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=La Crosse Encephalitis=
{{SK}} LACV; LaCrosse virus; LAC encephalitis; Lax encephalitis
'''La Crosse encephalitis''' is an [[encephalitis]] caused by an [[arbovirus]] (the '''La Crosse [[virus]]''') which has a [[mosquito]] [[vector (biology)|vector]] ([[Aedes|''Aedes'']] ''triseriatus'').  It occurs in the [[Appalachian]] and [[Midwestern]] regions of the [[United States]].  Recently there has been an increase of cases in the South East of the United States.  An explanation to this may be that the mosquito Aedes albopictus is also an effecient vector of La Crosse virus.  Aedes albopictus is a species that has entered the US and spread across the SE of the US and replaced Aedes aegypti in most areas (which is not an efficient vector of LAC).


La Crosse (LAC) [[encephalitis]] was discovered in [[La Crosse, Wisconsin]] in 1963. Since then, the virus has been identified in several Midwestern and Mid-Atlantic states. During an average year, about 75 cases of LAC encephalitis are reported to the CDC. Most cases of LAC encephalitis occur in children under 16 years of age. LAC virus is a Bunyavirus and is a zoonotic pathogen cycled between the daytime-biting treehole mosquito, Aedes triseriatus, and vertebrate amplifier hosts (chipmunks, tree squirrels) in deciduous forest habitats. The virus is maintained over the winter by transovarial transmission in mosquito eggs. If the female mosquito is infected, she may lay eggs that carry the virus, and the adults coming from those eggs may be able to transmit the virus to chipmunks and to humans.
==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 virus|negative-sense ssRNA family of viruses]]. La Crosse encephalitis virus is also known as an [[arbovirus]]. La Crosse encephalitis virus is usually transmitted via [[mosquito]]s 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.


Historically, most cases of LAC encephalitis occur in the upper Midwestern states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the mid-Atlantic (West Virginia, Virginia and North Carolina) and southeastern (Alabama and Mississippi) regions of the country. It has long been suspected that LAC encephalitis has a broader distribution and a higher incidence in the eastern United States, but is under-reported because the etiologic agent is often not specifically identified.
==Historical Perspective==
In 1963, the cause of La Crosse encephalitis was discovered near La Crosse, Wisconsin by the Hooper Foundation.<ref name=Neurovirology> Tselis AC, Booss J. Neurovirology, Handbook of Clinical Neurology Series (Series Editors: Aminoff, Boller, Swaab). Newnes; 2014.</ref> 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]].<ref name="pmid14000396">{{cite journal| author=WHITMAN L, SHOPE RE| title=The California complex of arthropod-borne viruses and its relationship to the Bunyamwera group through Guaroa virus. | journal=Am J Trop Med Hyg | year= 1962 | volume= 11 | issue=  | pages= 691-6 | pmid=14000396 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14000396  }} </ref><ref name="pmid14261030">{{cite journal| author=THOMPSON WH, KALFAYAN B, ANSLOW RO| title=ISOLATION OF CALIFORNIA ENCEPHALITIS GROUP VIRUS FROM A FATAL HUMAN ILLNESS. | journal=Am J Epidemiol | year= 1965 | volume= 81 | issue=  | pages= 245-53 | pmid=14261030 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14261030  }} </ref>


Other similar diseases that are spread by mosquitoes include: Western and Eastern [[Equine Encephalitis]], [[Japanese Encephalitis]], [[St. Louis Encephalitis]] and [[West Nile Virus]].
==Classification==
La Crosse encephalitis may be classified according to [[invasive|neuroinvasiveness]] into 2 groups: neuroinvasive and non-neuroinvasive.<ref name=WVPubHealth> 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 </ref> 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]].<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on March 1, 2016.</ref>


==Symptoms==
==Pathophysiology==
La Crosse encephalitis virus is usually transmitted via [[mosquito]]s to the human host. La Crosse encephalitis virus contains [[negative-sense ssRNA virus|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 virus|enveloped virion]] with a spherical [[capsid]]. The envelope contains G1 [[glycoprotein]]s. Neutralizing [[antibodies]] against these proteins block fusion of the virus with host cells and inhibit [[hemagglutination]]. The virus genome is over 12,000 [[nucleotide]]s in length, approximately 90-100 nm in diameter, and consists of three segments of various sized single-stranded [[RNA]] (negative sense and ambi-sense).<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref>


[[Symptom]]s include [[nausea]], [[headache]], [[vomit]]ing in milder cases and [[seizure]]s, [[coma]], [[paralysis]] and permanent [[brain damage]] in severe cases.
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 transmission|transovarial]] and [[venereal|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.<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>


LAC encephalitis initially presents as a nonspecific summertime illness with fever, headache, nausea, vomiting and lethargy. Severe disease occurs most commonly in children under the age of 16 and is characterized by seizures, coma, paralysis, and a variety of neurological sequelae after recovery. Death from LAC encephalitis occurs in less than 1% of clinical cases. In many clinical settings, pediatric cases presenting with CNS involvement are routinely screened for herpes or enteroviral etiologies. Since there is no specific treatment for LAC encephalitis, physicians often do not request the tests required to specifically identify LAC virus, and the cases are reported as aseptic meningitis or viral encephalitis of unknown etiology.
La Crosse encephalitis virus is transmitted in the following pattern:<ref name=SIBSwiss> Bunyaviridae. SIB Swiss Institute of Bioinformatics http://viralzone.expasy.org/viralzone/all_by_species/82.html Accessed on March 1, 2016 </ref>
#Virus attaches to host receptors though Gn-Gc [[glycoprotein]] [[dimer]], and is [[endocytosis|endocytosed]] into [[Vesicle (biology)|vesicles]] in the [[Host (biology)|host cell]].
#Fusion of [[biological membrane|virus membrane]] with the [[cell membrane|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 [[genome]]s.
#The ribonucleocapsids buds at [[Golgi apparatus]], releasing the virion by [[exocytosis]].


Like with many [[infection]]s, the very young, the very old and the [[immunocompromised]] are at a higher risk of developing severe symptoms.
==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:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name=NYDeptofHealth> 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 </ref><ref name=LACVMinnPH> La Crosse encephalitis fact sheet (2013). http://www.health.state.mn.us/divs/idepc/diseases/lacencephalitis/lc.html Accessed on March 1, 2016. </ref><ref name="pmid21932127">{{cite journal| author=Eckstein C, Saidha S, Levy M| title=A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis. | journal=J Neurol | year= 2012 | volume= 259 | issue= 5 | pages= 801-16 | pmid=21932127 | doi=10.1007/s00415-011-6240-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932127  }} </ref><ref name="pmid11260760">{{cite journal| author=De Kruijk JR, Twijnstra A, Leffers P| title=Diagnostic criteria and differential diagnosis of mild traumatic brain injury. | journal=Brain Inj | year= 2001 | volume= 15 | issue= 2 | pages= 99-106 | pmid=11260760 | doi=10.1080/026990501458335 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11260760  }} </ref>
 
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 50px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Similarities}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Differentials}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | Classic triad of [[fever]], [[nuchal rigidity]], and [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Photophobia]], [[phonophobia]], [[rash]] associated with [[meningococcemia]], concomitant [[sinusitis]] or [[otitis]], swelling of the [[fontanelle]] in infants (0-6 months)
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fever]], [[headache]], [[hemiparesis]]
| style="padding: 5px 5px; background: #F5F5F5;" |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
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Demyelinating disease]]s'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[lethargy]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[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
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Substance abuse]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Tremor]], [[headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, [[paranoia]], sudden [[panic]], [[anxiety]], [[hallucination]]s
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Electrolyte disturbance]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fatigue]], [[headache]], [[nausea]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on deficient ions; clinically, [[edema]], [[constipation]], [[hallucination]]s; on [[EKG]], abnormalities in [[T wave]], [[P wave]], [[QRS complex]]; possible presentations include [[arrhythmia]], [[dehydration]], [[renal failure]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Stroke]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[aphasia]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on classification of stroke; presents with positional [[vertigo]], high [[blood pressure]], [[extremities|extremity]] weakness
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Intracranial hemorrhage]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[coma]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" | Lobar [[hemorrhage]], [[numbness]], [[tingling]], [[hypertension]], [[hemorrhagic diathesis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Trauma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[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.<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref>
 
===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 [http://www.cdc.gov/lac/tech/epi.html 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]].<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
 
===Complications===
Common complications of La Crosse encephalitis virus include:
*Recurring [[seizure]]s
*[[Coma]]
*Loss of basic [[motor skill]]s
*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]] [[seizure]]s.
 
==Diagnosis==
===Diagnostic Criteria===
Neuroinvasive vs non-neuroinvasive La Crosse encephalitis can be differentiated based on both clinical and laboratory findings. These include:<ref name=WVPubHealth> 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 </ref>
 
{| class="wikitable"
! style="text-align: center; font-weight: bold;" | La Crosse Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{unicode|☑}} 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
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid]] in, [[tissue]], [[blood]], or other body fluid, excluding [[cerebrospinal fluid]] '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} 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:<ref name=CDCLACV> La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016. </ref><ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid26595861">{{cite journal| author=Richie MB, Josephson SA| title=A Practical Approach to Meningitis and Encephalitis. | journal=Semin Neurol | year= 2015 | volume= 35 | issue= 6 | pages= 611-20 | pmid=26595861 | doi=10.1055/s-0035-1564686 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26595861  }} </ref>
*[[Fever]]
*[[Headache]]
*[[Nausea]]
*[[Vomiting]]
*[[Seizure]]s
*[[Altered mental status]]
*[[Fatigue]]
*[[Lethargy|Reduced alertness]]
 
===Physical Examination===
Common physical examination findings of La Crosse encephalitis include:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Somnolence]]
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|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:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*[[Serologic]] [[cross-reactivity]]
*Presence of [[IgM]] [[antibody|antibodies]]
*Persistence of [[IgG]] and neutralizing [[antibody|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.<ref name="pmid18160548">{{cite journal| author=de los Reyes EC, McJunkin JE, Glauser TA, Tomsho M, O'Neal J| title=Periodic lateralized epileptiform discharges in La Crosse encephalitis, a worrisome subgroup: clinical presentation, electroencephalogram (EEG) patterns, and long-term neurologic outcome. | journal=J Child Neurol | year= 2008 | volume= 23 | issue= 2 | pages= 167-72 | pmid=18160548 | doi=10.1177/0883073807307984 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18160548  }} </ref> 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==
==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.<ref name=IDSAEnceph> 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.</ref>
===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:<ref name=OHIOPubHealth> La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on February 25, 2016.</ref>
*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==
<gallery>
Image: Bunyaviridae08.jpeg| This electron micrograph reveals the morphologic traits of the La Crosse encephalitis virus, a Bunyaviridae virus family member. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


No specific therapy is available at present for La Crosse encephalitis, and management is limited to alleviating the symptoms and balancing [[Body fluid|fluid]]s and [[electrolyte]] levels.
Image: Bunyaviridae07.jpeg| This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


==External links==
Image: Bunyaviridae05.jpeg| This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse encephalitis virus ribonucleoprotein particles (RNP). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
*[http://chppm-www.apgea.army.mil/ento/facts/lacrosse.pdf US Army fact sheet]
*[http://www.encephalitisglobal.com Encephalitis Global Inc.]Offering information and support to encephalitis survivors, caregivers and loved ones.


</gallery>
==References==
{{reflist|2}}


[[Category:Viruses]]
[[Category:Viruses]]
[[Category:Neurological disorders]]
[[Category:Neurology]]
[[Category:Viral diseases]]
 


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List of terms related to La Crosse encephalitis

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
Template:Unicode Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician AND
Template:Unicode Absence of a more likely clinical explanation
Template:Unicode Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, cerebrospinal fluid (CSF) OR
Template:Unicode Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
Template:Unicode Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen OR
Template:Unicode 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
Template:Unicode Fever and chills as reported by the patient or a health care provider AND
Template:Unicode Absence of neuroinvasive disease AND
Template:Unicode Absence of a more likely clinical explanation
Template:Unicode Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, or other body fluid, excluding cerebrospinal fluid OR
Template:Unicode Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
Template:Unicode 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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