01Approach to the Critical Patient/attcp27

Airway and Breathing

›Airway assessment priorities

›Bulbar dysfunction (dysarthria, dysphagia) indicating impending airway loss

›Declining GCS with loss of airway protective reflexes

›Early intubation for GCS <8 or inability to protect airway

›RSI preferred; avoid succinylcholine if acute flaccid myelitis with hyperkalemia risk

›Respiratory monitoring in acute flaccid myelitis

›Serial negative inspiratory force (NIF) and forced vital capacity (FVC)

›NIF less negative than -25 cmH2O or FVC <1 L triggers intubation

›Diaphragmatic or intercostal paralysis may develop rapidly over 24-48 hours

Hemodynamic Goals

›Hemodynamic targets

›Mean arterial pressure >65 mmHg

›Heart rate and blood pressure monitoring for autonomic instability

›IV fluid resuscitation for dehydration from GI losses or poor oral intake

Initial Stabilization

›Time-critical actions

›Empiric acyclovir 10 mg/kg IV q8h within 30 minutes for undifferentiated encephalitis

›Immediate LP if no contraindication; CT head first if focal deficits or papilledema

›Fingerstick glucose and bedside metabolic screen to exclude toxic-metabolic cause

›IV access x2, cardiac monitoring, continuous pulse oximetry, supplemental oxygen

›Escalation triggers

›ICU activation for encephalitis with GCS <13, seizures, or respiratory compromise

›Neurology consultation for all neuroinvasive West Nile virus cases

›Infectious disease consultation emergently

Key Decision Points

›Critical diagnostic forks

›Distinguish acute flaccid myelitis (asymmetric, areflexic, sensory-spared) from GBS (symmetric, demyelinating, sensory-involved)

02History/hx48

Onset and Timeline

›Abrupt onset of neurologic symptoms

›Incubation period 2-14 days after mosquito bite [1]

›Peak season July through September (Culex mosquito activity)

›Prodrome of fever, headache, fatigue, myalgia, nausea and vomiting preceding neurologic symptoms by days [4]

Neurologic Symptoms

›Core neurologic features

›Confusion, disorientation, stupor, personality change lasting >24 hours [1]

›Tremor (coarse, postural, predominantly upper extremities)

›Myoclonus (upper extremities and facial muscles, may persist during sleep)

›Ataxia and gait instability

›Asymmetric limb weakness progressing over 24-48 hours (acute flaccid myelitis)

›Dysarthria and dysphagia suggesting bulbar involvement

›Seizures (present in 3-6% of WNV encephalitis cases) [1]

Exposures and Risk Factors

›Epidemiologic exposures

›Outdoor activity during dusk-to-dawn hours in endemic area

›Geographic location with known WNV transmission activity

›Recent travel to endemic region

›Occupational outdoor exposure (agricultural workers, outdoor laborers)

›Transmission-related exposures

›Recent blood transfusion (longer incubation median 13.5-15 days) [1]

›Recent organ transplantation (longer incubation, more subtle presentation)

Past Medical and Immunologic History

›Immunocompromised state

›Solid organ transplant status and current immunosuppressive regimen

›Hematologic malignancy (lymphoma, leukemia)

›B-cell-depleting monoclonal antibody therapy (rituximab)

03Physical Exam/exam32

Vital Signs

›Vital sign patterns

›Fever in 88% of neuroinvasive cases [4]

›Tachycardia common; may reflect fever or autonomic dysregulation

›Hypotension or hypertension suggesting autonomic instability or myocarditis

Mental Status

›Level of consciousness

›GCS score documented serially

›Confusion, disorientation, stupor, coma spectrum

›Personality change or behavioral disturbance

Movement Disorder Findings

›Extrapyramidal signs (highly characteristic of WNV encephalitis) [1]

›Coarse postural tremor predominantly in upper extremities

›Myoclonus of upper extremities and facial muscles

›Rigidity and bradykinesia (parkinsonian features)

›Cerebellar ataxia and dysmetria

Cranial Nerve Exam

›Cranial nerve findings

›Facial weakness (often bilateral)

›Dysarthria and dysphonia

›Dysphagia and absent gag reflex indicating bulbar dysfunction

›Nystagmus or extraocular movement abnormalities

Motor Exam

›Motor findings in acute flaccid myelitis

›Asymmetric flaccid limb weakness

›Areflexia or hyporeflexia

›Preserved sensation (distinguishes from GBS)

›Fasciculations (anterior horn cell involvement)

04Differential Diagnosis/ddx28

Viral Encephalitides

›Arboviral and herpesviral causes

›Herpes simplex encephalitis (HSV-1): temporal lobe predilection on MRI, hemorrhagic CSF; empiric acyclovir mandatory

›Eastern equine encephalitis: severe course, high mortality, basal ganglia and thalamic involvement, geographic/seasonal overlap

›St. Louis encephalitis: closely related flavivirus, serologic cross-reactivity with WNV

›Powassan virus encephalitis: tick-borne flavivirus, rapidly progressive

›La Crosse encephalitis: predominantly pediatric, California serogroup

›Enteroviral meningoencephalitis: especially children, summer-fall seasonality, CSF lymphocytosis

Bacterial and Fungal Causes

›Non-viral CNS infections

›Bacterial meningitis: neutrophilic pleocytosis, low CSF glucose, Gram stain positive, rapid deterioration

›Tuberculous meningitis: subacute course, basilar meningeal enhancement, low CSF glucose

›Listeria meningoencephalitis: elderly and immunocompromised, rhombencephalitis pattern

›Cryptococcal meningitis: immunocompromised host, India ink positive, elevated opening pressure

Autoimmune and Inflammatory Causes

›Non-infectious encephalitides

›Anti-NMDAR encephalitis: psychiatric prodrome, movement disorders, younger patients, antibody testing required [8]

›Voltage-gated potassium channel complex encephalitis

›Acute disseminated encephalomyelitis (ADEM): post-infectious, white matter predominant

Metabolic and Structural Causes

›Non-infectious differentials

›Hepatic encephalopathy: elevated ammonia, asterixis, liver disease history

›Uremic encephalopathy: elevated creatinine and BUN

›Drug or alcohol toxicity: medication review, toxicology screen

›CNS lymphoma: immunocompromised, periventricular lesions, positive CSF cytology

›Carcinomatous meningitis: malignancy history, positive CSF cytology

Key Distinguishing Features of WNV Encephalitis

›WNV-specific clinical pattern

05Laboratory Tests/lt34

Cerebrospinal Fluid Analysis

›CSF findings in WNV encephalitis [1]

›Pleocytosis: mean 226 WBC/mm3 (range 1-7,950); lymphocytic predominance

›Early infection may show neutrophilic predominance before lymphocytic shift

›Protein: elevated, mean 101 mg/dL in encephalitis vs 76 mg/dL in meningitis

›Glucose: normal (distinguishes from bacterial and TB meningitis)

›Opening pressure: may be elevated; measure routinely

›WNV-specific CSF serology

›WNV IgM in CSF confirms CNS infection; IgM does not cross intact blood-brain barrier [1]

›Sensitivity >98% by day 8 of illness

›Initial negative IgM: repeat testing on or after day 8 if clinical suspicion persists

›CSF WNV RT-PCR

›Sensitivity 63% in immunocompromised vs 15% in immunocompetent patients [5]

›Send in all cases; more useful in transplant and immunosuppressed populations

Serum WNV Serology

›Blood-based WNV diagnostics

›WNV IgM serum: sensitive but does not confirm CNS involvement

›WNV IgG serum: presence without IgM indicates past (not acute) infection [1]

›Confirmatory PRNT (plaque reduction neutralization test): required for cross-reactive flavivirus exposures, atypical presentations, or suspected transplant-transmitted cases [1]

›IDSA/ASM 2024 microbiology lab guidance supports PRNT for flavivirus confirmation [13]

Routine Blood Work

›Hematologic and metabolic panel

›Complete blood count: WBC usually normal or mildly elevated

›Comprehensive metabolic panel: hyponatremia (SIADH), renal function, hepatic panel

›Blood cultures to exclude bacterial meningitis

›C-reactive protein and erythrocyte sedimentation rate (nonspecific, may be elevated)

›Rule-out testing panel

›HSV PCR (CSF and serum) — mandatory in all undifferentiated encephalitis

06Diagnostic Tests/dt37

Scoring Systems

›Clinical severity and prognostic tools

›GCS score: primary severity marker; GCS <13 indicates encephalitis rather than meningitis

›No validated WNV-specific severity score exists; general encephalitis prognostic factors apply

›Pooled ICU admission rate 42.1% in neuroinvasive disease [4]

›Pooled mortality 9.2% overall; 20% in age >=70; 30-40% in hematologic malignancy or transplant recipients [1]

›MRI signal abnormalities, meningeal involvement, and spinal cord involvement independently predict worse outcome [1]

MRI

›Brain MRI findings in WNV encephalitis

›Study of choice for neuroimaging; preferred over CT for parenchymal assessment

›Normal MRI in up to 30-37% of cases despite clinical encephalitis [1]

›T2/FLAIR hyperintensities: brainstem, thalami, basal ganglia, mesial temporal structures, cerebellum [5]

›Bilateral thalamic involvement: strong suspicion for WNV (shared pattern with Japanese encephalitis serocomplex) [12]

›Diffusion restriction (DWI): present in up to 50% of cases

›Leptomeningeal enhancement on post-gadolinium sequences

›Spinal MRI for acute flaccid myelitis

›T2/FLAIR hyperintensity in anterior horns (central grey matter pattern)

›Conus medullaris and cauda equina enhancement

›Anterior horn predominance distinguishes WNV myelitis from transverse myelitis

CT

›CT head indications and limitations

›CT head performed before LP if focal neurologic deficits, papilledema, GCS <13, immunocompromise, or new seizure

›CT often normal in WNV encephalitis; insufficient to exclude disease

›Useful to exclude mass lesion, hemorrhagic transformation, or herniation before LP

›CT chest if respiratory compromise or atypical clinical picture

Ultrasound

›Bedside ultrasound applications

›Cardiac point-of-care ultrasound (POCUS) for hemodynamically unstable patients

07Disposition/dispo31

ICU Admission Criteria

›Indications for ICU-level care

›All encephalitis patients with altered mental status (GCS <13)

›Acute flaccid myelitis with any respiratory compromise (NIF less negative than -25 cmH2O)

›Active seizures or non-convulsive status epilepticus

›Hemodynamic instability or suspected myocarditis

›Autonomic instability

›Inability to protect airway or requirement for mechanical ventilation

Inpatient Floor Admission

›Floor admission criteria

›WNV meningitis without encephalopathic features

›Stable vital signs and GCS >=13

›Able to maintain adequate oral hydration

›No respiratory compromise

›Reliable outpatient follow-up not feasible given severity

Consultation Requirements

›Required specialist consultations

›Neurology: all neuroinvasive WNV cases

›Infectious disease: all neuroinvasive WNV cases

›Pulmonology/critical care: respiratory failure or anticipated intubation

›Ophthalmology: chorioretinitis, uveitis, or visual symptoms

›Cardiology: suspected myocarditis or hemodynamic instability [12]

›Physical medicine and rehabilitation: early involvement for motor deficits

›Transplant team: reduce immunosuppression in transplant recipients

Discharge Criteria

›Safe discharge requirements

›Resolving mental status, GCS 15 and baseline cognitive function

›Stable neurologic exam without progressive weakness

08Treatment/t39

Empiric Antiviral Therapy

›HSV coverage until exclusion

›Acyclovir IV 10 mg/kg q8h for undifferentiated encephalitis [8]

›Continue until HSV CSF PCR returns negative

›Adjust dose for renal impairment: CrCl 25-50 mL/min give q12h; CrCl 10-25 mL/min give q24h

›Adequate IV hydration to prevent acyclovir nephrotoxicity

›No approved antiviral therapy exists specifically for WNV [1]

Supportive Care

›Core supportive measures

›IV fluid resuscitation for dehydration; maintenance IVF for NPO patients

›Aspiration precautions and formal swallow evaluation before oral feeding in patients with bulbar dysfunction [1]

›DVT prophylaxis with low molecular weight heparin in non-ambulatory patients

›Stress ulcer prophylaxis in mechanically ventilated or critically ill patients

›Glycemic control with target glucose 7.8-10 mmol/l in ICU patients

›Fever management with acetaminophen or NSAIDs

Seizure Management

›Acute seizure treatment

›Lorazepam IV 0.1 mg/kg (typically 4 mg IV) for active seizures; may repeat once [9]

›Diazepam IV 5-10 mg if lorazepam unavailable

›Midazolam IM 10 mg as alternative if no IV access

›Levetiracetam IV for seizure prophylaxis or recurrent seizures

›Loading dose 60 mg/kg IV (max 4,500 mg) for status epilepticus

›Maintenance 1,000-3,000 mg/day in divided doses

›Avoid phenytoin in encephalitis if alternative agents available (sodium channel blockade, drug interactions)

Investigational Therapies (Not Recommended Routinely)

›Therapies without proven efficacy

›IVIG: no proven benefit in controlled studies; not recommended outside clinical trials [1]

›High-titer WNV immune globulin: studied in Omr-IgG-am trial, no clinical benefit demonstrated [9]

09Special Populations/sp30

Pregnancy

›WNV in pregnancy considerations

›Vertical transmission documented; risk to fetus not fully quantified [11]

›Case reports of intrauterine WNV infection with fetal brain abnormalities

›Fetal MRI warranted if maternal WNV neuroinvasive disease confirmed

›Acyclovir use in pregnancy

›Acyclovir category B; considered safe for empiric use in pregnant encephalitis patients

›No specific WNV antiviral available; supportive care mainstay

›Corticosteroid avoidance particularly important given mortality risk [7]

›Obstetrics consultation and fetal monitoring for all pregnant patients with neuroinvasive WNV

Geriatric

›Age-related risk and management modifications

›Age >=50 years: strongest risk factor for neuroinvasive disease and death [1]

›Mortality 20% in age >=70 years vs 9.2% pooled overall [1]

›Incidence and case-fatality rate increase markedly with advancing age

›Cognitive baseline assessment critical for GCS interpretation

›Collateral history from family or caregiver essential

›Prior cognitive impairment may mask severity of encephalopathy

›Comorbidity burden amplifies mortality risk

›CKD, hypertension, and diabetes disproportionately prevalent in older adults [4]

›Aspiration risk higher; early swallow assessment and nasogastric feeding if needed

›DVT and pressure ulcer prophylaxis critical in immobilized elderly patients

Pediatrics

›WNV in pediatric patients

›Neuroinvasive disease rare but reported; spectrum similar to adults [11]

›Seizures may be more prominent presenting feature than in adults

›Encephalitis, meningitis, and acute flaccid myelitis all reported

›Fever and headache common; altered mental status requiring evaluation

10Background/b37

Epidemiology

›Epidemiologic data

›WNV is leading cause of mosquito-borne encephalitis in the United States [1]

›Approximately 1,300 neuroinvasive cases and 129 deaths reported annually in the US [1]

›80% of infections asymptomatic; approximately 20% cause WNV fever; <1% develop neuroinvasive disease [1]

›Neuroinvasive disease mortality approximately 9.2% overall [4]

›Mortality rises to 20% in age >=70 years and 30-40% in immunocompromised patients [1]

›Geographic distribution: widespread across North America, Europe, Africa, Middle East, Asia

›Seasonal peak July through September in temperate climates [1]

›Transmission routes: Culex mosquito bite (primary); blood transfusion; organ transplantation; intrauterine; breast milk (rare)

›Long-term sequelae >50%: fatigue 37-75%, memory loss 11-57%, concentration deficits 17-48%, depression 17-38%, muscle weakness 7-73% [1]

Pathophysiology

›Disease mechanism

›Neurotropic flavivirus (single-stranded RNA virus, Flaviviridae family) [11]

›Inoculation via Culex mosquito saliva during blood meal

›Initial replication in skin dendritic cells and local lymph nodes

›Seeding of spleen, lymph nodes, and visceral organs during primary viremia

›CNS invasion via hematogenous spread across blood-brain barrier or transaxonal transport

›Neuronal tropism

›Predilection for neurons of thalami, basal ganglia, brainstem, anterior horn cells

›Direct viral cytopathic effect and inflammatory neuronal necrosis

›Microglial activation and lymphocytic infiltration contribute to pathology

›Genetic susceptibility

›CCR5 delta32 polymorphism associated with increased neuroinvasive risk [11]

›Homozygous CCR5 delta32 deletion disrupts antiviral chemokine response

›Acute flaccid myelitis mechanism

›Anterior horn cell necrosis leading to lower motor neuron syndrome

›Motor-specific involvement with spared sensory neurons

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Discharge instructions for West Nile Virus Encephalitis

›What happened: you were diagnosed with West Nile virus encephalitis, a brain infection spread by mosquito bites

›No cure or specific antiviral treatment exists; the body clears the infection over weeks to months

›Recovery can take months; fatigue, memory problems, and weakness are common and may persist

›Medications after discharge

›Take all prescribed medications exactly as directed

›Do not stop anti-seizure medications without physician guidance

›Avoid alcohol, sedatives, and medications that lower seizure threshold

›Activity restrictions

›No driving until cleared by your neurologist (seizure risk)

›No operating heavy machinery or working at heights

›Rest and gradual return to activity as tolerated

›Mosquito bite prevention

›Use EPA-registered insect repellents (DEET, picaridin, IR3535) on exposed skin when outdoors

›Wear long sleeves and pants during peak mosquito hours (dusk to dawn)

›Eliminate standing water around home (breeding sites)

›No human WNV vaccine is currently available [1]

›Transmission information

›West Nile virus is not spread person to person through casual contact

›Do not donate blood or organs after recent WNV infection

›Follow-up appointments

›Neurology follow-up within 2-4 weeks of discharge

›Earlier follow-up if any new or worsening symptoms develop

›Rehabilitation (physical, occupational, speech therapy) as recommended

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

›Worsening confusion, decreased alertness, or inability to wake

›New seizure or prolonged shaking episode

12References/r16

Guidelines and Key Sources

›Primary references

›Gould CV, Staples JE, Guagliardo SAJ, et al. West Nile Virus. JAMA. 2025. [1]

›West Nile Virus Surveillance and Control Guidelines. CDC. 2025. [2]

›Petersen LR, Brault AC, Nasci RS. West Nile Virus: Review of the Literature. JAMA. 2013. [3]

›Roberts JA, Kim CY, Hwang SA, et al. Clinical, Prognostic, and Longitudinal Features of WNV Neuroinvasive Disease. Annals of Neurology. 2025. [4]

›Mbonde AA, Gritsch D, Harahsheh EY, et al. Neuroinvasive WNV Infection in Immunosuppressed and Immunocompetent Adults. JAMA Network Open. 2024. [5]

›Tetaj N, Bocci MG, Capecchi G, et al. WNV Neuroinvasive Disease and Cardiac Involvement in Critically Ill Patients. Frontiers in Medicine. 2026. [6]

›Poran I, Basharim B, Leibovici-Weissman Y, et al. Impact of Corticosteroid Therapy on Patients With West Nile Virus. J Infect Dis. 2026. [7]

›Bloch KC, Glaser C, Gaston D, Venkatesan A. State of the Art: Acute Encephalitis. Clin Infect Dis. 2023. [8]

›Venkatesan A, Michael BD, Probasco JC, Geocadin RG, Solomon T. Acute Encephalitis in Immunocompetent Adults. Lancet. 2019. [9]

›Kasule SN, Gupta S, Patron RL, Grill MF, Vikram HR. Neuroinvasive West Nile Virus Infection in Solid Organ Transplant Recipients. Transplant Infect Dis. 2023. [10]

›Zerbato V, Rossi B, Di Bella S, et al. West Nile Virus: Epidemiology, Prevention, Clinical Features, Diagnosis, Treatment. Annals of Medicine. 2026. [11]

›Guth JC, Futterer SA, Hijaz TA, et al. Bilateral Thalamic Involvement in West Nile Virus Encephalitis. Neurology. 2014. [12]

›Miller JM, Binnicker MJ, Campbell S, et al. IDSA/ASM Guide to Utilization of the Microbiology Laboratory 2024 Update. Clin Infect Dis. 2024. [13]

›Binks SNM, Saylor D, Easton A, Thakur KT, Irani SR. Encephalitis. Lancet. 2026. [14]

›Drazner MH, Bozkurt B, Cooper LT, et al. 2024 ACC Expert Consensus Decision Pathway on Myocarditis. JACC. 2025. [16]

Evidence & Review

Evidence & Review