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)
