“I feel like I have to think about breathing. I’m trying to get more exercise, but I can hardly walk around the block without feeling like I have to sit down.”
A 42-year-old mother of two teenagers articulates what it is like to live with myasthenia gravis. Her symptoms of two years — diplopia, extreme fatigue and an inability to hold her head erect — finally erupted in a myasthenic crisis that required mechanical ventilation for a week and multiple plasmapheresis exchanges. Three months after her crisis, she had a suprasternal thymectomy. Since her operation, periods of improvement led to tapering of her steroid dose, only to be followed by exacerbations and more plasmapheresis. This new sick role has shredded her former lifestyle. She can’t work. She just fights for disability benefits.
Nurses from many sectors of healthcare — EDs, critical care and med/surg units, apheresis and infusion centers, practitioners’ offices and home healthcare settings — encounter patients living with myasthenia gravis (MG), either in exacerbation, stability or remission. A thorough knowledge of the disease process, treatment and available community supports, is essential for nurses to promote maximal wellness and prevent complications in people with MG.
A Well-Known Disease
MG is one of the best understood of the autoimmune disorders, which include rheumatoid arthritis, glomerulonephritis and scleroderma. With advances in respiratory care and immunotherapy, this “grave” disease no longer lives up to its name (“myasthenia” is derived from the Greek words for muscle and weakness and “gravis” means weighty in Latin).1
However, because of its rarity (20 per 100,000 people) and wide range of clinical presentations, diagnosis can be delayed by months or years. Although it can strike at any age, MG usually afflicts women in their 30s and 40s and men after age 60.1
MG has at least five different forms with different ages of onset.2
Many patients with generalized MG may have an associated autoimmune disease.3 (Level B)
A transient form of MG occurs in 10% to 20% of infants born to myasthenic women, which results from the transplacental transfer of anti-acetylcholine (antiACh) antibodies.4
MG is a neuromuscular disorder characterized by a gradual symptoms onset of ocular, facial, bulbar and skeletal muscle weakness that typically worsens with fatigue and improves with rest. Periods of remission with intermittent exacerbations occur, although the course of the illness is extremely variable.4 At its onset, patients may present with diplopia and ptosis, because the disease often affects the ocular muscles first. Ocular myasthenia includes and is limited to this cluster of symptoms. In time, facial muscle involvement may become prominent. An attempt to smile results in a snarling expression, and chewing becomes tiresome. Head drop and proximal or distal (rarely) muscle weakness may occur. As the disease progresses, people may also develop difficulty swallowing, breathing and speaking, indicating bulbar muscle involvement. These people are at risk for choking, aspiration pneumonia and respiratory compromise. The inability to lay flat to sleep is characteristic of diaphragm involvement and is an emergent sign and symptom. With early diagnosis, treatment and lifestyle alterations, over time many people with MG achieve control of their symptoms and disease with limited or no disability.
A Problem at Neuromuscular Junctions
MG is a chronic disorder of neuromuscular junctions at which antibodies attack acetylcholine-receptor sites (AChRs), disabling normal impulse transmission. Normally, acetylcholine (ACh) is stored at the terminal end of axons and released at the neuromuscular synapse, where it binds with AChRs on the folds of post-synaptic muscle end plate membranes. When sufficient interactions between ACh and AChRs occur, effective neuromuscular transmission takes place, and a muscle contraction is stimulated. Normally, post-synaptic motor-end plates have many folds on which AChRs are situated. In acquired MG, the post-synaptic muscle membrane is distorted and simplified, having lost its folded shape.5 In addition, people with this disease have less available AChRs than normally expected.6 (Level A)
Therefore, when ACh is released, there are fewer sites for it to bind to. The severity of fatigue and weakness correlates with the reduced number of AChRs. The combination of these abnormalities reduces neuromuscular transmission, resulting in ineffective muscle contraction and fatigued muscles.
The thymus gland is implicated in the autoimmune process of the anti-ACh antibody production associated with the onset of MG. The thymus is active during infancy and early childhood in the development of systemic immunity, but it normally shrinks in size by adulthood. However, at least 75% to 80% of myasthenic patients with generalized MG are found to have either thymic hyperplasia or a thymoma.7 The exact cause of this thymic anomaly is unknown.
Diagnosis of Myasthenia Gravis
A patient’s history of gradual weakness with ocular and bulbar involvement often prompts practitioners to seek consultation with a neurologist. However, with myriad symptoms, MG can be a diagnosis of exclusion. Traditional studies (serum blood counts, electrolytes and renal and thyroid profiles) as well as computerized tomography can rule out the possibility of other diseases. Tests that pinpoint the diagnosis of MG include edrophonium (Tensilon) testing, repetitive nerve stimulation (RNS), single-fiber electromyography (EMG) and serum AChR antibody titers.1 Patients with generalized MG and who are seronegative for AChR antibodies may require a MuSK antibody assay to support the diagnosis of MG.1 MuSK is a muscle-specific, receptor tyrosine kinase that is found in the neuromuscular junction. These antibodies have been found predominantly in younger women who are AChR-antibody negative, predominantly experience bulbar problems and whose symptoms are less well-controlled with immunosuppression.2 In pure ocular MG, up to 50% of patients may be AChR-antibody negative despite having the typical ocular symptoms and responsiveness to immunosuppressive therapy.6
Testing with edrophonium is a first-line method to confirm suspected MG. It is often used with patients who have some degree of respiratory muscle involvement. Edrophonium is a short-acting drug that transiently improves muscular strength in the presence of MG by inhibiting the breakdown of ACh by the enzyme cholinesterase. The onset of a response to IV edrophonium is 30 seconds, and the effects last for five minutes.6 An improvement in muscular strength and a reduction of ptosis is considered a positive test.6 A placebo injection of saline may be given in addition to the edrophonium to increase the validity of the results.8
RNS and EMG assess neuromuscular transmission. In RNS, electric shocks are delivered at a rate of three per second to a proximal muscle nerve within the facial, deltoids, biceps or trapezius groups, while action potentials are recorded. A rapid reduction in the amplitude of evoked muscle action potential of at least 10% by the fourth or fifth trial is a positive response. A single-fiber EMG is a highly sensitive, but technically difficult, test during which the action potentials of adjacent muscle fibers innervated by a single nerve are recorded simultaneously. An abnormal amount of variation or “jitter” in the response of the adjacent muscle fibers is considered pathologic. Although positive results of both tests correlate highly with the diagnosis of MG, they can also be positive in other neuromuscular diseases.
The detection of serum AChR antibodies is the most specific test for the diagnosis of MG. The test has 80% to 96% sensitivity for patients with generalized MG disease.6 Patients in remission or with only ocular symptoms, however, may have a negative titer up to 50% of the time.6 As already discussed, MuSk antibody detection is also indicated in AchR-negative generalized MG patients. With all diagnostic testing, correlation of results with clinical symptoms is critical in confirming the diagnosis.
Dysphagia and Myasthenia Gravis9
- Is the patient taking a long time to eat?
- Does speech and swallowing worsen over the course of the meal?
- Is the patient coughing while eating?
- Is there nasal regurgitation with fluids or foods?
- Can the patient chew meat, breads, etc?
- Swallowing assessments by speech language pathologists with modified barium swallow may be indicated to assess for silent aspiration.