Lecture 2: Infections of the Central Nervous System Flashcards

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1
Q

Where does the cerebral spinal fluid act as a shock absorber?

A

Between the pia mater and arachnoid
(circulating around the brain and spinal cord)

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2
Q

What are the 3 connective tissues surrounding the brain?

A

Pia mater
Arachnoid
Dura mater

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3
Q

What is meningitis classified by?

A

Inflammation of the connective tissue layers surrounding the brain

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4
Q

What are capillaries throughout the body made of?

A

Endothelial cells

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5
Q

In the brain where are the endothelial cells packed more tightly together to produce tight junctions?

A

Sub arachnoid and perivascular space

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6
Q

What is known as the blood-brain barrier?

A

Sub arachnoid and perivascular space

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7
Q

What substances can pass the blood-brain barrier?

A

Lipid solubility - oxygen, carbon dioxide, ethanol, steroid hormones

Specific transport systems - sugars, amino acid

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8
Q

Why does the brain loose the arm of the immune response?

A

Antibodies are too large to cross the blood-brain barrier

Many antibodies are unable to pass the barrier due to their size

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9
Q

What are the common human flora associated with meningitis?

A

Streptococcus pneumoniae

Haemophilus influenzae

Neisseria meningitidis

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10
Q

What are all the bacteria associated with meningitis?

A

Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Escherichia coli
Streptococcus agalactiae
Listeria monocytogenes
Staphylococcus aureus

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11
Q

What are the pathogenic and host factors associated with meningitis?

A

Bacterial pathogenic factors:
Capsule - polysaccharide capsule
Adhesins - stick to endothelial surface

Host factors:
Cytokines
Selectins on endothelial surface
Integrins on neutrophils

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12
Q

How does bacterial invasion of meningitis occur to the cerebral spinal fluid (CSF)?

A

Bacteria adhere to capillary wall and enter CSF in low numbers

Local macrophages are stimulated by bacterial breakdown products and TNF and IL-I are produced
(fragments released = cytokine production)

TNF and IL-I initiate expression of selectin molecules on the endothelial cell surface.
Endothelial cell IL-8 causes neutrophils to express integrins

Neutrophils adhere to endothelium and enter CSF - breakdown of blood-brain barrier allows entry of albumin

CSF now contains bacteria, neutrophils and protein in significant quantities

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13
Q

What can pneumococci do to allow entry through the pharynx?

A

Pneumococci can switch capsule production on/ off

Makes it difficult for the pathogen to adhere

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14
Q

What does IL-I do in bacterial invasion of meningitis in the CSF?

A

Initiates expression on endothelial cells

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15
Q

What does IL-8 do in bacterial invasion of meningitis in the CSF?

A

They drive the expression of integrins on neutrophils

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16
Q

What does integrin do in bacterial invasion of meningitis in the CSF?

A

Causes cell-to-cell adhesion

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17
Q

How is a brain abscess diagnosed?

A

Fever
Headache
Vomiting
Photophobia
Rash
Abnormal behaviour

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18
Q

How is a brain abscess diagnosed?
(4 ways)

A

Lumbar puncture (needle into spine to extract for dialysis)

Computed tomography (generates 3D image from large series of 2D x-ray images)

Microbiologically - analysis of pus of CSF by microscope

Biochemistry - 3 samples of CSF

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19
Q

How is a brain abscess caused?

A

Infection of the brain tissue

Inflammatory response over several days forming abscess

Zone of swelling compressing the brain

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20
Q

How is a brain abscess diagnosed through biochemistry?

A

3 samples of CSF collected:
Protein analysis
Glucose determination
Microbiology

21
Q

What are the distinguishing features of tuberculous?

A

Increased WCC

90% monocytes/ lymphocytes

Very high protein

Decreased glucose

22
Q

What are the distinguishing features of viral meningitis?

A

Increased WCC (lower than bacterial)

95% lymphocytes

Protein: normal or increased

Glucose: normal

23
Q

What are the distinguishing features of bacterial meningitis?

A

WCC - very very high

95% neutrophils

Protein increased

Glucose - massive decrease

24
Q

What the basic parameters of WCC, protein & glucose in the blood?

A

WCC: <5/uL

Protein: <450 mg/L

Glucose: >40% blood

25
Q

How is tetanus diagnosed?

A

Clinical symptoms and a medical history that shows no tetanus immunization

26
Q

What are the signs of tetanus?

A

Trismus/ lockjaw - neck stiffness

Difficulty in swallowing

Elevated temperature, sweating, elevated blood pressure episodic rapid heart rate

Spasms

27
Q

What gram is tetanus toxin?

A

Gram positive

28
Q

What is the mode of action of tetanus toxin?

A

Acts internally as an endopeptidase cleaving the synaptic vesicle protein synaptovrevin.
Local failure of neuromuscular transmission can occur.

Affects spinal inhibitory neurons irreversibly where GABA and glycine are neurotransmitters

29
Q

What is tetanus toxin coded by?

A

Coded by a plasmid

30
Q

How is botulism diagnosed?

A

Demonstrates the botulinum toxin in patients serum or stool

Injecting serum or stool into mice and looking for signs of botulism that can be blocked by specific antisera

31
Q

What is the botulism mode of action?

A

Toxin in ingested food is absorbed by the duodenum and enters the blood

Affects the neurotransmitter release of Ach
(end up flaccid so muscles cannot work)

32
Q

What is Gullian-Barre syndrome?

A

Response to foreign antigens that are mis-targeted to host nerve tissues instead

Autoimmune disease triggered by previous infection

33
Q

How is Guillain-Barre syndrome diagnosed?

A

Depends on typical clinical findings

Done by discounting

Rapidly evolving flaccid paralysis
Absence of fever

34
Q

What are the targets in Guillain-Barre syndrome?

A

Gangliosides

35
Q

What percentage of patients with Guillain-Barre syndrome have a history of acute infection? What are the further division of infection?

A

75% (within the past 1-4 weeks)

20-30% - Campylobacter jejuni
20-30% cytomegalovirus or Epstein-Barr virus

36
Q

How is meningitis treated with Streptococcus pneumoniae infection?

A

Penicillin-sensitive: Penicillin G

Penicillin-intermediate: Ceftriaxone or cefotaxime

Penicillin-resistant: Ceftriaxone or cefotaxime and vancomycin

37
Q

How is meningitis treated with Haemophilus influenzae infection?

A

Ceftriaxone or cefotaxime

38
Q

How is meningitis treated with Neisseria meningitidis infection?

A

Penicillin-sensitive: Penicillin G or ampicillin

Penicillin-resistant: ceftriaxone or cefotaxime

Prophylaxis for close contacts

39
Q

How is meningitis treated with gram negative bacilli infection?

A

Ceftriaxone or cefotaxime

40
Q

How is meningitis treated with Listeria monocytogenes infection?

A

3-week course of IV ampicillin +gentamicin

41
Q

How is meningitis treated with Streptococcus agalactiae infection?

A

Penicillin G or ampicillin

42
Q

How is meningitis treated with Staphylococcus aureus infection?

A

Methicillin-sensitive = nafcillin

Methicillin-resistant = vancomycin

43
Q

How is viral meningitis treated?

A

Patients with mild cases - only cause flu-like symptoms

Fluids, bed rest
Possibly anticonvulsants
Corticosteroids to reduce brain inflammation

44
Q

How is a brain abscess treated?

A

Lowering increased intracranial pressure (osmotic diuretics & steroids, hyperventilating)

Intravenous antibiotics

Surgical aspiration or removal of brain abscess

45
Q

How is mild tetanus infection treated?

A

5000 units tetanus immunoglobulin IV or IM

Metronidazole 500mg IV for 10 days

Diazepam (5-20mg per day)

Tetanus vaccination

46
Q

How is severe tetanus infection treated?

A

Admission into intensive care

Tracheostomy - mechanical ventilation
Magnesium

47
Q

How is Botulism infection treated?

A

Inducing passive immunity (anti toxin immunoglobulin)

Remove contaminated food

Wounds treated

Antibiotics (aminoglycosides or clindamycin)

48
Q

How is Guillain-Barre syndrome treated?

A

Supportive care with monitoring of all vital functions

80% complete recovery
5-10% recover with severe motor disability
2-3% fatalities