Signs and Symptoms of Myasthenia Gravis
Myasthenia gravis presents with variable muscle weakness that worsens with fatigue and improves with rest, most commonly affecting ocular muscles initially with ptosis and diplopia, and potentially progressing to generalized weakness affecting bulbar, limb, and respiratory muscles in 50-80% of cases. 1
Primary Clinical Manifestations
Ocular Symptoms (Initial Presentation in 50% of Cases)
Ptosis (drooping eyelids) - Key characteristics:
- Worsens with prolonged upgaze
- Often asymmetric
- May show Cogan lid-twitch sign (brief overshoot of lid elevation when eyes move from downward to primary position)
- Contralateral ptosis may worsen upon manual elevation of the more involved eyelid 1
Diplopia (double vision) - Key characteristics:
- Variable and incomitant strabismus
- Pattern may change with fatigue or repetitive examination
- May temporarily improve with rest 1
Bulbar Symptoms
- Dysarthria (slurred speech)
- Dysphagia (difficulty swallowing)
- Difficulty chewing
- Difficulty holding up the head 1
Limb and Axial Muscle Weakness
- Proximal muscle weakness more common than distal
- Upper limbs often affected before lower limbs
- Neck muscle weakness 1
Respiratory Involvement
- Can lead to life-threatening respiratory failure (myasthenic crisis)
- Requires immediate medical attention 1
Distinctive Clinical Features
Fatigability
- Hallmark feature: weakness worsens with continued activity
- Improves after periods of rest
- Morning strength often better than evening strength 2, 3
Variability
- Symptoms fluctuate throughout the day
- Strabismus and diplopia may take on different patterns with fatigue 1
Diagnostic Physical Signs
- Slow ocular saccades
- Ice pack test: temporary improvement of ptosis after application of ice pack over closed eyes for 2 minutes 1, 4
- Normal pupillary responses (typically not affected)
- Note: Pupillary involvement should raise suspicion for alternative diagnoses like third nerve palsy 1
Subtypes and Special Considerations
Ocular Myasthenia Gravis
- Limited to levator, orbicularis oculi, and extraocular muscles
- Known as "the great masquerader" as it can mimic many types of incomitant strabismus 1
Generalized Myasthenia Gravis
- Affects large motor groups including bulbar, limb, and respiratory muscles
- May include ocular features 1
MuSK-Associated Myasthenia Gravis
- Distinct subtype with unique clinical features
- Often presents with prominent bulbar, facial, and neck weakness
- May have atypical presentation compared to acetylcholine receptor antibody-positive MG 5, 6
Warning Signs of Myasthenic Crisis
- Progressive weakness of respiratory muscles
- Increasing difficulty breathing
- Inability to clear secretions
- Requires immediate medical attention to prevent mortality 1
Key Diagnostic Clues
- Variable weakness that improves with rest
- Ocular involvement (ptosis and diplopia) as initial symptoms in most cases
- Normal reflexes despite weakness
- No sensory deficits
- Characteristic response to acetylcholinesterase inhibitors 7
Early recognition of these signs and symptoms is crucial as 50-80% of patients who initially present with ocular symptoms will develop generalized myasthenia gravis within a few years, which can lead to significant morbidity and mortality if not properly managed 1.