Multiple Sclerosis

Question 1

What is multiple sclerosis

Answer 1

• this is an autoimmune inflammatory disease that attaches myelinated axons in the centre nervous system

Question 2

How do you recognise MS

Answer 2

• patients medical history

- physical examination

Question 3

What is an episode of multiple sclerosis defined as when investigating multiple sclerosis

Answer 3

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

Question 4

What are the most common symptoms of multiple sclerosis

Answer 4

• sensory and motor problems - can experience numbness or tingling down arms and legs, or an electric current sensation down he back of the legs or useless hand syndrome
• vision problems; vision blurriness or loss or diplopia
• slow progressive or subacute motor defeicts

Question 5

What symptoms of MS occur in less than 5% of patients

Answer 5

• Bladder dysfunction
• Heart intolerance
• Paroxysmal symptoms
• Pain
• Movement disorders
• Dementia

Question 6

When do patients with MS tend to feel worse

Answer 6

People tend to feel worst when there is heat, temperature change in their symptoms and they can have recurrence of symptoms typically the vision loss, but other things can show up and when they cool down this then disappears
- this is because heat causes nerves to conduct less efficiently

Question 7

what are the types of MS that can occur

Answer 7

relapsing remitting
primary progressive
secondary progressive

Question 8

describe the three types of MS that can occur

Answer 8

relapsing remitting
- this is when an attack will occur but then go back to baseline - this is the most common type and affects 75-90% of patients

primary progressive
- patient never relapses and progressively gets worse

secondary progressive
- between relapses the disease gets worse

Question 9

even if the patient does not …

Answer 9

even if patient does not have a lot of relapses the disease may be progressing sub clinically.

Question 10

what do we mean by relapse in MS

Answer 10

• inflammation waves entering the brain

Question 11

what part of the brain do lesions tend to be in in MS

Answer 11

• periventricular, they can be in any part of the brain but need to have a periventricular lesions
• there are some cases in which the spinal cord will have a lesion and the brain won’t

Question 12

What type of MRI scan can be used for spotting inflammation in multiple sclerosis

Answer 12

T2/FLAIR lesions

Question 13

what contrast can be used to enhance the areas of inflammation

Answer 13

• gadolinum

Question 14

describe what the MRI has to show for MS to be diagnosed

Answer 14

T2/FLAIR lesions disseminated in space: (>1 area) in >= 2 CNS areas

• lesions can be in periventricular, juxtacortical, infratentorial, or spinal cord
• *Lesion in corpus callosum is also indicative of MS because they are rare in other conditions

and

• *T2/FLAIR lesions disseminated in time (ie, occurring at different points in time)
• e.g. 1 lesion at baseline and then, on follow-up MRI, have a new T2 and/or Gd-enhancing lesion

Question 15

what else can the MRI show in MS

Answer 15

can show brain atrophy

Question 16

How do you diagnose MS

Answer 16

MRI and lumbar puncture

Question 17

How does a lumbar puncture show that you have MS

Answer 17

• done in sterile environment with atruamtic needle which means that there is no damage to the dura
• it compares components of the CSF to the plasma (such as presence of blood cells and lymphocytes)
• measures neurofilaments - if the neurofilamnets are high than it is indicative of ongoing nerve loss

Question 18

what are neurofilaments

Answer 18

= neurofilaments are the protein component of axons

Question 19

what are olgioclonal bands

Answer 19

• can see olgiocloncal bands in the CSF and not in the plasma = this is a hallmark of chronic inflammatory process

Question 20

How do you diagnose MS

Answer 20

• Neurological symptoms need to occur in more than one place in the CNS (brain, spinal cord, optic nerve) (dissemination in space) AND
• It needs to be a chronic condition i.e. two different points (dissemination in time).
• Rule out all other diagnoses.

Question 21

what are the two important things in diagnosis of MS

Answer 21

1. Time is important in diagnosis – by definition it is a chronic disease so you have to show that it is not a one off therefore lesions should be seen at two different times
2. it should not only affect one part of the nervous system, there should be lesions in different part of the nervous system

Question 22

Why do we have a diagnostic criteria

Answer 22

• We have a diagnostic criteria so we can have a homogenous population so we can test a drug or treatment
• sometimes you have to be able to make a diagnosis so that we can treat
• to rule out other possible diagnosis

Question 23

what are other differential illnesses in comparison to MS

Answer 23

• Cerebrovascular disease
• Syphilis
• Lyme borreliosis
• SLE
• Vitamin B12 deficiency
• Rare hereditary diseases

Question 24

describe the genetic component of MS

Answer 24

There is a genetic component but it is not very relevant (in terms of producing offspring chances are relatively low).

Question 25

what gene is MS associated with

Answer 25

- HLA-DRB1*1501-DQB1*0602 haplotype on chromosome 6p21 western populations

Question 26

What are the causes of MS

Answer 26

• The cause of MS is relatively unknown. Can possible due to: o Viral infection of neurons. o Mitochondrial dysfunction. o Release of heat shock.

Question 27

inflammation versus neurodegernation

Answer 27

= not sure if MS is caused by the inflammation causing neurodegernation or the neurodegernation causing inflammation

Question 28

what is the pathology of MS

Answer 28

- this is when axons are still present but there is no myelin around them

Question 29

What are the cells involved in MS

Answer 29

* Neurons * Astrocytes (reactive astrocytosis) * Oligodendrocytes = pathology most seen in this * Microglia

Question 30

what is a proactive lesion

Answer 30

- activated microglia and loss of myelin | - lymphocyte infiltration around the blood vessel

Question 31

what is a chronic active lesion

Answer 31

- lymphocyte spread out around the lesions | - macrophages engulf myelin and sit on the lesions edge

Question 32

what is a chronic inactive lesions

Answer 32

- attempt at demyelination - however there is already significant demyelination and axonal loss - forms an astrocytic scar

Question 33

what are the two types of treatment programmes that can be used in MS

Answer 33

escalation - this is when you start with a drug that is not very effective but has less side effects and if the disease breaks through then you prescribe a better drug induction - this is when you go early and hit hard with the most effective drugs in the hope that you can preserve things for as long as possible

Question 34

name some first line and second line escalation drugs

Answer 34

First line - Injectables = IFNb and GA - Orals – DMF and teriflunomide - Ocrelizumab – monoclonal antibodies - IV - Natalizumab – monoconal antibodies – blocks the activation marker for lymphocytes that go into the blood brain barrier - IV - Cladribine – anti proliferation drug Second line (more aggressive) - Fingolimod - oral - Natalizumab - IV - Cladribine - oral - Alemtuzumab - IV

Question 35

name some induction drugs that are used

Answer 35

- Alemtuzumab – a anti CD52 - IV - Mitoxantrone - HSCT - Ocrelizumab- IV

Question 36

what drug is used in attacks of inflammation

Answer 36

high dose prednisolone