Flashcards in CNS Infections Deck (63):
List 3 non-infectious causes of meningitis
Drugs (e.g. NSAIDs, Abs, IVIGs)
Inflammatory conditions (e.g. sarcoid, connective tissue disorders, SLE, vasculitis)
Distinguish between the terms neurotropic, neuroinvasive and neurovirulent
Neurotropic: capable of replicating in nerve cells
Neuroinvasive: capable of entering or infecting the CNS
Neurovirulent: capable of causing disease within the nervous system
Infection of the spinal cord
What is secondary encephalitis?
Results from complications of a current viral infection where the virus spreads to the brain (usually via the blood)
What is the main cause of viral encephalitis?
List 5 other viral causes of encephalitis besides enteroviruses
HSV-2 (genital herpes)
What are the later stage symptoms of viral encephalitis?
Personality and behavioural changes
Hallucinations and altered consciousness
Coma and death
What is the pathological basis of post-infectious encephalomyelitis and what is its typical course?
Possibly autoimmune in nature; characterised by absence of virus but presence of inflammation and demyelination
Can occur within a few days after infections (e.g. measles, mumps, rubella, chickenpox)
What is Guillain-Barre syndrome? What is its typical course?
An acute inflammatory demyelinating disease following infection with several viruses (e.g. EBV, CMV, HIV) but not requiring active infection (outbreak occurred following administration of inactivated influenza vaccine in 1976)
Results in partial or complete paralysis
75% of patients resolve within weeks
What is the cause/epidemiological association, prognosis and main pathology in Reye's syndrome?
Occurs post-infection with influenza or chickenpox in children, especially if aspirin was administered during the initial fever
25% case-fatality rate
Cerebral oedema occurs without inflammation
Give an example of a chronic demyelinating disease. When does it typically occur?
Sub-acute sclerosing panencephalitis
Occurs as a late sequel to measles infection
How does AIDS encephalopathy occur? How many patients develop the AIDS dementia complex?
When HIV infection causes immunodeficiency, the virus' neurovirulence becomes apparent
50% of patients develop progressive dementia
Give 3 examples of viruses which spread via peripheral nerve axons
Yellow fever virus
Why can viruses spread via peripheral nerve axons?
Because neurons do not express MHC class I and therefore cannot be targeted by CTLs
Where in the neuron does viral replication take place?
In the cell body as this is the site of protein synthesis
How do viral progeny travel between neurons?
Released progeny can cross synaptic junctions
List 5 viruses which enter the CNS via the bloodstream
HIV (in monocytes)
Give 2 examples of viruses entering the CNS via the olfactory bulb
What is the effect of viruses which replicate in non-neuronal cells on CNS architecture?
Cause demyelination (e.g. if replication occurs in oligodendrocytes)
Describe the structure of rabiesvirus
Bullet-shaped -ive ssRNA virus with a helical capsid and envelope
What is the immune system's main mechanism of defence against rabiesvirus?
Rabiesvirus must replicate within nerve cells and this results in rabies glycoprotein being expressed on the cell surface, providing a good target for Abs
What is the neuroinvasiveness and neurovirulence of rabiesvirus?
What are the 3 characteristic symptoms of rabies infection?
Muscle spasm and terror on attempt to drink
Why can vaccination be used as a form of treatment for rabies infection?
Because there is a window of opportunity between initial infection and infection of the CNS depending on where the bite occurs; it takes ~10 days to elicit an Ab response and takes 12-60 days for infection to reach the CNS
List 2 alpha herpesviruses
Describe the structure of the alpha herpesviruses
Linear dsDNA inside an enveloped icosahedral virion
Is growth in nerve cells obligatory for the alpha herpesviruses?
What is the neuroinvasiveness and neurovirulence of the alpha herpesviruses?
What is gingivostomatitis?
Mouth swelling and lesions (occurs post-exposure to HSV-1 in young children)
What % of people harbour latent HSV in sensory nerve ganglia (trigeminal or sacral)? How is the genome stored?
20%; genome maintained as an episome coated with histones
Where is latent VZV harboured?
DRG of a peripheral nerve supplying sensory innervation to an area covered by rash
What is the effect of VZV reactivation?
Shingles (painful blisters) over the whole dermatome of the peripheral nerve that harboured the latent virus
Is growth in nerve cells an obligatory part of the poliovirus' life cycle?
What is the neuroinvasiveness and neurovirulence of poliovirus?
Describe the structure of poliovirus
+ve ssRNA with an icosahedral capsid
What family and genus does poliovirus belong to?
How does poliovirus cause cell death?
It is cytocidal (kills the cells in which it replicates)
What is the non-neuroinvasive course of poliovirus?
Virus is ingested, and enters and replicates in the GALT before being excreted in the faeces
What types of viruses cause enterovirus meningitis?
All coxsackie B types
Coxsackie A7 and A9
What are the 2 classifications of bacterial meningitis?
Aseptic (culture negative)
What are the 3 most common causes of infectious meningitis in infants, children and adults?
H. influenza (type B)
What are the 3 most common causes of infectious meningitis in neonates and infants <3 months?
E. coli and other GNRs
Group b Streptococcus
Why are H. influenza, N. meningitidis and S. pneumoniae the most common causes of infectious meningitis?
They are best at evading the immune system as they are encapsulated (polysaccharide capsule, avoid C' fixation and phagocytosis)
What are the 10 steps involved in the pathogenesis of meningitis?
1) Colonisation of nasopharyngeal mucosa
2) Invasion of bloodstream
3) Survival and multiplication
4) Crossing of BBB
5) Invasion of meninges and CNS
6) Increased BBB permeability
7) Pleocytosis (increased WCC in the CSF)
8) Increased ICP
9) Release of pro-inflammatory compounds
10) Neuronal injury
What are the most common symptoms seen in a meningitis presentation?
Altered mental state
What is the common presentation seen in children with meningitis?
Altered mental state
What is meningococcaemia?
Skin rash caused when N. meningitidis disseminates into the bloodstream
What investigations can be performed for a possible case of meningitis?
Blood: FBE, ESR, culture, PCR
CSF: pressure, biochemistry (for proteins, glucose), microscopy (WBCs, RBCs, Gram stain), culture, PCR (for viruses, bacteria)
Skin scraping: microscopy (Gram stain), culture, PCR
Neuroimaging: CT, MRI, PET
What are the normal parameters in CSF analysis?
Pressure: 60% of blood
What are the findings of CSF analysis in viral meningitis?
WCC: 100s lymphocytes
Gram stain: negative
What are the findings of CSF analysis in bacterial meningitis?
WCC: 1000s neutrophils
Gram stain: positive
What are the findings of CSF analysis in meningitis caused by TB?
WCC: 100s lymphocytes
Gram stain: ZN positive
Why must CSF be analysed as soon as possible following collection?
Delay can cause cell lysis
What is "scary" about CSF analysis?
Many parameters may be normal or misleading in the setting of serious disease
How is bacterial meningitis treated?
What type of antibiotic is used to treat bacterial meningitis?
3rd generation cephalosporin
What is added to the treatment regime for neonates with bacterial meningitis?
What is the most common complication of meningitis?
Why is the use of steroids to treat meningitis in children in developed countries controversial?
Studies on children in developing countries showed no impact on long term sequelae
Studies on adults in developed countries showed opposite
What is meningoencephalitis commonly treated with?
What is the main difference in presentation between meningitis and encephalitis?
Encephalitis has altered conscious state
What is the most common cause of encephalitis?