Cerebral Inflammation

Question 1

What is meant by the terms:

Meningitis
Encephalitis
Cerebral Vasculitis

Answer 1

Meningitis - inflammation of the meninges caused by viral or bacterial infection, many inflammatory cells found within the subarachnoid space

Encephalitis - inflammation of the brain caused by infection or autoimmune mechanisms

Cerebral Vasculitis - inflammation of blood vessel walls (sometimes called angiitis)

Question 2

How was the Blood Brain Barrier discovered?

Answer 2

Discovered that dyes and tracers injected intravenously will accumulate in most tissues but not the brain

Question 3

How do we know the brain is rich in blood supply?

Answer 3

Dense vascularisation of the brain - no neuron is more than 100µm from a capillary as the pial vessels descend into the brain tissue

Question 4

What forms the blood brain barrier (BBB)?

Answer 4

Formed by the capillaries - due to extensive tight junctions between the endothelial cells

No fluid leakage across the capillary wall

Question 5

What does the tightness of the BBB allow for?

Answer 5

Solutes that can exchange across peripheral capillaries cannot cross the BBB

Allows the BBB to control the exchange of these substances using specific membrane transporters to transport in and out of the CNS

Question 6

Why is the BBB important?

Answer 6

Blood-borne infectious agents have reduced entry into CNS tissue

Question 7

What happens when the endothelial layer of the BBB becomes disrupted after trauma?

Answer 7

Contents of the blood can move into brain

e.g. fibrinogen is seen in the brain blood vessels and the brain tissue around it after trauma

Glial cells react and astrocytes retract leading to the breakdown of the BBB

Basement menbrane change allows for collagven disruption, often collagen builds up - possible sclerosis for vessels

Question 8

What are initial symptoms of encephalitis?

What are the subsequent symptoms of encephalitis?

Answer 8

Initial:
Flu-like symptoms
Pyrexia (high body temperature)
Headache

Subsequent Symptoms:
Confusion or disorientation
Seizures or fits
Changes in personality and behaviour
Difficulty speaking
Weakness or loss of movement 
Loss of consciousness - associated with Brain swelling

Question 9

What are the most common causes of encephalitis?

Answer 9

Viral infections:

Herpes Simplex
Measles
Varicella (chickenpox)
Rubella (German measles)

Question 10

What are other causes of encephalitis?

Answer 10

Mosquito, tick and other insect bites

Bacterial and fungal infections

Trauma - disruption of BBB leading to subsequent encephalitis

Autoimmune

Question 11

How do we treat encephalitis and what does it depend on?

Answer 11

Depends on underlying cause:

Antivirals e.g. acyclovir
Steroids
Antibiotics/antifungals
Analgesics
Anti-convulsants
Ventilation

Question 12

What is Multiple Sclerosis (MS)?

Answer 12

Autoimmune demyelinating disease of the CNS - inflammation going on in the brain leading to resultant inflammation

Autoimmune attack on the BBB = demyelinating disease

Question 13

How do most patient present initially?

Answer 13

Relapsing - remitting episodes (due to inflammatory activity)

80% present initially with relapses and remissions over a period of time - linked to inflammatory activity

So relapses in MS is due to inflammatory activity

Question 14

What occurs long-term to patients with MS?

Answer 14

Deficits increase over time due to axonal loss - no more remissions

Secondary progression of MS is thought to be due to axonal loss in the brain and spinal cord

Question 15

What is the cellular pathology of MS?

Answer 15

Inflammation

Demyelination

Axonal loss

Neurodegeneration

Question 16

How do MR scans show MS?

Answer 16

Shows periventricular white matter changes - disappearing white matter regions

Question 17

Why do symptoms of MS vary so much?

Answer 17

Random disorder that can occur in the white matter anywhere in the CNS

Amount and location of the damage varies so much

Question 18

What are the characteristics of inflammation at a cellular level in MS?

Answer 18

Perivascular cuffing - infiltration of immune cells into the substance of the brain

These form cuffs around vessels - (ring of dots on microscope image)

Largely T-cells but also B-cells

Question 19

What are the main features of Meningitis?

Why is Meningitis a big issue?

Answer 19

Irritation, inflammation and swelling of the meninges

Meningism symptoms:
Stiff neck
Photophobia
Nausea & vomiting

6th most common infectious disease killer
Affects more than 5 million people per annum worldwide
Leaves 1 in 5 of the infected people with an impairment

Question 20

What are the most common causes of Meningitis?

Answer 20

Bacterial usually:

Meningococcal – the most common cause of bacterial meningitis in UK

Pneumococcal

Haemophilus Influenzae type b (Hib)

Streptococccal – the main cause in newborn babies

Question 21

What are the other causes of Meningitis?

Answer 21

Viral - very rarely life-threatening

Fungal