B6.044 Multiple Sclerosis

Question 1

initial cell type damaged in RRMS

Answer 1

oligodendrocyte (CNS)

Question 2

function of oligodendrocyte

Answer 2

form myelin
sends out processes to axon and wraps around it
-up to 50 processes

Question 3

what mediates pathology in RRMS

Answer 3

t cells (major), b cells, macrophages, antibodies, complement

Question 4

what are some mechanisms that may contribute to development of pathology in patients with progressive MS?

Answer 4

less immune mediated than RRMS (doesn’t respond to disease modifying therapies)
some mechanisms:
-axonal degradation
-altered blood flow
-dysfunctional mitochondria
-increased production of ROS from increased energy expenditure via increased Na+ channels in demyelinated sections of axons
-glutamate excitotoxicity
-iron accumulation (catalyst for ROS and RNS)

Question 5

why are MS relapses reduced during 3rd trimester of pregnancy?

Answer 5

placenta produces estrogens (estriol)

Question 6

how does estrogen likely reduce relapses in MS?

Answer 6

lymphocyte modulation (as this is the primary driver of RRMS)

Question 7

how might estrogen affect overall pathogenesis of MS

Answer 7

anti oxidant
lymphocyte modulation
neuroprotection
remyelination

Question 8

how could you test effectiveness of estrogen treatments in RRMS

Answer 8

estrogen + DMT vs DMT alone in RRMS

Question 9

what are concerns with use of mitoxantrone in secondary progressive MS

Answer 9

cardiomyopathy

leukemia

Question 10

how do you limit adverse events associated with mitoxantrone

Answer 10

evaluate LVEF

limit lifetime exposure