01Approach to the Critical Patient/attcp76

Immediate priorities

›Airway and mental status threats

›Declining GCS or inability to protect airway

›GCS <= 8 is threshold for definitive airway

›Rapid sequence intubation preparation

›Pre-oxygenate before induction

›Status epilepticus

›Continuous or prolonged seizure activity

›Non-convulsive status epilepticus on EEG

›Herniation signs

›Fixed and dilated pupils

›Decerebrate or decorticate posturing

›Cushing triad: hypertension, bradycardia, irregular respirations

›Hemodynamic and respiratory stabilization

›Shock physiology

›SBP < 90 mmHg or MAP < 65 mmHg

›IV fluid resuscitation with isotonic crystalloid

›Respiratory failure

›SpO2 < 92% on room air

›Aspiration risk from reduced consciousness mandates airway caution

›Fever management

›High fever worsens neuronal injury

›Antipyretics to target normothermia

›Empiric treatment before diagnostic confirmation

›Acyclovir 10 mg/kg IV every 8 hours empirically for HSV encephalitis until excluded

›Class I recommendation; do not delay pending LP or MRI results

›Continue until CSF HSV PCR returns negative

›Empiric antibacterial coverage if bacterial meningitis cannot be excluded

02History/hx68

Symptom onset and timeline

›Prodromal phase

›Incubation period 5-15 days after mosquito bite

›Range reported as 2-14 days

›Exact bite date often unknown

›Febrile prodrome 1-7 days before neurologic onset

›Fever, headache, malaise, myalgia

›Nausea and vomiting common

›Neurologic progression

›Confusion and disorientation

›Onset typically rapid over hours to days

›Delirium pattern common in elderly

›Tremor and movement abnormalities

›Parkinsonian-type tremor correlates with substantia nigra involvement

›Ataxia and unsteadiness

›Seizures

›Focal or generalized

›May present as subtle motor movements in obtunded patients

›Constitutional symptoms

›Fever pattern

›Often high and persistent

›Rigors may accompany

›Anorexia and weight loss

›Common in SLE compared to other arboviruses

›Retro-orbital pain and photophobia

Exposure and risk factors

›Mosquito exposure history

›Outdoor activity at dusk or dawn

03Physical Exam/exam61

Neurologic assessment

›Consciousness and cognition

›GCS score

›Motor, verbal, eye-opening components documented separately

›Serial GCS to trend trajectory

›Orientation and attention

›Person, place, time, situation

›Attention testing: digit span or month-backward

›Speech and language

›Dysarthria suggests brainstem or cerebellar involvement

›Aphasia suggests cortical involvement

›Motor and movement examination

›Tremor characterization

›Resting tremor consistent with parkinsonian-type SLE

›Action tremor vs. resting tremor distinction

›Tone and strength

›Hypertonia in basal ganglia involvement

›Acute flaccid paralysis suggests anterior horn cell involvement

›Cerebellar signs

›Finger-nose-finger dysmetria

›Heel-shin ataxia

›Tandem gait

›Cranial nerve examination

›Pupillary size and reactivity

›Asymmetry suggests uncal herniation

›Fixed dilated pupil is emergency

›Extraocular movements

›Nystagmus with cerebellar involvement

04Differential Diagnosis/ddx61

Viral encephalitides

›West Nile virus encephalitis

›Most important clinical mimic of SLE

›Clinically indistinguishable presentation

›Serologic cross-reactivity makes differentiation challenging

›PRNT required for definitive differentiation

›Distinguishing features favoring WNV

›Maculopapular rash more common in WNV (33-50% vs 7% in SLE)

›Flaccid paralysis more characteristic of WNV

›Herpes simplex encephalitis (HSV-1)

›Critical to exclude; specific antiviral therapy available

›Temporal lobe predilection on MRI (hemorrhagic T2 signal)

›CSF may have red blood cells

›CSF HSV PCR is diagnostic standard

›Empiric acyclovir mandatory until excluded

›Other arboviral encephalitides

›Eastern equine encephalitis

›Higher case fatality rate (30-70%)

›More fulminant course

›La Crosse encephalitis

›Primarily in children

›Midwestern US distribution

›Powassan virus

›Tick-borne, not mosquito-borne

›More severe; 10-15% case fatality rate

Bacterial and other infections

›Bacterial meningitis/meningoencephalitis

›Distinguishing features

05Laboratory Tests/lt63

CSF analysis

›Lumbar puncture with opening pressure

›Opening pressure measurement

›Elevated in approximately 30% of SLE patients

›Normal is 7-18 cmH2O (lateral decubitus)

›Elevation suggests cerebral edema or ventricular outflow obstruction

›Cell count and differential

›Lymphocytic pleocytosis typical (10-200 cells/microL)

›Neutrophils may predominate in first 24-48 hours

›Very high WBC (> 500) suggests bacterial etiology

›Protein

›Mildly elevated (50-100 mg/dL)

›Very high protein suggests bacterial or fungal etiology

›Glucose

›Normal in viral encephalitis

›CSF to serum glucose ratio > 0.6 expected

›Xanthochromia

›Absent in SLE

›Presence suggests HSV or SAH

CSF microbiology and virology

›CSF PCR panel

›HSV-1 and HSV-2 PCR

›Sensitivity 96-98% for HSV encephalitis

›Negative PCR at > 72 hours from onset effectively excludes HSV

›VZV PCR

›Detects VZV vasculitis and encephalitis

›Enterovirus PCR

›Common cause of viral meningitis in summer months

06Diagnostic Tests/dt88

Scoring Systems

›Glasgow Coma Scale (GCS) for severity stratification

›GCS 13-15: mild neurologic impairment

›May be appropriate for monitored ward admission

›Serial reassessment mandatory

›GCS 9-12: moderate impairment

›High dependency or step-down care

›Strong consideration for ICU monitoring

›GCS <= 8: severe impairment

›ICU admission mandatory

›Definitive airway management required

›Infectious Diseases Society of America (IDSA) Encephalitis Criteria

›Encephalitis diagnostic criteria

›Altered mental status > 24 hours

›Plus at least 2 of: fever, seizures, new focal neurologic signs, CSF pleocytosis, EEG changes, MRI changes

›Supports systematic diagnostic approach

›Guides which patients require full encephalitis workup

›Bloch et al., Clinical Infectious Diseases 2023

›Encephalitis severity grading

›Mild: fever plus headache, no AMS

›Febrile illness or aseptic meningitis presentation

›Moderate: altered mental status without coma

›Severe: coma, status epilepticus, or respiratory failure

MRI

›MRI brain with and without gadolinium contrast

›Preferred imaging for encephalitis

›Superior to CT for detecting parenchymal inflammation

›Recommended before LP if any signs of elevated ICP or mass effect

›Sequences: T1, T2, FLAIR, DWI, GRE or SWI, T1 post-contrast

›SLE-specific findings

›T2/FLAIR hyperintensities in deep grey matter

›Thalamic and basal ganglia involvement most characteristic

›Substantia nigra hyperintensity correlates with parkinsonian tremor

›MRI may be normal early in course

›Negative MRI does not exclude diagnosis

›Repeat MRI at 48-72 hours if initial scan unremarkable

›Leptomeningeal enhancement

›Gadolinium enhancement patterns

›Leptomeningeal enhancement indicates meningeal inflammation

›Parenchymal enhancement in more severe cases

›Enhancement pattern helps differentiate from HSV (temporal lobe)

›DWI and ADC sequences

›Diffusion restriction interpretation

›Cytotoxic edema in acute severe involvement

›Vasogenic edema more common in SLE

›Restricted DWI with high ADC suggests vasogenic edema

CT

›CT head without contrast (initial triage)

›Primary indications

›Exclude hemorrhage before LP

›Exclude mass lesion or herniation before LP

›Rapidly available in emergency setting

›Limitations in SLE

›CT is typically normal in acute viral encephalitis

›Low sensitivity for early parenchymal changes

›Does not replace MRI for parenchymal evaluation

›CT head with contrast

›When MRI contraindicated or unavailable

›Claustrophobia, metallic implants, pacemaker

›May show subtle enhancement in severe cases

›CT findings in advanced disease

›Cerebral edema with sulcal effacement

›Hypodensity in deep grey structures in severe cases

›CT criteria for safe LP

›Absent mass lesion

›No midline shift

›No obliteration of basal cisterns

›No uncal herniation

›IDSA recommendation

›CT required before LP in patients with focal deficits, papilledema, GCS < 13, or immunocompromise

Ultrasound

›Bedside ultrasound in SLE management

›Optic nerve sheath diameter (ONSD) measurement

›ONSD > 5 mm suggests elevated ICP

›Rapid non-invasive ICP surrogate in emergency setting

›Can be performed at bedside without radiation

›Transcranial Doppler (TCD)

›Cerebral blood flow velocity assessment

›Pulsatility index elevation correlates with elevated ICP

›Point-of-care ultrasound for procedural guidance

›Lumbar puncture guidance

›Ultrasound to identify interspinous space

›Particularly useful in obese patients or abnormal anatomy

›Vascular access

›Ultrasound-guided central line placement

›Ultrasound-guided peripheral IV access

›Lung ultrasound for complications

›Aspiration pneumonia surveillance

›B-lines suggest pulmonary edema or consolidation

›Subpleural consolidation with air bronchograms suggests pneumonia

›Pleural effusion detection

›Small effusions not visible on chest X-ray

07Disposition/dispo39

ICU admission criteria

›Indications for ICU level care

›GCS <= 8 or rapidly declining consciousness

›Requires airway management and continuous monitoring

›Continuous EEG monitoring indicated

›Status epilepticus

›Refractory to initial benzodiazepine therapy

›Continuous EEG mandatory

›Respiratory failure

›Mechanical ventilation requirement

›SpO2 < 88% despite supplemental oxygen

›Hemodynamic instability

›Vasopressor requirement

›Suspected sepsis physiology

Ward or monitored admission criteria

›Neuroinvasive disease without critical illness

›All confirmed or suspected SLE encephalitis

›Altered mental status without coma

›Seizure with return to baseline

›Inability to tolerate oral intake

›SLE meningitis

›Headache, fever, meningism without AMS

›Pending diagnostic confirmation

›Pending diagnostic workup

›CSF results awaited

›Acyclovir empirically initiated

Transfer criteria

›Transfer to higher level of care

08Treatment/t103

Empiric antiviral and antibacterial therapy

›Acyclovir (empiric HSV coverage)

›Dosing

›10 mg/kg IV every 8 hours

›Infuse over 1 hour

›Renal dose adjustment required

›Duration

›Continue until CSF HSV PCR confirmed negative

›Minimum 2-3 days before discontinuation if clinical improvement

›Rationale

›HSV encephalitis has specific effective therapy

›Mortality untreated HSV encephalitis approaches 70%

›IDSA guideline: Class I recommendation

›Empiric antibacterial therapy

›When bacterial meningitis not excluded

›Ceftriaxone 2 g IV every 12 hours

›Add ampicillin 2 g IV every 4 hours if Listeria risk (age > 50, immunocompromised, pregnancy)

›Dexamethasone 0.15 mg/kg IV every 6 hours for 4 days if S. pneumoniae suspected

›Discontinue when bacterial etiology excluded

›Negative blood cultures and negative CSF Gram stain/culture

›CSF consistent with viral pattern

Seizure management

›First-line seizure treatment

›Benzodiazepines for acute seizure termination

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

›May repeat once after 5 minutes

›Midazolam 10 mg IM if no IV access

›Second-line antiepileptic loading

›Levetiracetam 60 mg/kg IV (maximum 4500 mg)

›Infuse over 15 minutes

›Preferred due to lack of drug interactions and ease of titration

›Alternative second-line options

›Valproic acid 40 mg/kg IV (maximum 3000 mg) over 10 minutes

›Fosphenytoin 20 mg PE/kg IV at maximum 150 mg PE/min

›Refractory status epilepticus

›Third-line continuous infusion therapy

›Midazolam 0.2 mg/kg IV bolus then 0.05-2 mg/kg/hour continuous infusion

›Titrate to seizure suppression on continuous EEG

›Propofol as alternative

›1-2 mg/kg IV bolus then 1-15 mg/kg/hour infusion

›Monitor for propofol infusion syndrome in prolonged use

›Phenobarbital if midazolam and propofol fail

›20 mg/kg IV at maximum 60 mg/min

›Long-term antiepileptic therapy

›Levetiracetam maintenance dosing

›500-1500 mg IV or orally twice daily

›Continue for minimum 3-6 months after acute encephalitis

›Neurology guidance for tapering schedule

Supportive care

›ICP management

›Head of bed 30-45 degrees elevation

›Avoids Trendelenburg position

›Optimizes cerebral venous drainage

›Osmolar therapy for elevated ICP

›Mannitol 0.25-1 g/kg IV bolus

›Repeat every 6-8 hours as needed

›Target serum osmolality 300-320 mOsm/kg

›Hypertonic saline 3% 100-250 mL IV bolus as alternative

›Monitor serum sodium closely

›Target sodium 145-155 mmol/l in cerebral edema

›Fever management

›Acetaminophen 650-1000 mg orally or rectally every 6 hours

›First-line antipyretic

›Target normothermia; hyperthermia worsens neuronal injury

›Ibuprofen 400-600 mg orally every 6-8 hours as alternative

›Avoid in renal impairment

›Avoid in dehydrated patients

›Cooling blanket for refractory hyperthermia

›Core temperature target < 38 C

›SIADH management

›Fluid restriction

›Restrict free water to 800-1000 mL per day

›Avoid hypotonic IV fluids

›Sodium monitoring

›Serum sodium every 4-6 hours in acute phase

›Correct hyponatremia cautiously; avoid rapid correction > 8-10 mmol/l per 24 hours

›Isotonic saline for mild hyponatremia (sodium 125-134 mmol/l)

›Hypertonic saline 3% for symptomatic or severe hyponatremia (sodium < 125 mmol/l)

›Rate: 1-2 mL/kg/hour

›Stop infusion when sodium rises by 4-6 mmol/l or symptoms resolve

Investigational and adjunctive therapies

›Interferon alpha-2b

›Anecdotal evidence only

›Pilot study (Rahal et al. 2004): reduced severity and duration in small cohort

›Case reports in solid organ transplant recipients

›No randomized controlled trial data

›Dosing used in case reports

›IFN-alpha2b 5-10 million units subcutaneously daily

›Duration varied; continued until clinical improvement

›Reserved for severe or immunocompromised cases pending ID consultation

›Intravenous immunoglobulin (IVIG)

›Limited evidence in SLE

›Theoretical benefit from flavivirus-neutralizing antibodies in pooled immunoglobulin

›Used in transplant recipients with good outcomes in case series

›Dosing if used

›0.4 g/kg IV daily for 5 days

›Or 1 g/kg IV for 2 days

›Not routinely recommended; ID consultation required

›Agents to avoid

›Corticosteroids

›No proven benefit in arboviral encephalitis

›May worsen viral replication

›Use only if autoimmune encephalitis remains in differential

›Ribavirin

›Used empirically in some WNV cases without proven benefit

›No evidence supports use in SLE

›Not recommended

09Special Populations/sp89

Pregnancy

›Epidemiology and risk in pregnancy

›SLE in pregnancy is rare but reported

›No specific data on pregnancy-associated SLEV infection rates

›Vertical transmission has been documented with other flaviviruses (Zika)

›Risk of vertical SLEV transmission not well quantified

›Immunologic changes in pregnancy

›Relative immunosuppression may increase susceptibility to neuroinvasive disease

›Altered inflammatory response may modify clinical presentation

›Diagnostic considerations in pregnancy

›LP is generally safe in pregnancy

›Lateral decubitus position preferred

›Fetal monitoring before and after procedure in viable gestation

›MRI without gadolinium preferred in first trimester

›Gadolinium contrast crosses placenta; avoid unless essential

›MRI without contrast adequate for most encephalitis evaluation

›CT with abdominal shielding if MRI unavailable

›Treatment modifications in pregnancy

›Acyclovir is safe in pregnancy (Category B)

›Do not withhold empiric acyclovir

›Documented safety in acyclovir registry data

›Antiepileptic selection

›Levetiracetam: limited data but increasingly used in pregnancy

›Avoid valproic acid: teratogenic, associated with neural tube defects

›Fosphenytoin: Class D; use only if alternatives fail

›Mannitol: use with caution; theoretical risk of fetal dehydration

›Fetal monitoring

›Continuous fetal monitoring in viable gestation with altered consciousness

›Obstetrics consultation required for all encephalitis cases in pregnancy

Geriatric

›Age-specific epidemiology

›Age > 60 is the single strongest risk factor for neuroinvasive disease

›Incidence and case fatality rate increase steeply with age

›All US deaths from SLE 2003-2017 occurred in patients > 45 years

›Elderly represent majority of severe and fatal cases

›Delirium as presenting feature

›Encephalitis may present as delirium rather than classic fever/headache

›High index of suspicion required in older febrile delirious patients

›Diagnostic pitfalls in elderly

›Meningeal signs less sensitive in elderly

›Nuchal rigidity may be absent due to degenerative cervical disease

›Kernig and Brudzinski signs less reliable

›Atypical presentation frequency

›May present primarily as behavioral change or falls

›Baseline cognitive impairment confounds assessment

›Polypharmacy effects

›Multiple medications may mask or mimic encephalitic symptoms

›Drug-induced encephalopathy in differential

›Treatment modifications in elderly

›Reduced renal function requires acyclovir dose adjustment

›Acyclovir dose reduction for GFR < 25 mL/min

›Monitor for acyclovir-induced nephrotoxicity and neurotoxicity

›Benzodiazepines used cautiously

›Higher risk of respiratory depression

›Lower initial doses; reduce by 50%

›Antiepileptic drug interactions

›Polypharmacy increases interaction risk

›Levetiracetam preferred for simpler interaction profile

›Prognosis

›Higher mortality and more severe neurologic sequelae in elderly

›Cognitive deficits persist longer and may be permanent

Pediatrics

›Epidemiology in children

›SLE neuroinvasive disease is uncommon in children

›Adults and elderly most affected; children at low relative risk

›La Crosse virus more commonly causes pediatric arboviral encephalitis in US

›SLE may present as aseptic meningitis rather than encephalitis in younger patients

›Clinical features in children

›Presentation may differ from adults

›Fever and seizures are common presenting features

›Behavioral changes and irritability may predominate

›Tremor less commonly described than in adults

›Seizures

›Febrile seizures must be distinguished from encephalitic seizures

›Encephalitis suspected when post-ictal state prolonged or AMS persists

›Weight-based dosing in children

›Acyclovir (HSV empiric coverage)

›Neonates: 20 mg/kg IV every 8 hours

›Children < 12 years: 10-15 mg/kg IV every 8 hours

›Adolescents: adult dosing 10 mg/kg IV every 8 hours

›Lorazepam for acute seizures

›0.1 mg/kg IV (maximum 4 mg)

›May repeat once after 5 minutes

›Levetiracetam loading

›60 mg/kg IV (maximum 3000 mg in children under 16 years)

›Infuse over 15 minutes

›LP in children

›Lateral decubitus position

›Opening pressure measurement requires cooperation or sedation

›Prognosis in children

›Generally better outcome than elderly

›Majority recover without permanent neurologic deficits

10Background/b94

Epidemiology

›Incidence and disease burden

›Annual US case counts

›2003-2017 surveillance: 236 total neuroinvasive SLE cases reported to CDC

›Mean of approximately 16 cases per year during quiescent period

›Outbreak years produce significantly higher counts (1933 St. Louis outbreak: > 1000 cases)

›Geographic distribution

›Endemic across central and eastern US historically

›Re-emergence in California 2015-2020 documented

›Highest burden: Arkansas, Arizona, Mississippi, California, Florida

›Seasonal pattern

›Peak transmission July through September

›Correlates with Culex mosquito population peaks

›Most cases reported to CDC between August and October

›Case fatality and morbidity

›Overall case fatality rate 5-15%

›Increases steeply with age

›All deaths 2003-2017 in patients > 45 years

›Apparent to inapparent infection ratio

›1:100 to 1:1000; vast majority of infections are asymptomatic

›Only 1-2% of seropositive individuals develop neuroinvasive disease

›Sequelae in survivors

›Up to 50% of survivors with neuroinvasive disease have persistent cognitive deficits

›Attention, working memory, processing speed most affected

›Depression and fatigue frequently reported post-infection

›Transmission cycle

›Vector: Culex mosquito species

›Culex pipiens and Culex quinquefasciatus primary urban vectors

›Culex tarsalis primary vector in western US

›Crepuscular and nocturnal feeding behavior

›Amplifying hosts: wild birds

›Passerine birds develop high-level viremia

›Culex feeds on birds then incidentally bites humans (dead-end host)

›No person-to-person transmission documented

›No transmission by blood transfusion screening protocols

›NAT testing of blood supply implemented after WNV experience

Pathophysiology

›Viral entry and neuroinvasion

›SLEV is a positive-sense single-stranded RNA flavivirus

›Transmitted via Culex mosquito saliva during blood meal

›Initial viral replication in skin dendritic cells and lymph nodes

›Viremia follows seeding of visceral organs

›Blood-brain barrier penetration

›Mechanism not fully elucidated

›Direct infection of brain microvascular endothelial cells proposed

›Trojan horse mechanism via infected monocytes

›Peripheral viremia is brief (3-5 days) and low-level

›CNS inflammation

›Neuronal tropism

›Predilection for substantia nigra, thalamus, and basal ganglia

›Explains parkinsonian tremor as characteristic feature

›Hippocampus and cortex involved in severe cases

›Immune-mediated injury

›T-cell and macrophage infiltration in perivascular spaces

›Microglial activation and neuroinflammation

›Cytokine storm may contribute to neuronal injury

›Neuronal death mechanisms

›Direct viral cytopathic effect

›Apoptosis triggered by immune response

›Excitotoxicity from seizure activity

›SIADH mechanism

›Hypothalamic involvement triggers inappropriate ADH secretion

›Results in dilutional hyponatremia

›Exacerbates cerebral edema

›Complicates fluid management

Therapeutic Considerations

›No approved antiviral therapy for SLE

›Current treatment is supportive

›No flavivirus-specific antiviral has completed successful phase III trials

›Empiric acyclovir covers HSV until excluded (standard of care)

›Ribavirin, IFN-alpha, IVIG all lack RCT evidence for SLE

›Vaccine status

›No licensed SLE vaccine available

›Japanese encephalitis vaccine (cross-protective flavivirus) has theoretical benefit but not validated for SLE protection

›Rationale for supportive care priorities

›Fever control

›Pyrexia worsens neuronal excitability and metabolic demand

›Each 1 C increase in temperature raises cerebral metabolic rate approximately 6-8%

›Seizure control

›Seizures increase ICP and neuronal injury

›Non-convulsive status epilepticus associated with worse outcomes

›Normoglycemia

›Both hypo- and hyperglycemia worsen neurologic outcomes

›Target glucose 7.8-10 mmol/l in critical illness

›Long-term rehabilitation

›Neuropsychological testing at discharge and follow-up

›Documents baseline for recovery monitoring

›Guides rehabilitation planning

›Cognitive rehabilitation

›May improve attention and processing speed deficits

›Structured programs for working memory training

›Physical and occupational therapy

›For motor deficits, tremor, and functional impairment

›Early mobilization reduces complications of immobility

›Psychiatric support

›Depression screening post-SLE

›SSRIs appropriate for post-encephalitis depression

11Patient Discharge Instructions/pdi47

copy discharge instructions

›Diagnosis and nature of illness

›Diagnosis: St. Louis encephalitis — a viral brain infection transmitted by mosquito bites

›Caused by St. Louis encephalitis virus (SLEV), a flavivirus

›No person-to-person transmission; cannot spread from person to person

›No vaccine available to prevent infection

›Medications at discharge

›Take all prescribed medications exactly as directed

›Antiepileptic medication: do not stop without physician advice even if feeling well

›Acetaminophen for fever or headache as needed

›Do not drive or operate heavy machinery while taking antiepileptic medications

›Activity restrictions

›Activity as tolerated

›No driving until seizure-free for the period required by your province or state law

›Avoid swimming or heights until cleared by neurology

›Fatigue is expected; increase activity gradually

›Mosquito bite prevention

›Personal protection measures

›Apply DEET-containing insect repellent (20-30% DEET) to exposed skin

›Wear long sleeves and pants especially at dusk and dawn when Culex mosquitoes feed

›Treat clothing with permethrin for added protection

›Environmental measures

›Eliminate standing water around the home (buckets, birdbaths, flowerpot trays)

›Repair or install window and door screens

›Use air conditioning when available

›Expected recovery timeline

›Recovery information

›Mild cases may resolve within weeks

12References/r30

Guidelines and key sources

›Curren EJ, Lindsey NP, Fischer M, Hills SL. St. Louis Encephalitis Virus Disease in the United States, 2003-2017. Am J Trop Med Hyg. 2018. PMID 30182919

›US surveillance data 2003-2017; epidemiology, age distribution, outcomes

›Solomon T. Flavivirus Encephalitis. N Engl J Med. 2004. https://www.nejm.org/doi/full/10.1056/NEJMra030476

›Comprehensive review of flaviviral CNS disease including SLE

›Bloch KC, Glaser C, Gaston D, Venkatesan A. State of the Art: Acute Encephalitis. Clin Infect Dis. 2023. PMID 37485952

›IDSA-aligned systematic approach to encephalitis diagnosis and management

›Binks SNM, Saylor D, Easton A, Thakur KT, Irani SR. Encephalitis. Lancet. 2026. PMID 42134357

›Updated comprehensive encephalitis review including outcomes and sequelae

›Venkatesan A, Michael BD, Probasco JC, Geocadin RG, Solomon T. Acute Encephalitis in Immunocompetent Adults. Lancet. 2019. PMID 30782344

›Evidence-based management framework for viral encephalitis

›Venkat H, Krow-Lucal E, Kretschmer M, et al. Comparison of SLE and WNV neuroinvasive disease during concurrent outbreaks, Arizona 2015. Vector Borne Zoonotic Dis. 2020. PMID 32251616

›Clinical differentiation of SLE vs. WNV; rash prevalence data

›Rahal JJ, Anderson J, Rosenberg C, Reagan T, Thompson LL. Effect of Interferon-Alpha2b Therapy on St. Louis Viral Meningoencephalitis: Pilot Study. J Infect Dis. 2004. PMID 15319857

›Only clinical trial data for IFN therapy in SLE

›Hartmann CA, Vikram HR, Seville MT, et al. Neuroinvasive SLE in Solid Organ Transplant Recipients. Am J Transplant. 2017. PMID 28452107

›Immunocompromised host presentation and outcomes

›Greve KW, Houston RJ, Adams D, et al. Neurobehavioural Consequences of St. Louis Encephalitis Infection. Brain Injury. 2002. PMID 12419004

›Cognitive sequelae data; attention, memory, processing speed deficits

›Venkat H, Krow-Lucal E, Hennessey M, et al. Concurrent Outbreaks of SLE and WNV Disease — Arizona 2015. MMWR. 2015. PMID 26656306

›Outbreak characterization; public health reporting context

›Tyler KL. Acute Viral Encephalitis. N Engl J Med. 2018. https://www.nejm.org/doi/full/10.1056/NEJMra1708714

›Diagnostic framework for acute viral encephalitis

›Piantadosi A, Kanjilal S. Diagnostic Approach for Arboviral Infections in the United States. J Clin Microbiol. 2020. PMID 32938736

›Arboviral testing algorithm; PRNT and IgM ELISA guidance

›Miller JM, Binnicker MJ, Campbell S, et al. IDSA/ASM Guide to Microbiology Laboratory Utilization 2024. Clin Infect Dis. 2024. https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciae104

›Laboratory testing guidance for arboviral diagnosis

›CDC West Nile Virus Surveillance and Control Guidelines 2025. https://www.cdc.gov/mosquitoes/media/pdfs/2024/09/westnilevirus-surveillancecontrolguidelines_508.pdf

Evidence & Review