How should I take a history to diagnose myasthenia gravis?

How to Take a History to Diagnose Myasthenia Gravis

Focus your history on identifying fluctuating, fatigable muscle weakness that worsens with activity and improves with rest, particularly targeting ocular symptoms (ptosis, diplopia), bulbar dysfunction (dysarthria, dysphagia), and respiratory involvement, as these patterns are pathognomonic for myasthenia gravis. 1

Key Historical Features to Elicit

Pattern of Weakness (Most Critical)

• Ask specifically about fluctuation: Does weakness worsen as the day progresses or with repetitive use of the same muscles? 1, 2
• Inquire about improvement with rest: Do symptoms improve after periods of rest or in the morning after sleep? 1, 3
• Assess for fatigability: Does the patient experience increasing weakness with continued activity (e.g., chewing becomes harder during a meal, eyelids droop more after reading)? 1, 4

This fluctuating, fatigable pattern is the clinical hallmark that distinguishes myasthenia gravis from other neuromuscular disorders 5.

Ocular Symptoms (Often First to Appear)

• Ptosis: Ask if eyelids droop, whether unilateral or bilateral, and if it worsens with sustained upward gaze or reading 1, 4
• Diplopia: Inquire about double vision that is variable and changes with direction of gaze 1, 4
• Variable strabismus: Ask if eye misalignment changes during examination or throughout the day 1

Critical point: 50% of patients initially present with purely ocular symptoms, and 50-80% of these will progress to generalized disease within a few years 1, 4. Early recognition is therefore crucial.

Bulbar Symptoms

• Dysarthria: Does speech become slurred or nasal, particularly after prolonged talking? 1, 4
• Dysphagia: Does swallowing become difficult, especially with prolonged chewing or later in meals? 1, 4
• Facial weakness: Ask about reduced facial expressions or difficulty with facial movements 6
• Chewing fatigue: Does the jaw become tired when eating, requiring breaks during meals? 1

Limb Weakness

• Proximal > distal pattern: Ask specifically about difficulty with overhead activities (combing hair, reaching), climbing stairs, or rising from a chair 1, 4
• Asymmetric involvement: Weakness may affect one side more than the other 2

Respiratory Symptoms (Life-Threatening)

• Shortness of breath: Inquire about dyspnea with minimal exertion or at rest 1, 4
• Difficulty with deep breathing: Ask if the patient feels unable to take a full breath 1
• Orthopnea: Does breathing worsen when lying flat? 1

Critical pitfall: Respiratory muscle weakness represents the most life-threatening manifestation and can rapidly progress to respiratory failure (myasthenic crisis) 1, 4. Maintain a low threshold for urgent evaluation if any respiratory symptoms are present.

Essential Past Medical and Medication History

Associated Conditions

• Thymus pathology: Ask about known thymoma, as 10-20% of AChR-positive patients have thymoma 2, 7
• Other autoimmune diseases: Inquire about thyroid disease, lupus, rheumatoid arthritis, or other autoimmune conditions 6
• Recent immunotherapy: If patient has cancer, ask about immune checkpoint inhibitor therapy, as myasthenia gravis can be an immune-related adverse event 6

Medications That Worsen Myasthenia (Critical to Identify)

Ask specifically about current use of:

• Beta-blockers 1, 4
• IV magnesium 1, 4
• Fluoroquinolones (ciprofloxacin, levofloxacin) 1, 4
• Aminoglycosides (gentamicin, tobramycin) 1, 4
• Macrolide antibiotics (azithromycin, erythromycin) 1, 4
• Statins (can cause myopathy that confounds diagnosis) 6

These medications can precipitate or worsen myasthenic crisis and must be discontinued immediately if myasthenia gravis is suspected 1, 4.

Family and Demographic History

Age and Sex Pattern

• Women: Typical onset in third to fourth decade of life 1
• Men: Typical onset later in life 1
• Children: Ask about maternal myasthenia gravis (transient neonatal myasthenia) or family history of congenital myasthenia 1

Family History

• Inquire about family members with myasthenia gravis or other autoimmune diseases 7

Red Flags Requiring Urgent Evaluation

Myasthenic Crisis Indicators

• Respiratory distress with any degree of dyspnea at rest 1, 4
• Severe dysphagia with risk of aspiration 6
• Rapidly progressive weakness over hours to days 4
• Recent infection or medication change that may have precipitated crisis 8

Concurrent Life-Threatening Conditions

Ask about symptoms suggesting:

• Myocarditis: Chest pain, palpitations, syncope 6
• Myositis: Severe muscle pain (not typical of pure myasthenia gravis) 6

If patient has concurrent myositis or myocarditis (particularly in immune checkpoint inhibitor-related cases), mortality risk is significantly elevated 6.

Critical Distinguishing Features

What Myasthenia Gravis Is NOT

• Pupils are NOT affected: If pupillary abnormalities are present, consider alternative diagnoses like third nerve palsy 1, 4
• Pain is NOT typical: Myasthenia gravis causes weakness, not pain; if pain is prominent, consider myositis or other conditions 6
• Sensory symptoms are absent: No numbness or tingling (unlike Guillain-Barré syndrome) 6
• Consciousness is NOT altered: Patients remain fully alert unless sedated 6

Mimics to Consider in Differential

• Guillain-Barré syndrome: Ascending weakness, sensory involvement, elevated CSF protein 6
• Botulism: Descending paralysis, pupillary involvement, gastrointestinal symptoms first 6
• Lambert-Eaton myasthenic syndrome: Weakness improves with repeated use (opposite of myasthenia gravis) 9
• Brainstem stroke: Sudden onset, lateralizing signs 5
• Chronic progressive external ophthalmoplegia: Slowly progressive, no fluctuation 5

Structured History-Taking Algorithm

1. Screen for fluctuating weakness: "Do you have muscle weakness that gets worse with activity and better with rest?" 1, 3
2. If yes, characterize ocular involvement: "Do your eyelids droop? Do you see double? Does this worsen as the day goes on?" 1, 4
3. Assess bulbar function: "Do you have trouble swallowing? Does your speech become slurred? Does your jaw get tired when chewing?" 1, 4
4. Evaluate respiratory status: "Do you get short of breath with minimal activity? Can you take a deep breath?" 1, 4
5. Check for proximal limb weakness: "Do you have trouble lifting your arms overhead? Climbing stairs? Getting up from a chair?" 1, 4
6. Review dangerous medications: Systematically ask about beta-blockers, antibiotics (fluoroquinolones, aminoglycosides, macrolides), and IV magnesium 1, 4
7. Assess for thymoma: "Have you been told you have a thymus tumor?" 2, 7
8. Determine urgency: Any respiratory symptoms, severe dysphagia, or rapidly progressive weakness requires immediate intervention 1, 4

The diagnosis of myasthenia gravis is fundamentally clinical, based on the characteristic history of fluctuating, fatigable weakness with the specific distribution patterns described above 1, 2. Laboratory and electrodiagnostic testing confirm the diagnosis but should never delay urgent treatment if myasthenic crisis is suspected 4.