MS

Question 1

What is MS?

Answer 1

A slow, progressive and immunologically mediated disease of the CNS

Question 2

How is MS characterised?

Answer 2

By Inflammation and plaques of demyelination and axonal loss in the white matter of the brain and spinal cord

Question 3

What is demyelination?

Answer 3

Loss of mylon sheath that surrounds nerves

Question 4

What is Myelin?

Answer 4

Several layers of cytoplasmic membrane wrapped around axons
Helps to increase the speed of electrical signal transmission along the axon

Question 5

What mylenates axons in the CNS?

Answer 5

Oligodentrocytes

Question 6

What mylenates axons in the periphery?

Answer 6

Schwann cells

Question 7

How does demyelination disrupt neuroanl function?

Answer 7

Loss of function or hyperexcitability

Question 8

What does mylenation help with?

Answer 8

Conduction of signal down the nerve by facilitating action potential propagation

Question 9

What causes miscommunication?

Answer 9

Cross communitcation between adjacent nerves which are not isolated from each other

Question 10

What are plaques in MS?

Answer 10

Areas of scarring (sclerosis) due to demylenation, with associated inflammation, axonal loss and oedema

Question 11

Where are common locations for plaques?

Answer 11

Optic tract, spinal cors, brain stem and basal ganglia

Question 12

What does basal ganglia promote?

Answer 12

Balance and posture

Question 13

Symptoms of MS

Answer 13

Numbness and Tingling
Fatigue
Muscle Spasms
Vision problems
Cognitive problems

Question 14

What are MS risk factors?

Answer 14

Age, Obesity, genetics and sex

Question 15

How do genetics affect MS?

Answer 15

HLA on Chromosome 6 forms major histo-compatibility complex (MHC) and weakens asscosiations with CD58, CD6 and interleukin gene receptors

Question 16

How does sex affect MS?

Answer 16

Higher prevalance in women but not X-chromosome associated
Potential epigenetic or hormonal signals

Question 17

Environmental roles in MS

Answer 17

Virus/Bactiera - Epstein Barr virus
Smoking
Latitude
Lack of vitamin D and timing of exposure

Question 18

The development pathway of MS

Answer 18

Peripheral immune response with activation and proliferation of self-reactive T-cells

Interaction with adhesion molecules on brain endothelial cells leads to crossing of the BBB

Reactivation within the CNS leads to pro-inflammatory environment recruitment of more B cells, macrophages and microglia which results in autoimmune demylination

Question 19

What is a myelin encephalitogenic epitope?

Answer 19

Regions on myelin proteins that trigger an immune response

Question 20

What is relapsing/remitting MS?

Answer 20

Periods of disability (relapse) with stable period of recovery (remission)

Question 21

What is secondary progressive MS?

Answer 21

Follows relapsing/remitting and follows a slowly progressive clinical course

Question 22

What is primary progressive MS?

Answer 22

Steady increase in symptoms and severity without periods of remission

Question 23

What causes the symptoms of relapse periods?

Answer 23

The effects of cytokines and signalling cascade on neuronal function. Myelin and oligodendrocytes are destroyed, resulting in nerve transmission being slowed or blocked

Question 24

What does the physical location of plaques affect?

Answer 24

The type of motor, sensory, autonomic and cognitive symptoms of MS

Question 25

What causes relapse periods?

Answer 25

The limited ability of the CNS to repair or replace damage Neuronal plasticity allows the recovery of function

Question 26

What is the difference between relapse and exacerbation in MS?

Answer 26

Relapse is new symptoms caused by a new focal demylenating lesion in the CNS Exacerbation is the worsening of existing symptoms because of a focal demylenating lesion

Question 27

What are fluctuations in MS?

Answer 27

Transient changes in symptoms that do not represent a relapse or progression of disease. Common cause is increase in heat

Question 28

How is MS diagnosed?

Answer 28

Specialist neurologist 2 or more relapses in 2 years - dissemination of lesions with time 2 or more clinically defined lesions - dissemination of lesions in space MRI can be used to identify lesions Lumbar puncture can be used to measure oligo-clonal bands of IgG in CSF - inflammatory marker found in 70-80% of MS patients

Question 29

How are acute relapses of MS treated?

Answer 29

Oral or IV corticosteroids to shorten duration of relapse Oral methylprednisolone IV methylprednisolone - for patients who cannot tolerate oral or require hospitalisation

Question 30

Side effects of treatment for acute relapses of MS

Answer 30

Anxiety, insomnia, restlessness, depression, psychosis or euphoria

Question 31

What are disease modifying therapies in MS?

Answer 31

Drugs that will affect or modify the course of MS

Question 32

What do disease modifying therapies do in MS?

Answer 32

Suppress the inflammatory response and immune responses against myelin at a range of sites

Question 33

What does Dimethyl Fumerate do?

Answer 33

Used for treating relapsing/remitting MS but not active or progressive MS Suppresses T-cell activation Modifies dendritic cells Neuro-protects Immuno-suppresses

Question 34

What is Alemtuzumab?

Answer 34

Medication used to treat adults with active relapsing/remitting MS Monoclonal antibody treatment against pan-leukocytes Binds to CD52, found on T and B cells and induces deletion so that immune response is reduced

Question 35

What is Fingolimod?

Answer 35

Used to treat highly active relapsing/remitting MS in adults Binds to S1PR1 to reduce lymphocyte movement out of lymph tissues and prevents lymphocytes interacting with antigens Promotes oligodendrocyte survival and so myelin survives

Question 36

What is Natalizumab?

Answer 36

For rapidly evolving MS T lymphocytes are blocked from entering the CNS

Question 37

What do most MS disease modifying therapies target?

Answer 37

T and B cell activity to prevent them from attacking the nervous system Reduce levels of pro-inflammatory cytokines to reduce demyelination and neuronal damage

Question 38

Limitations of DMT

Answer 38

Not yet establised if long term treatment is significant Antibody based treatments have a problem due to the body producing antibodies to the drug themselves so effectiveness is inhibited

Question 39

What is Baclofen?

Answer 39

GABA-B receptor agonist that reduces activity of nerve cells responsible for muscle contractions. Leads to muscle relaxation and improved motor control

Question 40

What is Gabapentin?

Answer 40

Binds to voltage gated Ca2+ channels in the CNS and reduce influx of Ca2+ into nerve cells. Decreases release of glutamate which is responsible for transmitting pain

Question 41

What is Dantrolene?

Answer 41

Dantrolene affects muscle cells directly by interfering with the release of Ca2+ from the sacroplasmic reticulum which store Ca2+ ions Less Ca2+ is released, leading to muscle relaxation

Question 42

What is Tizanidine?

Answer 42

Alpha-2 adrenergic agonist which reduces the release of excitatory neurotransmitters like noradrenaline. Causes a decrease in nerve signal transmission and causes relaxation Works centrally

Question 43

How do benzodiazepines work?

Answer 43

Enhance GABA, reducing firing of nerves that cause spasticity and muscle contraction

Question 44

Why does spasticity occur?

Answer 44

Due to changes in the CNS, not due to demyelination of peripheral motor nerves

Question 45

How does Amitriptyline work as a medication for pain reduction?

Answer 45

Reduces entry of Ca2+ into nerve cells by blocking certain Ca2+ channels. Reduced release of glutamate and substance P, which transmit pain signals. Also blocks reuptake of serotonin and noradrenaline which reduces pain transmission