop significant memory, behavioral, and cognitive deficits that become apparent over time. 2, 4