L09 - Infection of the CNS I - Bacterial and Fungal Flashcards

1
Q

4 classes of CNS infections and affected area?

A

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)

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2
Q

List some groups of general clinical presentation of CNS infection.

A

Meningeal irritation

Encephalopathic signs

Increased intracranial pressure

Primary/ metastatic foci of infection

Systemic signs

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3
Q

List symptoms of meningeal irritation.

A

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)

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4
Q

Difference between Kernig and Brudzinski’s sign.

A

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

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5
Q

List some encephalopathic signs. (damage to brain parenchyma)

A

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)

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6
Q

Outcome of CNS infection involving medulla and pituitary gland?

A

Autonomic/ endocrine dysfunction:

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

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7
Q

List symptoms of raised intracranial pressure due to CNS infection?

A

 Headache

 Compress on medulla = vomiting

 Cushing’s reflex (increased BP)

 Unilateral pupil dilatation (due to uncal herniation)

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8
Q

Mechanism of Cushing’s reflex?

A

decrease in perfusion pressure to brain

> > Increase sympathetic tone, vasocontriction

> > Increase blood pressure to increase blood flow to brain

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9
Q

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

A

Pneumonia

Endocarditis

Sinusitis

Dental or facial infections

Skin rashes

Petechiae (circular, non-raised patches of haemorrhage)

Purpura (purple blood spots/ skin haemorrhage)

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10
Q

List some systemic signs due to CNS infection?

A

Fever

Leukocytosis

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11
Q

Why is CNS infection life-threatening? List sequelaes.

A

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

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12
Q

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

A

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

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13
Q

Mechanism/ principle causes of increased ICP?

A
  1. Production/absorption/obstruction of CSF.
  2. Oedema/ Pus collection in brain parenchyma,
  3. Obstruction of the flow of CSF.
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14
Q

Pathological causes of increased ICP?

A
Abscess formation 
Haematoma 
Cerebral edema 
Tumour 
Hydrocephalus
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15
Q

Difference between subfalcine and uncal herniation?

A
  • 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)
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16
Q

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

A

Acute = 1 to 5 days before presentation

Subacute/ chronic = 1 to 4 weeks +

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17
Q

Acute pyogenic meningitis symptoms?

A

 High fever (rarely hypothermia)

 Severe, generalized headache

 Neck stiffness / nuchal rigidity

 Lethargy

 Normal cerebral function till late stage

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18
Q

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

A

 Escherichia coli (K1)

 Streptococcus agalactiae (group B type III)

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

 Other Enterobacteriaceae: Citrobacter, Salmonell

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19
Q

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

A

 Streptococcus pneumoniae (routine immunization decrease incidence)

 Neisseria meningitidis (petechiae, purpura)

 Haemophilus influenzae serotype b (routine immunization decrease incidence)

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20
Q

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

A

 Streptococcus pneumoniae (>90 serotypes)

 Neisseria meningitidis (15 serotypes)

 Streptococcus suis

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21
Q

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

A

 Streptococcus pneumoniae

 Neisseria meningitidis

 Streptococcus suis

 Aerobic gram-negative bacilli

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22
Q

List the bacteria that typically cause pyogenic meningitis in Immunocompromised hosts

A

 Streptococcus pneumoniae

 Neisseria meningitidis

 Aerobic gram-negative bacilli

 Listeria monocytogenes

 Pseudomonas aeruginosa

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23
Q

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

A

Streptococus suis

Through wound > bloodstream > meninges

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24
Q

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

A

Streptococcus suis

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25
Q

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

A

Amoeba:

- Nagleria fowleri

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26
Q

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

A

Angiostrongylus cantonensis

> > Eosinophilic meningitis

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27
Q

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

A
 Staphylococcus aureus 
 Staphylococcus epidermidis 
 Aerobic gram-negative bacilli 
 Aspergillus spp 
 Other mold
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28
Q

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

A

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

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29
Q

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

A

 Mixed upper airway flora

 Aerobic gram-negative bacilli

30
Q

List the bacteria that typically cause disseminated strongyloidiasis?

A

Mixed gut flora

Enterobacteriaceae meningitis is typically associated with Strongyloidiases (nematode)

31
Q

Which pathogen is the most deadly in causing meningitis?

A

Enterobacteriaceae 50% mortality

Strep. pneu. 26%

Group B Strep. 20%

32
Q

4 Main stages and locations in pathogenesis of meningitis?

A

asymptomatic colonization

> > Bacteraemia

> > Meninges invasion

> > Multiplication, inflammatory damage in subarachnoid space

33
Q

Describe how meningitic pathogens can enter blood stream?

A

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

34
Q

Describe how meningitic pathogens can invade meninges after entering blood?

A

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

35
Q

Describe how meningitic pathogen causes inflammatory damage.

A

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

36
Q

Consequences of inflammatory reaction caused by meningitic pathogens?

A

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

37
Q

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

A

Enterobacteriaceae meningitis + Strongyloidiasis

38
Q

Clinical diagnosis of acute pyrogenic meningitis requires what tests?

A

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

39
Q

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

A
 High protein 
 Low glucose 
 High and predominant polymorph/ neutrophil count 
 Positive Gram smear (65-95%) 
 Positive culture (70-85%)
40
Q

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

A

If negative culture due to preceding antimicrobial treatment, proceed:

Positive bacterial antigen by latex agglutination test/ PCR

41
Q

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

A

highly likely Angiostrongylus cantonensis (nematode)

42
Q

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

A

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

43
Q

Empirical treatment of acute bacterial meningitis?

A

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

44
Q

Treatment for contacts of patients with meningitis?

A

Chemoprophylaxis with rifampicin, protect against:

 Neisseria meningitidis
 Haemophilus influenzae serotype b

45
Q

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

A

Areas of high attack rate (i.e. institutional outbreak)

High risk groups (i.e. asplenic, complement-deficient)

46
Q

List some viruses that commonly cause acute encephalitis?

A
Enteroviruses 
JEV
Mumps 
Herpes simplex 
Varicella zoster 
HIV
CMV
EBV
47
Q

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

A

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

48
Q

Common pathogens causing subacute/ chronic meningitis?

A

Mycobacterium tuberculosis

Crytococcus neoformans

Treponema pallidum (syphilis)

Less common: Brucella, Candida, Lyme disease, Amoeba (i.e. acanthoamoeba, Angiostrongylus)

49
Q

Pathogenesis of TB meningitis? Is pulmonary TB strongly associated?

A

Results from rupture of superficial infective granuloma on pia mater into subarachnoid space

Young patients often had concomitant progressive pulmonary / systemic disease

50
Q

Typical CSF findings for TB meningitis?

A

No accurate investigation:

  • Fluctuating CSF findings
  • Lymphocytic pleopcytosis
  • High protein
  • Low sugar
51
Q

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

A

False

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

52
Q

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

A

False

CXR TB foci <30%

53
Q

What culture medium is used for TB meningitis?

A

Sputum culture:

Lowenstein- Jensen medium

54
Q

Treatment for TB meningitis?

A

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

55
Q

Typical CSF findings for cryptococcal meningitis?

A
  • Lymphocytic / mononuclear pleocytosis (20-500 cells)
  • High protein, low glucose
  • Positive indian ink exam,
  • Positive fungal culture and CSF/ serum cryptococcal Ag
56
Q

Crytopcoccal meningitis affect which type of patients?

A

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

57
Q

Treatment for cyrtococcal meningitis?

A

IV amphotericin +/- fluorocytosine

Oral fluconazole

Repeated lumbar puncture to manage increased ICP

58
Q

2 sources and aetiology of Intracranial abscess?

A

1) Haematogenous: contiguous or distant foci
2) Direct inoculation: trauma/ iatrogenic

Usually Polymicrobial (aerobic + anaerobic)

59
Q

Pathogenesis of intracranial abscess?

A
  • Day 1-9: Early to late cerebritis
  • Day 10-14 or more:

Early to late collagen fiber capsule formation (fibrosis)

Tissue necrosis&raquo_space; hypodense area + hyperaemic margins

60
Q

CT/ MRI finding of brain abscess?

A

 Hypodense centre (leukocytes, necrotic debris)

 Outlying uniform ring enhancement surrounded by a variable hypodense region of brain edema

61
Q

Diagnostic tests of brain abscess?

A

Diagnostic aspiration/ drainage for gram stain and culture

CT/MRI

62
Q

Treatment of brain abscess?

A

Metronidazole, ceftriaxone, penicillin

Cross BBB, wide coverage

63
Q

List 4 contiguous focus and affected sites in brain abscess?

A

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

64
Q

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

A
 Streptococcus viridans group 
 Bacteroides 
 Prevotella 
 Fusobacterium 
 Peptostreptococcus
65
Q

3 distant foci of brain abscesses?

A

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

66
Q

Endocarditis causing brain abscess is typically due to which bacteria?

A

 Staphylococcus aureus
 Streptococcus spp.

same as penetrating trauma

67
Q

Brain abscess in immunocompromised is caused by which pathogens?

A
 Toxoplasma gondii 
 Enterobacteriaceae 
 Aspergillus 
 Mucor and moulds
(Hyperinfection by Strongyloides stercoralis carrying fecal flora into CSF)
68
Q

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

A

 Actinomycosis  Cysticercosis  Schistosomiasis

69
Q

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

A
Infection causes obstuction of sinuses 
i.e.
 Cavernous venous sinus (ophthalmic vein flow obstructed = eyes bulge out)
 Lateral sinuses 
 Sagittal sinuses
70
Q

Symptoms of suppurative intracranial thrombophlebitis

A

Motor deficits

Confusion

Seizures, convulsions

Cranial nerve palsies, orbital pain (cavernous sinus)

Headache, cranial nerve palsies, tinnitus…