Neurology · Topic 17 of 22

Encephalitis

Neurology · CNS infection

Encephalitis

Fever with altered mental status, seizures or focal deficits: start IV acyclovir at once, then confirm with MRI and CSF HSV PCR.

Key numbers

Start IV acyclovir 10 mg/kg empirically10 mg/kg IV q8h

CSF HSV PCR; repeat if early negativerepeat in 48–72 h

Confirmed HSV: acyclovir for 14–21 days14–21 days

Possible autoimmune encephalitis: subacute onset under 3 months< 3 months

01 · GiveStart IV acyclovir 10 mg/kg empirically

Start IV acyclovir 10 mg/kg every 8 hours (infused over 1 hour) as soon as encephalitis is suspected — do not wait for HSV PCR; continue until HSV and VZV are excluded.

02 · Look forFever with altered mental status

Encephalitis inflames the brain parenchyma: fever, headache and altered mental status, often with seizures or focal neurologic deficits; meningeal signs are usually mild.

03 · DoCSF HSV PCR; repeat if early negative

CSF PCR is the diagnostic test of choice for HSV, but it can be falsely negative early; if suspicion remains, repeat the lumbar puncture in 48–72 hours and keep acyclovir running.

Presentation

What you'll see

Olfactory seizures point to HSVOlfactory auras (rotten eggs, burnt meat) signal temporal lobe seizures and suggest HSV encephalitis; status epilepticus or coma marks severe inflammation and a poor prognosis.

Anti-NMDA receptor: psychosis, dyskinesias, autonomic instabilityAnti-NMDA receptor encephalitis, mainly in young women, starts with psychiatric symptoms, then seizures, orofacial dyskinesias or catatonia, depressed consciousness, autonomic instability and hypoventilation; screen for ovarian teratoma.

Diagnosis & monitoring

Work-up

Encephalitis CSF: lymphocytes, normal glucoseViral encephalitis CSF shows lymphocytic pleocytosis, normal glucose and mildly raised protein; red cells suggest hemorrhagic necrosis (HSV), and CSF may be normal in the first 8–24 hours.

Prevent acyclovir kidney injury: infuse slowly, hydrateAcyclovir crystallizes in renal tubules: infuse each dose over at least 1 hour with adequate hydration, dose obese patients by ideal body weight, adjust for renal function and follow creatinine.

Possible autoimmune encephalitis: subacute onset under 3 monthsPossible autoimmune encephalitis: onset over less than 3 months of memory deficits, altered mental status or psychiatric symptoms, plus new focal CNS findings, unexplained seizures, CSF > 5 cells/mm³ or suggestive MRI, with alternatives excluded.

Do right now

In this order

First moves

Start IV acyclovir 10 mg/kg empirically10 mg/kg IV q8h

→

Cover bacterial meningitis until it is excluded

→

Contrast MRI: temporal lobe edema in HSV

→

CSF HSV PCR; repeat if early negativerepeat in 48–72 h

Why each step

Start IV acyclovir 10 mg/kg empiricallyStart IV acyclovir 10 mg/kg every 8 hours (infused over 1 hour) as soon as encephalitis is suspected — do not wait for HSV PCR; continue until HSV and VZV are excluded.

Cover bacterial meningitis until it is excludedBecause bacterial CNS infection is hard to exclude at presentation, give empiric meningitis antibiotics alongside acyclovir until CSF results rule it out.

Contrast MRI: temporal lobe edema in HSVContrast-enhanced MRI is the imaging of choice and shows early orbitofrontal and temporal lobe edema in HSV encephalitis; CT is far less sensitive but quickly excludes contraindications to lumbar puncture.

CSF HSV PCR; repeat if early negativeCSF PCR is the diagnostic test of choice for HSV, but it can be falsely negative early; if suspicion remains, repeat the lumbar puncture in 48–72 hours and keep acyclovir running.

Management

Orders

Send neuronal antibodies in CSF and serumTest for neuronal autoantibodies in CSF as well as serum — serum-only testing risks false-negative and false-positive results — and results can take weeks.

Start immunotherapy before antibody results returnFor probable autoimmune encephalitis, start first-line immunotherapy (high-dose steroids, IVIG or plasma exchange) and the tumor search without waiting for antibody results; remove any teratoma.

Red flags & don'ts

Avoid harm

Relapse after HSV: think anti-NMDA receptor encephalitis complicationClinical decline within weeks of treated HSV encephalitis can be post-infectious anti-NMDA receptor encephalitis; it developed in about 6% of a recent HSV-1 cohort. Test for the antibody.

The rules

Know these

Confirmed HSV: acyclovir for 14–21 daysTreat confirmed HSV encephalitis with IV acyclovir for 14–21 days; stop earlier only when HSV and VZV have been excluded.

HSV or anti-NMDA receptor encephalitis?

Commonly confused

Typical onset	Fever, headache, confusion, seizures
Clue	Olfactory aura; temporal lobe edema on MRI
Confirm with	CSF HSV PCR
Look for	Renal function on acyclovir
Treat with	IV acyclovir 10 mg/kg every 8 hours

More detail

Reference

Show 6 reference facts

Second-line immunotherapy for autoimmune encephalitis is rituximab or cyclophosphamide, most often needed with delayed diagnosis or no tumor.

CSF IgM is more reliable than PCR for West Nile virus; CSF IgG and IgM may detect reactivated VZV better than PCR. Arboviral encephalitis peaks in warm months.

Consider CMV encephalitis in advanced HIV or other immunocompromise; confirm with CSF PCR and treat with ganciclovir.

Acute disseminated encephalomyelitis is post-infectious demyelination 1–3 weeks after an infection or vaccination; treat promptly with glucocorticoids, plus plasma exchange or IVIG.

Brain biopsy is reserved for patients who worsen, respond poorly to acyclovir or have an undiagnosed lesion, and is useful mainly when it targets an MRI abnormality.

Supportive care covers fever, dehydration, euvolemia, electrolyte disorders and seizure control; survivors often have lasting neurologic and cognitive deficits.

Pearl

Acyclovir first, answers later — and an early negative HSV PCR does not end the search.

Sources · Merck Manual Professional — Encephalitis · Acyclovir sodium injection prescribing information — DailyMed · Duerlund LS et al. Herpes Simplex Virus Type 1 Encephalitis: A Prospective Population-Based Cohort Study. Clin Infect Dis 2026;82:e1384–e1392 (recommended duration 14–21 days for confirmed HSV-1) · Graus F et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404 · Barry H et al. Anti-N-methyl-D-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull 2015;39:19–23 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).