De-myelinating diseases and MS Flashcards
What does demyelination refer to?
the preferential destruction of the myelin sheath of the axon
What may cause the loss of myelin?
the breakdown of normal myelin or abnormal production of myelin
Where is myelin derived in the CNS?
oligodendrocytes
What is the purpose of myelin?
insulation to allow fast conductance along cell membrane
What is primary demyelination?
where the primary pathology is demyelination - MS
What is secondary demyelination?
demyelination due to another disease i.e. AIDS, axonal degeneration, sub-acute sclerosing panencephalitis (from measles)
What toxins may produce demyelination?
cyanide, CO low grade poisoning, solvents
Where is MS most common?
north and west
What is the ratio of MS in males and females?
female 2:1
What is the age of onset of MS?
any although childhood and 50+ is rare
What is the definition of MS?
episodes of neurological deficit separated by time
Why is MS so difficult to diagnose?
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
What are the genetic linkages in MS?
MHC linkages
monozygotic concordance rates
Why is it suggested that MS could be caused by a virus?
patients with MS are more likely to have measles Ab in CSF
What are the clinical features?
acute or insidious, variable distribution
relapsing and remitting flare ups
common manefestations include: visual disturbances, parasthesia, spasticity of extremities, speech disturbance
What appears in MRI scans of MS?
looking for unmatched light areas (un-myelinated areas)
What is a common site for demyelination in MS?
around ventricles and corpus callosum - sometimes occipital lobe
What can be seen in lesions when cutting the surface of MS brain?
acute lesions are soft and pink
older chronic lesions are firm and pearly grey
Where are lesions commonly seen?
cranial nerve II - occipital nerve, corpus callosum, brain stem and spinal cord
What may MS lesions act as?
space occupying lesions
What are the types of MS plaques?
acute active plaques
chronic inactive plaques
chronic active plaques
shadow plaques
What are acute active plaques?
ongoing myelin breakdown
What are chronic inactive plaques?
little/no myelin, astrocytic/gliosis prominent
What are shadow plaques?
border between normal and affected matter not clearly defined
What is the feature of acute MS?
plaques are yellow/brown with an ill defined edge that blends into surrounding why matter
What is the feature of chronic MS?
plaques are grey brown lesions in white matter, classically situated around lateral ventricles
What are the histological features of MS?
- demyelination with chronic plaques
- inflammation - perivascular inflammation and oedema, -predominantly with lymphocytes
- gliosis - prominent feature of plaques
What are the potential reasons for MS?
sunlight
higher sausage consumption
vikings?
How is Vitamin D metabolised by the liver?
hydroxylated on C25 and then C1 in kidney
What is Vitamin D important in?
calcium balance in the immune response
How has MHC been brought into MS?
class II mapped to the same haplotype in norther-european populations
What was found in a canadian MS cohort?
confirmed linkage to HLA DRB1-15 although probably not that gene - closely related
What was the proposed gene close to DRB1-15?
Vitamin D Response Element
Why is it unlikely to be the HLA DRB1-15?
neg. patients still have MS, only 1 in 100 MS patients homozygous for it
What is HLA DRB1-15/0101?
a promotor polymorphism which confers vitamin D sensitivity in HLA DRB1 expression
Where else is high expression HLA DRB1-15/01 found?
other immune related diseases such as asthma, T1DM and ulcerative colitis
What happened in 2011 with regards Vit D and MS?
Oxford researchers found a link between MS and the enzyme CYP27B1 - an enzyme important in regulating vitamin D levels in the body
What did researchers at the McGill university in canada find?
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
