MG is an autoimmune disorder affecting the myoneural junction, characterized by varying degrees of weakness of the voluntary muscles. It is uncommon, being found between 9 to 30 cases in 1,000,000 people in the United States. It is more common in women during the second and third decades of life, but becomes more common in men after the fifth decade of life.
Pathophysiology
- Acetylcholine is normally released from the nerve terminal at the myoneural junction. The acetylcholine attaches to receptor sites on the motor endplate and stimulates muscle contraction. Continuous binding of acetylcholine is required for sustained muscle contraction.
- In MG, antibodies damage acetylcholine receptors and impair transmission across the myoneural junction, reducing stimulation resulting in voluntary muscle weakness, escalating with continued activity.
- 85% of MG cases feature these antibodies. Most cases have either thymic hyperplasia or a thymic tumor, with the thymus gland is believed to be the site of antibody production. In the 15% of cases without acetylcholine receptor antibodies, other antibodies appear to target a protein in the myoneural junction.
Clinical Manifestations
Manifestations are variable. MG is purely a motor disorder with no effect on sensation or coordination. There are two clinical types:
- Ocular: only the eye muscles are involved, featuring ptosis (characteristic) and diplopia.
- Generalized: the face (facial weakness; bland facial expression), throat (dysphagia, dysphonia), limbs (generalized weakness), and respiratory muscles (decreased vital capacity and respiratory failure; myasthenic crisis) are affected.
Diagnostic Examination
- Acetylcholinesterase Inhibitor Test: the administration of edrophonium chloride IV should resolve facial weakness and ptosis for about 5 minutes after 30 seconds. Immediate improvement represents a positive test, often confirming the diagnosis.
- Atropine (an anticholinergic) should be available to counteract side effects of bradycardia, asystole, bronchoconstriction, sweating, and cramping.
- In patients who have asthma and cardiac problems, the ice test is an alternative: place an ice pack over the eyes for 1 minute, after which ptosis should resolve temporarily if MG is present.
- Blood studies for acetylcholine antibodies can also confirm the diagnosis.
- Repetitive Nerve Stimulation (RNS) and Single-fiber Electromyography (EMG) detects delays, decreases, or failure of neuromuscular transmission and action potentials. These are about 99% sensitive in detecting MG, but can be uncomfortable for the patient.
- MRI of the thymus gland can reveal hyperplasia or enlargement.
Management
- Medical: focuses on (a) improving functioning and (b) reducing or removing circulating acetylcholine receptor antibodies. There is no cure for MG. Production of acetylcholine receptor antibodies does not stop.
- Therapeutic Plasma Exchange: (prev. plasmapheresis) is used to treat exacerbations. The patient’s plasma and its components are removed through a centrally placed large-bore double-lumen catheter. The blood and plasma are separated, with the blood being combined with replacement plasma and being reinfused. Patient response determines number of treatments. These are done on a daily or alternate-day basis.
- Pharmacologic:
- Pyridostigmine bromide, an anticholinesterase medication, is the first line of therapy. It inhibits the breakdown of acetylcholine, increasing the relative concentration of available acetylcholine at the neuromuscular junction. The dosage is gradually increased as the disease progresses until it reaches its daily maximum given in divided doses (often four).
- Adverse effects include diarrhea, abdominal cramps, and/or excessive saliva. These are relatively fewer side effects compared to other anticholinesterase medications.
- Immunomodulating (immunosuppresant) drugs aim to reduce the production of antibodies. Corticosteroids suppress the body’s immune response, correlating with clinical improvement. An initial dose of prednisone is given and maintained for 1 to 2 months, then tapered after once symptoms improve.
- Cytotoxic medications are used if steroids are ineffective. Azathioprine inhibits T lymphocytes and B cell proliferation and reduces acetylcholine receptor antibody levels. The therapeutic effect of these drugs may not be felt for 3 to 12 months. Leukopenia and hepatotoxicity are serious adverse effects warranting a monthly evaluation of liver enzymes and white blood cell count.
- IVIG can be used to treat exacerbations and, occasionally, is used on a long-term adjunctive basis. It involves the administration of pooled human gamma-globulin, with improvement occurring in a few days to a week. These effects typically only last for 28 days after infusion. Complications include headaches, migraine exacerbation, aseptic meningitis, and flulike symptoms.
- Procaine exacerbates the symptoms of MG and should be avoided. Inform the client’s dentists of the contraindication.
- Pyridostigmine bromide, an anticholinesterase medication, is the first line of therapy. It inhibits the breakdown of acetylcholine, increasing the relative concentration of available acetylcholine at the neuromuscular junction. The dosage is gradually increased as the disease progresses until it reaches its daily maximum given in divided doses (often four).
- Surgical: A Total Thymectomy can produce antigen-specific immunosuppression and result in clinical improvement. Optimal outcomes are found in patients younger than 60 years old with MG diagnosed within 3 years. It is the only treatment that can result in complete remission, occurring in approximately 35% of patients. Preoperative IVIG or therapeutic plasma exchange access can reduce postoperative mechanical ventilation. Weaning off of mechanical ventilation requires prior thorough respiratory assessment. Improvement may take as long as three years due to the long life of circulating T cells.
Myasthenic Crisis
Myasthenic Crisis is an exacerbation of the disease process characterized by severe generalized muscle weakness and respiratory or bulbar weakness that may result in respiratory failure. This may result from disease exacerbation or a specific precipitating event, most commonly being respiratory infection. Changes in medication, surgery, pregnancy, and specific drugs can exacerbate myasthenia. - Neuromuscular respiratory failure is the critical complication in myasthenic and cholinergic crises. Inadequate cough and gag reflexes (caused by bulbar weakness) result in poor airway clearance. - A downward trend of two respiratory function tests, a negative inspiratory force, and vital capacity are among the first clinical sign of respiratory compromise. - Endotracheal intubation and mechanical ventilation may be needed. Noninvasive positive-pressure ventilation uses an external vest-like device to provides support even without intubation. - Cholinesterase inhibitors are stopped during respiratory failure, and gradually restarted once improvement is demonstrated after plasmapheresis or IVIG.
Varying degrees of dysphagia, dysarthria, eyelid ptosis, diplopia, and prominent muscle weakness are symptoms of a myasthenic crisis. During crises, patients are placed in an ICU because of associated intense and sudden fluctuations in clinical condition.
- Ventilatory assistance is of utmost importance. Monitoring for respiratory status (rate, depth, sounds, pulmonary function parameters [vital capacity, negative inspiratory force]) should be continuous.
- Endotracheal intubation and mechanical ventilation may be needed.
- Draw blood for arterial blood gas analysis and serum electrolytes.
- If the abdominal, intercostal, and pharyngeal muscles are severely weak, the patient is unable to cough, take deep breaths, or clear secretions. Chest physiotherapy may have to be performed frequently.
- If the patient cannot swallow, enteral tube feedings may be required.
- Sedative and tranquilizing agents are avoided as they aggravate hypoxia and hypercapnia. These agents can cause respiratory and cardiac depression.
Nursing Management
MG is a chronic disease, and therefore most patients are treated on an outpatient basis. Most nursing care involves patient and family education. Educational topics for outpatient self-care include:
- Medication management: actions of medications, schedule, and consequences of delaying medication.
- Energy conservation: optimal rest periods throughout the day, keeping necessities on one floor of the living quarters, handicapped license plates to minimize walking distance, schedule activities during peak energy levels in the day. Use consistent routines, scheduling rest periods, and monitor for depression. Maintain a good sleep pattern.
- Strategies to help with ocular manifestations: ptosis in one or both eyelids impairs vision. Decreased eye movement, and diplopia also occur. To prevent corneal damage when eyes do not completely close, the patient is instructed to tape the eyes shut for short periods and to regularly instill artificial tears. Diplopia can be corrected by patching one eye or wearing prism glasses.
- Prevention and management of complications:
- Teach the patient and family about the signs and symptoms of myasthenic and cholinergic crises.
- To minimize the risk for aspiration, mealtimes should be held during the peak effects of anticholinesterase medication. Rest before meals is encouraged. Sitting upright should be done during meals. Soft foods are easier to swallow. Large meals should be had in the morning and smaller ones at night. Suctioning should be available at home, with the family members trained for its use.