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Myasthenia Gravis

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. 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.


MG is an autoimmune disorder of the postsynaptic neuromuscular junction . The antibody-mediated attack destroys or inactivates acetylcholine receptors.


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.

Bulbar MG presents with nasal speech, fatigue on chewing, nasal regurgitation and difficulty in swallowing.


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.

Limb muscle weakness is usually associated with oculomotor involvement. Extraocular muscles may be weak, causing dysconjugate gaze and diplopia. Asymmetric lid ptosis may be spontaneous or inducible after one minute of sustained upward gaze.

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.

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).

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.


Management of a patient with MG may necessitate consultation with several specialists, including neurologists, intensive care specialists, pulmonologists, physiotherapists and occupational therapists.

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.

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.

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 attained.

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.