Myasthenia Gravis: Causes, Symptoms, Diagnosis and Treatment

Myasthenia gravis is a chronic autoimmune neuromuscular condition that causes muscle weakness and severe fatigue.



    The term “myasthenia gravis” is Latin and Greek in origin, and means "grave muscle weakness."

    The condition primarily affects the skeletal muscles, or the muscles attached to bones and responsible for skeletal movement.

    M. Gravis



    As many as 60,000 Americans are living with the condition, the Myasthenia Gravis Foundation of America says, but the disease often goes undiagnosed.

    Currently, there’s no cure for myasthenia gravis. However, available treatments usually can control symptoms, allowing those diagnosed with the condition to lead relatively normal lives.

    In addition, most people with myasthenia gravis have a normal life expectancy.

    Signs and Symptoms of Myasthenia Gravis

    The muscle weakness caused by myasthenia gravis is typically at its worst after periods of physical activity and gets better following rest.

    However, the muscles that control eye and eyelid movement, facial expressions, chewing, talking, and swallowing are often affected, making certain everyday activities challenging.

    The onset of myasthenia gravis can be sudden in some people, and the degree of muscle weakness varies from person to person.

    The condition can be challenging to diagnose because its symptoms mirror those of several other conditions, including generalized fatigue, amyotrophic lateral sclerosis (ALS), and botulism.

    Although symptoms vary slightly from one person to the next, most people with myasthenia gravis will experience at least some of the following:

    • Weakness of the arms, hands, fingers, legs, and neck
    • Weakness of the eye muscles (a condition called ocular myasthenia)
    • Drooping of one or both eyelids (a condition called ptosis)
    • Blurred or double vision (a condition called diplopia)
    • Alterations in facial expressions
    • Problems swallowing
    • Shortness of breath
    • Difficulty speaking (a condition called dysarthria)

    In general, the following have been shown to worsen the symptoms of myasthenia gravis:

    • Fatigue
    • Illness
    • Stress
    • Extreme heat

    Medication such as beta-blockers, quinidine gluconate, quinidine sulfate, quinine, phenytoin, some anesthetics, and some antibiotics

    Even though some types of medication have been shown to worsen the symptoms of myasthenia gravis, they may still be used if it’s more important to treat another underlying health condition, such as an infection or high blood pressure.

    If drug treatment for another condition is worsening your myasthenia gravis, ask your doctor if there are other options.

    Myasthenic Crisis
    When the muscle weakness caused by myasthenia gravis worsens, affecting the muscles in your chest and diaphragm and reducing your ability to breathe, it’s called a myasthenic crisis.

    A myasthenic crisis can be triggered by an infection, stress, surgery, or an adverse reaction to a medication, although in many cases there’s no obvious cause.

    Respiratory failure caused by myasthenia gravis requires emergency medical care, often including the use of a mechanical ventilator to help you breathe while other therapies are administered to reverse the crisis.

    A myasthenic crisis is most commonly treated either with a blood product called intravenous immune globulin (IVIG), which provides antibodies in which the person is deficient, or plasma exchange (plasmapheresis, or PLEX), which removes the autoantibodies that attack the body’s own cells.

    Up to one in five people with myasthenia gravis experiences at least one myasthenic crisis after they’ve been diagnosed. If you’re feeling short of breath, particularly if you’re also having trouble speaking, coughing, chewing, swallowing, or holding your head up, seek medical help immediately.

    Causes and Risk Factors of Myasthenia Gravis

    Myasthenia gravis is caused by a breakdown in the normal communication between nerves and muscles that occurs at the neuromuscular junction, where your nerve cells connect with the muscles they control.

    Normally, at the neuromuscular junction, when your brain sends electrical signals or impulses down a motor nerve, the nerve endings release a neurotransmitter called acetylcholine, which attaches, or binds, to sites in your muscles called acetylcholine receptors. This activates the muscle and causes a muscle contraction.

    In people with myasthenia gravis, however, antibodies (proteins produced by your immune system to fight off infection) block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction, which prevents the muscle from contracting. This is typically caused by antibodies to the acetylcholine receptor.

    In addition, antibodies to a protein called muscle-specific kinase (MuSK) may also disrupt transmission at the neuromuscular junction.

    Researchers also think that a part of your immune system called the thymus gland, situated in the upper chest beneath your breastbone, may trigger or maintain the production of the antibodies that block the neurotransmitter acetylcholine.

    While the thymus is small in healthy adults, it's abnormally large in some adults with myasthenia gravis.

    In addition, tumors (which usually aren't cancerous) may be present in the thymus glands of people with myasthenia gravis, affecting antibody production. These tumors are called thymomas.

    The role of antibodies and the thymus gland in myasthenia gravis in some people is what makes the condition an autoimmune disorder — meaning that the immune system mistakenly attacks itself.

    However, some people have what’s called antibody-negative myasthenia gravis, which means the condition hasn’t been caused by antibodies blocking acetylcholine or MuSK. In these cases, antibodies against another protein, lipoprotein-related protein 4, play a part in the development of the condition.

    In addition, in rare instances, mothers with myasthenia gravis have children who are born with the condition because they pass antibodies blocking acetylcholine or MuSK to the fetus in the womb. This is called neonatal myasthenia gravis.

    However, if the condition is diagnosed and treated promptly, these children generally recover within two months of their birth.

    Congenital Myasthenic Syndrome

    Some children may also be born with a rare form of myasthenia gravis called congenital myasthenic syndrome.

    The condition is extremely rare, and unlike myasthenia gravis, congenital myasthenic syndrome is not an autoimmune disease. Instead, it’s caused by inherited genetic mutations of the CHRNE, RAPSN, CHAT, COLQ, or DOK7 gene.

    Like people with myasthenia gravis, children with congenital myasthenic syndrome experience muscle weakness (myasthenia) that worsens with physical activity. This typically begins in early childhood but can also appear in adolescence or adulthood.

    The muscles in the face, including those that control the eyelids, move the eyes, and enable chewing and swallowing, are most commonly affected. However, other skeletal muscles can also be affected.

    Because of the muscle weakness caused by congenital myasthenic syndrome, infants may have feeding difficulties and may experience delays in their development of motor skills, including crawling or walking.

    Myasthenia Gravis and COVID-19

    In August 2020, researchers in Italy described the development of myasthenia gravis in three adults with severe COVID-19 in an article published in the journal Annals of Internal Medicine.

    The three adults, who ranged in age from 64 to 71, developed their myasthenia gravis symptoms five to seven days after fever related to the new coronavirus first appeared. None of the three had prior history of neurologic or autoimmune disorders.

    However, all three were positive for antibodies that block acetylcholine. These antibodies, which have been shown to cause myasthenia gravis, may have been activated by COVID-19, the researchers say.

    One of the three developed respiratory failure — either as a result of the virus or myasthenia gravis.

    Although the potential links between COVID-19 and myasthenia gravis are concerning, as infections continue to rise globally, it’s important to note that these are the only three cases to have been reported so far.

    Still, if you have myasthenia gravis, it may place you at increased risk for serious illness from COVID-19. Talk to your doctor about steps you can take to minimize your risk.

    How Is Myasthenia Gravis Diagnosed?

    To determine if you have myasthenia gravis, your doctor will review your symptoms and medical history and give you a physical exam.

    A healthcare professional may also conduct the following tests:

    Neurological Exam This allows your doctor to check the following:

    • Reflexes
    • Muscle strength
    • Muscle tone
    • Senses of touch and sight
    • Coordination
    • Balance

    Ice Pack Test If you have weakness in your eyelids, your doctor may place an ice-filled bag on your eyelids for a couple of minutes. In people who have myasthenia gravis, the cooling effect of the ice may temporarily improve the function of the eyelid muscles.

    Blood Tests If your physical exam suggests myasthenia gravis, your doctor will likely order a blood test designed to detect antibodies to the acetylcholine receptor. And if that blood test is negative, you may be tested for muscle-specific kinase (MuSK) antibodies or other, less common antibodies.

    Repetitive Nerve Stimulation In this test, electrodes are attached to your skin over the muscles to be tested, and small pulses of electricity are used to measure the nerve's ability to send a signal to your muscle. Your doctor will test the nerve several times to see if its ability to send signals worsens with fatigue. This test may be uncomfortable.

    Single-Fiber Electromyography (EMG) Electromyography measures the electrical activity traveling between your brain and your muscle through a fine wire electrode inserted through your skin and into a muscle. This test may also be uncomfortable.

    Imaging Scans Your doctor may order a computed tomography (CT) scan or a magnetic resonance imaging (MRI) scan to see whether there's a tumor in your thymus.

    Pulmonary Function Tests To determine if and how your condition is affecting your breathing, your doctor may order pulmonary function tests, such as spirometry or plethysmography. In spirometry, you take a deep breath and blow into a mouthpiece. In plethysmography, you sit in an airtight room and breathe into a mouthpiece as instructed by a technician.

    In years past, doctors used what was called the edrophonium test, also called the Tensilon test, in which the chemical edrophonium was injected into a vein to see whether muscle strength suddenly yet temporarily improved. Edrophonium blocks the breakdown of acetylcholine. However, the FDA discontinued its use in 2018 because of a high rate of false positives “and the development of serological antibody testing as the gold standard for the diagnosis of MG.”

    Prognosis of Myasthenia Gravis

    With treatment, most people with myasthenia see significant improvements in their muscle weakness, and they can lead normal or nearly normal lives.

    Roughly 3 percent of people who develop the condition will die from it, and the risk for death is higher in those diagnosed at age 40 or older as well as those with thymoma.

    Still, given the low risk for early death associated with myasthenia gravis, the “gravis” part of the name is now considered a misnomer.

    In fact, some people with the condition may even experience remission — a temporary or permanent absence of symptoms. Their muscle weakness may disappear completely.

    If you experience remission, your doctor may discontinue your medication.

    In addition, up to 50 percent of people who undergo thymectomy surgery experience stable, long-lasting complete remission.

    Duration of Myasthenia Gravis

    Even if your myasthenia gravis goes into remission, it can still return. Indeed, once you’ve been diagnosed with the condition, you’ll likely be managing its symptoms for the rest of your life.

    Treatment and Medication Options for Myasthenia Gravis
    Myasthenia gravis is typically treated by a neurologist, and with treatment, the symptoms of myasthenia gravis can be well controlled. For example, a variety of therapies help to improve muscle weakness.

    Your neurologist will determine which treatment option is best for you based on the following:

    • Your age
    • The severity of your condition
    • The muscles affected
    • Any other medical conditions you have

    Medication Options

    Several different types of medication are used to treat myasthenia gravis.

    Anticholinesterase agents such as Mestinon (pyridostigmine) are designed to help improve communication between nerves and muscles. Although these medications won’t cure myasthenia gravis, they can improve muscle contraction and muscle strength in some people.

    Possible side effects include gastrointestinal upset, diarrhea, nausea, and excessive salivation and sweating.

    In addition, corticosteroids such as prednisone improve muscle strength by suppressing the immune system and disrupting production of the antibodies that cause myasthenia gravis.

    However, prolonged use of these medications can cause serious side effects, including bone thinning (osteoporosis), weight gain, diabetes, and increased risk of some infections. If your doctor prescribes corticosteroids, you may need to come in for regular visits to be monitored for any of these side effects.

    Your doctor might also prescribe immunosuppressants. As the name suggests, these drugs — Imuran (azathioprine), CellCept (mycophenolate mofetil), Neoral (cyclosporine), Trexall (methotrexate), and Prograf (tacrolimus) — alter your immune system to limit production of harmful antibodies.

    These drugs can take months to work and might be used with corticosteroids. Possible side effects include increased risk of infection and liver or kidney damage.

    Finally, Rituxan (rituximab) and Soliris (eculizumab) are monoclonal antibodies that may be used in the short term to treat a sudden worsening of symptoms in people with anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis.

    However, these drugs have several potentially serious side effects, including:

    • Increased risk for meningitis
    • Hypertension
    • Headache
    • Nasal inflammation
    • Musculoskeletal pain, including back pain
    • Abdominal pain, nausea, vomiting, and diarrhea
    • Increased risk for upper respiratory infections
    • Cough
    • Increased risk for urinary tract infections
    • Anemia
    • Peripheral edema

    Other medical procedures used in the treatment of myasthenia gravis include plasmapheresis and high-dose immune globulin injections — the same treatments as are used for myasthenic crises.

    In plasmapheresis, a filtering process like kidney dialysis, blood is routed through a machine that removes the antibodies that are causing your myasthenia gravis. However, the benefits are typically short-term, and the procedure may cause a drop in blood pressure, bleeding, heart rhythm problems, and muscle cramps.

    In high-dose intravenous immune globulin, injections of these drugs temporarily modify the immune system by infusing antibodies from donated blood. This provides your body with normal antibodies.

    The benefits of this approach are typically seen in less than a week and can last three to six weeks. Possible mild side effects include chills, dizziness, headaches, and fluid retention.

    Surgery

    For those with myasthenia gravis caused by a tumor in their thymus gland, surgical removal of the gland — in a procedure called a thymectomy — can help reduce symptoms. It may even cure some people with the condition by stopping the process that’s causing the disease.

    Even if you don't have a tumor in the thymus gland, removing it may improve your myasthenia gravis symptoms and allow you to stop taking medication.

    However, it can take years to notice the benefits of a thymectomy. And, in some cases, people may never notice improvements.

    Energy Conservation and Improved Home Safety
    In addition to any medical therapies you may use to control your symptoms, these self-care suggestions can help you to maximize your energy and improve your quality of life with myasthenia gravis

    Eat when you have good muscle strength, and take your time chewing your food, the Mayo Clinic recommends.

    Eat mostly soft foods, and avoid those that require more chewing, such as raw fruit or vegetables.

    Try eating small meals several times a day, rather than two or three big meals.

    Install grab bars or railings in areas of your home where you most need support, such as next to your bathtub or along any steps or staircases.

    Keep your floors clear of clutter, and remove area rugs that may cause you to trip or slip, particularly when tired.

    Clear your yard, sidewalks, and driveway of leaves, snow, and other debris that could cause you to fall.

    Use electric appliances for daily activities — like an electric toothbrush or an electric can opener — to help you conserve energy.

    Try to plan your daily activities ahead of time, so that you perform chores and errands at times when you have the most energy.

    Rest when you feel tired.

    Prevention of Myasthenia Gravis

    There is no way to prevent myasthenia gravis. However, if you have the condition, there are steps you can take to prevent your symptoms from worsening, including:

    Reduce stress. Stress is known to worsen muscle weakness and contractions in myasthenia gravis. Avoiding stressful situations at home or work can help, but given that it’s not always possible, it makes sense to find stress management strategies — like exercise, mindfulness meditation, hobbies — that work for you.

    Prevent infections. Myasthenia gravis symptoms can be triggered by common infections, and the condition places you at increased risk for some of them. Practicing good hand hygiene (washing your hands regularly) can help you avoid many common infections. If you develop an infection, get treated for it as soon as possible.

    Avoid getting too hot or too cold. Extreme heat or cold can trigger myasthenia gravis symptoms.

    Don’t overdo it. Exercising too much or working too hard can worsen myasthenia gravis symptoms. Know your limits and rest when needed.

    Seek accommodations at work if necessary. Pay attention to how you feel at work, and let your employer know if you need changes in your schedule or work environment to be more effective on the job. These organizations can help you learn more about your rights under the Americans With Disabilities Act and about possible accommodations that may help you at your job.

    Complications of Myasthenia Gravis

    While complications of myasthenia gravis are treatable, some can be life-threatening.

    Complications may include the following:

    Myasthenic crisis is a life-threatening condition that affects breathing and requires immediate treatment for the person to be able to breathe on their own.

    People with myasthenia gravis may also experience more severe symptoms from high blood pressure, diabetes, and heart disease than others.

    Thymus tumors, which usually are not cancerous, occur in about 10 percent of people with myasthenia gravis, according to the National Organization for Rare Disorders (NORD).

    People with myasthenia gravis are more likely to have underactive or overactive thyroid and autoimmune conditions, such as rheumatoid arthritis or lupus.

    Research and Statistics: Who Has Myasthenia Gravis?
    According to the Myasthenia Gravis Foundation of America, about 20 out of 100,000 people in the United States are living with myasthenia gravis.

    Myasthenia gravis occurs in all races, both genders, and at any age. However, it most commonly affects women in their 20s and 30s and men in their 50s and 60s.

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