HSV Encephalitis¶
VERSION: 1.1 CREATED: January 24, 2026 REVISED: January 24, 2026 STATUS: Draft - Pending Review
DIAGNOSIS: HSV Encephalitis
ICD-10: B00.4 (Herpesviral encephalitis), G05.1 (Encephalitis, myelitis and encephalomyelitis in viral diseases classified elsewhere)
SCOPE: Evaluation and management of herpes simplex virus encephalitis (HSVE) in adults. Covers empiric acyclovir, diagnostic workup including CSF PCR and neuroimaging, seizure management, and ICU care. Primarily addresses HSV-1 encephalitis (most common in adults). Excludes neonatal HSV, HSV-2 meningitis (Mollaret's), and other viral encephalitides.
CLINICAL SYNONYMS: Herpes encephalitis, HSVE, herpesviral encephalitis, HSV-1 encephalitis, acute necrotizing encephalitis
KEY CLINICAL FEATURES: - Acute/subacute presentation: Fever, headache, altered mental status (>90%) - Temporal lobe symptoms: Personality change, behavioral abnormalities, memory impairment - Seizures: Present in 60-70% (focal > generalized) - Focal deficits: Aphasia, hemiparesis (if dominant temporal lobe involved) - Prodrome: May have flu-like illness 1-4 days before - Absence of genital HSV lesions: Usually unrelated (HSV-1 reactivation in CNS)
HSV-1 vs HSV-2 in Adults:
| Feature | HSV-1 Encephalitis | HSV-2 Meningitis |
|---|---|---|
| Presentation | Encephalitis (focal, severe) | Meningitis (less severe) |
| Location | Temporal/frontal lobes | Meninges (not parenchyma) |
| Mortality untreated | 70% | Low |
| Recurrence | Rare | Common (Mollaret's) |
| Management | 14-21 days IV acyclovir | 7-14 days acyclovir |
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
⚡ TIME-CRITICAL EMERGENCY
Do NOT delay acyclovir. Empiric treatment within 6 hours of presentation dramatically improves outcomes. Mortality without treatment: 70%. With early treatment: <20%.
⚠️ ACYCLOVIR NEPHROTOXICITY
Ensure adequate hydration. Monitor renal function daily. Adjust dose for CrCl.
═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════
1. LABORATORY WORKUP¶
1A. Essential/Core Labs¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| CBC with differential | Infection workup, baseline | May show leukocytosis | STAT | STAT | — | STAT |
| CMP (BMP + LFTs) | Renal function (acyclovir dosing), hepatic function | Normal or mildly elevated | STAT | STAT | — | STAT |
| BUN/Creatinine | Baseline for acyclovir dosing | Normal (adjust acyclovir if elevated) | STAT | STAT | — | STAT |
| Blood glucose | Compare with CSF glucose | Document | STAT | STAT | — | STAT |
| PT/INR, PTT | Pre-LP coagulation status | INR <1.5 | STAT | STAT | — | STAT |
| Blood cultures (2 sets) | Exclude bacterial infection | Negative | STAT | STAT | — | STAT |
| Serum sodium | SIADH common in encephalitis | 135-145 mEq/L | STAT | STAT | — | STAT |
| ESR, CRP | Inflammatory markers | May be mildly elevated | URGENT | ROUTINE | — | URGENT |
1B. Extended Workup (Second-line)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| HIV antibody/antigen | Immunocompromised host evaluation | Document status | — | ROUTINE | — | ROUTINE |
| HSV-1/HSV-2 serology (IgG, IgM) | Not useful for acute diagnosis; documents prior exposure | Document (NOT diagnostic of encephalitis) | — | ROUTINE | — | ROUTINE |
| Procalcitonin | Bacterial vs viral differentiation | Low (<0.5) in viral | URGENT | ROUTINE | — | URGENT |
| TSH | Altered mental status workup | Normal | — | ROUTINE | — | ROUTINE |
| Ammonia | Altered mental status workup | Normal | URGENT | ROUTINE | — | URGENT |
| B12 | Encephalopathy workup | Normal | — | ROUTINE | — | ROUTINE |
| Urine drug screen | Altered mental status differential | Document | STAT | ROUTINE | — | STAT |
| Troponin | Stress cardiomyopathy | Normal or mildly elevated | URGENT | ROUTINE | — | STAT |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Serum autoimmune encephalitis panel | Post-HSV autoimmune encephalitis | Negative initially (may become positive later) | — | ROUTINE | — | ROUTINE |
| VZV serology | VZV encephalitis differential | Document | — | ROUTINE | — | ROUTINE |
| EBV serology | EBV encephalitis differential | Document | — | ROUTINE | — | ROUTINE |
| CMV PCR | Immunocompromised patients | Negative | — | ROUTINE | — | ROUTINE |
| Serum West Nile IgM | Endemic area, summer months | Negative | — | ROUTINE | — | ROUTINE |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain with and without contrast | STAT (within 24h) | Temporal lobe T2/FLAIR hyperintensity, hemorrhage, edema | Hemodynamic instability (get CT first) | STAT | STAT | — | STAT |
| CT head without contrast | If MRI delayed or unavailable | Temporal lobe hypodensity, hemorrhage, edema (less sensitive than MRI) | None in emergency | STAT | STAT | — | STAT |
| EEG | If seizures or altered mental status | Periodic lateralized epileptiform discharges (PLEDs), temporal slowing | None | STAT | STAT | — | STAT |
MRI Findings in HSVE: - Early (days 1-3): T2/FLAIR hyperintensity in medial temporal lobe, insular cortex, cingulate gyrus - Characteristic: Asymmetric, unilateral or bilateral (asymmetric) temporal involvement - May also involve: Orbitofrontal cortex, insular cortex - Spares: Basal ganglia (helps distinguish from other encephalitides) - Hemorrhage: Petechial hemorrhages common (T1 hyperintensity, susceptibility-weighted imaging) - Contrast enhancement: Variable; may be absent early
2B. Extended¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| MRI brain (repeat) | Day 3-7 if initial negative | Evolution of findings | Hemodynamic instability | — | URGENT | — | URGENT |
| Continuous EEG (cEEG) | If seizures, persistent AMS | Nonconvulsive seizures, PLEDs | None | — | STAT | — | STAT |
| CT angiogram | If vasculitis suspected | Normal (or vasculitic changes) | Contrast allergy | — | URGENT | — | URGENT |
2C. Rare/Specialized¶
| Study | Timing | Target Finding | Contraindications | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Brain biopsy | Refractory to treatment, diagnostic uncertainty | HSV inclusions (Cowdry type A) | Coagulopathy | — | EXT | — | EXT |
| PET scan | If autoimmune encephalitis suspected post-HSV | Temporal hypermetabolism | Hemodynamic instability | — | EXT | — | EXT |
LUMBAR PUNCTURE¶
Indication: ALL suspected HSV encephalitis (unless contraindicated)
Timing: STAT - Do NOT delay acyclovir for LP
Volume Required: 10-15 mL minimum
| Study | Rationale | Target Finding | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|
| Opening pressure | May be elevated in encephalitis | 10-20 cmH2O normal; often elevated | STAT | STAT | — | STAT |
| Cell count with differential (tubes 1 and 4) | Lymphocytic pleocytosis | 10-500 WBC/μL; lymphocyte predominant; RBCs may be present | STAT | STAT | — | STAT |
| Protein | Elevated in encephalitis | 60-100 mg/dL (mildly elevated) | STAT | STAT | — | STAT |
| Glucose | Usually normal in viral encephalitis | Normal (>40 mg/dL) | STAT | STAT | — | STAT |
| HSV PCR (CSF) | Definitive diagnosis | Positive (sensitivity 96%, specificity >99%) | STAT | STAT | — | STAT |
| HSV-1 and HSV-2 specific PCR | Distinguish HSV-1 vs HSV-2 | Document which type | STAT | STAT | — | STAT |
| VZV PCR | VZV encephalitis differential | Negative | STAT | STAT | — | STAT |
| Enterovirus PCR | Viral encephalitis differential | Negative | STAT | STAT | — | STAT |
| BioFire FilmArray ME Panel | Rapid multiplex PCR | HSV and other pathogens | STAT | STAT | — | STAT |
| Gram stain and bacterial culture | Exclude bacterial meningitis | Negative | STAT | STAT | — | STAT |
| Cytology | If malignancy suspected | Negative | — | ROUTINE | — | ROUTINE |
| Autoimmune encephalitis panel (CSF) | Post-HSV autoimmune encephalitis | Negative initially | — | ROUTINE | — | ROUTINE |
CSF Findings in HSVE:
| Parameter | Typical Finding |
|---|---|
| Opening pressure | Normal to mildly elevated |
| WBC | 10-500/μL (lymphocyte predominant) |
| RBCs | May be present (hemorrhagic encephalitis) |
| Protein | Mildly elevated (60-100 mg/dL) |
| Glucose | Normal |
| HSV PCR | Positive (may be negative in first 24-72 hours) |
Special Handling: HSV PCR refrigerated; process within 24 hours.
Contraindications: Signs of herniation, severe coagulopathy, mass effect on CT. Get CT first if concern.
CRITICAL NOTE: CSF HSV PCR may be negative in first 24-72 hours. If clinical suspicion high and initial PCR negative, repeat LP in 3-7 days and continue acyclovir.
3. TREATMENT¶
CRITICAL: Start acyclovir immediately upon suspicion. Do NOT wait for LP, MRI, or PCR results.
3A. Antiviral Therapy¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Acyclovir | IV | Empiric and definitive treatment | 10 mg/kg q8h :: IV :: q8h :: 10 mg/kg IV q8h (infuse over 1 hour); adjust for renal function; minimum 14 days, extend to 21 days if severe or immunocompromised | Severe renal impairment (adjust dose) | Renal function daily, hydration status, neurotoxicity | STAT | STAT | — | STAT |
| Acyclovir (renal adjustment) | IV | CrCl 25-50 mL/min | 10 mg/kg q12h :: IV :: q12h :: 10 mg/kg IV q12h if CrCl 25-50 mL/min | — | Cr daily | STAT | STAT | — | STAT |
| Acyclovir (renal adjustment) | IV | CrCl 10-25 mL/min | 10 mg/kg q24h :: IV :: q24h :: 10 mg/kg IV q24h if CrCl 10-25 mL/min | — | Cr daily | STAT | STAT | — | STAT |
| Acyclovir (HD) | IV | Hemodialysis | 10 mg/kg post-HD :: IV :: post-HD :: 10 mg/kg IV after each hemodialysis session | — | Post-HD levels | — | STAT | — | STAT |
Acyclovir Duration: - Standard: 14 days minimum - Severe disease/immunocompromised: 21 days - Repeat CSF PCR: NOT routinely recommended. Consider repeat LP near end of treatment only in select cases: (1) immunocompromised patients, (2) severe/complicated course, (3) clinical concern for treatment failure or relapse. If PCR still positive, extend treatment.
3B. Empiric Bacterial Coverage (Until Bacterial Ruled Out)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Ceftriaxone | IV | Empiric bacterial coverage | 2 g q12h :: IV :: q12h :: 2 g IV q12h until bacterial meningitis ruled out | Cephalosporin allergy | Renal function | STAT | STAT | — | STAT |
| Vancomycin | IV | Empiric DRSP coverage | 15-20 mg/kg q8-12h :: IV :: q8-12h :: 15-20 mg/kg IV q8-12h until bacterial ruled out | Renal impairment (adjust) | Trough 15-20, renal function | STAT | STAT | — | STAT |
| Dexamethasone | IV | If bacterial meningitis possible | 0.15 mg/kg q6h :: IV :: q6h x 4 days :: 0.15 mg/kg IV q6h ONLY if bacterial meningitis not ruled out; discontinue if HSV confirmed | — | Glucose | STAT | STAT | — | STAT |
Note: Discontinue empiric antibiotics and dexamethasone once HSV encephalitis confirmed and bacterial meningitis ruled out.
3C. Seizure Management¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Levetiracetam | IV/PO | Seizure treatment/prophylaxis | 1000 mg BID; 1500 mg BID; 2000 mg BID :: IV/PO :: BID :: Load 1000-2000 mg IV, then 1000-1500 mg BID; preferred first-line | Severe renal impairment (adjust) | Seizure frequency, behavior | STAT | STAT | — | STAT |
| Phenytoin | IV | Alternative for seizures | 20 mg/kg load; 100 mg TID :: IV :: load then TID :: 20 mg/kg IV load (max 50 mg/min), then 100 mg q8h or 300 mg daily; target level 10-20 | Bradycardia, AV block | Cardiac monitor during load, levels | STAT | STAT | — | STAT |
| Lacosamide | IV/PO | Alternative/adjunctive | 200 mg BID; 300 mg BID :: IV/PO :: BID :: Load 200-400 mg IV, then 200-300 mg BID | PR prolongation, severe cardiac disease | ECG, PR interval | — | STAT | — | STAT |
| Lorazepam | IV | Acute seizure termination | 2 mg; 4 mg :: IV :: PRN :: 0.1 mg/kg IV (max 4 mg); may repeat x1 in 5 min | Respiratory depression | RR, O2 sat | STAT | STAT | — | STAT |
Seizure Prophylaxis Considerations: - High seizure risk in HSVE (60-70%) - Consider prophylaxis for all patients during acute phase - Typical duration: Continue through acute illness and taper after 3-6 months if seizure-free - Long-term epilepsy occurs in ~25% of survivors
3D. Cerebral Edema / Elevated ICP Management¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Mannitol | IV | Elevated ICP | 0.5-1 g/kg bolus :: IV :: PRN :: 0.5-1 g/kg IV bolus over 15-20 min; may repeat q6h PRN; target serum osm <320 | Renal failure, hypotension | Serum osm, Na+, renal function | — | STAT | — | STAT |
| Hypertonic saline (3%) | IV | Elevated ICP | 250 mL bolus :: IV :: PRN :: 250 mL IV bolus for acute herniation; target Na 145-155 | — | Na+, serum osm | — | STAT | — | STAT |
| Head of bed elevation | — | ICP management | N/A :: — :: continuous :: Elevate HOB 30-45 degrees | — | ICP (if monitored) | STAT | STAT | — | STAT |
| Decompressive craniectomy | — | Refractory elevated ICP | N/A :: — :: :: Consider for malignant cerebral edema with impending herniation | Multifocal disease, poor prognosis | Neurosurgery consult | — | EXT | — | EXT |
3E. Supportive Care¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| IV fluids (isotonic) | IV | Hydration (prevent acyclovir nephrotoxicity) | NS 100-150 mL/hr :: IV :: continuous :: Maintain euvolemia; avoid dehydration (acyclovir crystallizes in renal tubules) | Cerebral edema (may need to restrict) | I/O, renal function, Na+ | STAT | STAT | — | STAT |
| Acetaminophen | IV/PO | Fever, headache | 650 mg q6h; 1000 mg q6h :: IV/PO :: q6h :: 650-1000 mg q6h; max 4 g/day | Severe hepatic impairment | Temperature | STAT | STAT | — | STAT |
| Ondansetron | IV/PO | Nausea | 4 mg q6h PRN; 8 mg q8h PRN :: IV/PO :: q6h PRN :: 4-8 mg IV/PO q6-8h PRN | QT prolongation | QTc if repeated dosing | STAT | STAT | — | STAT |
| Enoxaparin | SC | DVT prophylaxis (after stabilization) | 40 mg daily :: SC :: daily :: 40 mg SC daily; start after 48-72h if no hemorrhage | Active bleeding, recent hemorrhagic transformation | Platelet count, bleeding | — | ROUTINE | — | ROUTINE |
| Famotidine | IV/PO | Stress ulcer prophylaxis | 20 mg BID :: IV/PO :: BID :: 20 mg IV/PO BID | None significant | GI bleeding | — | ROUTINE | — | ROUTINE |
3F. Post-HSV Autoimmune Encephalitis¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Methylprednisolone | IV | Post-HSV autoimmune encephalitis | 1000 mg daily x 5 days :: IV :: daily x 5 days :: 1000 mg IV daily x 5 days; for secondary deterioration 2-6 weeks post-HSVE | Active untreated infection | Glucose, BP, psychiatric symptoms | — | URGENT | — | URGENT |
| IVIg | IV | Post-HSV autoimmune encephalitis | 0.4 g/kg/day x 5 days :: IV :: daily x 5 days :: 0.4 g/kg/day IV x 5 days | IgA deficiency | Renal function, infusion reactions | — | URGENT | — | URGENT |
Post-HSV Autoimmune Encephalitis: - Occurs in ~20-27% of HSVE patients - Typically 2-6 weeks after initial presentation - Associated with anti-NMDAR antibodies most commonly - Presents as secondary neurological deterioration - Requires repeat CSF with autoimmune panel - Treat with immunotherapy (steroids, IVIg, PLEX)
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neurology consult for diagnosis confirmation, antiviral guidance, and seizure management | STAT | STAT | — | STAT |
| Infectious disease consult for atypical course, treatment failure, or diagnostic uncertainty | URGENT | URGENT | — | URGENT |
| Critical care consult for ICU admission given altered mental status, respiratory failure, or elevated ICP | STAT | STAT | — | STAT |
| Neurosurgery consult for elevated ICP management, decompressive surgery, or brain biopsy consideration | — | URGENT | — | STAT |
| Epilepsy consult for refractory seizures and continuous EEG monitoring interpretation | — | URGENT | — | STAT |
| Physical therapy for mobility assessment and fall prevention given weakness and cognitive impairment | — | ROUTINE | — | ROUTINE |
| Occupational therapy for ADL assessment and early cognitive rehabilitation planning | — | ROUTINE | — | ROUTINE |
| Speech therapy for swallow evaluation given aspiration risk and aphasia therapy for temporal lobe involvement | — | URGENT | — | URGENT |
| Neuropsychology for formal cognitive assessment after acute illness to guide rehabilitation | — | — | ROUTINE | — |
| Social work for discharge planning and caregiver support given potential for significant disability | — | ROUTINE | — | ROUTINE |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately if worsening headache, confusion, or seizures develop (may indicate relapse or post-HSV autoimmune encephalitis) | STAT | — | STAT |
| Complete full 14-21 day acyclovir course to ensure viral eradication and prevent relapse | — | STAT | STAT |
| Follow seizure precautions including no driving, heights, or operating machinery due to high seizure risk | — | STAT | STAT |
| Report any new neurological symptoms weeks after discharge as post-HSV autoimmune encephalitis can occur 2-6 weeks later | — | ROUTINE | ROUTINE |
| Attend neurology follow-up in 2-4 weeks to assess recovery and screen for delayed complications | — | ROUTINE | ROUTINE |
| Expect that cognitive rehabilitation may be needed as memory and behavioral deficits are common after HSVE | — | ROUTINE | ROUTINE |
| Contact Encephalitis Society (www.encephalitis.info) for patient support and educational resources | — | ROUTINE | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Use fall precautions including walker and supervision due to weakness and cognitive impairment | STAT | STAT | STAT |
| Aspiration precautions including thickened liquids and upright positioning if bulbar involvement present | STAT | STAT | — |
| Maintain adequate hydration (2-3 L/day) to prevent acyclovir-induced nephrotoxicity | STAT | STAT | — |
| Follow seizure safety including no swimming alone and showers instead of baths due to ongoing seizure risk | — | ROUTINE | ROUTINE |
| Use cognitive pacing with scheduled rest periods to manage post-encephalitis fatigue | — | ROUTINE | ROUTINE |
| Do not drive until cleared by neurology due to seizure risk and potential cognitive impairment | — | STAT | STAT |
═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Autoimmune encephalitis | Subacute, psychiatric symptoms, movement disorder, may have tumor | CSF autoimmune panel, serum panel, CT body |
| Bacterial meningitis/abscess | More toxic, CSF with PMNs, low glucose | CSF Gram stain/culture, MRI |
| Other viral encephalitis | Geographic/seasonal clues, different MRI pattern | CSF viral PCR panel, serology |
| Tuberculous meningitis | Subacute, basilar meningitis, low glucose | CSF AFB, TB PCR, adenosine deaminase |
| Fungal meningitis | Immunocompromised, indolent course | CSF fungal culture, cryptococcal antigen |
| Primary CNS lymphoma | Immunocompromised, periventricular lesions | MRI pattern, CSF cytology |
| Glioblastoma | Focal deficits, ring-enhancing mass | MRI with contrast, biopsy |
| Cerebral vasculitis | Multifocal strokes, systemic symptoms | Angiography, vessel wall MRI, biopsy |
| Acute disseminated encephalomyelitis (ADEM) | Post-infectious, multifocal white matter | MRI pattern (multifocal), CSF |
| Posterior reversible encephalopathy (PRES) | Hypertension, posterior predominance | MRI pattern, BP history |
| Status epilepticus | Seizure history, EEG pattern | EEG, response to antiseizure meds |
| Toxic/metabolic encephalopathy | Drug exposure, organ failure | Toxicology, metabolic panel |
| Paraneoplastic encephalitis | Cancer history, antibody-positive | Paraneoplastic panel, CT body |
| Creutzfeldt-Jakob disease | Rapid dementia, myoclonus, DWI restriction | MRI pattern, 14-3-3, RT-QuIC |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Neurological exam (GCS, pupils) | q1-2h initially, then q4h | GCS stable or improving | Head CT, consider ICP monitoring | STAT | STAT | — | STAT |
| Seizure activity | Continuous if cEEG, otherwise q4h assessment | No seizures | Escalate antiepileptic therapy | STAT | STAT | — | STAT |
| Temperature | q4h | Afebrile | Antipyretics, infection workup | STAT | STAT | — | STAT |
| Renal function (Cr, BUN) | Daily | Cr stable | Adjust acyclovir dose, increase hydration | STAT | STAT | — | STAT |
| Serum sodium | q6-12h initially | 135-145 mEq/L | Evaluate for SIADH, cerebral salt wasting | STAT | STAT | — | STAT |
| Fluid balance (I/O) | q8h | Even balance; avoid dehydration | Adjust fluids | — | STAT | — | STAT |
| Mental status | q4-8h | Improving | Re-evaluate, repeat imaging | STAT | STAT | — | STAT |
| Signs of herniation | q1-2h if concern | Absent | Emergent intervention, neurosurgery | STAT | STAT | — | STAT |
| CSF HSV PCR (repeat) | Day 14-21 | Negative | Extend acyclovir if still positive | — | ROUTINE | — | ROUTINE |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| ICU admission | GCS <12; seizures; signs of elevated ICP; need for intubation; hemodynamic instability; rapidly worsening |
| Step-down/telemetry | GCS 12-14; stable on antiepileptics; no ICP concerns; improving |
| General floor | GCS 15; stable neurologically; no seizures; tolerating PO; can complete IV acyclovir |
| Discharge home | Completed 14-21 days IV acyclovir; neurologically stable; safe swallow; adequate support; outpatient follow-up arranged |
| Acute rehabilitation | Significant residual cognitive or motor deficits; requires intensive therapy |
| Long-term care | Severe persistent deficits; unable to live independently |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Acyclovir 10 mg/kg q8h for HSVE | Class I, Level A | Whitley et al. NEJM 1986 |
| CSF HSV PCR for diagnosis | Class I, Level A | Lakeman & Whitley. J Infect Dis 1995 |
| Early acyclovir improves outcomes | Class II, Level B | Raschilas et al. Clin Infect Dis 2002 |
| MRI superior to CT for HSVE | Class II, Level B | Domingues et al. J Neurol Sci 1997 |
| 14-21 day treatment duration | Class II, Level B | Gnann & Whitley. Clin Infect Dis 2002 |
| Repeat CSF PCR if clinical concern | Class III, Level C | Tyler. NEJM 2004 |
| Post-HSV autoimmune encephalitis | Class II, Level B | Armangue et al. Lancet Neurol 2018 |
| Seizure prophylaxis consideration | Class III, Level C | Misra et al. Seizure 2008 |
| Prognosis with early treatment | Class II, Level B | Skoldenberg et al. Lancet 1984 |
CHANGE LOG¶
v1.1 (January 24, 2026) - Citation verification: Corrected Whitley PMID (3001520), Armangue PMID (30049614)
v1.0 (January 24, 2026) - Initial template creation - Acyclovir dosing with renal adjustments - CSF interpretation and PCR timing - MRI findings description - Seizure management - Post-HSV autoimmune encephalitis recognition
APPENDIX A: Acyclovir Dosing by Renal Function¶
| CrCl (mL/min) | Dose | Frequency |
|---|---|---|
| >50 | 10 mg/kg | q8h |
| 25-50 | 10 mg/kg | q12h |
| 10-25 | 10 mg/kg | q24h |
| <10 | 5 mg/kg | q24h |
| Hemodialysis | 10 mg/kg | After each HD session |
| CRRT | 10 mg/kg | q12-24h (adjust based on clearance) |
Administration Notes: - Infuse each dose over at least 1 hour (prevents crystalluria) - Ensure adequate hydration (2-3 L/day if tolerated) - Monitor renal function daily - Acyclovir neurotoxicity (confusion, tremor, myoclonus) can occur, especially with renal impairment
APPENDIX B: CSF HSV PCR Interpretation¶
| Scenario | PCR Result | Interpretation | Action |
|---|---|---|---|
| Early presentation (<24-72h) | Negative | May be false negative | Continue acyclovir, repeat LP in 3-7 days |
| Day 3-7 of illness | Positive | Diagnostic | Continue acyclovir 14-21 days |
| Day 3-7 of illness | Negative | Likely not HSVE | Consider alternative diagnoses |
| End of treatment (day 14-21) | Positive | Ongoing viral replication | Extend acyclovir treatment |
| End of treatment | Negative | Treatment adequate | Complete therapy, monitor for relapse |
PCR Sensitivity/Specificity: - Sensitivity: 96-98% (after first 24-72 hours) - Specificity: >99% - May be negative in first 24-72 hours - Remains positive for 1-2 weeks even with effective treatment
APPENDIX C: Red Flags for Post-HSV Autoimmune Encephalitis¶
Timing: Typically 2-6 weeks after initial HSVE presentation
Clinical Features Suggesting Autoimmune Complication: - Secondary neurological deterioration after initial improvement - New movement disorder (choreoathetosis, orofacial dyskinesia) - New psychiatric symptoms (agitation, psychosis, catatonia) - Refractory seizures - Memory disturbance out of proportion to structural damage - Autonomic instability
Evaluation: - Repeat MRI (may show new or progressive changes) - Repeat LP with autoimmune panel (CSF > serum) - Anti-NMDAR antibodies most common - Other antibodies: GABA-B, AMPA, LGI1
Treatment: - First-line: IV methylprednisolone 1g daily x 5 days - IVIg 0.4 g/kg/day x 5 days - PLEX (5 exchanges) - Second-line: Rituximab, cyclophosphamide for refractory cases