Viral Infections 2 Flashcards
Viral encephalitis is a complication of
viral meningitis
clinically encephalitic syndrome
Progressive impairment of consciousness, seizures, mood and behavioral changes and focal neurologic signs (memory and orientation)
Causative agents of viral encephalitis
usually arboviruses (files, ticks, spiders, mosquitos) are epidemics,
while others are sporadic – many unknown etiology (treated as viral but agent never determined)
Molecular diagnosis of Viral encephalitis
is difficult (aseptic)
PCR and multiplex PCR
- Multiplexing allows for screening of multiple pathogens simultaneously
- Usually indicative of the infection, but other studies need to be considered (not diagnose unless other - imagining, symptoms, CSF analysis, etc.)
Viral encephalitis CSF analysis
↑ lymphocytes, normal glucose, moderate to ↑ protein
Viral encephalitis neuroimaging
cerebellar lesions, focal lesions in basal ganglia, subependymal, temporal and/or frontal lobe enhancement, white matter abnormalities
no cysts, granulomas, calsifications
Viral encephalitis treatment
primarily supportive
one important exception is HSV encephalitis - acyclovir
most common cause of nonepidemic encephalitis
Herpes viruses
If suspected, all should be started on acyclovir empirically
Who is at risk for viral encephalitis
- Extremes ages (e.g. newborns and elderly)
- Immunosuppression [HIV, orgon transplant, pregnant, steroids]
- Direct animal contact (i.e. live animal markets)
- Recreational activities that put you in contact with insects
- Vaccination status
- Geographical area and season
Herpes viruses
radiculitis
Radiculitis or radicular pain is pain that radiates along the path of a specific nerve as the response of pressure on the nerve root.
Sequelae
a condition which is the consequence of a previous disease or injury.
“the long-term sequelae of infection”
Ways HSV-1 can get into the CNS
1) Retrograde and anterograde transport through nerves (nerve hopping)
2) Infections of epithelial cells
- Most viruses that can cross the CNS barriers can cross the placenta
- All herpesviruses can cause CNS infections during primary infection or following reactivation from a latent state
Most common forms of Arbovirus in the US
Arbovirus reservoirs
Birds and other animals (such as horses) are the usual reservoir for the infection, and they are involved in its spread
Also seasonal, when mosquito breeding reaches its peak
Arbovirus encephalitis patients
Rabies historically
One of the oldest viruses in the historical record
Described in texts from early human civilizations
‘Rabies’ comes from Sanskrit word ‘rabhas’ which means “madness” (in 4,000 year old texts)
Rabies mortality
100% mortality in unvaccinated or untreated individuals
Rabies is usually acquired from
dog, bat, or other wild terrestrial animal bite
Incubation period of rabies
from 5 days to >6 months
varies dramatically related to how get into CNS - long way toe to head, short way neck to head
rabies CNS movement
Late stages of rabies
change tropism (now antigrade) - forward
movement to infect acinar cells of the salivary gland - saliva becomes the vector
fer of water - because saliva now vector - not want to wash away virus
Primary manifestation is
encephalitic syndrome:
behavioral alterations (aggressiveness, hydrophobia),
followed by dementia-like state with quadriparesis (weakness of all 4 limbs) then death
once show symptoms - death in days
rabies inflammation
Very little, yet pathology is very aggressive - negri bodies
rabies Histopathologic hallmark
Negri bodies
only seen postmortem
viral replication factories - interfeer with neuronal functioning
cause of neurological functions in rabies
functional defects rather then anatomical defects cause the neurological symptoms
in few cases rabies primary manifestation is
myelitic syndrome - mostly in patients treated with preexposure vaccination
Rabies is easily misdiagnosed as
Guillain-Barré syndrome - limiting factor in treatment
HIV evolutionarily
one of the newest viruses to affect humans
Even with antiretroviral therapy, HIV+ patients develop
psychomotor slowing,
mental status changes,
memory problems, and
apathy - encephalitic syndrome
called HIV-associated neurological disorders (HAND)
Infects CNS
early on infections, mostly by infected lymphocytes, and to a lesser extent by direct transcytosis across BMECs
Once in CNS, it infects microglia, macrophages, and monocytes, who become activated and signal for immune infiltration - more inflammation
cycle - infect microglia - cytokines - call more immune - if immune infected - bring more virus
HAND is believe to be a consequence of
the constant signaling
Without treatment, ___% of HIV+ patients will develop encephalitic syndrome
> 95
10% will be due to HIV itself
Rest, is due to opportunistic pathogens (bacterial, fungal, parasitic, and viral)
Only effective treatment for HIV is
HAART (highly active antiretroviral therapy)
Idea why not able to cure HIV
CNS cells possible reservoir for HIV, preventing complete clearance
Leading causes of death due to CNS-infection in HIV patients are:
cryptococcosis, toxoplasmosis, JC virus, CMV, and tuberculous meningitis
Viral myelitis Usually there is involvement of
meninges or brain parenchyma, but
for a few myelitic syndrome is the dominant feature
Acute vs transverse myelitis
Acute - grey matter only, more diffuse area affected
Transverse (TVM) - grey and white matter, usually restricted to a whole cross-section of the spinal cord, hence dysfunction below the level affected while function above such level is normal
Clinical features of Viral myelitis
are mostly determined by the location and extent of the injury rather than by the viral agent
Laboratory tests to identify agent for viral myelitis are critical
may be one of few viruses with treatment available
Viruses that cause Viral myelitis
Poliomyelitis is a
Enterovirus - colonizes the throat
and the GI tract
Enters through the mouth - disseminates through feces
also one of oldest viruses
___ of polio cases involve the brain, but
1%
encephalitis is subclinical - shows tropism for spinal cord
polio selectively replicates in
motor neurons (spinal cord) over sensory, and neurons over glia
polio gains entry into CNS by
directly infecting BMECs, or by retrograde axonal transport through peripheral nerves
Also shows dynein-directed movement along microtubules
Once inside CNS, polio kills the neurons it infects (unlike rabies - does not kill neuron)
polio serotypes
3 serotypes, with no cross immunereactivity
Polio Paradox
transmitted through fecal-oral route, but it didn’t become a sanitary problem until the 20th century - when in theory better hygiene - idea - before industrial age - worse hygiene - exposed to early in life - gain immunity
The success of the polio vaccines
has made polio a rare infection in the western world – vaccine targets all 3 serotypes
Still present in certain countries of the developing world (Africa, Asia)
treatment for spinal poliomyelitis
no specific treatment – vaccine has been the main weapon for eradication
Aggressive vaccination campaigns in the 50’s and 60’s lead to eradication in the 70’s - power of mass vaccination
Polio patients rarely die, but the
neurological sequela contributes to substantial lost of healthy life years
(measured as the number of Disability Adjusted Life Years, or DALYs)
Postpolio syndrome
symptoms appear decades after recovery from their initial illness, controversial since there is no evidence of viral infection
Best treatment
