Multiple Sclerosis Flashcards
What are the 3 theories for MS cause?
infectious theory
molecular mimicry
autoimmune disease
what is the prevalence of MS in Canada?
1:500-1:1000 (rare disease)
What is the first step to the autoimmune response for MS?
APC picks up foreign protein and binds to naive T cell receptor (CD28)
What types of cells are APCs?
macrophages
monocytes
dendritic cells
What is the second step to the autoimmune response for MS?
T cell becomes pro-inflammatory TH1 cell
What is the third step to the autoimmune response for MS?
TH1 activates pro-inflammatory cytokines, leading to an imbalance between pro- and anti-inflammatory cytokines
what is the fourth step to the autoimmune response for MS?
blood becomes jam packed with TH1 cells and adhere to the blood brain barrier (BBB) through adhesion molecules and dock to BBB
What is the fifth step to the autoimmune response for MS?
TH1 cells are still producing inflammatory mediators and activates proteases, which loosen the integrity of BBB. mediators can now get to CNS
what is the sixth step to the autoimmune response for MS?
TH1 cells in CNS find the protein (in this case, myelin) that looks like the protein presented by the APC, and the cycle continues in the CNS, damaging the myelin
what is white matter disease?
when immune cells damage myelin
What are some contributing factors associated with MS?
race (caucasian) age (25 and 38?) sex infection injury genetics diet/sunshine geography (hot spots)
what is the typical age range of onset for MS?
30-40yrs
what gender is more affected by MS?
3 women: 1 men
How do genetics play a role in MS?
slightly higher predisposition, but is not hereditary
HLA-DR2 allele
What is typically examined to determine MS?
CSF
what do you look for in CSF to diagnose MS?
oligoclonal IgG bands
why are oligoclonal IgG bands significant in MS?
shows antibodies against oligodendrocytes (produce myelin) in over 95% of MS patients
How is an MRI helpful in MS diagnosis?
look for white spots (peri-ventricular lesions) to indicate the immune system attacking myelin
also look for neurological atrophy
What are the requirements for a definitive MS diagnosis according to the McDonald clinical criteria?
1) clinical attacks +/- MRI must show spreading in time and space
2) 2 clinical attacks where each attack lasted more than 24hrs, and are at least 30 days apart
Does not require an MRI
What is the clinical course of MS?
Pt shows first clinical attack (above clinical threshold) and seek med attention
Symptoms go away for a while
Demyelination during early course of disease usually stays under clinical threshold
As disease progresses, attacks and relapses stay above clinical threshold, leading to permanent damage
What are some MS induced symptoms? which is the most common? state why each occurs. (6pts)
1) Fatigue/weakness (most common) - electrical energy needed to move is leaking out of damage myelinated fibers
2) Bladder control problems - bladder retention (not getting excitatory signal) or bladder leaker (not getting inhibitory signal)
3) Neuropathic pain - antibodies eating at myelin
4) Cognitive defects - nerve cells responsible for short/long term memory die (could lead to optic neuritis or sexual dysfunction depending on affected nerve fibres)
5) Ataxia (like you’re drunk) - nerve fibres eroding
6) Depression - unable to do what you could before
How much of a disability decrease is there if treatment is started at diagnosis compared to no treatment at all?
50%
How much of a disability decrease is there if treatment is started part way through disease course compared to no treatment at all?
~33%
what are the 4 kinds of MS? Which is most common?
Relapsing-remitting MS - most common
secondary progressive MS
primary progressive MS
progressive relapsing MS
