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Medication such as aminoglycosides that may exacerbate myasthenia gravis should be avoided Anticholinesterase drugs provide symptomatic benefit without influencing the course of the disease Neostigmine, pyridostigmine, or both can be used, the dose being determined on an individual basis The usual dose of neostigmine is 75 30 mg (average, 15 mg) taken four times daily; of pyridostigmine, 30 180 mg (average, 60 mg) four times daily Overmedication may temporarily increase weakness, which is then unaffected or enhanced by intravenous edrophonium Thymectomy usually leads to symptomatic benefit or remission and should be considered in all patients younger than age 60, unless weakness is restricted to the extraocular muscles If the disease is of recent onset and only slowly progressive, operation is sometimes delayed for a year or so, in the hope that spontaneous remission will occur Treatment with corticosteroids is indicated for patients who have responded poorly to anticholinesterase drugs and have already undergone thymectomy It is often introduced with the patient in the hospital, since weakness may initially be aggravated Once weakness has stabilized after 2 3 weeks or any improvement is sustained, further management can be on an outpatient basis Alternate-day treatment is usually well tolerated, but if weakness is enhanced on the nontreatment day it may be necessary for medication to be taken daily The dose of corticosteroids is determined on an individual basis, but an initial high daily dose (eg, prednisone, 60 100 mg) can gradually be tapered to a relatively low maintenance level as improvement occurs; total withdrawal is difficult, however Treatment with azathioprine may also be effective The usual dose is 2 3 mg/kg orally daily after a lower initial dose In patients with major disability, plasmapheresis or IVIG therapy may be beneficial It is also useful for stabilizing patients before thymectomy and for managing acute crisis Mycophenolate mofetil, an immunosuppressant, may provide symptomatic benefit and allow the corticosteroid dose to be reduced.
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The toxin of Clostridium botulinum prevents the release of acetylcholine at neuromuscular junctions and autonomic synapses Botulism occurs most commonly following the ingestion of contaminated home-canned food and should be suggested by the development of sudden, fluctuating, severe weakness in a previously healthy person Symptoms begin within 72 hours following ingestion of the toxin and may progress for several days Typically, there is diplopia, ptosis, facial weakness, dysphagia, and nasal speech, followed by respiratory difficulty and finally by weakness that appears last in the limbs Blurring of vision (with unreactive dilated pupils) is characteristic, and there may be dryness of the mouth, constipation (paralytic ileus), and postural hypotension Sensation is preserved, and the tendon reflexes are not
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affected unless the involved muscles are very weak If the diagnosis is suspected, the local health authority should be notified and a sample of serum and contaminated food (if available) sent to be assayed for toxin Support for the diagnosis may be obtained by electrophysiologic studies; with repetitive stimulation of motor nerves at fast rates, the muscle response increases in size progressively Patients should be hospitalized in case respiratory assistance becomes necessary Treatment is with trivalent antitoxin, once it is established that the patient is not allergic to horse serum Guanidine hydrochloride (25 50 mg/kg/d in divided doses) to facilitate release of acetylcholine from nerve endings sometimes helps to increase muscle strength Anticholinesterase drugs are of no value Respiratory assistance and other supportive measures should be provided as necessary Further details are provided in 33
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Muscle weakness, often in a characteristic distribution Age at onset and inheritance pattern depend on the specific dystrophy
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These inherited myopathic disorders are characterized by progressive muscle weakness and wasting They are subdivided by mode of inheritance, age at onset, and clinical features, as shown in Table 24 8 In the Duchenne type, pseudohypertrophy of muscles frequently occurs at some stage; intellectual retardation is common; and there may be skeletal deformities, muscle contractures, and cardiac involvement The serum creatine kinase level is increased, especially in the Duchenne and Becker varieties, and mildly increased also in limb-girdle dystrophy Electromyography may help confirm that weakness is myopathic rather than neurogenic Similarly, histopathologic examination of a muscle biopsy
Aminoglycoside antibiotics, eg, gentamicin, may produce a clinical disturbance similar to botulism by preventing the release of acetylcholine from nerve endings, but symptoms subside rapidly as the responsible drug is eliminated from the body These antibiotics are particularly dangerous in patients with preexisting disturbances of neuromuscular transmission and are therefore best avoided in patients with myasthenia gravis
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