Myasthenia Gravis

What happens in myasthenia gravis

When a nerve signals a muscle to contract, it releases acetylcholine, which binds to receptors on the muscle. In MG, antibodies attack these receptors (or related proteins such as MuSK or LRP4), so fewer signals get through. Muscles work at first but tire quickly with repeated use, which is the hallmark of the disease: fatigable weakness.

The thymus gland, behind the breastbone, plays a role. Many people with AChR-antibody MG have an overactive thymus, and about 10 to 15% have a thymus tumor (thymoma).

Symptoms

Weakness typically fluctuates, worsening later in the day or after exertion and improving after rest.

Eye muscles (ocular)

• drooping of one or both eyelids (ptosis)
• double vision

Eye symptoms are the first sign in over half of people. In about 15%, MG stays limited to the eyes (ocular myasthenia).

Face and throat (bulbar)

• slurred or nasal speech, especially after talking for a while
• difficulty chewing, with jaw fatigue during meals
• trouble swallowing, choking or fluid coming out of the nose
• a weak or "snarling" smile

Limbs and neck

• weakness in the arms (hard to brush hair) or legs (hard to climb stairs)
• neck weakness, with the head dropping forward

Breathing

• shortness of breath, especially lying flat, which can progress to a myasthenic crisis needing ventilator support

Triggers that worsen MG

• infections
• surgery and stress
• pregnancy and the postpartum period
• heat
• thyroid problems
• certain medicines: some antibiotics (aminoglycosides, fluoroquinolones, macrolides such as azithromycin), IV magnesium, beta-blockers, some anesthetic drugs, botulinum toxin and immune checkpoint inhibitors for cancer

Always tell clinicians and pharmacists you have MG before starting a new medicine.

Types

Diagnosis

• Examination: sustained upward gaze for 1 to 2 minutes to provoke drooping; repeated arm raising; the ice pack test (cold improves eyelid droop)
• Blood tests: AChR antibodies, MuSK antibodies and sometimes LRP4 antibodies
• Nerve tests: repetitive nerve stimulation showing a decreasing response, and single-fiber EMG, the most sensitive test
• Chest CT or MRI: to look for thymoma
• Thyroid tests and screening for other autoimmune conditions
• Breathing tests (vital capacity) when breathing weakness is a concern

Other conditions that can look similar include Lambert-Eaton syndrome, botulism, thyroid eye disease, brainstem stroke and motor neuron disease.

Treatment

Symptom relief

• Pyridostigmine: boosts acetylcholine at the nerve-muscle junction. Works within 30 to 60 minutes; side effects include cramps, diarrhea and excess saliva.

Immune therapies

• Corticosteroids (prednisone): effective, but long-term side effects mean doses are kept as low as possible.
• Steroid-sparing drugs: azathioprine, mycophenolate, tacrolimus or methotrexate, which take months to work.
• Newer targeted therapies for generalized AChR or MuSK disease: - complement inhibitors (eculizumab, ravulizumab, zilucoplan) for AChR-positive MG - FcRn blockers (efgartigimod, rozanolixizumab) that lower antibody levels - rituximab, especially effective in MuSK MG

Thymectomy

Surgical removal of the thymus is recommended for anyone with a thymoma. In AChR-positive generalized MG without thymoma, typically in adults under about 65, a large randomized trial showed thymectomy reduced symptoms and steroid needs.

Rapid treatments

• IV immunoglobulin (IVIG) or plasma exchange for crises, severe flare-ups and before surgery.

Myasthenic crisis

Hospital care, often in intensive care, with breathing support, plasma exchange or IVIG, and treatment of triggers such as infection.

Living with myasthenia gravis

• pace activities and rest between tasks
• schedule demanding activities when energy is best, often in the morning
• carry a medical alert card and a list of medicines to avoid
• get vaccinated against flu, COVID-19 and pneumococcus as advised (avoid live vaccines on immunosuppressants)
• plan pregnancy with your neurologist
• eat when pyridostigmine is working best if chewing is difficult

Outlook

Most people with MG achieve good control, and many reach minimal symptoms with treatment. Life expectancy is close to normal for most. Symptoms are often most severe in the first few years after onset.

Frequently asked questions

What are the first signs of myasthenia gravis?

The first signs are usually drooping eyelids and double vision that come and go and worsen at the end of the day. Others notice slurred speech, trouble chewing or swallowing, or arm and leg weakness that worsens with use and improves with rest.

What causes myasthenia gravis?

Myasthenia gravis is an autoimmune disease. The immune system makes antibodies that block or destroy acetylcholine receptors or related proteins where nerves meet muscles. The thymus gland is often involved. It is not inherited in most cases and is not contagious.

Is myasthenia gravis curable?

There is no guaranteed cure, but most people achieve good control with treatment. Some go into long-term remission, particularly after thymectomy. Newer targeted therapies have expanded options for people whose MG is hard to control.

What is a myasthenic crisis?

A myasthenic crisis is a severe worsening of MG in which breathing or swallowing muscles become too weak, sometimes requiring a ventilator. It is often triggered by infection, surgery or certain medicines and needs emergency hospital care.

Can myasthenia gravis affect only the eyes?

Yes. In ocular myasthenia, weakness is limited to the eyelids and eye muscles, causing drooping eyelids and double vision. Most people who will develop generalized MG do so within 2 years of eye symptoms starting.

What medicines should be avoided with myasthenia gravis?

Medicines that can worsen MG include some antibiotics (aminoglycosides, fluoroquinolones, macrolides), IV magnesium, beta-blockers, some anesthetic agents, botulinum toxin and immune checkpoint inhibitors. Check with your neurologist or pharmacist before starting any new medicine.