COMPOUND NERVE ACTION POTENTIAL - CNAP
 

ABSTRACT
Intraoperative recordings of compound nerve action potentials (CNAPs) can provide quick, reliable information on the status of peripheral nerves at the time of surgery. The technique is straightforward and can be easily used by those without a lot of previous experience in monitoring peripheral nerves. It requires no unusual instrumentation and is very cost-effective. It does not compromise routine surgical exploration of a peripheral nerve injury. The information provided by these studies is very useful in determining the best course of action to deal with a particular peripheral nerve injury. The indications of early, successful peripheral nerve regeneration observed in these studies cannot be obtained in any other way. Thus the method should not be viewed as a “monitor” of peripheral nerve activity—the information is diagnostic and essential. It is essential to use of this technique as a means of evaluating a peripheral nerve injury and deciding on the best way to deal with it.

BACKGROUND
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.
Although 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 is not a reasonable solution. Few studies have focused on the functional status of
the nerve. Over the years the compound nerve action potential (CNAP) has been found to be a useful tool toward this goal.
Some background knowledge on the response of nerves to injury is necessary to understand the findings of these neurophysiological studies. One objective will be to describe the changes that occur in injured nerves and to 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 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 to improve prospects for recovery. Some fascicles can be resected and repaired, and 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. Most injuries that are severe and yet leave the nerve in continuity affect in similar fashion the whole cross section of the nerve. However, some of these nerves have the ability to regenerate well and others do not. Operative nerve recording are equally important in these instances.
When some fascicles contain axons that are interrupted and others contain intact axons, a neuroma in continuity may develop in 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. There are many examples of large neuromas in continuity with significant portions of the nerve still showing conduction. Operative recordings, then, have accurately showing 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, there are many examples of lesions that are benign in appearance but that 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.
At the time of surgery the objective is to put neurophysiological findings into the context of patient history to gain some insight into 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 hr of injury. Within this 72 hr time period, axons distal to the point of injury may survive even if they are completely transected and may subsequently provide misleading information. If the surgery is a primary repair performed within 72 hr 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, it is usually better to plan surgery at approximately 2 to 4 months post injury. In this case, initial neurophysiological studies would be routine and would evaluate the extent of the initial injury. They also provide a basis of comparison for what can be seen operatively. Surgical exploration three months after injury may also indicate whether spontaneous regeneration has begun. The operative 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 division of the nerve. 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 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 hr of the initial injury, for the reasons cited previously. 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, which should be considered in appropriate circumstances.
A Sunderland grade 2 injury is axonotmetic, leading to 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 hr. 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 operative 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.
Sunderland grade 3 and grade 4 injuries represent greater obstacles to nerve regeneration. In these cases 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. Examination of this injury by operative recordings at 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. Grade 3 and grade 4 injuries are the most important to differentiate, 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 and to remove the offensive scar that blocks the regrowth of nerve.
A grade 5 injury results in a complete transection of nerve, either from a sharp or blunt insult. 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 that should be removed. Operative recordings can be helpful in this regard, demonstrating the point on the proximal stump 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.

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 those processes in 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, and the proximal part seals off at the point of division. Within 36 hr, 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 that 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 those of 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 that of 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, since 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 be an indication of ongoing regeneration at a very early stage but may also indicate ineffective regeneration at a later stage.

EQUIPMENT FOR INTRAOPERATIVE RECORDING

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 operative 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 operatively should have the ability to produce pulses of short duration (0.02–0.05 ms) and intensities up to 70 V. It is advocated 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, as is illustrated in Fig.1. Small-diameter fibers of normal nerve are less sensitive to short-duration stimulus pulses.
 

Fig. 1 The strength–duration relationship for stimulation shows that for normal fibers short-duration stimulus pulses require greater intensity. This phenomenon is particularly exaggerated at extremely short stimulus pulse durations. By comparison, regenerated axons are even less sensitive to short-duration stimulus pulses. This principle can be used to help discriminate the qualities of axons found in injured nerve. By using short-duration stimulus pulses, it can be selectively activate larger-diameter axons. Reprinted from [2].

The fine fibers of regenerating axons are even less sensitive to short-duration pulses than are equivalent normal fibers. Their strength–duration relationship is different than that of normal fibers with similar size. The responses that recorded to stimulation with short-duration pulses are, necessarily, from larger-diameter axons, and these may be a better indicator of effective regeneration. Additionally, these short-duration pulses reduce the amount of stimulus artifact.
The strength–duration relationship shows that with short-duration stimulus pulses much higher stimulus intensities must be used. It is 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 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 ground, such as the recording electrode. The stimulator may produce a current through any other electrical contact that the patient may have with 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 ground defeats stimulus isolation and spurious currents may result. 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 also 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 employ isolation amplifiers to augment stimulus isolation. The recorder portion of the EMG machine is optically isolated from ground by isolation amplifiers that reduce stimulus artifact even more, in addition to enhancing patient safety. Each recording channel will have a
positive (+) and negative (−) active input and also an isolation ground connection. This isolated 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 a so-called ground loop. 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 to reduce electrical interference. This connection is not essential, however, and routinely studies can be conducted 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 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. When a trace has been obtained that shows some stimulus artifact, the intensity of stimulation can be increased to a range of 6 to 8 V. 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 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. It is recommended to 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 lowermost part of the display screen. If this happens, it will be necessary to increase the low-frequency filter setting to 30 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 routinely used is between 2500 and 3000 Hz. This does not usually affect the shape of the CNAP, which 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, since 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 peripheral nerve.

ELECTRODES FOR INTRAOPERATIVE RECORDING AND STIMULATION

Examples of these electrodes can be seen in Fig.2, demonstrates the simple and convenient design of these electrodes. The requirements for electrodes include durability, reliability, and functionality.

Fig-2: Electrodes for stimulating and recording CNAPs can be made in many sizes, according to one’s needs. Illustrated here, Inomed electrodes. The stimulating electrode contains three contacts, and the recording electrode contains two. The inset enlargement of the electrode tips illustrates the curved hooks on which exposed nerve can be suspended. The tip separation of the recording electrodes can be adjusted according to the size of the nerve from which recordings are made.

The electrodes should withstand steam autoclaving and the rigors of routine handling together with other surgical instruments. They should have electrical characteristics that are conducive to safe stimulation and effective recording. The stimulating electrode contacts should never be made of silver. Although the resistance of silver wire is very low, stimulation through silver electrodes deposits silver salts that are toxic to nerve. Any metals used for tissue contact should have good tissue compatibility. The electrodes should have low electrical resistance, and they should resist tarnishing. They should also have adequate strength to hold their shape even under the weight and pull of nerves suspended on them. Stainless steel electrodes is effective, and their cost is modest compared to that of noble metals such as platinum.
The recording electrodes consist of two Teflon-insulated stainless steel electrodes approximately 8 cm long. For large-sized electrodes these are 1.125 mm in diameter, for medium-sized electrodes they are 0.875 mm in diameter, and for the miniature electrodes they are 0.625 mm in diameter. The ends are blunted and bent like a shepherd’s crook and can be used to pick up and suspend the nerve. The tips of these electrodes are separated by a distance of 5 to 7 mm for the large-sized electrodes, 3 to 5 mm for the medium-sized electrodes, and 2 to 3 mm for the miniature-sized electrodes. The distance between the tips of the recording electrodes determines, in part, the amplitude of the CNAP. If the distance between the tips of the recording electrodes is too small, the size of the CNAP will be reduced and inappropriate amounts of amplification may be required to see the CNAP. At high amplification, then, stimulus artifact could become a problem. This emphasizes the need to maintain an adequate distance between electrode tips, which should always be greater than the length of active nerve during the CNAP. If both recording tips are applied to a section of nerve that is simultaneously active, the size of the CNAP may be markedly reduced. The length of active nerve is considerably larger than one might imagine based on the anatomy of nodes of Ranvier. This is due to the fact that saltatory conduction in myelinated fibers is not simply regeneration of the action potential at successive nodes of Ranvier but rather a process in which several nodes of Ranvier (two to three) are activated simultaneously. One only needs to do simple arithmetic to show this. By considering the period of time required to produce an action potential at a single node of Ranvier and also the distance between nodes of Ranvier, a theoretical conduction velocity can be calculated. This theoretical conduction velocity is only one half to one third the observed conduction velocity in myelinated fibers. This fact dictates that action potentials must jump several nodes of Ranvier at a time. This process indicates that the length of active nerve is greater as a result of this phenomenon.
Therefore, a consistent distance between the tips of the electrodes must be maintained. One of the electrode tips must lie on the part of the nerve that is not active, and the other must contact the active part of the nerve.
The electrodes are soldered to a 4 meter length of flexible, Teflon-insulated wire that permits these wires to be led off of the sterile field. The Teflon insulation resists abrasion and is also unaffected by high-temperature autoclaving.
Appropriate plugs are used on the ends of these wires to permit attachment to the recording instrumentation. It should be noted that soldering to stainless steel requires special soldering flux and some skill. The stainless steel electrodes are then embedded into the acetal handles using methacrylate cement. Strain-relief is provided to the wires leaving the acetal handles to prevent bending fatigue and eventual breakage of the wires.
Similarly, stimulating electrodes are also fabricated with stainless steel electrodes and an acetal handle. However, in this case, three electrodes are embedded into the handle. These electrodes are also blunted and bent like a shepherd’s crook to support the suspended nerve. Tip separation is similar to that for the recording electrodes. This tripolar electrode is used to circumvent a special situation that exists when stimulating a nerve in continuity. Stimulation with a bipolar electrode produces two current paths, one short and one quite long. The longer current path is very undesirable because it leads to excessive stimulus artifact, especially when the distance between stimulating and recording electrodes is very short. In addition, it may permit the spread of stimulation over long lengths of the nerve when higher intensities of stimulation are used. The tripolar electrode breaks the longer current path and so reduces stimulus artifact and helps localize stimulation. In the tripolar electrode, the outermost electrodes are connected together so that there is no potential difference between them. There are still two current paths in this situation, but they are both short and localized to the region of contact with the nerve. There is very little spread of stimulation with the tripolar electrode.

Fig-3 Stimulation of nerve in continuity presents an unusual situation in which bipolar stimulation, top, produces two current paths. There is a very short path directly between electrodes, but there is also a second, longer path through the nerve and through the forearm. This second path passes beneath the recording electrode, producing large quantities of stimulus artifact. Tripolar stimulation, bottom, breaks the longer current path and localizes the stimulus to the region of electrode application. This dramatically reduces stimulus artifact, especially when the distance between recording and stimulating electrodes is short.

The electrodes must prove their durability, reliability, and functionality. To maintain these electrodes over many years, we recommend gas sterilization for routine use, though they will withstand occasional high-temperature steam autoclaving. They must be flash-sterilized should they become accidentally contaminated during a surgical procedure. Steam autoclaving, however, has a tendency to make plastics become brittle, and this eventually leads to a degradation of the electrodes. An occasional soaking in Instrument Milk (a cleaning and lubricating solution frequently applied to surgical instruments) will retard this degradation. The electrodes can be cleaned routinely with hot soap and water. In addition, their exposed metal tips will accumulate a protein coat of coagulum, and this should be periodically removed. Soaking the electrodes overnight in a solution of 30% bleach will soften and remove this coagulum.

ANESTHETIC CONSIDERATIONS

There are few pharmacologic considerations in making operative peripheral nerve recordings. Inhalational agents and narcotics do not affect peripheral nerve function, and neuromuscular blocking agents may or may not be used, depending upon personal preference. The latter may prevent evoked muscle contractions, but this information is only useful in an ancillary way. Peripheral nerve surgery often involves surgery on a limb, and it is common to apply a tourniquet to control bleeding. We do not use a tourniquet, but if one is used, it should be released at least 20 min prior to any neurophysiological studies. If the tourniquet pressure is maintained, the nerve may not be functional and the findings of CNAP studies may be misleading. Local anesthetics placed into or close to the nerve can also block nerve conduction.

RECORDING CNAPs INTRAOPERATIVELY

Once the level of a lesion to peripheral nerve has been determined by physical examination, patient history, and preoperative neurophysiological studies, surgical exploration can be carried out. A length of nerve is exposed that should include the site of the lesion. There are many examples of lesions that appear benign yet prove to be complete and offer no indication of early successful regeneration. Similarly, and there are examples of large neuromas in continuity that encompass only one or two fascicles and spare adjacent fascicles or when the whole cross section is involved but it still conducts responses. The visual appearance of a lesion in continuity may be deceptive. Sometimes it can be recorded from lengths of nerve as short as 4 cm. With this short distance, stimulus artifact can become an overpowering consideration, and longer lengths of nerve (8–10 cm) will facilitate recording. If a 4-cm length of nerve is not accessible, it may be necessary to stimulate or record percutaneously at a distant site. This can be accomplished by using skin electrodes or subdermal needle electrodes at some point down the length of the nerve. Usually the procedure starts by applying stimulus pulses of 0.02 ms duration and 6 to 8 V intensity. This stimulus is usually applied proximally, and recording electrodes are placed distally. When stimulation is applied distally and recordings made proximally, the size of the compound nerve action potential may be slightly reduced by fibers that are added to the nerve at proximal levels and are not subjected to the stimulating electrodes. The active fibers may thus become “buried” by the fibers that are not being stimulated and consequently do not produce action potentials. For this reason, a proximal response to distal stimulation may be reduced in size.
To record potentials from the distal electrodes, the amplifiers are set at a sensitivity of 200–500 μV/cm. A time window of 0.5–0.1 ms/cm is set. Under these conditions normal nerve will produce a clear CNAP. If no response can be seen, the sensitivity of the recorder will then be increased progressively down to 10 μV/cm. A small potential from regenerating nerve can be seen in Fig-4

Fif-4: This small CNAP was recorded from a section of nerve undergoing appropriate regeneration. The low amplitude and slow conduction velocity distinguish it from the CNAP of normal nerve. The presence of such a response is an indication for conservative treatment of a lesion.

If there is still no clear CNAP, the stimulation will be increased progressively to levels of 50 V or more. If there is still no visible CNAP, this indicates the absence of significant numbers of adequate fibers and dictates resection and repair. For initial recordings, it is recommended not use the signal-signal-averaging feature found on many EMG machines to enhance recordings of CNAPs. This technique is so sensitive that it may record very small numbers of fine fibers and indicate significant function in a segment of nerve that has no significant function. Once a CNAP is seen on each single trace, then average a number of traces will provide a clear, stable response for the patient’s record.

CRITERIA FOR APPRAISING A CNAP

If the CNAP is present, it will meet the following criteria. The putative response will be phase-locked to the stimulus, causing it to appear in a fixed position on the recorder screen each time a stimulus is delivered. It will appear “frozen” on the screen with repetitive stimulation, and its amplitude will always be less than 2 mV. A response larger than 2 mV is more likely a muscle action potential. In addition to being larger, evoked muscle action potentials usually have a longer duration than the CNAP. Thus an evoked response with a duration greater than 2 ms is likely to be a muscle response. Muscle responses also tend to be polyphasic, whereas CNAPs are not. The response should exhibit threshold behavior as the stimulus intensity is raised and lowered. It should also exhibit a maximum size with increased stimulation. If visible contraction of adjacent muscle can be seen during stimulation, the stimulus intensity can be lowered until the muscle contraction stops and a small CNAP can still be seen. This may help distinguish a muscle action potential from a CNAP. The duration of the CNAP should be less than 2 ms. Most CNAPs are not polyphasic, though under some particular conditions they may be. This may occur when some fascicles in the nerve are undergoing regeneration while others are recovering from a neurapraxic injury.
It is helpful to begin stimulation and recordings on a segment of nerve that is presumed to be normal. This may be a portion of the nerve proximal to a visible point of injury or an adjacent nerve accessible within the operative site. By stimulating and recording from a section of nerve that was functional preoperatively, one can verify that the instrumentation is working properly and one can be comfortable with an observation of no function in a section of adjacent nerve. A great advantage of the electrodes that we use is that they can slide along the length of nerve easily. In doing this, care must be taken to maintain good contact with the nerve. If these electrodes are held perpendicular to the floor, gravity becomes an ally, pressing the nerve against all of the contacts of the electrodes evenly. This ensures appropriate stimulating and recording conditions.
With this technique, proximal recordings from normal nerve can be compared to recordings made over and across a lesion in continuity and also distal to the lesion. Changes in the CNAP recorded at different levels of the nerve can then be related to the functional status of the nerve at those levels.
Often, there may be little anatomical indication of a lesion along the length of a nerve, and these operative recordings can localize the problem. Again, if one recorded proximally and slides the distal stimulating electrode along the length of the nerve, the recorded CNAP would be lost at the point where axonal continuity is lost. Resection of nerve at this point shows that the specimen removed contains mostly scar and few, if any, axons.
Intraoperative stimulation of peripheral nerve is often accompanied by evoked motor responses if the anesthetist has not blocked the neuromuscular junction. Although this observation may lend support to observations of peripheral nerve action potentials, it should not be used by itself as an indication of good functional connection with muscle. For example, there are patients with clear evoked motor activity who, preoperatively, had no voluntary control over a particular muscle following a nerve injury of long standing. With operative nerve stimulation there may be clear contractions of the muscle innervated.
Collectively, these findings indicate that, with extended time, small axons may regrow and reach their target muscles. However, the motor units that they form are too small to mediate voluntary movements. When all of these motor units are synchronized by electrical stimulation of their nerve supply, they may produce a visible contraction even though such contractions cannot be produced voluntarily. Thus the manifestation of a visible contraction of appropriate muscles may not be an indication of adequate functional nerve regeneration. Even though stimulation of the nerve above the lesion will exhibit this phenomenon, the lesion should still be properly resected and repaired if it does not transmit a recordable CNAP.
For very proximal root or spinal nerve injuries, it may become necessary to stimulate spinal nerves and record from nerve trunks. In the case of a root avulsion, this preganglionic injury (between dorsal root ganglion and spinal cord) to the sensory root will produce a relatively large and rapidly conducting CNAP.
If, by contrast, regeneration is occurring, the CNAP will be smaller and will have a slower conduction velocity in the range of 20–40 m/s. If there is a combination of postganglionic and preganglionic injury without effective regeneration, the recordings will be flat with no CNAP. For this type of extensive injury, the disruption of the axon proximal and distal to the dorsal root ganglion usually kills the cells of the dorsal root ganglion. For these cases sectioning spinal nerve or roots proximally prove the lack of proximal fascicular structure. Stimulation of the exposed elements in the neck and record from the sensory cortex using somatosensory evoked potentials (SEPs) to get some indication of connection of nerve roots to the central nervous system.
The complete absence of an SEP on stimulation of the nerve root indicates a complete avulsion and precludes surgical repair. The presence of an SEP upon nerve root stimulation should be viewed with some caution, however, since previous studies have shown that stimulation of even a very small number of fibers can produce
a normal SEP. If an SEP can be recorded following root stimulation, it should not be taken as evidence of normal function in the proximal parts of the root. Thus an absent SEP provides more definitive information than one that is present. When there is no SEP, one can accurately assume that there is no proximal connection.
Such findings can often be verified by preoperative EMG studies conducted on peripheral parts of the nerve. In the case of an avulsive injury, the intact sensory axons produce a normal CNAP in the distal sensory branches. The electrical characteristics of the distal axon remain fairly normal with stimulation, and recording distal to the dorsal root ganglion will reveal the presence of these surviving axons. However, needle EMG studies will indicate profound denervation in all of the muscles supplied by this root. The distal motor axons will all have undergone Wallerian degeneration. The combination of normal sensory studies together with profound denervation of muscle indicates a very proximal, avulsive injury. In addition, the complete absence of an SEP upon stimulation of these distal axons may also demonstrate a complete avulsion.

Indications for surgery:

Surgical exploration is performed not only when there is complete non function of the nerve, but when the nerve recovery is so minimal that it is useless in the long run and exploration having good expectation to improve the recovery. The second circumstance is debatable and vague.

There are important exceptions. These include injection injuries with incomplete loss but severe pain, gunshot wounds associated with partial loss and sustained pain, and a variety of other incomplete injuries affecting femoral or the more distal tibial nerve. Brachial plexus lesions with complete or incomplete functional loss at the
time of their evaluation.
Patients with tumors involving nerves usually had little or no functional loss preoperatively. Intraoperative CNAP recording is used to test fascicles entering and leaving intraneural tumors and to check progress of the dissection in other cases. For example, solitary neurofibromas involving nerves, major function in the innervating field of the particular nerve could be preserved despite total tumor removal by using intraoperative recordings and fascicular
dissection.
Of equal importance is the fact that when CNAPs are absent and a lesion in continuity resected, pathological studies confirmed that the lesion always neurotmetic or a Sunderland grade 4 nerve lesion. Such lesions had little
or no potential for spontaneous regeneration that might lead to useful function.
Optimal timing for recording varies according to the mechanism of injury.
In lengthier lesions like those produced by stretch and/or severe contusion, it takes longer for significant regeneration than can be recorded by direct CNAP studies. Thus most fracture-associated contusions and gunshot wounds can be tested operatively at 2 to 3 months post injury, whereas plexus stretch injuries are more reliably evaluated at 4 or 5 months after injury. On the other hand, recording can be done as an adjunct to tumor resection at any time and can be used as an investigative tool for entrapment or compressive neuropathies at any point in the course of these disorders.
Intraoperative recording is helpful in a relatively large number of patients with palsy of the accessory nerve. Loss of function in these patients is usually iatrogenic and due to lymph node biopsy or removal of a neck lesion and inadvertent damage to nerve distal to its innervation of sternocleidomastoid muscle. When the lesion is in continuity, operative CNAP studies are done. This approach lead to resection of about 50% of such accessory nerve lesions in continuity. These proved to be neurotmetic or Sunderland grade 4 nerve lesions. The other accessory nerve lesions in continuity has a neurolysis with a good outcome.
Although not essential for operative management of entrapment neuropathy, CNAP recordings when done had interesting features. A direct recording first is done proximal to the presumed entrapment site. The actual entrapment site was then defined by progressively moving the recording electrodes in a distal direction toward, into, and across the presumed entrapment site. Mild degrees of decreased conduction velocities were sometimes seen well proximal to an area of more severe conduction problems. Only in a few cases did this appear to be due to separate lesions or what has been described as a “double crush syndrome.” On the other hand, operative conduction across the area of entrapment was almost always more severely affected than might have been predicted by the preoperative EMG studies. This may relate to the fact that the distance between the stimulating and recording sites was less at the time of intraoperative recordings than at the time of EMG studies. These differences are usually most obvious in patients with ulnar entrapments at the elbow and those with presumed entrapment of the peroneal nerve over the region of the head of the fibula.
In few examples of true distal cubital tunnel syndrome did ulnar nerve entrapment appear clinically or neurophysiologically at the level of the two heads of flexor carpi ulnaris and distal to the olecranon notch. On the other hand, slowing of conduction velocity with ulnar nerve entrapment at the elbow usually appears to be maximal either just proximal to the olecranon notch or, more often, within the level of the olecranon notch itself. Thus most of the patients with ulnar nerve entrapment at the level of the elbow has neurophysiological findings indicating maximal lesioning just proximal to or in the notch. Also of interest are intraoperative recordings on patients with posterior interosseus nerve entrapments. The area of maximal abnormality in conduction, while usually beginning at the arcade of Frohse, appears to extend beyond that level distally and beneath the actual volar head of the supinator itself.
Some unusual entrapments or functional lesions to nerve can be further documented by intraoperative recording These have include radial nerve lesions at the level of the long head of the triceps, median as well as ulnar nerve entrapments by Struthers’ ligament, and irritative as well as compressive sciatic lesions just below the buttocks crease due to hamstring hypertrophy. There are many more lesions of plexus spinal nerves where thoracic outlet syndrome was suspected and intraoperative recordings showed conductive defects. These areas of reduced conduction velocity were more dramatic on the lower roots (especially C8 and T1) but at times were seen at C7 as well.
Conductive defects in these patients began at a spinal nerve or spinal nerve to trunk level but not more distally. By comparison, conduction velocities and amplitudes recorded from C5, C6, and usually C7 roots were almost always greater than those in lower roots in the patients with “true” thoracic outlet syndrome. In these cases there was often some weakness of hand intrinsic muscles in both the median and ulnar nerve distributions.

TROUBLESHOOTING

The operating room is generally regarded as a hostile setting for neurophysiological recording using electronic instrumentation. It is likely that those starting a program of intraoperative neurophysiology will encounter some problems, at least initially, and have to perform the task of troubleshooting.
Troubleshooting involves observation of existing conditions which may be problematic and knowing how to effectively deal with them. The powers of observation cannot be overemphasized. The sources of problems vary widely, though they can be put into several general categories. They may come in the form of the spontaneous and continuous electrical noise, which prevents recordings, or, more commonly, in the form of an inability to stimulate and record from sections of nerve that are known to be normal.
With electrodes applied to the nerve and the instrumentation adjusted to the settings described previously, one should view the display of the recording equipment. With the intensity of the stimulator turned all the way down, the trace should be relatively flat. If not, and the trace displays large regular and continuous excursions, there may be several sources for the interfering signal.
The most common of these is 60 Hz interference from electrical power sources. This can be readily identified by temporarily increasing the display to 10 or 20 ms per division. The most offensive devices would be those that contain electric motors. Hospital beds, pumps, and hot-air or fluid warmers are good examples. Turning these devices off may not prevent the interference, however, and they may have to be unplugged. Although older forms of fluorescent lighting were a significant problem in the past, modern fluorescent lighting rarely presents a problem. Sometimes, however, x-ray view boxes can produce an artifact, and these should be turned off when the problem is identified. Methodically unplugging, briefly, each of the devices identified as a possible source of the problem may help to eliminate the source of noise. If the source of the noise cannot be found, the electrodes should be disconnected from the EMG machine while the EMG machine is still recording. If the noise remains, it is most likely originating from the instrumentation itself, arriving there through electrical power lines. It may be necessary to plug the EMG machine into a different outlet. More commonly, however, the interference will disappear when the recording electrodes are unplugged, indicating that its source is from the recording electrodes. One should inspect the routing of the wires from the recording electrodes as they are passed off of the sterile field. If these wires are placed close to the power cords of other equipment, they may be the source of the interference. These wires should preferably be suspended in air from the operating table to the recording input; they should not be placed adjacent to any other metallic objects. In addition, these wires should not move, either from evoked muscle activity in the patient or simply from air currents around them. Movement, by itself, will produce electrical interference.
Patients on the operating table must not be connected to any true ground. Thus the reference for the electrosurgical unit (Bovie) and any other electrical equipment connected to the patient should not be grounded. The operating table itself is not grounded. Attaching the isolated ground from the EMG machine to the patient may help to eliminate the source of noise under these circumstances. This may be done using a large-surface-area disposable ground pad attached to the patient’s body at a point that is as close
to the recording site as is convenient.
With the recording electrodes attached to the EMG machine, the surgeon should be able to make contact between tissue and both recording electrodes, as the trace of the recorder remains flat. If there is a great deal of difference in the amount of noise displayed on the recorder as the surgeon touches both recording electrodes to the patient, there may be a broken or bad connection between the EMG machine and the recording electrodes. If only one of these electrodes actually makes connection with the patient, it will lead to excessive amounts of
noise. This may occur if one of the wires to the electrodes is broken or if there is poor contact between a wire and the plug attached to it. Bad electrical contact between the nerve and the electrodes will lead to a similar result and may occur if the electrodes have not been properly cleaned. It may be helpful to scrape the stainless steel surface of the electrodes that contact the nerve. This will produce a low-resistance junction that facilitates stimulation and recording.
Other sources of spontaneous, continuous interference include radio transmitting devices (telemetry), electrosurgical units, and spontaneous EMG. These sources of interference are high frequency and tend to fill the screen of the recorder. They may or may not be regular in appearance. In this case, it may be necessary to use the filters on the EMG machine to attenuate the noise, as was discussed previously. Occasionally, some unusual sources of interfering noise can be identified, including implanted stimulators and pacemakers.
Another challenge to monitoring is artifact related to the stimulus. Excessive stimulus artifact can be caused by a loss of stimulus isolation or by improper filter settings. Insufficient distance between stimulating and recording electrodes or insufficient distance between recording electrode tips may also lead to excessive stimulus artifact. A lack of adequate separation between stimulating and recording cables as they lead off the sterile field may capacitively produce excessive stimulus artifact. High-intensity stimulation or using long-duration stimulus pulses may also contribute to stimulus artifact problems. Although all recordings should contain some degree of stimulus artifact, it should not be so great as to prevent visualization of the CNAP immediately following it. In fact, if no stimulus artifact can be seen, it may be an indication of insufficient amplification or a failure of stimulation. As one becomes familiar with this technique, the appearance of a modest amount of stimulus artifact is comforting.
Another feature of recordings that one quickly adjusts to is the sweep speed of the recording instrument. This should be adjusted to approximately 1 ms/cm or a total sweep length of approximately 10 ms. If the display is set for too long a window of time, the CNAP will be lost in the stimulus artifact at the very beginning of the trace. Those accustomed to viewing SEPs will quickly appreciate that the CNAP has a much shorter latency and is a much faster event. The sweep required to view this event must be considerably faster than that required for the SEP.


CONCLUSIONS

Intraoperative neurophysiology is an exciting field that provides functional information to the surgical team. Despite the development of sophisticated new imaging techniques, these cannot provide the same kind of information that neurophysiological studies can. With respect to peripheral nerve, intraoperative neurophysiology provides diagnostic as well as prognostic information that cannot be learned in any other way. Preoperative EMG studies are very useful in evaluating the extent of a nerve injury, but even these cannot detect the electrical manifestations of very early regeneration. This can only be learned at the operating table. With this information in hand, the surgeon can decide on the proper course of action to treat the nerve injury. The assurance provided by these recordings gives him or her the proper feedback that his or her decisions are correct. The end result is that the patient will receive the benefits of surgery that will produce the best prospect for optimal recovery.
As with any new procedure, there will be apprehensions with implementation.
Operative recording of peripheral nerve activity provides useful information concerning nerve function at the time of surgery, and the results are certainly worth the small amount of extra effort required to obtain them. These recordings can be made quickly and reliably and represent an effective means of assessing the status of a segment of peripheral nerve. They provide assurance to the surgeon that the difficult decisions that must be made to deal with a lesion in continuity are based on good information and are not simply guided by intuition.

REFERENCES

1. Happel, L.T and Kline, D.G.,  . (2002). Intraoperative Neurophysiology of the Peripheral Nervous System. Neurophysiology in Neurosurgery: A Modern Intraoperative Approach. 2002, 169–194.
2. Happel, L.T., and Kline, D.G. (1991). Nerve lesions in continuity. In “Operative nerve repair
and reconstruction” (R.H. Gelberman, ed.), 1st ed, vol. 1, pp. 601–616. J.B. Lippincott,
Philadelphia.