Lecture - Meningitis

Question 1

CNS infections overview:

1. ____ _____ infections - they have high mortality and morbidity
2. What is the CNS vulnerable to? What happens if the intracranial pressure increases?
3. What is the clinical disease determined by? (3)
4. Present as?

Answer 1

1. Life threatening
2. It’s vulnerable to inflammation and oedema. Need prompt diagnosis and appropriate therapy to avoid mortality or complications

V sensitive to inflammation bc inflammation icnreases pressure in cranium and brain has nowhere to go so brainstem can get pushed through skull so loss of respiratory and cardiac fucntion = death

Can get ischameia too bc occludes blood supply to brain

3. Site of infection, infecting organism and host response
4. It is present as acute, subacute or chronic infections

Question 2

What are 4 CNS infections? What can you say about the symptoms?

Answer 2

1. Meningitis: infectious can by by bacteria, virus or fungi. Non-infectious can be lymphoma, leukaemia etc
2. Encephalitis (Generalised inflammation of brain) - mostly seen with viruses but also bac
3. Meningoencephalitis - Inflammation of meninges and brain. Again, usually virus but other things can cause too like bac or parasites
4. Abscesses - Just a very localised infetion somewhere in brain - wall of encapsualted leison in brain. Often silent and not until abcess starts to involve other area of brain (get bigger) and interefer with other processes like sight that you’ll start to see symptoms

With the symptoms - they may overlap so medical imaging is useful

Question 3

What are the 4 routes of infection? (into the CNS, I assume)

Answer 3

1. Haematogenous spread - most common, usually arterial, retrograde through veins (Occasionally enter through vein (retrograde = going against blood floor)
2. Direct inoculation - trauma, or iatrogenic
3. Contiguous spread - have a local infection in e.g. teeth and then it spreads (like how with septic arthritis, you can get osteomyelitis)
4. PNS into CNS - Certain viruses are able to use nerves like use PNS and travel up to get to CNS and use nerves to travel there and spread over brain

Question 4

Meningitis #1:

1. What is it? Like, what’s the meninges? What’re the three layers of the brain?
2. What’re three things to say about meninges/CSF in terms of sterility, finding any organism and inflammation?

Answer 4

1. It’s the inflammation/irritation of meninges and CSF. They are membranes surrounding CNS which line and protect the brain and spinal cord. The three layers: dura, arachnoid (has SCF where you look for organism) and pia.
2. Meninges/CSF are sterile in health, finding any organism is potentially significant and they are sensitive to inflammation

Question 5

What’re the three classifications of meningitis?

• what sort of infection (bacterial, viral etc)
• an interesting fact lol
• how to tell which one

Answer 5

1. Acute:
   - purulent, pyogenic - bacterial (pyogenic meningitis = acute bacterial infection)
   - The bac will be commensals and have capsules (When you are introudced of a new strain of the organism, that can cause problem. We’re tolerant to our own strains)
   - Notice an increase in neutrophils in CSF, which usually doesn’t contain neutrophils
2. Aseptic:
   - viral (have virus in blood and it spreads - viraemia)
   - usually mild, self limiting (acute was serious af)
   - enteroviruses, herpes etc
   - increase in lymphocytes in CSF
3. Chronic:
   - bacterial - TB, syphilis
   - fungal
   - increase in lymphocytes in CSF

Question 6

Aetiology:

1, What two things can lead to a bacterial infection?

2. What about viruses - why not high morbidity/mortality like the other three?
3. What fungi?
4. What parasites

Answer 6

1. Respiratory commensals that have capsules or trauma/injuey (get staph aureus)
2. They’re usually milder and self-liming like influenza
3. Fungi like HIV
4. Parasites like protozoa

Question 7

Clinical features of meningitis:

1. What are the 7 signs and symptoms? Bear in mind that the symptoms are variable and overlap other CNS infections
2. What’s the classic triad of symptoms that might not always be present?
3. What about the symptoms in infants?

Answer 7

1. Signs and symptoms:
   - fever
   - neck stiffness (Bc of inflam in mengines, they can’t tilt head down to chest (swelling and inflam))
   - photophobia
   - lethargy, committing, diarrhoea (general signs of infection)
   - neurological: altered mental state, seizures, headache
   - cold/pale extremities (sepsis - circulatory collapse)
   - rash
2. Neck stiffness, fever and headache (Not all three present tofether but any of these symtoms should make you suspicious. High fever is most common = usually with infection and could be menin)
3. They have generalised symptoms - lethargy, irritability, poor feeling. They’ll also have high pitched crying.
   - Hard to see in infants bc dont respond to infections like adults to - they just have generalised response like drowsy etc so non-specific. They do this no matter what infection and how serious bc theur immune system and all not fully developed.

Question 8

Clinical features #2 of meningitis:

1. What is the rash characteristic of? What does petechiae mean? What about purpuric? What is the non-blanching test?
2. What are the Kernig’s/Brudzinski’s signs?
3. Prodromal symptoms of meningitis?

Answer 8

1. N. meningitidis
   - petechiae: see these tiny little dots early
   - purpuric: Large haemorragic rashes - advanced disease so progressed to sepsis (infection in blood) so get disseminated coagnualtion or something so get tiny little clots and these can embolise and they get trapped in blood vessels in periphery and get ischaema and necrosis (see this late)
   - the rash should be non-blanching: Rash in menin is non-blanching so if you push a glass tumblr against rash then it will maintain colour and not lose it
2. Meningeal irritation but low sensitivity and specificity. Another investigation that can be done. Look at inflam and irritation of menin - not specific to menin. They don’t tell you much but still something
3. Nausea, vomitting, fatigue, malaise, lethargy, cough, pharyngitis, headache, myalgia
   - Can have non-specific - you might not consider meningitis

Question 9

Clinical features #3 meningitis:

1. What are some complications?
2. What are some risk groups?

Answer 9

1. Death, amputation, deaf/blind, epilepsy, cognitive issues
2. Age (infants, elderly and adolescents bc can swap strains when you kiss), immunosuppressed, trauma, etc

Question 10

Neisseria meningitidis:

What’s the virulence like?

Answer 10

Well, it has a capsule and IgA protease for immune evasion. It has pilli, porins and LOS

The capsule can help it to survive intracellularly, it’ll prevent complement activation, it has this sialic acid which is found within us so immune system wont recognise bac as threat.

The IgA protease: Cleaving secretory IgA - it’s meant to coat bacteria and ahesions so they cant stick to host cells and they have this protease to cleave it so they can still bind to host cell in mucosal surface

Pili: imp for adhesion to epithelia and endothelia so way to enter CSF

Porins: Bacteria can translocatie through the endothelil barreris to get into blood or CSF

LOS: LPS - this LOS is slightly differnet to LPS but it’s still programmed to recognise LOS as thraeat so cause inflammation (aka LOS works like LPS essentually)

Question 11

What’s the pathogenesis for meningitis?

Answer 11

Looking at resp commensals - the ycross mucosa and enter blood and hv emchansims they can survive in blood (like hving capsuke) and then cross BBB (mechaisms of that not fully understood) and get into CSF and then their products (LOS) induced inflammation, cytokines and all so increase intracranial pressure = negative outcomes

Once in CSF, can re-enter blood anf then get sepsis (can get both or one)

Question 12

How to diagnose meningitis?

Answer 12

CSF sample of choice - still gold-standard. But antimicrobialis prior to smaple taken can reduce the test thing so yeah, still need to test and not rule out treatment even if have been given antimic

Appearance of fluid: normal is crystal clear

Measure: protein, glucose, WBC count

• if acute bacterial then will increase WBC, decrease glucose and increase protein.
• If aseptic (viral) then increase WBC, normal glucose and increase proteins

Gram stain can be used for initial antimicrobial therapy (it is affected by prior antimicrobials)

Bacteria: culture CSF and do antimicrobial sensitive. Blood cultures useful when you have sepsis.

Bacterial and viruses: Do PCR bc best for viral detection
-not affected by prior antimicrobials

Question 13

What’s treatment of meningitis ?

Answer 13

Definitely prompt empiric antimicrobial therapy for bacterial meningitis and then change once sensitive known