June is Myasthenia Gravis Awareness Month

Diagnosis

Myasthenia Gravis Foundation of America clinical classification (2)[C]:

• Class I: any eye muscle weakness, possible ptosis, no other evidence of muscle weakness elsewhere
• Class II: eye muscle weakness of any severity; mild weakness of other muscles:
  • Class IIa: predominantly limb or axial muscles
  • Class IIb: predominantly bulbar and/or respiratory muscles
• Class III: eye muscle weakness of any severity; moderate weakness of other muscles:
  • Class IIIa: predominantly limb or axial muscles
  • Class IIIb: predominantly bulbar and/or respiratory muscles
• Class IV: eye muscle weakness of any severity; severe weakness of other muscles:
  • Class IVa: predominantly limb or axial muscles
  • Class IVb: predominantly bulbar and/or respiratory muscles (can also include feeding tube without intubation)
• Class V: intubation needed to maintain airway

History

The hallmark of MG is fatigability.

• Fluctuating weakness, often subtle, that worsens during the day and after prolonged use of affected muscles; may improve with rest
• Early symptoms are transient with asymptomatic periods lasting days or weeks.
• With progression, asymptomatic periods shorten, and symptoms fluctuate from mild to severe.
• 50% of patients present with ocular symptoms (ptosis and/or diplopia). Eventually, 90% of patients with MG develop ocular symptoms.
• Ptosis might be unilateral, bilateral, or shifting from eye to eye.
• 15% present with bulbar symptoms.
• 5% present with proximal limb weakness alone.

Physical Exam

• Ptosis may worsen with propping of opposite eyelid (curtain sign) or sustained upward gaze.
• “Myasthenic sneer,” in which the midlip rises but corners of mouth do not move
• Muscle weakness is usually proximal and symmetric.
• Test for muscle fatigability by repetitive or prolonged use of individual muscles.
• Important to test and monitor respiratory function

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

• Anti-AChR antibody (74–85% are seropositive):
  • Generalized myasthenia: 75–85%
  • Ocular myasthenia: 50%
  • MG and thymoma: 98–100%
  • Poor correlation between antibody titer and disease severity (1)[C]
  • False-positive results in thymoma without MG, Lambert-Eaton myasthenic syndrome, small cell lung cancer, and rheumatoid arthritis treated with penicillamine
• Anti-MuSK antibody:
  • Used if MG is suspected and patient seronegative for AChR antibodies
  • Strong correlation between titer and disease severity (1)[C]
• LRP4 and clustered anti-AChR:
  • Used if MG suspected and patient seronegative for AChR antibodies
• Thyroid and other autoimmune testing anti-striated muscle (anti-SM) antibody:
  • Present in 84% of patients with thymoma who are ,40 years of age
  • Can be present without thymoma in patients 40 years of age
• Chest radiographs or CT scans may identify a thymoma.
• MRI of brain and orbits to rule out other causes of cranial nerve deficit

Test Interpretation

• Lymphofollicular hyperplasia of thymic medulla occurs in 65% of patients with MG, thymoma in 15%.
• Immunofluorescence: immunoglobulin (Ig) G antibodies and complement on receptor membranes in seropositive patients

From 5-Minute Clinical Consult, 31st edition, by Frank J. Domino, MD, et al (2023)