Multiple Sclerosis 1 Flashcards
What is optic neuritis?
Inflammation of the optic nerve
What are the main symptoms of optic neuritis? 2
Pain and loss of vision
Can optic neuritis be visualised using fundoscopy?
No, it is frequently not visible as it is retro bulbar
What is the prognosis of optic neuritis, what percentage return to visual acuity within 6/12?
95%
What is the treatment for optic neuritis, does this effect final acuity?
High dose steroids - these speed up recovery but have no effect on final acuity
What percentage of people who have suffered from optic neuritis go on to develop MS within 10 years?
50%
What is transverse myelitis?
Inflammation inside the spinal cord
What is Lhermitte’s sign/phenomenon?
Sudden sensation resembling an electric shock which passes down the back of the neck and onto the spine and may radiate into the arms and legs, usually triggered by bending your head forward towards your chest
Is transverse myelitis normally severe? What is the prognosis?
Normally mild, with a good prognosis
What are the 3 main symptoms of transverse myelitis?
1) Often purely sensory symptoms
2) Lhermitte’s sign
3) May affect the bladder
What percentage of people with transverse myelitis go on to develop MS?
50%
Is MS mainly a clinical or imaging diagnosis?
Mainly a clinical diagnosis
What criteria can be used for diagnosing MS?
Macdonald criteria 2010 (2nd revision)
In what situation could you diagnose clinically definite MS?
Optic neuritis and transverse myelitis at different times
In which 4 situations is a clinical diagnosis of MS not definite?
1) Clinically isolated syndrome (CIS)
2) Myelitis and optic neuritis at the same time
3) Recurrent myelitis
4) Recurrent or sequential optic neuritis
What is the most common cause of neurological disability in young people?
MS
Is MS more common in females or males?
Females (2:1)
What is the most common age of onset of MS?
30-40 years
In which ethnicity is susceptibility to MS highest?
Northern Europeans, US Caucasians, Canadians
Prevelance of MS is strongly dependent on latitude, which factors can this be attributed to?
Environmental factors such as habitat, diet and infections
MS is a disease of which body system?
CNS
What is MS?
Autoimmune disease - inflammatory reaction in the CNS which causes loss of myelin and slowing of nerve conduction. Get areas of demyelination and loss of axons
Give 2 possible mechanisms of demyelination in MS?
1) immune mediated - macrophages destroy myelin
2) Antibody mediated destruction of myelin
Give 9 disease modifying treatments used in MS?
1) Interferon beta 1-b
2) Interferon beta 1-a
3) Glatiramer acetate
4) Teriflunamide
5) Dimethyl fumarate
6) Fingolimod
7) Natalizumab
8) Alemtuzumab
9) Mitoxantrone
How does interferon beta treatment reduce the number of relapses in MS and when is it most effective?
1) Reduces the number of relapses by 1/3
2) Effective early in the disease course - no evidence on long term effect on disability
TYSABRI (Natalizumab) is the first humanized mAb approved for the treatment of MS, how is it thought to work?
It inhibits adhesion molecules on the surface of immune cells, its is thought to work by preventing immune cells from migrating into the bloodstream and into the brain where they can cause inflammation and potentially damage nerve fibres and their insulation
Which molecules on the activated leucocyte and the BBB are the key components involved in immune cell adhesion and migration?
1) Activated leucocyte - a4-integrin
2) BBB - VCAM-1
Which molecule on the activated leucocyte is blocked by Natalizumab?
a4-integrin - prevent it interacting with VCAM-1 on the BBB
Name 3 new oral treatments for MS?
1) Fingolimod
2) Teriflunomide
3) Dimethyl fumarate
Fingolimod (a new oral therapy to treat MS) is what kind of drug?
Sphingosine 1-phosphate (S1P) receptor modulator
How simply does Fingolimod work to treat MS?
It prevents T cell invasion of the CNS by trapping encirculating lymphocytes in peripheral lymph nodes
How does Fingolimod trap circulating lymphocytes in peripheral lymph nodes?
Fingolimod causes the internalisation of the receptor S1P1 (on the T cell)
This blocks the T cell from moving out of lymph nodes while sparing immune surveillance by circulating memory T cells
What are the 2 main side effects identified for Fingolimod?
1) 2 incidences of fatal herpes virus infection (type 1 encephalitis and disseminated zoster)
2) Bradychardia after 1st dose
What is the difference in relapse rate between Fingolimod and IM interferon 1a?
Fingolimod caused a 52% relapse reduction rate compared to IM interferon 1a
What are the 4 types of MS?
1) Relapsing -remitting MS - periods where symptoms flare up aggressively followed by periods of good or complete recovery
2) Secondary progressive MS - initially diagnosis of relapsing-remitting and over time frequency of relapses decreases but disability increases
3) Primary progressive MS - form in which disability increases from outset
4) Progressive relapsing MS - Disability increases from the outset but along the way have periods of relapse where symptoms flare up aggressively with remission but never full recovery
Although symptoms and inflammation can relapse and remit, what is the course of axonal loss in MS?
Gradual increase in axonal loss - straight line graph
What would brain imaging of someone with MS show over time?
Brain atrophy
What percentage of MS patients are confined to a wheelchair within 10 years of diagnosis?
15%
What are the 2 main categories of treatment in MS?
1) Symptomatic treatments - management of the acute relapse (corticotherapy)
2) Modifying course treatments
What 7 things do symptomatic treatments for MS relapses aim to treat?
1) Fatigue
2) Mood problems
3) Pain
4) Pain
5) Sensory problems
6) Genitosphincteral problems
7) Tremor
8) Spasticity
What is benign MS?
A version of relapsing-remitting MS with very mild attacks separated by long periods with no symptoms
What are the 7 potential targets for neuroprotective therapy in MS?
1) Inflammatory mechanisms
2) Excitotoxic mechanisms
3) Energy depletion
4) Genetic determination
5) Apoptotic mechanisms
6) Depletion of growth factors
7) Demyelination induced damage
Is MS treatable?
yes, but not curable
What are the 3 main current problems in MS management?
1) We don’t know if treating the relapsing phase aggressively helps delay or prevent the progressive process
2) Still no effective treatment for progressive MS
3) There is no way of telling benign patients at the start of the disease
What is the most common type of MS?
Secondary progressive MS - relapsing phase followed by progressive phase
