Myasthenia gravis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Diagnosis
Pulmonary function test
Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about a patient's ability to breathe adequately. The vital capacity (VC) may be monitored at intervals in order not to miss a gradual worsening of muscular weakness. Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles.
Pathological findings
Immunofluorescence shows IgG antibodies on the neuromuscular junction. (Note that it is not the antibody which causes myasthenia gravis that fluoresces, but rather a secondary antibody directed against it.) Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts. Both these techniques are currently used for research rather than diagnostically.
Associations
Myasthenia Gravis is associated with various autoimmune diseases, including:
- Thyroid diseases, including Hashimoto's thyroiditis and Graves' disease
- Diabetes mellitus type 1
- Rheumatoid arthritis
- Lupus, and
- Demyelinating CNS diseases
Seropositive and "double-seronegative" patients often have thymoma or thymic hyperplasia. However, anti-MuSK positive patients do not have evidence of thymus pathology.
Treatment
Treatment is by medication and/or surgery. Medication consists mainly of cholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG. For emergency treatment, plasmapheresis or IVIG can be used as a temporary measure to remove antibodies from the blood circulation.
Medication
- Cholinesterase inhibitors: neostigmine and pyridostigmine can improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor. Usually doctors will start with a low dose, eg 3x20mg pyridostigmine, and increase until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating. Side effects, like perspiration and diarrhea can be countered by adding atropine. Pyridostigmine is a short-lived drug with a half-life of about 4 hours.
- Immunosuppressive drugs: prednisone, cyclosporine, mycophenolate mofetil and azathioprine may be used. It is common for patients to be treated with a combination of these drugs with a cholinesterase inhibitor. Treatments with some immunosuppressives take weeks to months before effects are noticed.
Plasmapheresis and IVIG
If the myasthenia is serious (myasthenic crisis), plasmapheresis is used to remove the putative antibody from the circulation. Similarly, intravenous immunoglobulins (IVIG) are used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks.
Surgery
Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential neoplastic effects of the tumor. However, the procedure is more controversial in patients who do not show thymic abnormalities. Although some of these patients improve following thymectomy, some patients experience severe exacerbations and the highly controversial concept of "therapeutic thymectomy" for patients with thymus hyperplasia is disputed by many experts and efforts are underway to unequivocally answer this important question.
There are a number of surgical approaches to the removal of the thymus gland: transsternal (through the sternum, or breast bone), transcervical (through a small neck incision), and transthoracic (through one or both sides of the chest). The transsternal approach is most common and uses the same length-wise incision through the sternum (breast bone)used for most open-heart surgery. The transcervical approach is a less invasive procedure that allows for removal of the entire thymus gland through a small neck incision. There has been no difference in success in symptom improvement between the transsternal approach and the minimally invasive transcervical approach.[1]
Thymoma is relatively rare in younger (<40) patients, but paradoxically especially younger patients with generalized MG without thymoma benefit from thymectomy. Of course, resection is also indicated for those with a thymoma, but it is less likely to improve the MG symptoms.
Contraindicated medications
Myasthenia gravis is considered an absolute contraindication to the use of the following medications:
Prognosis
With treatment, patients have a normal life expectancy, except for those with a malignant thymoma (whose lesser life expectancy is on account of the thymoma itself and is otherwise unrelated to the myasthenia). Quality of life can vary depending on the severity and the cause. The drugs used to control MG either diminish in effectiveness over time (cholinesterase inhibitors) or cause severe side effects of their own (immunosupressants). A small percentage (around 10%) of MG patients are found to have tumors in their thymus glands, in which case a thymectomy is a very effective treatment with long-term remission. However, most patients need treatment for the remainder of their lives, and their abilities vary greatly. It should be noted that MG is not usually a progressive disease. The symptoms may come and go, but the symptoms usually do not get worse as the patient ages. For some, the symptoms decrease after a span of 3–5 years.
References
External links
- The Myasthenia Gravis Foundation of America
- The Myasthenia Gravis Association (MGA) in the United Kingdom & the Republic of Ireland