California Encephalitis

Updated: May 14, 2021
Author: Folusakin O Ayoade, MD; Chief Editor: Michael Stuart Bronze, MD 



California encephalitis (CE)  is a relatively common, reportable, childhood central nervous system (CNS) disease transmitted by mosquito bite. It is second in importance to West Nile viral encephalitis among the mosquito-borne viral diseases in the United States, with about 68 cases reported yearly. 

La Crosse virus neuroinvasive disease cases report La Crosse virus neuroinvasive disease cases reported in the United states from 2010-2019. Courtesy of CDC and ArboNET (

The condition was named California encephalitis after the first human case  was described in Kern County, California, in 1946 [1]  even though most cases in the United States are rarely from California or the West coast. Since first described, most cases of CE have been associated with La Crosse (LAC) virus, a closely related virus to CE virus. La Crosse virus was first isolated from the brain of a 4-year-old boy who died of encephalitis  in La Crosse County, Wisconsin.

 Most infections due to CE virus are asymptomatic, and the majority of infected individuals who develop symptoms recover completely; however, up to 10% of patients develop behavioral problems or recurrent seizures. Severe disease often manifests as encephalitis (inflammation of the brain) and can cause seizures, coma, and paralysis. Mortality rates are low (< 1%).



California encephalitis (CE) is caused by a group of viruses that belong to the genus Bunyavirus and the family Bunyaviridae. This largest family of RNA viruses has more than 350 named isolates with worldwide distribution. Bunyaviruses are spherical, lipid membrane–enclosed viruses that are 90-110 nm in diameter. They contain 3 negative-sense RNA segments and an enveloped nucleocapsid. The nucleocapsid protein is believed to be immunogenic.

It Is caused by 3 serogroup of bunyaviruses that are  closely related. California encephalitis virurs (CEV),  rarely causes human infection. La Crosse virus  and Jamestown Canyon,  more commonly cause human diseases

La Crosse virus is the most common cause of arboviral-induced pediatric encephalitis in the United States. The principal vector is Aedes triseriatus, a forest-dwelling, tree-hole–breeding mosquito of the north central and northeastern regions of the United States. La Crosse virus is maintained in the mosquito via transovarial transmission supplemented by venereal transmission and amplification during summer by mosquitoes feeding on viremic chipmunks, foxes, squirrels, and woodchucks. During winter, the virus survives in infected mosquito eggs.[2]

Aedes. triseriatus and Aedes. albopictus are important  vectors and Aedes  japonicus also may be involved in virus maintenance and transmission (ref Alternating cycles of infection occur between the mosquito and the vertebrate hosts, including humans. The mosquitoes obtain the virus after a blood meal from hosts who are in the viremia stage. 

La Crosse virus transmission cycle. The virus is m La Crosse virus transmission cycle. The virus is maintained by vertical transmission in Aedes triseriatus mosquitoes; the virus winters in infected eggs that are usually deposited in tree holes or in artificial containers holding rainwater. Horizontal transmission (by viral amplification in small vertebrates, eg, squirrels and chipmunks, and venereally among adult mosquitoes) is required to supplement vertical transmission. The role of deer in viral amplification is uncertain. Human infections are incidental to the transmission cycle.

After inoculation via a mosquito bite (usually the female mosquito), the virus undergoes a local replication at the original skin site. A primary viremia occurs, with seeding of the reticuloendothelial system, mainly the liver, spleen, and lymph nodes.

With continued virus replication, a secondary viremia occurs, with seeding of the CNS. The probability of CNS infection depends on the efficiency of viral replication at the extraneural sites and the degree of viremia. The virus invades the CNS through either the cerebral capillary endothelial cells or the choroid plexus. Rarely, the virus is isolated from brain tissue.

Antibodies against the G1 part of the virus neutralize the virus, block fusion, and inhibit hemagglutination. They are also important in virus clearance and recovery and in prevention of reinfection.


Several epidemiologic factors influence arboviral encephalitis, including (1) the season, (2) the geographic location, (3) the regional climate conditions (eg, spring rainfall), and (4) patient age.

The highest incidence of arboviral encephalitis in the United States is in the midwestern states. Most cases occur in the late summer to early fall, although, in subtropical endemic areas (eg, the Gulf States), some cases occur in winter. Outdoor activities, especially in woodland areas, are associated with an increased risk of infection.

Historically, La Crosse encephalitis has been reported in 28 states, mostly from the northern Midwestern states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases have been reported from mid-Atlantic ,  southeastern  and northeastern states (West Virginia, Virginia, Kentucky, Georgia  North Carolina, and Tennessee). 

La Crosse virus neuroinvasive disease cases report La Crosse virus neuroinvasive disease cases reported by state, 2010-2019. Courtesy of CDC and ArboNET (

California encephalitis is more common in males than in females, probably because of more outdoor exposure. Clinical disease occurs almost exclusively in children aged 6 months to 16 years (peak, 4-10 y). The older the patient, the less likely he or she is to develop the clinical illness Sometimes it could  underrecognized in terms its prevalence and severity.

Patient Education

For patient education information, see the Brain and Nervous System Center, as well as Encephalitis.



History and Physical Examination

The incubation period of California encephalitis is usually 3-7 days. A prodromal phase of 1-4 days commonly precedes the onset of encephalitis. This phase manifests as any or all of the following:

  • Fever

  • Chills

  • Nausea

  • Vomiting

  • Headache

  • Abdominal pain

The encephalitis is characterized by fever and somnolence, which may progress to obtundation. Although most patients make uneventful recoveries, electroencephalographic findings are abnormal 1-5 years later in 75% of cases, emotional lability is persistent in 10%, and epilepsy is a chronic problem in 6%-10% of all diagnosed cases. Although uncommon, frank neurologic deficit can also occur.[3] Twenty percent of children develop focal neurologic signs (eg, asymmetrical reflexes, Babinski signs), and 10% of patients develop coma. Periodic lateralizing epileptiform discharges (PLEDS) can be seen in the temporal lobe. The total duration of illness rarely exceeds 10-14 days.

Two reports in the literature have described LaCrosse encephalitis manifesting as signs and symptoms of herpes simplex encephalitis.[4, 5]

In adults, infection is asymptomatic or causes a benign febrile illness or aseptic meningitis.

Physical findings may include the following:

  • Fever

  • Lethargy

  • Focal neurologic findings (eg, aphasia)

  • Incoordination

  • Focal motor abnormalities

  • Paralysis


Complications may be associated with more severe disease. These include the following:

  • Epilepsy (commonest and most serious)
  • Cognitive and memory deficits
  • Lethargy
  • Aphasia
  • Incoordination
  • Focal motor abnormalities
  • Paralysis


Diagnostic Considerations

California encephalitis should be high on the differential diagnosis list in (1) patients who live in or have recently traveled to an endemic area and in (2) patients with a history of exposure with fever, change in mental status, headache, or seizure.

Conditions to consider in the differential diagnosis of California encephalitis include the following:

  • Other arbovirus encephalitides[6]

  • Herpes simplex encephalitis

  • Varicella zoster encephalitis

  • Powassan virus encephalitis

  • Bacterial, tuberculous, or fungal meningitis

  • Carcinomatous meningitis

  • CNS vasculitis

  • Aseptic meningitis

Differential Diagnoses



Approach Considerations

The diagnosis of California encephalitis is based on immunology, because the virus is not present in blood or secretions during clinical CNS disease. The diagnosis can be established as follows:

  • Specific immunoglobulin M (IgM) and neutralizing antibodies to the virus in serum or cerebrospinal fluid (CSF) using enzyme-linked immunosorbent assay (ELISA) technique: IgM is usually but not always present during acute illness.
  • A 4-fold increase in the antivirus antibody titer between the acute and the convalescent periods, although this may not be observed in every case [7]
  • In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry and virus culture of autopsy tissues can also be useful. Only a few state laboratories or other specialized laboratories, including those at the Centers for Disease Control and Prevention (CDC), are capable of performing this specialized testing.

Antibody studies

Significant antibody titers include levels of more than 320 by hemagglutination inhibition, more than 128 by complement fixation, more than 256 by immunofluorescence, or more than 160 by plaque reduction neutralization test.

 A licensed indirect fluorescent antibody test is available for IgG and IgM antibodies to La Crosse virus and may be useful in diagnosis.[7]

CSF examination

In general, the findings are nonspecific and similar to other presentations of viral meningoencephalitis.

CSF examination may reveal the following:

  • Normal to mildly elevated pressure level
  • Normal glucose level and normal to mildly elevated protein level
  • Initially, a polymorphonuclear leukocytic pleocytosis followed by lymphocytic or monocytic leukocytosis is present.

Complete blood count and chemistry

The complete blood count (CBC) is usually within the reference range or might show mild leukocytosis. Peripheral leukocytosis in excess of 15,000 WBCs/µL is not uncommon. Chemistry findings are usually within the reference range, but hyponatremia (low serum sodium level) has been observed in up to 20% of patients in at least one case series.[3]

Polymerase chain reaction

Polymerase chain reaction (PCR)  for the diagnosis of La Crosse encephalitis and Metagenomic next-generation sequencing (NGS) of the  CSF has the potential to identify a broad range of pathogens in a single test (ref DOI: 10.1056/NEJMoa1803396). This studies  still in the research stage.


De los Reyes and colleagues found that children with La Crosse encephalitis who have PLEDS on electroencephalograms have a higher rate of complications.[8]

CT Scanning and MRI

Neuroimaging using conventional computed tomography (CT) scanning and magnetic resonance imaging (MRI) is not helpful in establishing the diagnosis of California encephalitis. In very severe cases, CT scanning might show nonspecific enhancement. 

Left image of a CT scan of an 8-year-old boy with Left image of a CT scan of an 8-year-old boy with severe La Crosse encephalitis complicated by uncal herniation (obtained on the second hospital day) reveals brain edema with associated obliteration of perimesencephalic cisterns (arrows). On the right, a T2-weighted magnetic resonance image obtained from a 7-year-old boy with severe La Crosse encephalitis shows focal areas of increased signal intensity in the right temporoparietal and left frontotemporal regions (arrows).

Histologic Findings

On pathologic examination, as with all viral encephalitides, there is a widespread degeneration of single nerve cells, with neuronophagia and scattered foci of inflammatory necrosis involving the gray and white matter. The brain stem is relatively spared. Perivascular cuffing with lymphocytes and plasma cells occurs, as well as patchy infiltration of the meninges. 

Brain biopsy specimen from a 7-year-old boy with s Brain biopsy specimen from a 7-year-old boy with severe La Crosse encephalitis (hematoxylin and eosin stain, 200X). Perivascular infiltration with mononuclear cells is present on light microscopy. This biopsy material tested positively for La Crosse virus antigen on direct immunofluorescence assay.


Approach Considerations

No specific antiviral treatment for California encephalitis is approved at this time. Supportive care is therefore the mainstay of management. La Crosse virus has in vitro sensitivity to ribavirin, and treatment of one unusual case diagnosed with brain biopsy has been reported.[9]  Valinomycin, a potassium ionophore, exhibited activity against La Crosse virus in multiple cell types in a dose-dependent manner, suggesting a potential therapeutic target to disrupt virus replication.[10]  

Because neurologic complications are the most severe and closely linked to disease mortality, control of seizures and optimal neurologic support are vital components of management. Patient isolation during acute illness is unnecessary. Bed rest is always recommended until recovery.


No vaccines are available at this time.

Preventive measures include the following:

  • Insect repellents
  • Mosquito control by controlling the breeding sites, including elimination of manufactured containers and use of spray insecticides.
  • Wearing long sleeves for outdoor activities
  • Mosquito prevention techniques, possibly including the repellant effect of certain essential oils [11]


Medication Summary

Supportive care is the mainstay of treatment. The drugs in supportive care consist of agents capable of ameliorating neurologic complications. Antipyretics are used as needed. No antiviral agent is available, and no vaccine is available for preexposure protection.

Anticonvulsant Agents

Class Summary

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.

Phenytoin (Dilantin, Phenytek)

Phenytoin may act in the motor cortex, where it may inhibit the spread of seizure activity. The activity of brain stem centers responsible for the tonic phase of grand mal seizures may also be inhibited.

Individualize the dose. Administer a larger dose before retiring if the dose cannot be divided equally. The rate of infusion must not exceed 50 mg per minute to avoid hypotension and arrhythmia.

Diazepam (Valium)

Diazepam depresses all levels of the CNS (eg, limbic, reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Alternatively, lorazepam can be used when indicated.


Class Summary

These agents are helpful in relieving the associated lethargy, malaise, and fever associated with the disease.

Acetaminophen (Acephen, Feverall, Tylenol)

Acetaminophen inhibits the action of endogenous pyrogens on heat-regulating centers. It reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increases the dissipation of body heat via sweating and vasodilation.