16 Infections of the CNS

Question 1

define meningitis

Answer 1

a serious disease in which there is inflammation of the meninges, caused by viral or bacterial infection, and marked by intense headache and fever, sensitivity to light, and muscular rigidity.

Question 2

route of infection in meningitis (4)

Answer 2

1 blood-borne, commonest
2 parameningeal suppuration, meaning from infection in tissues surrounding the brain e.g. ear (otitis media) and sinuses (sinusitis)
3 direct spread through defect in the dura, CSF leak, if leaking out then there’s a route for organisms to go in e.g. post surgery, trauma
4 direct spread through the cribiform plate (rare)

Question 3

complications of meningitis

Answer 3

death
subdural collection- pressure
cerebral vein thrombosis
hydrocephalus, build up of CSF, may need long term drainage
deafness, 9-15% (Hib)
convulsions
visual/motor/sensory deficit

Question 4

causes of bacterial meningitis and age groups (5)

Answer 4

Neisseria meningitidis= children/young adults (vaccines have reduced this)
Streptococcus pneumonia= elderly and children<2 (usually pneumonia but can cause meningitis if into CSF)
Haemophilus influenzae type b, Hib= children<5 (vaccines have reduced this)
Escherichia coli= neonates
Listeria monocytogenes= neonates/immunocompromised (good at crossing placenta, high risk foods like unpasteurised cheeses and pate)

Question 5

why do we worry about infection getting into CSF

Answer 5

normally doesn’t have bacteria so don’t have response ready there to clear it
blood brain barrier, prevents toxic things getting in but makes it hard to get drug across to treat infection

Question 6

what drugs are more likely to cross BBB

Answer 6

small lipophilic compounds

Question 7

inflammatory process in meningitis

Answer 7

triggered by components in cell wall
migration of neutrophils to the CSF, release of proteolytic products and toxic O radicals, which damaged vascular endothelium reducing BBB, leaking of CSF
take advantage of this in treatment so can get drug through damaged BBB

Question 8

pathogenesis of bacterial meningitis

Answer 8

organisms commonly sit in nasopharynx
get into blood stream, bacteraemia, through pili (binding) endocytosis and separating junctions (increased in immunosuppressed and smokers, mucosal damage allowing invasion)
in blood stream, immune system usually clears it but if doesn’t then they start to multiply, causing inflammatory cascade leading to sepsis
OR survives in blood stream and gets into CSF
now in site where takes a while for inflammatory cascade to happen, multiples
infection in subarachnoid space

Question 9

symptoms of meningitis

Answer 9

global headache
neck and back stiffness- specific for this
nausea and vomiting due to raised intracranial pressure
photophobia- sensitivity to bright lights
these symptoms can occur in other conditions like UTIs, subarachnoid haemorrhage (usually sudden headache not gradual), malignancy

Question 10

meningitis symptoms in infants

Answer 10

typical signs not often present
flaccid
fever and vomiting often the only sign
strange cry
convulsions

Question 11

physical signs of meningitis

Answer 11

don’t need them, mainly due to ongoing blood stream infection
fever
rash petechial/purpuric, bleeding into skin because of damage, take sample GLASS TEST
meningeal irritation
- kernig’s positive due to hamstring spasm
- neck stiffness, unable to put chin on chest
- brudzinskis sign- neck flexion causes flexion of hip and knees

Question 12

most important test in meningitis suspicion

Answer 12

lumbar puncture
most rapid test
distinguish between bacterial and viral causes
BUT risk of herniation of bottom of the brain due to rise in pressure, do neuroimaging first if has long history, focal neurology, drowsy etc

Question 13

CSF changes in meningitis

Answer 13

raised leucocytes
reduced glucose in bacterial and TB not viral
in bacterial- raised neutrophils
in viral and TB- raised lymphocytes
raised proteins

Question 14

what is meningococcal disease

Answer 14

Meningococcal is a bacteria that enters the body, however
meningococcal disease does not always lead to meningitis. It only
leads to meningitis if the bacteria affects the meninges of the brain

Question 15

risk factors for poor outcomes in meningitis

Answer 15

older
otitis media or sinusitis
absence of rash
tachycardia
positive blood culture
low CSF fluid white cell count

Question 16

how is meningitis managed (5)

Answer 16

antibiotics
adequate oxygenation to protect brain
prevention of hypoglycaemia and hyponatraemia
anticonvulsants
decrease intracranial hypertension in extreme setting

Question 17

ideal antibiotic features for meningitis (4)

Answer 17

bactericidal
good activity against likely pathogens
sufficient penetration into CSF at non-toxic doses
low levels of endotoxin (cell wall component) release when organisms killed (theoretical)

Question 18

penetration of antibiotics into CSF is enhanced by (6)

Answer 18

high lipid solubility
low molecular weight
low degree of ionisation
high serum concentration
low degree of protein binding
meningeal inflammation

Question 19

3 main groups of CSF penetration

Answer 19

1 penetrate inflamed and non-inflamed meninges even at standard doses
e.g. metronidazole, trimethoprim, chloramphenicol (but bacteriostatic and resistance)

2 penetrate inflamed meninges or at high doses (tend to use)
e.g. benzylpenicillin, cephalosporin (3rd gen)

3 penetrate poorly
e.g. gentamicin, erythromycin, tetracycline

Question 20

chloramphenicol use in meningitis

Answer 20

use with caution
reserve for allergic patients good penetration into CSF and brain tissue, IV and oral
bacteriostatic
resistance in Hib and pneumococci
rare= can get irreversible aplastic anaemia, grey baby syndrome
reserve agent for penicillin allergy, otherwise use other more effective treatment

Question 21

what’s first line treatment in meningitis, benefits and drawback

Answer 21

ceftriaxone (main)/cefotaxime
activity against penicillin resistant pneumococci and ampicillin resistant Hib
good penetration
doesn’t cover listeria

Question 22

benzylpenicillin in meningitis

Answer 22

no longer used empirically
4 hourly, high doses
lowers seizure threshold
reserved for sensitive strains

Question 23

order benzylpenicillin, chloramphenicol and cefotaxime/ceftriaxone in order of highest penetration into BBB and lowest

Answer 23

chloramphenicol
cefotaxime/ceftriaxone
benzylpenicillin

Question 24

choice of antibiotic depends on.. (5)

Answer 24

age
clinical risks
allergies
gram film result
local and national sensitivity data

Question 25

empirical treatment in child<2 months

Answer 25

benzylpenicillin and gentamicin (cover e.coli), don’t have tight BBB, organisms exposed to in delivery or pregnancy through placenta

Question 26

empirical treatment in child>2 months and adults

Answer 26

cefotaxime or ceftriaxone (and amoxicillin if >60 years or immunocompromised, to cover listeria)

Question 27

treatment in meningococcus

Answer 27

benzylpenicillin if sensitive/ cefotaxime or ceftriaxone

Question 28

treatment in pneumococcus

Answer 28

benzylpenicillin if sensitive/ cefotaxime or ceftriaxone

add vancomycin if risk of resistant stain (travel to high incidence countries)

Question 29

treatment in hib (rare)

Answer 29

cefotaxime or ceftriaxone (chloramphenicol)

Question 30

length of treatment

Answer 30

meningococcus= 7 days
pneumococcus= 14 days
hib= 7 days
listeria= at least 21 days

Question 31

meningitis and steroids

Answer 31

use steroids to dampen immune response
give prior to antibiotics for beneficial effect
risk of GI bleeding
reduces long term morbidity in children with hib meningitis (dexamethasone given)

Question 32

prevention and control of meningitis

Answer 32

vaccines

chemoprophylaxis- reduce secondary cases in close contacts (rifampicin or ciprofloxacin)

Question 33

presentation of brain abscess

Answer 33

focal neurological signs
raised intracranial pressure
headache
maybe fever

Question 34

define abscess

Answer 34

a swollen area within body tissue, containing an accumulation of pus

Question 35

define brain abscess

Answer 35

an abscess caused by inflammation and collection of infected material

Question 36

routes of brain abscess (3)

Answer 36

1 direct spread via venous connections (ear and sinus infections)
2 haematogenous spread (complication of endocarditis)
3 direct implantation (trauma or surgery)

Question 37

pathophysiology of brain abscess

Answer 37

• cerebritis with central inflammation
• ring of cerebritis (infection) surrounding a necrotic centre
• capsule formation (limits spread)
• can rupture, pus into CSF
  drainage just as important as antibiotics

Question 38

bacteria in brain abscess

Answer 38

usually streptococcus milleri
middle ear- usually enterobacteriaceae
staph skin organisms
where it comes from helps decide which bacteria it is

Question 39

treatment of brain abscess

Answer 39

surgical and medical
s= drainage, excision via craniotomy
m= antibiotics

Question 40

choice of antibiotic in abscess depends on (4)

Answer 40

1 site of abscess
2 predisposing factors
3 history of allergies
4 result of gram film and culture

Question 41

antibiotic treatment of abscess by source

Answer 41

dental, sinus, haematogenous source= ceftriaxone and metronidazole, narrow down to benzylpenicillin and metronidazole if strep/anaerobic

otogenic source (ear)= ceftazidime, benzylpenicillin and metronidazole OR meropenem

post-operative/traumatic= vancomycin and meropenem

high dose for 6-8 weeks, 3 IV, 3-5 oral