Viral Encephalitis - AuCoin Flashcards
T/f: helminths may invade the CNS
true
CNS infections occur within which two areas?
cranium and spinal column
What are the common features of CNS infections?
fever
headache
altered mental status
focal neurologic deficits
Clinical presentation of a CNS infection may be acute, subacute, or chronic depending on the (blank) factors of the innfecting agent and its location
virulence factors and locations
Viremia and CNS invasion begins via the colonization of…
mucosal surfaces
Which Ig neutralizes viruses and prevents attachment tot he mucosal surface and cell penetration
IgA
Most CNS viruses replicate at (neuronal/non-neuronal) sites
non-neuronal sites
Is viremia established before or after invasion of the CNS via the BBB?
before moving through the BBB
Even if the cililary action of the respiratory system is passed, what cells kill viruses in the lower respiratory tract?
alveolar macs
Gastric acidity inactivates most (viruses/viral capsules)
viruses
Gastric enzymes inactivate most (viruses/viral capsules)
viral capsules
Bile disrupts what part of the virus?
viral envelope; its a lipid!
what are the acid resistant viruses that can survive in the GI tract?
enterovirus
adenovirus
reovirus
parvovirus
Where does enterovirus have its primary replication/
peritonsillar lymphatics
Peyer’s patches
lamina propria of intestine
vascular and endothelial cells
(blank) cells mediate viral penetration from the gut lumen to the lymphoid cells
M cells
What sites does the virus spread to to cause viremia?
liver
spleen
muscle
After viremia, particles are cleared by what cell class?
phagocytic cells
Viruses like measles, mumps, and herpes grow and are transported in what cell type?
phagocytic cells
What is the advantage for a virus to replicate in the immune cells?
prevents phagocytosis and neutralization via circulating Ab
What are the four mechanisms of viral invasion of the CNS?
- invasion directly across cerebral capillary endothelial cells of the BBB
- infection of glial w/o endo infection
- transport via immune cells
- via olfactory or peripheral nerves
endo cells of the BBB secrete what type of basement membrane?
laminin basement membrane
Perivascular (blanks) lies close to the BBB vessel wall
perivascular macrophages and pericytes
What are pericytes responsible for in the BBB?
tight junction formation
vesicle trafficking amongst endo cells
How do infected monocytes gain access to the CNS?
via normal turnover perivascular macrophages or as a result of proinflammatory mediators like CCL2
HTLV1 gains access to the BBB via which transport protein?
GLUT1
Passage of virus through endo cells of the BB can release which two inflammatory cytokines?
IL6
IFNg
HSV1 enters peripheral neurons via which transport protein?
nectin 1
Nectin 1 is expressed on the cell (soma/axon)
axon
Spread of HSV1 from axon to soma is facilitated by hijacking of the (blank)
axonal retrograde transport system
Which two viruses are released at a synapse and use a retrograde trans-synaptic pathway to infect neighboring cells/
HSV1
rabies virus
Measles virus dissemination between neighboring neurons occurs via (blanks) between neighboring cells
microfusions (two termini that are actually touching vs. crossing the synaptic cleft)
Reactivation of HSV1 uses (retrograde/anterograde) transport to infect neighboring neurons
anterograde; from soma to axon termini exits via axonal varicosities then reinfects epithelial cells
Which two proteins does HSV1 use to reinfect epithelial cells during reactivation/
nectin 1
herpesvirus entry medator (HVEM)
Production of CNS dz requires viral (blank) and penetration of susceptible cells
attachment
viral entry into the (blank) leads to dispersion of virus within the CSF in contact with meningeal cells
subarachnoid space
virus in the CSF can spread to which cell types?
glia and neurons
T/F: the INITIAL inflamm response to virus int the CNS is immunologically specific to the virus
true; consists of lympho’s sensitized to the virus
Blood vessles that carry viral load lie in the (blank) space above the (blank) covering of the brain
in the subarachnoid space above the pia mater
Monocytes respond to virus-specific (protein/glycolipid) that diffuses or is transported to the luminal surface of the endothelium
protein
After the dev of a CNS inflamm response, alterations in the BB permit what to pass?
CSF serum proteins INCLUDING IG
Intracerebral accumulation of Ig is seen as an increase of CSF-serum ratios that persist for how long after infection?
several weeks
Are T or B cell responses more important for viral clearance from the CNS?
T cell
chronic viral infx happen in what type of patients/
pts with depressed CELL MEDIATED immunity
HSV causes hemorrhage in which lobe the brain/
temporal
viral infections produce what type of inflammatory infiltrate?
mononuclear
Viral meningitis is ID’d by a high (blank) count in the CSF
WBC
what is the most common cause of meningitis?
viral meningitis
Which bacteria may also cause meningitis?
strep pneumo
N. meningitidis
Listeria monocytogenes
Acute meningitis has its Sx onset over what period of time/
hours to days
what does aseptic meningitis mean?
its viral
T/F: pyogenic bacteria are the cause of aseptic meningitis
false
The cause of aseptic meningitis is not apparent after initial eval of (blank)
stains and cultures of CSF
Is viral meningitis more or less severe than bacterial meningitis?
less severe
T/F: viral meningitis, while less severe, still needs aggressive Tx
false; resolves on its own
Most viral meningitis cases in the US happen during the summer and are caused by….
enterovirus
What are the three most common causes of aseptic meningitis?
non-polio enterovirus
mumps
herpesvirus
What are the less common causes of aseptic meningitis?
Arboviruses Lymphocytic choriomeningitis virus (LCMV) Human immunodeficiency virus Adenovirus Influenza virus Measles virus
viral meningitis occurs in what age group?
younger than 5
What is one of the most common ways of kids getting enteroviral meningitis?
Changing a diaper/going to the bathroom and not washing your hands
What is the triad of symptoms in meningitis
/
sudden onset fever
headache
stiff neck
What are the additional symptoms of meningitis?
Nausea
Vomiting
Photophobia (sensitivity to light)
Altered mental status
How long do the symptoms of meningitis last?
7-10 days
T/F: people with normal immune systems recover completely from aseptic meningitis
true
What types of samples are taking for testing for aseptic meningitis/
blood or CSF
what is the leading cause of ID’d aseptic meningitis?
enterovirus
what is the route of transmission of enterovirus/
fecal-oral spread
Swimming in (blank) contaminated water can lead to enterovirus infx
sewage contaminated :( fucking yuck
in order, what are the most common enteroviruses that cause meningitis?
echovirus
coxsackie virus B2 and A9
T/F: Enterovirus D68 does not cause meningitis
true
which coxsackie causes hand foot mouth syndrome/
coxsackie a
what is another word for hand foot mouth ?
herpangia; ulcers in oropharynx w/ sore throat
what type of coxsackie causes pleurodynia and myocarditis?
coxsackie b
T/F: both coxsackie A and B can cause meningitis
true
T/F: both coxsackie a and b can cause mild paralysis
true
How do you Dx coxsackie virus meningitis?
PCR of enterovirla RNA in CSF
Is there a Tx for Coxsackie virus
nope
Which type of virus may be transmitted via pool water?
echovirus
Besides meningitis, what other Sx may echovirus have?
URI, fever, infantile diahrrea, hemorrhagic conjunctivitis
T/F: echovirus may also cause hand foot mouth disease
true
how do you Dx echovirus?
PCR
is there a Tx for echovirus?
nope
Are serologic tests useful for echoviral infx?
nope; multiple serotypes and no common Ag
What fluids can transmit coxsackie and echo viruses?
feces, ENT secretions, blister fluid
Mumps is the most common cause of aseptic meningitis and encephalitis in which population group?
unvaccinated
meningitis occurs in what percent of mumps patients?
10-30%
T/F: mumps meningitis can occur without parotitis
true
T/F: mumps meningitis is self limiting
true
What age group and gender is most likely to get mumps?
males 5-9 years old
how many serotypes of mumps are there?
only one
how is mumps transmitted?
respiratory droplets
Mumps spreads via the blood to which organs?
testes
ovaries
pancreas
meninges
what is in the mumps vaccine?
live, attenuated vaccine
Which virus is transmitted via aerosol inhalation of the secretions and excretions of house mice and hamsters?
lymphocytic choriomeningitis
T/F: most cases of LCM are asymptomatic
true
What are the symptoms of LCM?
flu like, fever, headache, myalgia, and malaisde
is there a treatment for LCM?
nope
How do you test for LCM?
serologic testing for IgM or IgG
what percent of encephalitis cases remain unknown to the etiology
?
1/2
Of the ID’d cases of encephalitis, what percent were due to viruses?
2/3
What are the criteria for encephalitis?
altered consciousness for 24 hours or more
fever
seizures
focal neurologic findings
cerebrospinal fluid (CSF) pleocytosis or
electroencephalogram (EEG) or neuroimaging findings
Which six members of the herpes virus family can cause neurologic disease?
herpes simplex virus-1 (HSV-1) herpes simplex virus-2 (HSV-2) varicella-zoster (VZV) Epstein-Barr (EBV) cytomegalovirus (CMV) human herpes virus-6 (HHV-6)
T/F: when herpesvirus infects the CNS, the presentation is nonspecific
true; makes it hard to know what is going on
Prompt Dx of HSV based CNS infection requires what?
neuroimaging
Why is it important to get an early Dx of HSV CNS infx?
progressive neurologic deficits, seizures, and death may happen
T2 weighted images will show increased signal where with an HSV infection?
temporal lobes
T2 weighted images will show increased signal where with a VZV infection?
multiple areas of infarction in both hemispheres
what is the geographic limit of the inflammation in HSV1 infx of the CNS?
insular cortex; BUT DOES INVOLVE THE CINGULATE GYRUS
HSV1 and HSV2 cause encephalitis via (anterograde/retrograde) transmission
retrograde from a peripheral site on the face along a nerve axon and to the brain
The HSV virus lies dorman in the ganglion of the (blank) nerve
trigeminal
Does HSV use the trigeminal to gain access to the brain?
not necessarily; pathway unclear
what other cranial nerve besides 5 may be involved in HSV infections?
olfactory nerve; explains temporal lobe involvement
What causes tissue injury in HSV encephalitis?
viral killing of neurons
What is the most common cause of viral encephalitis, causing 10% of all cases?
HSV
in immunocompetent adults, HSV1 accounts for what percent of HSV encephalitis?
90%
What must you do to Dx HSV encephalitis?
MRI and PCR of HSV DNA from teh CSF
Most pts with HSV encephalitis have a CSF (blank)cytosis
pleocytosis >5WBC/mm3 with lymphocytic predominance
What are the protein and glucose levels like in HSV enceph?
elevated protein (80-85) and normal glucose
What is the drug of choice for HSV enceph?
Acyclovir
VZV goes latent in the (blank)
dorsal root ganglia
VZV CNS infections can result in what two dz?
enceph or vasculopathy
T/F VZV CNS infx can occur during primary infx or during reactivation
true
During primary VZV infx, acute (blank) happens to 1 in 400 children younger than 15
acute cerebellar ataxia
acute disseminated encephalomyelitis occurs in 1 in 2500 cases of (blank)
VZV
Describe the CSF profile of ADEM?
standard for encephalitis:
pleocytosis with lympho predominance, normal glucose, elevated protein
T/F; VZV encephalitis is caused by VZV vasculopathy
true
Dx of (enceph/vasculopathy) can be made using VZV -specific Ab or PCR of VZV DNA in the CSF
vasculopathy
For fucks sake like it wasn’t bad enough, what ELSE can VZV do in the CNS?
cause meningitis
What is the tx for VZV CNS infx?
acyclovir
How is HCMV transmitted?
via blody fluids
T/F: HCMV only causes acute dz
false; acute and reactivates
What Sx can HCMV mimic acutely?
mono
What are the major neuro complications of HCMV
retinitis
enceph
neuropathy
in what group of pts do you get neuro complications from HCMV?
immunocompromised
T/F: HCMV can cause congenital malformations
true
Infected neurons and glial cells develop cytoplasmic and intranuclear (blanks) of HCMV
inclusions
At what T cell level does HCMV enceph occur?
lower than 50
What’s the CSF look like in HCMV enceph?
nonspecific…..
mild lympho pleocytosis
mild elevation in protein
What’s the really bad form of HIV-associated HCMV eneph that kills you in a month?
ventriculoencephalitis
How do you Dx HCMV enceph?
CMV DNA from CSF via PCR
What two drugs are given in CNS invasive HCMV?
gancyclovir and foscarnet
If you see the ventricles outlined in a T2 MRI and they have encephalitis, what virus is causing it?
HCMV; ventriculoencephalitis
Primary EBV infx has what symptom profile?
mono like; cervical LAD, exudative pharyngitis, splenomegaly
What are the complications of CNS infx of EBV?
meningitis
encephalitis
transverse myelitis
Guillain-Barre syndrome
HHV-6 infects what type of cell?
T cells
HHV causes what exanthem in infants?
exanthem subitum (roseola)
What particular group of pts gets enceph from HHV-6
allogenic BMTs
Describe the CSF profile in HHV-6 enceph?
lymphocytic pleocytosis
elevated protein
normal glucose
Describe the general onset for roseola?
sudden high fever
after a few days the rash subsides
just as the child is getting better a red rash appears, BEGINS ON TRUNK AND SPREADS TO LEGS AND NECK
does not itch, lasts 1-2 days
How do you Dx HHV-6 enceph?
CSF PCR or serum serology
How do you treat HHV-6 enceph?
gancyclovir and foscarnet
What are the vector borne viral enephalitis family?
Arboviruses
WHich arboviruses may cause enceph?
California encephalitis virus (La Crosse virus) West Nile virus St. Louis encephalitis Eastern equine encephalitis Western equine encephalitis Venezuelan equine encephalitis
California encephalitis virus is transmitted by what fucking bug?
god damn mosquitoes
What CE subtype most often causes encephalitis?
La Crosse Virus–californians like to play LaX!
IN what age group and in what season do we see the most cases of CE?
<16y, during the summer
Half the patients with CE develop (blanks)
seizures
T/F: most patients with CE suffer long term brain damage from the seizures
false; most recover completely. 1% mortality is due to asceptic meningitis
T/F: people seropositive for CE are protected against reinfection
true
What part of the US do we normally see CE?
Eastern US, WTF!
What type of mosquito is the vector for West Nile virus?
Aedes albopticus; female Asian tiger mosquito
Birds, especially CROWS, are susceptible to this virus
West Nile virus
What two age groups are at higher risk of getting west nile?
children and elderly
How does west nile travel in the body and what is its target organ?
spreads via monocytes and macrophages, targets the brain
What percent of people with WNV are symptomatic?
only 1%
What is the range of symptoms of WNV?
flu like to encephalitis; Headache, nausea, high fever, malaise, myalgia, backache, neck stiffness
Is there a vaccine and/or treatment for WNV?
nope
What are the two ways to diagnose WNV?
virus specific IgM in the serum or CSF!
what is the vector for St. Louis virus
mosquitoes, of course
T/F: St. louis encephalitis has outbreaks in the US
true
when are SLE outbreaks common?
late summer and early fall
Serious SLE (blank) infections cause headache, nausea, high fever, malaise, myalgia, backache, and neck stiffness
neuroinvasive
What is the mortality of SLE? What group is most susceptible?
3-30%; elderly
How do you diagnose SLE?
serodiagnosis of IgM in serum OR CSF!
What are some clinical pearls that point you towards SLE?
Onset in early fall
working outside/landscaping
CSF negative for WNV
EEE has what type of vector?
it is an arbovirus
What is the reservoir of EEE?
wild birds!
What is the mortality rate of EEE?
33%
(blank) type infections of EEE can hapen in horses in the US
epizootic
Severe headaches, nausea, vomiting, fever; changes in mental status, seizures and coma are suggestive of?
EEE
T/F: survivors of EEE are left with permanent brain damage
true; think about getting kicked in the head by a horse
How is EEE diagnosed?
isolating virus or detecting rise in Ab titer
Is there a vaccine or antiviral for human infection of EEE? Horses?
No for humans, yes for horses
What region of the US is infected with EEE?
East coast, south east
EEE may have similar symptoms at onset to (blank)
meningitis
Is Western equine encephalitis more or less severe than EEE?
less severe
Where is WEE found?
West of Mississippi and South America
What is the mortality rate of WEE?
2%
T/F: WEE has a vaccine for horses but not for humans
true
Is the reservoir horses or birds in Venezuelan equine encephalitis?
horses
Where is VEE found?
South and Central America
What are the symptoms of VEE? Is it fatal?
flu like symptoms, only fatal to those with weak immune systems
T/F: VEE has a vaccine for both horses AND people
true
What types of people are vaccinated against VEE?
laboratory and military
what is the most common form of polio?
abortive poliomyelitis
What are the Sx of abortive polio?
mild, febrile illness characterized by headache, sore throat, nausea, and vomiting
T/F: nonparalytic polio presents as meningitis
true
In (blank) polio, the major finding is FLACCID paralysis
paralytic polio
In paralytic polio, involvment of which brain structure can lead to respiratory failure?
brainstem
What specific type of meningitis is involved in paralytic polio?
meningoencephalitis
Which two types of polio have spontaneous recovery?
abortive and nonparalytic
Is the motor nerve damage permanent following polio muscle spasms?
yes, that’s why they are in wheel chairs
If the spinal cord is involved in polio, what type of meningitis is it?
meningomyeloencephalitis
Poliomyelitis is an acute infection of the (blank) and the motor neurons of the spinal cord and brain stem
meninges
The Salk and Sabin vaccines are used for(blank)
polio
Where is polio still ENDEMIC?
Nigeria, Pakistan, and Afghanistan
How do you Dx polio?
Acute onset of flaccid paralysis, or recovery of poliovirus from stool sample or swab of pharynx
How many polio serotypes are there?
three
T/F: protection from one polio serotype will protect against them all
FALSE; little immune cross reactivity, therefore you need unique Abs to all three
Which polio vaccine is the killed vaccine?
Salk (inactivated vaccine)
Which polio vaccine is the live attenuated vaccine?
Sabin, ORAL vaccine
After the polio virus is ingested, where does it first establish infection?
GALT, tonsils, peyer’s patches, invades the M cells and replicates in the monoctyes
From the initial site of infection, where does polio travel?
regional lymph nodes, virus rep’s in the monocytes
After establishing in regional lymph nodes, where does polio go?
into the blood to cause plasma viremia
Once plasma viremia of polio is established, how does it cross the BBB?
via the endothelium
Polio replicates in the (blank) cells of the spinal cord
anterior horn cells
Replication of polio in the spinal cord leads to cell destruction and (blank)
paralysis
How is polio shed from the body?
via the feces
Weakness in one leg seen in polio is known as…
Equinus foot
AIDS dementia results from infection of what two cell types in the brain?
macrophages and microglial cells
What are the Sx of AIDS dementia?
slow deterioration of intellectual abilities
AIDS dementia is similar to what other degenerative dz?
Alzheimer’s
What are the other reasons that someone with AIDS could have neurologic deterioration?
from an opportunistic infection
What are some of the opportunistic infections that can cause neuro symptoms in AIDS pts?
CMV
HSV encephalitis
cryptococcal meningitis
what is the most common neuro complication of late stage HIV infection?
subacute or chronic HIV enceph presenting as dementia
What percent of AIDS pts progress to dementia?
3%
Once the constitutional symptoms of AIDS have been established, what is the frequency of dementia?
2/3
in what age group is AIDS dementia most common?
kids; more than 60% :(
what are specific cognitive losses in AIDS dementia?
(loss of retentive memory, inattentiveness, language disorder, and apathy) abnormalities of motor function
What is the survival after AIDS dementia onset?
3-6 months, may be longer if treated
What changes in the CSF do we see in pts with AIDS dementia?
normal, maybe a slight elevatoin in protein
T/F: HIV can be isolated from the CSF
true
Can the AIDS dementia complex be caused by a CMV infection?
no, it is a direct result of HIV
T/F: rabies can infect all animals
true
How is rabies transmitted?
animal bites
How long is the incubation period of rabies virus?
2 weeks to a year
What phase of rabies is this: Fever, nausea, headache, spread to CNS from muscle
prodrome phase
What phase of rabies is this: Hydrophobia, anxiety, paralysis, coma, death (~100%)
neurologic phase
After being bitten, what is the treatment protocol?
Administration of BOTH the vaccine AND human rabies IgG
What speical type of inclusion bodies does rabies show that is diagnostic?
Negri bodies
What are the two methods of rabies Dx?
cytologic detection of Negri bodies or immunochemical detection of viral antigen in brain tissue
Rabies is spread through what animal secretion?
saliva
Rabies virus remains in the site of infection, (aka blank), for days to months before moving to the CNS
muscle
Rabies virus initially infects the CNS how?
infects nerve endings by binding to receptors
T/F: rabies in humans also spreads to the salivary glands
true; via afferent nerves
After rabies invades the CNS, what happens to the brain?
ecephalitis and neuronal degeneration
Rabies travels via (antero/retro)grade axoplasmic transmission to the DRG and spinal cord
retrograde
What are the first symptoms of rabies after the initial incubation period?
fever malaise headache fatigue GI
How long is the incubation period of rabies?
60-365 days
What is hydrophobia in rabies?
pain associated with swallowing water, the desire to not drink
T/F: hallucinations and seizures are common in rabies
true
Seizures in rabies can lead to what serious complication?
paralysis leading to respiratory failure
What is the cause of death from rabies?
Coma then death via pulmonary complications
In the incubation phase of rabies, pts are asymptomatic
true
What is the viral load like in the incubation phase of rabies/
low titer, virus still in muscle
At what point are Abs to rabies formed/
once it reaches the neurologic phase; can be found in serum and CNS
the symptoms of fever, vomiting, nausea, headache are part of the (blank) phase of rabies
prodrome
In the prodrome phase of rabies, the virus titer is (low/high) and is present in the CNS and brain
LOW titer, but present in the brain!
In the neurologic phase of rabies, the virus titer is (high/low) and in the brain and other sites
high titer and now the virus is everywhere
Prion diseases are disorders of protein….
conformation
What is the most common prion disease?
Creutzfeldt-Jakob disease (CJD)
What are the symptoms of CJD?
dementia, ataxia, and myoclonus
What is the prognosis of CJD?
death within 1 year of onseet
What is the most common age group for CJD?
60-65
what is the incubation period of CJD?
5-20 years
Prions reproduce by bindning the normal cellular isoform of the prion protein (PrPc/PrPsc) and making it the disease causing form
normal: PrPc
dz: PrPsc
T/F: prions don’t have nucleic acids
true
Da fuck is scrapie?
prion dz of sheeps and goats
what are the three ways of getting CJD?
- sporadic
- familial
- acquired
What are the ways of acquiring CJD?
eating contaminated meat
transplant of tissues with prions or use of contaminated surgical instruments
Da fuck is Kuru?
form of CJD involving only tremors and ataxia seen only in the Fore tribes of new Guinea
What are the histologic characteristics of CJD?
spongiform degeneration of the grey matter
What region of the brain undergoes the greatest change in CJD?
cerebral cortex
CJD is characterized by the presence of many (blanks) from 1-50um in diameter
round vacuoles
T/F: CSF analysis is the gold standard for Dx of CJD
false; rarely helpful!