What is the approach to diagnose and manage myasthenia gravis?

Workup of Myasthenia Gravis

Begin with serologic testing for acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies, followed by electrodiagnostic studies with repetitive nerve stimulation or single-fiber EMG if antibodies are negative, while simultaneously assessing for respiratory compromise with pulmonary function testing. 1, 2

Clinical Recognition

Key Presenting Features

• Fatigable or fluctuating muscle weakness is the hallmark, typically affecting proximal muscles more than distal muscles 1, 2
• Ocular symptoms including ptosis and diplopia are present in the majority of patients at onset, with 50-80% progressing to generalized disease within a few years 1, 2
• Bulbar involvement manifests as dysarthria, dysphagia, facial weakness, and neck weakness 2
• Pupils are characteristically spared—any pupillary abnormality should immediately redirect you toward third nerve palsy or other diagnoses, not myasthenia 1

Bedside Testing

• Ice pack test: Apply ice over closed eyes for 2 minutes in patients with ptosis—this is highly specific for myasthenia gravis, particularly for ocular symptoms 1, 2

Serologic Workup

First-Line Antibody Testing

• AChR antibodies are positive in 80-85% of generalized MG but only 40-77% of ocular MG 1, 3
• Antistriated muscle antibodies should be ordered simultaneously, especially important preoperatively as 30-50% of thymoma patients have MG 1

Second-Line Antibody Testing (if AChR negative)

• Muscle-specific kinase (MuSK) antibodies are present in 5-8% of patients 1, 3
• Lipoprotein-related protein 4 (LRP4) antibodies account for <1% of cases 1, 3
• Approximately 10% remain seronegative for all known antibodies 3

Electrodiagnostic Studies

When Antibodies Are Negative or Diagnosis Uncertain

• Single-fiber EMG has >90% sensitivity for ocular myasthenia and is the most sensitive test 1, 2
• Repetitive nerve stimulation is less sensitive, positive in only one-third of ocular MG cases 2
• Standard EMG and nerve conduction studies may be normal early in disease and are operator-dependent 1

Critical pitfall: Electrodiagnostic studies require specialized equipment and expertise—negative results do not exclude the diagnosis if clinical suspicion is high 1

Respiratory Assessment

Pulmonary Function Testing

• Measure negative inspiratory force (NIF) and vital capacity (VC) in all patients with generalized symptoms 1, 2, 4
• Repeat frequently in hospitalized patients with moderate-to-severe disease, as respiratory compromise can develop rapidly 1, 4
• This is non-negotiable for any patient with bulbar symptoms or shortness of breath 1

Imaging Studies

Thymic Evaluation

• Chest CT or MRI to evaluate for thymoma in all patients with confirmed MG 1
• 10-20% of AChR-positive patients have thymoma, and approximately 30-50% of thymoma patients have MG 1, 3
• Preoperative antibody testing is mandatory for any patient with suspected thymoma to avoid respiratory failure during anesthesia 1

Differential Diagnosis Imaging

• Orbital CT/MRI if thyroid eye disease is suspected—look for tendon-sparing muscle enlargement which distinguishes it from myasthenia 1
• Brain MRI may be needed to exclude brainstem strokes that can mimic MG 1

Additional Diagnostic Considerations

CSF Analysis

• Typically normal in myasthenia gravis—this helps distinguish it from Guillain-Barré syndrome where CSF protein is elevated by week 2 1

Disease Classification

• Use the Myasthenia Gravis Foundation of America (MGFA) classification to guide treatment intensity 2:
  • Class I: Ocular MG only
  • Class II: Mild generalized weakness
  • Class III: Moderate generalized weakness
  • Class IV: Severe generalized weakness
  • Class V: Myasthenic crisis requiring intubation

Critical Medications to Avoid During Workup

• β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides can all exacerbate myasthenic symptoms and should be strictly avoided 1, 2, 4
• Educate patients immediately about these contraindications to prevent iatrogenic crisis 4

Differential Diagnoses to Exclude

Pupil-Sparing Ocular Motility Disorders

• Third nerve palsy: Requires immediate neuroimaging for aneurysm or ischemia if pupil is involved 1
• Thyroid eye disease: Look for proptosis, eyelid retraction, and mechanical restriction on forced duction testing 1
• Botulism: Consider symmetric cranial nerve palsies with gastrointestinal symptoms 1
• Lambert-Eaton syndrome: Distinguished by autonomic symptoms and incremental response on repetitive stimulation 1