1B cerebral inflammation

Question 1

Define meningitis

Answer 1

• Inflammation of the meninges caused by viral or bacterial infection
• Usually subarachnoid- milky white exudate on autopsy over surface of brain

Question 2

Define encephalitis

Answer 2

Inflammation of the brain caused by infection or autoimmune mechanisms

Question 3

Define cerebral vasculitis

Answer 3

Inflammation of blood vessel walls (sometimes called angiitis)

Question 4

Define myelitis

Answer 4

Inflammation of spinal cord

Question 5

How was the BBB found?

Answer 5

If you inject dye intravenously into animals, it will accumulate in most tissues except brain unless brain is compromised

Question 6

What is the vascularisation like of the brain?

Answer 6

• It’s very densely vascularised (20% of cardiac output is to brain)
• No neuron is >100μm from a capillary

Image shows pial vessels (in pia) on surface of brain then capillaries going down in brain substance

Question 7

What is the BBB formed from?

Answer 7

BBB capillaries have extensive tight junctions at the endothelial cell-cell contacts, massively reducing solute and fluid leak across the capillary wall

Question 8

What is the BBB’s function?

Answer 8

• Because of the tightness of the BBB capillaries, solutes that can exchange across peripheral capillaries can’t cross the BBB
• Allows the BBB to control the exchange of these substances using specific membrane transporters to transport into and out of the CNS (influx and efflux transporters)
• Blood-borne infectious agents have reduced entry into brain tissue

Question 9

Describe what happens when the BBB gets compromised

Answer 9

1) BBB gets compromised through stroke or physical trauma for example

2) Blood components leak into brain including fibrinogen

3) Over time the astrocytes react to the fibrinogen leakage by withdrawing their end feet from the walls of the vessel, compromising BBB even more

4) BBB compromise also leads to build up of collagen in basement membrane which hardens the vessel walls leading to small vessel disease in brain

Question 10

What are the symptoms of encephalitis?

Answer 10

• Initially they are flu-like with pyrexia and headache
• Subsequently within hours, days or weeks:
  
  • Confusion or disorientation
  • Seizures or fits
  • Changes in personality and behaviour (frontal lobe)
  • Difficulty speaking (left hemisphere)
  • Weakness of loss of movement (motor cortices)
  • Loss of consciousness (brain stem)

Question 11

What are the causes of encephalitis?

Answer 11

• Most commonly viral infection:
  
  • Herpes simplex
  • Measles
  • Varicella (chickenpox)
  • Rubella (German measles)
• Other causes:
  
  • Mosquito, tick and other insect bites
  • Bacterial and fungal infections (e.g. even bacterial meningitis can lead to encephalitis if it goes on long enough)
  • Trauma: skull fracture can lead to CSF escaping out of nose or ears (rhinorrhoea or otorrhoea)
  • Autoimmune

Question 12

What treatment is given for encephalitis?

Answer 12

Depends on underlying cause:

• Antivirals e.g. acyclovir
• Antibiotics/antifungals
• Analgesics (for symptoms)
• Anticonvulsants (prophylactically since brain damage can cause convulsions)
• Steroids
• Ventilation

Question 13

Define multiple sclerosis

Answer 13

An autoimmune demyelinating disease of CNS

Question 14

What supposedly happens in MS?

Answer 14

• We’re producing antibodies against our myelin proteins (fatty sheath surrounding axons of neurons)
• In MS we get random demyelination of certain areas of brain

Question 15

How can MS present clinically?

Answer 15

• Most commonly as a relapsing remitting form of disease- where someone has focal neurological symptom which resolves quickly but a few months later they come in with a different neurological symptom
  
  • Different symptoms occur depending on where demyelination happens
• Eventually you stop going into remission and go into secondary progression- where you accumulate neurological deficit

Question 16

What are the initial relapses in MS linked to?

Answer 16

Inflammatory activity

Question 17

What is progression of MS linked to?

Answer 17

Neurodegeneration aka axonal loss:

• demyelination may not necessarily do away completely with a specific function because we can get some remyelination and regain some activity
• However ultimately neurones start dying

Question 18

Summarise the main 4 pathophysiological traits of MS

Answer 18

• Inflammation
• Demyelination
• Axonal loss
• Neurodegeneration

Question 19

What does the imaging show?

Answer 19

• Dark staining is white matter
• There’s a loss of dark staining (and therefore white matter) in the deep white matter on left side of brain
• There are spots of demyelination too on right side near lateral ventricle
• In spinal cord section we can see near dorsal horns (at top of image) that there are white spots where there is demyelination

Question 20

What do we see at a cellular level in MS?

Answer 20

Perivascular immune cell infiltration (CD3 T cells and CD20 B cells) aka perivascular cuffing

Question 21

What does this imaging show?

Answer 21

MRI of brain of 25 yr old woman with relapsing-remitting MS

Question 22

What does the autopsy of these brains show?

Answer 22

Demyelination can be subtle in some cases and extensive in others.

Symptoms vary because the amount and location of damage to the nervous system is different in each person with MS.

Question 23

What are some bacterial causes of meningitis?

Answer 23

• Meningococcal – the most common cause of bacterial meningitis in UK
• Pneumococcal
• Haemophilus Influenzae type b (Hib)
• Streptococcal – the main cause in new-born babies

Question 24

Other than bacterial, what are some causes of meningitis?

Answer 24

• Viral: very rarely life-threatening
• Fungal