Myasthenia Gravis – Diagnosis And Treatment
Myasthenia gravis is an immunologically mediated disease in which antibodies are directed against the acetylcholine receptor, causing disturbances in the functionality of acetylcholine receptors and in neuromuscular transmission, leading to muscle fatigue. Muscle fatigue can become pseudo-paralytic, with transient paresis which improve at rest and anticholinesterase medication.
There are two clinical forms, cephalic or superior form and generalized form. In most cases, the disease begins at the cephalic muscles, especially in the eye muscles, and for 15% of patients symptoms are limited to this level (ocular myasthenia). Bulbar muscles is then affected and generally within about three years disease spreads to other muscle groups.
Myasthenia Gravis Diagnosis
The clinical diagnosis of myasthenia gravis is not difficult in typical cases. It is easier in bulbar forms of the disease, when oculo-bulbar clinical signs are persistent. Beside this signs appear skeletal muscle fatigue, which is more pronounced in the second part of the day and is relieved by rest. An important step in diagnosis of myasthenia gravis is the evidence that fatigue is caused by effort. The key element in the diagnosis of myasthenia gravis is improvement of deficits after administration of anticholinesterase medication.
In myasthenia gravis patients, the number of acethylcholine receptors at the neuromuscular joint is low, resulting a decreased interaction between acethylcholine and its receptor. Acethylcoline is metabolized by an enzyme called acetylcholinesterase. Pharmacologic inhibition of acetylcholinesterase will increases the concentration acethylcoline, improving muscle contraction. Edrophonium is a short-acting anticholinergic that improves muscle fatigue in myasthenia gravis patients.
For this test is needed a dose of 1 mg of a total dose of 10 mg of edrophonium solution, administered intravenously. If no response is noted, is injected the rest of the dose (9 mg). Bradycardia may occur due to excessive cholinergic stimulation of the heart and for this reason this test should be combined with atropine.
Edrophonium test has a low sensitivity in ocular form of myasthenia gravis and may present both false-positive and false-negative results. Other disease such as amyotrophic lateral sclerosis and cavernous sinus lesions may have a positive result at this test.
Combination between edrophonium test, electromyography and ocular tonography increase the chance of diagnosis in ocular form of the disease.
Anti-acetylcholine receptor antibodies
Anti-acetylcholine receptor antibodies are useful in diagnosing myasthenia gravis . This antibodies are present in 90% of patients with generalized form of myasthenia gravis and in 50-70% of patients with ocular form of the disease MG.
Other tests useful in myasthenia gravis diagnosis are represented by CT and MRI (especially in diagnosing thymus abnormalities), electromyography and ice pack testing (useful in diagnosing ocular form of the disease).
Myasthenia Gravis Treatment
Pharmacological therapy in myasthenia gravis include anticholinesterase medication and immunosuppressive therapy.
These drugs inhibit acetylcholinesterase, allowing a longer interaction between acetylcholine and its receptor. The most used drugs in this class are:
- Pyridostigmine (Mestinon) is the most commonly used, being considered first-line drug in the treatment of myasthenia gravis. Can be administered orally, has a long half-life time and reduced cholinergic side effects. Drug effects start at 15-30 minutes after administration, reach a maximum at 1-2 hours, and the effect lasts 3-5 hours. Most patients require 5-6 tablets per day.
- Prostigmine or neostigmine has a long duration of action and can be administered both orally and intramuscularly at varying intervals, according to patient response. It has a shorter but stronger duration of action than mestinon and cholinergic side effects are more frequently.
- Ambenomium chloride (Mytelase) is useful in generalized form of the disease. It is the most efficient drug used in resistant forms of myasthenia gravis to other anticholinergic drugs.
Immunosuppressive therapy is including corticosteroids and other immunosuppressive drugs.
- Corticosteroids are part of the common treatment for myasthenia gravis, considering the autoimmune nature of the disease. Are used especially in the ocular form of the disease and in unresponsive bulbar and generalized forms. At the beginning of the treatment, corticosteroids are worsening the symptoms over a period of 10-14 days. It was observed that under treatment with corticosteroids, areas of thymic hyperplasia have disappeared or their number has reduced.
- Other immunosuppressants. Are effective in unresponsive cases to corticosteroids, in unresponsive cases to other therapies or in cases that did not have a favorable response after thymectomy (surgical removal of the thymus). The most common drugs are: azathioprine, cyclophosphamide, 6-mercaptopurine and cyclosporine.
Plasmapheresis is useful in myasthenia gravis especially in resistant forms, in preoperative preparation for thymectomy, in unimproved cases after surgery and in myasthenic crisis. Clinical improvements are temporary, for a period of 4-6 weeks.
Thymectomy, surgical removal of the thymus is considered the most effective method of treatment in myasthenia gravis. Patients with thymoma present a more pronounced muscular fatigue. Although thymoma metastases rarely, by local invasion may give serious complications. Pure ocular form of myasthenia gravis is not usually an indication for thymectomy. After thymectomy, approximately 80% of patients are asymptomatic under medication or achieve complete remission in 5 years after thymectomy.