Myasthenia gravis

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Background

  • Autoantibody degradation, dysfunction, and blockade of acetylcholine receptor at the NMJ[1]
  • Thymus is abnormal in 75% of patients
    • Thymectomy resolves or improves symptoms in most patients, especially those with a thymoma
  • No sensory, reflex, pupillary, or cerebellar deficits

Drugs that may unmask or worsen myasthenia gravis

  • Antibiotics (Aminoglycosides, Clinda, Fluoroquinolones, Vancomyacin)[2]
  • Cardiovasular drugs (Beta blockers, procainamide)
  • Other (Botox, quinines, Magnesium)

Drugs Usually well-tolerated in myasthenia gravis but occasionally associated with an exacerbation

  • Local anesthetics
  • Antibiotics (Tetracycline/doxy, Macrolides, Flagyl, nitrofurantoin)
  • Anticonvulsants (carbamazepine, ethosuximide, gabapentin, phenobarbital, phenytoin)
  • Butyrophenones (haldol)
  • Phenothiazines (chlorpromazine/prochlorpromazine)
  • Calcium Channel Blockers
  • Steroids
  • Opthalmic drugs (betaxolol/timolol/proparacaine)
  • Other (Iodinated contrast agent)

Clinical Features

  • Muscle weakness
    • Proximal extremities
    • Neck extensors
    • Facial/bulbar muscles (dysphagia, dysarthria, dysphonia)
  • Ocular weakness
    • Ptosis
    • Diplopia
    • CN III, IV, or VI weakness

Differential Diagnosis

Drug-induced myasthenia

Weakness

Evaluation

  • Symptoms worsen with repetitive use / as the day progresses[4]
    • Ice Pack Test- should improve symptoms temporarily (usually ptosis; high specificity)
      • Place ice-pack on eyes for 2 mins, if ptosis decreases by ≥2mm the test is positive
  • Acetylcholine receptor antibodies (AcHR-Ab). Positive in 80-90% of generalized MG and 40-55% in Ocular MG.

Myasthenic versus cholinergic crisis

Flaccid paralysis resulting from cholinergic crisis can be distinguished from myasthenia gravis by the use of the drug edrophonium, which worsens the paralysis caused by cholinergic crisis, but strengthens the muscle in the case of myasthenia gravis. (Edrophonium is an cholinesterase inhibitor hence increases the concentration of acetylcholine present).

  • Myasthenic Crisis
    • Respiratory failure is feared complication
    • Much more common
    • Due to medication non-adherence, infection, surgery, tapering of immunosuppressants, meds
  • Cholinergic Crisis
    • Excessive anticholinesterase medication may cause weakness and cholinergic symptoms
    • Rarely if ever seen with dose limitation of pyridostigmine to less than 120mg q3hr
    • If on usual dose of meds assume exacerbation due to MG even with cholinergic side effects
  • Edrophonium (Tensilon) test to distinguish the two is controversial
    • Give 1-2mg IV slow push. If any fasciculations, respiratory depression, or cholinergic symptoms within a few minutes, problem is likely cholinergic crisis (no more edrophonium). If no evidence of cholinergic excess, give total of 10mg and observe improvement in case of myasthenic crisis.
    • Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm
    • Thus, need to be on a monitor, with atropine on hand
    • Treatment: Atropine

Management

Always evaluate:[5]

  • Tidal volume
  • Forced Vital capacity (normal is >25cc/kg in MG)
  • FEV
  • Negative inspiratory force (NIF) (normal is -80 to -100 and greater than +20 respiratory support indicated)
  • Ability to handle secretions

Medications

  • Pyridostigmine and neostigmine primarily used for symptomatic relief but does not alter course of crisis[6]
    • Note that in myasthenic crisis, acetylcholinesterase inhibitors are discontinued to avoid excessive bronchial secretions
    • Continued use of these meds also prevents assessment of other treatment modalities and can increase muscle weakness if used in excess
    • Primary medications in crisis are IVIG and plasmapheresis
  1. Pyridostigmine
    • If patient's usual dose has been missed the next dose is usually doubled
    • PO route: 60-90mg q4hr
    • IV route: 1/30th of the PO dose (2-3mg) by slow IV infusion
  2. Neostigmine
    • 0.5mg IV
  3. Intubation
    • If possible avoid depolarizing AND non-depolarizing agents
      • If patient requires paralysis use non-depolarizing agent at smaller dose
      • If must use depolarizing agents, will need higher doses
  4. Plasmapherisis
  5. IVIG

Disposition

  • Typically MICU or neuro ICU, consideration for thymectomy if not done already
  • Consideration for corticosteroids or other immunosuppressants (i.e. corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine)

See Also

References

  1. Medications and Myasthenia Gravis (A Reference for Health Care Professionals) PDF
  2. UpToDate Clinical manifestations of myasthenia gravis may 2016
  3. Sanders DB, Guptill JT. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome. Continuum. 2014 Oct;20(5)
  4. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders
  5. Emergency Medicine Practice -- Weakness: A systemic approach to acute non-traumatic neurologic and neuromuscular causes Dec 2002
  6. Wendell LC and Levine JM. Myasthenic Crisis. Neurohospitalist. 2011 Jan; 1(1): 16–22.

Authors:

Ross Donaldson