What is Myasthenia Gravis?

What is Myasthenia Gravis?

Myasthenia gravis is a B-cell mediated autoimmune disorder that attacks the neuromuscular junction, causing fluctuating muscle weakness that worsens with activity and improves with rest, potentially progressing to life-threatening respiratory failure. 1

Core Disease Mechanism

The disease fundamentally disrupts normal nerve-to-muscle communication at the neuromuscular junction. 1 Here's how it works:

• Acetylcholine normally crosses the synapse from nerve to muscle during an action potential, binding to receptors that trigger muscle contraction 2
• Autoantibodies attack these acetylcholine receptors, preventing proper signal transmission and causing the characteristic weakness 1
• Antibodies are found in nearly all patients with generalized disease (approaching 100%) and in 40-77% of patients with ocular-only disease 2, 1
• Extraocular muscles are particularly vulnerable due to their twitch fiber composition and fewer acetylcholine receptors, explaining why eye symptoms are so common 2, 1

Clinical Presentation Patterns

Ocular Manifestations (Often First to Appear)

• Ptosis (drooping eyelids) - may be unilateral or bilateral 1, 3
• Diplopia (double vision) from extraocular muscle weakness 1, 3
• Variable strabismus (eye misalignment) that changes during examination 1, 3
• Slow ocular saccades (rapid eye movements) 3

Generalized Manifestations

• Bulbar symptoms: difficulty chewing, swallowing (dysphagia), and slurred speech (dysarthria) 1, 3
• Neck weakness causing difficulty holding up the head 1, 3
• Proximal limb weakness affecting arms and legs more than hands and feet 3, 4
• Respiratory muscle weakness - the most serious manifestation that can progress to respiratory failure requiring ventilatory support 1, 3

The Hallmark Clinical Features

Fluctuating weakness is the defining characteristic - symptoms worsen with continued muscle use and improve with rest. 1, 3 This distinguishes myasthenia from most other neuromuscular disorders.

• Fatiguability worsens as the day progresses or with repetitive use of affected muscles 1, 3
• Variable presentation during examination - the pattern of weakness can change even during a single visit 1, 3
• Temporary improvement with rest or ice application (ice pack test) is characteristic 1, 3
• Known as "the great masquerader" because it can mimic many types of eye movement disorders and other conditions 2, 1

Disease Classification and Subtypes

By Distribution

• Ocular myasthenia gravis: affects only the levator, orbicularis oculi, and extraocular muscles 2, 1
• Generalized myasthenia gravis: affects larger muscle groups and may include ocular features 2, 1

By Severity (MGFA Classification)

• Class I: Ocular symptoms only (ptosis, diplopia) 4
• Class II: Mild generalized weakness 4
• Class III: Moderate generalized weakness 4
• Class IV: Severe generalized weakness 4
• Class V: Myasthenic crisis requiring intubation 4

By Age and Antibody Pattern

Different subtypes include early-onset MG, late-onset MG, thymoma-associated MG, muscle-specific kinase (MuSK) MG, and seronegative MG, each with distinct clinical characteristics and treatment responses. 5

Natural History and Progression

50% of patients initially present with ocular symptoms only, but 50-80% of these will develop generalized disease within a few years. 1, 4 This progression pattern makes early recognition critical.

• Progression typically follows a pattern: ocular → bulbar → limb → respiratory involvement 3
• Myasthenic crisis (respiratory failure requiring ventilatory support) represents the life-threatening complication 1, 4
• Thymoma is present in 10-20% of patients with acetylcholine receptor antibody-positive disease 4

Epidemiology

• Incidence: 0.04 to 5 per 100,000 people per year 2, 1
• Prevalence: 0.5 to 12.5 per 100,000 people 2, 1
• No geographic or racial predilection in adults 2, 1
• Women typically affected in third to fourth decade of life, men later 1
• Increased risk with autoimmune thyroid disease and thymoma 2

Pediatric Forms

• Transient neonatal myasthenia: passed from mother via transplacental transmission 2, 1
• Congenital myasthenia: not immune-mediated 2, 1
• Juvenile autoimmune myasthenia: similar mechanism to adult form 2, 1

Critical Clinical Pitfalls

Failure to recognize respiratory compromise is the most dangerous pitfall - respiratory function can deteriorate rapidly, progressing to myasthenic crisis. 3, 4 Regular pulmonary function monitoring with negative inspiratory force (NIF) and vital capacity (VC) is essential. 3

Certain medications can precipitate or worsen myasthenic symptoms and must be avoided: 3, 4

• Beta-blockers
• IV magnesium
• Fluoroquinolone antibiotics
• Aminoglycoside antibiotics
• Macrolide antibiotics

Distinguishing myasthenic crisis from cholinergic crisis (overdose of anticholinesterase medications like pyridostigmine) is critical, as they require opposite treatments - one needs more medication, the other needs immediate withdrawal of all anticholinesterase drugs. 6

Management Principles

Early recognition and neurologist referral are essential for proper diagnosis and treatment initiation. 1, 4

• Thymectomy is indicated when thymoma is present, and may substantially reduce symptoms in specific age-based and immune-based patient groups 2, 1
• Treatment goals include preventing morbidity and mortality from generalized disease, reducing diplopia, improving eye alignment, and restoring normal function 1
• Monitoring for respiratory compromise is critical to prevent life-threatening complications 1, 4