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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Fatigable weakness worsens with use and improves with rest
- Ocular symptoms are common: ptosis and diplopia
- Sensation and reflexes are normal
- Screen for thymoma with chest imaging
- Myasthenic crisis requires ICU plus IVIG or plasma exchange
Overview
MG is an autoimmune postsynaptic neuromuscular junction disorder, usually due to acetylcholine receptor antibodies. MuSK and LRP4 antibodies account for some seronegative cases.
Epidemiology
It has a bimodal distribution and is associated with thymic hyperplasia, thymoma, autoimmune thyroid disease, and exacerbations from infection, surgery, pregnancy, and drugs.
Clinical Features
Symptoms
Fluctuating ptosis/diplopia
Chewing fatigue, dysphagia, nasal speech
Proximal weakness worse later in day
Dyspnea, weak cough, secretion difficulty
No sensory symptoms
Signs
Fatigable ptosis with sustained upgaze
Diplopia without pupillary involvement
Normal sensation and reflexes
Neck flexor or proximal weakness
Respiratory distress or bulbar weakness
Investigations
First-line
AChR antibodiesHighly specific; common in generalized MG
MuSK antibodyIf AChR negative or bulbar phenotype
FVC/NIFIf crisis suspected
Second-line
Ice pack testImproves ptosis in ocular MG
Repetitive nerve stimulation/Single-fiber EMGDecrement or increased jitter
Chest CT/MRIEvaluate thymoma
Specialist
Thyroid testingAutoimmune thyroid disease coexistence
ICU monitoringCrisis and respiratory compromise
1
Symptomatic
- Pyridostigmine first-line
- Monitor cholinergic side effects
- Eye and bulbar precautions
- Avoid MG-worsening drugs
2
Immunotherapy
- Corticosteroids for persistent generalized symptoms
- Steroid-sparing azathioprine/mycophenolate etc.
- Rituximab for selected MuSK/refractory disease
- Specialist biologics in refractory AChR-positive MG
3
Thymus
- Thymectomy for thymoma
- Consider thymectomy in AChR-positive generalized MG
- Less benefit in pure ocular or MuSK MG
- Long-term follow-up
4
Crisis
- ICU and airway monitoring
- IVIG or plasma exchange
- Treat trigger such as infection
- May hold pyridostigmine if secretions compromise airway
Complications
- Myasthenic crisis: Respiratory or bulbar failure
- Aspiration: Dysphagia/weak cough
- Thymoma: Requires imaging
- Medication worsening: Fluoroquinolones, aminoglycosides, magnesium, beta-blockers
USMLE Step 2 CK Exam Tips
- 1Fatigable ptosis/diplopia with normal pupils = MG
- 2Weakness worsens with use and improves with rest
- 3Normal sensation/reflexes distinguish from GBS
- 4All MG needs chest imaging for thymoma
- 5Pyridostigmine is first-line symptomatic therapy
- 6Crisis = IVIG or plasma exchange plus airway support
- 7Magnesium can worsen MG
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