SCOPE: Acute HSV-1 encephalitis in adults — the most common cause of sporadic fatal encephalitis. Covers emergent empiric acyclovir, LP with HSV PCR, MRI findings, seizure management, and monitoring for complications (cerebral edema, SIADH, refractory status epilepticus). Excludes neonatal HSV, HSV-2 meningitis (Mollaret), CMV/EBV/VZV encephalitis, and autoimmune encephalitis (though post-HSV autoimmune encephalitis is addressed).
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
Indication: Diagnostic — ALL patients with suspected encephalitis. Do NOT delay acyclovir for LP.
Timing: STAT. Start acyclovir BEFORE LP if any delay anticipated.
Volume Required: 15-20 mL (extra for PCR, cytology, autoimmune panel)
Study
ED
HOSP
OPD
Rationale
Target Finding
Opening pressure
STAT
ROUTINE
-
Elevated in some cases; monitor for ICP issues
Normal or mildly elevated (usually <300 mm H2O)
Cell count with differential (tubes 1 and 4) (CPT 89051)
STAT
ROUTINE
-
Lymphocytic pleocytosis typical; RBCs may be present (hemorrhagic encephalitis); tube comparison for traumatic tap
WBC 10-500 cells/µL (lymphocyte predominant); RBC may be elevated (hemorrhagic necrosis)
Protein (CPT 84157)
STAT
ROUTINE
-
Mildly to moderately elevated
Elevated (50-200 mg/dL typical; can be higher)
Glucose with paired serum (CPT 82945)
STAT
ROUTINE
-
Usually NORMAL in HSV (distinguishes from bacterial/TB/fungal)
Normal (>60% serum glucose ratio); low glucose argues against HSV
HSV-1/2 PCR (CSF) (CPT 87529)
STAT
ROUTINE
-
GOLD STANDARD diagnostic test; sensitivity 96-98%, specificity ~99%. May be NEGATIVE in first 72h — if clinical suspicion high and initial PCR negative, REPEAT at 3-7 days
Positive (HSV-1 in >90% adult cases; HSV-2 in neonatal/meningitis)
Gram stain and bacterial culture (CPT 87205+87070)
STAT
ROUTINE
-
Exclude bacterial meningitis
No organisms
BioFire FilmArray ME Panel (CPT 87483)
STAT
ROUTINE
-
Rapid multiplex PCR — includes HSV-1/2, VZV, enterovirus, CMV, HHV-6, and bacterial pathogens; result in ~1 hour
HSV-1 detected (or other pathogen identified)
VZV PCR (CSF)
URGENT
ROUTINE
-
VZV encephalitis in differential; especially immunocompromised and elderly
Negative (positive → VZV encephalitis — treat with IV acyclovir)
CMV PCR (CSF)
-
ROUTINE
-
If immunocompromised (HIV/transplant)
Negative
EBV PCR (CSF)
-
ROUTINE
-
If immunocompromised; CNS lymphoma differential
Negative
HHV-6 PCR (CSF)
-
ROUTINE
-
Post-transplant encephalitis; temporal lobe involvement similar to HSV
Primary differential diagnosis; also detect post-HSV autoimmune encephalitis
Negative initially; recheck if relapse
Oligoclonal bands, IgG index (CPT 83916)
-
ROUTINE
ROUTINE
Intrathecal antibody production; MS differential
May be positive (non-specific)
Cytology (CPT 88104)
-
ROUTINE
-
Exclude leptomeningeal malignancy
Negative
AFB smear and culture (CPT 87116)
-
ROUTINE
-
TB meningitis if subacute or basilar
Negative
VDRL (CSF) (CPT 86592)
-
ROUTINE
-
Neurosyphilis screen
Negative
Special Handling: HSV PCR sample can be refrigerated; do NOT freeze. Process CSF rapidly for cell count. Save extra CSF (frozen at -80°C) for future studies if needed.
Repeat LP indications: If initial HSV PCR negative but clinical suspicion high → repeat at 3-7 days. Also repeat if clinical deterioration at 2-4 weeks (relapse → send autoimmune encephalitis panel).
1-1.5 mL/kg :: - :: continuous :: 1-1.5 mL/kg/h continuous to prevent acyclovir nephrotoxicity; bolus 500-1000 mL if dehydrated
Volume overload, CHF
I/O; Cr daily; urine output >0.5 mL/kg/h
STAT
STAT
-
STAT
Empiric antibiotics (vancomycin + ceftriaxone)
-
-
N/A :: - :: per protocol :: Standard meningitis dosing. Continue until bacterial meningitis excluded by CSF results (Gram stain negative, BioFire negative, cultures negative at 48-72h). See Bacterial Meningitis template for dosing
See Bacterial Meningitis template
Standard
STAT
STAT
-
STAT
Dexamethasone
IV
-
0.15 mg/kg :: IV :: q6h :: 0.15 mg/kg IV q6h x 4 days — give empirically with antibiotics until bacterial meningitis excluded. Discontinue when bacterial excluded. Role in HSV encephalitis itself is CONTROVERSIAL — some evidence for reducing edema but no clear mortality benefit; not standard of care for isolated HSV
Uncontrolled infection (relative)
Glucose; GI prophylaxis
STAT
STAT
-
STAT
Levetiracetam (if seizures)
IV
-
1000-1500 mg :: IV :: BID :: 1000-1500 mg IV load; then 500-1000 mg IV/PO BID; max 3000 mg/day. Seizures occur in 40-60% of HSV encephalitis
Severe renal impairment (dose adjust)
Renal function; behavioral side effects
STAT
STAT
-
STAT
Lorazepam (seizure rescue)
IV
-
0.1 mg/kg :: IV :: - :: 0.1 mg/kg IV (max 4 mg); repeat x1 in 5 min if needed
60 mg/kg :: IV :: q8h :: 60 mg/kg IV q8h or 90 mg/kg IV q12h; infuse over 1-2h with aggressive hydration. For proven or suspected acyclovir resistance (immunocompromised, HIV)
Cr daily; Ca, Mg, K, PO4 BID (causes severe electrolyte wasting); hydration 1-2 L NS before each dose
-
EXT
-
EXT
Decompressive craniectomy
-
-
N/A :: - :: once :: For malignant cerebral edema with impending herniation, unresponsive to medical ICP management; consider if age appropriate and prognosis not already dismal
Bilateral massive necrosis; moribund patient
Post-op neuro checks; ICP monitoring; wound care
-
-
-
STAT
Immunotherapy for post-HSV autoimmune encephalitis
IV
-
1g/day :: IV :: daily x 5 days :: If relapse at 2-6 weeks with new anti-NMDAR antibodies: IV methylprednisolone 1g/day x 5 days + IVIG 0.4 g/kg/day x 5 days; second-line: rituximab
Active HSV infection (ensure viral replication controlled)
NMDAR antibody titers; clinical response; viral PCR to confirm HSV not reactivated
Clinical improvement; repeat LP at end of treatment — if HSV PCR still positive, continue additional 7 days
Suspected HSV, PCR negative x2
Consider stopping at 7-10 days if: two negative HSV PCRs (initial + repeat at 3-7 days), MRI not consistent with HSV, alternative diagnosis established
Clinical stability; alternative diagnosis confirmed
Immunocompromised patients
21 days minimum
Repeat LP with PCR before stopping; ensure negative PCR before discontinuation
Transition to oral
Oral valacyclovir 1g PO TID x 3-6 months after IV course is INVESTIGATIONAL; some centers use for immunocompromised; not standard of care
NOT appropriate directly from ED for suspected HSV encephalitis — always admit. Discharge from hospital when: completing IV acyclovir course (or transitioned to monitoring); improved consciousness (GCS 15); no active seizures; stable neurologic exam; safe swallowing; rehabilitation arranged; follow-up confirmed
Admit to floor (monitored bed)
Mild encephalitis (GCS 13-15); stable; low seizure burden; able to cooperate with neuro checks
Admit to ICU / Neuro-ICU
GCS <13; active seizures or status epilepticus; need for continuous EEG; respiratory compromise; signs of elevated ICP; hemodynamic instability
Transfer to higher level
Need for neuro-ICU not available; need for neurosurgery (decompressive craniectomy); continuous EEG not available
Inpatient rehabilitation
Moderate-severe cognitive deficits (memory impairment, aphasia); motor deficits; able to participate in 3h/day therapy
Skilled nursing facility
Unable to tolerate intensive rehabilitation; requires ongoing nursing care