Multiple Sclerosis Flashcards
What is MS?
It is a chronic disease of the CNS. It is a disease of myelin. Axons are surrounded by myelin sheath formed by oligodendrocytes. Myelin sheath supports nerve impulse transmission. MS is a demyelinating disease where myelin sheath is damaged.
What are symptoms of MS?
Symptoms depend on where demyelination occurs. e.g. optic neuritis or face pain or loss of function of both legs. Relapses of MS can happen for example once a year of once every few years, the symptoms will get worse for few weeks and then will get better but the level of disability will increase with each attack
What are different types of MS?
- Relapsing remitting
- Secondary progressive
- Primary progressive
- Progressive relapsing
Are available treatments ok for all types of MS?
No, most available treatments are targeted towards relaping-remitting form of MS, not progressive forms. This is because it takes many years to get to the disability stage and clinical trials cannot run that long
How can we diagnose MS?
- Dissemination in time and space (at least 2 attacks in 2 areas)
- MRI scan
- Spinal fluid test
- Evoked responses
Usually MS is diagnosed with MRI scan but in more difficult to diagnose cases, spinal fluid test is performed for IgG oligoclonal bands
What are risk factors for MS?
- Genetic: HLA-DR1501, having first degree relative with MS, being a female
- Environmental: EBV infection, dietary fatty acids, vitamin D deficiency, smoking
What is pathophysiology of MS?
It is not exactly understood but it is believed that auto- T and B cells activate in periphery and cross blood brain barrier, recognise myelin as foreign and drive the immune response, secreting cytokines, activating macrophages etc. leading to inflammation. It is believed that mainly CD4 T cells drive the immune response in MS because of molecular mimicry and epitope spreading, however, within active MS lesions there are CD8 T cells and macrophages found not CD4 T cells.
Why is it hard to make new therapies for MS?
- Pathogenesis of MS is not fully understood
- Difficult access to brain and spinal cord
- Most therapies used were developed for example for RA and then also adapted to be used in MS
- When to start therapy is tricky because some people will have benign and some disabling MS and you don’t know what their disease will be like
What are new and emerging therapies for MS?
- Steroids
- IFN-B
- Natalizumab
- Rituximab
- Fingolimod
- Alemtuzumab
- Ocrelizumab
- Opicinumab
Steroids?
They will lead to improvement in short term but in long term there will be no improvement
IFN-B?
Leads to decreased rick of relapse but does not fully stop the relapse
Natalizumab?
Inhibition of immune cell trafficking humanised into-alpha4 intern antibody. Stops crossing BBB. It shows 68% decrease in annual relapse and 64% decrease in disability progression. However, unfortunately it leads to PML (reactivation of JC virus within the brain). This is why it is given to patients with more aggressive forms of MS.
Rituximab?
anti-CD20, response of approximately 30%
Fingolimod?
a sphingosine-1-phosphate (S1P) agonist. It prevents CCR7 positive lymphocytes from exiting lymph nodes. It has significant clinical effects
Alemtuzumab?
anti-CD52, depletion of B and T cells
Ocrelizumab?
anti-CD20, B cell depletion
Opicinumab?
anti-LINGO-1. LINGO-1 is expressed on neurone and oligodendrocytes, it acts as negative regulator of oligodendrocytes differentiation. Blocking it promotes demyelination, neuroaxonal protection and repair. The problem is, opicinumab needs to cross BBB to work and most antibodies stay in the periphery
Autologous HSC transplantation (HSCT)?
Used as rescue following intense immunosuppression and in very advanced MS.
