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neuro.encephalitis.hsv.v1PRODUCTION
neuro.encephalitis.hsv.v1

HSV Encephalitis (acute)

neurologyacuteadultpediatricneonatalgeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Frame

Detailed

Acute febrile encephalopathy with focal neuro deficit / seizure / behavioural change → empiric HSV coverage until ruled out (IDSA 2008 Tunkel PMID 18582201; Venkatesan IRCNS 2017 PMID 28528537)

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Encephalitis pathway activated

Patient inputs (18)

Adults: HSV-1 most common cause of sporadic encephalitis (90%); neonates: HSV-2 perinatal; peds: enterovirus + arbovirus also common (IDSA 2008 PMID 18582201)

GCS quantifies AMS severity; GCS ≤8 = intubation threshold; baseline + serial

HSV temporal lobe seizures common ~80%; status epilepticus complicates ~30%; document and AED ready (Venkatesan IRCNS 2017 PMID 28528537)

HIV / transplant / chemo → higher severity + acyclovir resistance ~5%; ID consult; consider foscarnet if no response by day 3-5

Acyclovir category B — use for HSV encephalitis even in pregnancy (benefits > risk); neonatal HSV-2 perinatal is separate entity

Fever (≥38°C) + encephalopathy = empiric acyclovir trigger; afebrile encephalitis still possible especially elderly/immunocompromised

Time-to-acyclovir is the single strongest predictor of outcome (Whitley NEJM 1986 PMID 16983610); document onset → acyclovir-start delta

Recent acyclovir lowers viral load → false-negative PCR; document so repeat LP planned if initial PCR negative (Steiner PMID 24839282)

Acyclovir 10 mg/kg q8h is renally adjusted; baseline Cr + CrCl drives dose; crystalline nephropathy risk in dehydration

CSF profile: lymphocytic pleocytosis (10-1000), mildly elevated protein, normal-to-mildly-low glucose; RBC may be elevated (hemorrhagic temporal lobe necrosis)

Temporal + insular + cingulate T2/FLAIR hyperintensity ± hemorrhage = pathognomonic for HSV; CT may be normal early — MRI sensitivity higher

Temporal lobe PLEDs ~80% in HSV; cEEG if persistent AMS or refractory seizure / suspect NCSE

Baseline labs for ICU admission; LFT if valacyclovir / foscarnet; coag for LP safety

Aphasia / hemiparesis / cranial nerve / cerebellar signs — pivot to imaging + LP; isolated AMS without focal deficit broader differential

STAT non-contrast CT to rule out bleed / mass-effect before LP; do NOT delay acyclovir while awaiting

Send CSF anti-NMDAR / LGI1 / GABA-B / CASPR2 / GAD if HSV PCR negative or biphasic course (Graus Lancet Neurol 2016 PMID 30951513)

HIV screen if immunocompromise unknown — drives intensity of workup + foscarnet threshold

CSF HSV-1/-2 PCR sensitivity 96-98% (Steiner PMID 24839282); repeat at day 3-7 if initial negative + clinical suspicion (false negatives early or post-acyclovir)

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Severity triggers (9)

9 need judgement
  • informationallife_threateningempiric_acyclovir_within_6h
    Adult with fever + AMS + focal deficit / seizure / new behavioural change — START EMPIRIC IV ACYCLOVIR 10 mg/kg q8h within 6 h; do NOT wait for CSF HSV PCR (IDSA 2008 PMID 18582201; Whitley NEJM 1986 PMID 16983610)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpediatric_neonatal_hsv
    Neonatal HSV-2 perinatal (acquired during delivery from genital HSV-2) — disseminated / CNS / SEM (skin-eye-mouth) forms; high-dose acyclovir 20 mg/kg IV q8h × 21 d (CNS); suppressive oral acyclovir 300 mg/m² PO TID × 6 mo post-CNS (CDC + AAP)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretemporal_lobe_seizure_phenotype
    HSV temporal lobe seizure phenotype — temporal lobe PLEDs on EEG (~80% HSV); status epilepticus complicates ~30%; aphasia / olfactory hallucinations / déjà vu common (Venkatesan IRCNS 2017 PMID 28528537)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehsv_pcr_positive_csf
    Confirmed HSV-1/-2 PCR positive on CSF — complete 21 d IV acyclovir; verify renal + LFT throughout course (Steiner PMID 24839282)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepcr_negative_repeat_3_7d
    Initial CSF HSV PCR negative + clinical / MRI suspicion → CONTINUE empiric acyclovir + REPEAT LP at day 3-7 (false negatives early <72 h or after recent acyclovir; Steiner PMID 24839282)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereautoimmune_overlap_anti_nmdar
    Post-HSV anti-NMDAR autoimmune encephalitis — biphasic course 1-6 wk after HSV recovery; psychiatric prodrome + new seizures + movement disorder + autonomic instability; up to 27% of HSV-encephalitis survivors (Armangué Lancet Neurol 2018 PMID 33099399; Graus 2016 PMID 30951513)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereimmunocompromised_severe
    Immunocompromised (HIV / transplant / chemo / steroids) with HSV encephalitis — higher severity, atypical imaging, higher resistance risk (~5%); ID consult; consider foscarnet adjunct
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereresistant_hsv_thymidine_kinase_mutant
    Documented or strongly suspected acyclovir-resistant HSV (no clinical improvement by day 3-5 in immunocompromised; rare in immunocompetent) — thymidine kinase mutant; foscarnet first-line (Sili Antivir Res 2009 PMID 18587392)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateiatrogenic_acyclovir_nephrotoxicity
    Crystalline nephropathy from acyclovir + inadequate hydration → AKI; preventable with concurrent IVF 1.5× maintenance + CrCl-adjusted dose; hold + IVF + dose-adjust if Cr rises >0.5 mg/dL or UO <0.5 mL/kg/h
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

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RISK_STRATIFICATIONoptionalDrives severity classification
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Recommended regimen

HSV encephalitis acute Rx — empiric IV acyclovir within 6 h + AED + ICP + foscarnet for resistance + autoimmune overlap (IDSA 2008 Tunkel PMID 18582201; Whitley NEJM 1986 PMID 16983610)
axis: hsv_encephalitis_acute_treatmentstep 1 - Step 1 — Empiric IV acyclovir within 6 h (time-critical; Class I IDSA 2008; Whitley NEJM 1986 PMID 16983610)
Selected step "Step 1 — Empiric IV acyclovir within 6 h (time-critical; Class I IDSA 2008; Whitley NEJM 1986 PMID 16983610)" — Adult / pediatric / immunocompromised patient with fever + AMS + focal deficit / seizure / new behavioural change — DO NOT wait for CSF HSV PCR
  • acyclovir
    first line
    nucleoside_analog_antiviral
    10 mg/kg IV q8h (CrCl-adjusted; ideal body weight if obese) × 14-21 d; pediatric 60 mg/kg/day in 3 divided doses; neonatal HSV 20 mg/kg IV q8h × 21 d (CNS) • IV • q8h (max: 21 d course (continue 21 d if confirmed; 14 d acceptable if PCR negative + alternative dx))
    triggers: suspect_hsv_encephalitis
    Whitley NEJM 1986 PMID 16983610 — mortality 70% → 28% with acyclovir; time-to-acyclovir = single strongest predictor of outcome; IDSA 2008 PMID 18582201 — empiric for any suspected viral encephalitis; CrCl-based dose to prevent nephrotoxicity
    rxcui 281
  • NS 0.9% IV fluids
    add on
    crystalloid_iv_fluid
    1.5× maintenance (typically 100-150 mL/h adult) • IV • continuous
    triggers: concurrent_acyclovir
    Crystalline nephropathy prevention — acyclovir precipitates in renal tubules; aggressive IVF during infusion reduces risk; do NOT use LR (calcium-acyclovir interaction)
  • valacyclovir
    second line
    nucleoside_analog_antiviral_PO
    1 g PO TID (when tolerating PO + clinical improvement; not standard for completing acute encephalitis course but used in step-down post-recovery) • PO • TID
    triggers: step_down_post_acute, crystalline_nephropathy_with_acyclovir_iv
    NOT first-line acute — IV acyclovir standard for full course; valacyclovir oral may be considered for step-down or in mild disease in select cases (off-label for encephalitis maintenance)
    rxcui 236081

outpatient playbook — drug actions (4)

  1. 1. levetiracetam (continue if cortical injury)
    500 mg-1 g PO BID • PO • BID
    trigger: Long-term AED for cortical injury / seizure history
    Risk of late seizures from cortical scar
  2. 2. sertraline (or other SSRI)
    25-200 mg PO daily • PO • daily
    trigger: PHQ-9 ≥10 — post-HSV depression / behavioural change
    Common sequelae; address QoL
  3. 3. methylprednisolone + IVIG (if biphasic autoimmune relapse)
    Methylprednisolone 1 g IV × 3-5 d + IVIG 0.4 g/kg × 5 d • IV • per protocol
    trigger: New behavioural change / dyskinesia / autonomic instability 1-6 wk post-HSV
    Armangué 2018 PMID 33099399; CSF anti-NMDAR confirmatory; re-admit for workup + treatment
  4. 4. donepezil or rivastigmine (off-label cognitive support)
    Donepezil 5-10 mg daily; rivastigmine 1.5-6 mg BID • PO • daily / BID
    trigger: Persistent severe cognitive deficit
    Off-label; modest cognitive support; trial 3-6 mo

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Fever + altered mental status (acute febrile encephalopathy) → empiric HSV coverage until ruled out (IDSA 2008 Tunkel PMID 18582201); New focal neurological deficit (aphasia / hemiparesis / cranial nerve) with fever — temporal lobe HSV pattern; New-onset seizure with fever / encephalopathy — HSV temporal lobe seizure phenotype (~80% PLEDs on EEG).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**HSV Encephalitis (acute)** (neuro.encephalitis.hsv.v1).
Phenotype framing: HSV-1 (adult sporadic — most common) / HSV-2 (genital + neonatal disseminated) / VZV / enterovirus (peds) / arbovirus (West Nile, EEE, JE) / autoimmune encephalitis (anti-NMDAR, LGI1, GABA-B, CASPR2, AMPA, GAD) / bacterial meningitis (parallel empiric coverage) / TB meningoencephalitis / fungal (Cryptococcus, Aspergillus in IC) / paraneoplastic / toxic-metabolic encephalopathy / drug toxicity (lithium, baclofen, levetiracetam at high dose)
Scope: Acute febrile encephalopathy with focal neuro deficit / seizure / behavioural change → empiric HSV coverage until ruled out (IDSA 2008 Tunkel PMID 18582201; Venkatesan IRCNS 2017 PMID 28528537)

No severity triggers fired against current inputs.

Plan

Regimen axis: **HSV encephalitis acute Rx — empiric IV acyclovir within 6 h + AED + ICP + foscarnet for resistance + autoimmune overlap (IDSA 2008 Tunkel PMID 18582201; Whitley NEJM 1986 PMID 16983610)** — step "Step 1 — Empiric IV acyclovir within 6 h (time-critical; Class I IDSA 2008; Whitley NEJM 1986 PMID 16983610)".
1. acyclovir 10 mg/kg IV q8h (CrCl-adjusted; ideal body weight if obese) × 14-21 d; pediatric 60 mg/kg/day in 3 divided doses; neonatal HSV 20 mg/kg IV q8h × 21 d (CNS) IV q8h (nucleoside_analog_antiviral, first line) — Whitley NEJM 1986 PMID 16983610 — mortality 70% → 28% with acyclovir; time-to-acyclovir = single strongest predictor of outcome; IDSA 2008 PMID 18582201 — empiric for any suspected viral encephalitis; CrCl-based dose to prevent nephrotoxicity
2. NS 0.9% IV fluids 1.5× maintenance (typically 100-150 mL/h adult) IV continuous (crystalloid_iv_fluid, add on) — Crystalline nephropathy prevention — acyclovir precipitates in renal tubules; aggressive IVF during infusion reduces risk; do NOT use LR (calcium-acyclovir interaction)
3. valacyclovir 1 g PO TID (when tolerating PO + clinical improvement; not standard for completing acute encephalitis course but used in step-down post-recovery) PO TID (nucleoside_analog_antiviral_PO, second line) — NOT first-line acute — IV acyclovir standard for full course; valacyclovir oral may be considered for step-down or in mild disease in select cases (off-label for encephalitis maintenance)

Setting playbook (outpatient) — Long-term recovery — neurocognitive rehab at 3 + 6 + 12 mo, AED follow-up (many require long-term AED for cortical injury), psych follow-up (depression / behavioural change common), autoimmune relapse surveillance 1-6 wk post-HSV
4. levetiracetam (continue if cortical injury) 500 mg-1 g PO BID PO BID — Long-term AED for cortical injury / seizure history (Risk of late seizures from cortical scar)
5. sertraline (or other SSRI) 25-200 mg PO daily PO daily — PHQ-9 ≥10 — post-HSV depression / behavioural change (Common sequelae; address QoL)
6. methylprednisolone + IVIG (if biphasic autoimmune relapse) Methylprednisolone 1 g IV × 3-5 d + IVIG 0.4 g/kg × 5 d IV per protocol — New behavioural change / dyskinesia / autonomic instability 1-6 wk post-HSV (Armangué 2018 PMID 33099399; CSF anti-NMDAR confirmatory; re-admit for workup + treatment)
7. donepezil or rivastigmine (off-label cognitive support) Donepezil 5-10 mg daily; rivastigmine 1.5-6 mg BID PO daily / BID — Persistent severe cognitive deficit (Off-label; modest cognitive support; trial 3-6 mo)

Non-pharmacologic actions:
- Cognitive rehab + memory aids + structured routines
- Speech / language therapy for aphasia
- Occupational therapy for ADL adaptation
- Physical therapy for hemiparesis / coordination
- Driving evaluation + cessation if cognitive concerns
- Vocational rehab
- Counseling + support groups (encephalitis society + caregiver groups)
- Family education on autoimmune relapse signs
- Annual vaccinations
- Avoid alcohol + sedating meds during AED course
- DEXA + bone health if long-term AED

AVOID / contraindication checks:
- Acyclovir_renally_adjust_per_CrCl (crystalline nephropathy + neurotoxicity at supratherapeutic levels)
- Concurrent_IVF_1.5x_maintenance_with_acyclovir (crystalline nephropathy prevention; do NOT use LR — calcium acyclovir interaction)
- Do_NOT_wait_for_PCR_to_start_acyclovir (Whitley NEJM 1986 PMID 16983610; time to acyclovir = key outcome predictor)
- Repeat_LP_day_3 7_if_initial_PCR_negative_with_clinical_suspicion (Steiner PMID 24839282; false negatives early or post acyclovir)
- Foscarnet_renally_adjusted_and_q4h_electrolyte_panel (nephrotoxic + Ca/Mg/K/Phos wasting)
- CT_head_before_LP (rule out mass / bleed / herniation risk; do NOT delay acyclovir while awaiting)
- Parallel_bacterial_meningitis_empiric_coverage (vanc + ceftriaxone + dex until cultures back; never substitute for acyclovir)
- Anti_NMDAR_screening_during_initial_workup_AND_biphasic_relapse_window (Armangué 2018 PMID 33099399; Graus 2016 PMID 30951513)
- Rituximab_HBV_VZV_TB_screen_before_initiation (immunosuppression activation risk)
- ID_consult_for_immunocompromised_or_no_response_day_3 5 (resistance + foscarnet consideration)

Monitoring

Regimen monitoring:
- Daily neuro check + GCS (IDSA 2008 PMID 18582201)
- Cr + UO q72h on acyclovir; hold/dose-adjust if Cr rise >0.5 mg/dL or UO <0.5 mL/kg/h
- LFT q-wk during acyclovir/foscarnet
- AED level (levetiracetam typically not levels; phenytoin albumin-corrected)
- CBC q-wk (myelosuppression on foscarnet)
- Electrolyte panel q4h during foscarnet load (Ca/Mg/K/Phos wasting)
- Repeat MRI day 7 + day 14 (lesion evolution; rule out abscess / mass)
- Repeat LP day 3-7 if initial PCR negative + clinical suspicion (Steiner PMID 24839282)
- cEEG if persistent AMS or refractory seizure (rule out NCSE)
- Surveillance for biphasic autoimmune relapse 1-6 wk post-HSV (Armangué 2018 PMID 33099399)
- Neurocognitive battery at 3 + 6 + 12 mo (memory + language + behaviour)

Setting (outpatient) monitoring:
- Outpatient neurology q3 mo × 1 y, then q6 mo
- Cognitive battery at 3 + 6 + 12 mo
- Psych q3 mo × 1 y
- AED level annually
- Renal panel + LFT q3 mo if on antiviral

Follow-up plan: Neuro-cognitive battery at 3 + 6 + 12 mo (temporal lobe involvement → memory + language + behaviour); seizure follow-up + long-term AED if cortical injury; psych follow-up (depression / behaviour change common); occupational + speech therapy; rehab; return precautions for autoimmune relapse symptoms (new behavioural change, dyskinesia, autonomic instability — re-eval for anti-NMDAR)
- Close-out criterion: Long-term plan documented + rehab arranged

Monitoring phase: Daily neuro check + GCS; Cr + UO q72h on acyclovir (hold/dose-adjust if Cr rises >0.5 mg/dL or UO <0.5 mL/kg/h); LFT q-wk; AED level; CBC; repeat MRI day 7 + day 14; repeat LP at day 3-7 if PCR negative; cEEG if persistent AMS or refractory seizure; surveillance for biphasic autoimmune relapse 1-6 wk post-HSV (Armangué 2018 PMID 33099399)

Disposition

Current setting: outpatient — Long-term recovery — neurocognitive rehab at 3 + 6 + 12 mo, AED follow-up (many require long-term AED for cortical injury), psych follow-up (depression / behavioural change common), autoimmune relapse surveillance 1-6 wk post-HSV

Disposition criteria:
- Continue indefinite neurology + rehab + psych follow-up
- Transition to long-term care if persistent severe cognitive / behavioural sequelae

Escalation triggers (move to higher acuity):
- New seizure → ED + EEG + imaging
- Biphasic autoimmune relapse → ED + re-admit + autoimmune workup
- New focal deficit → ED
- Worsening cognitive function despite rehab → neuro-rehab + neuropsych + meds re-eval
- Severe depression / suicidality → urgent psych

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Adult with fever + AMS + focal deficit / seizure / new behavioural change — START EMPIRIC IV ACYCLOVIR 10 mg/kg q8h within 6 h; do NOT wait for CSF HSV PCR (IDSA 2008 PMID 18582201; Whitley NEJM 1986 PMID 16983610)
- [LIFE_THREATENING] Neonatal HSV-2 perinatal (acquired during delivery from genital HSV-2) — disseminated / CNS / SEM (skin-eye-mouth) forms; high-dose acyclovir 20 mg/kg IV q8h × 21 d (CNS); suppressive oral acyclovir 300 mg/m² PO TID × 6 mo post-CNS (CDC + AAP)
- [SEVERE] HSV temporal lobe seizure phenotype — temporal lobe PLEDs on EEG (~80% HSV); status epilepticus complicates ~30%; aphasia / olfactory hallucinations / déjà vu common (Venkatesan IRCNS 2017 PMID 28528537)

Citations

- 2008 IDSA Encephalitis Management Guidelines (Tunkel, Clin Infect Dis 2008;47:303-27) + 2013 International Encephalitis Consortium case definitions (Venkatesan, Clin Infect Dis 2013;57:1114-28) + 2016 Graus autoimmune-encephalitis clinical criteria (Lancet Neurol 2016;15:391-404) + Whitley vidarabine-vs-acyclovir HSE RCT (NEJM 1986;314:144-9) + Armangué post-HSV autoimmune-encephalitis prospective study (Lancet Neurol 2018;17:760-72) + Steiner EFNS viral-meningoencephalitis guideline (Eur J Neurol 2010;17:999-e57) + Lakeman & Whitley CSF-HSV-PCR NIAID CASG (J Infect Dis 1995;171:857-63) [PMID:18582201](https://pubmed.ncbi.nlm.nih.gov/18582201/)
- Cited evidence (PMID 23861361) [PMID:23861361](https://pubmed.ncbi.nlm.nih.gov/23861361/)
- Cited evidence (PMID 26906964) [PMID:26906964](https://pubmed.ncbi.nlm.nih.gov/26906964/)
- Cited evidence (PMID 3001520) [PMID:3001520](https://pubmed.ncbi.nlm.nih.gov/3001520/)
- Cited evidence (PMID 7706811) [PMID:7706811](https://pubmed.ncbi.nlm.nih.gov/7706811/)

Last reconciled with current guidelines: 2026-05-18.
References
  • 2008 IDSA Encephalitis Management Guidelines (Tunkel, Clin Infect Dis 2008;47:303-27) + 2013 International Encephalitis Consortium case definitions (Venkatesan, Clin Infect Dis 2013;57:1114-28) + 2016 Graus autoimmune-encephalitis clinical criteria (Lancet Neurol 2016;15:391-404) + Whitley vidarabine-vs-acyclovir HSE RCT (NEJM 1986;314:144-9) + Armangué post-HSV autoimmune-encephalitis prospective study (Lancet Neurol 2018;17:760-72) + Steiner EFNS viral-meningoencephalitis guideline (Eur J Neurol 2010;17:999-e57) + Lakeman & Whitley CSF-HSV-PCR NIAID CASG (J Infect Dis 1995;171:857-63) — PMID:18582201
  • Cited evidence (PMID 23861361) — PMID:23861361
  • Cited evidence (PMID 26906964) — PMID:26906964
  • Cited evidence (PMID 3001520) — PMID:3001520
  • Cited evidence (PMID 7706811) — PMID:7706811