B7-092 Multiple Sclerosis Flashcards
most common demyelinating disease affecting the central nervous system
multiple sclerosis
CNS myelin comes from
oligodentrites
PNS myelin comes from
Schwann cells
what kind of deficit pattern does MS cause?
multifocal
discrete areas of transient inflammatory deyelination
MS is thought to result from […] response to antigens in myelin
autoimmune
damaged myelin disrupts […]
saltatory conduction
(slows/stops propagation at nodes of Ranier)
people living in what areas of the world have the highest risk of getting MS?
temperate zones (northern US, Europe, Canada)
when migrating from a high-risk to low-risk area, chances of getting MS decrease if migration occurred before what age?
20
late infection with […] provides a 3-fold increased risk of developing MS
EBV
shares epitopes with myelin basic protein
EBV
theories of geographical distribution of MS [3]
hygiene hypothesis
molecular mimicry (EBV)
low levels of vitamin D
signs and symptoms of MS are dependent on
location of lesion
common symptomatic locations of MS plaques [3]
optic nerve
brain stem/cerebellum
spinal cord
asymptomatic lesions commonly occur where?
cerebral hemispheres
diagnostic criteria for MS
two or more lesion of the CNS separated in space and time without other explanation
(can use MacDonald criteria to account for radiologic findings)
supportive findings of MS [3]
multifocal white matter lesions on MRI
CSF oligoclonal bands
CSF pleocytosis <50 cells
inflammation around penetrating venules that run perpendicular to the ventricles
dawson fingers
many people have T2 hyperintensities on MRI but without [….], they should not be diagnosed with MS
clinical abnormalities
what would you expect to seen on CSF analysis in an MS patient
oligoclonal bands
elevated IgG
elevated IgG index
maybe elevated protein
maybe elevated WBC
85% of MS patients have what type?
relapsing-remitting MS
(50% of these patients develop secondary progressive MS)
15% of MS patients have what type?
primary progressive MS
symptoms develop over hours or days
can worsen for several weeks
slowly subside over several weeks or months
relapsing remitting MS
recurrence of previously experienced symptoms not related to current inflammation
often seen in the setting of systemic infection (UTI, pneumonia)
psedoexacerbation
no steroids
gradual progression
spinal myelopathy is common
progressive MS
progressive course following a relapsing remitting course
secondary progressive MS
first presentation of neurological symptoms from inflammatory demyelination
clinically isolated syndrome
(often a retrospective diagnosis, can be monofocal or multifocal)
used to guide prognosis of MS
expanded disability status scale (EDSS)
poor prognostic factors for MS [7]
male
older age
multifocal
onset with motor, cerebellar, bladder/bowel symptoms
high frequency of relapses
severe relapses
high lesion load on MRI
used to shorten the duration of relapse
high dose steroids
(not used in pseudo exacerbation)
treatment for MS related fatigue
methylphenidate
treatment for MS spasticity
baclofen (oral or pump)
MOA: suppression of gamma interferon
beta interferon
MOA: competes with MBP for antigen presentation
glatiramer acetate
MOA: inhibits pyrimidine synthesis inhibiting clonal expansion lymphocytes
teriflunomide
MOA: decreases lymphocyte proliferation through Nrf2 pathway
dimethyl fumurate
MOA: sphingosine-1-phosphate receptor modulator trapping lymphocytes in lymph nodes
flingolimod/siponimod
MOA: anti-alpha 4 integrin antibody preventing lymphocytes from crossing BBB
natalizumab
MOA: purine nucleoside analog cytotoxic to lymphocytes
cladribine
MOA: anti CD52 antibody causing prolonged lymphocyte depletion
alemtuzumab
MOA: anti CD20 antibody depleting B cells
rituximab/ocrelizumab
side effects: beta interferon
flu like symptoms
side effects: glatiramer acetate
injection site reaction
side effects: teriflunomide
liver dysfunction, hair loss
side effects: dimethyl fumurate
lymphopenia, liver dysfunction
side effects: fingolimod/siponimod
first dose bradycardia
herpes virus infections
rare PML
side effects natalizumab
higher risk of PML
rebound
side effects: cladribine
liver toxicity
risk of infection
rare PML
side effects: alemtuzumab
risk of autoimmunity
infections
side effects: rituximab
infections
malignancy
rare PML
interferes with antigen presentation
glatiramer acetate
prevent clonal expansion [2]
teriflunomide
dimethyl fumurate
prevent the movement of lymphocytes from the lymph node into circulation
fingolimod
siponimod
prevent the movement of lymphocytes from the circulation to brain
natalizumab
(rebound phenomenon if suddenly stopped since all the lymphocytes can suddenly move in)
kill lymphocytes [3]
cladribine
alemtuzumab
rituximab
main function of myelin
enable saltatory conduction
[…] loss is a pathological feature of MS
axon
are DMARDs helpful for secondary progressive MS?
no
what happens to the action potentials where the disease has caused demyelination?
the action potential conduction is slower and can even be blocked when the signal are moving faster (increased temperature)
pathology of what parts of the nervous system can result from MS? [4]
axonal transection
brain atrophy
demyelination
neuronal degeneration
radiographic hallmark of acute MS lesion
gadolinium T1 enhancing lesion due to breakdown of the BBB
immunotherapy is effective for what type of MS?
relapsing-remitting
what MRI finding are you less likely to see in progressive forms of MS?
gadolinium T1 enhancement (hallmark of acute lesions)
treatment for secondary progressive MS?
supportive -can use steroids to shorten duration and provide symptom management
DMARDs are not effective
red flags for psuedo exacerbation [2]
recent infection
symptoms they’ve had before
90% of MS patients will have […] in the CSF
oligoclonal bands
what feature of MS accounts for reduced processing speeds
demyelination
main pathological feature that leads to demyelination
perivenular inflammation
T2 hyperintensities in the corpus callosum emanting from the ventricles
Dawson’s fingers
a few scattered white matter lesions are normal in people over what age?
50
does not confer risk of MS
symptoms continuously worsen from onset of disease
no history of clear cut attacks
primary progressive MS
A progression of RR-MS characterized by continuous worsening of neurological function that occurs independently of exacerbation events
secondary progressive MS
Exacerbations occur.
Symptoms remit almost completely between exacerbations.
relapsing-remitting MS
how long can an MS relapse last?
average 6-8 weeks
Note: this is from Dr. Google, I just wanted an idea of when to consider progression, please don’t stake your test score on it haha
concordance rate of MS in monozygous twins
30%
represent antibodies generated within the CNS
oligoclonal bands
concordance rate of MS in dizygotic twins
7%
concordance rate of MS in siblings
about 3%
