Intensity

The lowest stimulation intensity that is needed to produce an evoked potential is known as the threshold intensity. As the intensity increases the latency decreases and amplitude increases. The latency and amplitude change is not linearly related to the stimulation intensity, and the changes occur up to a maximum. Beyond this limit, further increase in stimulation intensity does not affect the evoked potentials. Central components of the evoked potentials reach maximum amplitude earlier than peripheral components. This occurs because of “central amplification” of the stimulus (3). Central amplification refers to the ability of a peripheral stimulus to activate more fibers in central pathways than in peripheral nerves. Consequently, with gradually increasing stimulus intensity, cortical and subcortical evoked potentials will cease to become larger at a lower intensity than peripheral evoked potential. This is discussed in more detail in Chapter 4.

Intensity of stimulation is measured differently for different types of evoked potentials. For SEPs, the intensity is milliampere (mA) of electrical stimulation. BAEP stimulation intensity is measured by the decibel (dB) of the auditory clicks. Intensity of stimulation of PRVEP depends on the contrast ratio between the light and dark patterns.

Duration

Duration of the stimulus is closely related to the intensity. It refers to the time that the stimulus is applied. Increasing the duration of the stimulus has an effect similar to increasing intensity. Longer duration stimuli will result in shorter latency and higher amplitude of the evoked potential waveforms with the same caveats as noted above for intensity.

Rate

The stimulus rate is the number of stimuli delivered per second. It is often denoted in hertz (Hz), but this is incorrect, as Hz implies that the stimulus is sinusoidal. The stimulus rate must be such that the entire evoked potential waveform of interest is recorded before the next stimulus is delivered. Thus, the rate is dependent on the latency of the evoked potential waveforms. Short latency waveforms require a shorter time window of recording and can be acquired using faster stimulation rates. Long latency potentials require a longer time window of recording and need a slower stimulation rate. For BAEP waveforms, a recording time (or sweep) of 10 to 15 ms can be used with a stimulation rate of 50/s. On the other hand, VEP waveforms often require a sweep of 200 ms, and so must be obtained with a slow rate of about 1 to 2/s. If the stimulation rate is too fast, the evoked potential from one stimulus starts before the evoked potential from the previous one has been completed. This results in steady state evoked potentials. Steady state evoked potentials are not routinely used clinically. The stimulation rate should not be an integer of 60, as alternating current (AC) in power lines in the United States is generated at 60 Hz (it is 50 Hz in some parts of the world). If the stimulation rate is an integer of 60, differential amplifiers may be unable to eliminate the electrical artifact from the evoked potentials recording.

Figure 1.2

Median nerve SEP waveform latency variations.

Age: 56 years

Sex: Female

Stimulation rate: 5.7/s

Filters: 30–1,500 Hz

Scale: Amplitude = 0.5 μV/div; Latency = 3 ms/div

Side: Right

Stimulation duration: 0.2 ms

Stimulation intensity: 16.4 mA

Number of repetitions: 1,213

Median nerve conduction velocity (median nerve to EP waveform): 46 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
EP	9.90
N13	13.9
P13	13.2
N18	16.8	2.31 (P13–N18)
N20	19.8	1.08 (N20–P22)

Interpeak Latencies
Waveforms	Latency (ms)
EP–N20	9.90
EP–P13	3.30
P13–N20	6.60

Discussion: The N13 waveform is thought to arise from the cervical spinal cord and the P13 (and P14) waveform from the nucleus cuneatus. In this example, the P13 waveform has a shorter latency than the N13 waveform even though its generator is rostral to the generator of the N13 waveform. This suggests that individual waveforms cannot be considered to arise from single generators. In reality, each waveform receives contributions from several generators and each generator contributes to multiple waveforms.

SEP, somatosensory evoked potential.

In general, with slower rates of stimulation, the evoked potential waveform morphology is better, latency shorter, and amplitude higher. Faster rates stress neural transmission, particularly through synapses, resulting in longer latencies and lower amplitudes. However, the slower the rate, the longer it takes to acquire the data which may compromise patient cooperation. The optimal stimulation rate must be a compromise between evoked potential morphology and speed of acquisition. In some laboratories, evoked potentials will be obtained with a “fast” rate initially. If the evoked potential is normal at this rate, the test is complete. However, if it is abnormal, the evoked potential will be repeated at a slower rate. Occasionally, an evoked potential is normal with the slow rate, but abnormal with fast rate. How such a test is interpreted is controversial. Some would interpret an evoked potential as normal if it is normal at any stimulation rate. On the other hand, some would interpret an evoked potential abnormal if it is abnormal at any stimulation rate. The author’s practice is the former (Figures 1.3A and B).

Repetitions

The number of repetitions refers to the number of evoked responses that must be averaged to produce a reliable evoked potential. The smaller the amplitude of the evoked potential and higher the amplitude of noise (low signal-to-noise ratio), the more repetitions will be needed. The number of repetitions needed is reduced if the signal-to-noise ratio is improved. To some extent this can be done by increasing stimulus intensity and duration and reducing noise. Higher number of repetitions leads to better evoked potential waveform morphology and reproducibility (Figures 1.4A–E). The number of repetitions that are recommended for each type of evoked potentials modality will be discussed in the respective chapters.

Replication

Replication should not be confused with repetitions. Whenever an evoked potential is obtained, it must be reproduced at least once to ensure that the waveforms recorded are reproducible. This is known as replication of the evoked potential. When evoked potentials are not very reproducible, more than one replication may be necessary to confirm the presence of low amplitude waveforms. Most modern evoked potential machines acquire two repetitions simultaneously; that is, alternate stimuli are used to create two different averages.

Properties

Recording electrodes must be able to conduct neural signals without distortion. They must be made of material that resists polarization and does not interact with skin or other human tissue with which it makes contact. Electrodes coated with gold, platinum, or silver coated with silver chloride are most often used. Periodically the electrode’s resistance must be checked. This is the opposition to direct current flow and is measured with an ohmmeter. Electrode resistance should be no more than a few ohms, and if it is very high, a breach in the integrity of the electrode should be suspected. Electrode impedance is the opposition to AC flow. Rather than measuring the integrity of the electrode, impedance evaluates the connection of the electrode to skin or soft tissue and is measured by an impedance meter. Electrode impedance should be below 5,000 Ω (4). Higher impedances degrade the ability of the amplifier to average low amplitude signals.

Figure 1.3 (A and B)

Effect of stimulation rate on BAEP waveforms.

Age: 49 years

Sex: Male

Filters: 150–3,000 Hz

Ear inserts (add 0.9 ms): Yes

Side: Right

Click polarity: Rarefaction

Stimulation intensity: 70 dBnHL

Masking intensity: 40 dBnHL

Number of repetitions: 2,000

Stimulation rate: 51.1/s

Scale: Amplitude = 0.05 μV/div; Latency = 1 ms/div

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
I	N/A	N/A (I–In)
III	4.88
V	6.84	0.27 (V–Vn)
Vc	6.86
		N/A (V/I ratio)

Interpeak Latencies
Waveforms	Latency (ms)
I–Vc	N/A
I–III	N/A
III–Vc	1.98

Stimulation rate: 11.1/s

Scale: Amplitude = 0.1 μV/div; Latency = 1 ms/div

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
I	2.40	0.07 (I–In)
III	4.66
V	6.64	0.35 (V–Vn)
Vc	6.72
		5.0 (V/I ratio)

Interpeak Latencies
Waveforms	Latency (ms)
I–Vc	4.32
I–III	2.26
III–Vc	2.06

Discussion: Faster stimulation rates can cause degradation in waveform morphology, loss of amplitude, and prolongation of latency. A BAEP obtained with a fast stimulation rate of 51.1/s is shown (A). Notice that the wave I is difficult to identify, despite the sensitivity being set at 0.05 μV/div. In the same patient, when the rate is slowed to 11.1/s (B), the wave I is clearly seen despite the sensitivity being lower (0.1 μV/div). Additionally, the wave V latency is shorter with the slower rate. It is the author’s practice to consider a study normal if it is normal at any stimulation rate.

BAEP, brainstem auditory evoked potential.

Figure 1.4 (A–E)

Effect of number of repetitions on VEP waveforms.

Age: 43 years

Sex: Male

Stimulation rate: 2.1/s

Filters: A = 1–100 Hz; B = 10–100 Hz; C = 1–30 Hz

Preauricular–preauricular distance: 38 cm

Scale: Amplitude = 2 μV/div; Latency = 20 ms/div

Eye: Right

Visual angle: 30′

Visual acuity: 20/20

Corrective lenses: Yes

(A)

Number of repetitions: 1

(B)

Number of repetitions: 10

(C)

Number of repetitions: 50

(D)

Number of repetitions: 100

(E)

Number of repetitions: 200

Discussion: This PRVEP shows the utility of increasing repetitions. In Figure A, only one repetition is shown. Figures B, C, D, and E have 10, 50, 100, and 200 repetitions, respectively. With 1 and 10 repetitions, the P100 waveform cannot be identified. With 50 repetitions, the P100 waveform can be identified, but has poor morphology and reproducibility. As the number of repetitions is increased to 100, a much more clearly defined P100 waveform is seen, and this changes only slightly with 200 repetitions. When the evoked potential waveform ceases to change with additional repetitions, averaging is adequate.

PRVEP, pattern reversal visual evoked potential; VEP, visual evoked potential.

Types

Surface and needle electrodes can be used to record evoked potential signals. Electroencephalogram (EEG) cup electrodes are the type of surface electrodes used most often. These electrodes are 5 to 10 mm in diameter. Before electrodes are applied, the skin is prepared with a mild abrasive to remove oils and dead skin. The electrode is attached with collodion or paste depending on the indication of the study. Collodion application takes longer and should be performed in a room with adequate ventilation due to the smell of the chemical. It stays attached to the patient for longer period of time. After the electrode has been attached, the cup is filled with conductive jelly to ensure adequate contact between the electrode and skin. Acetone is used to dissolve the collodion and remove the electrode. Conductive electrode paste can also be used to attach electrodes to skin. This method is much quicker, however it is not as secure as collodion and electrodes can be dislodged more easily.

Needle electrodes can also be used to record evoked potentials. Because they are more invasive than surface electrodes, needle electrodes are not typically used for outpatient evoked potential studies. They can be applied more quickly than surface electrodes as skin preparation is not necessary. This is useful when evoked potentials are performed in the operating room (OR). Needle electrodes have high impedance which can improve signal quality when the amplifier’s input impedance is also high.

Placement

Electrode placement depends on the type of evoked potential being recorded. VEP recording electrodes are placed on the scalp, whereas BAEP electrodes are placed on the scalp and mastoids. SEP electrodes are placed on not only the scalp, but also the neck, spine, and limbs. The exact placement is determined by locating anatomical landmarks. Electrodes placed close to each other are used for recording near-field potentials, while electrodes placed at a distance are better at demonstrating far-field potentials.

Basics

Amplifiers have the task of taking signals that are of very low amplitude and isolating them from background noise. The signals are then amplified to a degree that can be measured and appropriate calculations are performed. Amplifiers consist of an input board, selector switches, differential amplifier, and filters.

Input board

The input board, sometimes also called the jack box or head box, is a small box that is placed near the patient. Electrodes attached to the patient are plugged into receptacles in this box. The input signals are amplified by the input board before they are transmitted to the main unit of the evoked potential machine. This allows the biologic signal to be amplified before any exogenous noise is introduced as the signal travels through cables. Receptacles in the input board also limit the amount of current that can flow from the machine to the patient, so patients cannot receive electrical shocks from the machine.

Selector switches

Selector switches allow pairing two electrode inputs into the amplifier. This allows the amplifier to compare the signal between the two electrodes. It is with selector switches that recording montages are created.

Differential amplifier

The basic principle of a differential amplifier is that it magnifies and displays the difference between two inputs. Each differential amplifier has two main inputs called Input 1 and Input 2; previously these were also called Grid (G) 1 and G2. Because Input 1 is often close to the site generating the potential of interest, it is also referred to as the Active electrode, whereas Input 2 is referred to as the Reference electrode.

The output of a differential amplifier is the difference between Input 1 (G1, active) and Input 2 (G2, reference) electrodes. Even though one electrode is called “active” and the other “reference,” both contribute to the ultimate waveform. The display convention used determines if the waveforms deflect upward or downward. At times, more than one electrode can be linked to create one reference (Input 2, G2) electrode. An example of this would be linking the two ears as a single reference.

Because the differential amplifier displays the difference between two inputs, signals that are similar in both inputs will be subtracted. This is known as rejection of the common mode signal. An example of signal that is often rejected because it is in common mode is ECG artifact. Since the ECG artifact is seen in both electrodes, it is subtracted or rejected. However, if the ECG artifact is of different amplitudes in the two electrodes, only some of it will be rejected, and a low amplitude artifact may be seen in the output. The ability of a differential amplifier to reject common mode signal is measured by the common mode rejection ratio (CMRR). The CMRR is defined as the “ratio of amplifier output produced by a signal applied differentially over the amplifier output produced by the same signal when applied in common mode” (1). Contemporary evoked potential machines should have a CMRR of at least 10,000:1 (4).

Averaging

Neurophysiologic signals such as evoked potentials that have amplitude that is lower than the accompanying noise can only be visualized with averaging (5). Averaging involves adding successive responses and dividing the sum by the number of responses. Since the evoked potential is time locked to the stimulus and always occurs at the same latency while noise is random, averaging allows reduction of noise and emergence of the evoked potential signal. Averaging involves digitization of the analog signal in an analog-to-digital (A/D) converter. The digital signal is averaged and then converted back to analog form for display.

The number of responses that need to be averaged to resolve an evoked potential waveform depends on the amplitude of the waveform of interest versus the amplitude of noise. This relationship is called the signal to noise ratio. As discussed earlier, the lower the signal to noise ratio, the more responses that need to be averaged. If the signal to noise ratio is increased, either by increasing the amplitude of the signal or reducing the noise, fewer responses need to be averaged. Averaging improves the signal to noise ratio by a factor equal to the square root of the number of repetitions averaged. It is a common misperception that averaging increases the amplitude of the signal, which is incorrect. It reduces the amplitude of the noise.

Filters

Evoked potentials contain waveforms of a limited frequency range. Filters are used to eliminate unwanted waveforms that are below and above the frequencies of interest. By eliminating low and high frequency activity that is not of interest, fewer repetitions are needed to resolve low amplitude evoked potential waveforms. Analog filters are applied to the signal before it is digitized.

Analog filters are divided into low- and high-frequency filters (LFFs and HFFs). LFFs reduce the amplitude of low frequency activity, and HFFs similarly affect high frequencies. Filters are further named based on the frequency of sine waves whose amplitude they reduce by a fixed percentage, usually 30%. Thus, a 1 Hz LFF will reduce the amplitude of 1 Hz activity by 30%, and amplitude of activity slower than 1 Hz will be reduced more than 30%. The activity range between the LFF and HFF is referred to as the bandpass. Properties of filters are based on sine waves, and biological signals are not sine waves. It is not possible to determine the exact frequency of evoked potential waveforms, and most evoked potentials contain waveforms of many different frequencies. Consequently, filter settings are intentionally set with a broad bandpass so as not to eliminate any waveform of interest. Filters can also distort the shape of waveforms causing them to appear slightly earlier or later. This is called phase shift; progressively greater LFF cause a phase advance (waveforms appear earlier) and progressively lower HFF cause a phase lag (waveforms appear later) (Figures 1.5A–C).

Another special type of filter affects only a very narrow frequency band. This is known as a notch filter. Most often this is a 60 Hz filter in the US as the electrical AC is at this frequency. In other parts of the world, a 50-Hz band filter is available.

Digital filters are used after the signal has been digitized. Several types of digital filters are available and one that is used occasionally in clinical evoked potentials is called “smoothing” (1). Smoothing uses a computer algorithm to average three to five consecutive data points to help eliminate noise and “smooth” out waveforms. Smoothing can be used more than once on a waveform. However, it should be used sparingly as it can affect waveform morphology (Figures 1.6A–C). Digital filtering, however, does not cause phase shifts.

Artifact rejection

Artifact rejection is another technique used to help resolve low-amplitude signals such as evoked potentials. Amplifier input voltage is set so that signals of excessively high voltage that are unlikely to be of interest are automatically rejected and not included in the average. This prevents the average from being contaminated from these high-amplitude signals. The limits of artifact rejection should be set so that signals of interest are not affected. Artifact rejection allows a reduction of the number of responses that need to be averaged. However, if the artifact rejection level is set too low, too many responses will be rejected, increasing the time and responses needed to average.

Absolute latency

The absolute latency, also referred to as the peak latency, is measured from the start of the stimulus to peak of the waveform of interest. The onset latency is the time from stimulus onset to the start of the waveform. This latter latency measure is not routinely used as the onset of a waveform is much harder to determine than the peak (Figure 1.8).

The absolute latency of a waveform is the time an impulse takes to travel from the point of stimulation to the generator of the waveform of interest. Because the stimulus is applied to end organ, absolute latency measures conduction in the peripheral and central nervous system (or in the case of VEP, the retina). A lesion of the peripheral nervous system, such as demyelination of a peripheral nerve, can cause the absolute latency to be prolonged.

Interpeak latency

Interpeak latency (IPL) is the latency between two peaks of the same evoked potential. It represents the time an impulse takes to travel between the presumed generators of the waveforms. IPLs are useful in eliminating the peripheral nervous system contribution to the latency. If the IPL between two waveforms that are both in the central nervous system is determined, only central nervous system conduction is measured. This is particularly helpful in SEP and BAEP. In SEP, the IPL between the upper and lower spinal cord (for upper and lower extremity SEP) and brain can determine central conduction time (CCT). IPL measurement is preferred to absolute latency measurements as they are less variable and not influenced by peripheral nervous system pathology (Figure 1.8).

Peak to peak amplitude

Peak to peak amplitude is the most commonly used amplitude measurement. It is a measure of the voltage difference between successive peaks of opposite polarity. The amplitude of the ascending limb, descending limb, or the average of both is determined (Figure 1.9). Whichever method is used, it is important to be consistent within a laboratory and the normative data must have been obtained with the same method.

Figure 1.7

Automated tagging of peroneal nerve SEP waveforms.

Age: 18 years

Sex: Male

Stimulation rate: 5.7/s

Filters: 30–3,000 Hz

Scale: Amplitude = 0.2 μV/div; Latency = 8 ms/div

Side: Right

Stimulation duration: 0.2 ms

Stimulation intensity: 30.9 mA

Number of repetitions: 1,503

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
LP	N/A
P21 (31)	32.0
N24 (34)	37.1
P27 (37)	43.9	0.18 (P27–N35)
N35 (45)	50.4

Interpeak Latencies
Waveforms	Latency (ms)
LP–P27	N/A

Discussion: Before looking at waveform latencies, the interpreting physician must first evaluate the waveforms and confirm that they have been properly tagged. This is a peroneal nerve SEP, and absolute latencies of peroneal SEP are 10 ms less than tibial nerve SEP. The waveforms are correspondingly called P21, N24, and P27. In some laboratories, for simplicity, the nomenclature for tibial nerve SEP is retained for peroneal nerve SEP, that is, the previously noted waveforms are called P31 waveform, N34 waveform, and P37 waveform. A PF waveform is not recorded as that is the site of stimulation. All waveforms have been incorrectly tagged. The waveform tagged P21 is actually the P27. Notice that this waveform is seen not only in the CPz–C5S and CP4–C5S derivations, it is also seen in the CPz–FPz derivation. It is not seen in the FPz–C5S and CP3–C5S derivations. If this waveform was a subcortical P21, it should not have been seen in the CPz–FPz derivation (it would have been in “common mode” in both electrodes), and it should have been seen in the FPz–C5S and CP3–C5S derivations. The waveform marked with the arrow is the P21, and it follows the properties of the subcortical response discussed earlier. If this was not noticed and the absolute latencies relied upon as provided, the interpretation for this study would have been that it was abnormal due to prolongation of the P27 waveform. In fact, the interpretation should be that it is a normal study since the latency of the P27 waveform is actually 32.0 ms (upper limit of normal for P27 waveform is 37.0 ms).

SEP, somatosensory evoked potential.

Figure 1.8

Latency measurements of SEP waveforms.

Age: 30 years

Sex: Male

Stimulation rate: 5.7/s

Filters: 30–1,500 Hz

Scale: Amplitude = 0.5 μV/div; Latency = 3 ms/div

Side: Left

Stimulation duration: 0.2 ms

Stimulation intensity: 10.1 mA

Number of repetitions: 750

Median nerve conduction velocity (median nerve to EP waveform): 52 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
EP	9.3
N13	10.6
P13	12.9
N18	16.1	1.78 (P13–N18)
N20	18.2	1.52 (N20–P22)

Interpeak Latencies
Waveforms	Latency (ms)
EP–N20	8.90
EP–P13	3.60
P13–N20	5.30

Discussion: Waveform latencies can be determined either to their onset or peak. Peak latencies are used more often in evoked potentials as onset may be difficult to identify. In this example, the N20 waveform onset latency can be either where the light or dark arrow is placed. The peak latency is where the N20 waveform is tagged. More important than peak (or absolute) latencies are IPL. IPLs are more accurate than absolute latencies in determining central conduction.

IPL, interpeak latency; SEP, somatosensory evoked potential.

Baseline to peak amplitude

The baseline to peak amplitude is the voltage from the baseline to the peak of the waveform of interest. The baseline is the immediate post stimulus period of the evoked potential (Figure 1.9). This measurement may be difficult to determine as the baseline may not be horizontal.

Amplitude ratio

The ratio of the peak to peak amplitude of two waveforms of the same evoked potential can be determined and is thought to be a more sensitive amplitude measurement than peak to peak amplitude of a single waveform. This is commonly used in BAEPs where wave V/I amplitude ratio is measured. Amplitude ratios can also be used to compare the same waveform obtained after stimulation of the left and right side or recorded from different locations. This is done with PRVEP where the P100 waveform can be compared after left and right sided stimulation. The P100 waveform recorded from parasagittal electrodes can also be compared (Figure 1.9).

Figure 1.9

Amplitude measurements of VEP waveforms.

Age: 39 years

Sex: Female

Stimulation rate: 3.9/s

Filters: 1–100 Hz

Preauricular–preauricular distance: 33 cm

Scale: Amplitude = 5 μV/div; Latency = 25 ms/div

Eye: Right

Number of repetitions: 100

Visual angle: 30′

Visual acuity: 20/25

Corrective lenses: No

Absolute Latency
Derivation	N75 (ms)	P100 (ms)	N105 (ms)	N145 (ms)
MO–MF	80.0	102.0		128.0
MO–AU	80.0	101.0		126.0
Oz–AU	80.0	101.0		126.0
MF–AU			106.0
LO–MF	82.5	101.0		125.0
RO–MF	82.5	103.0		127.0

Amplitude
Derivation	N75–P100 (μV)	P100–N145 (μV)	Mean (μV)
MO–MF	12.2	16.1	14.2
MO–AU	10.5	14.6	12.6
Oz–AU	9.68	13.0	11.3
LO–MF	4.95	8.55	6.8
RO–MF	10.7	14.2	12.5

P100 Amplitude Ratio
Location	Ratio
OS–OD	1.2
LO–RO	1.8

Discussion: Amplitude of a waveform can be measured from baseline to peak or from peak to peak. The latter is used more often in evoked potentials since identifying peaks is more reliable than identifying the baseline. In the example shown, the baseline to peak (narrow line) P100 waveform amplitude is not as reliable as the N75–P100 waveform peak to peak amplitude (broad line). Peak to peak amplitudes can be measured for the descending or ascending limb of the peak, or it can be an average of the two. The above example displays amplitudes of the descending and ascending limb, but it is the average that is used in the author’s laboratory. Amplitude ratios are used in PRVEP to compare parasagittal P100 waveforms (those obtained from LO–MF and RO–MF derivations) and the P100 waveforms obtained after left and right eye stimulation. In the above example, the parasagittal waveform amplitude ratio is within normal limits, as is left and right eye P100 waveform amplitude ratio (PRVEP to left eye stimulation not shown).

PRVEP, pattern reversal visual evoked potential; VEP, visual evoked potential.

Intraindividual variability

Many factors within a patient may affect an evoked potential. Foremost is the attention level. Cortical responses are of higher amplitude when the patient is awake than if they are drowsy or asleep. If the patient is awake when the study is obtained on one side and falls asleep when the other side is acquired, there may be considerable variability of the evoked potential (6). This is seen most remarkably in tibial nerve SEP (Figures 1.10A and B). If the background activity or noise increases, the evoked potential may become more difficult to visualize as the signal to noise ratio is lower. A drop in blood pressure may make the amplitude of the evoked potential lower, which also reduces the signal to noise ratio. This is seldom seen in an outpatient setting, but may occur when evoked potentials are performed in an intensive care unit and OR. When there are lesions of the cerebral cortex, evoked potentials may be more variable.

Interindividual variability

Evoked potentials can vary considerably between individuals. Sex and body or head size, which are related, can have a significant effect on evoked potential waveform latency. Age can also have an effect on evoked potentials. The biggest change is from infancy to maturity, but changes can also occur with old age. Anatomical variability of neural structures may also cause morphological differences in the evoked potentials. An example of this is the P37 cortical waveform obtained after tibial nerve stimulation. Because the leg somatosensory cortex is near the vertex, the P37 waveform is typically best recorded contralateral to the side of waveform generation (ipsilateral to side of stimulation since dorsal column pathway fibers decussate in the medulla). However, occasionally the P37 waveform is better recorded over the vertex or ipsilateral to site of waveform generation.

Latency prolongation

Prolongation of the latency of a waveform implies that there is slowing of the conduction velocity of the neural pathways from the point of stimulation to the neural generator of the waveform. The slowing is often caused by a lesion along the pathway. When recording evoked potentials, the slowing of interest is that which affects the central nervous system. However, when absolute latencies are evaluated, peripheral nerve conduction is also measured. For example, a delayed N20 waveform absolute latency of the median nerve SEP may be due to demyelinating peripheral neuropathy or a brainstem lesion affecting the medial lemniscus (Figure 1.11). Similarly, prolongation of the P100 waveform of the PRVEP may be due to ocular problems or an optic chiasm lesion.

IPL assessments are much more accurate for evaluating the central nervous system. These measures allow assessment of neural pathways between generators of two waveforms. For example, for median nerve SEPs, the waves EP–N20 (EP to N20 waveform) IPL assesses neural pathways between the brachial plexus and the contralateral somatosensory cortex and the waves P14 to N20 IPL provides an assessment of the fibers between the nucleus cuneatus and the contralateral somatosensory cortex. Diseases of the peripheral nervous system are much less likely to affect IPL (Figure 1.11). Similarly, BAEP waves I to V IPL allows assessment of the auditory pathway after removing the contributions of the peripheral hearing apparatus. It is not unusual to see a prolonged wave V absolute latency with a normal wave I to V IPL. This suggests a lesion at or before the cochlea and not of the central nervous system. The VEP is unique in that only the P100 waveform is measured, so IPL cannot be determined.

Absolute latencies and IPLs are compared to normative data to see if they exceed the upper limit of normal latency measures. Even if these measurements do not exceed the upper limits of normal, it is useful to compare latencies from side to side. If greater than maximal allowable asymmetry is noted, the side with slower conduction may be abnormal (Figures 1.12A and B).

Amplitude reduction

A reduction in the amplitude of evoked potential peaks is most often accompanied by latency prolongation. The lower amplitude can be explained by temporal dispersion if conduction is slowed. However, at times amplitude reduction is noted without latency prolongation (Figures 1.13A and B). Whereas this may imply axonal loss in the pathway being tested, it may also be due to technical reasons or evoked potential variability. If reduced amplitude is the only significant finding in an evoked potential study, it is seldom designated as abnormal. Most evoked potential laboratories do not have normative data for amplitude. Amplitude ratios are used more often than absolute amplitude values. They are less susceptible to technical issues and normal evoked potential variability.

Figure 1.11

Latency prolongations of median nerve SEP waveforms.

Age: 60 years

Sex: Male

Stimulation rate: 5.7/s

Filters: 30–1,500 Hz

Scale: Amplitude = 0.5 μV/div; Latency = 3 ms/div

Side: Left

Stimulation duration: 0.2 ms

Stimulation intensity: 21.9 mA

Number of repetitions: 1,000

Median nerve conduction velocity (median nerve to EP waveform): 39 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
EP	12.8
N13	16.3
P13	17.3
N18	20.2	1.09 (P13–N18)
N20	22.7	1.07 (N20–P22)

Interpeak Latencies
Waveforms	Latency (ms)
EP–N20	9.90
EP–P13	4.50
P13–N20	5.40

Discussion: Absolute latencies are a measure of both peripheral and central conduction velocity. IPLs are a more accurate method of evaluating central nervous system conduction. In this example, absolute latencies of all waveforms, including the EP and N20 waveforms, are prolonged. However, when the waves EP–N20 IPL and other IPLs are evaluated, it is evident that the absolute latency prolongation is due to a peripheral nervous system process. This is further supported by what appears to be a slowing of median nerve conduction velocity. It is cautioned that supramaximal stimulation is not applied to the peripheral nerve in the evoked potentials laboratory, and so the conduction velocity should be interpreted with the understanding that all nerve fibers may not have been stimulated.

IPL, interpeak latency; SEP, somatosensory evoked potential.

Figure 1.12 (A and B)

Latency asymmetries of tibial nerve SEP waveforms.

Age: 41 years

Sex: Female

Stimulation rate: 5.7/s

Filters: 30–3,000 Hz

Scale: Amplitude = 0.5 μV/div; Latency = 8 ms/div

(A)

Side: Left

Stimulation duration: 0.3 ms

Stimulation intensity: 24.3 mA

Number of repetitions: 1,500

Tibial nerve conduction velocity (tibial nerve to T12S): 43 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
PF	9.9
LP	24.2
P31	29.9
N34	34.0
P37	38.6	1.45 (P37–N45)

Interpeak Latencies
Waveforms	Latency (ms)
PF–P37	28.7
LP–P37	14.4

(B)

Side: Right

Stimulation duration: 0.3 ms

Stimulation intensity: 29.0 mA

Number of repetitions: 1,500

Tibial nerve conduction velocity (tibial nerve to T12S): 43 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
PF	9.4
LP	24.4
P31	31.2
N34	36.0
P37	43.0	1.49 (P37–N45)

Interpeak Latencies
Waveforms	Latency (ms)
PF–P37	33.6
LP–P37	18.6

Discussion: Absolute and interpeak latencies are compared to normative data to determine if pathology exists. Additionally, latencies should be compared from side to side in the same patient. At times, latencies can be within normal limits, but a significant difference is present between the two sides. If this latency difference is beyond the upper limit of normal, even if the latencies themselves are within normal limits, the study is considered abnormal. In this example, left (A) and right (B) tibial nerve SEP are shown. The waves LP–P37 IPL are asymmetric (14.4 ms vs. 18.6 ms), with a shorter latency after left-sided stimulation. Both IPLs, however, are within normal limits. Because of this asymmetry, this study is considered abnormal.

IPL, interpeak latency; SEP, somatosensory evoked potential.

Figure 1.13 (A and B)

Low amplitudes of median nerve SEP waveforms.

Age: 56 years

Sex: Female

Stimulation rate: 5.7/s

Filters: 30–1,500 Hz

Scale: Amplitude = 0.5 μV/div; Latency = 3 ms/div

(A)

Side: Left

Stimulation duration: 0.2 ms

Stimulation intensity: 12.5 mA

Number of repetitions: 1,500

Median nerve conduction velocity (median nerve to EP waveform): 60 m/s

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
EP	9.72
N13	14.0
P13	13.4
N18	17.4	1.04 (P13–N18)
N20	20.6	0.57 (N20–P22)

Interpeak Latencies
Waveforms	Latency (ms)
EP–N20	10.88
EP–P13	3.68
P13–N20	7.20

(B)

Side: Right

Stimulation duration: 0.2 ms

Stimulation intensity: 14.9 mA

Number of repetitions: 1,002

Median nerve conduction velocity (median nerve to EP waveform):

Absolute Latencies
Waveform	Latency (ms)	Amplitude (μV)
EP	10.0
N13	13.6
P13	15.1
N18	17.7	1.33 (P13–N18)
N20	20.9	1.41 (N20–P22)

Interpeak Latencies
Waveforms	Latency (ms)
EP–N20	10.9
EP–P13	5.1
P13–N20	5.8

Discussion: Low amplitude of evoked potential waveforms is seldom considered an abnormal finding unless latencies are also prolonged. Many patient-related factors (i.e., sleep), technical factors, and pathology can cause an amplitude reduction. In this median nerve SEP example, the N20 (and EP) waveform has a lower amplitude after stimulation of the left median nerve (A) compared to the right median nerve (B). Despite the amplitude asymmetry, this is considered a normal study. The latency of the N20 waveform is within normal limits.

SEP, somatosensory evoked potential.

Figure 1.14 (A and B)

W-shaped VEP waveform.

Age: 49 years

Sex: Male

Stimulation rate: 3.9/s

Filters: 1–100 Hz

Preauricular–preauricular distance: 34 cm

Scale: Amplitude = 2 μV/div; Latency = 25 ms/div

(A)

Eye: Right

Number of repetitions: 200

Visual angle: 30′

Visual acuity: 20/50

Corrective lenses: No

Absolute Latency
Derivation	N75 (ms)	P100 (ms)	N105 (ms)	N145 (ms)
MO–MF	78.0	118.0		155.0
MO–AU	78.0	118.0		155.0
Oz–AU	78.0	118.0		155.0
MF–AU			136
LO–MF	78.0	129.0		160.0
RO–MF	78.0	131.0		161.0

Amplitude
Derivation	N75–P100 (μV)	P100–N145 (μV)	Mean (μV)
MO–MF	5.97	7.26	6.62
MO–AU	4.11	6.61	5.36
Oz–AU	3.61	5.72	4.67
LO–MF	6.91	8.23	7.57
RO–MF	7.93	8.39	8.16

P100 Waveform Amplitude Ratio
Location	Ratio
OS–OD	1.02
LO–RO	1.08

(B)

Eye: Right

Number of repetitions: 200

Visual angle: 60′

Visual acuity: 20/50

Corrective lenses: No

Absolute Latency
Derivation	N75 (ms)	P100 (ms)	N105 (ms)	N145 (ms)
MO–MF	72.5	110.0		143.0
MO–AU	73.0	109.0		139.0
Oz–AU	73.0	110.0		139.0
MF–AU			111.0
LO–MF	73.5	117.0		144.0
RO–MF	71.0	112.0		146.0

Amplitude
Derivation	N75–P100 (μV)	P100–N145 (μV)	Mean (μV)
MO–MF	7.68	5.62	6.65
MO–AU	6.46	4.48	5.47
Oz–AU	4.95	2.60	3.78
LO–MF	5.90	3.95	4.93
RO–MF	5.35	1.21	3.28

P100 Amplitude Ratio
Location	Ratio
OS–OD	1.02
LO–RO	1.50

Discussion: The P100 waveform can have an abnormal morphology, and the most common such abnormality is a bi-fed peak, called a W-shaped P100 waveform. This may occur because of technical reasons, patient physiology, or visual pathway problems. In example (A), a W-shaped P100 waveform is noted after right eye stimulation. This patient also had reduced visual acuity (20/50). The PRVEP was repeated with 60′ check size (B). With the larger check size, the P100 waveform morphology improved, and there is no longer a W-shaped waveform. In this case, the W-shaped waveform occurred due to reduced visual acuity.

PRVEP, pattern reversal visual evoked potential; VEP, visual evoked potential.

Abnormal waveforms

The shape of the waveform is not used in isolation as a determinant of abnormality. This can be very variable depending on not only technical factors but also patient factors, such as alertness and anatomical variations. One type of abnormal waveform seen commonly is a bi-fed peak. This is most commonly seen with a PRVEP P100 waveform, where it is referred to as a “W-shaped” waveform (Figures 1.14A and B). Even this is frequently due to technical reasons because of how it is recorded (as discussed earlier), but sometimes it may be due to pathology.

Absence of waveforms

Complete loss of all waveforms of an evoked potential may be suggestive of severe pathology in the pathway being tested. Before this determination is made, it is important to confirm that technical problems did not cause this finding. Rechecking all components of the evoked potential machine, including the amplifiers and electrodes is very important. If all waveforms except the first are absent, pathology involving the pathway being tested is much more likely (Figure 1.15). This is because presence of the first waveform documents delivery of adequate stimulation to the neural structures.

Localization

The site of abnormality can be localized in the evoked potentials by determining the pattern of abnormalities. When IPLs are prolonged, the lesion is between these two waveforms. IPL prolongations over progressively smaller regions further clarify the site of abnormality. For example, prolongation of the waves I–V IPL implies a lesion between the vestibulocochlear nerve and the inferior colliculus. In the same patient, if the wave III–V IPL is prolonged but the waves I–III IPL is not, the lesion is most likely between the superior olivary complex and inferior colliculus (Figure 1.16). Different evoked potentials can be used jointly for localization determination as well. An example of this would be if a median SEP is normal but the tibial nerve SEP shows LP–P37 IPL prolongation. The most likely site of abnormality would be above the cauda equina and below the mid cervical level.