Multiple Sclerosis Flashcards
What is the combination of diseases that lead to the onset of damage to the CNS and thus multiple sclerosis?
Dyemyelinating disease
Autoimmune disease
Inflammatory disease
What increase the risk of MS?
Family link increase by 40% 2-3 fold increase in women Caucasian/northern hemisphere Triggering infection Vitamin D deficiency
What is the cycle that causes MS?
Immune cells attack myelin -> Inflammatory response -> Myelin debris accumulation in lesions -> Immune cells attack myelin
What are the different types of MS?
Relapsing Remitting MS (RRMS)
Secondary progressive MS (SPMS)
Primary progressive MS (PPMS)
Progressive Relapsing MS (PRMS)
What is RRMS?
This is most common type, 85% of cases.
Discrete attacks that evolve over days to weeks, then decree of recovery over weeks to months
In between attacks, no worsening of neurological function
What is SPMS?
Initial relapses, gradual neurological deterioration, not accute attacks
What is PPMS?
Steady functional decline from onset
No relapses
What is PRMS?
Steady functional decline from onset, with later superimposed acute attacks
When can PPMS and PRMS be distinguished?
When the relapses occur in PRMS?
What is typical in relapsing remitting MS and how is this shown in MRI movies?
Lesions
Reveal bright red spots, brain lesions that grow and shrunk and disappear over 12 months
Each video runs through 24 scans of a different cross-section, taken at weekly or monthly intervals
What is the autoimmune cascade of MS lesions?
Look at Diagram pg 96
1) Microglia and/or macrophages respond to myelin based protein as antigen
2) Local immune response intiated, reease of cytokines and pro-inflammatory mediators and cytotoxic agents
3) Antigen presenting cells recruit T and B cells from circulation
4) Full immune response
5) Microglia and astrocytes isolate lesion via reactive gliosis (glial scar around lesion)
6) Anti-inflammatory T cells terminate response
7) Episode resolves until next flare up
Why is demyelination a problem?
Myelin sheath generated by oligodendrocytes, and they coat long axons in CNS and PNS, that is essential for fast, directional action potential propagation, to relay signals across neurones.
Loss of myelin = disrupted AP propagation and degneration of axons
Action potential generation process
1) Depolarisation open Na+ channels -> Na+ floods into cell down electrochemical gradient -> depolarises the membrane even more
2) K+ channels open -> K+ floods out of cell down its electrochemical gradient -> Na+ channels inactivate preventing further depolarisation -> repolarises the membrane
3) K+ channels inactive -> Ion pumps and transporters use energy from ATP or counter-transport to re-establish resting membrane conditions
What is saltatory confuctance and what effect does MS have on this?
Mechanism for increasing speed and reliability of conduction; by glial cells coating axons in myeling sheets.
Ion channels are clustered at unmyelinated Nodes of Ranvier
Action potential jumps between nodes
In MS: demyelination =failure of conductance, leaks due to lack of myelin shealths and action potential will no longer propogate
What can MS disrupt?
Sensory input
Infomation processing
Signal transduction
Motor output
