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The natural history of myasthenia gravis (MG), once often fatal, is rarely lethal today. The prevalence of MG in the United States has been estimated to be 14 per 100,000 persons, but it is thought that the number of cases of the disease is most likely myasthenia gravis, myesthenia gravis, miasthenia, miesthenia. Two age-related incidence peaks occur in patients with MG. During the second to third decade of life, women with MG outnumber men by a 2:1 ratio. A second peak occurs during the seventh to eighth decade in
PATHOPHYSIOLOGY
MG is an autoimmune disorder of the postsynaptic neuromuscular junction . The antibody-mediated attack destroys or inactivates acetylcholine receptors, and the
CLASSIFICATION AND CLINICAL PRESENTATION
MG presents as bulbar, ocular or generalized muscular weakness. Bulbar weakness affects the muscles used in chewing, swallowing and phonation. Ocular weakness is the presenting complaint in 50 to 66 percent of individuals with MG and develops later in another 30 to 35 percent of patients. Ninety percent of individuals with ocular myasthenia eventually develop generalized weakness.
Most patients with MG present with ptosis, diplopia or photosensitivity. Ptosis usually occurs asymmetrically and is associated with lid-closure weakness. Lid lag that increases after one minute of sustained upward gaze is a positive finding for ptosis. Reading or driving exacerbates diplopia. Photosensitivity is caused by weakness in the pupillary constrictor muscles. Extraocular muscle
Bulbar MG presents with nasal speech, fatigue on chewing, nasal regurgitation and difficulty in swallowing. Physical examination may
DIAGNOSTIC EVALUATION
On neurologic examination, patients with MG have intact sensation, cognition and higher cortical functions. Deep tendon reflexes may be normal or diminished. The most important feature is muscular weakness. Gait may be secondarily impaired. The patient's limb muscle weakness may be variable and may follow a proximal pattern. Fatigability can be demonstrated even in strong muscles
Limb muscle weakness is usually associated with oculomotor involvement. Extraocular muscles may be weak, causing dyseonjugate gaze and diplopia. Asymmetric lid ptosis may be spontaneous or inducible after one minute of sustained upward gaze. The patient
Edrophonium chloride testing ("Tensilon test") uses administration of acetylcholinesterase inhibitors to identify individuals in whom the neuromuscular junction is disabled. Acetylcholinesterase inhibitors improve neuromuscular transmission by increasing the
It should be remembered that a positive edrophonium chloride test result is not specific for MG. Diseases associated with immature reinnervated neuromuscular junctions, such as extraocular cranial neuropathy or motor neuron disease, may also show symptom improvement after administration of this agent. If findings are equivocal, a trial of pyridostigmine bromide (Mestinon) may be of
Electromyography can also aid in establishing the diagnosis of MG by demonstrating failure of neuromuscular transmission as a decreasing motor response on slow repetitive electrical nerve stimulation (two cycles per second) administered before and after
MANAGEMENT
Management of a patient with MG may necessitate consultation with several specialists, including neurologists, intensive care specialists, pulmonologists, physiotherapists and occupational therapists. In addition, it is important to recall that a number of
Medical Therapy. Acetylcholinesterase inhibitors block the degradation of acetylcholine at the neuromuscular junction. These agents increase neurotransmitter availability to damaged acetylcholine receptors. Pyridostigmine bromide is the most commonly used agent for ocular and generalized MG. It should be started at 30 to 60 mg orally three to four times per day. Drug effects begin within 30 to 45 minutes after administration and persist for three hours. In severe MG, a dosage of 120 mg every three to four hours may
Prednisone produces significant improvement in 75 percent of patients with MG and a lesser degree of improvement in the remainder. Patients with bulbar or moderate to severe generalized MG have a high likelihood 148 percent) of experiencing a disease exacerbation within the first 10 days of prednisone use. These patients may require hospital admission for plasma exchange. Thus,
Prednisone is typically started at a dose of 60 to 80 mg per day. Patients with mild generalized MG may be started on 15 to 20 mg per day on an outpatient basis. In these patients, the dosage is gradually increased in 5-mg increments until maximal improvement is
If a patient shows marked strength improvement after six to eight weeks of treatment, steroids may be individually tapered. Prednisone is slowly tapered to 60 to 80 mg every second day by lowering the alternate day dosage by 20 mg every two to four weeks. Thereafter, the dose may be gradually reduced over a period of one year according to clinical response. When symptoms cease, prednisone may be stopped, and the patient should be assessed for permanent disease remission. Most patients, however,
Patients who respond poorly to prednisone require alternative immunosuppressive therapy, such as azathioprine, 100 to 250 mg per day, or cyclosporine (Sandimmune, Neoral), 125 to 200 mg two times per day. Each of these drugs inhibits T-cell activity, albeit through different mechanisms. If a patient develops flu-like symptoms when azathioprine therapy is initiated, the drug should be
Symptom improvement may be seen within three to six months after initiation of azathioprine therapy and typically peaks at one to two years. Cyclosporine works more rapidly, usually producing improvement after one to two months of therapy, and its effectge.
Surgical Therapy. Some experts recommend thymectomy in patients with a thymoma or those with generalized MG who are between puberty and age 60.64 Patients with MG that is confined to the ocular muscles do not usually require thymectomy. Thymic hyperplasia occurs in 70 percent of patients with MG, and 10 percent of patients with MG have a thymorea.E Although no rigorous
Thymoma should be suspected in patients with antistriated muscle antibodies in the serum because 90 percent of patients with a thymoma (as compared with 27 percent of all patients with MG) have this finding. MG develops in 30 percent of patients with a
Patients with severe MG should be pretreated with three to five cycles of plasma exchange before surgery. Pyridostigmine bromide is given intravenously at approximately one-thirtieth of the normal oral dose. Thirty-five percent of patients experience clinical remission after thymectomy, and about half improve to the point that the need for immunosuppressive therapy is reduced. Patients
Treatment oŁ Myasthenic Crisis. The diagnosis of myasthenic crisis is made in the presence of a forced vital capacity that is less than 15 mL per kg or difficulty clearing secretions. The airway should be urgently stabilized, and the patient should be admitted to an
PREGNANCY AND MYASTHENIA GRAVIS
The effect of pregnancy on MG cannot be predicted. Abortion has not been shown to improve symptoms of MG. Muscular status in postpartum women often deteriorates within two to six weeks after delivery. Magnesium sulfate must be avoided in pregnant women with MG because high levels of magnesium inhibit acetylcholine release. Administration of magnesium sulfate to these patients may result in apnea and respiratory arrest. Regional anesthesia with lidocaine rather than procaine is preferred because