L09 - Infection of the CNS I - Bacterial and Fungal

Question 1

4 classes of CNS infections and affected area?

Answer 1

1) Meningitis (Ventriculitis) = Subarachnoid space, arachnoid & pia mater
2) Encephalitis (-myelitis) = Brain/spinal cord parenchyma
3) Abscess (intracranial/intraspinal) = Intracerebral/spinal, epidural/subdural
4) Suppurative intracranial thrombophlebitis = Major venous sinus (cavernous, lateral, sagittal)

Question 2

List some groups of general clinical presentation of CNS infection.

Answer 2

Meningeal irritation

Encephalopathic signs

Increased intracranial pressure

Primary/ metastatic foci of infection

Systemic signs

Question 3

List symptoms of meningeal irritation.

Answer 3

1) Headache (trigeminal V1, C2)

2) Neck stiffness (C2, 3, 4):
- Kernig’s sign,
- Brudzinski’s sign

3) Photophobia (irritation of basal meninges at diaphragma sellae)

Question 4

Difference between Kernig and Brudzinski’s sign.

Answer 4

1) Kernig’s sign: stiff hamstring = cannot straighten leg when hip is flexed to 90o (resistance, involuntary spasms)
2) Brudzinski’s sign: flex neck causes hips and knee flex

Question 5

List some encephalopathic signs. (damage to brain parenchyma)

Answer 5

1) Alteration of conscious state (especially encephalitis)

2) Focal neurological signs (especially brain abscess):
- Loss of function (i.e. paralysis, sensory loss)
- Irritative (i.e. focal tonic, clonic epilepsy and generalized seizures)

Question 6

Outcome of CNS infection involving medulla and pituitary gland?

Answer 6

Autonomic/ endocrine dysfunction:

 Labile blood pressure / heart rate / rhythm
 Hypothalamic dysfunction (relative renal insufficiency)
 Diabetes insipidus

Question 7

List symptoms of raised intracranial pressure due to CNS infection?

Answer 7

 Headache

 Compress on medulla = vomiting

 Cushing’s reflex (increased BP)

 Unilateral pupil dilatation (due to uncal herniation)

Question 8

Mechanism of Cushing’s reflex?

Answer 8

decrease in perfusion pressure to brain

> > Increase sympathetic tone, vasocontriction

> > Increase blood pressure to increase blood flow to brain

Question 9

List some primary/ metastatic foci of infection due to CNS infection?

Answer 9

Pneumonia

Endocarditis

Sinusitis

Dental or facial infections

Skin rashes

Petechiae (circular, non-raised patches of haemorrhage)

Purpura (purple blood spots/ skin haemorrhage)

Question 10

List some systemic signs due to CNS infection?

Answer 10

Fever

Leukocytosis

Question 11

Why is CNS infection life-threatening? List sequelaes.

Answer 11

1) Permanent neurological dysfunction: neurons generally do not regenerate
2) Increased ICP due to edema&raquo_space; brain herniation + brainstem compression on foramen magnum
3) Damaged meninges: hydrocephalus&raquo_space; brain herniation + brainstem compression

Question 12

Symptoms and signs of permanent neurological dysfunction due to CNS infections?

Answer 12

 Sensory neural deafness
 Mental retardation
 Epilepsy (especially encephalitis, brain abscess)
 Paralysis

Question 13

Mechanism/ principle causes of increased ICP?

Answer 13

1. Production/absorption/obstruction of CSF.
2. Oedema/ Pus collection in brain parenchyma,
3. Obstruction of the flow of CSF.

Question 14

Pathological causes of increased ICP?

Answer 14

Abscess formation 
Haematoma 
Cerebral edema 
Tumour 
Hydrocephalus

Question 15

Difference between subfalcine and uncal herniation?

Answer 15

• subfalcine = Large supratentorial mass in one hemisphere causes subfalcine herniation
  » cingulate gyrus compressed and herniate through tentorial incisura
• Uncal = medial temporal lobe herniate through tentorial incisura to compress midbrain (i.e. oculomotor nerve compression = unilateral pupil dilation)

Question 16

Time elapsed before presentation of symptoms in acute and subacute/chronic meningitis?

Answer 16

Acute = 1 to 5 days before presentation

Subacute/ chronic = 1 to 4 weeks +

Question 17

Acute pyogenic meningitis symptoms?

Answer 17

 High fever (rarely hypothermia)

 Severe, generalized headache

 Neck stiffness / nuchal rigidity

 Lethargy

 Normal cerebral function till late stage

Question 18

List bacteria that typically cause neonatal meningitis- 0 to 8 weeks (birth canal).

Answer 18

 Escherichia coli (K1)

 Streptococcus agalactiae (group B type III)

 Listeria monocytogenes (unboiled dairy, e.g. ice-cream)

 Other Enterobacteriaceae: Citrobacter, Salmonell

Question 19

List the bacteria that typically cause pyogenic meningitis in 3 months – 18 years

Answer 19

 Streptococcus pneumoniae (routine immunization decrease incidence)

 Neisseria meningitidis (petechiae, purpura)

 Haemophilus influenzae serotype b (routine immunization decrease incidence)

Question 20

List the bacteria that typically cause pyogenic meningitis in 18 years – 50 years

Answer 20

 Streptococcus pneumoniae (>90 serotypes)

 Neisseria meningitidis (15 serotypes)

 Streptococcus suis

Question 21

List the bacteria that typically cause pyogenic meningitis in >50 years

Answer 21

 Streptococcus pneumoniae

 Neisseria meningitidis

 Streptococcus suis

 Aerobic gram-negative bacilli

Question 22

List the bacteria that typically cause pyogenic meningitis in Immunocompromised hosts

Answer 22

 Streptococcus pneumoniae

 Neisseria meningitidis

 Aerobic gram-negative bacilli

 Listeria monocytogenes

 Pseudomonas aeruginosa

Question 23

List the bacteria that typically cause pyogenic meningitis associated with exposure to pigs?

Answer 23

Streptococus suis

Through wound > bloodstream > meninges

Question 24

List the bacteria that typically cause pyogenic meningitis, deafness and low-grade fever?

Answer 24

Streptococcus suis

Question 25

List the pathogen that typically cause pyogenic meningitis after contaminated freshwater exposure?

Answer 25

Amoeba: | - Nagleria fowleri

Question 26

List the pathogen that typically cause pyogenic meningitis after Ingestion of raw mollusk?

Answer 26

Angiostrongylus cantonensis >> Eosinophilic meningitis

Question 27

List the bacteria that typically cause pyogenic meningitis after head trauma/ neurosurgery?

Answer 27

```  Staphylococcus aureus  Staphylococcus epidermidis  Aerobic gram-negative bacilli  Aspergillus spp  Other mold ```

Question 28

List the bacteria that typically cause pyogenic meningitis after Post-shunting / intraventricular drains ?

Answer 28

 Staphylococcus aureus  Staphylococcus epidermidis  Aerobic gram-negative bacilli  Proprionibacterium acne

Question 29

List the bacteria that typically cause pyogenic meningitis after Radiotherapy for nasopharyngeal CA?

Answer 29

 Mixed upper airway flora |  Aerobic gram-negative bacilli

Question 30

List the bacteria that typically cause disseminated strongyloidiasis?

Answer 30

Mixed gut flora Enterobacteriaceae meningitis is typically associated with Strongyloidiases (nematode)

Question 31

Which pathogen is the most deadly in causing meningitis?

Answer 31

Enterobacteriaceae 50% mortality Strep. pneu. 26% Group B Strep. 20%

Question 32

4 Main stages and locations in pathogenesis of meningitis?

Answer 32

asymptomatic colonization >> Bacteraemia >> Meninges invasion >> Multiplication, inflammatory damage in subarachnoid space

Question 33

Describe how meningitic pathogens can enter blood stream?

Answer 33

Asymptomatically colonizes nasopharyngeal mucosa: 1) Fimbriae bind to CD46 receptor to cause phagosome transport across epithelium 2) Breakdown intercellular tight junctions at submucosa 3) Evade mucosal IgA >> enter blood

Question 34

Describe how meningitic pathogens can invade meninges after entering blood?

Answer 34

1) Bacterial capsule inhibits Neutrophil phagocytosis, Complement, Mannose binding lectin 2) Bind to laminin receptor on brain microvascular endothelium, breakdown tight junctions 3) Cross BBB by endocytosis

Question 35

Describe how meningitic pathogen causes inflammatory damage.

Answer 35

Multiplication in subarachnoid space (low level of complement, Ab, WBC) >> Release endotoxin/ cell wall components >> activate Toll-like receptors (TLR) on endothelial cells, macrophages >> NFκB cascade pathway releases many pro-inflammatory cytokines (e.g. IL-1, IL-6, TNF) >> inflammation of subarachnoid space

Question 36

Consequences of inflammatory reaction caused by meningitic pathogens?

Answer 36

1) Increased permeability of vascular endothelium, blood brain barrier = inflammatory exudation, vasogenic cerebral edema, cerebral ischaemia 2) Septic thrombosis of vessels = cerebral infraction, permanent neurological deficit

Question 37

Serpentine, itchy skin lesion is typically associated with what type of CNS infection?

Answer 37

Enterobacteriaceae meningitis + Strongyloidiasis

Question 38

Clinical diagnosis of acute pyrogenic meningitis requires what tests?

Answer 38

1) CT scan to Exclude space-occupying lesion (e.g. brain abscess) 2) Lumbar puncture** and CSF analysis 3) 2 concomitant positive blood cultures

Question 39

Typical CSF findings of acute bacterial meningitis? (think protein, gluose, WBC count, culture, smear)

Answer 39

```  High protein  Low glucose  High and predominant polymorph/ neutrophil count  Positive Gram smear (65-95%)  Positive culture (70-85%) ```

Question 40

What test is given for acute pyrogenic meningitis for patients with previous antibiotic therapy ?

Answer 40

If negative culture due to preceding antimicrobial treatment, proceed: Positive bacterial antigen by latex agglutination test/ PCR

Question 41

CSF with prominent eosinophilia is typical of what type of meningitis?

Answer 41

highly likely Angiostrongylus cantonensis (nematode)

Question 42

Which patients with acute meningitis may have atypical differential WBC counts?

Answer 42

 Neutropenia  Steroid treatment  AIDS  Very early stage of meningitis

Question 43

Empirical treatment of acute bacterial meningitis?

Answer 43

1) High dose IV antibiotics that cross BBB - Penicillin G (Vancomycin) - Ceftriaxone 2) May add adjunctive dexamethasone to decrease inflammatory complications 3) Anticonvulsants if indicated

Question 44

Treatment for contacts of patients with meningitis?

Answer 44

Chemoprophylaxis with rifampicin, protect against:  Neisseria meningitidis  Haemophilus influenzae serotype b

Question 45

Active immunzation against acute bacterial meningitis is indicated for what people?

Answer 45

Areas of high attack rate (i.e. institutional outbreak) High risk groups (i.e. asplenic, complement-deficient)

Question 46

List some viruses that commonly cause acute encephalitis?

Answer 46

``` Enteroviruses JEV Mumps Herpes simplex Varicella zoster HIV CMV EBV ```

Question 47

Explain why subacute/ chronic meningitis can be difficult to dx?

Answer 47

1) Chronic inflammation >> pathogens walled off by fibrosis >> need large amount of CSF by LP to detect 2) Require ventricular/ cisternal tapping surgery due to hydrocephalus

Question 48

Common pathogens causing subacute/ chronic meningitis?

Answer 48

Mycobacterium tuberculosis Crytococcus neoformans Treponema pallidum (syphilis) Less common: Brucella, Candida, Lyme disease, Amoeba (i.e. acanthoamoeba, Angiostrongylus)

Question 49

Pathogenesis of TB meningitis? Is pulmonary TB strongly associated?

Answer 49

Results from rupture of superficial infective granuloma on pia mater into subarachnoid space Young patients often had concomitant progressive pulmonary / systemic disease

Question 50

Typical CSF findings for TB meningitis?

Answer 50

No accurate investigation: - Fluctuating CSF findings - Lymphocytic pleopcytosis - High protein - Low sugar

Question 51

Culture positive and PCR positive rate is high for TB meningitis. True or False?

Answer 51

False  Ziehl-Neelsen smear positive (<15%): acid-fast bacilli  Culture positive (<50%)  PCR positive (50%)

Question 52

CXR for TB meningitis can find foci in majority of cases. True or False?

Answer 52

False CXR TB foci <30%

Question 53

What culture medium is used for TB meningitis?

Answer 53

Sputum culture: | Lowenstein- Jensen medium

Question 54

Treatment for TB meningitis?

Answer 54

1) anti-tuberculous agents that cross the blood brain barrier (isoniazid, rifampicin, pyrazinamide, ethambutol) 2) Steroid may decrease inflammatory complications

Question 55

Typical CSF findings for cryptococcal meningitis?

Answer 55

- Lymphocytic / mononuclear pleocytosis (20-500 cells) - High protein, low glucose - Positive indian ink exam, - Positive fungal culture and CSF/ serum cryptococcal Ag

Question 56

Crytopcoccal meningitis affect which type of patients?

Answer 56

underlying immunodeficiency, e.g. AIDS, steroid therapy, lymphoma

Question 57

Treatment for cyrtococcal meningitis?

Answer 57

IV amphotericin +/- fluorocytosine Oral fluconazole Repeated lumbar puncture to manage increased ICP

Question 58

2 sources and aetiology of Intracranial abscess?

Answer 58

1) Haematogenous: contiguous or distant foci 2) Direct inoculation: trauma/ iatrogenic Usually Polymicrobial (aerobic + anaerobic)

Question 59

Pathogenesis of intracranial abscess?

Answer 59

- Day 1-9: Early to late cerebritis - Day 10-14 or more: Early to late collagen fiber capsule formation (fibrosis) Tissue necrosis >> hypodense area + hyperaemic margins

Question 60

CT/ MRI finding of brain abscess?

Answer 60

 Hypodense centre (leukocytes, necrotic debris)  Outlying uniform ring enhancement surrounded by a variable hypodense region of brain edema

Question 61

Diagnostic tests of brain abscess?

Answer 61

Diagnostic aspiration/ drainage for gram stain and culture CT/MRI

Question 62

Treatment of brain abscess?

Answer 62

Metronidazole, ceftriaxone, penicillin Cross BBB, wide coverage

Question 63

List 4 contiguous focus and affected sites in brain abscess?

Answer 63

1) Otitis media/ mastoiditis >> temporal/ cerebellar 2) Sphenoidal >> frontal/ temporal 3) Frontoethmoidal >> Frontal 4) Dental root >> frontal

Question 64

List 5 bacteria that typically cause brain abscess at contiguous focus or distant focus (except endocarditis)

Answer 64

```  Streptococcus viridans group  Bacteroides  Prevotella  Fusobacterium  Peptostreptococcus ```

Question 65

3 distant foci of brain abscesses?

Answer 65

a) Congenital heart (right to left shunt) b) Pulmonary suppuration c) Endocarditis

Question 66

Endocarditis causing brain abscess is typically due to which bacteria?

Answer 66

 Staphylococcus aureus  Streptococcus spp. same as penetrating trauma

Question 67

Brain abscess in immunocompromised is caused by which pathogens?

Answer 67

```  Toxoplasma gondii  Enterobacteriaceae  Aspergillus  Mucor and moulds (Hyperinfection by Strongyloides stercoralis carrying fecal flora into CSF) ```

Question 68

Brain abscess by Focal infective lesions is caused by what pathogens?

Answer 68

 Actinomycosis  Cysticercosis  Schistosomiasis

Question 69

Suppurative dural venous sinus thrombosis / intracranial thrombophlebitis affects which cranial structures?

Answer 69

``` Infection causes obstuction of sinuses i.e.  Cavernous venous sinus (ophthalmic vein flow obstructed = eyes bulge out)  Lateral sinuses  Sagittal sinuses ```

Question 70

Symptoms of suppurative intracranial thrombophlebitis

Answer 70

Motor deficits Confusion Seizures, convulsions Cranial nerve palsies, orbital pain (cavernous sinus) Headache, cranial nerve palsies, tinnitus...