Myasthenia GravisDz

ICD-9 Code: 358.0.

ICD-10 Code: G70.0

Definition: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. It is characterized clinically by muscle weakness and immunologically by autoantibodies directed against the postsynaptic acetylcholine receptor. These autoantibodies are pathogenic, causing increased turnover and decreased surface expression of the acetylcholine receptor, which results in decreased muscle depolarization and weakness.

Etiology: Although most cases of myasthenia gravis are idiopathic, some patients have associated thymomas or thymic hyperplasia. Myasthenia gravis may also occur as a rare reaction to D-penicillamine therapy.

Demographics: Myasthenia gravis is rare, with a prevalence of approximately 14 per 100,000, and has a bimodal distribution. There is a slight female predominance among patients with disease onset in the second and third decades, and a male predominance among patients older than 50 years of age. There is a genetic predisposition, partly related to expression of the HLA-B8 and DR3 alleles.

Associated Conditions: Many patients with myasthenia gravis, particularly those with younger onset of disease, have associated thymomas (10% of patients) or thymic hyperplasia (70%). Myasthenia gravis is also associated with other autoimmune diseases, including thyroid disease (15% of patients), RA (4%), and SLE (2%).

Cardinal Findings: The characteristic clinical picture of myasthenia gravis is muscle weakness that worsens with repetitive use and improves with rest. Ocular muscle involvement is most common, and two-thirds of patients present with symptoms such as ptosis and diplopia. Symptoms typically worsen after strain and at the end of the day. Approximately 15% of patients have myasthenia gravis that remains limited to the ocular muscles. For the remainder, the disease progresses to involve the oropharyngeal (i.e., dysphagia, dysphonia, dysarthria) and limb muscles. When it affects the respiratory muscles, myasthenia gravis can be fatal. For approximately two-thirds of patients, maximum muscle weakness occurs in the first year of disease. Exacerbations may be associated with various factors such as emotional stress, infection, and thyroid disease. In addition, medications that affect neuromuscular transmission (e.g., aminoglycoside antibiotics, neuromuscular blockers, class I antiarrhythmics) may also exacerbate myasthenia gravis.

Diagnostic Tests: The diagnosis of myasthenia gravis may be accomplished by several means. Pharmacologic testing or the Tensilon test uses a short-acting acetylcholinesterase inhibitor (e.g., edrophonium) and may reveal dramatic improvement in muscle strength. Pharmacologic testing may be falsely negative in some patients with myasthenia gravis, particularly children.

Increased serum concentrations of antibodies directed against the acetylcholine receptor are seen in approximately 65% of patients with myasthenia gravis limited to ocular musculature and 85% of patients with more generalized myasthenia gravis. Anti–acetylcholine receptor antibody tests are avail- able from reference laboratories. The presence of anti–acetylcholine receptor antibodies is relatively specific, although false-positive results may be seen in patients with SLE and among healthy relatives of patients with myasthenia gravis.

Finally, electrophysiologic studies may aid in the diagnosis of myasthenia gravis by demonstrating characteristic abnormalities (e.g., decremental responses on repeated muscle stimulation).

Differential Diagnosis: Myasthenia gravis may be mistaken for Eaton- Lambert syndrome (commonly a paraneoplastic syndrome that affects the presynaptic segment of the neuromuscular junction), inflammatory myositis (i.e., PM, DM, inclusion body myositis), other myopathies, multiple sclerosis, and chronic fatigue syndrome.

Therapy: Myasthenia gravis therapy must be individualized. Long-acting anticholinesterase drugs (e.g., pyridostigmine) are the mainstay of therapy for most patients. Thymectomy is indicated in many patients with myasthenia gravis, particularly those with thymoma. Thymectomy may not be advisable for those for whom the risks of surgery may outweigh the potential benefit, including the elderly and those with purely ocular muscle involvement. Various immunomodulatory agents also have a role as therapeutic agents for patients with myasthenia gravis. Corticosteroids, often used initially at high doses (e.g., 1 mg/kg), achieve a response in ~75% of patients. Other immunomodulatory therapies that have been used include intravenous ϒ-globulin, plasma exchange, azathioprine, cyclosporine, and cyclophosphamide.

BIBLIOGRAPHY

Drachman DB. Myasthenia gravis. N Engl J Med 1994;330:1797–1803.PMID:8190158

Finley JC, Pascuzzi RM. Rational therapy of myasthenia gravis. Semin Neurol 1990;10:70–85.PMID:2189183