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PM3B Spring Term > Multiple sclerosis > Flashcards

Multiple sclerosis Flashcards

1
Q

what is multiple sclerosis?

A

An autoimmune disease of the central nervous system (brain & spinal cord)

MS typically affects young adults, with onset between 20 and 40 years of age

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2
Q

what are environmental factors/causes of MS?

A
  • lack of sunlight exposure - vitamin D
    -tobacco exposure
    -obesity
    -viral exposure - chances of getting EBV infection
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3
Q

genetic factors of MS?

A

There is an increased risk linked to close family members developing the disease

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4
Q

what are clinical presentations?

A

A key aspect of MS is the relationship between relapsing and remitting disease, and progressive disease.

Uhthoff’s phenomenon
Symptoms take a huge turn for
the worse upon an increase in
body temperature (e.g. upon
immersion in a hot bath)

Lhermitte’s sign
Electrical sensation running down the spine upon neck flexion

central - fatigue, depression, anxiety, unstable mood
visual - diplopia, optic neuritis, nystagmus
speech - dysarthia
throat - dysphagia
musculoskeletal- weakness, spasms, ataxia
sensation - pain, paraesthesias, hypoesthesias
bowel - incontinence, diarrhoea, constipation
urinary- incontinence, frequency and retention

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5
Q

what are 2 clinical presentation which helps with diagnosis of MS?

A

Uhthoff’s phenomenon
Symptoms take a huge turn for
the worse upon an increase in
body temperature (e.g. upon
immersion in a hot bath)

Lhermitte’s sign
Electrical sensation running down the spine upon neck flexion

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6
Q

what is the diagnosis of MS?

A

MRI: to detect white matter abnormalities and spinal lesions
McDonald diagnostic criteria

Diagnosis is a combination of time-course for clinical episodes, lesions detected by MRI and CSF markers

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7
Q

what is the pathology of MS

A

MS:
Loss of myelin sheaths (‘demyelination’) - immune attacking myelin
Axonal damage and neuronal loss
Inflammation in the brain and spinal cord
Inflammatory infiltrates mainly consist of lymphocytes and macrophages
The initial cause of inflammation in MS is not clear, and may be multifactorial

why is myelin is important - insulating layer covering the axon - made by lipid and has importance in action potential.

myelinated are much quicker than unmyelinated

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8
Q

what is the consequences of MS

A

a) acute loss of function
b) repairable damage
c) chronic damage

Axonal degeneration is a major cause of irreversible deficit with no effective therapy

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9
Q

what is the primary cause and pathology of relapse

A

conduction block

-demyelination, imflammation

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10
Q

what is the primary cause and pathology of remission

A

restoration of conduction
remyelination and decrease inflammation

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11
Q

what is the primary cause and pathology of positive phenomena (uhtoffs,lhermittes’s)

A

hyperexcitability - ectopic impulses and mechanosensitivity
demyelination

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12
Q

what is the primary cause and pathology of progression

A

persistent loss of conduction

demylination and axonal loss

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13
Q

what are the treatment used for?

A

Disease-modifying treatments

Symptomatic treatments

stoppable and repairable

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14
Q

steroids - example and use

A

Acute relapse episode
High dose corticosteroid

oral methylprednisolone, 500 mg daily, 3-5 days
i.v. methylprednisolone, 1g daily, 3-5 days

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15
Q

what should be done for relapse according to nice guidlines

A
  • hospitalisation
    -HIGH dose corticosteroid for 5 days
    to prevent immune response
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16
Q

what is Natalizumab
moa
use
dosages

A

Marketed as Tysabri
Monoclonal antibody which inhibits leucocyte migration into CNS
Anti-inflammatory effects

Mechanism of action:
binds to a4 subunit of a4b1 and a4b7 integrins, expressed on the surface of activated T-cells
Prevents binding of cells to receptors on the endothelium

Licensed for the treatment of adults with rapidly evolving severe relapsing-remitting multiple sclerosis (NICE TA127)

Linked to cases of Progressive multifocal leukoencephalopathy

Natalizumab is administered by intravenous infusion; the recommended dose is 300mg every 28 days.

cost : not cost-effective

17
Q

fingolimod
use

A

oral

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*

Sphingosine analogue
Sequesters lymphocytes in lymph nodes
Prevents them crossing BBB
Reduces rate of relapse

18
Q

Dimethyl fumarate
use

A

Thought to act as anti-inflammatory agent
Developed by Biogen as anti-MS therapy (as Tecfidera)

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 (NICE TA527)

19
Q

Alemtuzumab
use

A

Anti-CD52 antibody
CD52: antigens expressed on B and T cells
Reduces inflammatory response in early MS
Based on clinical trial vs beta interferon, this is now available on the NHS (as of NICE guideline, last update March 2020) (TA312)

20
Q

steriods
dosages
moa

A

Once-daily oral immunomodulator (NICE TA303)
Teriflunomide inhibits dihydro-orotate dehydrogenase
This is required for de-novo pyrimidine synthesis pathway needed by rapidly dividing lymphocytes

21
Q

Spasticity/spasms treatment

A

NICE guidelines 2022

first line
baclofen (GABAb receptor agonist, inhibits spinal reflexes)

Second line
Gabapentin (calcium channel blocker) (class C substance)
THC:CBD spray (4-week trial): when other treatment are not effective

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

22
Q

what can be used for pain symptoms

A

tryclic antidrepessent - amitriptyline
seratonin-noradrenaline repuptake inhibior - duloxetine
VCCB - gabapentin, pregablin

  • try the other 3

tramadol
capsacin cream

23
Q

what can be used for cognitive symptoms

A

donepazil
cognitive training programme

24
Q

what can be used in fatigue symptoms

A

Amantadine
Modafinil (except in people who are pregnant of planning pregnancy)
SSRI

25
Q

what can be used for emotional lability symptoms

A

Amitriptyline

26
Q

Vitamin D

A

Lower incidence of MS in countries with more sunlight
Some suggestion that Vitamin D may help prevent MS, leading to the idea that it could be useful in treating MS
No clinical trial evidence to support use of Vitamin D, not recommended by NICE as a treatment for MS

PM3B Spring Term (24 decks)

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