MS Flashcards
Decribe the pathophysiology of MS
There is inflammation of the myelin sheath which leads to demyleination, which exposes the axon and leads to axonal degeneration in the CNS.
Although the cause of MS is unknown, what are some potential causes (etiology)? (4)
- Immunological
- Genetic
- Environmental
- Infectious
What are some symptoms of MS? (4)
- Numbness, tingling
- Vision problems
- Walking difficulty
- Brain fog
What are 3 unique symptoms of MS?
- Lhermitte’s sign
- Uhtohoff’s phenomena (heat intolerance)
- MS hug - feels a tightness around the midsection
What are the 4 types of MS?
- Relapsing-remitting
- Primary progressive
- Secondary progressive
- Clinically isolated syndrome (CIS)
What are the 2 most common types of MS?
- Relapsing-remitting
- Secondary progressive
Describe relapsing-remitting MS
Cycles of remitting where there are no symptoms then relapse where the symptoms flare up. Cannot predict when relapses occur, it can be years in between or multiple per year.
Describe secondary progressive MS
Eventually, after relapsing and remitting for a long period of time, the person goes on to develop this type of MS where the person does not return back to their baseline after a relapse. Axon damage can only be repaired so many times - the majority of RR MS will turn into this.
Describe primary progressive MS
Individuals who have progressive disease right from the start. Never cycles, just has symptoms all the time. Mostly men who are diagnosed with this
Describe clinically isolated syndrome (CIS)
Someone has an episode of clinical symptoms, it resolves, then they never go on for a 2nd attack
Men vs. Women: Who is more affected by MS?
Women ~3:1
Remember the “Natural History of MS” chart. What is happening with brain volume, axonal loss, disability, and inflammation over time?
- Brain volume - shrinks over time at a higher rate with MS compared to normal
- Axonal loss - linear line over time
- Disability - RR cycles see disability go up and down until it progresses to secondary progressive, where the line only goes up
- Inflammation - with active relapses, inflammation is high. Eventually the inflammation goes down with time because the axons are already damaged, at that point the patient is going to be in secondary progressive MS.
The Expanded Disability Status Scale (EDSS) is a way of trying to classify the level of disability from MS. What number is the magic threshold? Why?
6
At this point, no longer able to walk 100m without some kind of assistance. A lot of studies focus on EDSS <6 so there is not much evidence at 6+. Also, formularies only approve drugs for people <6
What are 3 non-pharmacological ways to manage MS?
- Exercise
- Diet (just eating healthy, no specific diet)
- Complementary/alternative medicine
What are 3 pharmacological ways to manage MS?
- Treat acute relapses
- Treat/manage symptoms
- Prevent disease activity and progression
Define an MS relapse
New or worsening symptoms, last greater than or equal to 24 hrs, absence of fever (infection) or other causes, and be separated from previous relapse by greater than or equal to 30 days
How are MS relapses managed? (3)
- High-dose corticosteroids
- Methylprednisone IV (500mg-1000mg x3-5 days) - may or may not have oral taper
- Oral option = 1250mg prednisone = 1000mg IVMP - Non-responders may consider plasma exchange
- Not all relapses are treated
The #1 reason why people leave the workforce due to MS is because of what symptom?
Fatigue
Primary fatigue is caused by MS. Why?
More energy needed b/c of damaged CNS
Secondary fatigue is caused b/c of living with MS. Why? (4)
- Depression
- Pain
- Spasms
- Sleep disturbances
What are 4 non-pharmacological ways to manage MS fatigue?
- OT/PT
- Sleep hygiene
- Avoid excessive heat
- Exercise and diet
What are 3 pharmacological ways to manage MS fatigue?
- Amantadine
- Modafinil
- Methylphenidate
What are the drawbacks of amantadine, modafinil, and methylphenidate in MS use?
- Amantadine - insomnia/sleep disturbances
- Modafinil - headache, insomnia, SJS - also fetal abnormalities
- MPH - insomnia, anxiety, dizziness
Also, in general none of these work particularly well, can try, but success varies
What are 3 non-pharmacological ways to manage poor gait in MS?
- OT/PT
- Bracing/walking aids
- Exercise
What is the drug used to treat poor gait in MS? How do we feel about it?
Fampridine - we don’t really like it. Increases walking speed is all, doesn’t help walk better.
What are the side effects of fampridine? (5)
- UTI
- Insomnia
- Headache
- Dizziness
- Seizure risk (dose-dependent)
(Pregnancy and breastfeeding risk unknown)
What are the 2 non-pharm management methods for MS spasticity?
- Exercise
- Stretching
What are 3 drugs used to treat MS spasticity?
- Baclofen - GI issues, drowsiness
- Gabapentin - drowsiness, nausea, blurred vision
- Botulinum toxins - pain, bruising
What cannabis med is indicated in MS?
Sativex
When is Sativex indicated in MS?
Indicated as add-on treatment of spasticity and pain in MS
What are the potential ADRs of Sativex? (6)
1. Long-term cognition effects
2. Fatigue
3. Dizziness
4. Blurred vision
5. Tachycardia
6. Falls
What are the problems with using cannabis in MS treatment?
- Lack of evidence for use in any other MS symptoms
- Poor quality studies (or none) - Challenges:
- Dosage/ratio unknown
- Type of cannabinoid(s) to use
- Varying quantity/quality if street cannabis
- Finding cannabis “naive” study participants
What are the goals of MS disease-modifying therapies (DMTs)? (4)
- Attempt to slow the inflammatory process
- Decrease frequency and severity of relapses
- Decrease lesions on MRI
- Reduce accumulation of neurological impairment and disability over time (?)
With DMTs, _______ is better
earlier
What are the 5 injectable DMT MS medications?
- Interferon beta-1b
- Glatiramer acetate
- Interferon beta-1a
- Peginterferon beta-1a
- Ofatumumab
What are the 7 oral DMT MS medications?
- Fingolimod
- Dimethyl fumarate
- Teriflunomide
- Cladribine
- Siponimod
- Ozanimod
- Ponesimod
What are the 4 infused DMT MS medications?
- Natalizumab
- Alemtuzumab
- Ocrelizumab
- Rituximab
Every DMT MS med is an immunosuppressant except which 2?
- Interferon-beta - immunomodulating agent
- Glatiramer acetate - immunostimulator
What is the MOA of dimethyl fumarate?
Complex mechanism involving decreased CD40 B-cell and T-cell activation
What is the MOA of teriflunomide?
Inhibits expansion of lymphocytes in response to a stimulus
What is the MOA of fingolimod, siponimod, ozanimod, and ponesimod?
Continuous supression of peripheral lymphocytes
What is the MOA of natalizumab?
Compartmentalized immunosuppressant in the CNS only
What is the MOA of ocrelizumab and ofatumumab?
Inhibition of CD20 lymphocytes
What is the MOA of alemtuzumab and cladribine?
Actions consistent with a mechanism involving immune reconstitution
What is progressive multifocal leukoencephalopathy (PML)? (3)
- Opportunistic infection by JC virus (40-90% of population is JCV+)
- Destroys the cells that produce myelin (clumsiness, weakness, changes to vision and speech)
- No cure - “fix” reason for immunosupression (stop meds, plasma exchange if needed)
What DMT MS meds is PML mostly seen with? (4)
1. Natalizumab
2. Dimethyl fumarate
3. Fingolimod
4. Ocrelizumab
How often is interferon-beta-1b dosed?
How about interferon-beta-1a (2 for this one)?
1b = Every other day (SC)
1a = Weekly (IM) or 3/week (SC)
How often is peginterferon beta-1a dosed?
Every 2 weeks (SC)
How often is glatiramer acetate dosed? (2 different ones depending on brand)
- SC once daily
- SC 3/week
What is the unique side effect of glatiramer acetate?
Lipoatrophy - breakdown of fat tissue under the skin, resulting in divots. Caused after a lot of SC injecting of the drug.
How is ofatumumab dosed? (different on week 1-3 than week 5)
Week 1-3 = SC weekly
Week 5 = SC every 4 weeks
How often is teriflunomide dosed?
Once daily
What is the unique side effect of teriflunomide to be aware of?
Potetnial teratogen for MALES AND FEMALES
How often is dimethyl fumarate dosed?
BID (titrate BID for 1 week)
What is the unique side effect of dimethyl fumarate?
Lymphopenia
How often is fingolimod, siponimod, ponesimod, and ozanimod dosed?
OD
What is an important ADR to be aware of for fingolimod, siponimod, ponesimod and ozanimod?
Potential teratogen - need a washout period (2-3 months for fing, pones and ozan, 10 days for sip)
Siponimod is indicated for which MS types specifically?
SPMS
RRMS
What needs to be monitored when starting fingolimod?
First dose cardiac observation for 6 hours
How is cladribine dosed?
Once daily for 4 or 5 consecutive days beginning of each of the first 2 months of Years 1 and 2 of treatment
What is the unique ADR of cladribine to be aware of?
Potential teratogen for MALES AND FEMALES
How often is natalizumab dosed?
Every 4 weeks
What is the unique ADR of natalizumab to be aware of?
PML (especially if used > 2 years)
How often is ocrelizumab dosed?
Infused at week 0 and week 2, then every 24 weeks
What are 3 unique ADRs of ocrelizumab to be aware of?
- Infusion reactions - pre-medicate with IVMP and antihistamine 30-60 mins prior to infusion
- PML potential
- Potential teratogen
What should be screened for before using ocrelizumab?
Hep B (avoid ocre if +)
Ocrelizumab is indicated for which MS types?
PPMS
RRMS
How often is alemtuzumab dosed? (two courses)
First course - 12mg IV OD for 5 consecutive days
Second course - 12mg IV OD for 3 consecutive days at month 12 from additional course
What are 2 common ADRs of alemtuzumab to be aware of?
- Infusion reactions (up to 2 hours after infusion finished)
- Monitoring of ADR (especially autoimmune ones for 4 years after last dose)
What are some patient-specific factors to consider when choosing a DMT med? (4)
- Age
- Sex
- Lifestyle factors
- Pregnancy/breastfeeding
What are disease-specific factors to consider when choosing a DMT med? (3)
- Disease course
- Prognosis
- Disease activity
Vaccines in MS patients. Yay or nay?
Depends:
1. Inactivated vaccines - generally safe
2. Live and live-attenuated - generally not recommended (esp if taking DMT)
3. Wait until 4-6 weeks after relapse onset
