Understanding Myasthenia Gravis
Myasthenia gravis is an autoimmune disorder that affects the neuromuscular junction, causing variable muscle weakness that worsens with activity and improves with rest, potentially leading to life-threatening respiratory failure if generalized. 1
What is Myasthenia Gravis?
Myasthenia gravis (MG) is a B-cell mediated autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue. It occurs when antibodies attack components of the neuromuscular junction, disrupting normal transmission of nerve signals to muscles. 1
There are two main types:
- Ocular myasthenia gravis: Affects only the levator, orbicularis oculi, and extraocular muscles 1
- Generalized myasthenia gravis: Affects larger muscle groups and may include ocular features 1
Disease Mechanism
- Acetylcholine is normally released at the neuromuscular junction during an action potential and crosses the synapse to reach muscle fibers 1
- In myasthenia gravis, antibodies attack acetylcholine receptors, preventing proper nerve signal transmission 1
- Acetylcholine receptor antibodies are found in:
- Nearly all patients with generalized myasthenia gravis
- 40-77% of patients with ocular myasthenia gravis 1
- Extraocular muscles are particularly susceptible to fatigue due to their twitch fiber composition and fewer acetylcholine receptors 1
Who Gets Myasthenia Gravis?
- Affects people of all ages, races, and geographic regions 1
- Incidence: 0.04 to 5 per 100,000 people per year 1
- Prevalence: 0.5 to 12.5 per 100,000 people 1
- Adult onset typically occurs in:
- Women: Third to fourth decade of life
- Men: Later in life 1
- Risk factors include:
- Some children may develop:
- Transient neonatal myasthenia (passed from mother)
- Congenital myasthenia (not immune-mediated)
- Juvenile autoimmune myasthenia 1
Common Symptoms
- Ocular symptoms (often first to appear):
- Drooping eyelids (ptosis)
- Double vision (diplopia)
- Variable strabismus (misalignment of eyes) 1
- Generalized symptoms:
- Facial weakness
- Difficulty chewing and swallowing
- Slurred speech
- Difficulty holding up the head
- Limb weakness
- Respiratory muscle weakness 1
Key Characteristics
- Fluctuating weakness: Symptoms worsen with continued activity and improve with rest 1
- Fatiguability: Symptoms worsen as the day progresses or with repetitive use of affected muscles 1
- Variable presentation: The pattern of weakness can change during examination 1
- "Great masquerader": Can mimic many types of eye movement disorders 1
- Temporary improvement: Symptoms may temporarily improve with rest or application of ice (ice pack test) 1
Natural History and Complications
- 50% of patients initially present with ocular symptoms only 1
- 50-80% of those with initial ocular symptoms develop generalized myasthenia within a few years 1
- If generalized, MG can involve bulbar, limb, and respiratory muscles 1
- Life-threatening complication: Respiratory failure requiring ventilatory support 1, 3
- Increased risk for other autoimmune disorders, especially thyroid disease 2
Diagnosis
Diagnosis is based on:
- Clinical presentation of fluctuating muscle weakness 1
- Characteristic findings:
- Variable strabismus and ptosis that worsen with fatigue
- Improvement after rest or ice pack test
- Slow ocular saccades (rapid eye movements) 1
- Blood tests for acetylcholine receptor antibodies 4, 3
- Other antibody tests may include muscle-specific kinase (MuSK) and lipoprotein receptor-related protein 4 (Lrp4) 3
Treatment Options
Treatment goals include:
- Preventing morbidity and mortality from generalized myasthenia gravis 1
- Reducing double vision and improving eye alignment 1
- Restoring normal appearance and function 1
Treatment approaches include:
- Symptomatic treatment: Anticholinesterase drugs like pyridostigmine 4, 3
- Immunosuppressive therapy: Corticosteroids and other immunosuppressants 4, 3
- Thymectomy: Surgical removal of the thymus gland, especially if thymoma is present 1, 3
- Plasma exchange: Removes harmful antibodies from the blood 4, 3
- Intravenous immunoglobulin: Provides temporary immune modulation 4, 3
- Newer targeted therapies: Including monoclonal antibodies that target specific parts of the immune system 5, 3
Important Considerations
- Early recognition is crucial: Prompt diagnosis allows for appropriate treatment and prevention of complications 1
- Neurologist referral: Essential for proper management 1
- Individualized treatment: Different MG subtypes respond differently to various treatments 6
- Monitoring for respiratory compromise: Critical to prevent life-threatening complications 1
- Trigger avoidance: Infections, fever, physical/emotional exhaustion can worsen symptoms 4
Remember that with proper treatment, most people with myasthenia gravis can lead normal or nearly normal lives, though they may need ongoing medical care.