CNS Viruses Flashcards
What are some predictors of a bacterial etiology of Meningitis?
CSF glucose < 34
CSF protein > 220
CSF WBC count > 2000
CSF neutrophil count > 1180
The presence of any ONE of the above findings predicts bacterial etiology with >99% certainty
How does viral meningitis present?
What are the most common causes of viral meningitis?
- 80% caused by enterovirus (Echo, Coxsackie, Enterovirus 71)
- 10% attributed to Mumps (prior to MMR vaccine)
Recurrent aspetic meningitis is likely due to what?
HSV-2 (genital herpes)- look for Mollerat cells in the CSF and tx with acyclovir
Recurrent meningitis is likely due to:
•HIV and VZV
What are the most common causes of viral encephalitis?
•30% arbovirus (St. Louis, West Nile, La Crosse): Transmitted by mosquitos or ticks and predominantly a disease of children and the elderly
•23% enterovirus: Family epidemics via URI or GI infections
•27% Herpes simplex virus-Type 1 (HSV-1)
What are the symptoms (progression) of viral encephalitis?
Fever
Headache
Lethargy
Prodromal upper respiratory infection
- Confusion (parenchymal involvement)
- Seizures
- Coma
- Death
What should be on the Ddx for viral encephalitis?
Bacterial meningitis
Fulminant TB or fungal meningitis
Rocky Mountain Spotted Fever, Lyme disease
Brain abscess
Postinfectious or post-vaccinial immune mediated encephalitis (measles)
Bacterial endocarditis (measles)
CNS vasculitis
What is the prognosis of viral encephalitis?
Outcome depends on specific virus, timely treatment, and ICU care
HSV-1 responds to acyclovir
CMV responds to ganciclovir
Poorer prognosis associated with California, La Cross, Eastern Equine and West Nile when encephalitis develops
Rabies is uniformly lethal (if not treated)
Describe HSV encephalitis
Very rare (2-4 cases/1,000,000/yr) and can be the result of an acute infection OR more commonly reactivation of a latent infection
What is the classic site of damage in HSV encephalitis?
temporal lobe (MRI will show necrosis of the temporal love)
What genuses cause encephalitis via mosquito vector?
Flaviviruses (West Nile, St. Louis encephalitis)
Alphaviruses (Togaviruses) (Eastern, Western, and Venezuelan equine)
Bunyaviruses (Calfiornia encephalitis, La Crosse virus)
What viruses cause encephalitis via animal vectors?
Rhabdovirus (rabies)
Arenavirus (LCMV, lymphocytic choriomeningitis virus)
What is the structure of Flaviviruses (St. Louise and West Nile)?
Small, enveloped (+) strand RNA viruses (3 genera)
What are the genera of Flaviviruses and their associated diseases?
•Flaviviruses: ~70 members and many cause disease in humans
- Yellow fever virus - First human illness shown to be caused by a “filterable agent” (Walter Reed, 1901)
- Flavi (flavus) = yellow
•Pestiviruses: Animal pathogens
•Hepaciviruses: Hepatitis C virus
How do Flaviviruses replicate?
•Similar to picornaviruses, except virions are enveloped.
–Enters by receptor-mediated endocytosis
–(+) strand genome is translated into single polyprotein
–Polyprotein is cleaved
–Virions bud into intracellular organelles (ER & Golgi), are transported via the exocytic pathway and released at the cell surface
How are flavivirueses transmitted?
•All flaviviruses are transmitted by insect vectors and are found world-wide
–Most important group of arboviruses
–Many are considered “emerging” viruses
–In general, humans are not primary hosts
What diseases do flaviviruses cause in the U.S.?
–St. Louis encephalitis
–West Nile virus
–Dengue virus (travelers returning from abroad)
–Yellow fever (potentially)
Where is St. Louis Encephalitis virus epidemic?
•Epidemics occur throughout North, Central, and South America
–During ’80s and ’90s there were SLE epidemics in Colorado, California, Florida, Texas, and Arkansas
How does St. Louis Encephalitis present?
- HA with fever
- Aseptic meningitis
- Encephalitis
What is the incubation period for St. Louis Encephalitis?
between 4-21 days
What is the initial presentation of St. Louis Encephalitis?
–Onset is characterized by generalized malaise, fever, chills, headache, sore throat and/or cough
–Typical “influenza-like” symptoms
–Most infections do not progress beyond these symptoms
How does St. Louis Encephalitis present if secondary viremia occurs?
–Symptoms can be followed 1-4 days later by acute or subacute neurological signs associated with CNS disease
–CNS symptoms are similar to HSV encephalitis; various bacterial, fungal and parasitic infections causing brain abscesses; and brain tumors
How is St Louis Encephalitis tx?
No vaccines available; no antivirals thoroughly evaluated
The most effective means of control is reduction of the mosquito population
How does West Nile present?
- Febrile (Moderate to high fever), influenza-like illness with abrupt onset
- Headache, sore throat, backache, myalgia, arthralgia, fatigue
Rash, lymphadenopathy
Acute aseptic meningitis or encephalitis
Most fatal cases occur in the elderly
How is West Nile tx?
No vaccines for humans, but there is a vaccine for horses
Treatment involves supportive care
Describe Japanese Encephalitis virus
JEV is the most significant etiology of arboviral encephalitis worldwide
Found in SE Asia and the Far East
~45,000 cases reported/yr (Likely an underestimate)
Is there a vaccine for Japanese Encephalitis virus?
Vaccine is available- Recommended for at-risk travelers planning extended trips to rural areas (longer than 30 days
What is the structure of Togaviridae?
Small, enveloped, nonsegmented (+) strand RNA viruses
What are the genera of Togaviridae?
–Rubella virus (humans are only known host)
–Alphaviruses (transmitted by mosquitoes)
- Western equine encephalitis
- Eastern equine encephalitis
- Venezuelan equine encephalitis
How do togaviridae infections present?
•Ranges from asymptomatic infections, to general febrile illness, to devastating encephalitis
–Dependent on dose and age of patient
–Encephalitis occurs mainly in children and elderly
–Adults get mild disease with fever and drowsiness
What is the typical disease progression for togaviridae?
Fever for 7 to 11 days, then resolution…….Or:
Abrupt onset of encephalitis: Vomiting, dizziness, confusion, increasing loss of consciousness; Within 2-3 days patients become comatose and die
What is the structure of Bunyaviruses?
•Enveloped, segmented, single-stranded (-) sense RNA virus
More on Bunyaviruses
•Over 300 different species grouped in five genera
–California encephalitis virus and La Crosse virus (transmitted via mosquito)
What is the most common cause of arboviral-induced pediatric encephalitis in the U.S.?
•La Crosse virus
–Most patients recover completely
–Mortality rates are low (< 1%).
What is the structure of Rhabdoviridae (Rabies virus)?
Enveloped, nonsegmented (-) strand RNA virus
Characteristic bullet-shaped morphology
Have a single glycoprotein (G)
Attachment & fusion (pH-dependent)
Do not induce syncytia
What is the replication of rabies?
Replication strategy is the same as paramyxoviruses (measles & mumps), except rhabdoviruses enter cells by endocytosis
How does rabies present?
–Rabies virus causes a slow, progressive disease that characteristically involves the CNS.
- Due to the neurotropism of rabies virus envelope glycoprotein
- Replication is restricted to neuronal cells initially, but then disseminates to other organs
Rabies virus is found in high concentrations where during the final stages of disease?
in the salivary glands
What is the prognosis for Rabies?
Rabies is uniformly fatal if postexposure treatment is not administered
How is Rabies transmitted?
•Transmission usually results from an animal bite
–Nonbite exposures can occur (scratches, licks, aerosols)
Many unexplained cases in U.S. are associated with bats or being in relatively close proximity to bats
What is the incubation period of rabies?
Incubation period is usually long (2-3 months), but can be as short as 1 week
Dependent on bite proximity to CNS
Head, facial, neck bites develop fastest and show highest mortality
What are the phases of rabies infection?
- prodromal
- acute neurologic phase
- coma and death
Describe the prodromal phase of rabies
–2-10 days following exposure
–Includes malaise, fever, headache
Describe the acute neurologic phase of rabies
–Can occurs months to years after initial exposure
–Nervous system dysfunction
•anxiety, agitation (furious rabies)
–where encephalitis predominates
–common symptom is hydrophobia
•paralysis (paralytic or “dumb” rabies)
Describe the coma and death phase of rabies
–Occurs 2-7 days after acute neurologic phase
–Can last from 3 days up to ~ 1 month
Rabies
Describe the structure of Lymphocytic Choriomeningitis virus (LCMV) (Arenaviridae)
•Enveloped, segmented, ambisense RNA viruses
How does Lymphocytic Choriomeningitis virus (LCMV) (Arenaviridae) replicate?
•Virions contain two RNA segments
–Often contain cell ribosomes
–“Arena” is from arenosus = sandy
–Enter by endocytosis
- Replication occurs by a nonconventional “ambisense” strategy (below)
- Release by budding from the cell surface
How are arenoviruses transmitted?
Arenaviruses are transmitted by inhalation of aerosolized rodent excreta and saliva
How does LCMV present?
•Disease is characterized by two phases.
ØThe initial phase shows a prodrome of fever, headache, nausea, and vomiting which coincides with viremia.
ØAn aseptic meningitis usually begins about 10 days later.
What is the prognosis for LCMV?
Rarely fatal, most patients recover without serious neurological problems
NOTE: No arenavirus vaccines are available
Neurologic complications occur in 40% of AIDS patients. Name some.
- Acute aseptic meningitis (at seroconversion)
- Chronic meningitis
- HIV dementia complex
- Vacuolar myelopathy
- Peripheral neuropathy
- Cranial neuropathy
- Inflammatory myopathy
What opportunistic infections are most common with HIV?
–Toxoplasmosis is by far most frequent
–Cryptococcal meningitis
–TB
–JC virus à Progressive multifocal leukodystrophy (PML)
–CMV encephalitis
What CNS neoplasms are associated with HIV?
–Primary CNS lymphoma
–Metastatic Kaposi’s sarcoma (rarely goes to brain)
