What are the clinical manifestations of Myasthenia Gravis (MG)?

Clinical Manifestations of Myasthenia Gravis

Myasthenia gravis presents with fatigable, fluctuating muscle weakness that characteristically worsens with activity and improves with rest, most commonly affecting ocular muscles first (ptosis and diplopia), followed by bulbar, proximal limb, neck, and potentially life-threatening respiratory muscle involvement. 1, 2

Hallmark Clinical Features

The defining characteristic is fluctuating weakness that worsens with continued muscle use and improves with rest, distinguishing it from other neuromuscular disorders 1, 2. Symptoms typically worsen as the day progresses or with repetitive use of affected muscles 1. The pattern of weakness can change during a single examination, making MG a "great masquerader" that can mimic many other disorders 1.

Ocular Manifestations (Most Common Initial Presentation)

• Ptosis (drooping eyelids) is often the very first symptom, appearing unilaterally or bilaterally 1, 2, 3
• Diplopia (double vision) results from extraocular muscle weakness 1, 2
• Variable strabismus (misalignment of eyes that changes) is characteristic 1, 2, 3
• Slow ocular saccades (rapid eye movements) 1, 3
• Extraocular muscles are particularly vulnerable due to their twitch fiber composition and fewer acetylcholine receptors 1, 2
• 50% of patients initially present with purely ocular symptoms 1, 3

Bulbar Manifestations

• Dysarthria (slurred speech) 4, 1, 2, 3
• Dysphagia (difficulty swallowing) 4, 1, 2, 3
• Facial muscle weakness causing reduced facial expressions 4, 2, 3
• Difficulty chewing 1

Limb and Axial Muscle Involvement

• Proximal muscles are affected more than distal muscles 4, 2, 3
• Weakness is typically bilateral but can be asymmetrical 2, 3
• Neck weakness leading to difficulty holding up the head 4, 1, 2, 3
• Trunk muscle involvement affecting posture 2

Respiratory Manifestations (Most Serious)

• Respiratory muscle weakness represents the most life-threatening manifestation 4, 1, 2, 3
• Can rapidly progress to respiratory insufficiency or failure (myasthenic crisis) 4, 2, 3
• Requires close monitoring with pulmonary function tests including negative inspiratory force (NIF) and vital capacity (VC) 4, 2

Disease Progression Pattern

50-80% of patients who initially present with only ocular symptoms will develop generalized myasthenia gravis within a few years 1, 3. Progression typically follows a pattern from ocular → bulbar → limb → respiratory involvement 3.

Clinical Classification by Severity

The Myasthenia Gravis Foundation of America (MGFA) classification system guides management 3:

• Class I: Ocular symptoms only (ptosis, diplopia) 4, 3
• Class II: Mild generalized weakness with some interference with activities of daily living 4, 3
• Class III: Moderate generalized weakness 4, 3
• Class IV: Severe generalized weakness, limiting self-care, aids warranted, weakness limiting walking 4, 3
• Class V: Myasthenic crisis requiring intubation and ventilatory support 4, 3

Diagnostic Clinical Signs

• Temporary improvement with rest or ice pack application (ice pack test) is characteristic 1, 2, 3
• Variable presentation during examination is typical 1, 2
• Symptoms worsen with intercurrent infection, fever, or physical/emotional exhaustion 5

Critical Pitfalls to Avoid

All grades of myasthenia gravis warrant thorough work-up and intervention given the potential for progressive disease leading to respiratory compromise 4, 3. Failure to recognize early respiratory involvement can be fatal 2, 3.

Avoid these medications that can precipitate or worsen myasthenic weakness: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 4, 2, 3.

Concurrent Conditions to Consider

MG may occur with myositis and/or myocarditis, requiring evaluation with CPK, aldolase, troponin T, ECG, and echocardiography if respiratory insufficiency or elevated CPK is present 4. Respiratory symptoms may require evaluation to rule out pneumonitis or myocarditis 4.