Demyelinating disorders

Question 1

How much of the brain is grey matter?

Answer 1

50% Grey matter
50% White matter
Billions of cells communicate
Myelin sheath in key to rapid communication

Question 2

______ myelinate neurones in the CNS?

Answer 2

Oligodendrocyte

Question 3

what (developmentally) does myelination begin?

Answer 3

Myelination begins in third trimester
Rapid increase in myelination at birth
Continues throughout life

Question 4

Where do oligodendrocytes come from in CNS?

Answer 4

Oligodendrocyte precursor cells distributed in CNS (green stain)
Proliferate and differentiate into oligodendrocytes
Form myelin sheaths

Question 5

How is myelin wrapped around axons?

Answer 5

specialised plasma membrane - Concentrically laminated membrane structure
Lamella formed from fusion of opposed inner leaflets of plasma membrane
No intervening cytoplasm

Question 5

How is myelin wrapped around axons?

Answer 5

specialised plasma membrane - Concentrically laminated membrane structure
Lamella formed from fusion of opposed inner leaflets of plasma membrane
No intervening cytoplasm

Question 6

What is the connection between oligodendrocytes and the myelin wrap they give to CNS neurones?

Answer 6

Pedicle

Question 7

a myelinating cell myelinates one neuron. What type of cells are they?

Answer 7

PNS Schwann cell myelinates one PNS neuron

Question 8

Are all axons myelinated?

Answer 8

No, only large ones

Question 9

How large does an axon need to be in order to be myelinated in the CNS?

Answer 9

In CNS axons >0.2µm myelinated

Question 10

How large does an axon need to be in order to be myelinated in the PNS?

Answer 10

In PNS axons>1-2µm myelinated

Question 11

The ______ (larger/smaller) the axon, the _______ (fewer/more) wraps of myelin?

Answer 11

The larger the axon, the more wraps of myelin

Question 12

What is the ratio between axon diameter and total nerve fibre diameter?

Answer 12

Ratio between axon diameter and total nerve fibre diameter (axon plus myelin) is 0.5-0.9, optimal 0.77

Question 13

Length of myelin sheath approx _____mm in PNS with gaps between sheaths

Answer 13

Length of myelin sheath approx 1mm in PNS with gaps between sheaths (Nodes of Ranvier)

Question 14

Length of myelin sheath approx _____mm in PNS with gaps between sheaths

Answer 14

Length of myelin sheath approx 1mm in PNS with gaps between sheaths (Nodes of Ranvier)

Question 15

How is spiral wrapping done so precisely?

Answer 15

Myelination is thought to be dependent on neuronal activity
Communication via neuro-glial signalling molecules (gliotransmitters)

Question 16

In PNS how is myelination done?

Answer 16

Proteins expressed on axon surface interact with receptors on glial cells (eg neuroregulin 1 type 3 protein in PNS and Erb β receptors)
They have role in cells then differentiating into schwann cells to produce the myelin sheath
Heavily myelinated fibres have high level of proteins

Question 17

Heavily myelinated fibres have _______ (low/high) level of proteins ?

Answer 17

Heavily myelinated fibres have high level of proteins (axon surface to glial cells)

Question 18

Summarise 3 functions of myelin

Answer 18

Reduces loss of charge across the axon

Speeds up transmission of the action potential along the axon
Unmyelinated fibres 0.5-2m/s
Myelinated fibres 70-100m/s

Increases efficiency of the electrical transmission
Less ion channels needed, clustered at nodes of Ranvier

Question 19

How do nodes of Ranvier help to propagate action potentials?

Answer 19

Some of the current propagated by the action potential spreads passively to the next node due to the insulating effect of myelin (no/few channels increases membrane resistance to charge leakage) and

Question 20

What can damage myelin?

Answer 20

Mechanisms of damage
Brain injury
Ischaemia
Toxins
Metabolic
Neurodegenerative
Infective
Immune based

Question 21

what are “leukodystrophies”

Answer 21

Failure to myelinate: leukodystrophies

Question 22

define demyelination

Answer 22

Damage and loss of myelin sheath is termed demyelination

Question 23

do steroids help MS relapses?

Answer 23

They speed them up but do not alter the course of the nerve damage, just resolve the flare-up faster

Question 24

What is the direct pathological consequence of demyelination

Answer 24

Loss of myelin leads to slowing/blocking of nerve messages

Question 25

What are some of the symptoms of demyelination?
1
2
3
4
5
6
7
8
9
10

Answer 25

Visual impairment
Changes in cognition
Speech impairment
Balance problems
Incoordination
Sensory symptoms
Weakness
Bladder/bowel problems
Pain
Fatigue

Question 26

Core info about MS?

Answer 26

Central nervous system demyelination
Immune based disorder

Question 27

Does MS affect men more than women?

Answer 27

3 female:1 male

Question 28

What causes MS?

Answer 28

Cause: unknown!
Links to northern hemispheres…

Genetic 30%
Environmental: sun/vit d exposure
Infection ?EBV
Cigarette smoking
Obesity in early life

Question 29

Summarise mechanism of MS damage
-cells implicated
-Relapse/remmission pattern

Answer 29

Immune cells enter the brain and attack myelin (T cells)
Relapses = demyelination
Remissions = remyelination but may be incomplete
Failure of remyelination = ongoing symptoms and disability

Question 30

What’s the difference between primary progressive and secondary progressive disease in MS

Answer 30

Can go on to a progressive phase (secondary progressive MS) (if it does not it was not MS)
Some people have primary progressive disease from start

Question 31

How does MS lead to disability?

Answer 31

The location of the damage correlate to the symptoms, not the nature of the damage! NEUROLOGY CORE CONCEPT

Question 32

what damage can be seen on the spinal cord of this MRI?

Answer 32

Grey area of sclerotic damage (scarring)