Single-fiber electromyography (EMG) represents an even more sensitive method of detecting the defect in neuromuscular transmission. This technique demonstrates an inconstancy of the normally invariant interval between the firing of muscle fibers connected to the same motor unit (“jitter”—see “Single-Fiber Electromyography” in Chap. 2) or complete blocking of successive discharges from single muscle fibers belonging to the same motor unit. The test requires a great deal of cooperation from the patient and that contraction of a muscle be sustained at just the right amplitude in order to isolate single muscle fibers from the same unit. It is also possible to detect such pairs of fibers by electrical stimulation of a nerve. Nerve conduction velocities and distal motor latencies are normal unless there is a coincident polyneuropathy.
Neostigmine test Almost as valuable as electrophysiologic testing is testing with the cholinesterase inhibitors neostigmine and in the past, edrophonium a more rapidly acting agent. These drugs prolong and exaggerate the effects of ACh in the synapse and thereby produce an increment in muscle power in the patient with myasthenia. Edrophonium is variably available in the United States at the time of this writing but neostigmine affords a longer time for observation, as noted in the next paragraph. The tests are performed in the following manner. After the estimation of strength in a cranial (usually the levator palpebrae or an extraocular muscle) or limb muscle (by dynamometry), or vital capacity, neostigmine is injected intramuscularly in a dose of 1.5 mg. Atropine sulfate (0.8 mg) is generally given several minutes in advance to counteract the unpleasant muscarinic effects of neostigmine (salivation, sweating bronchorrhea, borborygmi, bowel cramps and, sometimes, diarrhea). Neostigmine may alternatively be given intravenously in a dose of 0.5 mg, but its effect is often too brief to be as useful. After intramuscular injection of neostigmine, objective improvement occurs within 10 to 15 min, reaches its peak at 20 min, and lasts up to 1 h, allowing for careful verification of the neurologic improvement. Many neurologists perform this test twice, once with an injection of saline as a control.
Alternatively, 1 mg (0.1 mL) of edrophonium is given intravenously; if this dose is tolerated and no definite improvement in strength occurs after 45 s, another 4 to 9 mg is injected. A total dose of 10 mg is rarely necessary. Most patients who respond do so after 3 to 5 mg has been administered. The mild muscarinic effects of edrophonium are blocked by pretreatment with atropine 0.8 mg subcutaneously as for neostigmine. The clinical effect of improved ptosis, extraocular movements, oropharyngeal function, arm and shoulder abduction, or vital capacity persists for no more than 5 min with edrophonium and 60 min with neostigmine.
One caution: with either drug, some patients deteriorate immediately, but briefly, as a result of an increase in pulmonary secretions. A positive test consists of visible (objective) improvement in muscle contractility, fusion of diplopia, or resolution of fatigable ptosis. Dynamometry and measurement of forced vital capacity serve as more objective markers of improvement, or lack of effect. The report of subjective improvement alone is not dependable and one must be distrustful of equivocal test results, which may occur with ocular palsies due to tumors, thyroid disease, Guillain-Barré syndrome (GBS), progressive supranuclear palsy, or carotid aneurysms (pseudoocular myasthenia).