CNS Infections: DNA Viruses and TSE Flashcards
What are two broad ways that virus can cross the BB to enter the CNS?
- Via trauma-induced breaches
2. By mimicking legal cargo
What are the three ways a virus can mimic legal cargo?
- Transcytosis across endothelial cell
- Infection of endothelial cell and subsequent transmission
- Inside infected lymphocytes / monocytes
How does a virus like Rabies enter the CNS?
Infects the PNS, then uses directional transport on microtubules to travel retrograde (+ end to - end) up the nerve axon to reach nuclei in the CNS.
How do most viral CNS infections begin?
Non-neuronal infections of epithelial cells, followed by infection of innervating peripheral neurons with synaptic transmission to CNS
What is neurotropic vs neuroinvasive vs neurovirulent?
Neurotropic = virus is able to infect a neuron or glial cell, regardless of outcome
Neuroinvasive = virus is able to enter the CNS after infecting a peripheral site
Neurovirulent = virus can cause disease by damaging nervous tissue
How do Mumps and Rabies differ in neuroinvasiveness vs neurovirulence?
Mumps and Rabies both commonly infect the CNS and are thus highly neuroinvasive
Mumps rarely causes severe disease while Rabies always does -> Rabies has high neurovirulence
What is the most common form of sporadic fatal encephalitis in adults? What lobe is most affected, and is it focal or diffuse?
HSV-1 encephalitis
Typically the temporal lobe
Focal lesion - with fever, altered consciousness / behavior, and disordered thinking
How is definitive diagnosis of HSV-1 encephalitis made?
Via MRI evidence of temporal lobe edema or hemorrhage, followed by PCR of CSF for HSV-1
What are the most common complications of varicella and zoster?
Encephalitis for both varicella and zoster
Zoster only -> post herpetic neuralgia (from reactivation in PNS dorsal root ganglia)
What does congenital varicella cause?
Mental retardation, cerebral atrophy, and non-CNS abnormalities
How is VZV encephalitis or meningitis diagnosed and treated and prevented?
Diagnosed via PCR of CSF
Treatment: Similar to herpes, Valacyclovir or famciclovir
Prevented via Zostavax! 20x normal Varivax dosage, for adults.
What is the most common cause of birth defects and childhood disabilities in the US?
Congenital cytomegalovirus - has transplacental transmission
What proportion of kids have clinical signs of CMV at birth if infected, and what are they?
10%: Intrauterine growth retardation, hepatosplenomegaly, microcephaly, other symptoms
Majority will develop longterm sequelae including mental retardation, seizures, blindness, deafness, and death
What do the other 90% end up with? This is another one of those “leading cause” things
10-15% of these will develop hearing / vision problems or intellectual impairment in their lives.
It is the leading cause of non-hereditary deafness in children
How is CMV treated?
Ganciclovir is the only treatment available -> remember bone marrow suppression
Who carries the Herpes B virus, where do they carry it, and what is the treatment?
Macaca old world monkeys, in saliva / other secretions.
Treatment is high doses of acyclovir and ganciclovir -> cause fatal encephalitis
What is the structure and relative size of the Polyomavirus family?
Circular dsDNA genomes, with relatively few genes -> highly dependent on cellular enzymes for DNA replication / gene expression
What are the two major viruses of the polyomavirus family?
- JC virus (JCV)
2. BK virus (BKV)
What does JCV cause in immunocompetent vs immunocompromised hosts?
Immunocompetent - mild respiratory disease
Immunocompromised - Progressive Multifocal Leukoencephalopathy (PML)
What causes pathology in PML?
Demyelination of deep cortical white matter via replication in oligodendrocytes, with minimal inflammatory processes going on
What are the normal clinical features of PML? How quick do these patients die?
Focal cerebral involvement: personality alterations, loss of motor skills or sensory loss, intellectual deficits.
It rarely involves cerebellar signs or brainstem
Patients die within 12 months without proper treating of immune system
When would a brain biopsy be needed?
When the pattern deviates from typical subcortical white matter, need to get differential from other possible pathogens: Toxoplasma gondii, Cryptococcus neoformans, Mycobacterium tuberculosis
What does BK virus cause in immunocompetent vs immunocompromised hosts?
Immunocompetent: Mild upper respiratory disease
Immunocompromised:
- Polyomavirus nephropathy, especially in renal transplant patients.
- Hemorrhagic cystitis, in bone marrow transplant patients.
What does PrP^sc mean vs PrP^c? What is their functional difference?
PrP^c = normal prion protein, sensitive to proteases, works in cell adhesion / signalling
PrP^sc = scrapie, referring to sheep transmissable spongiform encephalopathy. It is resistant to degradation by proteases, and infectious
PrP = PRNP = Prion Protein
