Lecture 2: Infections of the Central Nervous System Flashcards

(48 cards)

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
How is tetanus diagnosed?
Clinical symptoms and a medical history that shows no tetanus immunization
26
What are the signs of tetanus?
Trismus/ lockjaw - neck stiffness Difficulty in swallowing Elevated temperature, sweating, elevated blood pressure episodic rapid heart rate Spasms
27
What gram is tetanus toxin?
Gram positive
28
What is the mode of action of tetanus toxin?
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
What is tetanus toxin coded by?
Coded by a plasmid
30
How is botulism diagnosed?
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
What is the botulism mode of action?
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
What is Gullian-Barre syndrome?
Response to foreign antigens that are mis-targeted to host nerve tissues instead Autoimmune disease triggered by previous infection
33
How is Guillain-Barre syndrome diagnosed?
Depends on typical clinical findings Done by discounting Rapidly evolving flaccid paralysis Absence of fever
34
What are the targets in Guillain-Barre syndrome?
Gangliosides
35
What percentage of patients with Guillain-Barre syndrome have a history of acute infection? What are the further division of infection?
75% (within the past 1-4 weeks) 20-30% - Campylobacter jejuni 20-30% cytomegalovirus or Epstein-Barr virus
36
How is meningitis treated with Streptococcus pneumoniae infection?
Penicillin-sensitive: Penicillin G Penicillin-intermediate: Ceftriaxone or cefotaxime Penicillin-resistant: Ceftriaxone or cefotaxime and vancomycin
37
How is meningitis treated with Haemophilus influenzae infection?
Ceftriaxone or cefotaxime
38
How is meningitis treated with Neisseria meningitidis infection?
Penicillin-sensitive: Penicillin G or ampicillin Penicillin-resistant: ceftriaxone or cefotaxime Prophylaxis for close contacts
39
How is meningitis treated with gram negative bacilli infection?
Ceftriaxone or cefotaxime
40
How is meningitis treated with Listeria monocytogenes infection?
3-week course of IV ampicillin +gentamicin
41
How is meningitis treated with Streptococcus agalactiae infection?
Penicillin G or ampicillin
42
How is meningitis treated with Staphylococcus aureus infection?
Methicillin-sensitive = nafcillin Methicillin-resistant = vancomycin
43
How is viral meningitis treated?
Patients with mild cases - only cause flu-like symptoms Fluids, bed rest Possibly anticonvulsants Corticosteroids to reduce brain inflammation
44
How is a brain abscess treated?
Lowering increased intracranial pressure (osmotic diuretics & steroids, hyperventilating) Intravenous antibiotics Surgical aspiration or removal of brain abscess
45
How is mild tetanus infection treated?
5000 units tetanus immunoglobulin IV or IM Metronidazole 500mg IV for 10 days Diazepam (5-20mg per day) Tetanus vaccination
46
How is severe tetanus infection treated?
Admission into intensive care Tracheostomy - mechanical ventilation Magnesium
47
How is Botulism infection treated?
Inducing passive immunity (anti toxin immunoglobulin) Remove contaminated food Wounds treated Antibiotics (aminoglycosides or clindamycin)
48
How is Guillain-Barre syndrome treated?
Supportive care with monitoring of all vital functions 80% complete recovery 5-10% recover with severe motor disability 2-3% fatalities