La Crosse encephalitis
Synonyms and keywords: LACV; LaCrosse virus; LAC encephalitis; Lax encephalitis

# Overview
La Crosse encephalitis is a mild infection of the central nervous system. La Crosse encephalitis virus belongs to the Group V negative-sense ssRNA family of viruses. La Crosse encephalitis virus is also known as an arbovirus. La Crosse encephalitis virus is usually transmitted via mosquitos to the human host. The amplification pattern of La Crosse encephalitis virus has been extensively studied. La Crosse encephalitis virus is contracted by the bite of an infected mosquito, primarily Aedes triseriatus. La Crosse encephalitis virus must be differentiated from other diseases that cause fever, headache, seizures, and altered mental status. There are approximately 70-115 cases of La Crosse encephalitis virus per year in the United States, most commonly affecting infants and children between the ages of 6 months and 15 years old. La Crosse encephalitis virus usually clears in 1 to 2 weeks and rarely recurs. Less than 1% of cases result in mortality. The diagnostic method of choice for La Crosse encephalitis virus is laboratory testing. There is no treatment for La Crosse encephalitis virus; the mainstay of therapy is supportive care.

# Historical Perspective
In 1963, the cause of La Crosse encephalitis was discovered near La Crosse, Wisconsin by the Hooper Foundation. La Crosse encephalitis was first discovered within the brain during the autopsy of a 4 year old boy who died from encephalitis. Upon further microscopic histopathological analysis by Whitman and Shope, it was confirmed that the La Crosse encephalitis virus was genetically related to the California encephalitis virus.

# Classification
La Crosse encephalitis may be classified according to neuroinvasiveness into 2 groups: neuroinvasive and non-neuroinvasive. La Crosse encephalitis virus belongs to the Group V negative-sense ssRNA virus within the Bunyaviridae family of viruses, and the genus Orthobunyavirus. La Crosse encephalitis virus is also known as an arbovirus, or an arthropod-borne virus. The La Crosse virus is the principal member of the California encephalitis serogroup, which contains genetically similar viruses such as California encephalitis virus.

# Pathophysiology
La Crosse encephalitis virus is usually transmitted via mosquitos to the human host. La Crosse encephalitis virus contains negative-sense viral RNA; this RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. La Crosse encephalitis virus is made up of an enveloped virion with a spherical capsid. The envelope contains G1 glycoproteins. Neutralizing antibodies against these proteins block fusion of the virus with host cells and inhibit hemagglutination. The virus genome is over 12,000 nucleotides in length, approximately 90-100 nm in diameter, and consists of three segments of various sized single-stranded RNA (negative sense and ambi-sense).
La Crosse encephalitis virus is contracted by the bite of an infected mosquito, primarily Aedes triseriatus. The virus is maintained and amplified in Aedes triseriatus populations through transovarial and venereal transmission. The virus overwinters in the mosquito egg. Amplification also occurs in chipmunks and squirrels, upon which mosquitos feed. Humans are dead-end hosts for the virus, meaning there is an insufficient amount of La Crosse encephalitis virus in the blood stream to infect a mosquito. Subsequently, the disease cannot be spread to other humans. The incubation period is 5-15 days.
La Crosse encephalitis virus is transmitted in the following pattern:
- Virus attaches to host receptors though Gn-Gc glycoprotein dimer, and is endocytosed into vesicles in the host cell.
- Fusion of virus membrane with the vesicle membrane; ribonucleocapsid segments are released in the cytoplasm.
- Transcription occurs; viral mRNAs are capped in the cytoplasm.
- Replication presumably begins when sufficient nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
- The ribonucleocapsids buds at Golgi apparatus, releasing the virion by exocytosis.

# Causes
La Crosse encephalitis virus causes La Crosse encephalitis.

# Differentiating La Crosse encephalitis from Other Disases
La Crosse encephalitis virus must be differentiated from other diseases that cause fever, headache, seizures, and altered mental status, such as:

# Epidemiology and Demographics

## Incidence
There are approximately 80-100 cases of La Crosse encephalitis per year in the United States. There is significant under-diagnosis and under-reporting of less severe cases of La Crosse encephalitis.

## Age
La Crosse encephalitis commonly affects individuals between 6 months old and 15 years of age. Adults comprise the most under-diagnosed group.

## Seasonal
The majority of La Crosse encephalitis cases are reported in the summer months between July and September, and peaks in August.

## Geographic Location
The majority of La Crosse encephalitis cases are reported in the Midwestern United States, especially those living in rural and suburban settings surrounded by deciduous forests. Historically, most cases of La Crosse encephalitis occur in the Midwest states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the Southeast United States (Virginia, Virginia, North Carolina, Alabama and Mississippi).
Maps regarding geographic distribution of La Crosse encephalitis cases can be found here.

# Risk Factors
Common risk factors in the development of La Crosse encephalitis virus include:
- Young age
- Immunosuppression
- Residing or working in rural and suburban settings
- Mosquito contact
- Summer season
- Outdoor activities such as camping or hunting

# Natural History, Complications, and Prognosis

## Natural History
La Crosse encephalitis virus usually clears in 1 to 2 weeks and rarely recurs. Less than 1% of cases result in mortality.

## Complications
Common complications of La Crosse encephalitis virus include:
- Recurring seizures
- Coma
- Loss of basic motor skills
- Loss of coordination

## Prognosis
Prognosis for La Crosse encephalitis virus is generally good, with most individuals returning to full health in 2-3 weeks. However, approximately 20% of patients have residual seizures.

# Diagnosis

## Diagnostic Criteria
Neuroinvasive vs non-neuroinvasive La Crosse encephalitis can be differentiated based on both clinical and laboratory findings. These include:

## History and Symptoms
If possible, a detailed and thorough history from the patient is necessary. Common symptoms of La Crosse encephalitis include:
- Fever
- Headache
- Nausea
- Vomiting
- Seizures
- Altered mental status
- Fatigue
- Reduced alertness

## Physical Examination
Common physical examination findings of La Crosse encephalitis include:
- Fever
- Ataxia
- Seizures
- Somnolence
- Obtundation
- Myalgia
- Acute flaccid myelitis
- Hemiparesis

## Laboratory Findings
The diagnostic method of choice for La Crosse encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of La Crosse encephalitis include:
- Serologic cross-reactivity
- Presence of IgM antibodies
- Persistence of IgG and neutralizing antibodies
- Confirmation of arboviral-specific neutralizing antibodies in enzyme linked immunosorbent assay (ELISA)
- Mildly elevated white blood cell count
- Normal glucose levels

## CT
There are no CT findings associated with La Crosse encephalitis.

## EEG
On EEG, La Crosse encephalitis virus is characterized by periodic lateralizing epilepitoform discharges. However, results on imaging are not sufficient evidence to warrant La Crosse encephalitis virus diagnosis. In rare cases, EEG findings may resemble herpes simplex encephalitis.

# Treatment

## Medical Therapy
There is no treatment for La Crosse encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for La Crosse encephalitis, physicians often do not request the tests required to specifically identify the La Crosse encephalitis virus. These cases may be reported as aseptic meningitis or viral encephalitis of unknown etiology.

## Surgery
Surgical intervention is not recommended for the management of La Crosse encephalitis.

## Prevention
There are no available vaccines against La Crosse encephalitis virus. Primary prevention strategies include:
- Removal of standing water
- Screens on doors and windows
- When outdoors, wearing:
Insect repellent containing DEET
Long sleeves, pants; tucking in pants into high socks
- Insect repellent containing DEET
- Long sleeves, pants; tucking in pants into high socks

# Gallery
- This electron micrograph reveals the morphologic traits of the La Crosse encephalitis virus, a Bunyaviridae virus family member. From Public Health Image Library (PHIL). 
- This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). 
- This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL).