Multiple Sclerosis (Ferguson) Flashcards
MS is a disease which results in neurologic dysfunction due to the degradation of ______ (fatty substance which surrounds the nerve axon allowing for signal to be transmitted from one location in the CNS to another with greater speed and efficiency)
- _______ process causes ____ areas of demyelination with associated inflammation that slows down or completely interrupts transmission of neural activity
Myelin
- Autoimmune (AB against viral antigen that looks like myelin?), focal (doesn’t occur everywhere at the same time)
MS can present at nearly any age but is most typically seen in ________
- Affects greater than _____ patients in the US alone, ~10-20/100,000 in the population
Young 20-40 year olds
- 1,000,000 patients
Risk Factors of MS:
- Clear associations with both ____ and ____
- Individuals in _____ climates develop MS at a strikingly high frequency - probable link to what?
- _____ carry a 2-3x risk of development
- Those with first degree relatives carry a ____x risk of development - or if other autoimmune diseases present
- Environment, Genetics
- Northern - vitamin D deficiency
- Females
- 20-40x risk
What clinically isolated syndrome?
- One of the most common presentations of demyelinating disease
- Typically presents with complaints of progressive vision loss over days - “dirty dishwater” or “dense screen”, color desaturation
- Mild pain with extraocular movements - inflammation near tendinous insertion points
- Usually optic disc swelling can be seen after the first few days of symptoms
- Afferent pupillary defect
Tx?
Optic Neuritis
Tx. 1 gram of IV methyl-prednisone for 3-5 days
What can be seen on the Brain MRI that suggests a CIS?
Enhancing of the R optic nerve - optic neuritis
- BBB breakdown - contrast seeps into
What is the criteria for MS called?
- Required minimal lesion burden
- Lesions separated in space and time!
McDonald Criteria
If a patient does not fulfill the McDonald criteria for MS - only 1 lesion on MRI, no additional lesions –> what is his risk of developing MS in the future? Should he be started on disease modifying therapy at this time?
Some clinically isolated syndromes:
- Optic neuritis
- Brainstem syndrome
- Spinal cord syndrome
- Multifocal
Risk of development - ~20% in the future
- Should NOT be started on disease modifying therapies
What is the name of this MRI finding - pathognomonic for MS?
Dawson’s fingers - demyelinating plaques through the corpus callosum (T2 hyperintensities)
What additional work-up can be done to further establish a diagnosis of MS, but are not diagnostic in isolation?
- What are the abnormalities one can find with this? (3)
(Can be absent very early on; however, in general 95-97% will have + findings)
LP, CSF analysis!
- Oligoclonal banding, abnormally high IgG/albumin ratio, elevated IgG synthesis rate
What are the long term therapeutic goals for MS?
- _____ clinical relapses
- _____ new and enlarging lesions on MRI
- _____ disability accumulation
- Achieve a tolerable ___ profile
- ____ for long term safety
- Reduce
- Reduce
- Reduce
- side effect
- Monitor
What are the traditional agents, “Platform therapies,” for long term management of MS?
- ______
- 1-a IM weekly (Avonex)
- 1-a sc tiw (Rebif)
- 1-b sq eod (Betaseron/Extavia)
- Side effects?
- ______
- sq daily and tiw (Copaxone)
- Side effects?
- Beta interferon
- Malaise, headache, fevers, myalgias, elevated liver enzymes
- Glatiramer acetate
- Injection site reactions, lipoatrophy, injection related chest tightness, dyspnea, flushing
- ******Can use for pregnant patients
FYI - For traditional therapies, “platform agents”
Advantages
- Proven efficacy
- Excellent long-term safety
- Limited monitoring requirements
- New therapy regimens: double dose glatiramer, pegalated IFN-beta
Disadvantages
- Injectable administration
- Incomplete eficacy
- Adherence concerns
- Neutralizing antibody formation to interferon
- Bothersome side effects
Traditional Therapies:
- ______ dose interferon (____) is more efficacious than _____ dose interferon (____)
- ______ shows comparable efficacy to high dose interferon (Rebif)
- _____ compelling evidence to combine high dose interferon with glatiramer
- High (Rebif), Low (Avonex)
- Glatiramer (Copaxone)
- NO!
What are some oral therapies for the long term management of MS?
- ?
- ?
- ?
- Fingolimod (Gilenya)
- Teriflunomide (Augbagio)
- Dimethyl fumarate (Tecfidera)
What medication?
- MOA: sequesters lymphocytes in the lympnodes
- superior to low dose interferon
- can cause significant bradycardia, hypotension in some
- first dose must be monitored in office/hospital because of this
- Common side effects - HA, diarrhea, cough, lymphopenia
Fingolimod (Gilenya)
What clinically isolated syndrome?
- demyelination of the spinal cord
- Results in a wide range of neurological symptoms - hemi-sided weakness, sensory deficit, bowel-bladder dysfunction or some combination of all of the above depending on the location and size of the plaque
Steroids, PT, urology, bowel regimen
Transverse Myelitis
Diagnosis?
- Relapsing inflammatory demyelinating disease that most commonly affects optic nerves and the spinal cord, leading to sudden vision loss or weakness in one or both eyes, and loss of sensation and bladder function
- Does NOT typically cause the same volume of subcortical white matter lesions
- Can be assessed by ordering serum ________. How does this work?
- Treated with ______. (antibody binds to CD20, widely expressed on B cells, from early pre-B cells to later in differentiation; causes apoptosis)
Neuromyleitis Optica (Devic’s disease)
- NMO IgG antibody. Antibody to aquaporin 4 chloride channel
- Tx. Rituxumab (Rituxan)
