Viral Encephalitis Flashcards
Define encephalitis
Encephalitis – inflammation in the brain + neurological dysfunction
Viruses that cause encephalitis are ___
Viruses that cause encephalitis are neurotropic, meaning that are able to infect neural cells
Contrast neuroinvasiveness and neurovirulence
What is an example of a virus with low NI but high NV?
Neuroinvasiveness - ability to cross the BBB and enter the CNS
vs
Neurovirulence - ability to cause disease once in the CNS
HSV: low neuroinvasiveness but high neurovirulence (even if a little bit of it can get into the CNS, it’ll cause damage pretty much)
Two general methods of diagnosing encephalitis are ___
CSF evaluation via lumbar puncture
Brain imaging (MRI or CT +/- EEG)
What is the hallmark of encephalitis?
Altered mental status
**note: can present typically with non specific acute fever, headache, and focal neurological issues like seizures, weakness, speech disturbances**
What are the expected lab findings for viral encephalitis? (i.e. white count and glucose levels)
CSF: high WBC count, early PMNs, normal glucose
(vs meningitis where white count is much higher and glucose is lower)
What are the expected brain imaging findings for viral encephalitis? (abnormal/normal)
Neuroimaging is typically abnormal but there’s generally no typical pattern for individual infections
In general, Dx of viral encephalitis includes what 4 criteria?
Non specific: clinical findings, CSF eval, imaging
Specific: usually serology (IgM in peripheral blood), PCR tends not to work well b/c not enough virus to amplify and work with
With the exception of Herpes, most of the Rx of arbovirus is __
With the exception of Herpes, most of the Rx of arbovirus is supportive
What are the flavi viruses discussed?
West Nile virus
St Louis encephalitis virus
What are the Bunya virus members that cause encephalitis?
La Crosse (for this lecture but there’s also hanta virus)
Rhabdovirus members that cause encephalitis include __
Rabies virus
Togavirus members that cause encephalitis include ___ and ___
Eastern & Western Equine Encephalitis viruses
Describe the structure of WNV (envelope or no, shape of virion etc)
What type of sense/genome virus is it?
West Nile Virus:
Flavivirus
Enveloped icosahedral capsid
(+) sense single stranded RNA
Describe the transmission cycle of West Nile Virus
vector - culex mosquito
amplifier - birds (Passerine type, like crows and blue jays)
humans and horses - dead end hosts
**see below for cycle**
Why are birds amplifiers of West Nile Virus?
Name 4 other methods of transmission of WNV
Large capacity to amplify virus in birds
Other mechanisms of transmission:
solid organ transplant
blood tranfx
transplacental
breastfeeding
West Nile Virus replicates in ___ cells
Describe the viral replication cycle in these cells. Where does the virus go following replication?
West Nile Virus replicates in skin dendritic cells
Replication cycle (see image below):
viral attachment >> receptor-mediated endocytosis >> fusion >> uncoating >> translation etc >> making -ve ssRNA intermediate >> making more +ve ssRNA >> virion assembly >> furin cleavage
Virus replicates then goes into the lymphatics, then the blood stream, then the CNS
What is the function of Furin in the WNV transmission cycle?
Furin: is a host protease that cleaves off the last viral proteins before they go out of the cell
A patient comes to your clinic complaning of 1 week of headache, fatigue and nausea. The patient has not been eating well, is febrile to 102 degrees. PE is notable for lymphadenopathy and rash. What viral infection are you thinking of and how would you treat?
**assume pt is from central US**
West Nile fever
Rx: self resolves within 5 days
A pt with west nile virus encephalitis/encephalomyelitis may present with what symptoms?
Encephalitis:
Fever, altered mental status, seizures, movement disorders
Encephalomyelitis:
Flaccid paralysis with hyporeflexia
**Encephalitis is ½ the cases of folks; likes the anterior horn cells so it causes flaccid paralysis w/ hyporeflexia**
What are the diagnostics labs for west nile virus going to look like? Between PCR and IgM serology, which test would you use to Dx WNV infection?
Non specific labs: elevated white count (early PMNs), elevated protein, normal glucose (neg gram stain/culture)
Use CSF IgM and serum IgM, CSF might be +ve before serum
No PCR due to low sensitivity so use IgM ELISA
What is the Rx for WNV infection?
IVIG Rx (not really helpful) so really only supportive care
Since St Louis Encephalitis is transmitted by the same vector, has the same replication cycle, and is a +ve sense ssRNA Flavivirus like West Nile Virus, how are the 2 different?
Very much like West Nile virus but doesn’t really like anterior horn cells so no flaccid paralysis!!
What is the Dx and Rx of St Louis Encephalitis virus?
Dx: SLEV IgM from CSF or serum
Rx: there is none :/
Describe the characteristics of EEEV and WEEV
Togavirus/alphavirus
Have enveloped icosahedral capsid and (+) ssRNA genome
**replication cycle is pretty much the same as that of WNV**
What are symptoms of WEEV and EEEV?
Of the 2, which one affects infants more? Which one is more deadly?
How do you Dx/Rx these infections?
Symptoms: non specific viral symptoms
WEEV - affects more infants
EEEV - more deadly/neuroinvasive and most folks become permanently disabled
Dx: Serum or CSF IgM titers
Rx: ??
___ is a -ve sense segmented ssRNA Bunyavirus with an enveloped helical capsid that causes encephalitis
La Crosse virus
What is the tx of La Crosse virus?
Which populaion is mainly affected by this virus and where in the country do most cases occur?
Transmitted by Aedes mosquito
Has mammalian hosts (eastern chipmunk, tree squirrel and fox)
Causes disease mainly in children
Location: Ohio valley, Ohio, W. Virginia
Describe the presentation of La Crosse virus
How do you Dx/Rx this infection?
Presentation:
Headache, confusion, and lethargy
Seizures common
Dx: Serum or CSF IgM
What is Powassan virus?
Flavivirus transmitted by ticks (Ixodes scapularis, Ixodes cookei)
*see below for everything else*
___ is a -ve sense ssRNA , enveloped helical capsid virus in the Rhabdovirus family
Rabies
**note that it makes the proteins below:
Glycoprotein
Matrix protein
Nucleoprotein
Phosphoprotein
L-polymerase
Describe the rabies replication cycle
- G protein attaches to receptors on nerve and muscle cells
- Entry via endocytosis
- Membrane fusion with lysosome, release of nucleocapsid into cytoplasm
- Transcription of mRNA, translation of 5 structural peptides
- Accumulation of N alters N:RNA ratio, switch to replication of genome
- Coating of (-) strand with N,L, and P to form nucleocapsid
- Coating with M, G added as virus is processed through golgi apparatus
- Budding
Describe the pathogenesis of rabies
Enters ms cells and replicates very slowly
Motor nerves >> retrograde axonal transport >> CNS >> variable neuronal necrosis etc >> dissemination
Incubation time: long
Has eosinophilic inclusion bodies called negri bodies
Which antibodies are produced in response to rabies infection?
•Antibodies to G protein
–Neutralizing and protective (immune response too late, occurs afterCNS infection)
What is a unique clinical manifestation of rabies?
What are the two manifestations of CNS involvement in rabies infection?
Rabies has a very long incubation period
- Furious/Encephalopathic:
agitation, bizarre behavior, delirium, hallucinations, autononomic dysfunction, aerophobia, muscle spasms, myoclonus, seizures
- Paralytic: ascending flaccid paralysis, coma
How do you Dx/Rx rabies infection?
Dx:
CSF or saliva PCR
DFA staining of skin biopsy in the nape of the neck
Rx: none once neuro sysmptoms start
What is the post exposure prophylaxis protocol for rabies and who would you give it to?
PEP:
IG given at site of infection; vaccine @ diff site
Who: (see slide below)
What is the Rx for rabies?
Supportive really
