Myasthenia gravis is an autoimmune disease that affects the voluntary muscles in the body. It causes weakness and rapid fatigue of any muscles under voluntary control. The weakness gets worse with activity and improves with rest.
What causes myasthenia gravis?
Myasthenia gravis is caused by an autoimmune attack on the neuromuscular junctions. This is the place where nerve cells connect with the muscles they control. In myasthenia gravis, antibodies block or destroy these receptor sites, preventing the nerve signals from getting through to the muscles.
There are a few different antibodies that can contribute to this process. The most common ones are:
- Anti-acetylcholine receptor (AChR) antibodies – These block the receptors on the muscle cells that acetylcholine binds to in order to trigger muscle contraction.
- Anti-muscle specific kinase (MuSK) antibodies – These block the protein that helps organize and maintain the neuromuscular junction.
- Anti-LRP4 antibodies – These block another protein that helps maintain the structure of the neuromuscular junction.
When these antibodies interfere with signal transmission from the nerve to the muscle, muscle weakness occurs. The weakness tends to build up over time with continued use of the muscle.
What organs and systems are affected?
Although myasthenia gravis can potentially weaken any voluntary muscle in the body, certain muscle groups are more frequently affected than others:
Muscles controlling eye and eyelid movement
The extraocular muscles that control eye movements and the levator palpebrae superioris muscle that elevates the eyelids are commonly affected. This leads to symptoms like:
- Double vision (diplopia)
- Drooping eyelids (ptosis)
- Impaired eye movements
Eye and eyelid involvement occurs in over 50% of people with myasthenia gravis. For some people, it may be the only symptom.
Muscles of facial expression
Facial weakness can cause difficulty holding up the head or maintaining facial expressions.
Muscles involved in swallowing and speech
The muscles of the mouth, jaw, and throat are often involved, leading to symptoms like:
- Slurred speech (dysarthria)
- Nasal speech
- Drooling
- Choking or coughing when eating
This demonstrates impairment of the bulbar muscles, which are the muscles used for swallowing and speech.
Muscles of the neck and limbs
Weakness can occur in the muscles of the neck, shoulders, upper arms, forearms, thighs, and calves. This can cause symptoms like:
- Difficulty holding the head up
- Unable to raise the arms over the head
- Foot drop or stepping gait
Respiratory muscles
In very severe cases, the muscles involved in breathing can be affected. Weakness of the diaphragm and intercostal muscles makes breathing more difficult.
What are the stages of myasthenia gravis?
Myasthenia gravis can be classified into different stages depending on the distribution and severity of muscle weakness:
Ocular myasthenia
Only the extraocular muscles controlling eye movement and eyelids are affected. This is the mildest form, but can progress to other forms.
Mild generalized myasthenia
Muscle weakness is generalized but mild. Commonly affected muscle groups include facial muscles, muscles controlling swallowing and speech, and proximal limb muscles. But daily activities are still possible.
Moderate generalized myasthenia
Muscle weakness is significant enough to interfere with daily activities like brushing hair or climbing stairs.
Severe generalized myasthenia
Widespread muscle weakness affecting multiple muscle groups, including possible respiratory impairment requiring intubation or non-invasive ventilation.
Myasthenic crisis
Rapid worsening of muscle weakness over hours to days, often leading to respiratory failure. This is a medical emergency requiring hospitalization.
What tests help diagnose myasthenia gravis?
There are a few different tests that can help confirm a diagnosis of myasthenia gravis by demonstrating impaired neuromuscular transmission:
Antibody blood tests
Blood tests can detect antibodies against the acetylcholine receptor or muscle-specific tyrosine kinase:
- Anti-AChR antibodies are found in 85% of people with generalized myasthenia gravis and 50% with ocular myasthenia.
- Anti-MuSK antibodies are found in 40% of people who are negative for anti-AChR.
Edrophonium test
This test involves intravenous injection of edrophonium chloride, which temporarily improves neuromuscular transmission and muscle strength. A positive result is rapid improvement in muscle weakness after the injection.
Electromyography
Repeated nerve stimulation shows progressive decline in muscle response, representing impaired neuromuscular transmission.
Single-fiber EMG
Measures jitter and blocking between muscle fibers, which is increased with defective neuromuscular transmission.
How is myasthenia gravis treated?
Although there is no cure for myasthenia gravis yet, there are several treatment options available to help manage symptoms:
Acetylcholinesterase inhibitors
Medications like pyridostigmine help slow the breakdown of acetylcholine at the neuromuscular junction. This makes more acetylcholine available to stimulate muscle contraction.
Immunosuppressants
Drugs like prednisone, azathioprine, mycophenolate mofetil, and cyclosporine suppress the immune system to reduce antibody production.
Intravenous immunoglobulin
IVIg helps by binding up the harmful antibodies.
Plasmapheresis
This procedure filters the antibodies out of the blood.
Thymectomy
Removing the thymus gland can sometimes improve symptoms. This is often done for younger myasthenia patients.
What is the prognosis for myasthenia gravis?
With treatment, most people with myasthenia can have significant improvement in their muscle weakness and quality of life. Complete remission can occur in up to 20% of patients.
The outlook also depends on the type of myasthenia gravis:
- Ocular myasthenia has the best prognosis, with rare progression to generalized MG.
- Early-onset myasthenia patients who undergo thymectomy also tend to have better outcomes.
- Anti-MuSK antibody myasthenia may be more treatment resistant.
- Myasthenic crisis carries up to 15-20% mortality if ventilation support is delayed.
With modern treatments, the overall mortality rate of myasthenia gravis has declined to around 4% of patients.
Conclusion
Myasthenia gravis is an autoimmune disorder caused by antibodies blocking neuromuscular transmission. This results in weakness and rapid fatigability of voluntary muscles, especially ocular, bulbar, facial, and limb muscles. Diagnosis involves blood tests, edrophonium testing, and electrodiagnostic studies. Treatment includes acetylcholinesterase inhibitors, immunosuppression, plasmapheresis, and sometimes thymectomy. With comprehensive treatment, most patients can achieve good symptom control and quality of life.