Multiple sclerosis Flashcards
what is multiple sclerosis?
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
what are environmental factors/causes of MS?
- lack of sunlight exposure - vitamin D
-tobacco exposure
-obesity
-viral exposure - chances of getting EBV infection
genetic factors of MS?
There is an increased risk linked to close family members developing the disease
what are clinical presentations?
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
what are 2 clinical presentation which helps with diagnosis of MS?
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
what is the diagnosis of MS?
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
what is the pathology of MS
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
what is the consequences of MS
a) acute loss of function
b) repairable damage
c) chronic damage
Axonal degeneration is a major cause of irreversible deficit with no effective therapy
what is the primary cause and pathology of relapse
conduction block
-demyelination, imflammation
what is the primary cause and pathology of remission
restoration of conduction
remyelination and decrease inflammation
what is the primary cause and pathology of positive phenomena (uhtoffs,lhermittes’s)
hyperexcitability - ectopic impulses and mechanosensitivity
demyelination
what is the primary cause and pathology of progression
persistent loss of conduction
demylination and axonal loss
what are the treatment used for?
Disease-modifying treatments
Symptomatic treatments
stoppable and repairable
steroids - example and use
Acute relapse episode
High dose corticosteroid
oral methylprednisolone, 500 mg daily, 3-5 days
i.v. methylprednisolone, 1g daily, 3-5 days
what should be done for relapse according to nice guidlines
- hospitalisation
-HIGH dose corticosteroid for 5 days
to prevent immune response
what is Natalizumab
moa
use
dosages
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
fingolimod
use
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
Dimethyl fumarate
use
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)
Alemtuzumab
use
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)
steriods
dosages
moa
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
Spasticity/spasms treatment
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
what can be used for pain symptoms
tryclic antidrepessent - amitriptyline
seratonin-noradrenaline repuptake inhibior - duloxetine
VCCB - gabapentin, pregablin
- try the other 3
tramadol
capsacin cream
what can be used for cognitive symptoms
donepazil
cognitive training programme
what can be used in fatigue symptoms
Amantadine
Modafinil (except in people who are pregnant of planning pregnancy)
SSRI
what can be used for emotional lability symptoms
Amitriptyline
Vitamin D
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
