Medical Musing of the Week: Myasthenia Gravis

Overview

  • Most common d/o of neuromuscular transmission
  • Autoimmune disorder resulting in weakness of ocular, bulbar, limb & respiratory muscles
  • Ocular and Generalized sub types exist.
  • 50% of individuals presenting with ocular subtype will develop generalized myasthenia within two years

Etiology/Pathophysiology

  • Thymic tumor (10%)
  • Decrease in the number available AcH receptors at post synaptic membrane, which leads to inhibition of depolarization, action potential is not propagated.
  • Bimodal age distribution.  Women 30’s-40’s and men later in life 60’s-70’s

image

Clinical Manifestations

  • History:
    • Fatigue with increased activity
    • Blurry vision
    • Double vision
    • Difficulty chewing foods such as steak,
    • Bulbar weakness (dysarthria, dysphagia, fatigue while chewing)
    • Proximal limb weakness
  • PE:
    • Ptosis (pictured)
    • Fatigue w/ EOEM,
    • May appear expressionless
    • “Dropped head syndrome”inability to hold up head and neck
    • Respiratory symptoms: are the most serious clinical manifestation of MG.  Deemed “Myasthenia Crisis” (see below)
    • image
      Ptosis of the left eye.

Diagnosis

Laboratory Values

  • + Anti-AcHR immunoassay 85% sensitive for generalized and 50% sensitive w/ ocular
  • + Anti-MuSK (muscle specific kinase)
    • Bulbar symptoms are increasingly associated with +MuSK
    • + MuSK patients are less responsive to anticholinesterase medications and thymectomy
    • Respond well to Immunosuppresive therapy with Rituximab
  • + lpr4 antibody

Edrophonium (Tensilon) Test:

  • Reversible AcH inhibitor, administered MG patients with improvement in symptoms
  • Reserved for patients who do no demonstrate sero-positive blood results with continued high suspicion for MG
  • Dosing: 2mg at first and if improvement is demonstrated no further dose.  Administer additional 8mg within several minutes if no improvement.  Some sources suggest after the first 2mg wait 60 seconds and give another 2mg, etc until response is seen with a max of 10mg

Edrophonium Test in a child:

Edrophonium Test in a dog.  Because medicine is more fun when you get to watch a dog walk again!

Treatment

Medication:
  • Anticholinesterase Inhibitors
    • Pyridostigmine 30-60mg TID-QID
Thymectomy
  • Removal avoids spread of malignancy and treats MG
  • Positive prognosis when combined with medication management
Immunosuppression
Acute Relief
  • Improvement within a week and results lasting approximately 1 month
  • Benefits last weeks-months and usually takes one week for full improvement
  • IVIG
    • 2g/kg; typically administered over 5 days (400mg/kg/day)
  •  Plasmapheresis
    • 5 exchanges; 3-4L/exchange over 10-14 days
    • Provides short term reduction in anti-AcHR antibodies
Intermediate Relief
  • Improvement within 1-3 months
  • Glucocorticoids: 15-25mg/day
  • Cyclosporine: 4-5mg/kg/day
  • Tacrolimus: .07-.1mg/kg/day divided into BID dosing
  • Tacrolimus and Cyclosporine are being used w/ increased frequency as opposed to Azathioprine because of increased effectiveness, less side effets and quicker results.
Long Term:
  • Azanthropine: 50mg/day initially to test for s/e (titrate up to 2-3mg/kg)
  • Mycophenolate: 1-1.5g/day divided into BID dosing
Considerations/Complications
Myasthenia Crisis
  • Respiratory failure due to diaphragm and intercostal muscle fatigue
  • Respiratory therapy will monitor patients inspiratory and expiratory strength
  • Causes: Infection, surgery, medications, ineffective taper of immunosuppresive medications
    • Medications: Aminogylcosides, Quinolones, Macrolides, Beta Blockers, Non-deploarizing muscle relaxants (Paracuronium, Vecuronium, Atracurium), Local anesthetitcs, Botulinum toxin

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