Myasthenia gravis
What is Myasthenia gravis?
Myasthenia gravis is a chronic autoimmune neuromuscular disease that causes weakness in certain muscles group such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often involved in the disorder.The muscles that control breathing and neck and limb movements may also be affected. The hallmark of myasthenia gravis is muscle weakness that worsens after periods of activity and improves after periods of rest. This episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors.
There is no known cure for myasthenia gravis. Available treatments can only control symptoms and allow people to have a relatively high quality of life. Most individuals with the condition have a normal life expectancy. It's more common in younger women aged 20-40 and in older men older 60-80.
Myasthenia gravis is a chronic autoimmune neuromuscular disease that causes weakness in certain muscles group such as those that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are often involved in the disorder.The muscles that control breathing and neck and limb movements may also be affected. The hallmark of myasthenia gravis is muscle weakness that worsens after periods of activity and improves after periods of rest. This episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors.
There is no known cure for myasthenia gravis. Available treatments can only control symptoms and allow people to have a relatively high quality of life. Most individuals with the condition have a normal life expectancy. It's more common in younger women aged 20-40 and in older men older 60-80.
What causes Myasthenia Gravis?
Neurotransmitters are chemicals that neurons use to communicate information. Normally when electrical signals travel down a motor nerve, the nerve endings release a neurotransmitter called acetylcholine. Acetylcholine travels from the nerve ending and binds to acetylcholine receptors on the muscle. The binding of acetylcholine to its receptor activates the muscle and causes a muscle contraction. In Myasthenia gravis there's an error in the transmission of nerve signals to muscles which is interrupted at the neuromuscular junction.
Myasthenia gravis is an autoimmune disease whereby antibodies (self produced by the body) block, change or destroy the receptors for acetylcholine at the neuromuscular junction, this prevents the muscle from contracting. It is usually caused by antibodies to the acetylcholine receptor itself.
However other antibodies to proteins such as MuSK (Muscle-Specific Kinase) protein, can also impair transmission at the neuromuscular junction. (antibody-negative myasthenia gravis)
The role of the thymus in myasthenia gravis
The thymus is a gland that controls immune function. The role of the thymus in myasthenia is unclear, but 65% of patients have thymic hyperplasia, and 10% have a thymoma. About half of the thymomas are malignant. Thymus is largest in children and it grows gradually until puberty, and after which it decreases in size and is replaced by fat. Throughout childhood, the thymus is responsible for producing T-lymphocytes or T cells (part of immune system) that protects the body from viruses and infections.
In patients with myasthenia gravis, the thymus gland remains abnormally large. Some develop thymomas (tumors of the thymus gland) which are usually benign but they can become cancerous.
Scientists believe that the thymus gland may give incorrect instructions to immune cells, resulting them to attack its own cells and tissues (autoimmune response) and produce acetylcholine receptor antibodies which interrupts neuromuscular transmission.
Neonatal Myasthenia
Myasthenia gravis is rarely seen in infants but the fetus may acquire antibodies from a mother who myasthenia gravis. Neonatal myasthenia gravis is temporary and the child's symptoms usually disappear within 2-3 months after birth. Rarely, children of a healthy mother may develop congenital myasthenia.
Precipitating factors
Neurotransmitters are chemicals that neurons use to communicate information. Normally when electrical signals travel down a motor nerve, the nerve endings release a neurotransmitter called acetylcholine. Acetylcholine travels from the nerve ending and binds to acetylcholine receptors on the muscle. The binding of acetylcholine to its receptor activates the muscle and causes a muscle contraction. In Myasthenia gravis there's an error in the transmission of nerve signals to muscles which is interrupted at the neuromuscular junction.
Myasthenia gravis is an autoimmune disease whereby antibodies (self produced by the body) block, change or destroy the receptors for acetylcholine at the neuromuscular junction, this prevents the muscle from contracting. It is usually caused by antibodies to the acetylcholine receptor itself.
However other antibodies to proteins such as MuSK (Muscle-Specific Kinase) protein, can also impair transmission at the neuromuscular junction. (antibody-negative myasthenia gravis)
The role of the thymus in myasthenia gravis
The thymus is a gland that controls immune function. The role of the thymus in myasthenia is unclear, but 65% of patients have thymic hyperplasia, and 10% have a thymoma. About half of the thymomas are malignant. Thymus is largest in children and it grows gradually until puberty, and after which it decreases in size and is replaced by fat. Throughout childhood, the thymus is responsible for producing T-lymphocytes or T cells (part of immune system) that protects the body from viruses and infections.
In patients with myasthenia gravis, the thymus gland remains abnormally large. Some develop thymomas (tumors of the thymus gland) which are usually benign but they can become cancerous.
Scientists believe that the thymus gland may give incorrect instructions to immune cells, resulting them to attack its own cells and tissues (autoimmune response) and produce acetylcholine receptor antibodies which interrupts neuromuscular transmission.
Neonatal Myasthenia
Myasthenia gravis is rarely seen in infants but the fetus may acquire antibodies from a mother who myasthenia gravis. Neonatal myasthenia gravis is temporary and the child's symptoms usually disappear within 2-3 months after birth. Rarely, children of a healthy mother may develop congenital myasthenia.
Precipitating factors
- Infection
- Immunization
- Surgery
- Pregnancy and post-partum period
- Emotional stress
- Certain drugs (eg, aminoglycosides, quinine, magnesium sulfate, procainamide, beta blockers, calcium channel blockers)
Classification of Myasthenia Gravis
The Myasthenia Gravis Foundation of America Clinical Classification divides MG into 5 main classes:
The Myasthenia Gravis Foundation of America Clinical Classification divides MG into 5 main classes:
- Class I: Any ocular muscle weakness; all other muscle strength is normal
- Class II: Mild weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
- Class IIa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
- Class IIb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both
- Class III: Moderate weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
- Class IIIa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
- Class IIIb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both
- Class IV: Severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
- Class IVa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
- Class IVb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both
- Class V: Defined by the need for intubation, with or without mechanical ventilation, except when used during routine postoperative management. The use of a feeding tube without intubation places the patient in class IVb.
Symptoms of Myasthenia Gravis
Myasthenia gravis may affect any skeletal muscle but muscles that control eye and eyelid movement, facial expression, and swallowing are most frequently affected. Thus usually the first noticeable symptom is weakness of the eye muscles in 50% to 85% patients. In others, difficulty swallowing and slurred speech may be the first signs. Muscle weakness worsens as the affected muscle is used repeatedly and usually improve with rest. However, the symptoms tend to progress over time, usually reaching their worst within a few years after the onset of the disease.
The degree of muscle weakness varies greatly among individuals, ranging from a localized form limited to eye muscles (ocular myasthenia), to a severe or generalized form in which many muscles groups are affected.
Symptoms may include:
Myasthenia gravis may affect any skeletal muscle but muscles that control eye and eyelid movement, facial expression, and swallowing are most frequently affected. Thus usually the first noticeable symptom is weakness of the eye muscles in 50% to 85% patients. In others, difficulty swallowing and slurred speech may be the first signs. Muscle weakness worsens as the affected muscle is used repeatedly and usually improve with rest. However, the symptoms tend to progress over time, usually reaching their worst within a few years after the onset of the disease.
The degree of muscle weakness varies greatly among individuals, ranging from a localized form limited to eye muscles (ocular myasthenia), to a severe or generalized form in which many muscles groups are affected.
Symptoms may include:
- drooping of one or both eyelids (ptosis)
- blurred or double vision (diplopia) due to weakness of the muscles that control eye movements
- a change in facial expression
- difficulty swallowing
- Difficulty in chewing
- shortness of breath
- impaired speech (dysarthria)
- weakness in the arms, hands, fingers, legs, and neck.
|
|
Complications of Myasthenia Gravis
Myasthenic crisis Myasthenic crisis is a life-threatening condition whereby the muscles that control breathing become too weak and experience difficulty in breathing requiring a ventilator. Emergency treatment is needed to provide mechanical assistance with breathing. This is a medical emergency. Approximately 15 to 20 percent of people with myasthenia gravis experience at least one myasthenic crisis. Thymus tumors About 15 percent of people with myasthenia gravis have a tumor in their thymus as mentioned earlier. Most of these tumors, called thymomas, are benign but a very small proportion may turn malignant. Association with other thyroid disorders and autoimmune diseases Patients with myasthenia may concurrently have other thyroid disorders and autoimmune diseases like rheumatoid arthritis or lupus. |
Diagnosis of Myasthenia Gravis
The physician will first take a detailed medical history and conduct physical examination followed by tests to confirm diagnosis:
The physician will first take a detailed medical history and conduct physical examination followed by tests to confirm diagnosis:
- A physical and neurological examination. The doctor will conduct a physical examination with focus on the neurological system. The doctor will check muscle strength and tone, reflexes, coordination, balance, sense of touch, and look for impairment of eye movements.
- An edrophonium test. This test uses injections of edrophonium chloride to briefly relieve weakness in people with myasthenia gravis. The drug blocks enzymes that breakdown of acetylcholine and temporarily increases the levels of acetylcholine at the neuromuscular junction. It is usually used to test ocular muscle weakness.
- Ice pack test: An ice pack is placed on the eyelid for two minutes after which it is removed to see if the ptosis (droopy eyelid) improves.
- Blood test: Most patients with myasthenia gravis have abnormally elevated levels of acetylcholine receptor antibodies. In about half of the patients which do not have acetylcholine receptor antibodies, a second antibody (anti-MuSK antibody) is found. In some patients, neither of these antibodies is present, this is known as seronegative (negative antibody) myasthenia. Other antibodies that can be tested are Anti-lipoprotein-related protein 4 (LRP4) antibody and Anti-agrin antibody.
- Repetitive nerve stimulation: repeatedly stimulates a person’s nerves with small pulses of electricity to tire specific muscles. Muscle fibers in myasthenia gravis and other neuromuscular disorders do not respond well to repeated electrical stimulation compared to muscles from normal individuals.To diagnose myasthenia gravis, doctors will test the nerve many times to see if its ability to send signals worsens with fatigue.
- Single fiber electromyography (EMG): is considered the most sensitive test for myasthenia gravis which detects impaired nerve-to-muscle transmission. It involves inserting a fine wire electrode through your skin and into a muscle to test a single muscle fiber. EMG can be very helpful in diagnosing mild cases of myasthenia gravis when other tests fail to demonstrate abnormalities.
- Diagnostic imaging: Computed tomography (CT) or magnetic resonance imaging (MRI) of the chest may identify the presence of a thymoma.
- Pulmonary function testing. Measuring breathing strength can help predict if respiration may fail and lead to a myasthenic crisis.
Treatment of Myasthenia Gravis
Symptoms of myasthenia gravis can generally be controlled. There are several therapies available to help reduce and improve muscle weakness.
Symptoms of myasthenia gravis can generally be controlled. There are several therapies available to help reduce and improve muscle weakness.
- Thymectomy: Surgical operation to remove the thymus tumor which often is abnormal in 15% of Myasthenia Gravis patients can reduce symptoms and may cure some people, by re-balancing the immune system. Even if you don't have a tumor in the thymus gland, surgery to remove the thymus gland may improve your symptoms. Surgery can be open surgery or minimally invasive thymectomy like video assisted or robot assisted.
- Anticholinesterase medications: Medications such as mestinon or pyridostigmine, which slow the breakdown of acetylcholine at the neuromuscular junction and thereby improve neuromuscular transmission and increase muscle strength. Possible side effects may include gastrointestinal upset, nausea, and excessive salivation and sweating. Pyridostigmine is used for symptomatic treatment only. It does not treat the underlying disease.
- Immunosuppressive drugs: improve muscle strength by suppressing the production of abnormal antibodies. They include azathioprine, mycophenolate mofetil, tacrolimus, and rituximab. Side effects include nausea, vomiting, gastrointestinal upset, increased risk of infection, liver damage and kidney damage. Close blood monitoring and biopsies are required. These drugs are not a cure and they only improve symptoms. Side effects of immunosuppressants can be serious and may include nausea, vomiting, gastrointestinal upset, increased risk of infection, liver damage and kidney damage.
- Corticosteroids: such as prednisone inhibit the immune system and limit antibody production. Prolonged use can lead to serious side effects such as osteoporosis, weight gain, diabetes and increased risk of some infections.
- Plasmapheresis and intravenous immunoglobulin. These are possible options for those with severe myasthenia gravis. These treatments remove the destructive antibodies that attack the neuromuscular junction in their plasma. The effectiveness usually only lasts for a few weeks to months.
- Plasmapheresis is a procedure using a machine with a filtering process like dialysis to remove these antibodies in plasma and replace them with good plasma or a plasma substitute. Other risks associated with plasmapheresis include a drop in blood pressure, bleeding, arrythmias or muscle cramps. Some people may develop an allergic reaction to these solutions.
- Intravenous immunoglobulin is an injection of a highly concentrated antibodies donated from healthy donors that temporarily alters the immune system operates. It bindings to the antibodies that cause myasthenia gravis and remove them from circulation. IVIg has less side effects compared to plasmapheresis and immune-suppressant medications.
- Monoclonal antibody: Rituximab is an intravenous medication that helps to depletes certain white blood cells, altering the immune system and improving myasthenia gravis symptoms. Repeat infusions are often done over a few weeks.
Treatment of Neonatal Myasthenia Gravis
Neonatal Myasthenia Gravis is usually transient whereby it is transmitted vertically from an affected mother to her fetus. It occurs in 10-30% of neonates born to myasthenic mothers. It can occur any time during the first 7-10 days of life during which infants should be monitored closely for any signs of respiratory distress. Treatment with cholinesterase inhibitors is effective in this age group as well.
Neonatal Myasthenia Gravis is usually transient whereby it is transmitted vertically from an affected mother to her fetus. It occurs in 10-30% of neonates born to myasthenic mothers. It can occur any time during the first 7-10 days of life during which infants should be monitored closely for any signs of respiratory distress. Treatment with cholinesterase inhibitors is effective in this age group as well.
Lifestyle changes to cope with Myasthenia gravis
- Adjust your eating routine. As patients experience difficulty chewing and swallowing because of oropharyngeal weakness, they should try to eat when you have good muscle strength. Take your time when you chew your food and take a break between bites of food. Taking small meals several times a day may be easier to handle than 3 big meals. Eating mainly soft foods and avoid foods that require more chewing (meat and vegetables) may help too. If dysphagia develops, it is usually most severe for thin liquids because of weakness of pharyngeal muscles. To avoid nasal regurgitation or aspiration, liquids should be thickened
- Physical acitivity: Educate patients about the fluctuating nature of weakness and exercise-induced fatigability. Patients should be as active as possible but should rest frequently and avoid sustained physical activity.
- Safety precautions at home. Install grab bars or railings where you may need support, such as next to the bathtub or next to steps. Keep your floors dry and remove any loose rugs out of areas where you may walk.
- Use electric appliances and power tools. You may lose energy quickly when conducting tasks. Thus you can try using electric apppliances like electric toothbrush, electric can openers and other electrical tools to perform tasks when possible.
- Wear an eye patch. Consider wearing an eye patch if you have double vision, as this can help relieve the problem. Periodically switch the eye patch to the other eye to help reduce eyestrain.
- Plan: If you have chores, shopping or errands to do, plan the activity to coincide with the time at which you have the most energy.
