Myasthenia Gravis

Snapshot

• A 42-year-old woman presents to her primary care physician for fatigue. She reports that her fatigue is worse towards the end of the day. She also notes that while bathing her nephew in the shower her head would “drop.” At times when she is watching television or reading a book she sees double. Lastly, she would see her left or right eyelid droop after returning from work. On physical exam, there is right-sided ptosis after sustaining upward gaze for a few minutes. A tensilon test is performed, which is demonstrated in the clinical image below. Serologic studies return positive for anti-acetylcholine receptor antibodies. Preparations are made to have a computerized tomography scan of the chest.

Introduction

• Clinical definition
  • autoimmune disorder of the neuromuscular junction 
• Epidemiology
  • incidence
    • has a bimodal distribution
      • more common in younger women (< 40 years of age) and older men (> 50 years of age)
  • risk factors
    • HLA-B8
    • medications
      • penicillamine
      • aminoglycosides
• Pathogenesis 
  • autoantibodies directed against a protein of the neuromuscular junction
    • autoantibodies can be directed against
      • nicotinic acetlycholine receptor (AChR)
        • more common
      • muscle-specific receptor tyrosine kinase (MuSK)
    • categorized as a type II hypersensitivity reaction
  • T-cells play a role as well
    • thought to stimulate B-cell antibody production
• Associated conditions
  • thymoma 
  • thymic hyperplasia
• Prognosis
• most patients with ocular involvement progress to generalized myasthenia gravis

Presentation

• Symptoms
  • general feature
    • fluctuating muscle weakness
      • commonly weakness is worse with continued use
        • e.g., worse at the end of the day
    • true muscle fatigue
      • secondary to decreasing contractile muscle force
  • ocular symptoms
    • most common presenting symptoms
      • ptosis
      • diplopia
  • bulbar symptoms
    • dysphagia
    • dysarthria
    • fatigable chewing
  • proximal muscle weakness
• Physical exam
  • ice-pack test
    • place ice on the patient’s ptosis → ptosis improves
      • low temperatures change the kinetics of acetylcholinesterase, decreasing its activity
        • this increases the amount of acetylcholine in the synaptic cleft
  • edrophonium chloride (Tensilon test) 
    • only used in patients with ptosis or ophthalmoparesis
      • this allows for improvement in muscle strength to be observed
    • edrophonium is an acetylcholinesterase inhibitor that has a short duration of action
      • this increases the amount of acetylcholine in the synaptic cleft
    • can also be used to monitor treatment with pyridostigmine 
      • improvement in weakness indicates acetylcholine levels are subtherapeutic
• worsening of weakness indicates acetylcholine levels are supratherapeutic

Imaging

• Computerized tomography (CT) scan 
  • indication
    • to rule out a thymoma
  • view
• chest

Studies

• Labs
  • serologic testing for autoantibodies
    • anti-AChR
      • iinitial laboratory test to confirm the diagnosis
    • anti-MuSK
• Electromyogram (EMG)
• decremental decrease in the compound muscle action potential (CMAP)

Differential

• Lambert-Eaton myasthenic syndrome (LEMS) 
  • differentiating factor
    • muscle weakness that improves with use
    • autonomic manifestations
• Botulism
  • differentiating factor
    • poor or impaired pupillary response to light
• Thyroid ophthalmopathy

Treatment

• Medical
  • corticosteroids
    • indication
      • a chronic immunotherapy agent
    • drugs
      • oral prednisone
  • acetylcholinesterase inhibitors
    • indication
      • considered first-line for symptomatic management
    • drugs
      • pyridostigmine
    • adverse effects
      • abdominal cramping and diarrhea
      • bradycardia
      • sweating
      • bronchial secretion
• Procedural
  • intravenous immunoglobulins (IVIg) or plasmapharesis
    • indication
      • rapid immunotherapy for myasthenic crisis
• Surgical 
  • thymectomy
    • indication
• in patients with a thymoma, irrespective if the patient has myasthenia gravis or not

Complications

• Myasthenic crisis
  • respiratory weakness secondary to myasthenia gravis
• Increased sensitivity to non-depolarizing acetylcholine receptor blockers such as vecuronium