Multiple sclerosis Flashcards
What is optic neuritis and what does it cause?
Inflammation of the optic nerve - causes pain and loss of vision
What is the prognosis of optic neuritis (how many go on to return to visual acuity)?
95% return to visual acuity of 6/12 or greater within 12 months
What is the treatment for optic neuritis, does this affect final visual acuity?
High dose steroids - speed up recovery but have no effect on final visual acuity
What is the association between optic neuritis and MS?
50% of people who have suffered from optic neuritis go on to develop MS within 10 years
What is transverse myelitis, what is the prognosis and symptoms?
Inflammation inside the spinal cord - often pure sensory, may affect the bladder, experience Lhermittes phenomenon. It is often mild with a good prognosis
What is Lhermittes phenomenon?
Sudden, uncomfortable sensation which travels from your neck down your spine - like electric shocks going through your body
What is the association between transverse myelitis and MS?
50% of sufferers go on to develop MS
What kind of diagnosis is MS?
A clinical diagnosis
What criteria aid in the diagnosis of MS?
Macdonald criteria
How would optic neuritis and transverse myelitis occur in clinically definite MS?
Optic neuritis and transverse myelitis at different times
What 3 situations involving optic neuritis and transverse myelitis would not be clinically definite MS?
1) Myelitis and optic neuritis at the same time
2) Recurrent myelitis
3) Recurrent or sequential optic neuritis
What is the most common cause of neurological disability in young adults in the UK?
MS
Which sex is more susceptible to MS?
Females
What is the most common age of onset of MS?
30-40 years
What are the highest risk ethnicities and lowest risk ethnicities for MS?
Highest risk: Northern European, US Caucasians, Canadians
Lowest risk: African blacks, orientals
What is thought to be the reason behind the association between prevelance of MS and latitude?
Prevalence is strongly dependent on latitude - due to environmental factors such as habitat, diet, infections
What is MS?
A disease of the CNS - an inflammatory reaction in the CNS causes loss of myelin and slowing of nerve conduction, get areas of demyelination and loss of axons
What are thought to be the 2 main possible mechanisms behind demyelination in MS?
1) Immune cell mediated injury - auto Ab activate lymphocytes which activate macrophages and CD8+ cells to attack the axon myelin
2) Antibody mediated injury - Ab to myelin cause complement to attack the myelin of axons
What are disease modifying drugs?
Group of drugs used in the treatment of relapsing multiple sclerosis
What are the 4 types of disease progression in MS?
1) Relapsing-remitting MS - get flare ups and periods of improvement but generally relapses get worse over time
2) Primary progressive MS (10% of cases) - MS gets gradually worse over time with no periods of remitting
3) Secondary progressive MS - initially relapsing and remitting then becomes progressive and no longer get any periods of improvement
4) Progressive relapsing MS (
How effective is the DMD Interferon Beta - at which point is it most effective?
Reduces the number of relapses by 1/3
Effective early in the disease course
No evidence of long term effect on disability
What is the sight of injection, frequency and side effects of the DMD Betaferon 1b?
Subcut injection
Alternate days
Side effects = flu like symptoms, ISR
What is the sight of injection, frequency and side effects of the DMD Avonex 1a?
IM injection
Once weekly
Side effects = flu like symptoms
What is the sight of injection, frequency and side effects of the DMD Refib 1a?
Subcut injection
3 times a week
Side effects = flu like symptoms, ISR
What is the sight of injection, frequency and side effects of the DMD glatiramer acetate?
Subcut injection
Daily
Side effects = acute reaction
TYSABRI is the first humanised monoclonal Ab approved for the treatment of MS, how does it work?
Inhibits adhesion molecules on the surface of immune cells this is through to prevent immune cells from migrating from the blood stream into the brain where they can can cause inflammation and potentially damage nerve fibres and there insulation
How are humanized monoclonal Abs produced?
Using genetic engineering in mice
Which adhesion molecule on the activated leukocyte interacts with VCAM-1 on the blood brain barrier to enable immune cell adhesion and migration?
Alpha 4 integrin
Natalizumab prevents migration of immune cells across the blood brain barrier by selectively attaching to which molecule?
The adhesion molecule alpha 4 integrin found on activated leucocytes
Give the 3 new oral treatments for MS?
1) Fingolimod
2) Teriflunomide
3) Dimethyl Fumarate
What is the overall mechanism of action of fingolimod?
Sphingosine 1-phosphate (S1P) receptor modulator
Prevents T cell invasion of CNS
Traps circulating lymphocytes in peripheral lymph nodes
How does Fingolimod trap circulating lymphocytes in peripheral lymph nodes?
Fingolimod results in the internalisation of the receptor S1P1
This blocks lymphocyte movement movement out of the lymph nodes whilst sparing immune surveillance by circulating memory cells
How does the reduction in relapse rate compare between Fingolimod and interferon 1a?
52% reduction in relapse rate with fingolimod compared to Interferon 1a
Which virus has Fingolimod been associated with and which 1 side effect?
Associated with 2 incidences of fatal herpes zoster virus infection
Troublesome bradychardia after first dose
How can brain imaging help to diagnose MS?
see brain atrophy
What percentage of MS patients are confined to a wheelchair within 10 years of diagnosis?
15%
What are the 2 different types of treatment in MS?
1) Symptomatic treatments - management of the acute relapse, mainly corticotherapy
2) Modifying course treatments
What 7 problems can symptomatic treatments treat in MS?
1) Fatigue
2) Mood problems
3) Pain
4) Sensory problems
5) Tremor
6) Spasticity
7) Genitosphincteral problems
What are the 7 targets for neuroprotective therapy?
1) Inflammatory mechanisms
2) Excitotoxic mechanisms
3) Demyelination induced
4) Energy depletion
5) Genetic determination
6) Apoptotic mechanisms
7) Depletion of growth factors
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 phase
2) Still no effective treatment for progressive multiple sclerosis
3) There is no way of telling benign patients at the start of their disease
Is MS an autoimmune disease?
Yes
What is the most common course of the disease?
Relapsing phase followed by a progressive phase in most cases
