Intraoperative neurophysiology of the peripheral nervous system

30.1

Background

Over the course of the last four decades, there has been increasing interest in assessing segments of peripheral nerve during surgery. For example, the surgeon confronted by a neuroma in continuity has difficult decisions to make. He must determine the status of the nerve at the time of surgery and judge its potential to recover from injury. He must decide the best course of action to give the injured nerve the best prospect for an optimal recovery. While pathologic examination can provide anatomical information on the status of the nerve, this information is not available without removing a specimen. This may further damage a nerve already undergoing regeneration and thus is not a reasonable solution. Previously, few studies have focused on the functional status of the nerve. Over the course of four decades, we have explored the use of operative peripheral nerve recordings to facilitate the process of decision-making during the exploration and repair of a peripheral nerve injury . The compound nerve action potential (CNAP) has been found to be a useful tool toward this goal .

Some background knowledge of the response of nerves to injury is necessary to understand the findings of these neurophysiological studies. One objective of this chapter will be to describe the changes that occur in injured nerves and relate these to the process of regeneration in order to gain insight into the interpretation of intraoperative neurophysiological studies. The technical difficulties associated with recording nerve action potentials often prevent those with little experience from obtaining useful recordings. Therefore another objective will be to guide the reader with a detailed technical background. These technical issues may seem needlessly complex at times, but it is hoped that they may serve as a reference to address specific problems that may arise as one gains experience.

A nerve lesion that leaves the nerve in some degree of continuity may affect some parts of the nerve more than the others. Though it may be misleading, the term “partial” nerve injury is often applied in this circumstance. The use of this term seems to imply that some parts of the nerve fibers remain normal, while other parts are affected by injury. In such a lesion, it is more realistic to hold the position that none of the nerve is normal but some portions are more severely affected than others . Perhaps a better term for this situation would be a “mixed” injury to the nerve. Often, some parts of the nerve can be treated differently in order to improve the prospects for recovery. Some fascicles can be resected and repaired, while others can simply be neurolysed. In this “split repair,” those portions of the nerve that are minimally influenced by the surgeon will show a faster functional recovery than those that had to be resected and repaired. Thus they will also ultimately regenerate more effectively. Those portions of the nerve that require resection and repair must be identified in order to remove the growing scar and a developing neuroma . Such a neuroma could grow and compress the adjacent functional fibers . Thus in a mixed injury, those portions of the nerve that had good function initially will also be subject to further damage postoperatively should a growing neuroma develop.

In situations where some fascicles contain axons that are interrupted and others contain intact axons, a neuroma in continuity may develop in a part of the nerve. This occurs as regrowing axons fail to project in length and fold back onto themselves. The entangled, growing neurites increase in volume and begin to compress the intact axons. This results in a progressive loss of function long after the initial insult to the nerve. We have seen many examples of large neuromas in continuity, such as that seen in Fig. 30.1A , with significant portions of the nerve still showing conduction. Operative recordings, then, have accurately shown that the proper course of surgical treatment is to do a split repair, resecting only those fascicles involved in a neuroma and sparing those that remain intact. This ensures that the patient will have the best outcome for the injury he or she has sustained.

Similarly, as in Fig. 30.1B , we have seen many examples of lesions that are benign in appearance but show no electrical conduction. Visual inspection alone might deceive the surgeon, suggesting that this lesion might regenerate without repair. In most cases, such a severe lesion will not show significant regeneration, and the best course of action would be to resect and repair it.

Human peripheral nerve is easily injured by stretch. The sensitivity of nerve to stretch has been studied in detail and shows that a nerve, stretched 8%, undergoes a disturbance of intraneural circulation . If this disturbance in intraneural circulation is the total extent of pathology, the changes in nerve function may be transient. It is easy to appreciate that a mild insult of this sort might occur through a retraction mechanism. If the retraction is short-lived, there may be little or no postoperative findings. The longer this retraction is maintained, however, the more the likelihood of some postoperative pathology increases. An 8% stretch may also produce a breakdown in the blood–nerve barrier , and this could lead to a more significant injury. With a greater degree of stretch, beyond 18%–20%, especially if it occurs acutely, will likely produce a structural change . It is clear that the human peripheral nerve is very sensitive to stretch injury. Notice that the degree of stretch is expressed as a percentage of nerve length. This is particularly important with respect to minimally invasive surgery. If only a short length of nerve is mobilized, the amount of stretch that can be tolerated by the nerve is very small. Indeed, a greater degree of safety would be produced if a longer length of the nerve was mobilized.

At the time of surgery the objective is to put neurophysiological findings into the context of patient’s history to gain some insight toward the anatomy of the nerve without having to biopsy it. Preoperative neurophysiological studies may be helpful in describing the lesion, though these studies should not be done within 72 hours of injury. Within this 72-hour time period, axons distal to the point of injury may survive even if they are completely transected and subsequently provide misleading information . If the surgery is a primary repair performed within 72 hours of injury, preoperative neurophysiological studies may not be helpful. If the nerve is bluntly and completely transected, a delayed early repair may be planned at 3 weeks. Lesions in continuity, however, are more difficult to deal with. In the case of a secondary repair when a lesion in continuity is suspected, we will usually plan surgery at approximately 2–4 months postinjury. In this case, initial neurophysiological studies would be routine and would evaluate the extent of the initial injury. They also provide a basis for comparison of what can be seen intraoperatively. Surgical exploration 3 months after injury may also indicate whether spontaneous regeneration has begun. The intraoperative electrophysiology supplements information that was learned preoperatively to provide a perspective of the extent of injury to the nerve. Once the extent of the injury has been determined, the optimal surgical treatment can be provided.

Sunderland has classified nerve injuries into five categories ranging from mild functional change to the complete division of the nerve . This classification is described in Fig. 30.2 . Operative recordings can facilitate an understanding of the degree of injury as described by Sunderland. A Sunderland grade 1 injury that is neurapraxic leaves the axon in continuity. There may be mild changes to myelin but little other anatomic change. As long as the axon remains connected to the cell body, it remains functional even though a localized conduction block exists at the point of injury. This can be determined easily at the operating table by stimulating and successfully recording from a section of axon that is distal to the point of injury. Preoperative electromyogram (EMG) would show similar findings and the needle EMG study would show little or no evidence of denervation. Again, these recordings should not be made within 72 hours of the initial injury for the reasons cited above. A functional block of conduction at the site of injury does not affect conduction in the axon distally. A demonstration of normal nerve excitation and conduction in the nerve distal to the point of injury is proof of axonal integrity. An important exception to this is the avulsive injury that divides the sensory axon proximal to the dorsal root ganglion but spares the distal axon in the nerve. The distal axon would exhibit normal excitation and conduction properties, and yet it would be disconnected from the central nervous system. Preoperative EMG studies—as well as radiographic studies—should alert the surgeon to this possibility. This possibility should be considered in appropriate circumstances and will be treated later in this chapter. A Sunderland grade 2 injury is axonotmetic, leading to the Wallerian degeneration of the axon distal to the point of injury. This degeneration causes the distal axon to lose its properties of electrical excitability over the course of 72 hours. No peripheral nerve action potential can be seen if all of the fibers of the nerve under study have degenerated. This injury, however, is associated with little derangement of the connective tissue elements of the nerve. Spontaneous nerve regeneration is likely with this degree of injury and, if the timing of surgical exploration is appropriate, early indications of axonal regeneration can be seen across the site of injury. This is one of the great advantages of intraoperative recordings. Routine preoperative EMG studies would not show these early indications of regeneration. The electrical characteristics of these regenerating axons distinguish them from normal axons, as will be discussed later. Sunderland grades 3 and 4 injuries represent greater obstacles to nerve regeneration. In this case the injury is neurotmetic, altering the connective tissue components of the nerve. A grade 3 injury is a mix of axonotmetic and neurotmetic injuries and is associated with mild derangement of connective tissue and mild scar formation. Operative electrical studies of this injury after 3 months may also show indications of early spontaneous regeneration suggesting conservative surgical treatment. However, a grade 4 injury is neurotmetic and will be associated with much greater scar formation and a formidable barrier to nerve regeneration. Electrical recordings performed at 3 months after injury would not show indications of early regeneration if this scar blocks regrowing axons. Grades 3 and 4 injuries are the most important to discriminate since the heavy scar of grade 4 injury will not permit spontaneous regeneration. This lesion in continuity must be resected and repaired, in order to provide the best chance for optimal recovery, removing the offensive scar that blocks the regrowth of nerve . A grade 5 injury results in the complete transection of nerve either from a sharp or blunt insult. A grade 5 injury obviously requires surgical repair. Blunt injuries may include those that, by stretching, pull the nerve completely apart. In both of these cases a complete repair of the nerve is necessary. However, with blunt injury it is often difficult to determine the length of injured nerve which should be removed. Intraoperative recordings can be helpful in this regard, demonstrating the point on the nerve where viable axons remain. Then, once the nerve is sectioned at this point, one can visibly determine if a fascicular pattern remains at this level. In this way, one can determine whether the entire scar has been removed before the repair is begun .

30.2

Nerve regeneration

In order to understand neurophysiological findings obtained during surgery, it is necessary to understand the process of nerve regeneration. This process is complex and particularly so in humans. There is a significant difference in the processes of regeneration between lower mammals, such as the rat, and the human. In lower mammals, nerve regeneration is much more effective and complete, so much so that in some experimental settings, it even becomes difficult to prevent nerve regeneration. Rat nerves usually show significant regeneration even in the most adverse circumstances. By contrast, peripheral nerve regeneration in humans is not nearly so effective and regenerated axons never regain the electrical properties of their original counterparts. For this reason, one needs to be particularly careful in applying the results of research conducted on lower mammals to the human .

When an axon is divided, the distal part undergoes Wallerian degeneration . The proximal part seals off at the point of division. Within 36 hours, multiple sprouts of growing neurites appear at the sealed end of the proximal axon . These sprouts will give rise to several small, growing axons, each attached to the single proximal axon. The point of injury becomes a branch point, and it is not uncommon to see axon counts distal to the point of injury, which are higher than proximal axon counts. These growing axons are much smaller in diameter and have distinctive electrical properties . Their thresholds are markedly higher than normal nerves, and they are particularly insensitive to short-duration stimulus pulses in part because of the increased capacitance of their membranes. Their conduction velocities fall into a range that is much lower than a normal nerve. As the process of nerve regeneration continues, these axon sprouts elongate. During effective regeneration, some of these fine fibers will eventually die back in order to allow remaining fibers to increase in caliber . If these small diameter fibers do not increase in diameter, they are unlikely to form an effective junction with muscle. Motor axons must achieve a critical diameter in order to produce a useful motor unit. Should many fine fibers persist, the motor units formed will not lead to significant muscle strength . The presence of fine fibers may not only be an indication of ongoing regeneration at a very early stage but may also indicate ineffective regeneration at a later stage.

30.3

Equipment for intraoperative recordings

Operative recordings of peripheral nerve action potentials can be easily accomplished with many types of commercially available EMG machines. These offer both stimulating and recording capabilities that are appropriate for the intraoperative setting . Evoked potential instrumentation can also be used though it is usually more complex and difficult to use in such a simple setting. The stimulator used intraoperatively should have the ability to produce pulses of short duration (0.02–0.05 ms) and intensities up to 70 V. We advocate the use of very-short-duration stimulus pulses to reduce stimulus artifact. Short-duration stimulus pulses may also help discriminate the types of fibers that might be present. This is illustrated in Fig. 30.3 . Small diameter fibers of normal nerve are less sensitive to short-duration stimulus pulses . The fine fibers of regenerating axons are even less sensitive to short-duration pulses than equivalent normal fibers. Their strength–duration relationship is different than that of normal fibers with similar size. The responses that we record to stimulation with short-duration pulses are, necessarily, from larger diameter axons and these may be a better indicator of effective regeneration. In addition, these short-duration pulses reduce the amount of stimulus artifact, and this will be discussed further in a later section .

The strength–duration relationship as seen in Fig. 30.3 also shows that with short-duration stimulus pulses much higher stimulus intensities must be used . We have found that in some cases, when short-duration pulses are used, stimulus intensities as high as 70 V are required to excite regenerating axons. As long as pulse duration is kept short, these intensities can be used safely. However, if long-duration pulses are used at this intensity, the energies transferred by the stimulator can become dangerous and electrical burns may be possible. This is an additional reason for using short-duration pulses.

The stimulus should be properly isolated from the ground in order to prevent electrical currents from leaking into the recorder or through some other part of the patient’s body. With no stimulus isolation a potential difference applied between stimulating electrodes also represents a potential difference with any other electrode that may be connected to the ground, such as a recording electrode seen in Fig. 30.4 . The stimulator may produce a current through any other electrical contact that the patient may have with the ground. Though stimulus isolation is engineered into the EMG machine, this engineering can be defeated through poor application. If the wires leading to the stimulating electrodes are shielded, the resulting capacitance to the ground defeats stimulus isolation and may result in spurious currents. The cable connecting stimulating electrodes to the instrumentation should not be shielded. The same process may occur if these wires are draped against a metal surface such as the operating table or next to other wires. The resulting capacitive coupling defeats the stimulus isolation engineered into the EMG machine. This may produce excessive stimulus artifact or may even put the patient at risk for accidental electrical shock. Care should be exercised in the positioning of wires connecting the stimulator to the stimulating electrodes. When possible, suspend these wires in the air, away from any other wires or metal objects. It may also help to separate the stimulating cable from the recording cable as it is led off the sterile field to the EMG machine.

Most modern recording instrumentation now employs isolation amplifiers to augment stimulus isolation. The recorder portion of the EMG machine is optically isolated from the ground by isolation amplifiers. These isolation amplifiers serve to reduce stimulus artifact even more, in addition to enhancing patient safety. Each recording channel will have a positive (+) and a negative (−) active input and also an isolation ground connection. This isolation ground connection is not a true ground and would not be connected to any other part of the EMG machine. It cannot become part of the so-called ground-loop because the recording channels are optically isolated from any other connections. Thus, when properly connected, the patient is not attached to any true ground. The isolation ground connection on the EMG machine may safely be attached to the patient and may help reduce electrical interference. This connection is not essential, however, and we routinely conduct studies with no ground connection at all.

The recording sensitivity should initially be set to approximately 100 µV/cm or 1 mV for full-screen deflection . At this sensitivity, one should clearly see the stimulus artifact at the beginning of the trace. If not, it will be necessary to troubleshoot in an effort to detect the source of the problem. Troubleshooting will be discussed in a later section. When a trace that shows some stimulus artifact has been obtained, the intensity of stimulation can be increased to a range of 6–8 V (3-5 mA). If no nerve action potentials can be seen under these conditions, the recording sensitivity can be progressively increased to approximately 20 μV/cm. At this sensitivity the stimulus artifact should be quite large, and one may have to inspect the tail of the stimulus artifact closely to determine if a CNAP is present. The stimulus artifact decays as an exponential curve and the shape of this curve is dramatically affected by the settings of filters .

The slope of the exponential decay of the stimulus artifact is most affected by the low-frequency filter setting. We would normally begin recording with a low-frequency filter setting of about 10 Hz. At this setting the exponential decay is relatively slow and causes the tracing to be fairly flat. However, some amplifiers would saturate under these conditions, and the trace would appear flat at either the uppermost or the lowermost part of the display screen. If this happens, it will be necessary to increase the low-frequency filter setting to 30 Hz or even 100 Hz. Under these conditions the slope of the stimulus artifact will be much steeper and the amplifier should emerge from saturation. However, this may make the CNAP difficult to see.

The high frequency filter setting that we routinely use is between 2500 and 3000 Hz. This does not usually affect the shape of the CNAP that has an equivalent frequency of approximately 500–2700 Hz. It will remove extraneous high frequency noise from many other sources. The high frequency filter setting will not affect the rate at which the amplifier emerges from saturation. An important point to remember in selecting filter settings is that the CNAP should not be affected in an effort to reduce stimulus artifact or extraneous noise .

If an evoked potential machine is being used to record the CNAP, there may be a 60 Hz notch filter available. This should not be used under any circumstances. If a 60 Hz notch filter is used, it may produce an effect called “ringing.” With stimulation a dampened oscillation will become part of the stimulus artifact. This dampened oscillation may look very much like a CNAP and confuse the observer. For this reason, most EMG machines do not contain a 60 Hz notch filter. In any case, it is not advisable to use a 60 Hz notch filter when stimulating and recording from a peripheral nerve.