MedCompanion

HSV Encephalitis

CNS

Source: IDMP View on spectrum chart →
Patient + scenario modifiers
Patient
Clinical scenario / source

Annotations only — chart still shows the full chemistry of each drug.

1. Clinical Syndrome

Acute viral encephalitis caused by herpes simplex virus (HSV-1 in ~95% adult cases; HSV-2 dominant in neonatal disease). Classic presentation: subacute (3–7 days) fever + altered mental status + focal neurologic deficits (especially temporal lobe signs — aphasia, behavioral changes, complex partial seizures, anosmia). Untreated mortality >70%; with treatment, mortality 10–20% and survivors often with significant neurologic sequelae.

Excludes: other viral encephalitides (West Nile, EEE, Powassan, enteroviruses — overlapping presentation but require separate workups), autoimmune encephalitis (NMDAR, anti-LGI1 — increasingly recognized; can mimic), bacterial meningitis (more abrupt + nuchal rigidity dominant), post-infectious / ADEM, prion disease (CJD, slowly progressive).

2. Pathogens

Consider the patient: Any age (no immunocompromise required — HSV encephalitis affects immunocompetent hosts), prior cold sores (HSV-1 seropositive ~50–80% of adults — most don't develop encephalitis), recent fever / behavioral change / focal seizure.

Consider the case: Acute fulminant decline → treat empirically while CSF PCR pends. Bilateral temporal lobe findings on imaging are pathognomonic but not always present early.

Common

    • Herpes Simplex Virus 1

      **95% of adult HSV encephalitis.** Reactivation of latent virus in trigeminal ganglion; mechanism of CNS entry uncertain. Bilateral temporal lobe involvement classic but unilateral common early.

3. Empiric Therapy

TierFirst choiceAlternativesDurationComments
Admitted to ICU
  • 10 mg/kg · q8h (slow infusion ≥1 h, IBW dosing if obese) · IV · 14–21 days (longer end for severe disease, immunocompromised, persistently positive CSF PCR)
  • Foscarnet 40 mg/kg · q8h · IV

    **Acyclovir-resistant HSV** (rare; mostly in immunocompromised hosts on chronic ACV suppression). Renal dosing essential; significant nephrotoxicity + electrolyte derangements. (Not yet seeded.)

**14–21 days minimum.** Repeat CSF PCR before stopping in severe disease or immunocompromised — persistent positive = extend therapy.**Start ACV empirically before LP results** in any febrile patient with altered mental status + focal neuro deficits. Delay in treatment is the strongest predictor of poor outcome. **Hydration is essential** — ACV crystalluria + AKI dose-limiting; aim 1.5× maintenance during infusion. **Monitor for neurotoxicity** in AKI / elderly: confusion + tremor + myoclonus mimic the encephalitis itself.

4. Directed Therapy

Diagnostic workup (alongside empiric ACV):

  • LP: lymphocytic pleocytosis (10–500 WBC/mm³ typical, lymph-predominant), elevated protein (>50), normal glucose. RBCs in CSF classic but not specific (hemorrhagic component).
  • CSF HSV PCR: sensitivity 96%, specificity ~99% within 2–10 days of symptoms. Early (<48 h) and late (>14 d) PCR can be falsely negative — repeat in 3–7 d if clinical suspicion remains high.
  • MRI brain with contrast: bilateral temporal lobe + insular + cingulate gyrus T2/FLAIR hyperintensity + restricted diffusion classic. Hemorrhagic transformation common. (CT often normal early.)
  • EEG: periodic lateralized epileptiform discharges (PLEDs) from temporal regions support diagnosis.

Don't stop ACV based on early negative CSF PCR if MRI / EEG / clinical picture supports — repeat LP in 3–7 d.

Adjuncts:

  • Steroids: controversial. Limited RCT data (DexEnceph ongoing); some guidelines suggest dexamethasone for significant edema, but not routine.
  • Anticonvulsants: as needed for clinical seizures; some give empiric prophylaxis given high seizure rate.
  • Repeat CSF PCR before stopping in severe disease — if persistently positive at 21 days, extend therapy + consult ID.

Co-infection: rare but consider VZV (zoster sine herpete), enteroviruses, autoimmune encephalitis (NMDAR-Ab) — workup runs in parallel with empiric ACV.

HSV-2 in neonates / immunocompromised: same drug (ACV 20 mg/kg q8h × 21 d for neonates), same empiric urgency. Pediatric ID + neonatology involvement.

5. Monitoring

Resolution: mental status, focal deficits, seizure control. Many survivors have residual cognitive / behavioral deficits; rehabilitation involvement early.

Repeat imaging: MRI at 1–2 weeks if not improving — looking for ongoing inflammation, hemorrhagic transformation, alternative diagnoses.

Repeat CSF PCR before stopping ACV in severe disease or immunocompromised — persistent + viremia despite ACV warrants extension or foscarnet switch.

Toxicity: Cr + BUN q48h; mental status changes (distinguish from encephalitis itself); hydration status; serum acyclovir levels (in suspected toxicity); CBC.

Pearls

START ACYCLOVIR EMPIRICALLY — delay = worse outcome. 10 mg/kg IV q8h × 14–21 days for adults; 20 mg/kg q8h × 21 days for neonates. RBCs in CSF + temporal lobe MRI + acute fever + AMS = HSV until proven otherwise. Empiric ACV in any encephalitis workup — no harm if eventually not HSV, fatal harm if HSV not treated. Renal dosing matters — failure to adjust drives crystalluria, AKI, neurotoxicity. Early ACV resistance is rare in immunocompetent hosts; concern in immunocompromised on chronic suppression — foscarnet is salvage. Autoimmune encephalitis (NMDAR-Ab) increasingly recognized and can present similarly — get CSF auto-Ab panel in parallel especially if young + psychiatric features + non-specific imaging.

References