What are the clinical presentation and treatment options for myasthenia gravis?

Clinical Presentation of Myasthenia Gravis

Myasthenia gravis presents with fluctuating, fatigable muscle weakness that worsens with repetitive use and improves with rest, characteristically affecting ocular muscles first (ptosis and diplopia), followed by bulbar muscles (dysarthria, dysphagia), and potentially progressing to life-threatening respiratory failure. 1, 2

Cardinal Features of Weakness

The hallmark pattern involves:

• Fluctuation throughout the day - symptoms vary in severity and can present with completely different patterns depending on fatigue level or time of examination 1
• Fatigability - weakness worsens with sustained or repeated muscle use and improves after rest periods 1, 3
• Proximal predominance - proximal muscles are affected more than distal muscles 2

Ocular Manifestations (Most Common Initial Presentation)

Approximately 50% of patients present with purely ocular symptoms initially 4, 2:

• Ptosis - eyelid drooping that worsens with sustained upgaze and improves with rest 1
• Diplopia - double vision from asymmetric, variable extraocular muscle weakness 1
• Cogan lid-twitch sign - brief eyelid overshoot when returning gaze from downgaze to primary position 4
• Slow ocular saccades - reduced speed of rapid eye movements 4
• Pupils are characteristically spared - this is a critical distinguishing feature that differentiates myasthenia gravis from third nerve palsy and other causes of ophthalmoplegia 1, 5

Critical warning: 50-80% of patients presenting with isolated ocular symptoms will progress to generalized myasthenia within a few years, making early recognition essential 4, 2, 5.

Bulbar Manifestations

These symptoms are particularly concerning and require immediate evaluation 1:

• Dysarthria - slurred speech that worsens with prolonged talking 1, 2
• Dysphagia - difficulty swallowing, a red flag requiring urgent assessment 1, 2
• Facial muscle weakness - difficulty with facial expressions 2
• Hoarseness - may indicate bulbar involvement 1

Limb and Respiratory Manifestations

• Neck weakness - difficulty holding up the head, can progress to respiratory involvement 1, 2
• Difficulty climbing stairs - indicating proximal lower limb weakness 1, 2
• Respiratory muscle weakness - can lead to myasthenic crisis with respiratory failure requiring intubation 1, 2
• Bilateral but often asymmetric presentation - weakness typically affects both sides but may be unequal 2

Distinctive Diagnostic Signs at Bedside

Ice pack test - highly specific for myasthenia gravis 1, 2, 5:

• Apply ice pack over closed eyes for 2 minutes for ptosis 4, 5
• Apply for 5 minutes for strabismus 4
• Positive test shows reduction of ptosis by approximately 2 mm and reduction of misalignment 4
• This phenomenon relates to diminished anticholinesterase activity at cooler temperatures 4

Rest test - temporary improvement in weakness after resting the affected muscles can also aid diagnosis 4

Red Flags Requiring Urgent Evaluation

Watch for these life-threatening signs 1:

• Any respiratory symptoms including shortness of breath with light activity
• Progressive or new-onset dysphagia
• Neck or respiratory muscle weakness
• Hoarseness suggesting bulbar involvement

Common Pitfalls to Avoid

Do not dismiss the diagnosis if pupils are normal - pupillary sparing is expected in myasthenia gravis and helps distinguish it from third nerve palsy 1, 5. Conversely, if pupils ARE abnormal, immediately consider alternative diagnoses such as third nerve palsy, Horner syndrome, or brainstem lesions 5.

Do not assume ocular-only disease will remain localized - maintain vigilant monitoring for progression to generalized disease, which occurs in the majority of patients 4, 2, 5.

Recognize that strabismus and ptosis patterns can change completely during the same examination session due to fatigue, making serial assessments valuable 4, 1.

Associated Conditions

Patients have increased risk for 4:

• Autoimmune thyroid disease
• Thymoma - present in 10-15% of myasthenia gravis patients, and conversely, 30-50% of thymoma patients have myasthenia gravis 5

Disease Classification

The Myasthenia Gravis Foundation of America classification system 2:

• Class I - Ocular myasthenia only
• Class II - Mild generalized weakness
• Class III - Moderate generalized weakness
• Class IV - Severe generalized weakness
• Class V - Myasthenic crisis requiring intubation