CNS Viral Infections Flashcards
What type of meningitis is most common overall?
Viral is more common, but bacterial can be deadly, so important to distinquish
In how many days does a viral meningitis usually resolve?
7-10 days
What types of virus cause 80% of viral meningitis?
Enterovirus–> Echo, Coxsackie, Enterovirus 71
What virus is responsible for recurrent aseptic meningitis usually?
Herpes simplex virus-2 (HIV or VZV also can cause)
What are 5 symptoms of viral meningitis?
- Fever
- Malaise
- Headache
- Stiff neck
- Low back pain (usually overshadowed by headache)
What disease can cause viral meningitis due to not being vaccinated?
Mumps
What category of viruses cause 30% of viral encephalitis?
Arborviruses–> these are transmitted by a zoonotic vector, usually mosquitos or ticks, so have a strong seasonality
What type of viruses cause viral encephalitis and may cause mini-epidemics within families?
Enteroviruses (echo, coxsackie, enterovirus 71)
What virus causes a little over a quarter of cases of viral encephalitis and may be fatal if not treated?
Herpes Simplex virus-1–> tx with acyclovir
*70% mortality w/o tx = DO NOT MISS
What part of the brain is preferentially affected by herpes viral encephalitis?
Temporal lobe–> causes hemorrhagic necrosis; can be visualized via MRI
What causes HSV encephalitis generally (mode of infection)?
More often due to reactivation of latent virus than by initial acute infection
Other than MRI findings, what finding can be suggestive of Herpes encephalitis?
RBCs in the CSF
Definitive test for dx of HSV encephalitis?
PCR (false negatives do occur though)
Flaviviridiae cause what three human diseases?
- St. Louis encephalitis
- West Nile
- Japanese encephalitis
Flaviviridiae are small, ________, _________, ___ strand ____ viruses
Enveloped, nonsegmented, (+) RNA viruses
Flaviviridiae have their RNA translated by host ribosomes into a single polyprotein.. what are the fragments cleaved by host proteases called? Fragments cleaved by viral proteases?
Host protease–> trans
Viral–> cis
Where do flaviviridiae first replicate in the host? After the transient primary viremia where do they travel to and replicate?
Initially replicate in the endothelium or epithelial cells surrounding the bite site, then after primary viremia replicate in spleen, lymph nodes and macrophages (occurs 3-7 days post exposure)
How do Flaviviridiae end up causing encephalitis?
If the infection is not controlled by the immune system following the primary viremia, then a secondary viremia occurs and results in the severe systemic disease (encephalitis)
What three clinical syndromes can occur with St. Louis encephalitis?
- Febrile headache
- Aseptic meningitis
- Encephalitis
*in 80s and 90s outbreaks have occurred in Colorado, California, Texas, Florida, and Arkansas
After initial onset of symptom in St. Louis encephalitis including malaise, fever, headache, sore throat or cough, what symptoms can occur in 1-4 days indicating severe disease?
acute or subacute meningeal and neurological signs
What is treatment for SLE?
None.. there are no vaccines and antiviral therapy has not been evaluated. Mosquito control is the best means of control
*Fatality rate is low, but those that have fatal infections usually die within 1-2 weeks
How does the West Nile virus get into mosquitoes?
Mosquitoes get from feeding on birds, the virus then replicates in the salivary glands of the mosquito
Most infections with West Nile virus usually only have what 4 symptoms?
- febrile headache
- myalgia
- skin rash
- swollen lymph nodes
* only 1% will develop serious systemic disease
What symptoms are seen in patients that get severely ill from West Nile?
- Severe headache with high fever
- Neck stiffness, muscle weakness
- Stupor, disorientation, convulsions, tremors
- Coma, paralysis, and rarely, death
What is treatment for severe cases of West Nile?
Mainly supportive (I.V. fluids, respiratory support if needed)
Travelers should get vaccinated against Japanese encephalitis virus if traveling to what four parts of the world for over 1 month?
- Asia
- SE Asia
- India
- Eastern portions of former Soviet Russia
What 3 viruses of the Togaviridiae family can cause encephalitis?
Western, Eastern, and Venezuelan Equine viruses–> are called alphaviruses
(Same family that has Rubella-causing viruses, Rubavirus)
Togaviridiae are ________, ________, __NA (_) viruses
Enveloped, non-segmented, RNA (+) viruses
What is the first product translated by host polymerases in Togaviridiae replication?
viral polymerase–> then translates the +RNA to -RNA, which serves as a template for genomic and subgenomic polyproteins
Where do Western, Eastern and Venezuelan Equine virues replicate initially in the host?
In muscle and fibroblasts
Within 24 hours what does the primary viremia allow in EEV, WE viruses?
Allows for invasion of the CNS, with destruction of neurons
What symptom is seen for ~ 2 weeks foolowing EEV and WEV, then what suddenly follows?
Fever for ~2 weeks, then abrupt onset of encephalitis
*Infection can range from asymptomatic to non-specific febrile illness to the devastating encephalitis–> depends on age of the patient and the dose of virus received during inoculum
Once encephalitis sets in due to EEV/WEV/VEV what symptoms begin to develop? Outcome?
Dizziness and increasing loss of conciousness–> pts eventually become comatose and may die within the first few days of hospitilization. Incidence is quite low however
Which Bunyaviridiae virrus is the moss common cause of arboviral-induced pediatric encephalitis in the US?
LaCross encephalitis virus–> produces seizures and focal neurological signs in childen, but have a low mortality rate and rare sequlae
Bunyaviridiae are _______, ________, ____-strand, (_) __NA viruses
Enveloped, segmented, single-strand (-) RNA viruses
*are spherical
Other than LaCross virus, what other Bunyavirus can cause encephalitis?
California encephalitis virus
Rabies viruses are ________, ________ (_) __NA viruses
enveloped, non-segmented, (-) strand RNA viruses
*are probably he most widely distributed viruses known
What characteristic morphological shape do Rabies viruses have?
“bullet-shaped” morphology
Which particular Rhabdovirus is the causative agent of rabies?
Lyssavirus
How do Rhabdoviruses enter the host cell?
In a pH-dependent fashion following endocytosis (single glycoprotein with pH-dependent fusion activity)
Why does lyssavirus (rabies) affect the CNS?
Has a specific neurotropism for neural cells, so replication is restricted exclusively to neuronal cells
*after it reaches the brain it may spread to other organs
What is the primary mechanism of spread for rabies virus (lyssavirus)?
Is found in high concentrations in salivary glands, so is spread by bites, licking, inhalation of aerosols
How does lyssavirus reach the CNS?
Floowing the bite, virus enters muscles, where it replicates locally and is transported through peripheral sensory nerves to the spinal ganglia–> travels up the spinal cord to the brain
What three places in the brain does lyssavirus like to hang out?
- Limbic system
- Midbrain
- Hypothalamus
*Basal parts of brain
How does lyssavirus get into salivary glands?
Via efferent nerves to the submaxillary salivary glands (then replicates in high concentrations)
How long (range) is the incubation period for lyssavirus? What determines how long or short it is?
1 week- 1 to 2 months
Depends on bite site and its proximity to the CNS
What is a specific early symptom of rabies in the prodromal period that usually lasts 2-10 days following bite/exposure?
Abnormal sensations (itching, burning, numbness) around the bite site
What marks the beginning of the Acute neurological phase of rabies (stage 2)? What causes “hydrophobia”?
Nervous system dysfunction–> anxienty, agitation, paralysis, episodes of delirium
*hydrophobia caused by an exaggerated gag reflex (hypereflexia)
What usually occurs 2 - 7 days following the acute neurological phase in Rabies? How does death usually occur?
Coma (may last 3-30 days)
*Death typically follows from resulting respiratory arrest
What is treatment for Rabies? (3 things)
- Wash wound thoroughly
- Admin of human anti-rabies Ig to wound
- Multiple doses of rabies vaccine (to the thigh or deltoid)
*vaccination is effective due to the long incubation period of the virus
What is the most common vector of rabies in the US?
Skunk
*also foxes and raccoons; sometimes they put out bait with recombinant G protein to try to immunize the vectors
What kind of vaccines are Rabies vaccines?
inactivated vaccines produced in cell culture
What is the areniviridiae virus that can cause encephalitis?
Lymphocytic choriomeningitis virus (LCMV)
LCMV are _______, _______ _NA viruses
enveloped, segmented RNA viruses
*contain 2 RNA segments encoding 4 proteins
What do LCMV virions often contain that is unique?
Host cell ribosomes (arena is from arenosus, meaning “sandy”)
Uncoating, transcription, and replication of LCMV occurs by an uncoventional _________ strategy
ambisense
What does “ambisense” mean?
RNA segments encode several proteins and are read in both directions to produce more proteins than usual
What does the L strand of LCMV encode?
The virus’ RNA-dependent RNA polymerase (needed to make the (-) strands originally contained in the virus into (+) sense
What does the S strand of LCMV RNA encode?
Structural proteins
What is the reservoir for LCMV, in contrast to most others discuused here?
Rodents, including hamsters and mice
*can infect people working in labs or those inhaling feces dropped by house mice
The initial phase of LCMV infections usually involves what symptoms?
Fever, headache, N/V–> these coincide with the viremia
After about 10 days following the initial symptoms, what can follow? What is a rare sequela of LCMV infection
Aseptic meningitis
- sudden onset deafness can occur, but usually resolves with no serious neurological problems
- Cases of LCMV are rarely fatal
