What are some symptoms of encephalitis?
altered LOC, focal neurological deficits, seizures (moreso than in meningitis), coma, plus the usual symptoms you'd see with meningitis
About 50% of encephalitis cases are idiopathic, but What are some of the most common known causes?
1. HSV 1 and 2 (about 25%)
2. Varicella zoster
3. Postinfectious from measles, mumbps, rubella, etc
5. Arboviruses (depending on geogrphay)
7. Mumps, measles
What are the steps in diagnosing encephalitis?
1. consider in any patient with altered LOC, unexplained fever, seizures or new focal neurological deficits
2. CT scan
3. LP if safe to do so
4, Test CSF for WBC, protein, glucose
5. Can undergo PCR or serologic testing
What is the typical empirial drug of choice for viral encephalitis>
HSV encephaltis most often affects what part of the cortex? How about flaviviruses?
HSV = temporal lobe
Flaviviruses = basal ganglia and thalamus
What subtype of encephalitis is MRI crucial in diagnosing?
ADEM and othe rforms of postinfectious encephalitis
What three herpes viruses are associated with encephalitis? What subgroup of herpesviruses do these fall under?
HSV 1, HSV2, and VZV
they are all alpha herpes viruses
Where do alpha herpesviruses stay dormant?
What are some general characteristics of the herpes viruses?
genome? structure? virulence?
THey are large, enveloped icosahedral viruses with large dsDNA genomes (class 1)
They encode many proteins that serve to modulate the host cell immune response
also encode for several proteins that are required to promote viral DNA replications
Can cause lytic, persistent, latent and sometimes immortalizing infections.
Why is cell-mediated immunity essential for the control of herpes simplex infections?
they can create latent infections, so the infected cells need to be destroyed
Is HSV1 or 2 more likely to cuase encephalitis? meningitis?
HSV 1 = encephaltis
HSV 2 - aseptic meningitis
Although HSV and VZV are both herpes viruses, they cause encephalitis in slightly different ways. How?
HSV causes encephalitis when the reactivation of laten virus in neurons goes the "wrong direction" up to the CNS instead of tho the periphery.
In VZV, it's during the viremia that the virus reaches the CNS - so it can be in either the primary infection or in a reactivation event
How does acyclovir work?
It's a bioprecusor prodrug that is converted to an active form by being phosphorylated by thymidine kinase.
Once it's phosphorylated it looks like a nucleotide, but it lacks the 2' hydroxyl needed for chain continuation, so it acts as a chain terminator - interferes with DNA and RNA synthesis
What is postinfectious encephalitis and what form is most common?
It's encephalitis caused by a viral infection (mumps, measles, rubella, varicella, influenza, etc)
Acute disseminated encephalomyelities (ADEM) is the most common
It's basically inflammatory demyelination that occurs anywhere from days to 4 weeks post viral infection
What are some characteristics of the measles virus? Genome, structure, etc.
- ssRNA (group V)
What is a genetic component in a patient's ability to clear a measles infection withint deveoping encephalitis?
people who have genetic polymorphisms resulting in lower production of interferon alpha and interleukin 2 cannot mount an effective immune response, so they are more likely to develop neurological complications
Wha thappens in primary measles encephalitis (PME)?
in 1-3 out of 1000 patients
the virus invades and repliates in brain cells at the same time as when the rash presents - fever, heaahce, mental status changes, motor deficits, seizures
Treatment is supportive and there is a 15% mortality rate and a 25% rate of lifeling neurological problems
What happens in subacute sclerosing panencephalitis (SSPE)?
More rare (4-11 in 100,000)
usually children who contract measles before age of 2
They have acute infection which appears to resolve
symptoms free usually until their teen years
then they start to have behavioral problems, academic performance decline, the neurological dysfunction - all gradually worsen
Restulsf rom a "slow infection" of the brain where viral gene expression is reduced and defective viral particles build up and cause neuronal damage
usually die about 1-3 years after symptoms develop
What is the treatment for acute disseminated encephalomyelitis (ADEM)?
Corticosteroids to dampen the immune response
How does rabies lead to enterovirus?
1. virus inoculated through bite
2. virus replicates in muscle
3. Virion enters the peripheral nervous system
4. Passive ascent of virus via sensory fibers
5. replication in dorsal ganglion
6. rapid ascent in the spinal cord
7. infection of the spinal cord, brainstem, cerebellum
8. descending infection to eye, glands, skin an dother organs
What animal most often spreads rabies here?
What are some of the neurological symptoms you see in rabies encephalitis?
hydrophobia, pharyngeal spasms, hyperactivity, anxiety, depression, loss of coordination, paralysis, confusion, delerium
ultimately coma and death due to respiratory paralysis
What is the treatment for rabies?
the patinet has ot be passively immunized with rabies immune globulin (RIG = human antibodies against rabies) injected both at the site of the bite and intramuscularly
also need to be immunized with an inactivated rabies virus preparation