La Crosse virus (LACV) is an Orthobunyavirus transmitted by Aedes triseriatus mosquitoes and is the most common cause of pediatric neuroinvasive arboviral disease in the United States, ranking second overall behind West Nile virus. [1-2] It predominantly affects children (88% of cases aged <18 years; median age 8 years), with a case fatality rate of approximately 1% and significant long-term neurobehavioral morbidity. [1][3]
1. History
- Typical prodrome: Fever and headache beginning 3–4 days before presentation, progressing to vomiting for 1–2 days, then disorientation or seizures on the day of admission [4]
- Key HPI questions:
- Onset and duration of fever, headache, vomiting
- Seizure activity — type (focal vs. generalized), duration, number of episodes
- Mental status changes — confusion, lethargy, disorientation
- Outdoor exposure and mosquito bite history, especially in wooded/rural areas
- Geographic location and season (peak July–September) [1][5]
- Important negatives: No rash (distinguishes from other arboviral/rickettsial infections), no travel to tropical regions
2. Alarm Features
- GCS ≤12 at presentation — independently associated with clinical deterioration [4]
- Seizures at presentation — OR 10.31 for severe disease [3]
- Altered mental status — OR 6.36 for severe disease [3]
- Signs of increased intracranial pressure (13% of hospitalized children): papilledema, Cushing triad, posturing [4]
- Status epilepticus (~25% of those with seizures) [4]
- Cerebral herniation occurred in 2.4% of one large pediatric cohort [4]
- Hyponatremia — temporally associated with clinical deterioration (p=0.007) [4]
- Rising body temperature during hospitalization — associated with worsening (p=0.003) [4]
3. Medications
- No FDA-approved antiviral therapy — management is entirely supportive [2]
- Empiric acyclovir should be started pending HSV exclusion, as LACV encephalitis closely mimics herpes simplex encephalitis; acyclovir has no activity against LACV (an RNA virus) [4]
- Ribavirin has shown in vitro inhibition of LACV and has been used as compassionate therapy; a randomized trial was initiated but no definitive efficacy data exist [4]
- Antiepileptic drugs for seizure management (benzodiazepines acutely; levetiracetam or other AEDs for ongoing seizure control)
- Hypertonic saline or mannitol for elevated ICP management
- Avoid hypotonic fluids — risk of worsening hyponatremia and cerebral edema
4. Diet
- NPO if altered mental status or seizures with aspiration risk
- Fluid restriction may be warranted if SIADH/hyponatremia develops (21% of hospitalized children) [4]
- Isotonic IV fluids preferred; avoid free water excess
- No specific long-term dietary considerations
5. Review of Systems
- Neurologic: Headache, seizures, confusion, focal weakness, speech difficulty, behavioral changes
- GI: Vomiting (≥70% of cases), nausea, poor oral intake [4]
- Constitutional: Fever (≥70%), malaise, fatigue
- Ophthalmologic: Visual changes (papilledema screening)
- Respiratory: Assess for aspiration risk, need for airway protection (~25% required intubation) [4]
6. Collateral History and Family History
- Collateral: Baseline developmental/cognitive status in children (critical for assessing deficits); witnessed seizure description; timeline of symptom progression
- Exposure history: Rural/suburban residence near wooded areas; outdoor play habits; presence of tire dumps, tree holes, or standing water (breeding sites for Aedes triseriatus) [6-7]
- Family history: No hereditary predisposition; family history of seizure disorders may complicate assessment
- Social context: Appalachian region, lower socioeconomic status areas have higher incidence [8]
7. Risk Factors
- Age <16 years — children uniquely predisposed to symptomatic disease [1][9]
- Male sex (59% of cases) [1]
- Geographic location: Appalachian region (WV, NC, TN, OH account for 80% of cases); Great Lakes, mid-Atlantic, and southeastern U.S. [1][8]
- Season: Summer months (July–September peak; 81% of cases) [5]
- Rural/suburban residence near deciduous forests with Aedes triseriatus habitat [6]
- Lack of mosquito bite prevention measures
- Climate change is expanding vector range, with Aedes albopictus serving as a bridge vector [6]
8. Differential Diagnosis
- Herpes simplex encephalitis (HSE) — the most critical mimic; LACV can present with focal seizures, focal signs, periodic lateralizing epileptiform discharges (PLEDs), and hemorrhagic CSF pleocytosis, all features classically attributed to HSE [4]
- Enteroviral meningitis/encephalitis — milder forms of LACV may be confused with this
- Bacterial meningitis (including partially treated) — peripheral leukocytosis and elevated CRP in LACV can mimic bacterial infection [4]
- Other arboviral encephalitides: West Nile virus, Eastern equine encephalitis, Powassan virus, St. Louis encephalitis, Jamestown Canyon virus [10-11]
- Autoimmune encephalitis (anti-NMDA receptor, etc.)
- Acute disseminated encephalomyelitis (ADEM)
- CNS vasculitis, intracranial abscess, or tumor
9. Past Medical History
- Prior seizure disorder or epilepsy (complicates acute assessment)
- Immunocompromised state (may alter presentation and diagnostic approach)
- Previous arboviral infection (cross-reactive antibodies may confound serologic testing) [10-11]
- Developmental or neurobehavioral baseline (essential for measuring post-illness deficits)
10. Physical Exam
- Vital signs: Fever (often high), tachycardia; monitor for Cushing triad (hypertension, bradycardia, irregular respirations) suggesting elevated ICP
- Neurologic exam:
- GCS assessment — GCS ≤12 is a key prognostic marker [4]
- Focal neurologic deficits (16–25% of cases) [4]
- Meningismus/nuchal rigidity
- Pupil reactivity and fundoscopic exam for papilledema
- Motor tone, deep tendon reflexes, plantar responses
- General: Assess hydration status, look for signs of aspiration
- Skin: Absence of rash (helps distinguish from rickettsial disease, measles)
11. Lab Studies
- Serum:
- BMP — hyponatremia in 21% (monitor serially; worsening Na⁺ correlates with deterioration) [4]
- CBC — peripheral leukocytosis is common and can mislead toward bacterial diagnosis [4]
- CRP — may be elevated (was elevated in ~46% of tested patients), further mimicking bacterial infection [4]
- Blood cultures — to rule out bacteremia
- LACV-specific serum IgM (detectable 3–8 days post-symptom onset) [10]
- CSF:
- Cell count/differential — lymphocytic pleocytosis typical; hemorrhagic pleocytosis in ~25% [4]
- Protein — mildly elevated
- Glucose — typically normal
- CSF IgM for LACV — 90% sensitivity; IgM does not cross the blood-brain barrier, so its presence in CSF confirms intrathecal antibody production [10][12]
- HSV PCR — to rule out herpes simplex encephalitis (must be sent concurrently)
- Enterovirus PCR
- Confirmatory: Seroconversion or 4-fold rise in LACV-specific IgM/IgG between acute and convalescent sera (7–10 days apart) [10-11]
12. Imaging
- CT head (non-contrast): First-line in the ED to rule out mass lesion, hemorrhage, or herniation before lumbar puncture; often normal in LACV [4]
- MRI brain: More sensitive; may show cortical and subcortical signal abnormalities, but findings are often nonspecific or normal. Abnormal neuroimaging has been reported in severe cases [13]
- Imaging is not diagnostic for LACV — serves primarily to exclude other etiologies and assess for complications (cerebral edema, herniation)
13. Special Tests
- EEG:
- Indicated for all patients with seizures or altered mental status
- May show epileptiform discharges, including periodic lateralizing epileptiform discharges (PLEDs) — previously thought pathognomonic for HSE but seen in LACV [4]
- Epileptiform discharges on EEG independently predict long-term epilepsy (OR 13.45) [3]
- IgM antibody capture enzyme immunoassay (MAC-EIA): 100% sensitivity in serum, 90% in CSF in one study [12]
- NAAT/RT-PCR: Limited utility — only 5.3% of clinical specimens positive; may be useful in delayed seroconversion or immunocompromised patients [14]
- Plaque reduction neutralization test (PRNT): Confirmatory test to resolve cross-reactivity among California serogroup viruses [11]
- Glasgow Coma Scale — GCS ≤12 at admission predicts deterioration [4]
14. ECG
- Not a primary diagnostic tool for LACV encephalitis
- Consider ECG if:
- Hyponatremia is significant (risk of arrhythmia)
- Prolonged ICU stay with electrolyte derangements
- Monitoring for effects of antiepileptic medications
15. Assessment
- Typical presentation: School-aged boy in an endemic Appalachian/Midwestern area during summer, presenting with 3–4 days of fever and headache progressing to vomiting, then acute disorientation or seizures [4]
- Severity spectrum: Ranges from mild aseptic meningitis (13–17%) to severe encephalitis with status epilepticus and cerebral herniation [1][4]
- 43% of children with neuroinvasive disease had severe disease in a contemporary cohort [3]
- Complications:
- Status epilepticus (~25% of those with seizures) [4]
- Cerebral herniation (2.4%) [4]
- SIADH/hyponatremia (21%) [4]
- Long-term neurobehavioral deficits in 19–54% of children regardless of initial severity [3]
- Post-infectious epilepsy [3]
- Case fatality rate: ~1% overall; up to 8.6% in those with encephalitis specifically [1][5]
16. Treatment Plan
- Initial stabilization:
- ABCs — airway protection if GCS ≤8 or status epilepticus (~25% required intubation) [4]
- IV access, isotonic fluids, avoid hypotonic solutions
- Seizure management: IV benzodiazepines → second-line AED (levetiracetam, fosphenytoin)
- Empiric therapy:
- Start IV acyclovir immediately pending HSV PCR results — do not delay [4][15]
- Empiric antibiotics if bacterial meningitis cannot be excluded
- Discontinue acyclovir once HSV is ruled out
- Supportive care:
- Aggressive temperature management (fever worsens outcomes) [4]
- Serial sodium monitoring q6–8h; correct hyponatremia cautiously
- ICP management if signs of elevated ICP: head of bed elevation, osmotic therapy (mannitol or hypertonic saline), consider ICP monitoring in severe cases [4]
- No proven antiviral: Ribavirin has been used compassionately but lacks definitive efficacy data [4]
- Reportable disease: Notify state/local health department [16]
17. Disposition
- Admit all patients with suspected LACV encephalitis — virtually all neuroinvasive cases require hospitalization [4][17]
- ICU admission criteria:
- GCS ≤12 [4]
- Seizures at presentation (consider ICU monitoring) [4]
- Status epilepticus
- Signs of elevated ICP
- Need for intubation/airway protection
- Average hospitalization: ~6 days in children; 8.4 days in adults [4][17]
- Discharge criteria: Afebrile, no seizure recurrence, stable mental status, sodium normalized, able to tolerate oral intake
- Rehabilitation referral: 4 of 10 adults in one series required discharge to rehabilitation; severe pediatric cases may also need inpatient rehab [13][17]
- Specialist consultation: Pediatric neurology, infectious disease; neurosurgery if ICP monitoring needed
18. Follow Up / Return Precautions
- Neurology follow-up within 2–4 weeks for all patients — long-term neurobehavioral deficits are frequent (19–54%) and often underrecognized, even in mild disease [3][9]
- Neuropsychological testing recommended at 3–6 months post-discharge to assess for cognitive and behavioral deficits [3-4]
- EEG follow-up if epileptiform discharges were present during hospitalization — significant predictor of long-term epilepsy [3]
- Return precautions:
- New seizures or recurrence of seizures
- Worsening headache, confusion, or behavioral changes
- Persistent vomiting or inability to maintain hydration
- Fever recurrence
- Counseling: Mosquito bite prevention (DEET-containing repellents, protective clothing, eliminating standing water); no vaccine is currently available [2][6]
- Expected course: Most children become afebrile by hospital day 3; however, cognitive and behavioral recovery may take months to years, and some deficits may be permanent [4][13]
References
1. La Crosse Virus Disease in the United States, 2003-2019. — Vahey GM, Lindsey NP, Staples JE, Hills SL. The American Journal of Tropical Medicine and Hygiene. 2021.
2. La Crosse Virus: A Comprehensive Review of Its Emerging Public Health Importance. — Feng S, Feng X, Zhu W, et al. Viral Immunology. 2025.
3. La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity. — Boutzoukas AE, Freedman DA, Koterba C, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2023.
4. La Crosse Encephalitis in Children. — McJunkin JE, de los Reyes EC, Irazuzta JE, et al. The New England Journal of Medicine. 2001.
5. The Incidence Risk, Clustering, and Clinical Presentation of La Crosse Virus Infections in the Eastern United States, 2003-2007. — Haddow AD, Odoi A. PloS One. 2009.
6. Current Status of La Crosse Virus in North America and Potential for Future Spread. — Goldman T, Hamer DH. The American Journal of Tropical Medicine and Hygiene. 2024.
7. Spatial-Temporal Clusters of Host-Seeking Aedes Albopictus, Aedes Japonicus, and Aedes Triseriatus collections in a La Crosse Virus Endemic County (Knox County, Tennessee, USA). — Rowe RD, Odoi A, Paulsen D, Moncayo AC, Trout Fryxell RT. PloS One. 2019.
8. Geographically Persistent Clusters of La Crosse Virus Disease in the Appalachian Region of the United States From 2003 to 2021. — Day CA, Odoi A, Trout Fryxell R. PLoS Neglected Tropical Diseases. 2023.
9. La Crosse Virus Encephalitis in Children. — Ouellette CP. Current Opinion in Infectious Diseases. 2024.
10. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). — Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.
11. Diagnostic Approach for Arboviral Infections in the United States. — Piantadosi A, Kanjilal S. Journal of Clinical Microbiology. 2020.
12. Rapid Diagnosis of LaCrosse Encephalitis: Detection of Specific Immunoglobulin M in Cerebrospinal Fluid. — Dykers TI, Brown KL, Gundersen CB, Beaty BJ. Journal of Clinical Microbiology. 1985.
13. Neuropsychological and Functional Outcome After La Crosse Encephalitis in Marine Recruit: A Case Report and Literature Review. — Singh PG, Boutzoukas EM, Cagnina MC, Silva MA. Military Medicine. 2025.
14. Detection of La Crosse Virus RNA in Clinical Specimens Obtained From Children With La Crosse Infection. — Wang H, Everhart K, Oyeniran SJ, Leber AL. Journal of Clinical Virology : The Official Publication of the Pan American Society for Clinical Virology. 2026.
15. Acute Viral Encephalitis. — Tyler KL. The New England Journal of Medicine. 2018.
16. West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2023. — Padda H, Jacobs D, Gould CV, et al. MMWR. Morbidity and Mortality Weekly Report. 2025.
17. La Crosse Encephalitis: An Adult Case Series. — Teleron AL, Rose BK, Williams DM, Kemper SE, McJunkin JE. The American Journal of Medicine. 2016.