WK 10- CNS infections

Question 1

What are the protective mechanisms in place to protect the brain

Answer 1

Blood brain barrier and the blood CSF barrier

Question 2

What comprises the BBB

Answer 2

BBB is made from a basement membrane, surrounded by a solid endothelium and astrocytes with no gap junction
-prevents movement of solutes from the blood stream into the brain unless accompanied by a transporter

Question 3

What is the blood CSF comprised of

Answer 3

Blood vessel is surrounded by a thin basement membrane, fenestrated endothelium and choroid plexus epithelium
-fenestrated epithelium allows movement of some particlesq

Question 4

What are the 3 mechanisms that pathogens use to pass through the protective barrier of the brain

Answer 4

1. Grow across
2. Passive transcytosis
3. Carried in by immune cells ‘trojan horse’

Question 5

How do microbes grow across into the CNS

Answer 5

microbes can grow in the endothelial cells and then into the astrocytes or choroid plexus (ie polio and meningococus)

Question 6

What are the ways which microbes can undergo passive transcytosis

Answer 6

• transported across the intracellular vacuoles
• cross between endothelial cells by disrupting tight junctions
• secrete cytotoxic molecules that destroy the cell
• sepsis induced activation of the blood CNS barrier–> systemic release of bacterial components in blood causes release of chemokines and cytokines-> causes direct and indirect activation of the endothelial cells which makes them more permeable

Question 7

How are microbes carried in through inflammatory cells

Answer 7

infected inflamm cells can migrate into the brain and meninges, lyse and release the organism, or the organisms may pass from cell to cell

Question 8

How do viruses enter the CNS

Answer 8

• due to small size they can more easily transcytose→ also use leukocyte crossing
• herpes virus use anterograde transport into the brain from the peripheral cell body via olfactory nerve (travel through axonal terminals)

Question 9

With bacterial meningitis;

• what cells are present
• what happens to the levels of proteins and glucose

Answer 9

• Neutrophils
• Increased Proteins- as bacteria are made of protein
• Decreased glucose-> due to bacteria using glucose as an energy source
• positive gram stain and culture

Question 10

With viral meningitis;

• what cells are present
• what happens to the levels of proteins and glucose

Answer 10

• Monocytes

- Protein and glucose levels stay the same

Question 11

How is the CSF analysed in meningitis

Answer 11

•Sample 1: serology; PCR
–Viruses
•Sample 2: biochemistry
–Glucose
–Protein
•Sample 3: bacteriology
–Gram stain
–Culture

Question 12

What is meningitis

Answer 12

Infection of the meninges and CSF

Question 13

What is encephalitis

Answer 13

Infection of the brain tissue

Question 14

What is coning

Answer 14

Squeezing of the brain and brainstem through the foramen magnum as a result of swelling -> occurs when there is an increase in intracranial pressure

Question 15

What are the 3 most common causes of bacterial meningitis

Answer 15

→ haemophilus influenza (formally type b- other serotypes do cause disease but to a lesser extent), Neisseria meningitis, strep pneumonia (most significant)

Question 16

What gram stain is haemophilus influenzae

Answer 16

Gram negative cocco-bacilli

Question 17

Why have rates of bacterial meningitis caused by Hib recently decreased

Answer 17

Immunisation-> most children are protected via maternal Ab up until 3 months, then require immunisations

Question 18

What gram stain is neisseria

Answer 18

gram neg diploccocus

Question 19

What age group is most often affected by neisseria meningitis

Answer 19

Adolescents-> due to majority of adolescents harbouring the bacteria and being in close spaces-> like university

Question 20

How can neisseria meningitis cause bacterial meningitis

Answer 20

-transmitted by resp droplets→ enters pharyngeal regions→ move to non-cilliated resp cells and will sit on the surface and can move in and out of the cell→ can then get into membranes and into the blood stream and pass into CSF-> in the blood stream LPS triggers increased vascular permeability and DIC and a cytokine storm and can potentially cause sepitcaemia-> bacteria in the CSF causes swelling of the brain and a rise in intracranial pressure along with potential blood clots and empyema (pus collection)

Question 21

What gram stain is strep pneumo

Answer 21

gram positive diplococcus

Question 22

Why do young people require multiple vaccines against strep pneumoa

Answer 22

-those who are less than 2 are not well covered by the vaccine→ young people do not have a good immune response against polysaccharide→ hence need a lot of boosters up until 2

Question 23

What bacteria causes neonatal sepsis

Answer 23

Can be caused by wide range of bacteria

-Most frequent are Escherichia coli, Listeria monocytogenes and GBS

Question 24

What is the triad of symptoms found in meningitis

Answer 24

Photophobia, fever, neck stiffness

-also have headache and decreased LOC

Question 25

Why is neck stiffness a symptom of meningitis

Answer 25

Due to the increased pressure and fluid within the meninges

Question 26

What is tuberculous meningitis

Answer 26

Meningitis triggered by a tuberculosis infection--> bacilli from the primary lesion will spread from the lungs into the blood and travel to the brain where they will establish caseating tubercles which are then able to rupture and spreasd into the subarachnoid space and into CSF--> in the CSF there will be a tuberculin reaction in the meninges and formation of adhesions that can block the nerves and blood vessels of the brain

Question 27

What are the viruses which cause viral meningitis

Answer 27

Enterovirus 71: May follow hand foot and mouth disease Herpes Simplex: May follow congenital infection with HSV-2 Mumps: a quite common complication Poliovirus, cocsackievirus, echovirus: Commonly seen especially due to echoviruses Japanese Encephalitis: India, Southeast Asia, Japan HIV: May occur early after infection

Question 28

What symptoms are associated with viral meningitis

Answer 28

-Headache, fever and general illness but less neck stiffness

Question 29

What does the CSF look like in viral meningitis

Answer 29

Clear and free of bacteria but may contain lymphocytes

Question 30

What causes fungal meningitis and who is it most common in

Answer 30

mainly caused by cryptoccocus neoformans | -fungi are opportunists so most common in immunocompromised

Question 31

What cause protozoal meningitis

Answer 31

Amoeba-> mainly in immunocompromised-> will cause focal paralysis, seizures, brainstem symptoms

Question 32

What are the symptoms of encephalitis

Answer 32

Characteristically signs of cerebral dysfunction such as abnormal behaviour, seizures, altered consciousness often with nausea, vomiting and fever

Question 33

What are the main causes of encephalitis

Answer 33

Viruses

Question 34

What kinds of viruses cause encephalitis

Answer 34

HSV (CMV, VZV), Polio, Flavivirus (JEV), rabies

Question 35

What bacteria can cause encephalitis

Answer 35

Treponema pallidum

Question 36

What fungi can cause encephalitis

Answer 36

cryptococcus neoformans

Question 37

What parasites can cause encephalitis

Answer 37

Toxoplasma gondii, Plasmodium falciparum

Question 38

How do each of the herpes virus cause encephalitis

Answer 38

HSV: Following primary infection in infants -A second form seen in adults probably due to viral reactivation in the trigeminal ganglia VZV: Encephalitis generally occurs as a sequelae to reactivation CMV: Either during primary infection in utero or reactivation as a complication of immunodeficiency (HIV) --> these viruses move in and out of the brain via axon terminals

Question 39

How symptoms does polio cause

Answer 39

-A minor illness with malaise, fever and a sore throat may occur--> the major illness may occur without preceding symptoms -Major illness involves paralysis of lower motor neuron innervated muscles--> Paralysis may extend from a single muscle to virtually every skeletal muscle→ including resp muscle

Question 40

How does the rabies virus spread from person to person

Answer 40

-Virus moves down from brain and into saliva where it can be transmitted through animal bite

Question 41

How can flavivirus cause encephalitis

Answer 41

-virus comes in through skin→ causes inflamm response→ the monocytes produce CCL2→ mediators are causing damage (chronic inflamm cause the symptoms)

Question 42

What are the 3 infectious stages for toxoplasma gondii

Answer 42

1. Sporozoites: contained in oocysts released in the faeces (of cats), ingested by intermediate hosts (humans) and undergo divisions leading to tachyzoites 2. Tachyzoites: rapidly multiplying organisms leading to acute infection 3. Bradyzoites: slowly multiplying organisms are released and form tissue cysts leading to chronic infection

Question 43

Who is most affected by toxoplasma gondii

Answer 43

Pregnant women-> tachyzoites can infect the fetus via the blood stream and cause abortion

Question 44

How does the tetanus toxin cause paralysis

Answer 44

Endospores produce toxins that block the release of inhib neurotransmitter GABA across the synaptic cleft-> produces dangerous overactivity of the muscle and failure to inhibit motor reflexes causing tetanic spasm (lockjaw)

Question 45

How does the botulism toxin cause paralysis

Answer 45

Endospores produced create a preformed toxin that is ingested and moves from the gut to the blood-> the toxin has a heavy and light chain and these inhibit SNARE proteins--> SNARE proteins are required for exocytosis of Ach from the neural terminal end--> no ACh is released meaning no musclar contraction= paralysis

Question 46

What is the difference in paralysis between tetanus and botulism induced

Answer 46

``` Tetanus= spastic paralysis due to no inhibition of muscle activity/contraction Botulism= flaccid paralysis due to no ACh release ```

Question 47

What is the chemoprophylaxis given to those who have come in contact with a patient who has neisseria meningitis infection

Answer 47

Rifampicin

Question 48

Based on symptoms, how can you differentiate between encephalitis and meningitis

Answer 48

``` Encephalitis= will have fever, headache, alterations in behaviour and personality and levels of consciousness and potentially seizures-> mental alterations are more pronounced in encephalitis as this is a result of infection of brain tissue Meningitis= will have fever, photophobia, neck stiffness and only small alterations in consciousness if the infection has progress ```

Question 49

What bacteria would be the most common cause of a brain abscess

Answer 49

Strep milleri

Question 50

What bacteria would most likely be found in an infection due to a penetrating trauma

Answer 50

Staph aureus, strep, clostridium