Dr. Shatdal Chaudhary, M.D.
Universal College of Medical Sciences,
• Encephalitis is an acute inflammatory process affecting the brain
• Viral infection is the most common and important cause, with
over 100 viruses implicated worldwide
• Incidence of 3.5-7.4 per 100,000 persons per year
• ~20,000 cases reported anually in USA
Causes of Viral Encephalitis
• Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, EpsteinBarr virus, human herpes virus 6
• Influenza A
• Enteroviruses, poliovirus
• Measles, mumps, and rubella viruses
• Arboviruses – examples: Japanese encephalitis; St. Louis encephalitis virus;
West Nile encephalitis virus; Eastern, Western and Venzuelan equine
encephalitis virus; tick borne encephalitis virus
• Bunyaviruses – examples: La Crosse strain of California virus
• Reoviruses – example: Colorado tick fever virus
• Arenaviruses – example: lymphocytic choriomeningitis virus
What Is An Arbovirus?
• Arboviruses = arthropod-borne viruses
• Arboviruses are maintained in nature through biological
transmission between susceptible vertebrate hosts by bloodfeeding arthropods
• Vertebrate infection occurs when the infected arthropod
takes a blood meal
Major Arboviruses That Cause
• Japanese encephalitis
• St. Louis encephalitis
• West Nile
• Eastern equine encephalitis
• Western equine encephalitis
• La Crosse encephalitis
• Flavivirus related to St. Louis
• Most important cause of
arboviral encephalitis worldwide,
with over 45,000 cases reported
• Transmitted by culex mosquito,
which breeds in rice fields
• Mosquitoes become infected by
feeding on domestic pigs and wild
birds infected with Japanese
encephalitis virus. Infected
mosquitoes transmit virus to
humans and animals during the
History of Japanese
• 1800s – recognized in Japan
• 1924 – Japan epidemic. 6125 cases, 3797 deaths
• 1935 – virus isolated in brain of Japanese patient
who died of encephalitis
• 1938 – virus isolated from Culex mosquitoes in
• Today – extremely prevalent in South East Asia.
30,000-50,000 cases reported each year.
Distribution of Japanese
Encephalitis in Asia, 1970-1998
West Nile Virus
• Primary host – wild
• Principal arthropod
vector – mosquitoes
• Geographic distribution
- Africa, Middle East,
Western Asia, Europe,
St. Louis Encephalitis
• Most common
human pathogen in the
• Leading cause of
Eastern Equine Encephalitis
• Caused by a virus transmitted to
humans and horses by the bite of
an infected mosquito.
• 200 confirmed cases in the US
• Human cases occur relatively
infrequently, largely because the
primary transmission cycle takes
place in swamp areas where
populations tend to be limited.
Western Equine Encephalitis
• 639 confirmed cases in
the US since 1964
• Important cause of
encephalitis in horses
and humans in North
America, mainly in the
Western parts of the US
La Crosse Encephalitis
• On average 75 cases per year
reported to the CDC
• Most cases occur in children under
16 years old
• Zoonotic pathogen that cycles
between the daytime biting treehole
mosquito, and vertebrate amplifier
hosts (chipmunk, tree squirrel) in
deciduous forest habitats
• 1963 – isolated in La Crosse, WI from
the brain of a child who died from
Summary – Confirmed and Probable
Human Cases in the US
Western Equine 1964-2000
• Malaise, Anorexia, Nausea and Vomiting
• Abdominal pain
• Altered level of consciousness
• Mild lethargy to Coma
• Behavioral changes, hallucinations, agitations,
personality changes, frank psychosis
• Focal neurologic deficits:
• Virtually every possible focal neurological disturbance
has been reported.
• Weakness: Hemiparesis with hyperactive tendon
• Cranial nerve deficits
• Involantary movements- tremors, myoclonic jerks
• Seizures >50% patients
• Detailed history critical to determine the likely cause of encephalitis.
• Prodromal illness, recent vaccination, development of few days →
Acute Disseminated Encephalomyelitis (ADEM) .
• Biphasic onset: systemic illness then CNS disease → Enterovirus
• Abrupt onset, rapid progression over few days → HSE.
• Recent travel and the geographical context:
• Africa → Cerebral malaria
• Asia → Japanese encephalitis
• High risk regions of Europe and USA → Lyme disease
• Recent animal bites → Tick borne encephalitis or Rabies.
• Forest worker, exposed to tick bites
• Medical personnel, possible exposure to infectious diseases.
• CSF examination: Should be performed in all the
patients until contraindicated
• Diagnosis is usually based on CSF
Mild increase in protein
Inrease cells with predominantly lymphocytes
Absence of bacteria on culture.
Viruses occasionally isolated directly from CSF
• Less than half are identified
• CSF PCR techniques
• Detect specific viral DNA in CSF
• Usually available for HSVCMV, EBV, HHV6, ENTEROVIRUS, VZV
• CSF CULTURE
MRI/ CT Scan
• Can exclude subdural bleeds, tumor, and sinus
• Help by
• Focal or diffuse ence4phalitis process
• In HSV encephalitis- 80% abnormalities in temporal lobe
• In HSV: Periodic focal temporal lobe spikes on a background of
slow or low amplitude activity.
• Is generally reserved for patients in whom CSF PCR fail to lead
a specific diagnosis
Reserved for patients who are worsening, have an undiagnosed
lesion after scan, or a poor response to acyclovir.
Treatment of raised ICP
• Fever, dehydration, electrolyte imbalances, and
convulsions require treatment.
• For cerebral edema severe enough to produce
herniation, controlled hyperventilation,
mannitol, and dexamethasone.
• Patients with cerebral edema must not be overhydrated.
• If these measures are used, monitoring ICP should be considered.
• If there is evidence of ventricular enlargement,
intracranial pressure may be monitored in
conjunction with CSF drainage.
• Acyclovir is a synthetic purine nucleoside analogue with
inhibitory activity against HSV-1 and HSV-2, varicella-zoster
virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus
• In order of decreasing effectiveness
• Acyclovir 10 mg/kg 8 hrly 14-21day
• Thymidine Kinase (TK) of uninfected cells does not use acyclovir as a
• TK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovir
• The monophosphate is further converted into diphosphate by
cellular guanylate kinase and into triphosphate by a number of
• Acyclovir triphosphate interferes with Herpes simplex virus DNA
polymerase and inhibits viral DNA replication.
• Acyclovir triphosphate incorporated into growing chains of DNA by
viral DNA polymerase.
• When incorporation occurs, the DNA chain is terminated.
• Acyclovir is preferentially taken up and selectively converted to the
active triphosphate form by HSV-infected cells.
• Thus, acyclovir is much less toxic in vitro for normal uninfected cells
because: 1) less is taken up; 2) less is converted to the active form.
• Ganicyclovir/Foscarnet: For CMV related CNS infection
• Ganicyclovir 5mg/kg (over 1 hr) 12 hrly during induction therapy
the od in maintenance therapy
• Foscarnet: 60mg/kg 8hrly during induction then maintenance 60120 mg/kg
• Synthetic adrenocortical steroid
• Potent anti-inflammatory effects
• Dexamethasone injection is generally administered initially via
IV then IM
• Side effects: convulsions; increased ICP after treatment;
vertigo; headache; psychic disturbances
• The mortality rate varies with etiology, and epidemics
due to the same virus vary in severity in different years.
• Bad: Eastern equine encephalitis virus infection, nearly 80% of
survivors have severe neurological sequelae.
• Not so Bad: EBV, California encephalitis virus, and Venezuelan
equine encephalitis virus, severe sequelae are unusual.
• Approximately 5 to 15% of children infected with LaCrosse virus
have a residual seizure disorder, and 1% have persistent
• Permanent cerebral sequelae are more likely to occur in
infants, but young children improve for a longer time
than adults with similar infections.
• Intellectual impairment, learning disabilities, hearing loss, and
other lasting sequelae have been reported in some studies.
Prognosis w/ Treatment
• Considerable variation in the incidence and severity of sequelae.
• Hard to assess effects of treatment.
• NIAID-CASG trials:
• The incidence and severity of sequelae were directly related to the age
of the patient and the level of consciousness at the time of initiation of
• Patients with severe neurological impairment (Glasgow coma score 6) at
initiation of therapy either died or survived with severe sequelae.
• Young patients (<30 years) with good neurological function at initiation
of therapy did substantially better (100% survival, 62% with no or mild
sequelae) compared with their older counterparts (>30 years); (64%
survival, 57% no or mild sequelae).
• Recent studies using quantitative CSF PCR tests for HSV indicate that
clinical outcome following treatment also correlates with the
amount of HSV DNA present in CSF at the time of presentation.
• None for most Encephalitides
• Appears to be 91% effective
• There is no JE-specific therapy other than supportive
• Live-attenuated vaccine developed and tested in China
• Appears to be safe and effective
• Chinese immunization programs involving millions of children
• Vero cell-derived inactivated vaccines have been
developed in China
• 2 millions doses are produced annually in China and Japan
• Several other JE vaccines under development