Excitability testing in clinical neurophysiology—what, why, and when?

In the last 30 years, there have been few significant changes to the routine neurophysiological evaluation of patients with suspected neuromuscular disorders. Motor and sensory nerve conduction studies, in combination with needle electromyography (EMG), continue to constitute the core of the clinical study. These tests provide clinically meaningful information regarding the presence and localization of the disease process. However, major limitations exist. As a tool for following the course of a disease to document either deterioration or improvement, both EMG and nerve conduction studies are relatively insensitive. Partially to address this need, motor unit number estimation methods have received significant recent attention. In addition, EMG and nerve conduction studies provide relatively little information regarding pathophysiological mechanisms underlying specific diseases, and are quite poor at distinguishing one entity from another. For example, nerve conduction studies can determine the presence of a sensorimotor axon-loss polyneuropathy, but are usually unable to provide any information about its etiology. Finally, many patients present with symptoms suggesting an underlying peripheral nerve disease, but have sparse or absent clinical signs. Such patients often do not show significant abnormalities on routine electrodiagnostic testing, frustrating both the patient and the physician. For more than a decade, Dr. Hugh Bostock and colleagues have been studying multiple aspects of axon excitability, with the combined goals of learning more about the basic mechanisms of nerve conduction and providing pathophysiological explanations for disturbances of function caused by specific disease entities. Although many methods of excitability testing are suited only to animal studies, the technique of threshold tracking has been developed as a noninvasive, well-tolerated method amenable to human testing. In a threshold tracking study, a mixed nerve is stimulated in an identical manner to a routine nerve conduction study, and maximal motor or sensory responses are recorded. A criterion response (either motor or sensory) is established, and the stimulus intensity is adjusted to maintain that response while the system is perturbed in any of a variety of ways. For example, a motor response of 40% of maximum might be chosen, following which the nerve could be rendered ischemic. A threshold tracking experiment would measure the intensity of the stimulus required to maintain the motor response at that criterion level over the time during and after the period of ischemia. If performed manually, altering stimulus intensity to maintain a constant response is laborious and time-consuming. However, a computer-controlled feedback system can be used to reduce the number of stimulus presentations, and to increase the accuracy of the determinations. Several aspects about this general paradigm deserve mention. First, although the method is called threshold tracking, the responses obtained are not threshold responses, but responses somewhere in the midrange of the stimulus–response curve. In fact, threshold responses are not appropriate for this technique, as a clear differentiation must be made between signal and noise. Second, while routine nerve conduction studies primarily assess the number of conducting axons and speed of conduction, threshold tracking assesses local membrane properties and is insensitive to the amount of axon loss that may be present. Finally, because the area of interest in a threshold tracking study is the nerve membrane Correspondence to: J.M. Shefner; e-mail: shefner@upstate.edu