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

Clinical Manifestations of Myasthenia Gravis

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

Ocular Manifestations (Most Common Initial Presentation)

• Ptosis (drooping eyelids) is often the first symptom, appearing unilateral or bilateral and characteristically worsening with prolonged upgaze or sustained activity 1, 2, 3
• Diplopia (double vision) results from extraocular muscle weakness and is highly variable in presentation 1, 2, 3
• Variable strabismus (eye misalignment) and slow ocular saccades are characteristic findings 1, 2
• 50% of patients initially present with purely ocular symptoms (MGFA Class I), but 50-80% of these will progress to generalized MG within a few years 2, 3
• Extraocular muscles are particularly vulnerable due to their twitch fiber composition and fewer acetylcholine receptors 2, 3

Critical diagnostic pearl: Pupils are NOT affected in myasthenia gravis—pupillary involvement should prompt consideration of alternative diagnoses such as third nerve palsy 3

Bulbar Manifestations

• Dysarthria (slurred speech) is common as facial and pharyngeal muscles fatigue with use 1, 2, 3
• Dysphagia (difficulty swallowing) affects many patients and characteristically worsens with prolonged chewing 1, 2, 3
• Facial muscle weakness causes reduced facial expressions and affects quality of life 1, 3
• Neck weakness may lead to difficulty holding up the head (head drop) 1, 2

Limb and Trunk Involvement

• Proximal muscles are affected more than distal muscles, following a characteristic pattern 1, 2, 3
• Weakness affecting shoulders and hips more prominently than hands and feet 3
• Weakness is typically bilateral but can be asymmetrical 1, 2
• Trunk muscles may be involved, affecting posture 2

Respiratory Manifestations (Most Life-Threatening)

• Respiratory muscle weakness represents the most serious manifestation and can rapidly progress to respiratory insufficiency or failure (myasthenic crisis) 1, 2, 3
• Respiratory fatigue with shortness of breath, particularly with exertion, is a warning sign 3
• Myasthenic crisis (MGFA Class V) requires intubation and ventilatory support 1, 3
• Close monitoring with pulmonary function tests (negative inspiratory force and vital capacity) is crucial 2, 3

Hallmark Clinical Characteristics

• Fluctuating weakness is the defining feature, with symptoms worsening with continued activity and improving with rest 1, 2, 3
• Fatigability is characteristic, with symptoms worsening as the day progresses or with repetitive use of affected muscles 1, 2, 3
• Variable presentation during examination is typical, with the pattern of weakness changing 2, 3
• Temporary improvement with rest or application of ice (positive ice pack test) is characteristic 1, 3
• Symptoms worsen with intercurrent infection, fever, and physical or emotional exhaustion 4

Disease Progression Pattern

• Progression typically follows a predictable sequence: ocular → bulbar → limb → respiratory involvement 2
• Disease can progress from ocular-only to generalized MG in 50-80% of patients who initially present with ocular symptoms 1, 2, 3
• Respiratory infection (bacterial or viral) is the most frequent trigger for exacerbations 4

MGFA Clinical Classification System

• Class I: Ocular MG only (ptosis, diplopia) 1, 3
• Class II: Mild generalized weakness 1, 3
• Class III: Moderate generalized weakness 1, 3
• Class IV: Severe generalized weakness 1, 3
• Class V: Myasthenic crisis requiring intubation 1, 3

Critical Clinical Pitfalls to Avoid

• Failure to recognize early respiratory involvement can be fatal—all grades of MG warrant thorough evaluation given potential for rapid progression to respiratory compromise 1, 3
• Certain medications can precipitate or worsen myasthenic crisis: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics must be avoided 1, 2, 3
• MG may occur with concurrent myositis and/or myocarditis, requiring evaluation with CPK, aldolase, troponin T, ECG, and echocardiography if respiratory insufficiency or elevated CPK is present 3
• MG is considered a "great masquerader" as it can mimic many types of eye movement disorders 3
• Atypical presentations in young children with nonspecific symptoms require careful consideration of MG in the differential diagnosis 1

Associated Conditions

• Thymoma is present in 10-20% of patients with acetylcholine receptor antibody-positive MG 1, 3
• Association with other autoimmune diseases such as hyperthyroidism, Hashimoto's disease, systemic lupus erythematosus, and rheumatoid arthritis is common, particularly in early-onset MG 5, 6