La Crosse encephalitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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.[1] 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.[2][3]

Classification

La Crosse encephalitis may be classified according to neuroinvasiveness into 2 groups: neuroinvasive and non-neuroinvasive.[4] 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.[5]

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).[6]

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.[5]

La Crosse encephalitis virus is transmitted in the following pattern:[7]

  1. Virus attaches to host receptors though Gn-Gc glycoprotein dimer, and is endocytosed into vesicles in the host cell.
  2. Fusion of virus membrane with the vesicle membrane; ribonucleocapsid segments are released in the cytoplasm.
  3. Transcription occurs; viral mRNAs are capped in the cytoplasm.
  4. Replication presumably begins when sufficient nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
  5. 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:[8][9][10][11][12]

Disease Similarities Differentials
Meningitis Classic triad of fever, nuchal rigidity, and altered mental status Photophobia, phonophobia, rash associated with meningococcemia, concomitant sinusitis or otitis, swelling of the fontanelle in infants (0-6 months)
Brain abscess Fever, headache, hemiparesis Varies depending on the location of the abscess; clinically, visual disturbance including papilledema, decreased sensation; on imaging, a lesion demonstrates both ring enhancement and central restricted diffusion
Demyelinating diseases Ataxia, lethargy Multiple sclerosis: clinically, nystagmus, internuclear ophthalmoplegia, Lhermitte's sign; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)

Acute disseminated encephalomyelitis: clinically, somnolence, myoclonic movements, and hemiparesis; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders

Substance abuse Tremor, headache, altered mental status Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, paranoia, sudden panic, anxiety, hallucinations
Electrolyte disturbance Fatigue, headache, nausea Varies depending on deficient ions; clinically, edema, constipation, hallucinations; on EKG, abnormalities in T wave, P wave, QRS complex; possible presentations include arrhythmia, dehydration, renal failure
Stroke Ataxia, aphasia, dizziness Varies depending on classification of stroke; presents with positional vertigo, high blood pressure, extremity weakness
Intracranial hemorrhage Headache, coma, dizziness Lobar hemorrhage, numbness, tingling, hypertension, hemorrhagic diathesis
Trauma Headache, altered mental status Amnesia, loss of consciousness, dizziness, concussion, contusion

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.[6]

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.[5]

Complications

Common complications of La Crosse encephalitis virus include:

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:[4]

La Crosse Encephalitis Subtype Clinical Presentation Laboratory Findings
Neuroinvasive
Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician AND
Absence of a more likely clinical explanation
Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, cerebrospinal fluid (CSF) OR
Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen OR
Virus-specific IgM antibodies in cerebrospinal fluid, with or without a reported pleocytosis, and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
Non-neuroinvasive
Fever and chills as reported by the patient or a health care provider AND
Absence of neuroinvasive disease AND
Absence of a more likely clinical explanation
Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, or other body fluid, excluding cerebrospinal fluid OR
Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen

History and Symptoms

If possible, a detailed and thorough history from the patient is necessary. Common symptoms of La Crosse encephalitis include:[6][8][13]

Physical Examination

Common physical examination findings of La Crosse encephalitis include:[5]

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:[5]

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.[14] 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.[15]

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:[5]

  • 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

Gallery

References

  1. Tselis AC, Booss J. Neurovirology, Handbook of Clinical Neurology Series (Series Editors: Aminoff, Boller, Swaab). Newnes; 2014.
  2. WHITMAN L, SHOPE RE (1962). "The California complex of arthropod-borne viruses and its relationship to the Bunyamwera group through Guaroa virus". Am J Trop Med Hyg. 11: 691–6. PMID 14000396.
  3. THOMPSON WH, KALFAYAN B, ANSLOW RO (1965). "ISOLATION OF CALIFORNIA ENCEPHALITIS GROUP VIRUS FROM A FATAL HUMAN ILLNESS". Am J Epidemiol. 81: 245–53. PMID 14261030.
  4. 4.0 4.1 Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016
  5. 5.0 5.1 5.2 5.3 5.4 5.5 La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on March 1, 2016.
  6. 6.0 6.1 6.2 La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016.
  7. Bunyaviridae. SIB Swiss Institute of Bioinformatics http://viralzone.expasy.org/viralzone/all_by_species/82.html Accessed on March 1, 2016
  8. 8.0 8.1 M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.
  9. Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016
  10. La Crosse encephalitis fact sheet (2013). http://www.health.state.mn.us/divs/idepc/diseases/lacencephalitis/lc.html Accessed on March 1, 2016.
  11. Eckstein C, Saidha S, Levy M (2012). "A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis". J Neurol. 259 (5): 801–16. doi:10.1007/s00415-011-6240-5. PMID 21932127.
  12. De Kruijk JR, Twijnstra A, Leffers P (2001). "Diagnostic criteria and differential diagnosis of mild traumatic brain injury". Brain Inj. 15 (2): 99–106. doi:10.1080/026990501458335. PMID 11260760.
  13. Richie MB, Josephson SA (2015). "A Practical Approach to Meningitis and Encephalitis". Semin Neurol. 35 (6): 611–20. doi:10.1055/s-0035-1564686. PMID 26595861.
  14. de los Reyes EC, McJunkin JE, Glauser TA, Tomsho M, O'Neal J (2008). "Periodic lateralized epileptiform discharges in La Crosse encephalitis, a worrisome subgroup: clinical presentation, electroencephalogram (EEG) patterns, and long-term neurologic outcome". J Child Neurol. 23 (2): 167–72. doi:10.1177/0883073807307984. PMID 18160548.
  15. The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.
  16. 16.0 16.1 16.2 "Public Health Image Library (PHIL)".




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