Myasthenia Gravis (2)

Question 1

In which patients is MG more common in?

Answer 1

Females under the age of 50 (peaks in 20s/30s)
-but overall its a rare disease
-over 50 it is more common in males

Question 2

Muscle contraction physiology background

Answer 2

Depolarization of cell - influx of sodium/calcium causes action potential to travel

travels to end of nerve and causes release of acetylcholine which binds to the acetylcholine receptors on post synaptic nerve causing contraction

Question 3

MG pathophysiology

Answer 3

Normal: acetylcholine binds to acetylcholine receptors, binding enhanced by muscle specific tyrosine kinase (MuSK)

MG: Decreased amount of acetylcholine receptors due to…

1. production of anti-acetylcholine receptor antibodies
   -these bind to the receptor and block ACh from binding
2. MuSK receptor antibodies which will attack and destroy the receptors as well

when action potential reaches nerve terminal and ACh is released, has nowhere to bind, contraction does not occur - manifesting in muscle fatigue

Question 4

Which other organ is involved in the pathophysiology of MG?

Answer 4

Thymus
-thymus abnormality occurs in 75% of patients with MG
-65% have a hyperplastic thymus (inflamed)
-10-15% have thymomas - tumors on the thymus

Question 5

How is MG diagnosed? (4)

Answer 5

1. Antibodies
   -blood test, looks for the presence of anti-AchR antibodies or presence of MuSK antibodies
2. Electrodiagnostic testing
   -repetitive nerve stimulation, records action potentials, in MG there is >10% reduction
3. Tensilon Test
   -give patients IV edrophonium - this is an anticholinesterase… giving this gives ACh more time to bind, so if improvement in muscle strength is seen with this that is how it’s diagnosed
4. Ice pack test
   -used in patient when Tensilon test is contraindicated - put ice pack over eye for 2-5 minutes, improvement in ptosis indicates likely MG

Question 6

Clinical presentation./course of disease

Answer 6

Muscle fatigue - biggest factor in all patients

Usually improvement following rest/sleep

Chronic condition - remissions and exacerbations can occur

Unrelated acute infections may worsen symptoms and cause crisis

Extraocular muscles (EOMs) are affected first

Question 7

Common symptoms of MG (4)

Answer 7

Diplopia (double vision)
Ptosis (droopy eyelids)
Difficulty chewing
Difficulty swallowing

Question 8

Goals of treatment for MG

Answer 8

It cannot be cured
Goal is to bring relief of symptoms, improve QOL, and prevent MG crisis

Question 9

What is the first line treatment for MG?

Answer 9

Pyridostigmine

Question 10

Pyridostigmine MOA

Answer 10

anticholinesterase (inhibits cholinesterase, the enzyme that breaks down acetylcholine - allowing there to be more time for Ach to try to bind to the receptors)

Question 11

Pyridostigmine administration considerations

Answer 11

-take 60 mg up to 3 times daily for max strength - should be adjusted based on patient specifics (give highest dose at the time of day when they are most symptomatic)

-effect peaks at 45 minutes
so, patients with difficulty chewing/swallowing should take it prior to meals (so that it has effect when they eat)

Overdose can increase weakness

Question 12

Pyridostigmine ADRs

Answer 12

Cholinergic side effects: SLUD
Salivation
Lacrimation (tears)
Urination
Defecation

The reason we see these is because Ach effects the Parasympathetic nervous system
-it has an effect on smooth muscles, blood vessels, and slows heart rate
and this drug inhibits those parasympathetic effects

Question 13

Corticosteroid use for MG and dosing/duration considerations

Answer 13

In some cases, anticholinesterases may not work - prednisone or prednisolone can be used
-start at low dose and increase in small increments
-keep at goal dose for 1 month, then start to taper down
-total duration should be 2-4 months

Question 14

Which 2 immunosuppressant agents can be used for MG?

Answer 14

Azathioprine
-as monotherapy or added to steroids

Cyclosporine
-reserved for those unresponsive to azathioprine

Question 15

What are 3 secondary immunosuppressant agents that can be used for MG?

Answer 15

Mycophenolate mofetil (MMF)
-remember this is contraindicated in pregnancy and this disease is more common in females of child bearing age

Tacrolimus

Cyclophosphamide
-last line - if intolerant to steroids, azathioprine, cyclosporine, and MMF

Question 16

Thymectomy is indicated for which patients?

Answer 16

Patients with thymomas (tumors on thymus)
(removal of thymus = thymectomy)

Question 17

Myasthenic crisis

Answer 17

This is a medical emergency
Occurs due to weakening of respiratory muscles which causes difficulty breathing
-intubation needed

Often confused with cholinergic crisis - first stop anticholinesterase medications when this occurs

2 treatment options:
1. Intravenous Immunoglobulin (IVIG)
-used short term for severe exacerbations (or prior to surgery)
-ADRs: volume overload, renal failure, aseptic meningitis

2. Plasmapheresis
   -short term for severe exacerbations (or prior to surgery)
   -antibodies are removed from blood, blood is returned to patients
   -5 exchanges administered over 10-14 days

Question 18

What is the most common cause of myasthenic crisis

Answer 18

Concurrent infection

Question 19

Which medications have a BBW for worsening MG?

Answer 19

Quinolone antibiotics
(ciprofloxacin, levofloxacin, etc.)
-important to remember these are contraindicated in patient with MG