L37 Bacterial infection of CNS

Question 1

Acute vs Chronic meningitis?

Answer 1

Acute: meningeal symptoms from few hours to few days;

Chronic: over weeks, CSF remains abnormal for >4 weeks

Question 2

What is the dural venous sinus?

Answer 2

It is where the periosteal and meningeal layers separate

Question 3

CSF is produced at the choroid plexus in the ventricles > flow?

Answer 3

1. To the 3rd ventricle > 4th ventricle through cerebral aqueduct
2. Flows into subarachnoid space by the lateral and medial apertures + spinal canal
3. CSF removes waste and provide buoyancy from within the subarachnoid space
4. Excess CSF will be absorbed by arachnoid villi > drained to superior sagittal sinus

Question 4

Clinical presentations of acute bacterial meningitis can be non- specific, e.g. acute onset of fever and headache.

What are the signs of meningeal irritation? (4)

Answer 4

1. Nuchal rigidity: neck stiffness, inability to flex the neck
2. Kernig’s sign: when thigh is flexed and knee at 90 degrees, subsequent extension of knee is painful
3. Brudzinski’s sign: when patient lies supine, lifting the patient’s head off the couch causes lifting of legs involuntarily
4. Jolt accentuation of headache: increase headache when head is turned horizontally 2-3 times

Question 5

List some examples of the below manifestations in acute bacterial meningitis

1. Eye effects
2. Mental alteration
3. Hemorrhage
4. Raised ICP

Answer 5

1. Photophobia, diplopia
2. Confusion, coma
3. Petechiae, ecchymosis
4. • Early: headache, vomiting, papilloedema
   • Late: CN3,6 palsies, hemiparesis

Question 6

What are the signs of raised ICP in neonates? (3)

Answer 6

• Bulging fontanelle
• Enlarged cranium
• Seizures

Question 7

What are the general risk factors for acute bacterial meningitis?

Answer 7

1. Immunocompromised: complement deficiency, splenectomy, HIV
2. NPC - post-radiotherapy may lead to deformities of the bone > prone to invasive strep pneumoniae infection
3. Skull base fracture
4. Otitis media
5. Cranial trauma, CSF shunts (placement of CSF shunt systems to treat hydrocephalus before)

Question 8

What are the most common organisms causing bacterial meningitis in neonates (infants <3m)? (3)

Answer 8

MC:
Group B strep >
E.coli >
Listeria monocytogenes

Question 9

What are the specific risk factors for neonatal bacterial meningitis? (3)

Answer 9

1. Maternal GBS colonisation
2. Prematurity
3. Prolonged rupture of membrane during labor

Question 10

How can neonatal meningitis be prevented?

Answer 10

1. Screening at 35-37 weeks for GBS

2. Intrapartum antibiotic prophylaxis (penicillin/ampicillin)

Question 11

What are the MC organisms for bacterial meningitis in children >3m?

Answer 11

similar to adults (5)

+ Haemophilis influenzae

Question 12

What are the MC organisms for bacterial meningitis in adults? (5)

Answer 12

1. Strep pneumoniae
2. N. meningitidis
3. Strep suis
4. Listeria monocytogenes
5. M. tuberculosis

Question 13

What are the specific risk factor(s) for bacterial meningitis in

a) children >3m
b) adults?

Answer 13

a) pre-existing acute otitis media

b) Debilitated (weak), Elderly, Diabetic

Question 14

What can be done to prevent bacterial meningitis in children >3m? (4)

Answer 14

Vaccination x4

1. PCV 13
   - Pneumococcal conjugate vacine
2. Hib vaccine
3. Meningococcal group C+ Y
4. BCG (in children immunisation programme)

Question 15

What can be done to prevent bacterial meningitis in adults? (3)

Answer 15

1. PCV13 + booster PPSV23 (Pneumococcal polysaccharide vaccine)
2. Meningococcal A/C/W/Y-135 (for travellers to endemic areas)
3. Meningococcal group B (teenagers)

Question 16

Procedure-related meningitis/ Intra-cranial shunts can be causes for meningitis.
What are the usual organisms? (2)

Prevention is by infection control

Answer 16

1. S.aureus/ MRSA

2. GN rods

Question 17

Prophylaxis for pneumococcal meningitis?

Answer 17

PCV13/
PPSV23
vaccine

Question 18

Streptococcus pneumoniae can be commonly found in which organ?

It causes the highest morality of meningitis (20%), can causes cerebral edema, CN palsy etc.

What is the treatment ?

Answer 18

Nasopharynx

1. IV Cefotaxime as empirical treatment until organisms sensitivity is available >

depending on resistance, IV penicillin G > IV cefotaxime > IV vancomycin + rifampicin

2. Dexamethasone -.15mg/kg, IV Q6h x4/7 may reduce mortality and hearing loss

Question 19

Neisseria meningitidis can be normally found at?

What are the commonest presentations in patients infected?

Answer 19

Nasopharynx

• Petechiae, purpura 50%

Question 20

Neisseria meningitides can have a rapid progression , and may even cause Waterhouse-Friderichsen syndrome. What is that?

Treatment?

Answer 20

Waterhouse-Friderichsen syndrome - shock, DIC, bilateral adrenal hemorrhage

> adrenocortical insuffciency

Treatment: Cefotaxime

Question 21

What are the preventive measures for meningococcal meningitis?

Answer 21

1. Group A/C/Y/W-135 vaccine
2. Group B vaccine
3. Rifampicin for close contacts, not necessary for medical personnel

Question 22

Which organism infect infants from 1 month to 3 years old most?

What serotype is the most virulent?

It causes cerebral oedema, hydrocephalus, CN palsy (e.g. deafness)

How to prevent?

Answer 22

Haemophilus influenzae; Type B

Hib vaccine, rifampicin for close contacts

*Cefotaxime is given for treatment, ampicillin if sensitive

Question 23

Which organism causing meningitis is found in pigs thus butchers, and associated with high incidence of deafness?

Treatment?

Answer 23

Streptococcus suis
(Group D strep)

High dose benzylpenicillin 14-21 days

Question 24

List the 4 routes of entry of bacterial meningitis.

Answer 24

1. Hematogenous spread (MC)
   e. g. nasopharyngeal epithelium
2. Direct contiguous spread
   - e.g AOM, sinusitis
3. Direct inoculation
   - e.g. open skull fracture
4. Vertical transmission

Question 25

Causative organisms invade the meninges via various BBB receptors, and replicate in the ________________due to local immunodeficiency. Then there is immune system activation and cytokine production. What are the effects? (3)

Answer 25

subarachnoid space 1. Increase BBB permeability > vasogenic edema > increase CSF outflow resistance > hydrocephalus > interstitial edema 2. Increase ROS by bacterial toxin > cytotoxic edema 3. Altered cerebral blood flow (CBF), reduced perfusion pressure, ischemia ALL = Increase intracranial pressure - cerebral ischemia, brain herniation

Question 26

What initial investigations to be done in suspected meningitis? (5)

Answer 26

1. CT to rule out any mass lesion before LP - if mass is present in brain/ elevated ICP, LP may lead to brain herniation 2. CSF for microbiological investigations; by lumbar puncture 3. Plasma glucose 4. Blood culture 5. Serology for viral studies: throat swab, stool culture

Question 27

If there is increased opening pressure (normal 10-20cm H2O) in CSF puncture, it suggested?

Answer 27

increased ICP from cerebral edema

Question 28

What microbiological tests to be done in CSF sample?

Answer 28

1. Gram stain (H.influenzae) 2. ZN stain and rapid DNA detection for TB 3. India ink for Cryptococcus 4. Bacterial culture 5. Latex agglutination for bacterial + Cryptococcus antigens

Question 29

What is the typical CSF interpretation in bacterial meningitis? (5)

Answer 29

1. Cloudy appearance 2. Increase in WBC per ul 3. Polymorphs as predominant cells (>80%) compared to lymphocytes 4. Reduced glucose, <2.2 (due to increase consumption + reduced glucose transport to brain) 5. Increased Protein (g/L) >0.5, plasma protein leakage due to inflammation

Question 30

What is the typical CSF interpretation in TB meningitis? (5)

Answer 30

1. Opalescent appearance 2. Increase in WBC per ul 3. Predominant cells: L**>P 4. Very high protein 5. Low glucose <2.2

Question 31

What is the typical CSF interpretation in viral meningitis? (5)

Answer 31

1. Clear appearance 2. Increase in WBC per ul 3. Predominant cells: P early, L late 4. >0.5 protein (elevated) 5. Normal glucose

Question 32

CSF interpretation: 1. Clear appearance 2. Increase in WBC per ul 3. Predominant cells: L>P 4. >0.5 protein (elevated) 5. <2.2 glucose Ddx?

Answer 32

Cryptococcal meningitis ~TB but TB has opalescent appearance

Question 33

CSF interpretation in subarachnoid hemorrhage?

Answer 33

1. Xanthochromic appearance (yellowish) 2. Greatly elevated WBCs 3. Crenated RBC as predominant cells 4. Very high protein 5. Normal glucose

Question 34

What is the normal WBC count per ul in CSF? What is the predominant cell L/P in CSF?

Answer 34

<4 - Lymphocytes Others: Protein: 0.15-0.45 g/L Glucose: 2.8-4.2 mmol/L

Question 35

What is defined as significant reduced CSF glucose when compared to plasma glucose?

Answer 35

CSF glucose <50% plasma glucose

Question 36

Name 5 causative agents for chronic meningitis?

Answer 36

1. Mycobacterium tuberculosis 2. Cryptococcus neoformans 3. Treponema pallidum (syphilis) 4. Amoeba (Naegleria fowleri) 5. HIV

Question 37

Both TB and Cryptococcus neoformans can cause granulomatous meningitis. For TB meningitis, L>P in CSF, and patient has insidious onset of headache, confusion, fever. How to diagnose TB meningitis? (2)

Answer 37

1. BAL for PCR (sputum is not sensitive enough) | 2. CSF for antigen detection

Question 38

What are the risk factors for Cryptococcal meningitis?

Answer 38

1. Immunocompromised: AIDS, malignancy, steroid therapy, DM 2. SLE 3. Alcoholism

Question 39

Pathogenesis of Cryptococcal meningitis: Inhalation of yeast > harmless airway colonisation > ______? Pathology: SOL with granuloma and mucinous exudate What to expect in CSF investigations?

Answer 39

Neurotropic; 1. Increased opening pressure 2. India ink +ve 3. Culture: Sabouraud agar 4. Serology: Latex agglutination test for antigen - for monitoring treatment response

Question 40

Cryptoccocal meningitis: what test to do other than CSF investigation? (2)

Answer 40

1. Blood culture | 2. Latex agglutination test - for monitoring treatment response

Question 41

What is the treatment for Cryptococcal meningitis? (2)

Answer 41

1. IV amphotericin B + flucystosine | 2. Life-long fluconazole prophylaxis in AIDS patients

Question 42

What are the risk factors for brain abscess formation? (7)

Answer 42

1. Hematogenous - MC infective endocarditis 2. Contiguous spread: - Bronchiectasis, sinusitis, AOM, dental caries 3. Direct inoculation - Open fracture, post-neurosurgical patient

Question 43

What can be observed in CT brain if brain abscess? (2)

Answer 43

Ring-enhancing lesion (1) with surrounding vasogenic edema (1)

Question 44

Treatment for brain abscess? (3)

Answer 44

1. Drainage | 2. Antibiotics: 3rd generation cephalosporin (cefotaxime/ ceftriaxone) + metronidazole