Multiple Sclerosis Flashcards
What is the conventional/pathological definition of MS?
Inflammatory disease of the CNS characterised by demyelination and variable degrees of axonal loss and gliosis.
What is the clinical/pretheoretical definition of MS?
You need to have 2 episodes of inflammation/dysfunction in the CNS separated by time and place (ie 2 or more white matter structures), with no other aetiology
What is the typical MS pathology?
Perivenular inflammation
Demyelination
Gliosis: astrocytes which lead to fibrosis in brain
Variable axonal loss
How many people in the UK have MS?
120,000 (~50% are undiagnosed so there may be more)
When is MS onset?
20s-40s
What is the sex ratio like for MS?
Women are more likely to get it than men and then number of women getting it is increasing
Why is there an increasing MS incidence in women?
Increase in fat consumption Epstein-Barr virus Smoking (accelerates MS) Parity : fewer kids Sunlight exposure (women using more sunscreen)
How does pregnancy affect MS?
The relapse rate drops during the 2nd and 3rd trimester and rebounds post-partum
This is probably due to pregnancy-induced immunosuppression
What is MS distribution like around the world and why?
There is less MS near the equator bc:
increased sunlight
possibly a virus
What is uhthoff’s phenomenon?
When it gets hotter, MS symptoms worsen
What proof is there that MS is related to environmental changes?
If you emigrate before 15 you take up the incidence of the place you moved to
Babies born in which month are more likely to get MS and why?
April (winter pregnancy) - reversed in southern hemisphere
Possibly bc mother gets less vitamin D
What proof is there that vit D is important in MS?
Danish newborn screening: Higher vitD had 50% chance less of MS
Finnish Maternal Vit D: Low vit D in early pregnancy x2 risk for kid
Monozygotic twins - lower vitD = higher MS risk
May also be related to be immobility
What amount of vit D is advised for MS?
5000 units/day
What is the contribution of genetics to MS?
Increased familial risk proportional to degree of relatedness
Many genes are affecting MS
Genetics support an immunological basis to the aetiology of MS
What are most genes affecting MS related to (hint: a protein)?
HLA
Others affect Vit D
What proof is there that the human microbiome has an affect in MS?
The EAE rodent model (injected with CNS tissue):
Germ free mice –> don’t get MS
With germs –> get MS
What are HERVS?
Human endogenous retroviruses
parts of our genomes that code for retroviruses
What role do HERVS have in MS?
Higher measure of HERV-W family envelope protein in MS
Found evidence of viral capsule in CNS in MS - areas of inflammation surrounding it
but antiviral vaccines have not helped MS
What are the courses of MS?
relapsing and then remitting
Primary-progressive: continue to worsen without remitting from the start
Secondary progressive: go from relapsing and remitting and go on to be progressive in 40-50s
Progressive-relapse
Which is the most common course of MS?
relapsing remitting
What is the connection between secondary and primary progressive
Probably the same thing except in primary the relapses were not noticed
TRUE or FALSE?
If we do an MRI on an MS patient we see the same number of ‘bright spots’ on MRI as the number of relapses that patient has had.
FALSE
We see more bright spots
What are the 3 main areas MS affects?
optic nerve
Brain stem
Spine
What are the optic nerve symptoms of MS?
pain on eye movement
Losing the ability to distinguish colour
blurry central vision
What are the spinal symptoms of MS?
Weakness
Numbness and tingling
Sphincter dysfunction
What are the brain stem symptoms of MS?
Double vision (diplopia) Ataxia
What are the miscellaneous symptoms of MS?
Fatigue Pain Cognitive Decline Depression/anxiety Spasticity
What happens to MS patients’ employment over time?
Half of patients are unemployed within 10 yrs of diagnosis
What score is used to tell how disabled a person is?
EDSS (0=good, 10= dead)
Up to what EDSS scores are people with MS employable?
3 (up till this point they have no problems)
What happens to an MS patient’s life span?
It decreases by 8-12 yrs
What can we see on MS MRI scans?
T2 scan shows area of white (hyperintensitiy) - in white matter of ventricles
How can we tell if a bright spot on an MRI is new?
Use gadolinium (shows where the BBB broke down recently by leaking through)
shows if BBB was affected in the last 6-8 weeks
What tests do you give a suspected MS patient?
blood tests to check for inflammation
Visual evoked potential
MRI
how do we treat acute relapses?
steroids - reduce the duration of relapses
Why are steroids not so good to give patients?
They dont influence outcome
Can’t give them more than 2 times a year
side effects: avascular necrosis
What happens in avascular necrosis and how do we treat it?
infarct of the femour head
needs hip replacement
If an MS patient has sensory loss, weakness in both legs, and difficulty walking, what part of the CNS to we MRI?
cervical and thoracic areas
NOT brain bc then it would be asymmetrial
What is natalizumab?
A MAb which prevents inflammatory cells from entering the brain through the BBB
What are the side effects of natalizumab?
Pogressive multifocal leukal encephalopathy
What causes PML?
JC virus causing progressive brain inflammation
What increases risk of PML with natalizumab?
Previous immunosuppression
What happens when you take someone with PML off of natalizumab?
Immune reconstitution: all immune cells go to brain (bad!)
Name some disease modifying MS treatments
Beta-interferon Glatiramer Teriflunomide Dimethyl Fumerate Alemtuzumab
What effect does beta-interferon have on MS?
Slowed progression was shown
Halved symptoms and death
Very expensive (but worth it!)
How do disease modifying MS treatments work?
reduce number of relapses –> slow progression
What are the consequences of delaying MS treatment?
Relapses
Cerebral atrophy (shrinkage)
Earlier onset of progression
Dementia
Death
