01Approach to the Critical Patient/attcp39

Immediate airway priorities

›Airway compromise triggers

›GCS < 8 or rapidly declining mental status

›Inability to protect airway

›50% of neuroinvasive EEE cases required mechanical ventilation in case series

›Respiratory failure from aspiration or central hypoventilation

›SpO2 < 92% on supplemental oxygen

›Rising PaCO2 with fatigue

›Proceed to rapid sequence intubation if airway not protected

›Ketamine or etomidate induction acceptable

›Succinylcholine or rocuronium for paralysis

Hemodynamic and neurologic monitoring

›Monitoring bundle

›Continuous cardiac monitoring and pulse oximetry

›Telemetry for arrhythmia from electrolyte disturbance

›QTc monitoring if antiemetics administered

›Neuro vital signs every 1–2 hours

›GCS trend for deterioration

›Pupillary size and reactivity

›Cushing triad recognition

›Hypertension with bradycardia signals elevated intracranial pressure

›Irregular respirations

ICP escalation triggers

›Elevated intracranial pressure management

›Head of bed elevation 30 degrees

›Neutral head positioning to optimise venous drainage

›Avoid tight cervical collars

›Osmotic therapy for refractory ICP elevation

02History/hx35

Exposure and onset

›Epidemiologic exposure history

›Outdoor activities in endemic forested wetland areas

›Atlantic Coast, Gulf Coast, Great Lakes, New England states

›17 of 19 US cases in 2024 from New England

›Seasonal window June–October, peak late August

›Recent travel to swamp, marsh, or deciduous wetland regions

›Agricultural, forestry, or outdoor recreational occupation

›Incubation period 4–10 days after mosquito bite

›Timeline from last outdoor exposure

Prodrome and neurologic symptoms

›Constitutional prodrome

›Fever and chills

›Fever present in 100% of patients in case series

›Rigors and malaise

›Arthralgias and myalgias

›Median 5 days of prodrome before CNS symptom onset in older children and adults

›Abrupt onset without prodrome in infants

›Nausea and vomiting

›Photophobia

›Neurologic symptom progression

›Headache

›Confusion and personality change

›Focal deficits: hemiparesis, dysarthria, facial droop

›Seizures

›Rapid progression to stupor or coma within hours to days

›Timeline of neurologic deterioration from family or witnesses

03Physical Exam/exam35

Vital signs

›Vital sign assessment

›Temperature

›Fever universal in neuroinvasive EEE

›Hyperthermia may worsen cerebral edema

›Cardiovascular response to ICP

›Cushing triad: hypertension, bradycardia, irregular respirations

›Tachycardia from systemic febrile illness

Neurologic examination

›Mental status

›Glasgow Coma Scale

›Progression from confusion to obtundation to coma

›Baseline GCS for trajectory tracking

›Orientation and attention testing

›Memory and language function

›Meningeal signs

›Nuchal rigidity

›Kernig sign

›Brudzinski sign

›Focal neurologic deficits

›Motor examination

›Hemiparesis or monoparesis

›Posturing response: decorticate or decerebrate

›Cranial nerve examination

›Facial droop and dysarthria

›Oculomotor palsies

›Seizure activity observation

›Subtle motor manifestations of nonconvulsive seizures

04Differential Diagnosis/ddx32

Viral encephalitides

›Herpes simplex encephalitis (HSV-1)

›ICD-10: B00.4

›Temporal lobe predominance on MRI contrasts with basal ganglia pattern of EEE

›Treat empirically with acyclovir until HSV PCR returns negative

›West Nile virus encephalitis

›ICD-10: A92.31

›Lower case fatality (~10%) versus EEE (~41%)

›May show anterior horn cell involvement causing flaccid paralysis

›La Crosse encephalitis

›Primarily school-aged children

›Case fatality less than 1%

›St. Louis encephalitis

›ICD-10: A83.3

›Geographic overlap with EEE endemic areas

Bacterial and other infections

›Bacterial meningitis

›ICD-10: G00.9

›CSF neutrophilic pleocytosis mimics early EEE

›Low CSF glucose distinguishes bacterial from viral etiology

›Tuberculous meningitis

›Subacute basilar meningeal enhancement

›Lymphocytic pleocytosis with very low glucose

Autoimmune and structural diagnoses

›Autoimmune encephalitis

›Anti-NMDA receptor encephalitis

›Psychiatric prodrome, CSF lymphocytic pleocytosis

›Positive serum or CSF antibody panel

05Laboratory Tests/lt35

Serology and CSF analysis

›Lumbar puncture and CSF analysis

›Opening pressure

›Elevated in encephalitis with cerebral edema

›Contraindicated if papilledema or focal mass lesion on CT

›Cell count and differential

›Pleocytosis initially neutrophilic (mean 60% neutrophils) transitioning to lymphocytic

›High CSF WBC greater than 500 per mm3 is a poor prognostic marker

›Protein and glucose

›Elevated protein (median approximately 100 mg/dL equivalent)

›Normal glucose distinguishes viral from bacterial etiology

›May have elevated red blood cells in hemorrhagic cases

›EEE-specific serology

›IgM antibody by ELISA or microsphere immunoassay (serum and CSF)

›Appears within first week of illness

›Repeat testing at 8 or more days after symptom onset if initial test negative and suspicion remains high

›Commercially available immunofluorescence assay has reduced sensitivity early

›Median diagnosis delay 24.5 days in one outbreak series due to initially negative serologies

›Confirmatory plaque reduction neutralization test (PRNT) via public health laboratory

›State health department submission required

Metabolic and haematologic labs

›Serum metabolic panel

›Sodium

›Hyponatremia at or below 130 mmol/L is a poor prognostic indicator

›Avoid hypotonic fluids; monitor closely

›Comprehensive metabolic panel for hepatic and renal function

›Coagulation studies if coagulopathy suspected

›Complete blood count

06Diagnostic Tests/dt45

Scoring Systems

›Modified Rankin Scale (mRS)

›Used to quantify functional disability at discharge and follow-up

›Score 0–6 from no symptoms to death

›Majority of EEE survivors have mRS 3–5 at discharge

›Glasgow Coma Scale

›Guides airway management decisions

›GCS below 8 indicates impaired airway protection

MRI

›MRI brain with and without contrast (modality of choice)

›T2/FLAIR hyperintensities in basal ganglia and thalami

›Hallmark pattern distinguishing EEE from HSV encephalitis

›Mesial temporal lobe involvement also described

›Brainstem involvement in approximately 43% of cases on MRI

›Cortical involvement in severe disease

›Hyperintense ring encapsulation around basal ganglia and thalamus reported

›Meningeal enhancement less common than in bacterial meningitis

›Periventricular white matter changes seen in some cases

›Prognostic value

›Numerous and symmetrical MRI abnormalities predict worse neurologic outcome

›Abnormal in 100% of comatose patients

›Diffusion-weighted imaging (DWI)

›Restricted diffusion in basal ganglia and thalami in acute phase

›MRI superior to CT for early detection of encephalitic changes

CT

›CT head without contrast

›Initial imaging for rapid exclusion of haemorrhage or mass lesion

›Abnormal in approximately 66% of EEE patients

07Disposition/dispo20

ICU admission

›ICU admission criteria

›All neuroinvasive EEE cases require ICU-level care

›Altered mental status, seizures, focal deficits, or meningismus

›98% of reported cases required hospitalisation; average stay 10 days among survivors

›Mechanical ventilation requirement

›Declining GCS or inability to protect airway

›Aspiration risk in obtunded patients

Specialist consultation before disposition

›Mandatory consultations

›Neurology for seizure management and continuous EEG oversight

›Infectious disease for workup coordination and IVIG or steroid consideration

›Public health department notification required by law

›Neurosurgery if refractory ICP or mass lesion identified

›Critical care intensivist for ventilator management

Discharge and rehabilitation

›Discharge criteria

›Neurologically stable with improving or plateaued deficits

›Seizure-free on oral antiepileptic regimen

›Able to protect airway and maintain adequate oral intake

›Most survivors require discharge to inpatient rehabilitation facility

›Long-term neurologic follow-up arranged prior to discharge

›Occupational, physical, and speech therapy referrals

08Treatment/t63

Empiric antimicrobial therapy

›Empiric coverage until EEE confirmed

›Acyclovir IV 10 mg/kg every 8 hours for HSV encephalitis coverage

›Continue until HSV CSF PCR returns negative

›Renally dose adjust: CrCl 25–50 mL/min reduce to q12h; CrCl less than 10 mL/min q24h

›Vancomycin IV for bacterial meningitis coverage

›Target trough 15–20 mg/L or AUC 400–600 mg·h/L

›Weight-based dosing 25–30 mg/kg every 8–12 hours

›Ceftriaxone IV 2 g every 12 hours for gram-negative and pneumococcal coverage

›Add ampicillin IV 2 g every 4 hours if age over 50 or immunocompromised for Listeria coverage

›Dexamethasone 0.15 mg/kg every 6 hours for 4 days if bacterial meningitis suspected

›Administer 15–30 minutes before or with first antibiotic dose

›Discontinue if bacterial meningitis excluded

Seizure management

›Antiepileptic therapy

›Levetiracetam first-line for seizure management

›Loading dose 20–60 mg/kg IV (maximum 4500 mg) over 15 minutes

›Maintenance 1000–3000 mg IV every 12 hours

›Lorazepam for active seizures

›0.1 mg/kg IV (maximum 4 mg per dose); repeat once in 5 minutes if needed

›Transition to second-line agent if refractory to two benzodiazepine doses

›Nonconvulsive status epilepticus treatment

›Levetiracetam or lacosamide IV for first-line management

›Continuous EEG guidance for titration

›Second-line antiepileptics if levetiracetam fails

›Valproate sodium IV 20–40 mg/kg over 5–10 minutes (maximum 60 mg/kg/day)

›Phenytoin or fosphenytoin if valproate contraindicated

Immunomodulatory therapy

›IVIG administration

›Limited retrospective evidence suggests earlier administration may reduce long-term disability

›Average 5 days post-admission in N=17 retrospective series by Wilcox et al. (Neurol Neuroimmunol Neuroinflammation 2021)

›Total dose 2 g/kg IV divided over 2–5 days

›Results remain inconclusive; no randomised controlled trial data available

›Reasonable to consider in severe neuroinvasive disease in consultation with infectious disease

›High-dose methylprednisolone

›Used in some centres for immunomodulation in severe EEE

›1000 mg IV daily for 3–5 days as used in case series

›Meta-analysis of steroids for viral encephalitides showed no survival benefit

›Risk of immunosuppression may outweigh benefit; decision requires case-by-case judgement

›Monitor for hyperglycaemia, hypertension, and secondary infection

ICP and electrolyte management

›Intracranial pressure management

›Head of bed 30 degrees with neutral head positioning

›Avoid hypercarbia (target PaCO2 35–40 mmHg in ventilated patients)

›Short-term hyperventilation to PaCO2 30–35 mmHg as bridge for acute herniation only

›Mannitol 0.25–1 g/kg IV over 20 minutes for elevated ICP

›Repeat every 4–6 hours as needed

›Monitor serum osmolality; hold if osmolality exceeds 320 mOsm/kg

›Hypertonic saline 3% at 1–2 mL/kg IV bolus for acute ICP elevation with concurrent hyponatremia

›Continuous infusion titrated to sodium target 145–155 mmol/L in refractory ICP

›Fluid and electrolyte management

›Avoid hypotonic fluids; hyponatremia at or below 130 mmol/L is prognostically significant

›Isotonic saline as maintenance fluid

›Target euvolemia; avoid fluid overload worsening cerebral oedema

›Sodium monitoring every 4–6 hours in active correction phase

›Correct no faster than 10–12 mmol/L per 24 hours to avoid osmotic demyelination

Supportive care

›Fever management

›Acetaminophen 650 mg oral or IV every 4–6 hours for fever reduction

›Cooling blanket or surface cooling device for refractory hyperthermia

›Target normothermia; hyperthermia worsens neuronal injury

›Enteral nutrition

›NPO if altered mental status or aspiration risk; nasogastric tube placement

›Initiate enteral feeds within 24–48 hours of ICU admission if intubated

›Parenteral nutrition if enteral route not tolerated

›DVT prophylaxis

›Mechanical prophylaxis (sequential compression devices) in all immobilised patients

›Pharmacologic prophylaxis when seizure risk stabilised and no coagulopathy

09Special Populations/sp39

Pregnancy

›Pregnancy considerations in EEE

›Vertical transmission risk is theoretical; no well-documented cases of congenital EEE

›Arboviral infection in pregnancy associated with adverse fetal outcomes in animal models

›Fetal monitoring recommended in hospitalised pregnant patients

›Medication safety

›Acyclovir: Category B; generally considered safe in pregnancy for HSV coverage

›Levetiracetam: Category C; use if benefit outweighs risk for seizure control

›Valproate contraindicated in pregnancy due to teratogenicity; use alternative AED

›Dexamethasone: Category C; use if bacterial meningitis suspected

›Mannitol: Use with caution; may cause fetal dehydration; discuss with obstetrics

›Obstetrics consultation mandatory for all pregnant patients with neuroinvasive EEE

›Delivery timing decision based on maternal-fetal risk-benefit assessment

Geriatric

›Geriatric considerations in EEE

›Age 60 years and older at highest risk for neuroinvasive disease and death

›Age 70 and older has highest case fatality rate of any age group

›Bimodal risk distribution; geriatric patients form one high-risk peak

›Atypical presentations more common

›Delirium may be the predominant neurologic manifestation

›Meningismus may be absent despite meningeal involvement

›Medication management

›Renal dose adjustment for acyclovir, levetiracetam, and vancomycin

›Reduce benzodiazepine doses; higher risk of respiratory depression

›Polypharmacy and drug interaction screening

›Baseline cognitive impairment complicates neurologic assessment

›Advance directive review and goals of care discussion early in admission

10Background/b48

Epidemiology

›Incidence and geographic distribution

›Rare in absolute terms: 193 cases reported to CDC from 2005–2024

›99% of reported US cases are neuroinvasive

›Highest case fatality rate of any arboviral encephalitis in the US at approximately 41%

›Geographic distribution

›Endemic in Atlantic Coast, Gulf Coast, Great Lakes, and New England states

›17 of 19 US human cases in 2024 from New England (MMWR 2026)

›Expanding geographic range with northern and inland spread documented

›Seasonal epidemiology

›Cases occur June–October with peak in late August

›Increased precipitation in preceding year associated with amplified mosquito vector populations

›Long-term sequelae

›More than 50% of survivors develop long-term neurologic sequelae

›Cognitive impairment, aphasia, personality disorders, seizures, paralysis, cranial nerve dysfunction

›ICD-10 code: A83.2 (Eastern equine encephalitis virus disease)

Pathophysiology

›Vector and transmission cycle

›Primary transmission: Culiseta melanura mosquito maintains enzootic cycle in wild birds

›Aedes, Coquillettidia, and Culex species serve as bridge vectors to humans and horses

›Humans and horses are dead-end hosts; no person-to-person or horse-to-person transmission

›One documented cluster of solid organ transplant-associated transmission to 3 recipients from infected donor

›Transfusion transmission: Not documented but theoretically possible during viremic phase

›Viral neuroinvasion

›EEEV is a positive-sense single-stranded RNA alphavirus in family Togaviridae

›Neurotropic virus with predilection for basal ganglia, thalami, and mesial temporal structures

›Inflammatory cascade after neuroinvasion causes cytotoxic oedema, neuronal death, and demyelination

›Humoral immunity important for clearance; B-cell deficient patients at higher risk

11Patient Discharge Instructions/pdi23

copy discharge instructions

›Discharge instructions for Eastern Equine Encephalitis

›You were treated for Eastern Equine Encephalitis (EEE), a rare but serious brain infection spread by mosquito bites

›There is no specific antiviral medication; your treatment focused on supportive care and preventing complications

›Recovery can take weeks to months; many survivors experience lasting neurologic effects

›Medications at discharge

›Take all prescribed anti-seizure medications exactly as directed; do not stop without your neurologist's approval

›Take all other prescribed medications as directed

›Activity and diet

›No driving until cleared by your neurologist, particularly if you had seizures

›Follow a soft or modified diet if you have swallowing difficulty

›Attend all scheduled rehabilitation appointments (physical, occupational, speech therapy)

›Prevention after discharge

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

›Wear long-sleeved shirts and long pants when outdoors in wooded or wetland areas

›Avoid outdoor activities at dawn and dusk when mosquitoes are most active

›Eliminate standing water around your home (birdbaths, flowerpots, gutters)

›Return to the emergency department immediately if you experience

›New seizure or worsening seizure activity

›Sudden decline in mental status or increasing confusion

›New weakness, numbness, or difficulty speaking

›Fever greater than 38.3 degrees Celsius returning after discharge

›Inability to keep medications down due to vomiting

›Any sudden or severe headache

12References/r24

Guidelines and key sources

›Primary references

›Staples JE, Gould CV. Eastern Equine Encephalitis in the US. JAMA. 2025. doi:10.1001/jama.2025.9073

›Comprehensive review of 193 CDC-reported cases 2005–2024

›Epidemiology, clinical features, management, and outcomes

›Garcia-Dominguez MA, Moonis M, Kipkorir V, Srichawla BS. The Clinical and Radiographic Features of Eastern Equine Encephalitis: A Single-Center Retrospective Case Series. Medicine. 2024. PMID: 39969305

›Detailed MRI and CT imaging characterisation

›Prognostic correlates of neuroimaging abnormalities

›Wilcox DR, Collens SI, Solomon IH, Mateen FJ, Mukerji SS. Eastern Equine Encephalitis and Use of IV Immunoglobulin Therapy and High-Dose Steroids. Neurology Neuroimmunol Neuroinflammation. 2021. PMID: 33172962

›N=17 retrospective series evaluating IVIG and steroid use

›Earlier IVIG associated with reduced long-term disability

›Ruiz C, Gibson G, Rojas S, Friend K. Eastern Equine Encephalitis Virus: A Case Report and Brief Literature Review. Vector Borne Zoonotic Dis. 2024. PMID: 37870590

›Case report with literature review of therapeutic strategies

›Ladzinski AT et al. Clinical Characteristics of the 2019 Eastern Equine Encephalitis Outbreak in Michigan. Open Forum Infect Dis. 2023. PMID: 37180595

›Outbreak series with clinical characteristics and diagnostic delays

›Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA. Clinical and Neuroradiographic Manifestations of Eastern Equine Encephalitis. N Engl J Med. 1997;336:1867–1874

›Landmark NEJM series defining MRI and CT patterns in EEE

›Mermel LA. Association of Human Eastern Equine Encephalitis With Precipitation Levels in Massachusetts. JAMA Netw Open. 2020. doi:10.1001/jamanetworkopen.2019.20261

›Epidemiologic study linking precipitation to EEE case frequency

›Strelau KM et al. Notes From the Field: Increase in Eastern Equine Encephalitis Virus Activity - Vermont, 2023–2024. MMWR. 2026. PMID: 42060520

›Emerging geographic expansion into northern New England

›Lindsey NP, Staples JE, Fischer M. Eastern Equine Encephalitis Virus in the United States, 2003–2016. Am J Trop Med Hyg. 2018. PMID: 29557336

›National surveillance data and epidemiologic trends

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

›Foundational review of viral encephalitis differential diagnosis and management

Evidence & Review

Evidence & Review