What Is Myasthenia Gravis? What Causes Myasthenia Gravis?

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Main Category: Neurology / Neuroscience
Article Date: 22 Feb 2010 - 0:00 PDT

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In Myasthenia gravis, also known as Goldflam disease, a neuromuscular disease, the muscles under our voluntary control become easily tired and weak because there is a problem with how the nerves stimulate the contraction of muscles. Typically, the muscles around the eyes are affected first, causing the eyelids to droop; some patients also develop double vision.

Muscles we cannot control voluntarily, such as the heart muscles, are not affected.

Myasthenia gravis is an autoimmune disorder, in which circulating antibodies cause weakness by blocking acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. The disease is treated with immunosuppressants or cholinesterase inhibitors. Although there is no cure, treatment is effective in alleviating symptoms of arm/leg weakness, double vision, drooping eyelids, speech difficulties, chewing, swallowing and breathing. In fact, many people with the disease become completely free of symptoms after treatment.

Symptoms generally worsen with physical activity and improve after resting or a good night's sleep.

Affecting 1 or 2 people in every 10,000, myasthenia gravis is one of the less common autoimmune disorders. Myasthenia gravis (MG) is distinguished from congenital myasthenic syndromes (which have similar symptoms) in that MG responds well to immunosuppressive interventions, while congenital myasthenic syndromes do not.

Myasthenia gravis more commonly occurs in women under 40 years and men over 60. However, it may affect individuals of any age.

According to Medilexicon's medical dictionary:

Myasthenia gravis is " a disorder of neuromuscular transmission marked by fluctuating weakness and fatigue of certain voluntary muscles, including those innervated by brainstem motor nuclei; caused by a marked reduction in the number of acetylcholine receptors in the postsynaptic membrane of the neuromuscular junction, resulting from an autoimmune mechanism."

What are the signs and symptoms of myasthenia gravis?

A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign.

Muscle weakness severity varies greatly among patients with MG. Sometimes the weakness may be in a localized form, such as just the eye muscles, while in other cases it may be in a severe or generalized form in which many muscles are affected; even those that control breathing.

• The main feature of myasthenia gravis is the patient's susceptibility to fatigue (fatigability, fatiguability).
• Muscles become progressively weaker during periods of activity
• Muscles improve after periods of rest
• Eye muscles - in over 50% of patients the first signs and symptoms involve eye muscles, including such problems as ptosis (drooping of one or both eyelids), diplopia (double vision), and blurred vision (which may be intermittent). For about 15% of patients only the eye muscles are affected - in such cases their condition is known as ocular myasthenia.
• Facial muscles - for approximately 15% of patient the first symptoms involve the throat and face muscle. In such cases individuals may have problems with:
  
  
  • Speaking (dysarthria) - depending on which muscles are affected, speech may become soft or nasal.
  • Swallowing (dysphagia) - the patient may choke easily, making eating, drinking, swallowing pills harder. Sometimes when the individual tries to drink, the liquid comes out of his/her nose.
  • Chewing - muscles used for chewing may weaken considerably during a meal, especially if the person has been eating something hard or chewy, such as a steak.
  • Facial expressions - some people may develop an unusual or different smile if certain facial muscles are affected.
• Limbs - the arm and leg muscles may weaken, affecting such activities as lifting or walking (the patient's walk may seem like a waddle). When limb muscles are affected, this generally occurs in conjunction with other muscles in the body, such as the throat, eyes or face.

See a doctor if you have problems:

• Breathing
• With your vision
• Swallowing
• Chewing
• Walking

Myasthenic crisis - this is when the respiratory muscles become paralyzed. The patient requires assisted ventilation to stay alive. In patients with already weakened respiratory muscles, myasthenic crises may be triggered by infection, fever, an autonomic nervous system, an adverse reaction to some medication, or emotional stress.

What are the causes of myasthenia gravis?

Myasthenia gravis is an autoimmune disease.

What is an autoimmune disease? It is an illness that develops when the person's body tissues are attacked by their own immune system. Our immune system is a complex organization within the body which is designed to find and destroy foreign undesirable invaders, such as bacteria, toxins, or viruses. If somebody has an autoimmune disease their abnormal antibodies, which circulate in the blood, attack desirable things (things that should be protected and not destroyed), such as body tissues.

In the case of myasthenia gravis, antibodies are produced that block or destroy muscle receptor cells, resulting in fewer available muscle fibers. Our nerves communicate with our muscles by releasing neurotransmitters (type of chemicals) which fit precisely into receptor sites on the muscle cells (muscle receptor cells). Consequently, there is inadequate communication between the nerves and affected muscles; the muscles cannot contract properly and become tired and weak very easily - with fewer receptor sites the muscles receive fewer nerve signals.

Why some people's immune systems make antibodies that attack muscle receptor cells is still unknown. Experts say that the thymus gland (located in the upper chest beneath the breastbone) is probably associated with the production of the abnormal antibodies. The thymus gland is large during infancy and small during adulthood; however, a significant number of adult patients with myasthenia gravis have an abnormally large thymus gland. About 1 in 10 myasthenia patients have a non-cancerous tumor of the thymus gland.

We suspect, but are not sure wheter certain medications or viruses might trigger the onset of myasthenia gravis. Symptoms among patient who already have the disease may worsen with some medications, such as beta blockers, calcium channel blockers, quinine, and some antibiotics. Many believe some people have a genetic propensity to developing the disease.

The following are known to make symptoms worse:

• Emotional/mental stress
• Illness
• Some medications
• Tiredness
• Very high temperatures

Diagnosing myasthenia gravis

Patients who experience undue weakness which improves with rest have the hallmark signs of myasthenia gravis (MG) - it is a key sign. A GP (general practitioner, primary care physician) may also suspect MG if the patient has impaired eye movements or muscle weakness which is not accompanied by the loss of the ability to feel things. Nevertheless, as MG shares signs and symptoms with some other conditions, the diagnosis will need to be confirmed.

MG patients whose muscles are weak respond well to the application of ice to the affected area. Some doctors may try this initially as they gather data to help them make a diagnosis.

If the patient sees a GP who suspects possible MG, he/she will most likely be referred to a neurologist (a doctor specialized in the human nervous system) to confirm diagnosis. The following diagnostic tests will probably be ordered:

Edrophonium test - this test is usually only ordered when other tests have not yet yielded a conclusive diagnosis. Edrophonium chloride (Tensilon, Reversol) or neostigmine (Prostigmin) is injected into a vein - the drug clocks the breakdown of acetylcholine by cholinesterase (cholinesterase inhibitors) and temporarily increases the levels of acetylcholine at the neuromuscular junction - put simply, edrophonium bocks an enzyme that breaks down acetylcholine, the chemical that transmits signals from the nerve ending to the muscle receptor sites. Some patients may experience a brief period in which muscle weakness is relieved, especially those with weakness in the eye muscles.

Blood tests - the aim here is to identify certain antibodies:

• One test is for antibodies against the acetylcholine receptor. This test has a reasonable sensitivity of 80% to 90%. However, it may be as low as 50% in ocular myasthenia patients (those with just eye muscle weakness).
• Some MG patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein. A blood test may detect those antibodies.
• In some rare cases, when the doctor may want to rule out Lambert-Eaton syndrome, the blood test will attempt to detect antibodies against a voltage-gated calcium channel.

Repetitive nerve stimulation - electrodes are attached to the skin over the affected muscles. Small electrical pulses are sent through the electrodes to measure how well the nerves send a signal to the muscle. The electrical pulses will be applied several times to determine whether signals get worse when the muscle is tired.

Single-fiber electromyography (EMG) - this measures the electrical activity that flows between the brain and the muscle. A very fine wire electrode is inserted through the skin, into the muscle. Some patients may find this test uncomfortable. In a more precise version of this test, called single-fiber EMG, a single muscle fiber is tested.

Imaging scans

• A chest X-ray is commonly performed, as it may point towards alternative diagnoses, such as Lambert-Eaton due to a lung tumor, and comorbidity (the presence of one or more disorders/diseases in addition to a primary disease/disorder, or the effect of such additional disorders or diseases).
• A CT (computed tomography) or MRI (magnetic resonance imaging) scan may be performed to identify a thymoma (tumor in the thymus gland). CT or MRI scans are better at detecting thymomas than X-rays.

Pulmonary function test (spirometry) - the aim here is to determine whether the patient is breathing adequately. The forced vital capacity (the maximum amount of air a person can expel from the lungs after a maximum inspiration) may be periodically measured so as not to miss a gradual worsening of muscular weakness in the lungs. MG patients with severe symptoms are at risk of respiratory failure due to exhaustion of the respiratory muscles. Respiratory failure is when there is inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges.

Muscle biopsy - this is only done if the diagnosis is in doubt and a muscular condition is suspected. A needle or small incision is used to remove a small sample of muscle. The patient will receive a local anesthetic.

What are the treatment options for myasthenia gravis?

There is no cure for myasthenia gravis. However, most therapies (treatments) are very effective in controlling symptoms. In fact, the majority of MG patients who undergo treatment become completely free of symptoms, and can lead normal (or near normal) lives. In some cases, all that is required to relieve symptoms are adequate sleep and rest.

Cholinesterase inhibitors - such as pyridostigmine (Mestinon) block the action of the chemical that normally makes the muscle relax after it has contracted - they improve communication between nerves and muscles. This medication is very effective for patients with mild MG symptoms; helping the affected muscles contract properly and maintain good strength. Some side effects may include nausea and/or stomach cramps.

Steroids or Immunosuppressants - prednisolone (a steroid drug) or azathioprine (an immunosuppressant drug) may alter the body's immune system and lower the production of antibodies that cause MG. It usually takes about four weeks for the effects of steroids to appear, while azathioprine may take from three to six months.

These medication are usually very effective; either significantly reducing symptoms or getting rid of them altogether.

This type of medication is usually only given to patients who could not have their thymus gland surgically removed, or those whose symptoms did not improve after surgery.

Removal of the thymus gland (thymectomy) - about 15% of MG patients have a tumor in their thymus gland. In such cases a thymectomy is required - the gland is surgically removed.

It is unclear whether the risks of removing the thymus gland outweigh the benefits for MG patients who don't have a tumor. If the patient's symptoms are mild, only involve the eyes, or if he/she is over 60 years of age most doctors will not recommend surgery.

Surgically removing the thymus gland improves symptoms for over 70% of MG patients, and eliminates symptoms completely for 30%. Improvements gradually appear over a period of 12 months; in some cases this may take longer (up to 3 years).

Plasmaphoresis and immunoglobulin therapy - this therapy, which is given in hospital, is used for patients with severe symptoms; specifically patients with life-threatening breathing or swallowing problems.

• Plasmaphoresis - the procedure depletes the body of blood plasma without depleting the body of its blood cells. Blood is removed from the body, the plasma is separated from the cells, the cells are then suspended in saline (or a plasma substitute or donor plasma), and the reconstituted solution is returned to the patient. Put simply - the blood is taken out of the patient, the abnormal antibodies that cause MG are removed, and the blood is placed back into the patient.
• Intravenous immunoglobulin therapy - normal antibodies that alter the way the immune system acts are injected into the patient.

Although extremely effective with rapid results, the benefits last no longer than a few weeks. This treatment is a short-term one, used only if the patient is extremely ill.

What are the possible complications of myasthenia gravis?

Myasthenic crisis - the respiratory muscles become so weak that the patient cannot breathe properly. This is potentially a life-threatening complication and requires emergency treatment with mechanical breathing assistance. Plasmaphoresis and immunoglobulin therapies, as well as medications help patients recover.

Thymus tumors - approximately 15% of MG patients have a tumor in the thymus gland. In most cases it is a benign (non-cancerous) tumor. This is treatable.

Thyroid problems - the thyroid gland secretes hormones that regulate our metabolism; it is located in the neck. MG patients may have either an overactive thyroid (hyperthyroidism) or an underactive one (hypothyroidism).

Lupus - an autoimmune disease where the body's immune system becomes hyperactive and attacks normal, healthy tissue. This results in symptoms such as inflammation, swelling, and damage to joints, skin, kidneys, blood, the heart, and lungs.

Rheumatoid arthritis - a chronic (long lasting), progressive and disabling auto-immune disease condition that causes inflammation (swelling) and pain in the joints, the tissue around the joints, and other organs in the human body. Rheumatoid arthritis usually affects the joints in the hands and feet first, but any joint may become affected. Patients with rheumatoid arthritis commonly have stiff joints and feel generally unwell and tired.

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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