AuCoin: Viral Encephalitis Flashcards
When can CNS infections be associated with significant morbidity and mortality?
when they occur w/i the cranium or spinal column
How do most patients with CNS infections present?
fever
headache
altered mental status
focal neuro deficits
Viruses can colonize select mucosal surfaces in the body. If one has previous contact with a virus, the mucosa of the gi and resp tract may be coated with IgA. What does IgA do?
IgA neutralizes the virus and prevents attachment and subsequent cell penetration
How can certain viruses end up infecting/invading the CNS?
- replicate at non-neuronal sites (initially at the location where they entered)
- establish viremia
- cross the BBB to invade the CNS
For example, (blank) initially multiply in the peritonsillar lymphatics, Peyer’s patches, the lamina propria of the intestine, and vascular and endothelial cells
(blank) may mediate virus penetration from the gut lumen to lymphoid cells
From this initial site, the virus then disseminates to circulatory system (e.g., liver, spleen, and muscle), where further multiplication augments the (blank)
enteroviruses; M cells; viremia
After viremia, viral particles are normally cleared by (blank)
However, viruses may also elude host clearance by associating with certain cells
Some viruses (e.g., measles, herpes, mumps) grow and are transported in (blank)
phagocytic cells; phagocytic cells
What are 4 ways in which viruses can invade the CNS?
- invasion directly across cerebral capillary endothelial cells
at the BBB. - Infection of glia w/o evidence of infection
- Transport via immune cells (monocytes) b/w cerebral capillary endothelial cells
- Olfactory or peripheral nerves
To cross the BBB and enter the CNS hematologically, inflammation occurs and proinflammatory mediators compromise the BBB. Passage of viruses through endothelial cells can release (blank) and (blank)
IL6 and IFNgamma
Production of disease in the CNS requires what three things?
- viral attachment/penetration of susceptible cells
- spread w/i the nervous system
- induction of cellular changes
Viral entry into the subarachnoid space leads to dispersion of virus within CSF in contact with (blank) cells
Spread of virus may then occur to (blank) and (blank)
meningeal; glia; neurons
Once viral infection of the CNS occurs, inflammatory cells usually accumulate. What cells appear?
lymphocytes sensitized by the virus
After development of a CSF inflammatory response, alterations in the BBB permit the traversal into CSF of serum proteins, including (blank)
immunoglobulins
T/F: Intracerebral accumulation of Ig is reflected by an increase in the CSF-to-serum ratios of specific Ig that persist for several weeks after infection
True
An intact host immune response is important for clearance of virus from the CNS. Which cells, T or B cells, seem to be more important in this response?
T cells
inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges
meningitis
How is meningitis identified?
pleocytosis - abnormal WBCs in the CSF
Acute meningitis is clinically defined as a syndrome characterized by the onset of meningeal symptoms over the course of (blank).
hours to several days
Common etiologic agents of acute meningitis are (blank)
viruses (mostly enteroviruses)
also bacteria like S. pneumo and N. meningitidis
The cause of the meningitis is not apparent after initial evaluation and routine stains and cultures of CSF; not caused by pyogenic bacteria
aseptic meningitis
3 most common causes of aseptic meningitis?
nonpolio enteroviruses (85-95%)
mumps viruses
herpesviruses
When do most cases of viral meningitis occur? What are they caused by? Who mostly gets viral meningitis?
summer (warm weather and sparse clothing facilitates fecal-oral spread of enteroviruses); enterovirus; children t wash their hands properly
Symptoms of meningitis caused by enterovirus?
headache fever stiff neck nausea vomiting photophobia altered mental status
How long do symptoms of viral meningitis last?
7-10 days, and then it resolves
T/F: Enteroviruses have been recovered from wastewater and sewage; and disease has been reported after swimming in sewage-contaminated seawater
True
Most common enterovirus causing meningitis?
echoviruses
Group A – herpangina (ulcers in oropharynx, fever, sore throat)
Also called “Hand-foot-and-mouth disease” due to ulcer formation
Group B – pleurodynia (fever and severe pleuritic-type chest pain)
Myocarditis (fever, chest pain, and signs of congestive heart failure)
Both A & B can cause aseptic meningitis and mild paralysis
Coxsackie virus
Transmitted via fecal-oral route; may be transmitted in pool water; one of the leading causes of aseptic viral meningitis; may also cause hand foot and mouth disease
echovirus
2 non-polio enteroviruses that can cause stiff neck and photophobia after hanging out at a campground pool?
coxsackievirus
echovirus
In an unimmunized population, (blank) is one of the most common causes of aseptic meningitis and encephalitis
mumps
The most common neurologic manifestation of infection with mumps virus and is usually a benign and self-limited process
meningitis
Important properties:
Causes painful swelling of the parotid gland
It occurs primarily in childhood, transmitted via respiratory droplets
Only a single serotype
Clinical information:
Infects the upper respiratory tract spreads via blood to parotid glands, testes, ovaries, pancreas, and, in some cases, meninges
Diagnosis is made clinically, although testing is available
Low incidence in US
Prevention consists of immunization with the live, attenuated vaccine
Mumps
Important properties:
Transmitted by aerosol inhalation, ingestion of contaminated food
House mouse or hamsters common reservoirs (secretions & excretions)
Worldwide distribution with low case fatality rate (
Lymphocytic choriomeningitis (arenaviridae)
Defined as an inflammatory process of the brain parenchyma associated with clinical or laboratory evidence of neurologic dysfunction
encephalitis
Criteria for encephalitis?
- altered consciousness for 24+ hours w at least one of the following:
fever seizures focal neurologic findings CSF pleocytosis EEG or neuroimaging findings
Six members of this family of virus cause viral encephalitis
Herpes virus
**HSV-1, HSV-2, VZV, EBV, CMV, HHV-6
How does the herpes virus, which lies dormant in the ganglion of the trigeminal cranial nerve, cause encephalitis?!
retrograde transmission of the virus from a peripheral site on the face –> moves along a nerve axon –> to the brain
Why do you suppose HSV infection causes cell death and tissue injury in HSV encephalitis?
direct viral killing of neurons, and also immune-mediated mechanisms of cell death
The most common identified cause of viral encephalitis?
HSV-1
**some caused by HSV-2
How do you diagnose HSV encephalitis? What will WBC count be like? Glucose? Protein?
MRI PCR of HSV DNA in the CSF CSF pleocytosis (mostly lymphocytes) protein elevated glucose normal
How to treat HSV encephalitis?
acyclovir
T/F: CNS infection (encephalitis or vasculopathy) can occur during primary infection by Varicella Zoster virus or after viral reactivation from latency (shingles)
True!
This occurs in 1/2500 cases of VZV infection after primary infection; lymphocyte pleocytosis; normal glucose; elevated protein
acute disseminated encephalomyelitis (ADEM)
How is VZV encephalitis caused?
vasculopathy
A ubiquitous human virus (90-100% antibody seroprevalence in adults); transmitted via body fluids and organ transplants; causes acute infection and reactivation disease from latent virus; initial infection is often clinically silent, may produce a mononucleosis
CMV
3 neuro complications caused by HCMV?
retinitis
encephalitis
neuropathy
**can cause congenital defects, too
In HCMV, infected neurons and glial cells enlarge and develop cytoplasmic and intranuclear (blank)
inclusions (“owl-eyes”)
Who is most likely to get CMV encephalitis? How do you diagnose CMV encephalitis?
immunocompromised patients, esp AIDS patients with CD4 T cell count <50 cells/mL; CMV DNA from CSF by PCR
How do you treat CMV encephalitis?
gancyclovir + foscarnet
When CMV invades the CNS, it can cause this type of encephalitis that can be visualized on MRI
ventriculoencephalitis
CNS disease occurs in ~1% of (blank) cases and can cause, meningitis, encephalitis, transverse myelitis, and Guillain-Barré syndrome; Patients with (blank) present fever, headache, altered consciousness, seizures, and focal neurologic deficits
EBV infectious mononucleosis; EBV encephalitis
A ubiquitous viral infection of T lymphocytes that causes a spectrum of disease on primary infection
Causes exanthem subitum (roseola) in infants
Virus then becomes latent and can periodically reactivate to cause disease
It is recognized as a cause of encephalitis in immunocompromised adults, particularly patients with allogeneic bone marrow transplants
HHV-6
How to diagnose HHV-6 encephalitis? How to treat it?
CSF PCR; like CMV, use gancyclovir and foscarnet
Which vector borne viruses can cause encephalitis?
California encephalitis virus West nile virus St. Louis encephalitis EEE WEE VEE
arbovirus transmitted via mosquito; La Crosse virus is the most common subtype causing encephalitis; seizures; aseptic meningitis
California encephalitis virus
arbovirus transmitted via mosquitoes and crows; spreads via macrophages; children and elderly at higher risk; symptoms range from flu-like to encephalitis
West Nile virus
arbovirus transmitted via mosquitoes that bite infected birds; occurs mostly in late summer/early fall; symptoms range from flu-like to encephalitis; more serious neuroinvasive infections may occur
**if it’s not West Nile, think…
St. Louis encephalitis
arbovirus transmitted from mosquitoes to birds to humans; also infects horses; Severe headaches, nausea, vomiting, fever; changes in mental status, seizures an coma occurs; survivors are left with brain damage
Eastern equine encephalitis
Similar to EEE but less severe
Western equine encephalitis
Arbovirus like EEE found predominantly in South and Central America
Venezuelan equine encephalitis
In paralytic poliomyelitis, flaccid paralysis is the predominant finding, but (blank) involvement can lead to life-threatening respiratory paralysis
Painful muscle spasms also occur, motor nerve damage is permanent
In paralytic polio, the (blank) and brain parenchyma (meningoencephalitis) are involved
brainstem; meninges
T/F: If the spinal cord is also involved in paralytic polio, the term meningomyeloencephalitis is often used
True
an acute viral infection of the meninges and the motor neurons of the spinal cord and the brainstem.
poliomyelitis (polio)
How is polio virus transmitted? Where does it initially replicate inside its host? Then where does it spread and replicate?
fecal oral route; in the GALT of the oropharynx and small intestine; then spreads to blood and crosses BBB, enters spinal cord and replicates causes cell destruction and paralysis
May result from HIV infection of the macrophages and microglial cells of the brain; patients may undergo slow deterioration of their intellectual abilities and exhibit other signs of a neuro disorder; similar to the early stages of Alzheimer disease
AIDS-related dementia
What is the most common neuro complication in late stages of HIV infection?
subacute or chronic HIV encephalitis presenting as dementia
The frequency of AIDS-related dementia is far higher after what point in the disease?
after the constitutional symptoms and opportunistic infections of AIDS have become established
In children with AIDS, (blank) is more common than all opportunistic infections, more than 60 percent of children eventually being affected
dementia
Describe the dementia experienced by AIDS patients. How long do patients typically survive after the onset of dementia?
slow, progressive dementia (loss of memory, attentiveness, language, and apathy, as well as abnormalities in motor function); 3-6 month survival after onset
T/F: Evidence of CMV infection may occur but evidence indicates that the AIDS dementia complex is a result of direct infection with HIV
True
Describe the 3 stages of rabies before coma and death occur. During which stage is there a high titer of virus detected, along with detectable antibody in the serum?
incubation period: 60 days to 1 year;
prodrome phase: fever, nausea, vomiting, headache, lethargy;
**neurologic phase: hydrophobia (pain associated with swallowing water)
anxiety, seizures, hallucinations
paralysis –> respiratory failure
coma and death due to neurologic and pulmonary complications
**high titer and detectable antibody in neuro phase
How is rabies transmitted? Where does the virus remain initially? How does it end up infecting the CNS?
bite of a rabid animal; remains at the site of infection for days to months (in the muscle) before involving CNS; virus eventually infects nerve endings by binding to receptors on neurons - it ascends in the spinal cord to infect the brain
After the rabies virus invades the brain and spinal cord, (blank) develops and neurons degenerate
encephalitis
typically presents with dementia, ataxia, myoclonus, is relentlessly progressive, and generally causes death within a year of onset
It usually affects people aged 45–75, most commonly appearing in people between the ages of 60–65, 5-20 year incubation period
Prions reproduce by binding the normal cellular isoform of the prion protein (PrPC), stimulating conversion of PrPC into disease-causing isoform (PrPSc)
Prions are devoid of nucleic acid; all infectious agents possess genomes that direct the synthesis of their progeny
Creutzfeldt-Jakob disease
Most common human prion disease
CJD
Three types of Creutzfeldt-Jakob disease?
sporadic: cause not known
familial: genetic defect in prion protein gene
acquired: contaminated meat or transplant
What will you see histologically in CJD?
spongiform degeneration in the brain - “spongy” appearance of brain
