De-myelinating diseases and MS

Question 1

What does demyelination refer to?

Answer 1

the preferential destruction of the myelin sheath of the axon

Question 2

What may cause the loss of myelin?

Answer 2

the breakdown of normal myelin or abnormal production of myelin

Question 3

Where is myelin derived in the CNS?

Answer 3

oligodendrocytes

Question 4

What is the purpose of myelin?

Answer 4

insulation to allow fast conductance along cell membrane

Question 5

What is primary demyelination?

Answer 5

where the primary pathology is demyelination - MS

Question 6

What is secondary demyelination?

Answer 6

demyelination due to another disease i.e. AIDS, axonal degeneration, sub-acute sclerosing panencephalitis (from measles)

Question 7

What toxins may produce demyelination?

Answer 7

cyanide, CO low grade poisoning, solvents

Question 8

Where is MS most common?

Answer 8

north and west

Question 9

What is the ratio of MS in males and females?

Answer 9

female 2:1

Question 10

What is the age of onset of MS?

Answer 10

any although childhood and 50+ is rare

Question 11

What is the definition of MS?

Answer 11

episodes of neurological deficit separated by time

Question 12

Why is MS so difficult to diagnose?

Answer 12

never on first time
second episode is usually different to first
lesions in brain are desiminated in time and space
several more common explanations exist for initial symptoms

Question 13

What are the genetic linkages in MS?

Answer 13

MHC linkages

monozygotic concordance rates

Question 14

Why is it suggested that MS could be caused by a virus?

Answer 14

patients with MS are more likely to have measles Ab in CSF

Question 15

What are the clinical features?

Answer 15

acute or insidious, variable distribution
relapsing and remitting flare ups
common manefestations include: visual disturbances, parasthesia, spasticity of extremities, speech disturbance

Question 16

What appears in MRI scans of MS?

Answer 16

looking for unmatched light areas (un-myelinated areas)

Question 17

What is a common site for demyelination in MS?

Answer 17

around ventricles and corpus callosum - sometimes occipital lobe

Question 18

What can be seen in lesions when cutting the surface of MS brain?

Answer 18

acute lesions are soft and pink

older chronic lesions are firm and pearly grey

Question 19

Where are lesions commonly seen?

Answer 19

cranial nerve II - occipital nerve, corpus callosum, brain stem and spinal cord

Question 20

What may MS lesions act as?

Answer 20

space occupying lesions

Question 21

What are the types of MS plaques?

Answer 21

acute active plaques
chronic inactive plaques
chronic active plaques
shadow plaques

Question 22

What are acute active plaques?

Answer 22

ongoing myelin breakdown

Question 23

What are chronic inactive plaques?

Answer 23

little/no myelin, astrocytic/gliosis prominent

Question 24

What are shadow plaques?

Answer 24

border between normal and affected matter not clearly defined

Question 25

What is the feature of acute MS?

Answer 25

plaques are yellow/brown with an ill defined edge that blends into surrounding why matter

Question 26

What is the feature of chronic MS?

Answer 26

plaques are grey brown lesions in white matter, classically situated around lateral ventricles

Question 27

What are the histological features of MS?

Answer 27

- demyelination with chronic plaques - inflammation - perivascular inflammation and oedema, -predominantly with lymphocytes - gliosis - prominent feature of plaques

Question 28

What are the potential reasons for MS?

Answer 28

sunlight higher sausage consumption vikings?

Question 29

How is Vitamin D metabolised by the liver?

Answer 29

hydroxylated on C25 and then C1 in kidney

Question 30

What is Vitamin D important in?

Answer 30

calcium balance in the immune response

Question 31

How has MHC been brought into MS?

Answer 31

class II mapped to the same haplotype in norther-european populations

Question 32

What was found in a canadian MS cohort?

Answer 32

confirmed linkage to HLA DRB1-15 although probably not that gene - closely related

Question 33

What was the proposed gene close to DRB1-15?

Answer 33

Vitamin D Response Element

Question 34

Why is it unlikely to be the HLA DRB1-15?

Answer 34

neg. patients still have MS, only 1 in 100 MS patients homozygous for it

Question 35

What is HLA DRB1-15/0101?

Answer 35

a promotor polymorphism which confers vitamin D sensitivity in HLA DRB1 expression

Question 36

Where else is high expression HLA DRB1-15/01 found?

Answer 36

other immune related diseases such as asthma, T1DM and ulcerative colitis

Question 37

What happened in 2011 with regards Vit D and MS?

Answer 37

Oxford researchers found a link between MS and the enzyme CYP27B1 - an enzyme important in regulating vitamin D levels in the body

Question 38

What did researchers at the McGill university in canada find?

Answer 38

a link between 4 SNP and the 25OHD levels. Higher levels of 25OHD are associated with a decreased level of MS. The alterations in these polymorphisms were across tens of thousands of northern populations all of european decent