Diseases of White Matter

Question 1

what is secondary loss of myelin?

Answer 1

when an axon dies, the surrounding myelin will die off as well

Question 2

what are the two types of demyelinating disorders?

Answer 2

leukodystrophies (dysmyelinating)

myelinoclastic group

Question 3

what is the pathogenesis of a leukodystrophy?

Answer 3

metabolic derangement affecting proteins that keep myelin alive

Question 4

what is the pathogenesis of a myelinoclastic process?

Answer 4

myelin is under attack

Question 5

are axons spared in demyelinating disorders?

Answer 5

yes

Question 6

what are the four most common leukodystrophies?

Answer 6

Krabbe, adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy

Question 7

what is the age of onset, inheritance pattern and protein defect in Krabbe disease?

Answer 7

infants and children, AR, galactocerebroside-beta-galactosidase

Question 8

what is the age of onset, inheritance pattern and protein defect in adrenoleukodystrophy and adrenomyeloneuropathy?

Answer 8

young/old, XLR (except infantile form of ALD, which is AR), ABCD1

Question 9

what is the age of onset, inheritance pattern and protein affected for metachormatic leukodystrophy?

Answer 9

all ages, AR, arylsulftase A

Question 10

describe the characteristic gross pathological changes in leukodystrophies

Answer 10

widespread and confluent demyelination with sparing of the U-fibers (low metabolic turnover)

Question 11

how are most leukodystrophies diagnosed?

Answer 11

via biochemical analysis

Question 12

what are the two types of myelinoclastic disorders that we need to know?

Answer 12

multiple sclerosis

parainfectious disorders

Question 13

what is the epidemiology of MS?

Answer 13

attacks young to middle aged, 2:1 F:M

Question 14

lesions of MS have what character?

Answer 14

distributed over time and space

Question 15

attacks of demyelination follow what time course?

Answer 15

they are remitting and relapsing (i.e. they come and go)

Question 16

what are the gross characteristics of MS plaques?

Answer 16

they are sharply demarcated, asymmetrical, widespread

Question 17

histologically what cells are present in MS plaques acutely?

Answer 17

lymphocytes and histiocytes in the perivenular region

Question 18

histologically what cells are present in MS plaques chronically?

Answer 18

astrocytes, hence they are gliotic

Question 19

what is understood about the pathogenesis of MS?

Answer 19

CD4 cells react against myelin basic protein; macrophages are responsible for the actual demyelination
CD8 cells are present

Question 20

what are the genetic factors in play with MS?

Answer 20

HLA-DR2

also, first degree relatives are at 15 fold greater risk

Question 21

what lab tests are available for MS?

Answer 21

MBP in the CSF (not major basic protein, myelin basic protein)
IgG in CSF
oligoclonal bands of Ig in CSF

Question 22

what are parainfectious disorders?

Answer 22

autoimmune response against an infectious agent pathologically targets myelin

Question 23

what is the histological change present in parainfectious disorders?

Answer 23

perivenular demyelination with chronic inflammation