What is MS?
Autoimmune inflammatory demyelinating disease of the CNS, causing progressive neurodegeneration
There are various sub-types of MS; list 5 of these.
1) Acute MS (Marburg's Disease)
2) Relapsing-remitting
3) Progressive relapsing
4) Secondary progressive (no replases)
5) Primary progressive (later onset)
6) Benign (mild w/ no conversion)
Which of these is the most common and what its average duration?
Relapsing-remitting, accounts for roughly 80%. Duration roughly 10 years. 80% in turn of these will go on to secondary progression
What is the essential lesion in MS?
A demyelinated plaque; identified at any site where myelin sheaths are present
Why are symptoms and the disease course so varied between individuals with MS?
The amount and location of damage to the nervous system is different in each person with MS; particular symptoms may be caused by damage in different parts of a system
True or false: extensive lesions in MS often follow the lateral ventricles
True
True or false: lesions are uncommon at the substantia nigra
False; they are common here, and also at many levels of the pyramidal tracts, leading to severe motor symptoms. Also common in pons.
True or false: lesions in MS may occur at any point along the spinal cord axis
True
Why might spinal cord lesions often appear shrunken?
Due to loss of axons as well as myelin sheaths
True or false: lesions in the spinal cord affect only the white matter and follow a predictable pattern
False; they can affect both grey and white matter, and do not follow a pattern.
True or false: perivascular immune cell infiltration is observed in MS
True - CD4/8+ T-cells and CD20 B-cells are seen.
True or false: the demyelination in MS is largely B-cell mediated
False; it is largely macrophage-mediated
How can actively demyelinating lesions be identified?
By the presence of macrophages containing myelin debris
True or false: inflammatory mediators release free radicals and cytotoxic mediators that create a reversible block of electrical signals as well as demyelination
True; this results in transient symptoms. Immunomodulatory therapies aim to stop these effects
List 3 mechanisms of inflammatory neuronal dysfunction observed in MS
1) Release of free radicals by peripheral immune cells/activated microglia
2) Glutamate released by microglia; excitotoxicity
3) Cytotoxic cytokine release by immune cells/microglia (TNF, IL-1B, IFN-gamma)
4) Mitochondrial dysfunction
What is the difference between the borders of chronic silent lesions and active lesions?
Chronic silent lesions have well-defined borders; those of active lesions are more ragged
True or false: demyelinated lesions are characterised by a lack of oligodendrocytes but relative preservation of axons
True
True or false: inflammation leads to more long-term symptoms than demyelination
False; rather it causes the transient reversible symptoms, with demyelination causing long-term symptoms
True or false; MRI lesion load and rate of appearance of new lesions correlates well with clinical progression
False; it correlates poorly
Disease progression correlates well with atrophy of what?
Grey matter atrophy
True or false: grey matter demyelination is extensive and often covers a greater area than white matter demyelination
True
True or false: cortical demyelination is associated with meningeal inflammation
True
What structures are found in the meninges of MS cases with more active and shorter progression?
Tertiary lymphoid-like structures