Multiple Sclerosis Flashcards
Is MS just a demyelinating disease?
No. It also causes axonal loss.
Two viruses associated with MS?
EBV (which is responsible for most of the bad things in the world)
HHV-6
Two bacterial pathogens with a less robustly proven association with MS?
Chlamydia pneumoniae
Mycoplasma
What is the age range for peak incidence of MS?
The slides give two different ranges:
Most cases begin in 15 - 45 year olds.
Peak incidence is at 25 - 35 years old.
What is the female to male ratio of people with MS?
2:1 (mostly women, but definitely lots of men get it)
What’s interesting about the geographic distribution of MS?
It’s most prevalent in temperate latitudes. (why that is, we don’t know)
What is the strongest genetic risk factor for MS? Why is this important?
HLA-DRB1501 (an MHC II molecule)
That’s consistent with this being an autoimmune disease.
Are environmental triggers important in people who are genetically predisposed to MS?
Yep. (Concordance rate between identical twins is only 30%)
Most common form of MS?
RRMS - relapsing remitting MS
9 typical signs/symptoms of MS?
Focal UMN weakness Focal numbness / parethesias (tingling, often in band-like pattern) Optic neuritis Dysarthria (speech difficulties) Lhermite's Uhthoff's Dyscoordination / poor balance Spastic bladder Spasticity, esp in legs.
What is Lhermitte’s phenomenon? What does it indicate?
Flexion of neck causes parathesias. Indicates that nerves are demyelinated.
What is Uhthoff’s phenomenon?
Symptoms of MS get worse when patient is overheated. Demyelinated nerves’ conduction speeds steeply drop when temperature increases.
4 clinical patterns of MS? Briefly describe each.
RRMS - relapsing remitting MS - symptoms intermittent, with return to baseline.
SPMS - secondary progressive MS - deficits that happen in intermittent attacks tend to persist.
PPMS - primary progressive MS - gradual decline in function.
PRMS - progressive relapsing MS - gradual decline in function accompanied by intermittent attacks that remit.
Without treatment, how many years does it take for 50% of MS patients to need help walking? Has this improved with treatment?
About 15 years. We’re not sure how effect disease-modifying therapy is at delaying progression - it has only existed since 1993.
Why are MS lesions gadolinium enhancing on T1 MRI?
Immune infiltration / inflammatory cytokines disrupt the BBB.
Is MS thought to begin in the CNS?
No, it’s thought to be triggered by some immunogenic something in the periphery.
3 pathological results of the immune inflammation in MS?
Demyelination
Axonal loss
Brain atrophy
2 histological features of MS?
Lipid(myelin)-laden macrophages.
Perivascular lymphocytosis.
To MS lesions respect vascular territory?
Nope.
What does FLAIR-weighted MRI show you about MS?
Area of demyelination.
What are “black holes” on a T1 MRI in MS?
Areas of axon loss.
What are 4 potential self antigens involved in MS? (probably only 1 is important to know, though)
Myelin basic protein (most important)
Proteolipid protein
Myelin oligodendrocyte glycoprotein
Myelin associated glycoprotein
What’s key to diagnosing MS?
There must be distinct lesions separated in space and time. (can be clinically, or as old / new lesions seen on an MRI)
What are “Dawson’s fingers”? What do they indicate?
On a FLAIR weighted MRI, ovoid hyperintense regions oriented perpendicular to the ventricles. They indicate demyelination (in perivenular areas).
Other than clinical examination and MRI, what are 2 tests used to diagnose MS?
Evoked potentials (eg. light in eye -> occipital cortex) LP for lymphocytes and increased IgG
What 4 demyelinating diseases must you exclude when diagnosing MS?
Lyme
Sarcoid
B12 deficiency
HIV
What two tracts in the CNS does MS have a particular affinity for? Signs associated with lesion there?
Optic nerve -> optic neuritis.
MLF (medial longitudinal fasciculus) -> INO (internuclear opthalmoplegia - can’t adduct in horizontal gaze)
Where does an MS lesion causing bilateral symptoms of both weakness and parathesias probably localize?
Spinal cord (would be hard to do all that with one lesion in the brain).
Do all gadolinium-enhancing lesions cause symptoms?
Nope. Only about 1 in 5-10 do.
What characteristic must the elevated CSF IgG levels have in order to be consistent with MS?
Must be oligoclonal. Monoclonality would suggest lymphoma.
Treatment of moderate/severe acute MS flare-ups? 3 things.
IV steroids
Physical therapy
Symptomatic treatment
Name a few different mechanisms of disease modifying therapies for MS?
Type 1 interferon (most common?)
Myelin basic protein analog (soak up auto-Abs)
Anti-alpha 4 integrin antibody (block migration)
Trap T cells in lymph nodes
Block lymphocyte proliferation
Block cell proliferation in general
