Multiple Sclerosis

Question 1

In MS patients, what is the typical history they present with that defines the condition?

Answer 1

Current neurological symptoms or a previous neurological episode, lasting at least 24 hours, without evidence of infection, fever, or encephalopathy.

Question 2

What are the most common symptoms of MS? (3)

Answer 2

Sensory/motor problems (numbness, tingling, useless hand syndrome)
Vision loss, blurriness or diplopia
Slow progressive or sub-acute motor deficits

Question 3

What symptoms do less than 5% of MS patients have at onset? (5)

Answer 3

Bladder dysfunction
Heat intolerance
Pain
Movement disorders
Dementia

Question 4

What are the 5 characteristic symptoms of demyelination?

Answer 4

Optic neuritis or internuclear ophtalmoplegia
Lhermitte’s symptom
Uhthoff phenomenon
Paroxysmal symptoms
“Useless hand” (proprioceptive defect)

Question 5

What type of condition is MS?

Answer 5

Chronic

Question 6

What processes are involved in MS? (3 words)

Answer 6

Inflammation
Demyelination
Degeneration

Question 7

What does an MRI detect on MS patients? (2)

Answer 7

Inflammatory demyelinating lesions

Brain atrophy

Question 8

Lesions are disseminated in ____ and ____.

Answer 8

Space (two separate areas of the CNS)

Time (two different points in time)

Question 9

What is gadoliniuim?

Answer 9

A contrast - used to enhance areas of inflammation

Question 10

Lesions in what area are indicative of MS (because they are rare in other conditions)?

Answer 10

Corpus callosum

Question 11

Why are lumbar punctures done in MS?

Answer 11

To test the CSF for oligoclonal bands (in health, should be positive in plasma and negative in CSF) and neurofilaments

Question 12

What type of needle is now used for LPs?

Answer 12

Atraumatic

Question 13

To diagnose MS, you need to… (4)

Answer 13

Exclude other causes
Find neurologic deficits
Dissemination in space
Dissemination in time

Question 14

What diseases mimic MS? (8)

Answer 14

Cerebrovascular disease
Syphilis
Lupus
Vasculitis
B12 def
Neuromyelitis optica
Sjogrens
Lyme's

Question 15

How many people worldwide have MS?

Answer 15

About 2.5 million

Question 16

How many people in the UK?

Answer 16

> 100 000 people

Question 17

How many people are diagnosed each year?

Answer 17

5000 people

Question 18

MS is the most common cause of…?

Answer 18

Non-traumatic neurological disability

Question 19

By how many years is life expectancy reduced by in MS patients?

Answer 19

10-15 years

Question 20

Is MS genetic?

Answer 20

To some extent, but environment is more important.

Question 21

What causes preactive lesions? (5)

Answer 21

Viral infections
Mitochondrial dysfunction
Anti-neuronal and anti-myelin antibodies
Reactive oxygen species
Neurodegeneration 

These lead to neuronal, axonal and oligodendrocyte damage, as well as oligodendrocyte stress.

Question 22

What do oligodendrocytes do?

Answer 22

Make myelin

Question 23

Between which vertebrae do you go for LP?

Answer 23

L3 and L4

Question 24

What is seen in a pre-active lesion?

Answer 24

Microglia are activated and there is loss of myelin

Question 25

What is seen in an active lesion?

Answer 25

Macrophages are recruited that engulf myelin

Question 26

What is seen in a chronic active lesion? | What is seen in a chronic inactive lesion?

Answer 26

Macrophages at the lesion edge | Demyelination and axonal loss progression, then an astrocytic scar

Question 27

What comes first - CNS inflammation or neurodegeneration?

Answer 27

We don't know! CNS inflammation could cause an immune response that causes neurodegeneration. Alternatively, neurodegeneration could cause an immune response that causes inflammation.

Question 28

What is the therapeutic hierarchy for MS? Start from the bottom.

Answer 28

Anti-inflammatory, neuroprotection, remyelination, neuro-restoration

Question 29

What symptoms require symptomatic treatment? (7)

Answer 29

``` Neuropathic pain Spasticity Bladder and bowel dysfunction Fatigue Depression UTIs Tremors ```

Question 30

What can patients do to improve their condition?

Answer 30

Smoking cessation Exercise Diet Sleep

Question 31

What are the methods of treatment? (7)

Answer 31

``` Lymphocyte trafficking Targeted immune regulation Symptomatic treatment Vaccine and tolerisation Anti-proliferation agents Interferons Targeted mabs/fc-ab ```

Question 32

What are the two main pathways of treatment?

Answer 32

Maintenance-escalation and induction

Question 33

How many licensed induction therapies are there at present?

Answer 33

Only one

Question 34

What are the first line medications for escalation therapy?

Answer 34

Injectables: IFNb and GA Orals: DMF and Teriflunomide Natalizumab (highly active)

Question 35

What are the first line medications for induction therapy?

Answer 35

Alemtuzumab Mitoxantrone HSCT

Question 36

What are the second line medications?

Answer 36

Fingolimod Natalizumab Alemtuzumab HSCT

Question 37

How is IFNb administered? How many times a week? What is the major side effect?

Answer 37

Sub-cut or IM 3 times Flu-like symptoms

Question 38

How is GA administered? How many times a week?

Answer 38

GA Sub-cut Daily or 3 times

Question 39

How is teriflunomide administered? What are the two major risks?

Answer 39

Orally Liver toxicity Teratogenic

Question 40

How is natalizumab administered? How many times a month?

Answer 40

IV | Monthly

Question 41

How is fingolimob administered? What is the major risk?

Answer 41

Oral | Arrhythmia

Question 42

How often is alemtuzumab administered? What are the major side effects?

Answer 42

Yearly | Autoimmune thyroid disease and Goodpasture’s