Progressive Neuromuscular Disorders Pt 3: MG

Question 1

MG: Epidemiology

• Motor disorder characterized by fluctuating, localized skeletal muscle weakness & fatigue
• Acquired autoimmune dz

Answer 1

MG: Pathophysiology

Presents as 1 of 3 serotypes
▻ Anti-AChR
▻ MuSK
▻ Seronegative MG (SNMG)

Question 2

• An acquired autoimmune neuromuscular junction disorder, is c/b antibodies that are directed toward skeletal muscle nicotinic ACh receptors & muscle-specific kinase

Answer 2

• Is the most treatable of the chronic neurologic disorders

Question 3

• May be made worse by or induced by penicillamine (Cuprimine), used in the treatment of RA, but in most cases is idiopathic
• Course varies from mild, w/ocular sx’s of ptosis & diplopia, to severe cases w/generalized weakness & resp involvement

Answer 3

• Is c/b an autoimmune process in which antibodies attack acetylcholine (ACh) receptors, resulting in a dec # of ACh receptor (AChr) sites @ the neuromuscular junction
• ACh lvls are ok, just prevented from binding w/the receptor sites
• AChE acetylcholinesterase is the enzyme that normally terminates this activity

Question 4

Clinical Manifestations

• Ocular, bulbar, or generalized presentations
  > Diplopia (result of EOM weakness)
  > Ptosis (unilat or bilat)
• Often seek medical care for muscular weakness/fatigue

Answer 4

• Weakness in facial & throat muscles - bland facial expression, dysphonia
• Generalized weakness - affecting all extremities, intercostal muscles

Question 5

• The primary feature of MG is increasing weakness w/sustained muscle contraction
• Muscle weakness is greatest > exertion or @ the end of the day
• Purely a motor disorder w/no effect on sensation or coordination

Answer 5

• Reflexes normal
• Poor posture
• Bland expression
• Dysphonia
• Resp compromise

Question 6

___ ___ are the 1st to appear in about 16% of MG pts, & refer to symptomatology involving CN’s IX, X, XI, & XII that emerge from the medulla of the brainstem

Answer 6

Bulbar symptoms

Question 7

• Weakness of the facial muscles produces an expressionless face w/droopy eyelids, smoothed features, & a tendency for the mouth to hang open; smile → snarl d/t weakness
• Dysphagia & a nasal quality to speech

Answer 7

• Laryngeal involvement produces dysphonia (voice impairment) & inc the pt’s risk for choking & aspiration
• In severe cases, resp muscle weakness may occur, which may necessitate intubation & mechanical ventilation. Generalized weakness of intercostal muscles results in dec vital capacity & subseq resp failure

Question 8

• MG course varies w/remissions & exacerbations; clinical manifestations may progress slowly or quickly & fluctuate day to day; dz severity varies greatly

Answer 8

• Bulbar weakness - muscles of the jaw, face, palate, pharynx, larynx, & tongue - facial nerve, vagus, & hypoglossal nerves

Question 9

Exacerbations: Precipitating Factors

Rapid Development
▻ Infection
▻ Pregnancy
▻ Anesthesia

Answer 9

Temporary Increases
▻ Vaccination
▻ Menstruation
▻ Temp extremes

Question 10

Management

• Dx of MG is based upon clinical assessment as well as analysis of diagnostic tests
• Serological tests, EMG, & the edrophonium test (Tensilon test) aid in establishing a dx

Answer 10

• An assay for AChR antibodies is essential for making a dx of MG
• The AChR-binding antibodies are found in roughly 80% of pts w/generalized MG but only 55% of pts w/ocular MG

Question 11

?

Is a diagnostic tool used to evaluate neuromuscular transmission & measures muscle action potential >repeated nerve stimulations

Answer 11

Repetitive nerve stimulation

Question 12

EMG

• A decrementing response to repeated stimulation is indicative of muscle fatigue

Decrementing = a reduction in the response of the nervous system to repeated stimulation

Answer 12

• A chest CT scan is routinely performed to eval the pt w/MG for thymoma; is more sensitive than plain x-rays
  > Surgical approach to MG management is thymectomy

Question 13

?

Is a medication that is a reversible inhibitor of AChE

Improves neuromuscular transmission by inc ACh stimulation of the AChRs that are avail

Answer 13

Pyridostigmine

Question 14

?

Is a shorter-acting AChE inhibitor

Answer 14

Neostigmine

Question 15

Immunosuppressant rx’s to treat MG -

prednisone
Imuran (azathioprine)
Cellcept (mycophenolate mofetil)
Cytoxin (cyclophosphamide)

Answer 15

Addl therapies

▻ IVIG
▻ Plasmapheresis

Question 16

Edrophonium aka Tensilon Test

Positive

▻ Inc in muscle strength; improvement in facial weakness & ptosis

Answer 16

Negative

! No changes observed >incremental doses
! NOTE - that >incremental doses
Increases in ACh cause buildup in parasympathetic ANS as well

Result - bronchospasm, bradycardia, & diarrhea r/t inc in muscarinic receptors

ATROPINE - muscarinic BLOCKER & therefore the antidote

Question 17

• Edrophonium or Tensilon is a short-acting, but very RAPID-acting IV anticholinesterase med
• Temporarily improves neuromuscular transmission by inhibiting AChE [acetylcholine enzyme]; will lead to inc muscle strength in pts w/MG

Answer 17

• Acetylcholine inhibitor Tensilon (edrophonium chloride) given in small doses IV
• Inhibitor stops the breakdown of acetylcholine thereby inc avail @ the neuromuscular junction
• Facial weakness, ptosis, is resolved for about 5 min - then test is (+) for MG

Question 18

• Is also used to test for undermedication (cholinergic crisis 2° to overdose of anticholinesterase drug)

Answer 18

• Clinical manifestations are facial muscle fasciculations, sweating, excessive salivation, & constricted pupils
• In this case, the Tensilon doesn’t improve muscle weakness but actually inc the weakness

Question 19

?

Is on hand to counteract when used diagnostically

s/e’s - bradycardia, sweating, cramping

Answer 19

Atropine

Question 20

! When this test is being conducted, is essential that IV atropine sulfate be present

! IV atropine sulfate is the antidote; it counteracts any severe cholinergic reactions (cardiac dysrhythmias or abd cramping)

Question 21

Acetylcholinesterase inhibitor test

• A short-acting anticholinesterase like edrophonium chloride (Tensilon) or neostigmine methylsulfate (Prostigmin) is given via IV to the pt
• These rx’s inhibit cholinesterase (an enzyme that breaks down ACh in the neuromuscular junction)
• This allows for more ACh to bind to the remaining ACh receptors

Answer 21

• Pt is assessed for improvement in muscular strength & also given an IV infusion of a placebo & assessed
• Improvement in muscle strength w/the med is a strong indicator that pt has MG

Question 22

• If edrophonium chloride (Tensilon) is used the effects of the med wear off within 3-5 min of the inj
• Neostigmine methylsulfate (Prostigmin) has a longer duration 1-2 hrs which allows for a better analysis

Answer 22

• Dosing: 2 mg of edrophonium is admin IV as a test dose
  Monitoring HR - bradycardia or v-fib may develop

Question 23

• Follow-up
  > After observing for about 2 min, if no clear response develops up to 8 addl mg of edrophonium is injected

Answer 23

• A double-blind protocol w/a saline inj as placebo has been advocated
• Testing should be performed w/pt free of all cholinesterase-inhibitor meds

Question 24

Cholinergic s/e’s of edrophonium

• May incl inc salivation & lacrimation
• Mild sweating, flushing, urgency & perioral fasciculations

! Atropine should be readily avail to reverse effects of edrophonium in case of hemodynamic instability

> extra precautions esp important in elderly pts

Answer 24

Positive test

• Most myasthenic muscles respond in 30-45 sec >inj
• Improvement in strength that may persist for up to 5 min
• Requires objective improvement in muscle strength
  ! Subjective or minor responses, like reduction of a sense of fatigue, shouldn’t be over-interpreted

Question 25

? During sustained, forced eyelid closure pt is unable to bury the eyelashes and, after 30 sec, is unable to keep the lids fully closed

Answer 25

"Peek" sign

Question 26

Medications/Goals 1. Provide symptomatic treatment to inc the avail of ACh 2. Immunosuppression 3. Alter immunopathogenic mechanisms 4. Immunomodulatory effect w/thymectomy 2 meds commonly used - * Mestinon (Pyridostigmine) * Prostigmine (Neostigmine) = muscarine stimulation

Answer 26

! Important safety note = pts MUST get these meds @ the prescribed times to provide optimal muscle strength Also important to adhere to med schedule(s) followed @ home e.g., often taking Pyridostigmine 30-60 min before meals to minimize difficulty w/chewing & swallowing

Question 27

Muscarinic Effects * Inc GI motility * Inc GI secretion * N/V * Abd cramping * HR slowed * BP dec * Pupil constriction

Answer 27

* Inc glandular secretions * Excessive salivation * Sweating, flushing * Blurred vision * Inc bronchial secretions; bronchospasms **Antidote: Atropine**

Question 28

Treatment ▻ Plasmapheresis - Treatment in exacerbations - Plasma removed - antibodies believed to cause MG removed & re-infused - Daily x5

Answer 28

▻ IV IgG - 2nd line treatment for MG; supplies antidote antibodies 1. Given as acute therapy (as a rapidly acting but relatively short-lasting treatment for an autoimmune dz that is itself short-lasting (days to wks) or is currently flaring [e.g., given for GBS] 2. For chronic autoimmune dz (given approx once every 1-3 mos over time for long-term immunosuppression) ▻ Min s/e's incl HA, local skin rxn @ infusion site, & flu-like sx's

Question 29

Treatment ▻ Thymectomy = surgical removal of the thymus gland can produce antigen-specific immunosuppression & result in clinical improvement > May take up to 3 yrs for pt to benefit from this d/t long life of circulating T cells

Answer 29

Diet ▻ Professional eval for chewing and swallowing ▻ May need thickened liquids or even enteral feedings

Question 30

Contraindicated Medication Anything that blocks muscle activity, such as magnesium, calcium channel blockers, & any meds like antacids & laxatives that contain Mg ⋫ anesthetics ⋫ anti-dysrhythmics - calcium channel blockers, Mg ⋫ some abx ⋫ quinine ⋫ antipsychotics ⋫ barbiturates ⋫ opioids

Answer 30

⋫ sedative-hypnotics ⋫ cathartics ⋫ diuretics ⋫ thyroid preparations ⋫ tranquilizers ⋫ Novocain (advise DMD of MG) ⋫ muscle relaxants

Question 31

? Occurs d/t excessive anticholinesterase medication & is potentially secondary to the pt taking too much of the prescribed MG med

Answer 31

Cholinergic crisis

Question 32

? Is an exacerbation of MG weakness that provokes an acute ep of resp failure that is often c/b a resp infection from viral or bacterial agents ⋫ Inc in weakness ⋫ Inability to clear secretions, swallow, or breathe ! Improves temporarily w/Tensilon

Answer 32

Myasthenic crisis

Question 33

Myasthenia Crisis ⋫ Resp, muscles, bulbar weakness ⋫ Myasthenia sx: weakness, incontinence, fatigue ⋫ HTN; inc HR ⋫ Acute treatment strategies; more meds!

Answer 33

Cholinergic Crisis ⋫ Muscle twitching to the point of resp weakness - provide adequate ventilatory support ⋫ Cholinergic sx: hypersecretions, inc resp secretions, n/v, hypermotility (cramping) ⋫ Hypotension ⋫ Improve w/atropine (1 mg IV may be needed)

Question 34

Education ✓ Precipitating factors ✓ Med management ✓ Strategies to conserve energy

Answer 34

✓ Measures to minimize risk for aspiration ✓ Emergency care