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Flashcards in CNS Infections Deck (63):
1

List 3 non-infectious causes of meningitis

Malignancy
Drugs (e.g. NSAIDs, Abs, IVIGs)
Inflammatory conditions (e.g. sarcoid, connective tissue disorders, SLE, vasculitis)

2

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

3

Define myelitis

Infection of the spinal cord

4

What is secondary encephalitis?

Results from complications of a current viral infection where the virus spreads to the brain (usually via the blood)

5

What is the main cause of viral encephalitis?

Enteroviruses

6

List 5 other viral causes of encephalitis besides enteroviruses

Mumps
VZV
Influenza
HIV
HSV-2 (genital herpes)

7

What are the later stage symptoms of viral encephalitis?

Personality and behavioural changes
Seizures
Partial paralysis
Hallucinations and altered consciousness
Coma and death

8

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)

9

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

10

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

11

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

12

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

13

Give 3 examples of viruses which spread via peripheral nerve axons

Rabies virus
Yellow fever virus
HSV

14

Why can viruses spread via peripheral nerve axons?

Because neurons do not express MHC class I and therefore cannot be targeted by CTLs

15

Where in the neuron does viral replication take place?

In the cell body as this is the site of protein synthesis

16

How do viral progeny travel between neurons?

Released progeny can cross synaptic junctions

17

List 5 viruses which enter the CNS via the bloodstream

Poliovirus
Mumps virus
Measles virus
Coxsackievirus
HIV (in monocytes)

18

Give 2 examples of viruses entering the CNS via the olfactory bulb

Coronavirus
HSV

19

What is the effect of viruses which replicate in non-neuronal cells on CNS architecture?

Cause demyelination (e.g. if replication occurs in oligodendrocytes)

20

Describe the structure of rabiesvirus

Bullet-shaped -ive ssRNA virus with a helical capsid and envelope

21

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

22

What is the neuroinvasiveness and neurovirulence of rabiesvirus?

High

23

What are the 3 characteristic symptoms of rabies infection?

Aggression
Thirst
Muscle spasm and terror on attempt to drink

24

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

25

List 2 alpha herpesviruses

HSV
VZV

26

Describe the structure of the alpha herpesviruses

Linear dsDNA inside an enveloped icosahedral virion

27

Is growth in nerve cells obligatory for the alpha herpesviruses?

Yes

28

What is the neuroinvasiveness and neurovirulence of the alpha herpesviruses?

Low neuroinvasiveness
High neurovirulence

29

What is gingivostomatitis?

Mouth swelling and lesions (occurs post-exposure to HSV-1 in young children)

30

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

31

Where is latent VZV harboured?

DRG of a peripheral nerve supplying sensory innervation to an area covered by rash

32

What is the effect of VZV reactivation?

Shingles (painful blisters) over the whole dermatome of the peripheral nerve that harboured the latent virus

33

Is growth in nerve cells an obligatory part of the poliovirus' life cycle?

No

34

What is the neuroinvasiveness and neurovirulence of poliovirus?

Low neuroinvasiveness
High neurovirulence

35

Describe the structure of poliovirus

+ve ssRNA with an icosahedral capsid

36

What family and genus does poliovirus belong to?

Picornaviridae
Enterovirus

37

How does poliovirus cause cell death?

It is cytocidal (kills the cells in which it replicates)

38

What is the non-neuroinvasive course of poliovirus?

Virus is ingested, and enters and replicates in the GALT before being excreted in the faeces

39

What types of viruses cause enterovirus meningitis?

All coxsackie B types
Coxsackie A7 and A9
Many echoviruses

40

What are the 2 classifications of bacterial meningitis?

Culture positive
Aseptic (culture negative)

41

What are the 3 most common causes of infectious meningitis in infants, children and adults?

H. influenza (type B)
N. meningitidis
S. pneuomoniae

42

What are the 3 most common causes of infectious meningitis in neonates and infants <3 months?

E. coli and other GNRs
Group b Streptococcus
Listeria monocytogenes

43

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)

44

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

45

What are the most common symptoms seen in a meningitis presentation?

Fever
Vomiting/nausea
Headache
Stiff neck
Altered mental state
Photophobia
Seizures

46

What is the common presentation seen in children with meningitis?

Non-specific:
Fever
Vomiting/nausea
Irritability
Reusing food/drink
Altered mental state
Bulging fontanelle

47

What is meningococcaemia?

Skin rash caused when N. meningitidis disseminates into the bloodstream

48

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

49

What are the normal parameters in CSF analysis?

Pressure: 60% of blood

50

What are the findings of CSF analysis in viral meningitis?

Pressure: normal
Appearance: clear
WCC: 100s lymphocytes
RCC: 0
Gram stain: negative
Protein: 60%

51

What are the findings of CSF analysis in bacterial meningitis?

Pressure: increased
Appearance: cloudy
WCC: 1000s neutrophils
RCC: 0
Gram stain: positive
Protein: >1.0
Glucose: <40%

52

What are the findings of CSF analysis in meningitis caused by TB?

Pressure: increased
Appearance: cloudy
WCC: 100s lymphocytes
RCC: 0
Gram stain: ZN positive
Protein: 1.0-5.0
Glucose: <30%

53

Why must CSF be analysed as soon as possible following collection?

Delay can cause cell lysis

54

What is "scary" about CSF analysis?

Many parameters may be normal or misleading in the setting of serious disease

55

How is bacterial meningitis treated?

Resuscitation/life support
Fluids
Antibiotics
Steroids
Contact prophylaxis

56

What type of antibiotic is used to treat bacterial meningitis?

3rd generation cephalosporin

57

What is added to the treatment regime for neonates with bacterial meningitis?

IV gentamicin

58

What is the most common complication of meningitis?

Hearing loss

59

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

60

What is meningoencephalitis commonly treated with?

Aciclivor

61

What is the main difference in presentation between meningitis and encephalitis?

Encephalitis has altered conscious state

62

What is the most common cause of encephalitis?

HSV

63

What vaccines are available for encephalitis?

Group C