Multiple Sclerosis Flashcards
What type of disease is MS?
Chronic disease of the CNS
- Effects the brain and the spinal cord
Describe the prevalence of MS?
2.8 million people affected worldwide
- Not the most prevalent disease but arguably one of the most vtraumatic diseases
When is MS commonly diagnosed? Why is this a concern?
Commonly diagnosed between the ages of 20-40 years old
Diagnosed when 20 years old - Live many years with it and be disabling
What is the concern of MS in younger adults?
Most common form of non-traumatic disability in young adults
Describe the difference in MS between males and females? Severity differences?
Women are affected approx. 3:1
Males tend to have a more severe disease course than females
Describe the pathophtsiology of MS?
Myselin sheath gets damaged
Axon gets exposed and open for damage –> get damage and see complications of MS
Something in the immune system that causes the body to attck the myelin
Something that happens to the myelin and myselin calls in immune system –> Immune system attacks the myelin sheath
Describe the distribution of MS? Therapy?
High in North America –> Canada and the USA, western side of Europe
MS incidence higher in northern climates; speculated that vit D deficiency may contribute
Individuals often supplemented higher with vitamin D - likely no benefit
What are two hypothesis that can describe the variation in distribution of MS?
Due to vitamin D levels –> Due to the lack of vitamin D (nothing found definitively)
Do not have acess to diagnostics; not picking it up to diagnose in those areas –> More prominent worries
Describe the etyiology of MS. Examples?
Immunological:
- Myelin sheath is attcking itself do know their is an immune component
Genetic
- First degree relative with MS - Higher risk but not purely genetic
Environmental
- Sunlight, gestation time (born in May higher risk of MS), agriculture (pesticides, gas wells, agriculture)
Infectious
-Infectious: Epstein Barr Virus
- Followed veterans for decades, 32x more likely to develop MS if you had the Epstein
Describe the overall summary of the etyiology of MS
Something you have in genetic makeup and something you are exposed too –> Leads to MS
What are some symptoms of MS? Most common side effects?
Lhermitte’s Sign
-Uhtohoff’s Phenomena
-“MS Hug”
Big Ones –> Nu8mbness, tingling, fatigue, and pain, vision problems, weakness
Describe the cognitive sx that may occur in MS?
Brain fog, difficulty thinking
What is the most common early symptom of MS?
Vision problems common early on
Can’t see out of one eye or both eyes
What is a common commorbidity in MS that makes symptom presentation complicated?
Wheelchair is common; a lot of these sx are invisble
Do not present with outward sx
Are the symptoms an individual experiences with MS the same in primary disease and in a relapse? Prognosis?
Sx can change in different relapses
Someone presents with first clinical sx as(optic neuritis) –> Better prognosis
Define the following:
-Lhermitte’s Sign
-Uhtohoff’s Phenomena
-“MS Hug”
Lhermittes –> Tuck head down –> Shooting pain downwards
Uhtohoffs –> Heat intolerance – sx get worse and cannot handle the heat
MS Hug –> Tightness around mid-section, sensation around mid-section
What is an issue with the symptoms of MS?
Can write off these sx – Do not always think of MS
Not uncommon to see someone get a diagnosis and say they have had these sx for a long time until a sx ike vision loss makes them go to ER
Describe the different types of MS
Describe relapses of MS in regards to symptoms and timing
Cannot predict when relapses will occur
Cannot predict what will happen in a relapse
Define Relapsing-Remitting MS. Prognosis?
Patients have discrete attacks over days to weeks with some recovery over weeks to months
Function us relatively stable between attacks
- 30% of cases will will convert to Secondary progressive MS (SPMS) after 10 yrs
Define secondary progressive MS.Medications?
Progression of disability may occur in the abscence of active MS or with continued active MS (after 10 years, 30% of RRMS convert to SPMS)
- Medications can delay/possibly prevent the conversion of RRMS to SPMS
- Clinicians may treat SPMS with DMT’s
Define primary progressive MS. Therapy?
- Around 10% of cases
Characterized by steady deterioration of fucntion from onset
- Ocrelizumab is the only officially indicated PPMS medication
Define clinically isolated syndrome (CIS). Medications?
A single dymylenating event event and not fully diagnostic criteria of MS
Starting meds can delay, but NOT likely prevent, conversion to MS
Describe the prevalence of the different types of MS
85%-90% will have relapsing-remitting and then eventually leads to secondary progressive (hard to predict but on average 15-20 years)
–> Cannot predict what the disease will do
Body can repair the myselin a bit, cannot repair the axon
10-15% are primary progressive –> Right from the start have progressive
- Continual increasing disability over time
- Men tend to have the progressive phenotype
What is a clinically isolated syndrome example?
Clinically Isolated Syndrome
E.g. loss vision but never had a second attack or waiting for clinical attack
What use to be required for a diagnosis of MS? Is this still the recommendation?
Use to need a second clinically attack in 2 years to be diagnosed with MS
Now:
- If have MS will send them to imaging right away to start Disease modifiable therapy
Regarding diagnosis of MS, what are some critical points?
Lesions that corespond to the sx you are having
Example: Lesion on the optic nerve
Enhancing Lesion –> Active inflammation –> Often have clinical sx but not always
identifying MS earlier now rather than later
MRI earlier now
Describe the natural history of MS (IMPORTANT) Issue?
Over time, see axonal loss
Remitiiing-Relapsing course turns into secondary progressive
Brain volume shrinking
Relapses –> Inflammation is high
- Over time as the dx progressqes and moves into the more progressive state,inflammation decreases over time
Majority of drugs available are doing something to limit the inflammation
- Drugs do not work as no inflammation there to work on
Progresisve phase –> less inflammation than relapsing-remitting
- limited drug options as the drugs work on inflammation
How can the progression of MS be measured?
Expanded Disability Status Scale
What is the purpose of the EDSS? Relavence as pharamcists?
A way of trying to classify and cetagorize the level of disability someone has
6 is the threshold: Dx has progressed to a level to where they can cannot mobilize (walk independtly over 100 metres)
Only know how the drugs work in those who are in 6 or 5.5 or less
Is MS a major cause of death in individuals with the disease?
Majority of people do not die from MS
Often not the cause of death in the majority of people
What are some limitations of the EDSS?
Only know how the drugs work in those who are in 6 or 5.5 or less
Limits what we have for people
- RCT’s only with EDSS of less than 6, drug coverage only lists those drugs for those with that score
Focuses on mobility; a lot of other sx in MS
- Does not capture cognition or even upper limb mobility
- If in wheel chair and lower limbs affected, may have strong upper body strength
What are some non-pharamcological strategies for the management of MS?
Exercise (major one)
Diet
Complementary / alternative medicine:
a) Hyper-baric chambers
b) Bee-sting therapy
c) Liberation Therapy (CSSVI)
Describe exercise as a non-pharmacological management strategy of MS
Exercise is a major one
Not the case to just rest, exercise
Not high intensity: Just something to get moving
Describe diet as a non-pharamcological strategy for the management of MS
Diets : No evidence to suggest one diet over another
Eat a well balanced diet
Describe Liberation Therapy ? Efficacy?
Lberation therapy (CSSVI)
MS is due to buildup of iron in the brain and due to the vein running down the brain is occluded
Stent or open the vein up
Pt’s supposebly did well
People travelled to oyher countries
Stents often only seen in arteries; stents in veins likely to move and some people died
RCT’s –> No benefit to this therapy; even inventor turned back
Could have been placebo effect; expensive
- Risk > Benefit
What are some of the pharmacological strategies for the management of MS?
Treat acute relapses
Treat / manage symptoms (Can treat them the same way as we would in someone who does not have MS )
Prevent disease activity and progression
Define a relapse in MS
New or worsening symptoms
Last ≥24 hrs in length
Absence of fever (infection) or other causes,
Seperated from previous relapse by ≥30 days
Describe the therapy for relapse management in MS
High-dose corticosteroids
Methylprednisolone 500mg – 1000mg IV x 3-5 days
May or may not have oral taper
Oral options
1250mg prednisone = 1000mg IVMP
Non-responders – may consider plasma exchange
Not all relapses are treated
What is the most common therapy for a relapse of MS? Is IV more effective than oral?
Treat with high dose corticosteroids
Usually IV methylprednisone 3 to 5 days
- May see a taper (physician preference) and may not see a taper done
Oral works just as well and just as effective –> No more adverse effects
When treating a relapse of MS with corticosteroids, when are certain routes of administration used?
Oral: More convenience, cheaper
IV over oral: Can’t swallow, a lot of tablets for someone, comes down to convenience
Describe two critical factors regarding steroid usage in the management of a MS relapse
1) May speed recovery but does not alter the course of the disease
2) Oral steroids have similar efficacy to IV
Are all relapses of MS treated? If not, when do we treat MS relapses?
No
If involving optic nerves, will often treat that
If numbness in hands and legs, may not look at treating that
What can be done for the management of an MS relapse if an individual does not respond to high dose corticosteroids?
If hit with high dose CS’s and no/minimal response:
Plasma exchange –> Swap out the plasma and reintroduction of plasma with replacement fluid - Removal of natibodies from the blood
Very rarely done
What are some comorbidities that can occur in MS? How are they treated?
Bladder dysfunction
-Constipation, Diarrhea,
Bowel dysfunction
- Urgency
Depression
Fatigue
Pain
Sexual dysfunction
Spasticity
Tremor
Vertigo / dizziness
Walking / gait
Individuals who have comorbidities and need to look at these separately and address them
- Do not treat them any differently than a person without MS
Describe the fatigue of MS
Not just super tired
Fatigue is severe enough to disrupt function and cannot be in the work force anymore
> 90% of patients experience
Describe the causes of fatigue in the different forms of MS
What are some non-pharamcological strategies for management of fatigue in MS?
OT / PT
Sleep hygiene
Avoid excessive heat
Exercise and diet
Describe the role of occupational therapy in MS
Occupational therapy has a huge role to play in people with MS managing daily activities
- Fatigue and cognition issues: How can they manage the activities of daily living
Describe the pharmacological therapies for fatigue in MS
Amantadine
Modafinil
Methylphenidate
Describe the pharmacological options for management of fatigue in MS and its dose, adverse effects and efficiacy
Do not work well
Try them but may not have success
Medications not superior to placebo with more adverse effects and not recommended
Describe the prevalence of gait disturbances in MS
> 90% of patients
Non-pharmacological Management of Gait Disturbances in MS
OT / PT
Bracing / walking aids
Exercise
What are some pharamcological option(s) for the managemnt of gait disturbances in MS? Dose, risks, coverage?
Fampridine
- Indication for MS to increase walking speed –> increased speed of 25 foot walk
This drug allowed people to walk faster
People want to walk better and not faster
EDS criteria –> if really wanna try something
Describe the prevalence of spasticity in MS
Up to 70% of patients wille xperience
Describe non-pharamcological treatment of spasticity in MS
Exercise
Stretching
Phsyio-therapists are able to provide exercise to work at home
Describe the pharamcological options for muscle spasticity in MS
Botox can help with spasticity –> 1-2 weeks to have effect
Baclofen is the most common for this one
What is anotehr pharamcologicla agent that can. be used for pain and spasticity management in MS?
Indicated as an add on treatment
–> Baclofen and not working
What are the potential adverse drug reactions from Sativex? Most common?
Describe the efficacy/evidence for cannabis use in MS
Lack of evidence for use in any other MS symptoms
Poor quality studies (or none)
What are some challenges regarding determining efficacy of cannabis in MS?
Dosage/ratio unknown
Type of cannabinoid(s) to use
Varying quality/quantity if street cannabis
Finding cannabis “naïve” study participants
What is the main therapy for disease managemnt in MS?
Disease-modifying therapies (DMT)
Describe the efficacy/effects of DMT’s in MS
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 (?)
When should DMT be initiated in MS?
Earlier Treatment is better
Older –> Unlikely to see a reduction in long term progression of disability
- Earlier is better –> Time is brain
What do DMT’s attempt to do overall in MS?
Slow down the inflammatory process and stop the dmage from occurring
First DMT
Very first drug for MS Betaseron –> Canada in 1996
Could only do tx with CS for the acute things occurring
Describe the indication of DMT for the types of MS? Exception?
All for relapsing and remitting
Ocrelizumab –> Relapse-remitting and primary progressive
Siponimod - Secondary Progressive MS
Describe the available DMT agents
Describe the mechanism of action of DMT
Immunomodulators: Tinker with the immune system; make changes to it
Immunosuprresnats –> Not same as chemotx or anti-rejection drugs
- Suppresses the immune system but not completely wiping it out
- No need for isolation
Describe the DMT, WHO classification and effect on immune system
What is PML?
Progressive multifocal leukoencephalopathy
Describe what PML is?
Rare, but often fatal
Opportunistic infection by JC virus (john Cunningham)
40-90% of population is JCV+
–> Doesn’t cause sx usually and many have had it
Infection in the brain and now immune system cannot get into the brain
Destroys the cells that produce myelin
–>Clumsiness, weakness, changes to vision and speech (similar to MS relapse, concern with natalizumab)
Describe the treatment for PML?
No cure – “fix” reason for immune suppression
Stop meds (plasma exchange if needed)
Symptomatic care, stop the drug they are one, wait and see
What drugs is PML associated with? Risk factors?
Seen with natalizumab (major), dimethyl fumarate, fingolimod, ocrelizumab
Increased risk: JCV+, prior immunosuppressant, >2 years use (natalizumab) (risk increased)
Is JCV + a contraindication to use of these agents?
Can stay on drug if they are JCV +
- Can pick up PML on an MRI early on
- More monitoring required
- Can stay on after 2 years and know they are JCV+
If risk is higher not an automatic reason to come off of it
Describe Interferon beat-1B
Injectable
Describe interferon beta-1a
Injectable
Describe peginteferon beta-1a
Describe glatiramer acetate
Injectable
Describe ofatatunumab
Injectable
Describe teriflunomaide
Oral
Describe dimethyl fumurate
Oral
Describe fingolimod
Oral
Describe siponomod
Oral
Describe ozanimod and ponesimod
Oral
Describe cladbridine
Oral
Disappointment – did not have long term effect that was expected
Infections with this one are critical
Describe natalizumab
Infusion
Describe ocrelizumab
Infusion
Describe alemtuzumab
Infusion
Define immune reconstitution therapy. Which DMT’s are immune reconstitution therapies?
Immune reconstitution therapy (IRT) is a treatment that involves temporarily suppressing the immune system to allow it to renew itself
e.g. Alemtuzumab, Cladibrine
Describe rituximab
Used off-label in MS
Indicated in non-Hodgkin’s lymphomas, RA
Anti-CD20 MAB
Potential for PML
SK dosing:
500-1000mg at Week 0, 2, and then q 6/12
Listed on SK formulary as of Nov 1, 2022
Saskatchewan drug plan put it on formulary even though its off label
Significantly cheaper and works just as well without a lot of side effects
Dosed every 6 months
Can be used in children
–> Fongolimid is the only drug with an indication in children (10 and up)
Similar adverse effects to ocrelizumab
Used for secondary progressive, persistent progressive, relapsing-remitting
Describe the efficcay of the available DMT therapies. Is this how we select a DMT for a patient based solely on efficacy?
Alemtuzumab –> Most efficacy
Line of no difference: 1.0
Comparable to placebo – all better than placebo
Way less relapses of alemtuzumab
Some drugs work way better than another – do not pick drugs just on how well they work, other factors to be considered
How a DMT be chosen for a patient?
describe induction vs escalation techniques in the intiation of a DMT in MS
Induction – Hit them with that high efficacy drugs, then put them on lower efficacy to maintain
Escalation – Start at least effective then move upwards
NOW –> Offered the higher efficacy ones now and maintained on them
Describe the risk of preganancy and MS?
Genetic component but not an absolute risk to pass it on to children
Risk of symptomatic treatments in pregnancy not affected by MS – condition you are treated
Describe the DMT therapies and usage in preganncy
Which DMT”s are teratogens?
Teriflunomide
Fingolimod
Siponimod
Ozanimod/Ponesimod
Clabridine
Ocrelizumab
Describe tx of MS in preganncy
ANti-CD20 therapies can be used in women wishing to get pregnant
Current evidence suggests that women can safely start trying to concieve without delay following ant–CD20 therapy
Women wil relapsing-remitting MS are at incr4eased risk in the post-partum period, and so prompt treatment post-partum is reocmmended
Where women wish to breastfeedm they should be encourage to do so alongside therapy resumption where their tretament of choice is an anti-CD20 monoclonal antibody
Describe vaccinations and MS
Inactivated vaccines = generally safe (e.g. flu shot)
Live and live-attenuated = generally not recommended (esp if taking DMT)
How long should be waited after a relapse for an individual to get a vaccine?
Wait until 4-6 weeks after relapse onset
Complex patients on complex drugs…so consider referring
If travelling as example and a vaccine not sur eof (yellow-fever as example) – REFER
If starting a new DMT, when should an indivdiual get a vaccination?
Need vaccination before starting medication –> 4-6 weeks before starting medication
Describe specific DMT agents and Covid Vaccines
COVID vaccines – “boosters” for anti-CD20 DMTs (Ocreluzamab, Rituximab, ateluminuzab)
Immune system not building up enough of a response
Describe Saskatchewan coverage of DMT in MS
Pharmacists cannot apply for EDS for MS DMT
Specific panel that meets and discusses the cases – specific criteria to start a new drug and maintain a new drug
Mandate: Insuring that they meet the criteria for the drug
