Cerebral Inflammation

Question 1

Define meningitis, encephalitis and cerebral vasculitis

Answer 1

Meningitis – inflammation of the meninges caused by viral or bacterial infection

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

Cerebral vasculitis – inflammation of blood vessel walls (sometimes called angiitis)

Question 2

How does infection appear in the arachnoid?

Answer 2

Can see a milky white exudate covering the surface of the brain in the subarachnoid space which is caused by an inflammatory reaction of bacterial/viral origin.

Question 3

What originally suggested the existence of the blood brain barrier?

Answer 3

In the late 19th and early 20th centuries, it was noted that dyes, and other tracers, injected intravenously, accumulated in most tissues, but were excluded from most areas of the CNS.This suggested the existence of a Blood-Brain Barrier.

Question 4

Describe vascular network of the CNS

Answer 4

Densely vascular as pial vessels give rise to capillaries in the brain substance. No neuron is more than 100 micrometres from a capillary. 20% of cardiac output supplies the brain.

Question 5

What forms the basis of the blood brain barrier?

Answer 5

BBB capillaries have extensive tight junctions at the endothelial cell-cell contacts, massively reducing solute and fluid leak across the capillary wall. Astrocytes project endfeet which encircle the BBB further fortifying it and preventing leakage.

Question 6

Describe the layers around the brain

Answer 6

Capillary projection from the pial vessel is first surrounded by the Virchow-Robin space which are fluid-filled spaces that surround small arterioles, capillaries and venules in the brain. The Glia Limitans membrane then lines it which is the outermost layer of neural tissue of the brain which lies under the pia mater. composed of a dense multilayered meshwork of astrocyte processes, covered by an outer basal lamina that makes intimate contact with cells of the pia mater. Finally the leptomeninges (pia and arachnoid) join together.

Question 7

What is the role of the blood brain barrier?

Answer 7

Because of the “tightness” of the BBB capillaries, solutes that can exchange across peripheral capillaries cannot cross the BBB. This 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 CNS tissue.

Question 8

What are symptoms of encephalitis?

Answer 8

Initially, flu-like symptoms with pyrexia. Progressive symptoms within few hours/days include:
confusion or disorientation
seizures or fits
changes in personality and behaviour
difficulty speaking
weakness or loss of movement
loss of consciousness

Question 9

What is encephalitis most commonly caused by?

Answer 9

A viral infection, usually Herpes Simplex, Measles, Varicella (chickenpox) or Rubella (German measles).

Question 10

What are 4 less common causes of encephalitis?

Answer 10

Mosquito, tick and other insect bites
Bacterial and fungal infections
Trauma
Autoimmune

Question 11

What are 6 treatments for encephalitis?

Answer 11

Antivirals e.g. acyclovir
Steroids
Antibiotics/antifungals
Analgesics
Anti-convulsants
Ventilation 
Treatment depends on underlying cause

Question 12

What is multiple sclerosis and what is it characterised by?

Answer 12

Multiple sclerosis is an autoimmune disorder where antibodies are produced against own myelin. Characterised by a relapsing-remitting pattern of disease where axonal loss is linear and progressive. As spikes in inflammation occur, depending on what part of brain is affected, symptoms may appear and then inflammation + symptom resolved with treatment. Eventually as inflammation becomes more consistent, neurological deficit is irreparable and starts accumulating.

Question 13

What is secondary progression in multiple sclerosis?

Answer 13

Remission period lost and instead a gradual accumulation of neurological deficits occur and inflammatory activity decreases but axonal loss is significant and consistently progressive at this point.

Question 14

What are 4 cellular pathological signs of multiple sclerosis?

Answer 14

Inflammation, Demyelination, Axonal loss, Neurodegeneration

Question 15

Why do symptoms in multiple sclerosis vary?

Answer 15

Depends on part of brain that is affected by demyelination - as this varies between people, so do the symptoms. Can see loss of white matter in affected part of brain

Question 16

What cells are responsible for the inflammation in MS?

Answer 16

Perivascular immune cell infiltration (CD3 T-cells and CD20 B-cells) occurs.

Question 17

What is meningitis? Describe epidemiology

Answer 17

Irritation, inflammation and swelling of the meninges. 6th most common infectious disease killer and affects more than 5 million people per annum worldwide. Leaves 1 in 5 of the infected people with an impairment.

Question 18

What are 4 bacterial causes of meningitis?

Answer 18

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 19

What are hallmark signs of meningitis?

Answer 19

Common symptoms include: sudden fever, severe headache, nausea or vomiting, double vision, drowsiness. Hallmark sign is sensitivity to bright light and a stiff neck. Also may be a rash that does not fade when glass is pressed against it.

Question 20

What causes the hallmark signs of meningitis?

Answer 20

While arachnoid mater and pia mater are inflammed, dura mater experiences little to no inflammation. However, leaking CSF may activate dura mater’s neural fibres which are able to detect pain and so, contribute to neck pain and nuchal rigidity. Photophobia caused by pain mediated by first branch of trigeminal nerve which innervates the meninges.

Question 21

What are hallmark symptoms of encephalitis?

Answer 21

Fever, acute onset seizures, change in behavior, confusion and disorientation.

Question 22

How is meningitis treated?

Answer 22

IV fluids, antibiotics, oxygen, steroids (corticosteroids reduce inflammation by suppressing immune system). Lumbar puncture used to collect CSF for culture but also, low glucose in CSF indicates presence of pathogen. Inflammation reduced as it causes more damage than the actual infection.

Question 23

How is encephalitis treated?

Answer 23

Antiviral medicine, steroid injections, Ig therapy,

plasmapheresis, surgery to remove abnormal growths.