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California Encephalitis
Article Last Updated: Jun 14, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Coauthor(s):
Emad Soliman, MD, MSc, Consulting Staff, Department of Neurology, St John's Riverside Hospital;
Norvin Perez, MD, Clinical Assistant Professor of Emergency Medicine, Albert Einstein College of Medicine; Consulting Staff, Department of Emergency Medicine, Montefiore Medical Center;
Eduardo Gotuzzo, MD, Adjunct Professor, Department of Medicine, University of Alabama School of Medicine
Editors: Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veteran's Administration Medical Center; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Author and Editor Disclosure
Synonyms and related keywords:
California encephalitis, La Crosse virus, encephalitis, meningitis, antiviral, vaccine, brain abscess, St. Louis encephalitis, eastern equine encephalitis
Background
California encephalitis is an arbovirus-induced, arthropod-borne encephalitis or encephalomeningitis. The virus is transmitted to humans through a mosquito bite.
The condition was named California encephalitis after the first human case (caused by a virus called California virus) was described in Kern County, California in 1946. Since then, most cases have been associated with La Crosse 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.
Pathophysiology
After inoculation via a mosquito bite, 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.
Frequency
United States
Several factors influence the epidemiology of arbovirus encephalitis, including (1) the season, (2) the geographical location, (3) the regional climate condition (eg, spring rainfall), and (4) patient age.
- Midwestern states carry the highest incidence in the United States. Most cases occur in the late summer to early fall. The incidence is approximately 75 cases per year. Increased incidence occurs with outdoor activities, especially in woodland areas.
- La Crosse encephalitis has been reported in 28 states; in areas where the disease is endemic, the incidence exceeds that of bacterial meningitis before the introduction of the Haemophilus influenzae vaccine. La Crosse encephalitis may be underrecognized, not only in terms of its prevalence but also in terms of its severity.
Mortality/Morbidity
Most patients with clinical symptoms recover completely; however, 20% of patients develop behavioral problems or recurrent seizures. Mortality rates are low ( <1%).
Sex
Incidence is higher in males than females, probably because of more outdoor exposure.
Age
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.
History
The incubation period is usually 3-7 days. A prodromal phase of 1-4 days commonly precedes the onset of encephalitis. This phase manifests as fever, chills, nausea, vomiting, headache, and abdominal pain.
- Encephalitis occurs as fever, somnolence, and obtundation.
- Seizures occur in 50% of children, and 20% of children develop focal neurologic signs (eg, asymmetrical reflexes, Babinski signs).
- Ten percent of patients develop coma.
- The total duration of illness rarely exceeds 10-14 days.
- Epilepsy develops in 20% of patients, especially those who had seizures during the acute illness.
- In adults, infection is asymptomatic or causes a benign febrile illness or aseptic meningitis.
Physical
Fever, lethargy, aphasia, incoordination, focal motor abnormalities, and paralysis may occur.
Causes
- La Crosse virus, one of the bunyaviruses (ie, negative polarity single-stranded RNA viruses with a helical and enveloped nucleocapsid), causes California encephalitis. La Crosse virus is the most common cause of arboviral-induced pediatric encephalitis in the United States.
- The Aedes triseriatus mosquito (forest-dwelling tree hole mosquito) transmits La Crosse virus. 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.
Brain Abscess
Eastern Equine Encephalitis
St. Louis Encephalitis
Other Problems to be Considered
Other arbovirus encephalitides
Herpes simplex encephalitis
Bacterial, tuberculous, or fungal meningitis
Carcinomatous meningitis
CNS vasculitis
Lab Studies
- According to the Centers for Disease Control and Prevention (CDC) guidelines for the diagnosis of arbovirus encephalitis, febrile illness or mild aseptic meningitis or encephalitis (with onset during a period when the transmission of the virus is likely) occurs with one of the following:
- A 4-fold increase in the antivirus antibody titer between the acute and the convalescent periods
- Virus isolation from tissue, blood, or cerebrospinal fluid (CSF): Note that La Crosse virus has not been isolated from CSF.
- Specific immunoglobulin M (IgM) antibodies to the virus detected using enzyme-linked immunosorbent assay (ELISA) technique during the acute illness
- 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.
- CSF examination reveals 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 leucocytosis is present.
- Complete blood cell count is usually within the reference range or might show mild leucocytosis. Chemistries are usually within the reference range.
- Use of the polymerase chain reaction for the diagnosis of La Crosse encephalitis is still in the research stage.
Imaging Studies
- Neuroimaging using conventional CT scans and MRI is not helpful in establishing the diagnosis of California encephalitis.
- In very severe cases, a CT scan might show nonspecific enhancement (see Image 3).
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 brainstem is relatively spared. Perivascular cuffing with lymphocytes and plasma cells occurs, as well as patchy infiltration of the meninges (see Image 2).
Medical Care
- No antiviral agent is available.
- Supportive care is the mainstay of treatment.
- Treat seizures or any neurologic symptoms.
- No vaccine is available for preexposure protection.
- Patient isolation during acute illness is unnecessary.
Activity
Bed rest is always recommended until recovery.
Deterrence/Prevention
- Insect repellents
- Mosquito control by controlling the breeding sites and use of spray insecticides
- Wearing long sleeves for outdoor activities
Complications
- Twenty percent of patients develop behavioral problems or recurrent seizures.
Prognosis
- Most patients recover completely, although 20% of patients develop behavioral or recurrent seizures. Mortality rates are low (<1%).
Patient Education
Medical/Legal Pitfalls
- Failure to keep the diagnosis of California encephalitis in mind can lead to serious consequences. The condition should be high on the differential list when a patient comes from an endemic area or has a history of exposure with change in mental status, headache, or seizure.
| Media file 1:
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. |
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Media type: Image
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| Media file 2:
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. |
 | View Full Size Image | |
Media type: Photo
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| Media file 3:
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). |
 | View Full Size Image | |
Media type: CT
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California Encephalitis excerpt Article Last Updated: Jun 14, 2006
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