CNS Viruses Flashcards

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Q
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2
Q

What are some predictors of a bacterial etiology of Meningitis?

A

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

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3
Q

How does viral meningitis present?

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4
Q

What are the most common causes of viral meningitis?

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  • 80% caused by enterovirus (Echo, Coxsackie, Enterovirus 71)
  • 10% attributed to Mumps (prior to MMR vaccine)
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5
Q

Recurrent aspetic meningitis is likely due to what?

A

HSV-2 (genital herpes)- look for Mollerat cells in the CSF and tx with acyclovir

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6
Q

Recurrent meningitis is likely due to:

A

•HIV and VZV

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7
Q

What are the most common causes of viral encephalitis?

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•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)

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8
Q

What are the symptoms (progression) of viral encephalitis?

A

Fever

Headache

Lethargy

Prodromal upper respiratory infection

  • Confusion (parenchymal involvement)
  • Seizures
  • Coma
  • Death
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9
Q

What should be on the Ddx for viral encephalitis?

A

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

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10
Q

What is the prognosis of viral encephalitis?

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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)

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11
Q

Describe HSV encephalitis

A

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

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12
Q

What is the classic site of damage in HSV encephalitis?

A

temporal lobe (MRI will show necrosis of the temporal love)

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13
Q

What genuses cause encephalitis via mosquito vector?

A

Flaviviruses (West Nile, St. Louis encephalitis)

Alphaviruses (Togaviruses) (Eastern, Western, and Venezuelan equine)

Bunyaviruses (Calfiornia encephalitis, La Crosse virus)

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14
Q

What viruses cause encephalitis via animal vectors?

A

Rhabdovirus (rabies)

Arenavirus (LCMV, lymphocytic choriomeningitis virus)

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15
Q

What is the structure of Flaviviruses (St. Louise and West Nile)?

A

Small, enveloped (+) strand RNA viruses (3 genera)

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16
Q

What are the genera of Flaviviruses and their associated diseases?

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•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

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17
Q

How do Flaviviruses replicate?

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•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

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18
Q

How are flavivirueses transmitted?

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•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

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19
Q

What diseases do flaviviruses cause in the U.S.?

A

–St. Louis encephalitis

–West Nile virus

–Dengue virus (travelers returning from abroad)

–Yellow fever (potentially)

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20
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21
Q

Where is St. Louis Encephalitis virus epidemic?

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•Epidemics occur throughout North, Central, and South America

–During ’80s and ’90s there were SLE epidemics in Colorado, California, Florida, Texas, and Arkansas

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22
Q

How does St. Louis Encephalitis present?

A
  • HA with fever
  • Aseptic meningitis
  • Encephalitis
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23
Q

What is the incubation period for St. Louis Encephalitis?

A

between 4-21 days

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24
Q

What is the initial presentation of St. Louis Encephalitis?

A

–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

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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
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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
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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
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How is West Nile tx?
No vaccines for humans, but there is a vaccine for horses Treatment involves supportive care
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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)
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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
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What is the structure of Togaviridae?
Small, enveloped, nonsegmented (+) strand RNA viruses
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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
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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
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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
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What is the structure of Bunyaviruses?
•Enveloped, segmented, single-stranded (-) sense RNA virus
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More on Bunyaviruses
•Over 300 different species grouped in five genera –California encephalitis virus and La Crosse virus (transmitted via mosquito)
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What is the most common cause of arboviral-induced pediatric encephalitis in the U.S.?
•La Crosse virus ## Footnote –Most patients recover completely –Mortality rates are low (\< 1%).
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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
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What is the replication of rabies?
Replication strategy is the same as paramyxoviruses (measles & mumps), except rhabdoviruses enter cells by endocytosis
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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
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Rabies virus is found in high concentrations where during the final stages of disease?
in the salivary glands
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What is the prognosis for Rabies?
Rabies is uniformly fatal if postexposure treatment is not administered
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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
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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**
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What are the phases of rabies infection?
- prodromal - acute neurologic phase - coma and death
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Describe the prodromal phase of rabies
–2-10 days following exposure –Includes malaise, fever, headache
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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)
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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
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Rabies
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Describe the structure of Lymphocytic Choriomeningitis virus (LCMV) (Arenaviridae)
•Enveloped, segmented, ambisense RNA viruses
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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
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How are arenoviruses transmitted?
Arenaviruses are transmitted by inhalation of aerosolized rodent excreta and saliva
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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.
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What is the prognosis for LCMV?
**Rarely fatal**, most patients recover without serious neurological problems NOTE: No arenavirus vaccines are available
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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
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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
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What CNS neoplasms are associated with HIV?
–Primary CNS lymphoma –Metastatic Kaposi’s sarcoma (rarely goes to brain)
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