What Causes Myasthenia Gravis?

The severe weakness of myasthenia gravis may lead to respiratory failure, which requires immediate emergency medical care.

Myasthenia gravis is rare chronic autoimmune disorder that causes skeletal muscle weakness. Skeletal muscles, also called voluntary muscles, are those that produce movement in the body, for example, the muscles in the arms or legs and those that control facial movements. The muscle weakness caused by myasthenia gravis fluctuates and worsens following activity and improves after rest. 

Symptoms of myasthenia gravis may have a sudden onset and can include:

• Fluctuating muscle weakness and fatigue that worsens with activity and improves with rest
  • Limb weakness may be felt closer to the trunk where the limbs originate, than farther away at the hands or feet though it can affect any part of the body 
  • Weakness progresses from mild to severe over weeks or months
  • There may be periods of worsening symptoms and periods of remission 
• Eye symptoms
  • Weakness of the eye muscles 
  • Drooping eyelids
  • Blurred or double vision 
• Bulbar symptoms (named after the nerves that originate from the bulblike part of the brain) 
  • Weakness and fatigue in the neck and jaw
  • Problems with speaking 
  • Difficulty chewing or swallowing
  • Difficulty holding up the head

For most patients, myasthenia gravis has no known cause (it is idiopathic). Myasthenia gravis is an autoimmune disease and for an unknown reason the immune system of affected patients makes antibodies against the receptor sites of the chemical communication between nerve fibers and muscle cells (called the neuromuscular junction). These receptor sites are destroyed faster than the body can replace them, and muscle weakness results. 

The thymus gland controls immune function and it is thought to be associated with myasthenia gravis. Thymus gland disorders are common in patients with myasthenia gravis: 85% have thymic hyperplasia, 75% have thymic disease, and 10–15% have thymoma. It is believed the thymus gland may give incorrect instructions to developing immune cells, causing the immune system to attack its own cells and tissues.

Certain triggers may cause symptoms of myasthenia gravis to worsen, such as:

• Exposure to extreme heat 
• Emotional stress
• Infection 
• Systemic illness
• Pregnancy
• The menstrual cycle

Certain drugs may precipitate or worsen myasthenia gravis symptoms, including:

• Antibiotics 
• Penicillamine 
• Beta-blockers
• Lithium
• Magnesium
• Procainamide
• Verapamil
• Quinidine
• Chloroquine
• Prednisone
• Timolol
• Anticholinergics
• Neuromuscular blocking agents 
• Nitrofurantoin 
• Cancer immunotherapy

A doctor will first perform a physical and neurological exam. The neurological portion checks muscle strength and tone, sensation of touch, muscle coordination, and impairment of eye movements. 

Other tests to help diagnose myasthenia gravis include: 

• Blood tests to check for certain antibodies
  • Anti–acetylcholine receptor (AChR) antibody 
  • Anti-MuSK antibody
  • Anti-lipoprotein-related protein 4 (LRP4) antibody
  • Anti-agrin antibody
  • Antistriational antibody 
  • Anti-cortactin antibody
• Edrophonium test - uses injections of edrophonium chloride to briefly relieve weakness in people with myasthenia gravis
• Electrodiagnostic tests
  • Repetitive nerve stimulation
  • Single fiber electromyography (EMG)
• Imaging tests
  • CT scan
  • Magnetic resonance imaging (MRI)
  • Chest X-rays
  • Pulmonary function tests to measure breathing strength 

Treatment for myasthenia gravis is based on several factors, including the profile of antibodies in the blood, the age of onset, the presence or absence of a thymic disorder, and the distribution of weakness.

Therapy for myasthenia gravis is included the following:

• Symptomatic therapy
• Anticholinesterase (AchE) inhibitors
• Pyridostigmine or neostigmine for maintenance 
• Rapidly acting or short-term immunomodulating agents: Intravenous immune globulin (IVIg)
• Plasmapheresis
• Long-term immunosuppression with medications
  • Prednisone 
  • Azathioprine (Imuran)
  • Mycophenolate mofetil (CellCept)
  • Cyclosporine (Sandimmune, Neoral, Gengraf)
  • Tacrolimus (Envarsus XR, Protopic, Astagraf XL)
  • Methotrexate (Otrexup, Xatmep, Trexall)
  • Rituximab (Rituxan, Truxima)
  • Cyclophosphamide 
• New immunotherapies: eculizumab (Soliris)
• Investigational agents for the treatment of myasthenia gravis  
  • Ocrelizumab (Ocrevius)
  • Abatacept (Orencia)
  • Daclizumab (Zinbryta)
  • Belimumab (Benlysta)
  • Bortezomib (Velcade)
  • Fc receptor modulators (FcRn–IgG) 
  • Human monoclonal antibodies: brodalumab (Siliq), ixekizumab (Taltz), and secukinumab (Cosentyx)
  • Toclizumab (Actemra)
  • Autologous stem cell transplantation 
  • 3,4-Diaminopyridine
  • Tirasemtiv 
• Thymectomy – surgical removal of the thymus gland

The severe weakness of myasthenia gravis may lead to respiratory failure, which requires immediate emergency medical care. This is called a myasthenic crisis.

Certain long-term immunomodulating drugs used in the treatment may predispose patients to complications. Long-term steroid use may cause or aggravate osteoporosis, cataracts, high blood sugar (hyperglycemia), weight gain, avascular necrosis of hip, high blood pressure (hypertension), opportunistic infection, and an increased risk of gastritis or peptic ulcer disease. 

Other complications of immunomodulating therapy include infections such as tuberculosis, systemic fungal infections, and Pneumocystis carinii pneumonia. Immunosuppressive drugs may also have cancer-causing effects.

With proper diagnosis and treatment, most patients with myasthenia gravis have a near-normal life expectancy. 

Risk factors for poor prognosis include:

• Age over 40 years
• Short history of rapidly progressive disease
• Thymoma