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Effect of reference point on visual evoked potentials: clinical relevance
Electroencephalography and clinical Neurophysiology, 1988, 71:319-322
319
Elsevier Scientific Publishers Ireland, Ltd. EEG 03530
Short communication
Effect of reference point on visual evoked potentials: clinical relevance Pang-Ying Shih, Michael J. Aminoff, Douglas S. Goodin and Mary M. Mantle Clinical Neurophysiology Laboratories, Department of Neurology, University of California, San Francisco, CA ( U.S.A.) (Accepted for publication: 8 March 1988)
Summary For clinical purposes the VEP is generally recorded from the mid-occipital region referenced to the vertex or mid-frontal region. This may lead to interpretive errors that can be avoided if a relatively inactive reference point, such as linked mastoids, is used simultaneously. The additional recording derivation may also be helpful in clarifying aberrant or ambiguous wave forms. The diagnostic yield from the two montages is similar, although the linked-mastoid reference provides a greater number of technically inadequate recordings due to smaller size of P100 and increased contamination by muscle artifact.
Key words: Evoked potentials; P100; N100; VEPs; Reference point
It has been known for some years that the occipital component of the P100 response of the visual evoked potential (VEP) elicited by pattern reversal is associated with a synchronously occurring negativity (N100) that can be recorded at the vertex and more anteriorly (Asselman et al. 1975; Erwin 1980; Spitz et al. 1986). Any dissociation of these 2 responses may lead to distortion of the P100 response (Chiappa 1983; Spitz et al. 1986), or to a normal looking P100 response when the occipital component is actually absent (Spitz et al. 1986) if VEPs to full-field stimulation are recorded using a standard Oz-Fz or Oz-Cz montage. Spitz et al. (1986) have therefore stressed the importance of using either a non-cephalic or a relatively inactive cephalic reference point (such as the ears or mastoids), in addition to the more conventional Fz (or Cz) reference in order to reduce interpretive errors and to more easily separate normal variants from pathological responses. In our laboratory, we have for some years routinely recorded VEPs to monocular full-field stimulation using both an active scalp reference (Cz) and a relatively inactive reference (linked mastoids). We therefore reviewed our experience to determine, first, whether one of these reference points was superior to the other in diagnostic yield and in permitting VEPs to be recorded reliably without excessive artifact. Our second aim was to determine whether the 2 recording derivations were complementary in together providing information not always obtained from one derivation alone.
Correspondence to: Dr. M.J. Aminoff, Box 0114, Room 794-M, Department of Neurology, University of California, San Francisco, CA 94143 (U.S.A.).
Methods Monocularly elicited VEPs were recorded in 30 healthy adult volunteers (15 men, 15 women) who served as normal controls, and in 250 patients (151 women and 99 men) ranging in age from 10 to 70 years, referred for study over a 3 year period from January 1, 1984. Gold-plated recording electrodes were placed at Oz, Cz, and over each mastoid process, so that a recording could be made simultaneously between Oz and Cz, and Oz and linked mastoids (M1 + M2), with a ground electrode on the forehead. In 8 of the 30 normal volunteers, electrodes were also placed at Pz, Fz, and the back of the neck over the seventh cervical spinous process, to permit recordings between Oz and Pz, and recording from Fz, Cz, Pz, Oz and the linked mastoids to a C7 (non-cephalic) reference point. Subjects were seated comfortably in a quiet darkened room 1 m away from the screen of a television, and instructed to fixate on a small dot at its center with one eye while the other was covered with a patch. A black and white checkerboard pattern was generated on the television screen by an electronic pattern generator. The screen (field) size measured 11 o vertically and 14 o horizontally at the subject's eye, and the check size was 52 rain. Luminance of the dark checks was 6.31 ft-L, and of the light checks was 31.6 ft-L, giving a contrast between the black and white checks of 67%. The checks were made to reverse at a rate of approximately 2 Hz, and 128 responses were recorded and averaged using a Grass 10 evoked potential system with the low- and high-frequency filters set at 1 and 100 Hz, and with the line filter on. At least 2 trials per eye were always obtained, to ensure the replicability of the findings. In evaluating the VEPs obtained in patients, attention was confined to the PI00 response. This was regarded as abnormal if it was absent or if either its absolute latency or the latency
0168-5597/88/$03.50 © 1988 Elsevier Scientific Publishers Ireland, Ltd.
320
P.-Y. SHIH ET AL.
difference between eyes exceeded 3 S.D.s (Table I) above the normal control mean established in our laboratory from the 30 healthy volunteer subjects (60 eyes).
,6,
B
OZ--CZ ~ OZ--PZ
Results
OZ--M1 + M2
Normal subjects Normal latency values obtained from our group of 30 normal subjects are shown in Table I. The mean latency was significantly shorter in women than in men with either recording derivation ( P < 0.0005), a sex difference that has been reported by others (Stockard et al. 1979). We found no significant difference in latency of the response when linked mastoids were used as the reference point rather than Cz. In all normal subjects, a response was present when the recording derivation was Oz-Cz. However, in 10 of the 60 instances (30 pairs of eyes), no VEP could be recorded with the linked-mastoid reference. Using individual pairwise statistical analysis, there was no significant difference in latency measured in the 2 recording derivations although in 12 of the 50 instances in which a response was present in both derivations, the latency was longer by 2 msec or more in one or the other. The response obtained with the Cz reference had a longer latency than with the linked-mastoid reference in 7 cases, whereas the converse was true in the remaining 5. In 5 of these 12 instances this latency difference was as much as 5 or 6 msec, and in 1 of these 5 it was 9 msec. In the 8 normal subjects in whom recordings were made from an array of electrodes from front to back, and referenced also to the seventh cervical spinous process and the linked mastoids, we found that the VEP obtained from 3 eyes of the 16 did not include an N100 component, while the VEP in 2 other instances had a conspicuous N100 anteriorly but no corresponding positive component occipitally (Fig. 1). In both cases, the 'P100 response' recorded between Oz and Cz was normal.
TABLE I Normal latency values for P100 of the VEP (30 subjects; 60 eyes). Mean latency (msec)
Mean latency + 3 S.D. (msec)
Maximal latency difference between eyes * (msec)
106 102
116 116
6 8
Cz reference Male Female
Linked-mastoid reference Male Female
107 100
* M e a n + 3 S.D.
116 113
8 9
M1 + M2--CV7 F Z - - C V 7 ~ ~ % , ~ CZ--CV7 PZ--CV7 OZ--CV7
20
ms
Fig. 1. Monocular pattern reversal VEPs recorded in 2 normal subjects from an array of electrodes over the head. The upper 3 sets of traces show VEPs recorded from Oz using 3 different cephalic reference points. The lower 5 sets of traces show responses from Oz, Fz, and each of the 3 cephalic reference points referred to an indifferent non-cephalic electrode placed over the seventh cervical spinous process (CV7). In each case, 2 trials are superimposed. A: occipital P100 response but no anterior N100. B: anterior N100 but no occipital P100 response. It should be noted that in the Oz-Cz derivation, which is commonly used clinically, there is in B an apparent P100 response due to the anterior N100 which is recorded in G2 of the differential amplifier.
Patients The VEPs elicited from 366 eyes were entirely normal with both the Cz and linked-mastoid reference. The VEP obtained from 3 eyes using Cz as reference was clearly normal, but in one of these the response obtained with the linked-mastoid reference was characterized by an absent occipital positivity, suggesting that an N100 peak at the vertex was responsible for the normal response in the Oz-Cz derivation. In the other 2 instances, the response in the Oz-M1 + M2 derivation had an uninterpretable W-configuration with 40 or 50 msec between the 2 positivities, which were of equal amplitude, and the Oz-Cz derivation showed a single peak which we presume to represent the P100, although we could not be sure about this. In 1 patient the VEP from one eye was of abnormal configuration regardless of the reference point. The VEP was delayed in the Oz-Cz derivation in 7 instances in which the Oz-M1 + M2 recording was uninterpretable due to excessive artifact. In 5 instances the VEP was delayed in the Oz-M1 + M2 derivation, but was present unambiguously and of normal latency in the Oz-Cz recording. In 70 cases, the VEP elicited at
EFFECT OF REFERENCE POINT ON VEPs TABLE 1! Results of monocular pattern reversal visual evoked potentials recorded at Oz with reference to Cz and to linked mastoids. Cz reference
Linked-mastoid reference
393
367
Abnormal Delayed Absent Configuration
77 10 1
75 11 1
Uninterpretable
19
46
Normal
Oz with both the Cz and M1 + M2 reference was abnormally delayed, and in 10 other instances there was no reproducible response in either recording derivation. Uninterpretable VEPs from 1 eye due to a W-configuration using the Cz reference were of normal configuration and latency with linked mastoids. Uninterpretable responses due to poor reproducibility and contamination by artifact were obtained with the linked-mastoid reference in 26 instances, while an additional 18 were uninterpretable with both techniques. Among the 26 instances in which only the VEP recorded between Oz and M1 + M2 was uninterpretable, the response recorded with the Cz reference was normal in 19 and abnormally delayed in 7. The VEP results we obtained with the 2 reference points are contrasted in Table It.
Discussion
The derivation used for recording the VEP is generally selected to enhance the identification of the P100 response. Field studies of the VEP to monocular full-field stimulation have shown that the occipital component of the P100 response is maximal in amplitude near the mid-occipital region, declining with more anterior locations, and that, with 50-60 rain checks, a negative peak of similar latency occurs at the vertex (Cz) electrode (Asselman et al. 1975; Erwin 1980; Chiappa 1983: Spitz et al. 1986). The exact transition site between positivity and negativity varies in different individuals; it is usually between Cz and Pz, but may occur more posteriorly. In either case, the Oz-Cz bipolar derivation will generate a large Pl00 peak by the summation of activity of opposite polarity in the differential amplifier. The negativity (N100) recorded at Cz extends anteriorly and is often most conspicuous frontally when recorded using a non-cephalic reference point (Chiappa 1983). Recording of VEPs between Oz and a mid-frontal reference thus leads to an amplified P100 response, just as does the Oz-Cz derivation. The variability in the distribution and relative size of these 2 potentials in normal subjects is, however, considerable. Thus, of the 16 normal eyes tested using an array of recording
321 electrodes, there was no N100 component in the VEP elicited from 3, and in another 2 the occipital positivity was missing but the N100 was preserved anteriorly (Fig. 1). Moreover, in 8 of the remaining 44 normal eyes tested (all of which had a normal VEP in the Oz-Cz derivation), there was no response recorded between the occipital region and linked mastoids, suggesting that the occipital positivity was absent in these subjects. It is possible that in these normal subjects the site of the occipital positivity was displaced more posteriorly than the usual Oz electrode site. Even if this is the case, however, the variability of this site means that the absence of either an NI00 or an occipital positivity, at least as determined at a single electrode position, cannot be regarded in itself as abnormal. If the anterior negativity recorded at Cz or mid-frontally is not completely synchronous with the occipital positivity, recording between Oz and either of these 2 active reference points may produce a broad, irregular, poorly defined or bilobed P100 (i.e., a positive peak interrupted by a negative wave) that makes interpretation difficult or results in latency shifts. Some have suggested that VEPs with aberrant wave forms, i.e., with an ambiguous major P100, have a similar clinical significance (regardless of their latency) to that of a delayed but normally formed VEP (Jones and Blume 1985). They have emphasized that such aberrant wave forms are not found in normal control subjects, although this is contrary to our own experience and to that of others (Stockard et al. 1979). In occasional subjects the major positive component of the VEP extends more anteriorly than usual and may even encompass the Cz electrode placement (Chiappa 19831, so that recording between Oz and Cz then leads to a small or an apparently absent P100 response, or to an inverted response. h has been suggested that such interpretive errors can generally be avoided if the VEP is recorded between Oz and a relatively inactive reference point as well as between Oz and Cz or the mid-frontal region. An earlobe or mastoid site may be active and with monocular full-field stimulation a low amplitude, positive peak can sometimes be recorded there with the same latency as the occipital PI00 (Asselman et al. 1975: Chiappa 1983). With an earlobe or mastoid reference, then, there may be some attenuation of the Pl00 response due to in-phase cancellation between active (Oz) and reference sites m the differential amplifier. More commonly, however, there is a virtual lack of activity at the mastoids, supporting their use as a reference point for VEP studies in addition to an active ~calp reference such as Fz (Spitz et al. 1986). Spitz et al. (1986) reported that the sole use of ()z-Fz montage could lead to the misinterpretation of an absent P100 at Oz (which they regarded as abnormal) as a normal response because of the wave form generated by the anterior N100. They therefore emphasized the need for recording between Oz and a relatively inactive site such as the ear or mastoid process. Indeed, they found an absent P100 in their Oz-Ml derivation in 9 patients with a preserved NI00. Form our findings, as mentioned above, absence of P100 in the ()z-linked mastoid derivation cannot be considered abnormal. It is possible that the occipital Pl00 is sometimes more posterior than usual, and simply recording from Oz may occasionally miss it. Field
322 studies in subjects with loss of only the P100 at Oz or the anterior N100 are required to determine the relevance of this finding, but have not yet been undertaken by us or others, at least in a systematic manner. Thus, it may be that there is no single 'best' reference for VEP recordings. We found the diagnostic yield obtained by recording the VEP between Oz and either Cz or a linked-mastoid reference to be comparable (Table II). Use of a linked-mastoid reference, however, provided less satisfactory recordings because of the smaller size of the P100 (due to loss of additive effect in the differential amplifier from the anterior N100) and increased contamination by muscle artifact. Thus, in 26 instances we found uninterpretable VEPs due to artifact using this reference, but responses that were unambiguously present when Cz was the reference point; in no instance was the converse true. Nevertheless, there were 5 instances where the occipital P100 was unambiguously present and delayed using a linked-mastoid reference, but was of normal latency and configuration using a Cz reference. It could be argued that in these 5 cases the use of the linked-mastoid reference gave a more accurate result than the other recording derivation. In 3 of these 5, the patients had clinical symptoms suggestive of optic nerve involvement on the side with the abnormal VEP, and in 1 other the optic disk was suspected to be abnormally pale. In addition, in 1 case the linked-mastoid recording montage clearly complemented the findings in the Oz-Cz derivation in that the VEP obtained using the mastoid reference was normal, whereas the VEP obtained simultaneously using a Cz reference had an uninterpretable W-shaped configuration. Thus, the concurrent use of the linked-mastoid reference only infrequently provides additional information to that provided by the standard montage. Nonetheless, it requires no additional recording time and may resolve some ambiguities, thus obviating the necessity of having to resort to more timeconsuming and expensive methods of resolving ambiguities, such as hemi-field stimulation, the stimulation of upper and lower fields, or use of different check sizes (Halliday et al. 1977, 1982; Blumhardt and Halliday 1979). However, the comparative value of these different techniques remains to be evaluated.
P.-Y. SHIH ET AL. References
Asselman, P., Chadwick, D.W. and Marsden, C.D. Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain, 1975, 98: 261-282. Blumhardt, L.D. and Halliday, A.M. Hemisphere contributions to the composition of the pattern-evoked potentials waveform. Exp. Brain Res., 1979, 36: 53-69. Chiappa, K.H. Evoked Potentials in Clinical Medicine. Raven Press, New York, 1983. Erwin, C.W. Pattern reversal evoked potentials. Am. J. EEG Technol., 1980, 20: 161-184. Halliday, A.M., Barrett, G., Halliday, E. and Michael, W.F. The topography of the pattern-evoked potential. In: J.E. Desmedt (Ed.), Visual Evoked Potentials in Man: New Developments. Clarendon Press, Oxford, 1977: 121-133. Halliday, A.M., Barrett, G., Carroll, W.M. and Kriss, A. Problems in defining the normal limits of the visual evoked potential. In: J. Courjon, F. Maugnirre and M. Revol (Eds.), Clinical Applications of Evoked Potentials in Neurology. Raven Press, New York, 1982: 1-9. Jones, D.C. and Blume, W.T. Aberrant wave forms to pattern reversal stimulation: clinical significance and electrographic 'solutions.' Electroenceph. clin. Neurophysiol., 1985, 61: 472-481. Spitz, M.C., Emerson, R.G. and Pedley, T.A. Dissociation of frontal N100 from occipital P100 in pattern reversal visual evoked potentials. Electroenceph. clin. Neurophysiol., 1986, 65: 161-168. Stockard, J.J., Hughes, J.F. and Sharbrough, F.W. Visually evoked potentials to electronic pattern reversal: latency variations with gender, age, and technical factors. Am. J. EEG Technol., 1979, 19: 171-204.
319
Elsevier Scientific Publishers Ireland, Ltd. EEG 03530
Short communication
Effect of reference point on visual evoked potentials: clinical relevance Pang-Ying Shih, Michael J. Aminoff, Douglas S. Goodin and Mary M. Mantle Clinical Neurophysiology Laboratories, Department of Neurology, University of California, San Francisco, CA ( U.S.A.) (Accepted for publication: 8 March 1988)
Summary For clinical purposes the VEP is generally recorded from the mid-occipital region referenced to the vertex or mid-frontal region. This may lead to interpretive errors that can be avoided if a relatively inactive reference point, such as linked mastoids, is used simultaneously. The additional recording derivation may also be helpful in clarifying aberrant or ambiguous wave forms. The diagnostic yield from the two montages is similar, although the linked-mastoid reference provides a greater number of technically inadequate recordings due to smaller size of P100 and increased contamination by muscle artifact.
Key words: Evoked potentials; P100; N100; VEPs; Reference point
It has been known for some years that the occipital component of the P100 response of the visual evoked potential (VEP) elicited by pattern reversal is associated with a synchronously occurring negativity (N100) that can be recorded at the vertex and more anteriorly (Asselman et al. 1975; Erwin 1980; Spitz et al. 1986). Any dissociation of these 2 responses may lead to distortion of the P100 response (Chiappa 1983; Spitz et al. 1986), or to a normal looking P100 response when the occipital component is actually absent (Spitz et al. 1986) if VEPs to full-field stimulation are recorded using a standard Oz-Fz or Oz-Cz montage. Spitz et al. (1986) have therefore stressed the importance of using either a non-cephalic or a relatively inactive cephalic reference point (such as the ears or mastoids), in addition to the more conventional Fz (or Cz) reference in order to reduce interpretive errors and to more easily separate normal variants from pathological responses. In our laboratory, we have for some years routinely recorded VEPs to monocular full-field stimulation using both an active scalp reference (Cz) and a relatively inactive reference (linked mastoids). We therefore reviewed our experience to determine, first, whether one of these reference points was superior to the other in diagnostic yield and in permitting VEPs to be recorded reliably without excessive artifact. Our second aim was to determine whether the 2 recording derivations were complementary in together providing information not always obtained from one derivation alone.
Correspondence to: Dr. M.J. Aminoff, Box 0114, Room 794-M, Department of Neurology, University of California, San Francisco, CA 94143 (U.S.A.).
Methods Monocularly elicited VEPs were recorded in 30 healthy adult volunteers (15 men, 15 women) who served as normal controls, and in 250 patients (151 women and 99 men) ranging in age from 10 to 70 years, referred for study over a 3 year period from January 1, 1984. Gold-plated recording electrodes were placed at Oz, Cz, and over each mastoid process, so that a recording could be made simultaneously between Oz and Cz, and Oz and linked mastoids (M1 + M2), with a ground electrode on the forehead. In 8 of the 30 normal volunteers, electrodes were also placed at Pz, Fz, and the back of the neck over the seventh cervical spinous process, to permit recordings between Oz and Pz, and recording from Fz, Cz, Pz, Oz and the linked mastoids to a C7 (non-cephalic) reference point. Subjects were seated comfortably in a quiet darkened room 1 m away from the screen of a television, and instructed to fixate on a small dot at its center with one eye while the other was covered with a patch. A black and white checkerboard pattern was generated on the television screen by an electronic pattern generator. The screen (field) size measured 11 o vertically and 14 o horizontally at the subject's eye, and the check size was 52 rain. Luminance of the dark checks was 6.31 ft-L, and of the light checks was 31.6 ft-L, giving a contrast between the black and white checks of 67%. The checks were made to reverse at a rate of approximately 2 Hz, and 128 responses were recorded and averaged using a Grass 10 evoked potential system with the low- and high-frequency filters set at 1 and 100 Hz, and with the line filter on. At least 2 trials per eye were always obtained, to ensure the replicability of the findings. In evaluating the VEPs obtained in patients, attention was confined to the PI00 response. This was regarded as abnormal if it was absent or if either its absolute latency or the latency
0168-5597/88/$03.50 © 1988 Elsevier Scientific Publishers Ireland, Ltd.
320
P.-Y. SHIH ET AL.
difference between eyes exceeded 3 S.D.s (Table I) above the normal control mean established in our laboratory from the 30 healthy volunteer subjects (60 eyes).
,6,
B
OZ--CZ ~ OZ--PZ
Results
OZ--M1 + M2
Normal subjects Normal latency values obtained from our group of 30 normal subjects are shown in Table I. The mean latency was significantly shorter in women than in men with either recording derivation ( P < 0.0005), a sex difference that has been reported by others (Stockard et al. 1979). We found no significant difference in latency of the response when linked mastoids were used as the reference point rather than Cz. In all normal subjects, a response was present when the recording derivation was Oz-Cz. However, in 10 of the 60 instances (30 pairs of eyes), no VEP could be recorded with the linked-mastoid reference. Using individual pairwise statistical analysis, there was no significant difference in latency measured in the 2 recording derivations although in 12 of the 50 instances in which a response was present in both derivations, the latency was longer by 2 msec or more in one or the other. The response obtained with the Cz reference had a longer latency than with the linked-mastoid reference in 7 cases, whereas the converse was true in the remaining 5. In 5 of these 12 instances this latency difference was as much as 5 or 6 msec, and in 1 of these 5 it was 9 msec. In the 8 normal subjects in whom recordings were made from an array of electrodes from front to back, and referenced also to the seventh cervical spinous process and the linked mastoids, we found that the VEP obtained from 3 eyes of the 16 did not include an N100 component, while the VEP in 2 other instances had a conspicuous N100 anteriorly but no corresponding positive component occipitally (Fig. 1). In both cases, the 'P100 response' recorded between Oz and Cz was normal.
TABLE I Normal latency values for P100 of the VEP (30 subjects; 60 eyes). Mean latency (msec)
Mean latency + 3 S.D. (msec)
Maximal latency difference between eyes * (msec)
106 102
116 116
6 8
Cz reference Male Female
Linked-mastoid reference Male Female
107 100
* M e a n + 3 S.D.
116 113
8 9
M1 + M2--CV7 F Z - - C V 7 ~ ~ % , ~ CZ--CV7 PZ--CV7 OZ--CV7
20
ms
Fig. 1. Monocular pattern reversal VEPs recorded in 2 normal subjects from an array of electrodes over the head. The upper 3 sets of traces show VEPs recorded from Oz using 3 different cephalic reference points. The lower 5 sets of traces show responses from Oz, Fz, and each of the 3 cephalic reference points referred to an indifferent non-cephalic electrode placed over the seventh cervical spinous process (CV7). In each case, 2 trials are superimposed. A: occipital P100 response but no anterior N100. B: anterior N100 but no occipital P100 response. It should be noted that in the Oz-Cz derivation, which is commonly used clinically, there is in B an apparent P100 response due to the anterior N100 which is recorded in G2 of the differential amplifier.
Patients The VEPs elicited from 366 eyes were entirely normal with both the Cz and linked-mastoid reference. The VEP obtained from 3 eyes using Cz as reference was clearly normal, but in one of these the response obtained with the linked-mastoid reference was characterized by an absent occipital positivity, suggesting that an N100 peak at the vertex was responsible for the normal response in the Oz-Cz derivation. In the other 2 instances, the response in the Oz-M1 + M2 derivation had an uninterpretable W-configuration with 40 or 50 msec between the 2 positivities, which were of equal amplitude, and the Oz-Cz derivation showed a single peak which we presume to represent the P100, although we could not be sure about this. In 1 patient the VEP from one eye was of abnormal configuration regardless of the reference point. The VEP was delayed in the Oz-Cz derivation in 7 instances in which the Oz-M1 + M2 recording was uninterpretable due to excessive artifact. In 5 instances the VEP was delayed in the Oz-M1 + M2 derivation, but was present unambiguously and of normal latency in the Oz-Cz recording. In 70 cases, the VEP elicited at
EFFECT OF REFERENCE POINT ON VEPs TABLE 1! Results of monocular pattern reversal visual evoked potentials recorded at Oz with reference to Cz and to linked mastoids. Cz reference
Linked-mastoid reference
393
367
Abnormal Delayed Absent Configuration
77 10 1
75 11 1
Uninterpretable
19
46
Normal
Oz with both the Cz and M1 + M2 reference was abnormally delayed, and in 10 other instances there was no reproducible response in either recording derivation. Uninterpretable VEPs from 1 eye due to a W-configuration using the Cz reference were of normal configuration and latency with linked mastoids. Uninterpretable responses due to poor reproducibility and contamination by artifact were obtained with the linked-mastoid reference in 26 instances, while an additional 18 were uninterpretable with both techniques. Among the 26 instances in which only the VEP recorded between Oz and M1 + M2 was uninterpretable, the response recorded with the Cz reference was normal in 19 and abnormally delayed in 7. The VEP results we obtained with the 2 reference points are contrasted in Table It.
Discussion
The derivation used for recording the VEP is generally selected to enhance the identification of the P100 response. Field studies of the VEP to monocular full-field stimulation have shown that the occipital component of the P100 response is maximal in amplitude near the mid-occipital region, declining with more anterior locations, and that, with 50-60 rain checks, a negative peak of similar latency occurs at the vertex (Cz) electrode (Asselman et al. 1975; Erwin 1980; Chiappa 1983: Spitz et al. 1986). The exact transition site between positivity and negativity varies in different individuals; it is usually between Cz and Pz, but may occur more posteriorly. In either case, the Oz-Cz bipolar derivation will generate a large Pl00 peak by the summation of activity of opposite polarity in the differential amplifier. The negativity (N100) recorded at Cz extends anteriorly and is often most conspicuous frontally when recorded using a non-cephalic reference point (Chiappa 1983). Recording of VEPs between Oz and a mid-frontal reference thus leads to an amplified P100 response, just as does the Oz-Cz derivation. The variability in the distribution and relative size of these 2 potentials in normal subjects is, however, considerable. Thus, of the 16 normal eyes tested using an array of recording
321 electrodes, there was no N100 component in the VEP elicited from 3, and in another 2 the occipital positivity was missing but the N100 was preserved anteriorly (Fig. 1). Moreover, in 8 of the remaining 44 normal eyes tested (all of which had a normal VEP in the Oz-Cz derivation), there was no response recorded between the occipital region and linked mastoids, suggesting that the occipital positivity was absent in these subjects. It is possible that in these normal subjects the site of the occipital positivity was displaced more posteriorly than the usual Oz electrode site. Even if this is the case, however, the variability of this site means that the absence of either an NI00 or an occipital positivity, at least as determined at a single electrode position, cannot be regarded in itself as abnormal. If the anterior negativity recorded at Cz or mid-frontally is not completely synchronous with the occipital positivity, recording between Oz and either of these 2 active reference points may produce a broad, irregular, poorly defined or bilobed P100 (i.e., a positive peak interrupted by a negative wave) that makes interpretation difficult or results in latency shifts. Some have suggested that VEPs with aberrant wave forms, i.e., with an ambiguous major P100, have a similar clinical significance (regardless of their latency) to that of a delayed but normally formed VEP (Jones and Blume 1985). They have emphasized that such aberrant wave forms are not found in normal control subjects, although this is contrary to our own experience and to that of others (Stockard et al. 1979). In occasional subjects the major positive component of the VEP extends more anteriorly than usual and may even encompass the Cz electrode placement (Chiappa 19831, so that recording between Oz and Cz then leads to a small or an apparently absent P100 response, or to an inverted response. h has been suggested that such interpretive errors can generally be avoided if the VEP is recorded between Oz and a relatively inactive reference point as well as between Oz and Cz or the mid-frontal region. An earlobe or mastoid site may be active and with monocular full-field stimulation a low amplitude, positive peak can sometimes be recorded there with the same latency as the occipital PI00 (Asselman et al. 1975: Chiappa 1983). With an earlobe or mastoid reference, then, there may be some attenuation of the Pl00 response due to in-phase cancellation between active (Oz) and reference sites m the differential amplifier. More commonly, however, there is a virtual lack of activity at the mastoids, supporting their use as a reference point for VEP studies in addition to an active ~calp reference such as Fz (Spitz et al. 1986). Spitz et al. (1986) reported that the sole use of ()z-Fz montage could lead to the misinterpretation of an absent P100 at Oz (which they regarded as abnormal) as a normal response because of the wave form generated by the anterior N100. They therefore emphasized the need for recording between Oz and a relatively inactive site such as the ear or mastoid process. Indeed, they found an absent P100 in their Oz-Ml derivation in 9 patients with a preserved NI00. Form our findings, as mentioned above, absence of P100 in the ()z-linked mastoid derivation cannot be considered abnormal. It is possible that the occipital Pl00 is sometimes more posterior than usual, and simply recording from Oz may occasionally miss it. Field
322 studies in subjects with loss of only the P100 at Oz or the anterior N100 are required to determine the relevance of this finding, but have not yet been undertaken by us or others, at least in a systematic manner. Thus, it may be that there is no single 'best' reference for VEP recordings. We found the diagnostic yield obtained by recording the VEP between Oz and either Cz or a linked-mastoid reference to be comparable (Table II). Use of a linked-mastoid reference, however, provided less satisfactory recordings because of the smaller size of the P100 (due to loss of additive effect in the differential amplifier from the anterior N100) and increased contamination by muscle artifact. Thus, in 26 instances we found uninterpretable VEPs due to artifact using this reference, but responses that were unambiguously present when Cz was the reference point; in no instance was the converse true. Nevertheless, there were 5 instances where the occipital P100 was unambiguously present and delayed using a linked-mastoid reference, but was of normal latency and configuration using a Cz reference. It could be argued that in these 5 cases the use of the linked-mastoid reference gave a more accurate result than the other recording derivation. In 3 of these 5, the patients had clinical symptoms suggestive of optic nerve involvement on the side with the abnormal VEP, and in 1 other the optic disk was suspected to be abnormally pale. In addition, in 1 case the linked-mastoid recording montage clearly complemented the findings in the Oz-Cz derivation in that the VEP obtained using the mastoid reference was normal, whereas the VEP obtained simultaneously using a Cz reference had an uninterpretable W-shaped configuration. Thus, the concurrent use of the linked-mastoid reference only infrequently provides additional information to that provided by the standard montage. Nonetheless, it requires no additional recording time and may resolve some ambiguities, thus obviating the necessity of having to resort to more timeconsuming and expensive methods of resolving ambiguities, such as hemi-field stimulation, the stimulation of upper and lower fields, or use of different check sizes (Halliday et al. 1977, 1982; Blumhardt and Halliday 1979). However, the comparative value of these different techniques remains to be evaluated.
P.-Y. SHIH ET AL. References
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