Multiple Sclerosis Flashcards

1
Q

Define Multiple Sclerosis

A

A neurodegenerative autoimmune condition that affects the CNS. Caused by a complex interaction of genetic and environmental triggers

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2
Q

What are the two interesting aspects of the incidence of MS

A
  1. The incidence has increased significantly over the last 100 years
  2. There are remarkable differences in incidence between continents and countries
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3
Q

How is MS characterised and what are the symptoms?

A

Characterised by multiple episodes of the same or different neurological symptoms separated by periods of remission.

Symptoms can include:
Weakness
Numbness
Loss of sense (taste, sight)
Loss of balance
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4
Q

What is Uhthoff’s phenomenon?

A

Symptoms of MS worsen upon an increase in body temperature e.g. hot bath

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5
Q

What does primary progression mean?

A

20% people, present with MS as the progressive form from the beginning

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6
Q

What does secondary progression mean?

A

This is when the patient initially suffers from periods of relapse and remission but then develops the progressive form

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7
Q

Describe the techniques used to diagnose

A

Diagnosis uses a combination of clinical observations, MRI and use of CSF markers.

MRI scans - detect white matter abnormalities and spinal lesions

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8
Q

What can be seen from CSF as the distinguishing factor for progressive form of MS?

A

Detection of oligoclonal bands (immunoglobulins not normally found in the CNS) in CSF is used to discriminate from other neurological disorders.

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9
Q

What is the biological basis of MS? and what are their consequences (3)

A
  1. Inflammation in the brain and spinal cord - acute loss of function
  2. Demyelination - repairable damage
  3. Axonal damage and neuronal loss - chronic damage
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10
Q

What is the cause of Inflammation a key biological feature of MS?

A

Cause = unclear

Autoimmune response - Immune cells infiltrate the CNS and attack cells within brain and CNS

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11
Q

Describe how inflammation causes the damage

A

Inflammatory infiltrates = Lymphocytes and Macrophages
Active MS plaques characterised by lymphocyte infiltration
Active plaques also contain numerous macrophages containing myelin at various stages of degradation.

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12
Q

What are the stages of myelin degradation?

A
  1. Myelin Whorls
  2. Myelin Proteins
  3. Neutral Lipids
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13
Q

What is the myelin sheath in the CNS made from? What is it made up of and it’s purpose?

A

Oligodendrocytes
Lipid 70% and Protein 30%
Provides insulation to help the electrochemical transmission of action potentials.

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14
Q

What impact does demyelination have on neurons? And what occurs after?

A

Negative impact on the ability of nerve cells to transmit action potentials
Remyelination occurs in the early stages of MS to re-store function. but eventually fails.

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15
Q

What is neurodegenaration the result of?

A

This is the culmination of demyelination and inflammation leading to axonal loss and neuronal cell death. Axonal degeneration is a major cause of irreversible deficit with no effective therapy

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16
Q

What % of spinal cord cross area is lost in those with progressive MS?

A

5%

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17
Q

What is the cause of relapse and what occurs (pathology?

A

Conduction block due to Demyelination and Inflammation

18
Q

What is the cause of remission and what occurs (pathology)?

A

Restoration of conduction due to Remyelination and Decreased inflammation

19
Q

What is the cause of positive/ Uhtoff phenomenaand what occurs (pathology)?

A

Hyper-excitability: ectopic impulses and mechanosensitivity due to Demyelination?

20
Q

What is the cause of progression and what occurs (pathology)?

A

Persistent loss of conduction due to demyelination and axonal loss

21
Q

What are the causes of MS?

A

Environmental:
Infection with Epstein Barr Virus
Decreased exposure to Vit D

Genetic:
Increased risk linked to close family member developing the disease
Risk alleles

22
Q

What therapy is available for an acute relapse episode?

A

High dose corticosteroid
Or
Oral methylprednisolone 500mg daily, 3-5 days
IV methylprednisolone 1g daily, 3-5 days

23
Q

How does Natalizumab (Tysabri) work?

A

It is a monoclonal antibody which inhibits leucoyte migration into CNS
Binds to a4 subunit of a4b1 and a4b7 integrins, expressed on activated T cells
Prevents binding of cells to receptors on the endothelium
Anti-inflammatory effects

24
Q

What are the NICE guidleines on the use of Natalizumab?

A

Licensed for adults with rapidly evolving severe relapsing-remitting MS
Deemed NOT cost-effective treatment in some groups of people - those who failed to respond to beta interferon

25
Q

What risk is there with using Natalizumab?

A

Linked to cases of Progressive multifocal leukoencephalopathy

26
Q

How does Fingolimod (Gileyna) work?

A

Sphingosine analogue
Sequesters lymphocytes in lymph nodes, prevents them from crossing the BBB
Reduces the rate of relapse
May become first line treatment

27
Q

What does NICE say about the use of Fingolimod?

A

Fingolimod is recommended as an option for the treatment of highly active relapsing–remitting multiple sclerosis in adults, only if:
they have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon, and
the manufacturer provides fingolimod with the discount agreed as part of the patient access scheme*

28
Q

What is Dimethyl fumarate?

A

Developed by Biogen as anti-MS therapy (as Tecfidera)

Thought to act as anti-inflammatory agent

29
Q

What does NICE say about the use of Interferons and glatiramer acetate?

A

Both beta interferon and glatiramer acetate have been used in a clinical setting for MS. Current NICE guidelines do not recommend use following cost/benefit analysis

Some patients may still be prescribed interferon beta if treatment started prior to changes in NICE guidelines

30
Q

What is Alemtuzumab?

A

Anti-CD52 antibody, reducing inflammatory response in early MS
Based on clinical trial vs beta interferon, this is now available on the NHS

31
Q

What is Teriflunomide

A

Once-daily oral immunomodulator
Teriflunomide inhibits dihydro-orotate dehydrogenase
This is required for de-novo pyrimidine synthesis pathway needed by rapidly dividing lymphocytes

32
Q

What are the pharmacological management options for Spasms?

A

First line:

  • Baclofen (GABAb receptor agonist, inhibits spinal reflexes)
  • Gabapentin (calcium channel blocker)

Second line:
According to NICE:
Tizanidine (alpha2 agonist, muscle relaxant)
diazepam, clonazepam (benzodiazepines, GABAa agonists, act at level of spinal cord to cause muscle relaxation)
dantrolene (ryanodine receptor agonist, muscle relaxant)

  • Intrathecal baclofen
  • Sativex
33
Q

What are the pharmacological management options for Bladder and bowel symptoms?

A

Sativex recently licensed; Botulinum toxin shows promise.
Conventional medications for retention (alfuzosin), urgency/incontinence (trospium, flavoxate) etc.
70-80% of patients

34
Q

What are the pharmacological management options for Pain?

A

WHO pain ladder (NICE recommends specialist referral)

80% of MS patients have pain.

35
Q

What are the pharmacological management options for Cognitive symptoms?

A

Donepazil sometimes used
Cognitive training programmes
60% of MS patients have cognitive symptoms

36
Q

What are the pharmacological management options for Fatigue?

A

Modafinil (NICE guidance awaited)

37
Q

What are the pharmacological management options for Emotionalism?

A

tricyclic antidepressant or SSRI

38
Q

What are the pharmacological management options for Depression/Anxiety?

A

Standard treatments

39
Q

What are the pharmacological management options for Walking?

A

Fampridrine. K+ Channel blocker, approved in USA

Use not indicated in UK

40
Q

Many MS patients self-medicate by smoking cannabis. What symptoms does this alleviate?

A

tremor and spasticity
pain associated with MS
Bladder function

Not recommended by NICE

41
Q

What is Lhermitte’s sign?

A

Electrical sensation running down the spine upon neck flexion