01Approach to the Critical Patient/attcp24

Immediate Stabilization

›Airway assessment and protection in encephalopathic patients

›Intubation for GCS <=8 or inability to protect airway

›Aspiration risk in obtunded patients

›Supplemental oxygen to maintain SpO2 >94%

›Hemodynamic monitoring

›IV access with fluid resuscitation for hypovolemia

›Continuous cardiac monitoring for arrhythmia

›Sepsis-mimicking presentation requires early resuscitation

Escalation Triggers

›Criteria for ICU-level care

›Altered mental status with GCS <13

›Recurrent or refractory seizures

›Signs of elevated intracranial pressure

›Autonomic instability

›Respiratory compromise requiring ventilatory support

Key Decision Points

›Time-critical actions in undifferentiated encephalitis

›Empiric IV acyclovir 10 mg/kg every 8 hours while ruling out HSV encephalitis

›Empiric antibiotics if bacterial meningitis cannot be excluded

›CT head before lumbar puncture if focal deficits, papilledema, immunocompromised, or seizure

›Lumbar puncture once mass effect excluded for CSF arboviral and HSV/VZV PCR

Pitfalls

›Common errors in critical presentation

›Anchoring on arboviral diagnosis without excluding treatable HSV encephalitis

›Delaying LP due to concern for elevated ICP without CT confirmation

›Failing to notify public health for suspected arboviral neuroinvasive disease

›Missing arboviral diagnosis outside summer months in irrigated agricultural regions

02History/hx32

Exposure History

›Mosquito exposure and vector risk

›Recent outdoor activity in endemic western or midwestern United States, Canada, or South America

›Agricultural or farming exposure

›Camping or rural residence without mosquito control

›Evening or nighttime outdoor activities during summer months

›Travel to endemic regions within preceding 2-7 days incubation period

Symptom Timeline

›Prodrome and progression pattern

›Febrile prodrome: fever, headache, malaise, anorexia, nausea and vomiting

›Onset of CNS symptoms: confusion, somnolence, personality change, altered mental status

›Progression to encephalitis: seizures, focal neurologic deficits, coma

›Acute onset during mosquito season (May through October in endemic areas)

Associated Symptoms

›Neurologic features

›Headache severity and quality

›Neck pain and stiffness

›Photophobia and phonophobia

›Gait instability or falls

›Behavioral or personality change

›Witnessed seizure activity

›Systemic features

›Fever course and peak temperature

›Myalgia and arthralgia to distinguish other arboviral illnesses

›Rash absence helps distinguish from dengue or West Nile fever

Risk Factors

›High-risk groups for severe neuroinvasive disease

›Infants under 1 year of age with highest case-fatality rate

03Physical Exam/exam28

Vital Signs

›Hemodynamic and temperature assessment

›Fever typically 38-40 degrees Celsius

›Autonomic instability in severe encephalitis: blood pressure lability, tachycardia

›Hypoxia suggesting respiratory compromise or aspiration

Neurologic Examination

›Level of consciousness

›Glasgow Coma Scale score and trend over time

›Orientation to person, place, time, and situation

›Attention and concentration deficits

›Meningeal signs

›Nuchal rigidity with passive neck flexion

›Kernig sign: inability to extend knee with hip flexed

›Brudzinski sign: involuntary hip/knee flexion with neck flexion

›Cranial nerve examination

›Pupillary size, symmetry, and reactivity

›Fundoscopic exam for papilledema suggesting elevated ICP

›Extraocular movement abnormalities

›Motor and sensory exam

›Focal motor deficits or asymmetry

›Tremor, myoclonus, or involuntary movements

›Gait assessment if ambulatory

Skin Examination

›Vector-borne disease clues

›Absence of vesicular rash helps differentiate from HSV or VZV

›Maculopapular rash pattern suggesting alternative arboviral diagnosis

›Tick attachment sites suggesting alternative vector-borne encephalitis

04Differential Diagnosis/ddx19

Infectious Encephalitis

›Highest-priority treatable alternatives

›HSV encephalitis: most common treatable cause; temporal lobe preference on MRI; treat empirically pending PCR

›VZV encephalitis: vesicular rash history; CSF VZV PCR; treat with IV acyclovir

›Bacterial meningitis: bacterial CSF profile; treat empirically with ceftriaxone and vancomycin

›Other arboviral encephalitides

›West Nile neuroinvasive disease: geographic overlap; flaccid paralysis pattern; IgM serology

›Eastern equine encephalitis: higher case-fatality 30-70%; more severe presentation; eastern US geography

›St. Louis encephalitis: older adults predominate; SIADH common; south-central US

›La Crosse encephalitis: children in eastern US; Aedes triseriatus vector

›Powassan encephalitis: tick-borne; northeastern US; year-round risk

Non-Infectious Encephalitis

›Autoimmune and paraneoplastic

›Anti-NMDA receptor encephalitis: psychiatric prodrome; movement disorders; young women

›LGI1 encephalitis: faciobrachial dystonic seizures; hyponatremia; older men

›Paraneoplastic encephalitis: occult malignancy; subacute onset

Non-Encephalitic Mimics

›Structural and metabolic causes

›Intracranial hemorrhage: sudden onset; head CT diagnostic

›Brain abscess: focal deficits; ring-enhancing lesion on MRI

›Toxic-metabolic encephalopathy: reversible with correction of metabolic derangement

›Drug toxicity or withdrawal: medication review; toxicology screening

05Laboratory Tests/lt36

Standard Workup

›Initial blood studies

›Complete blood count: lymphopenia common in early viral illness; thrombocytopenia in some arboviruses

›Complete metabolic panel: hyponatremia from SIADH in severe encephalitis; renal function for drug dosing

›Liver function tests: hepatitis mimics or coinfection

›Blood cultures x2 before antibiotics if bacterial meningitis not excluded

›Procalcitonin: may assist distinction of bacterial versus viral but not definitive

Inflammatory and Serologic Markers

›Infection and autoimmune markers

›ESR and CRP as nonspecific markers of systemic inflammation

›HIV antigen/antibody: immunocompromised state broadens differential

›Autoimmune encephalitis panel (serum): anti-NMDA, LGI1, CASPR2 if clinical concern

Arboviral Serology

›Virus-specific serologic testing

›WEE virus-specific IgM in serum: most sensitive early in neuroinvasive disease

›WEE virus-specific IgG for paired acute/convalescent confirmation (4-fold rise)

›Cross-reactivity with other alphaviruses possible; confirmatory plaque reduction neutralization test

›Submit via CDC or state public health laboratory as commercial testing limited

›PCR testing limitations

›RT-PCR on serum has low sensitivity after viremia clears (typically within first few days)

›CSF RT-PCR sensitivity low for WEE compared to serology

›Early viremic samples have higher RT-PCR yield

Cerebrospinal Fluid Analysis

›CSF interpretation

›Lymphocytic pleocytosis 10-200 cells/microlitre: typical viral encephalitis pattern

›Protein modestly elevated 50-150 mg/dL

›Glucose normal (>50% serum glucose) distinguishes from bacterial meningitis

›Early LP may show normal cell count; repeat in 12-24 hours if index of suspicion remains

06Diagnostic Tests/dt39

Scoring Systems

›Encephalitis severity and clinical decision tools

›No validated WEE-specific bedside scoring tool exists

›GCS as primary severity marker: score <13 indicates severe neurologic compromise

›Encephalitis Consortium criteria for encephalitis diagnosis

›Altered mental status >24 hours as major criterion

›Minor criteria include fever, seizures, focal deficits, CSF pleocytosis, EEG abnormality, neuroimaging abnormality

›Probable encephalitis requires 1 major and 2 minor criteria

›IDSA and ACEP recommend arboviral testing in all encephalitis cases with seasonal or geographic risk

MRI

›Brain MRI indications and findings in WEE

›MRI brain with and without contrast preferred over CT for encephalitis evaluation

›No pathognomonic WEE imaging signature established in evidence

›T2/FLAIR hyperintensity in basal ganglia or thalami reported in some arboviral encephalitides

›HSV encephalitis: temporal lobe and insular cortex T2/FLAIR hyperintensity (high sensitivity for HSV if present)

›Diffusion restriction in acutely edematous regions

›Leptomeningeal enhancement in meningoencephalitis

›Normal MRI does not exclude WEE; repeat in 3-5 days if clinical suspicion persists

CT

›Head CT indications in suspected encephalitis

›Non-contrast CT head before LP when any of the following present

›Immunocompromised state

›Prior CNS disease or shunt

›New-onset seizure

›Papilledema on fundoscopic exam

›Focal neurologic deficit

›Altered level of consciousness with concern for mass lesion

›CT sensitivity for early encephalitis low; normal CT does not exclude diagnosis

07Disposition/dispo22

ICU Admission

›Criteria for ICU-level care

›GCS <13 or rapidly declining level of consciousness

›Active or refractory seizures

›Airway compromise requiring intubation

›Autonomic instability or hemodynamic compromise

›Signs of elevated ICP requiring monitoring or intervention

›Need for continuous EEG monitoring

General Ward Admission

›Criteria for inpatient admission on general neurology or medicine ward

›Any confirmed or suspected encephalitis or meningitis requires admission

›Inability to tolerate oral fluids

›Diagnostic uncertainty requiring LP and monitoring

›Evolving neurologic symptoms without yet meeting ICU criteria

Consultation Requirements

›Specialist involvement

›Infectious diseases: arboviral testing coordination and empiric therapy guidance

›Neurology: seizure management, EEG interpretation, LP guidance

›ICU team: early involvement for potentially deteriorating patients

›Public health notification: mandatory reporting for suspected arboviral neuroinvasive disease

Discharge Criteria

›Safe discharge requires all of the following

›No evidence of CNS involvement after thorough evaluation

›Stable neurologic exam without evolving deficits

›Alternative benign diagnosis established

›Reliable follow-up and return precautions provided

08Treatment/t46

Empiric Therapy for Undifferentiated Encephalitis

›HSV coverage pending diagnostic workup

›IV acyclovir 10 mg/kg every 8 hours in adults

›Adjust for renal impairment: CrCl 25-50 mL/min give every 12 hours; CrCl 10-24 mL/min give every 24 hours

›Infuse over 1 hour with adequate hydration to prevent crystalline nephropathy

›Continue until HSV PCR result available; do not discontinue empirically before result

›Continue empiric bacterial meningitis coverage if CSF Gram stain or culture pending

›Ceftriaxone 2 g IV every 12 hours for meningitis coverage

›Vancomycin 15-20 mg/kg IV every 8-12 hours targeting trough 15-20 mg/L for MRSA coverage

›Dexamethasone 0.15 mg/kg IV every 6 hours x4 days if bacterial meningitis suspected

Antiviral Therapy for WEE

›Disease-specific antiviral treatment

›No approved antiviral therapy exists for WEE

›Supportive care is the mainstay of treatment

›Investigational agents under study but none recommended for routine clinical use

›Discontinue acyclovir once HSV PCR negative and arboviral diagnosis confirmed

Seizure Management

›First-line seizure treatment

›Lorazepam 0.1 mg/kg IV (maximum 4 mg per dose) for acute seizures

›May repeat once after 5 minutes if seizure continues

›Respiratory monitoring and resuscitation equipment at bedside

›Second-line for ongoing seizures or status epilepticus

›Levetiracetam 60 mg/kg IV loading dose (maximum 4500 mg) over 15 minutes

›Alternative: fosphenytoin 20 mg PE/kg IV at maximum 150 mg PE/min with cardiac monitoring

›Alternative: valproic acid 40 mg/kg IV over 10 minutes (avoid in pregnancy)

›Continuous IV antiseizure therapy for refractory status epilepticus

›Midazolam infusion 0.2 mg/kg IV bolus followed by 0.05-2 mg/kg/hour

›Propofol 1-2 mg/kg IV bolus followed by 20-200 mcg/kg/min infusion

09Special Populations/sp37

Pregnancy

›Maternal and fetal considerations in WEE

›Vertical transmission risk of arboviral encephalitis to fetus not well established for WEE specifically

›Multidisciplinary management with maternal-fetal medicine

›Continuous fetal monitoring in viable gestational age

›Maternal seizure management requires modified dosing

›Valproic acid contraindicated in pregnancy due to teratogenicity

›Levetiracetam preferred for seizure management in pregnancy

›Empiric acyclovir dosing unchanged in pregnancy

›Safety profile of acyclovir in pregnancy is established; continue if HSV cannot be excluded

›Mannitol use in pregnancy requires caution; fetal dehydration risk

›Consult MFM before administering osmotic therapy

›Delivery timing individualized based on maternal neurologic status and gestational age

Geriatric

›Age-specific considerations in older adults

›Older adults at increased risk for severe neuroinvasive WEE disease

›Higher case-fatality rate and prolonged recovery compared to younger adults

›Baseline cognitive impairment may obscure encephalopathy recognition

›Altered pharmacokinetics

›Acyclovir dose reduction required for age-related renal impairment

›Benzodiazepine use for seizures increases aspiration and falls risk

›Levetiracetam preferred over phenytoin due to drug interaction profile

›Functional assessment

›Document baseline functional and cognitive status from collateral history

›Early physiotherapy and occupational therapy to prevent deconditioning

›Long-term rehabilitation planning for sequelae

Pediatrics

›Age-specific considerations in infants and children

10Background/b31

Epidemiology

›Disease burden and distribution

›WEE is caused by Western equine encephalitis virus (WEEV), a New World alphavirus in the Togaviridae family

›Overall case-fatality rate approximately 3-15% in symptomatic cases

›Case-fatality higher in infants and older adults

›Most infections subclinical; estimated 1 in 1000 infected adults develop neuroinvasive disease

›Endemic to western and midwestern United States, Canada, and parts of South America

›Transmission peak May through October corresponding to Culex tarsalis mosquito activity

›Equine cases typically precede human cases in outbreak settings

›WEE epidemics dramatically declined in North America since 1980s; resurgence risk persists

›Mandatory reportable disease in all US states; case data collected by ArboNET CDC surveillance

Pathophysiology

›Mechanism of disease

›Vector: Culex tarsalis mosquito primary bridge vector; Culiseta melanura maintains enzootic cycle in birds

›Reservoir hosts: passerine birds and jackrabbits in North American enzootic cycle

›Viremia after mosquito bite with viral dissemination via hematogenous spread

›Neuroinvasion via olfactory epithelium, choroid plexus, or infected monocytes crossing blood-brain barrier

›Direct neuronal infection causing neuronal apoptosis, demyelination, and cerebral edema

›Robust innate and adaptive immune responses contribute to tissue damage

›WEE IgM detectable in serum within 7-10 days of illness onset; CSF IgM indicates neuroinvasion

›Long-term sequelae include cognitive deficits, emotional instability, seizure disorder, and motor deficits

Therapeutic Considerations

›Evidence base for management decisions

›No antiviral therapy has demonstrated clinical efficacy for WEE

›Ribavirin, interferon-alpha, and other candidates have in vitro activity but no human trial evidence

›Supportive care remains standard of care

›Empiric acyclovir recommended in all undifferentiated viral encephalitis pending HSV exclusion

›Delaying HSV treatment increases mortality from approximately 20% to 50-70% in untreated HSV encephalitis

11Patient Discharge Instructions/pdi25

copy discharge instructions

›Discharge information for patients and caregivers

›Diagnosis: you were evaluated for a viral brain infection (encephalitis) related to a mosquito-borne virus called Western equine encephalitis

›Treatment: there is no specific antiviral medication for this infection; your treatment focuses on symptom control and close monitoring

›Activity restrictions

›No driving or operating heavy machinery until cleared by your neurologist

›Avoid alcohol

›Plan for supervised home care if cognition or coordination is impaired

›Mosquito exposure prevention

›Use DEET-containing repellents on exposed skin during outdoor activities

›Wear long sleeves and pants at dawn and dusk when mosquitoes are most active

›Eliminate standing water around home (bird baths, planters, gutters)

›Screen windows and doors to reduce indoor mosquito entry

›Follow-up appointments

›Neurology follow-up within 1-2 weeks of discharge

›Infectious diseases follow-up as directed for convalescent serology if needed

›Primary care follow-up for functional and cognitive reassessment

Return to Emergency Department

›Return immediately to the emergency department for any of the following

›New or worsening confusion or altered behavior

›Seizure or shaking episode

›Sudden severe headache or headache that is worsening

›Vomiting that prevents taking medications or fluids

›New focal weakness, numbness, or speech difficulty

›Increasing sleepiness or difficulty waking

›Fever above 38.5 degrees Celsius that is not responding to acetaminophen

›Any rapid change in neurologic or functional status

12References/r13

Guidelines and Key Sources

›Primary references used in this document

›Tyler KL. Acute Viral Encephalitis. New England Journal of Medicine. 2018. (PMID: 30044931)

›Venkatesan A, Michael BD, Probasco JC, et al. Acute Encephalitis in Immunocompetent Adults. Lancet. 2019. (PMID: 30782344)

›Bloch KC, Glaser C, Gaston D, Venkatesan A. State of the Art: Acute Encephalitis. Clinical Infectious Diseases. 2023. (PMID: 37485952)

›Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update. IDSA and ASM. Clinical Infectious Diseases. 2024.

›Wang L, Zheng R, Li Z, Zhang L. Western Equine Encephalitis Virus: A Comprehensive Review. Virulence. 2025. (PMID: 41178425)

›Coates EE, Edupuganti S, Chen GL, et al. Safety and Immunogenicity of a Trivalent Virus-Like Particle Vaccine Against WEEV, EEEV, and VEEV. Lancet Infectious Diseases. 2022. (PMID: 35568049)

›Ronca SE, Dineley KT, Paessler S. Neurological Sequelae Resulting From Encephalitic Alphavirus Infection. Frontiers in Microbiology. 2016. (PMID: 27379085)

›Binks SNM, Saylor D, Easton A, et al. Encephalitis. Lancet. 2026. (PMID: 42134357)

›Aksamit AJ. Treatment of Viral Encephalitis. Neurologic Clinics. 2021. (PMID: 33223083)

›Whitley RJ, Gnann JW. Viral Encephalitis: Familiar Infections and Emerging Pathogens. Lancet. 2002. (PMID: 11853816)

›Reyna RA, Weaver SC. Sequelae and Animal Modeling of Encephalitic Alphavirus Infections. Viruses. 2023. (PMID: 36851596)

›Zacks MA, Paessler S. Encephalitic Alphaviruses. Veterinary Microbiology. 2010. (PMID: 19775836)

Evidence & Review

Evidence & Review