Multiple Sclerosis (spring) Flashcards
define Multiple Sclerosis
Multiple sclerosis is a complex progressive disease of the central nervous system (brain & spinal cord), often characterised by a relapsing/remitting disease course
Environmental factors for Multiple Sclerosis
Viral Exposure (Epstein Barr Virus)
Sunlight – Vit D
Tobacco exposure
Obesity
genetic factors for Multiple Sclerosis
There is an increased risk linked to close family members developing the disease
- 1st degree relatives (parent, children, sibling) have risk 2.5-5% developing MS
- An identical twin with MS raises the risk to 20-25%
Genome wide association study identified further immune related genes
clinical presentation/ symptoms of multiple sclerosis
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 does the diagnosis of multiple sclerosis involve?
MRI: to detect white matter abnormalities and spinal lesions
Diagnosis is a combination of time-course for clinical episodes, lesions detected by MRI and CSF markers
McDonald diagnostic criteria:
causes of multiple sclerosis
The pathology of MS results from a combination of inflammation, demyelination and neurodegeneration
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
Loss of myelin sheaths (‘demyelination’).
Axonal damage and neuronal loss.
Consequences of multiple sclerosis
a) acute loss of function
b) repairable damage
c) chronic damage
fill in the table…
list treatments for multiple sclerosis
(Disease-modifying treatments and Symptomatic treatments)
steroids
Natalizumab
Fingolimod
Dimethyl fumarate
Alemtuzumab
what are steroids used for in MS and what dose?
Acute relapse episode
High dose corticosteroid
- oral methylprednisolone, 500 mg daily, 3-5 days
- i.v. methylprednisolone, 1g daily, 3-5 days
Once-daily oral immunomodulator
Teriflunomide inhibits dihydro-orotate dehydrogenase
This is required for de-novo pyrimidine synthesis pathway needed by rapidly dividing lymphocytes
what is Natalizumab (Tysabri)
give its moa
what is it used for in MS?
dose?
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
Linked to cases of Progressive multifocal leukoencephalopathy
Natalizumab is administered by intravenous infusion; the recommended dose is 300 mg every 28 days.
what is Fingolimod (Gileyna)?
moa?
what does it do?
what is it used for in MS?
Sphingosine analogue
Sequesters lymphocytes in lymph nodes. Prevents them crossing BBB
Reduces rate of relapse
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
what is Dimethyl fumarate?
moa?
Developed by Biogen as anti-MS therapy (as Tecfidera)
Thought to act as an anti-inflammatory agent
why do current NICE guidelines not recommend beta interferon and glatiramer acetate for MS?
too costly compared to the benefit
what is Alemtuzumab?
what does it do in MS?
Anti-CD52 antibody
CD52: antigens expressed on B and T cells
Reduces inflammatory response in early MS
