Encephalitis: Definition, Epidemiology, Etiology

Encephalitis Definition

• Encephalitis involves inflammation of the brain parenchyma, leading to neurologic dysfunction and is often determined through clinical, laboratory, and imaging findings
• Altered consciousness, behavioral changes, cognitive impairment, and inflammation are characteristics of encephalopathy, typically due to metabolic or toxic conditions

Epidemiology

• Annually, around 5 cases of encephalitis occur per 100,000 people in the US between 1990 and 2017
• More than 1 million cases of encephalitis occur worldwide each year
• Common causes can include rabies, measles, and Japanese encephalitis virus

Etiology

• In a California Encephalitis Project review of 1,570 cases over 7 years, 16% had a confirmed or probable cause and 13% had a possible etiology
• Of the confirmed cases, 69% were viral, 20% were bacterial, 7% were prion-related, 3% were parasitic, and 1% were fungal

Reasons for Unidentified Etiology

• Reasons for not identifying the cause of encephalitis include undiscovered pathogens, uncommon or common presentations by common or uncommon pathogens, and incorrect testing procedures
• Additional reasons for unidentified etiology include using the wrong test, sample, or timing, or the condition is not an infection

Pathogenesis

• Encephalitis can occur through direct invasion (neurotropism), indirect invasion (immune inflammatory process), or hematogenous spread (most common)
• Respiratory entry points include measles, VZV, influenza, and mumps
• GIT entry points include poliovirus, coxsackie, and echovirus
• Skin entry points include arthropod-borne viruses, Rickettsia rickettsia, and trypanosomes

Rabies

• Rabies is transmitted through the bite of an infected animal, with dogs being the principal vector in 98% of cases worldwide
• Transmission may occur from unrecognized bat bites
• The US has sporadic cases, with 125 reported from 1960-2018
• International dog bites accounted for 36 cases (28%) and bats accounted for 89 acquired cases in US

Rabies Risks and Diagnosis

• Rabies is a risk wherever dogs are allowed to run free
• Diagnosis for rabies can include culture and PCR of saliva, CSF ab and RT-PCR, biopsy of the nape of the neck, brain biopsy, and corneal smear

Viral Causes: Togaviridae Family

• The Togaviridae family, genus alphaviruses includes Eastern Equine virus, Western Equine virus, and Venezuelan Equine virus

Flaviviridae

• The Flaviviridae consists of about 70 members, half of which are associated with human disease
• The spherical virion is enveloped in a 40-50 nm size, and has two envelope proteins of E and M
• It has an icosahedral capsid 25-30nm in size
• The virion contains a single stranded RNA genome that is linear, has a positive polarity and is about 1.1kb

Flaviviridae Viral Causes Locations

• St. Louis encephalitis (SLE) occurs in the USA
• Japanese encephalitis (JE) occurs in Asia
• Murray Valley encephalitis occurs in Australia and New Guinea
• West Nile Virus (WNV) occurs in Africa, the Middle East, and the USA
• Tick-borne Complex is a virus that occurs worldwide

Viral Causes: Bunyaviridae

• Bunyaviridae family causes California/La Crosse encephalitis (CE) and Rift Valley virus encephalitis

St. Louis Encephalitis (SLE)

• Occurs in the USA, Canada, and the Caribbean; in urban (eastern US) and rural (western US) environments during June-August
• It is spread by mosquitoes from a bird animal host
• Diagnosed through acute/convalescent sera with adults over 50 and females being more affected
• A clinical feature is dysuria, and ranges from 2-20% mortality and has a 25% sequelae

Western Equine Encephalitis (WEE)

• Occurs in the West and Midwest regions, affecting infants and adults over 50 years old
• The mortality rate from WEE is 5-15%
• Sequelae effects include moderate in infants and low in others
• Clinical features include headaches, altered consciousness, and seizures

La Crosse Encephalitis (CE)

• A California serogroup virus found in the US Midwest & NE and southern Canada, specifically in woodlands during June-September
• The virus is spread by Aedes mosquitoes from chipmunks, squirrels, and small mammals
• Diagnosed via acute/convalescent sera, mostly affecting children under 20, with males more than females
• Clinical feature includes seizures with rare mortality sequelae

Eastern Equine Encephalitis (EEE)

• Is found in the US Atlantic, Gulf coast, Caribbean, S. America & coasts, and is spread through mosquitoes from a bird and horse animal host
• Diagnosed through acute/convalescent sera, it affects <10 and >55 year olds
• Clinical features include CSF WBC > 1000/well
• There is between 50-70% mortality, and 80% sequelae (especially children <10 years)

Japanese Encephalitis (JE)

• Occurs in East & SEA, India, and is spread in rice fields from wild birds through Culex tritaeniorhynchus mosquitoes
• The virus can be diagnosed through acute/convalescent sera
• Common GIT symptoms include 7-50% mortality, and 30-70% sequelae (young & elderly): Parkinson's like syndrome

Clinical Findings: Viral Encephalitis

• Viral encephalitis presents as an acute-onset febrile illness with headache, altered consciousness, and disorientation
• Patients may exhibit behavioral and speech disturbances, seizures, and neurologic signs include hemiparesis and cranial nerve palsies
• Temporal lobe (HSV) findings of bizarre behavior, hallucinations, aphasia indicate HSVE
• Local paresthesia at the site of bite indicate Rabies
• Parkinsonian-like Syndrome findings indicate Japanese or WNV encephalitis

Laboratory Findings: Viral Encephalitis

• Peripheral WBC can show normal results or leukopenia
• CSF shows mononuclear pleocytosis (WBC 3)
• There is elevated protein (150mg/dl)
• Glucose is normal or slightly depressed
• RBCs are absent except in cases of HSV-1

Diagnostic Tools

• EEG and CT scan can be used
• MRI scan can also be used and is more sensitive and specific than a CT scan

Presumptive Therapy

• HSV: ACV
• CMV: GCV, Foscarnet
• HIV: ZVD
• Arboviruses: Supportive
• Cerebral Edema: Mannitol, hyperventilation
• Vaccine: JE

West Nile Virus (WNV) Encephalitis

• First US cases being reported in 1999 in New York City, with birds being a main reservoir for the virus as mosquitos are its main spreading vector
• Can be transmitted through transplanted organs, blood transfusions, breast milk, transplacental, and occupational

West Nile Virus Encephalitis

• It can be confirmed through a positive IgM capture ELISA
• It is found in the USA (spreading), Israel, and Mideast in urban and rural environments from June to October
• Spread through mosquitoes from birds, diagnosis includes acute/convalescent sera