What are the signs and symptoms of myasthenia gravis?

Signs and Symptoms of Myasthenia Gravis

Myasthenia gravis presents with fluctuating muscle weakness that worsens with activity and improves with rest, most commonly starting with ocular symptoms (ptosis and diplopia) before potentially progressing to bulbar, limb, and 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 worsens with prolonged upgaze or fatigue 3, 1, 2
• Diplopia (double vision) results from extraocular muscle weakness and is highly variable 3, 1, 2
• Variable strabismus (eye misalignment) that changes over the course of examination is characteristic 3, 1, 2
• Slow ocular saccades (rapid eye movements) are a distinctive finding 3, 1
• Cogan lid-twitch sign may be present, where the eyelid twitches when returning from downgaze to primary position 3
• Extraocular muscles are particularly susceptible due to their twitch fiber composition and fewer acetylcholine receptors 1, 2
• 50% of patients initially present with ocular symptoms only 1, 2

Bulbar Manifestations

• Dysarthria (slurred speech) is common as facial and pharyngeal muscles fatigue 3, 1, 2
• Dysphagia (difficulty swallowing) affects many patients and worsens with prolonged chewing 3, 1, 2
• Difficulty chewing, particularly noticeable during meals as jaw muscles tire 3, 1
• Facial muscle weakness causing reduced facial expressions and a characteristic "myasthenic snarl" when attempting to smile 1, 2

Limb and Axial Muscle Involvement

• Proximal muscle weakness affecting shoulders and hips more than distal muscles 3, 1, 2
• Neck weakness leading to difficulty holding up the head, particularly late in the day 3, 1, 2
• Weakness is typically bilateral but can be asymmetrical 2
• Variable motor weakness that changes in distribution and severity 3

Respiratory Manifestations (Most Life-Threatening)

• Respiratory muscle weakness represents the most serious manifestation and can rapidly progress to respiratory failure (myasthenic crisis) 3, 1, 2
• Respiratory fatigue with shortness of breath, particularly with exertion 3
• This requires urgent monitoring with pulmonary function tests including negative inspiratory force (NIF) and vital capacity (VC) 3, 1, 2

Hallmark Clinical Characteristics

• Fluctuating weakness is the cardinal feature—symptoms worsen with continued activity and improve with rest 1, 2, 4
• Fatiguability with symptoms worsening as the day progresses or with repetitive use of affected muscles 3, 1, 2
• Variable presentation during examination, with the pattern of weakness changing over time 3, 1, 2
• Temporary improvement with rest or application of ice pack (ice test) for 2-5 minutes is highly specific 3, 1, 2
• Symptoms worsen with fatigue, prolonged examination, fever, infection, or physical/emotional exhaustion 3, 5

Disease Progression Pattern

• 50-80% of those with initial ocular symptoms develop generalized myasthenia gravis within a few years 1, 2
• Progression typically follows from ocular to bulbar to limb to respiratory involvement 2
• The disease is characterized by relapses and remissions 6

Important Clinical Pitfalls

• Pupils are typically NOT affected—pupillary involvement should alert you to consider alternative diagnoses such as third nerve palsy 3
• Myasthenia gravis is considered a "great masquerader" as it can mimic many eye movement disorders 1
• Certain medications can precipitate or worsen symptoms: beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 1, 2
• Failure to recognize early respiratory involvement can be fatal—all grades warrant thorough evaluation given potential for progression to respiratory compromise 3, 1