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Steady-State and Transient Visual Evoked Potentials in Clinical Practice

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STEADY-STATE AND TRANSIENT VISUAL EVOKED POTENTIALS IN CLINICAL PRACTICE Gastone G. Celesia Department of Neurology William S. Middleton Memorial Veterans Hospital University of Wisconsin Madison. Wisconsin 53705 Neurophysiological studies in cats and primates have shown that the most effective stimulus for cortical neurons is contrast rather than absolute intensity of light.’.2 Barlow’ was the first to suggest that visual neurons may require a particular pattern of stimulation in order to produce a maximal response. Hubel and Wiesel’.* found that neurons respond selectively to visual patterns of progressively greater complexity at ascending levels in the hierarchy of the cortex. Cortical neurons practically ignore uniform illumination of the retina but are selectively activated by specific forms and shapes. It thus appears that at different levels of the visual system there are different optimal stimuli to activate the neuronal receptive fields (FIGURE 1). These findings in experimental animals have been extrapolated to humans and have led researchers to utilize complex visual stimuli to activate consistent response waveform^.'.^ Among the various stimuli tried, pattern-reversal checkerboard stimula- tion has emerged as a relatively simple method to obtain stable and reliable visual evoked potentials!,’ Thus, pattern-reversal stimulation has received wide acceptance as a tool for the assessment of visual dysfunctions. This success, however, should not deter us from the use of other visual stimuli and must be kept in perspective to avoid the temptation to select only one stimulus as the panacea for every visual diagnostic problem. The need of utilizing different visual stimuli and different recording methods to improve our diagnostic yield will be discussed in this presentation. METHODS Silver-silver chloride electrodes were applied to the scalp with collodion. Electrode impedance was always below 5000 ohms. The electrode placement of Halliday’s group’ was adopted in most of the recordings because of the extensive data base existing with these montages. A mid-occipital electrode (MO) was placed 5 cm above the external occipital protuberance. The lateral occipital electrodes were placed 5 cm to the left or to the right of the MO electrode. These electrodes were referred to a common midfrontal reference electrode 12 cm above the nasion. Electroretinogram (ERG) was monitored from silver-silver chloride electrodes placed with collodion over the periorbital region. The active electrode was positioned at the middle of the infraorbital ridge just below the eye, this electrode was then connected to a second electrode positioned 2.5 cm laterally to the outer canthus of the same eye. Input from the electrodes was led to eight preamplifiers adjusted to a bandwidth ranging from 0.3 Hz to 1 kHz. Preamplifier output was fed simultaneously to an oscilloscope and a minicomputer. The computer sampling rate was 3,700 samples/ sec. Three visual stimulation paradigms were tested in each subject. 290 oO77-8923/~2/03884l290 $1.75/0 @ 1982, NYAS
Transcript

STEADY-STATE AND TRANSIENT VISUAL EVOKED POTENTIALS IN CLINICAL PRACTICE

Gastone G. Celesia

Department of Neurology William S . Middleton Memorial Veterans Hospital

University of Wisconsin Madison. Wisconsin 53705

Neurophysiological studies in cats and primates have shown that the most effective stimulus for cortical neurons is contrast rather than absolute intensity of light.’.2 Barlow’ was the first to suggest that visual neurons may require a particular pattern of stimulation in order to produce a maximal response. Hubel and Wiesel’.* found that neurons respond selectively to visual patterns of progressively greater complexity a t ascending levels in the hierarchy of the cortex. Cortical neurons practically ignore uniform illumination of the retina but are selectively activated by specific forms and shapes. It thus appears that a t different levels of the visual system there are different optimal stimuli to activate the neuronal receptive fields (FIGURE 1). These findings in experimental animals have been extrapolated to humans and have led researchers to utilize complex visual stimuli to activate consistent response waveform^.'.^ Among the various stimuli tried, pattern-reversal checkerboard stimula- tion has emerged as a relatively simple method to obtain stable and reliable visual evoked potentials!,’ Thus, pattern-reversal stimulation has received wide acceptance as a tool for the assessment of visual dysfunctions. This success, however, should not deter us from the use of other visual stimuli and must be kept in perspective to avoid the temptation to select only one stimulus as the panacea for every visual diagnostic problem. The need of utilizing different visual stimuli and different recording methods to improve our diagnostic yield will be discussed in this presentation.

METHODS

Silver-silver chloride electrodes were applied to the scalp with collodion. Electrode impedance was always below 5000 ohms. The electrode placement of Halliday’s group’ was adopted in most of the recordings because of the extensive data base existing with these montages. A mid-occipital electrode (MO) was placed 5 cm above the external occipital protuberance. The lateral occipital electrodes were placed 5 cm to the left or to the right of the MO electrode. These electrodes were referred to a common midfrontal reference electrode 12 cm above the nasion.

Electroretinogram (ERG) was monitored from silver-silver chloride electrodes placed with collodion over the periorbital region. The active electrode was positioned at the middle of the infraorbital ridge just below the eye, this electrode was then connected to a second electrode positioned 2.5 cm laterally to the outer canthus of the same eye.

Input from the electrodes was led to eight preamplifiers adjusted to a bandwidth ranging from 0.3 Hz to 1 kHz. Preamplifier output was fed simultaneously to an oscilloscope and a minicomputer. The computer sampling rate was 3,700 samples/ sec.

Three visual stimulation paradigms were tested in each subject. 290

oO77-8923/~2/03884l290 $1.75/0 @ 1982, NYAS

Celesia: Steady-State and Transient VEP 29 1

I OBJECT I

RECEPTfVE FIELDS

-MONOCULAR -DIFFUSE LIGHT IS GOOD STIMULUS

POStTlON - IMPORTANT RESOLUTION i Cpntrart

-MONOCULAR

Eye -BI AR - D i R E L i G H T INEFFECTIVE

POSITION RESOLUTION

ORIENTATION

AREA 18

FIGURE 1. Diagram of the retino-geniculostriate pathways of primates showing at each level the optimal pattern of stimuli required to activate the receptive fields of the neurons. Note that neurons in the various layers of the lateral geniculate body (LGB) are predominantly innervated from one eye or the other. Interaction between the two eyes occurs at the cortical level.

- MQNOCULAR -DIFFUSE LIGHT IS POOR STIMULUS

-IMPORTANT RESOLUTION POSITION I CONTRAST

Paradigm A consisted of a pattern-reversal checkerboard. The pattern was projected from the rear onto a translucent screen. Pattern reversals were produced by a rapid lateral displacement of the checkerboard through one square. Monocular full-field stimulation was carried out with two sizes of squares (or checks), subtending 31’ 05” and 1’ 2’ of arc to the subject’s eye. For both sizes, the contrast between alternating checks was 57%. The rate of reversal was every 600 msec. The full-field luminance was 34 foot-lamberts (ft-L) with a background luminance of 0.06 ft-L.

292 Annals New York Academy of Sciences

Monocular half-field stimulation was carried out only with a check size of lo 2’. During half-field stimulation the subject fixated on a white dot placed lo of arc laterally from the stimulated hemi-field.

Paradigm B was used to determine the critical frequency of photic driving (CFPD) and consisted of flashes generated by a photic stimulator (Grass, Model PS-2), set at intensity 4 and placed 45 cm from the subject’s eye.

Stimulation began at low frequency of flashes and was gradually increased until no photic driving could be obtained. The following frequencies were used: 1, 20, 32, 44,53,62, and 73 Hz.

Paradigm C was used to produce the visual spectrum array and consisted of six trains of flashes of 8-sec duration. The frequency of flashes varied in each train. The following frequencies were applied: 7, 10, 13, 16, 19, and 22 flashes per second.

Transient Visual Evoked Potentials (T- VEPs)

T-VEPs are electrical potentials resulting from the transient change of brain waves following an intermittent photic stimulus. Conventionally, the term “transient” has been omitted but will be retained here for clarity.

Pattern T-VEPs are critically dependent on many parameters. Arden et aL9 have recommended the following parameters be controlled and specified: (1) stimulus luminance or brightness; (2) type of pattern (checkerboard, grating, etc.); (3) size of pattern specified in terms of visual angle; (4) total field size and shape and its relation to the fixation point, to be specified in terms of visual angle and retinal eccentricity; (5) method of presentation of the pattern (pattern reversal, brief pattern onset or off-set patterned light, etc.). The presentation rate of the pattern should also be specified. The effect of the rate of pattern reversal is shown in FIGURE 2. At reversal intervals less than 600 msec, the amplitude of the response is decreased. The amplitude becomes smaller proportionally to the decreased interval. At intervals equal or shorter than every 100 msec, the responses overlap and no individual response cycle can be related to any particular stimulus cycle. Intervals of 600 msec between each reversal is a satisfactory compromise to record undistorted T-VEPs in most subjects.

Researchers in the field have arbitrarily selected squares (or checks) of one size at one contrast level, although changes in these parameters are known to affect T-VEPs. Different check sizes produce responses of different amplitude. Potentials of maxi- mum amplitude are evoked by check sizes ranging from 11 min to 18 min subtense.” Asselman et al.” compared pattern-reversal checks of 57 rnin to small checks of 30 min with a constant field of 18 deg and found that the T-VEPs had identical latencies; however, the amplitude was slightly smaller for the larger checks. T-VEPs obtained with checks of less than I5 min are mostly due to stimulation of the macular region while the T-VEPs produced with checks larger than 15 min are the result of foveal and extrafoveal tim mu la ti on.'.^.^^ Refractive errors may affect both the latency and ampli- tude of evoked response^.'^.^' Van LithI3 has shown that the effect of refractive anomalies and medial eye opacities upon T-VEPs varies according to various check sizes and contrasts. Relatively large check patterns and contrasts greater than 50% circumvent this potential problem. Retinal eccentricity is another important variable. The effect of stimulation of discrete areas of the retina was studied by Celesia and Meredith.“ T-VEPs could be obtained at the fixation point with stimuli as small as 6 min and 54 sec subtense. No T-VEPs could be obtained with these small fields outside the 4-deg horizontal and vertical meridians. T-VEPs could, however, be elicited by

Celesia: Steady-State and Transient VEP 293

increasing the size of the stimulus. The size required to evoke a response increased in relation to the distance from the fixation point. These data support the invariance principle” stating that photopic stimuli presented anywhere in the visual field are equally effective if the stimuli are equivalent in terms of numbers of neurons activated.

The choice of the square size may have to be changed according to the region of the visual pathways to be studied. To detect small demyelinating lesions affecting optic nerve fibers originating from ganglion cells in the foveal region (the papillo- macular bundle), smaller checks with a small total field should be used. Hennerici el ~ 1 . ’ ~ have shown that a stimulus subtending 45 min of arc was more sensitive in detecting abnormalities of T-VEPs in multiple sclerosis patients than a stimulus field subtending 20 deg of arc at the subject’s eye. On the other hand, if the aim is to detect retrochiasmatic lesions, checks larger than 1 deg may be a better choice. Every subject

600 PATTERN 300 100

- CHECKS 31’

FIGURE 2. Effect of the rate of pattern reversal on the amplitude and morphology of evoked potentials. The number above the response refers to the interval in milliseconds between reversals. Note that the analysis time changes in each column.

undergoing a pattern-reversal stimulation should be tested for his or her ability to see the pattern, and should wear corrective glasses whenever appropriate.

Pattern reversal of squares can be produced with commercially available televi- sions, projectors, or LEDs. These instruments produce visual images with different characteristics and, evoke T-VEPs with different values. FIGURE 3 illustrates response obtained in normals with checks of roughly the same size but produced by three different stimulators. The smallest potentials were evoked by LEDs and the largest and most stable potentials by the projector. The mean amplitude and latency of these responses is tabulated in TABLE 1. The variation of T-VEPs was most likely related to the difference in contrast among the three stimuli and by the relative blur of the television and LED images compared to rile sharp edges of back-projected checks. Furthermore, LED checks were red-white. Colored checks cannot be considered a stimulus equivalent to black-white checks. These data are presented to emphasize the

294 Annals New York Academy of Sciences

lack of standardization of visual stimulators and the importance of monitoring the luminance, contrast, and sharpness of the visual images employed.

T-VEPs evoked by pattern-reversal as described in paradigm A of methods are influenced by age. With advancing age, there is an increase in peak latency of both the N , (N,o of International Classification) and PI (P,oo of International Classification) waves."

This increase is most prominent after age 40. It further varies with the luminance of the pattern. Shaw and Cant" did not detect any latency change with high luminance pattern. They did demonstrate changes in latencies with the same patterns a t lower levels of luminance. This increase in latency probably reflects a slowing of conduction velocity in the optic nerve and/or optic pathways. Age is an important variable that must be taken into account when establishing the boundary of normality. It is suggested that the boundaries of normal be placed 2.5 times above the standard

PROJEC. 1'2' T V 1'2' L E D 1'9'

"Pi

FIGURE 3. Comparison of T-VEPs recorded from the midoccipital region and evoked by projector, television, and LEDs in three normal subjects A. B, and C.

deviation of the regression line; 99.5% of normal subjects will have scores below this The effects of aging on the latency differences between the right and left eyes

are too small to be significant. The limit of normal for latency differences for N, is 5 msec (mean + 2.5 SD) and for latency differences of PI is 6 msec. Assuming a normal distribution for these parameters, the use of the mean + 2.5 SD reduces the overlap between normal and abnormal values to 0.5%. Similarly, a strict criterion of defining abnormal values as those responses with latencies falling beyond two and a half times the standard deviation of the mean was used by Halliday er al."

Recently controversy has risen concerning the topography of pattern T-VEPs to full- and half-field stimulation and the reliability of measuring amplitude asymme- tries to detect retrochiasmatic lesions.2' Most of the discrepancies result from the utilization of different electrode montages and stimulation parameters. Pattern stimulation with checks as described in paradigm A results in symmetrical T-VEP distribution over both occipital regions. In contrast to this symmetry, half-field

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296 Annals New York Academy of Sciences

stimulation (a field of 9 deg) results in T-VEPs with the largest amplitude over the lateral occipital scalp ipsilateral to the half-field stimulated.” Barrett et al.” suggested that this paradoxical lateralization of the major positive wave of T-VEP is related to the mesial location of the potential generators on the hemisphere contrala- teral to the field stimulated. The location of ipsilateral electrodes is optimal to record a potential from the posteromedial aspect of the contralateral occipital lobe. Analysis of our normative data indicates that the utilization of amplitude ratios will normalize interpersonal variations and permit statistical quantification of the data. The lateral occipital ratio was found to be useful. Lateral occipital ratio is defined as the amplitude in microvolts of T-VEP at occipital scalp contralateral to hemifield stimulated divided by the amplitude of T-VEP at occipital scalp ipsilateral to hemifield stimulated. The mean normal value of this ratio is 0.61 0.30. The boundary of normal for the lateral occipital ratio is 1.36 (mean 2.5 SD).

Steady-State Visual Evoked Potentials

Steady-state potentials are electrical events evoked by rapid repetitive sensory stimulation. Rapid continuous stimulation produces evoked responses of constant amplitude and frequency; each potential overlaps another so that no individual response can be related to any particular stimulus ~yc1e.l~ It is presumed that the brain has achieved a “steady-state” of excitability.

Steady-state visual evoked potentials (S-VEPs) are utilized for the determination of critical frequency of photic driving (CFPD). CFPD is defined as the highest frequency of photic driving response in flashes per second. Flash stimulation begins at low frequencies of flashes and gradually increases until no photic driving can be ~bta ined .~ . ’~ For each frequency tested, 200 to 300 samples are summated. CFPD is recorded simultaneously with ERGS at the retinal level (retinal CFPD) and with occipital scalp electrodes (cortical CFPD). The responses to flashes of high frequency consist of sinusoidal waves following the stimulus (FIGURE 4). Subharmonic waves are often seen, particularly at lower frequencies of flashes, both at the retinal and cortical levels. Retinal and cortical CFPD values are related to the intensity of the flash as well as to the brightness of the background illumination and the pupillary size. They are also influenced by age and decrease as age progresses.” In normals, retinal and cortical CFPDs have similar values. The following mean values were obtained: 72 flashes per second at ages 20 to 30; 69 flashes per second at ages 30 to 60; and 62 flashes per second above age 60. Under this stimulation condition, differences between retinal and cortical CFPD had to be higher than 10 flashes per second to be considered abnormal. Cortical CFPD was never greater than retinal CFPD.

Regan’ was the first to apply Fourier analysis to obtain a precise description of S-VEPs to harmonically simple light. He studied both phase and amplitude of S-VEPs. The method was effective in detecting retrobulbar S-VEPs were delayed and had low amplitude with monocular stimulation of the affected eye. In our laboratory we combine steady-state flash stimulation (paradigm C as described in methods) with Fourier analysis of the recorded EEG to obtain the visual evoked spectrum array.’’ Visual stimulation consists of 8-sec trains of flashes. Average compressed arrays are computed using the fast Fourier transform. Each array consists of the summation of two 4-sec epochs of EEG during a specific steady frequency of stimulation.

Quantification is achieved by calculating the ratios of spectral energy at each frequency for homologous regions of the right and left hemispheres. If the two hemispheres contain equal energy, the ratio would be one. Normal spectral ratios were

Celesia: Steady-State and Transient VEP 297

calculated for 19 normal subjects with recordings from 02-CZ and 01-CZ (Interna- tional nomenclature). Spectral ratios were less than or equal to 2.0 in all normal subjects.

Clinical Application of Visual Evoked Potentials

Visual disturbances can now be studied objectively with neurophysiological methods.7.1 1.20.26 Abnormalities in visual evoked potentials indicate dysfunction some- where along the visual pathways. Different disease processes affecting the same region will produce similar disturbances.

FIGURE 4. Evoked responses at different flash frequencies. Monocular stimulation of the left eye in a 23-year-old subject. Each response is a summation of 250 samples averaged for 204 msec. Numbers at the left of the response indicate flash frequency per second. Dots represent stimulus artifact. Note sinusoidal responses up to frequency of 76 flashes per second and absence of response at 85 flashes per second.

Utilizing the three major types of visual stimuli and data analysis described in the methods and after screening more than 500 patients with visual dysfunction, we have identified three abnormal profiles. These profiles permit the differentiation of involve- ment of the eye proper, the optic nerve, and the retrochiasmatic pathways.

In most instances, diseases of the vitreous, lens, anterior chamber, and cornea produce T-VEP amplitude attenuation without affecting their latencies, rovided that checks of high contrast and of a size larger than 20' of arc are However, these lesions are best diagnosed by clinical examination. Diseases of the retina and

298 Annals New York Academy of Sciences

optic nerve may result in pattern-reversal T-VEPs of low amplitude and delayed latencies. In most cases, the differentiation between the two can be made by identification of retinal lesions on fundoscopic examination. The simultaneous deter- mination of retinal and cortical CFPD is useful in these cases. A retinopathy will equally affect retinal and cortical CFPD while a lesion of the optic nerve will produce a dissociation of CFPD with normal retinal and decreased cortical CFPD (FIGURE 5). In more difficult cases, the differential diagnosis between retinal and optic nerve involvement may require the utilization of electroretinography with contact lens electrodes.

Unilateral retrochiasmatic lesions do not alter CFPD. On the other hand, bilateral destruction of the visual cortices will affect cortical CFPD while retinal CFPD remains normal (FIGURE 6). This CFPD dissociation is present to monocular stimula- tion of either eye as well as to binocular stimulation. CFPD dissociation related to optic nerve lesions is monocular. Three adult patients with cortical blindness related to bilateral infarction of the occipital cortex were studied with T-VEPs and CFPD. T-VEPs to pattern-reversal checks were present in every patient. The morphology of

WS d age64

20 Flashes/sec

34 Flashes/sec

42 Flashes/sec

0 msec 500

FIGURE 5. CFPD from stimulation of the right eye in a 64-year-old paraplegic with a 10-year history of progressive chronic myelopathy. Note normal ERG responses while cortical evoked responses were absent after the frequency of flashes was increased above 34 flashes per second. This dissociation between retinal and cortical CFPD suggests a dysfunction of the right optic nerve.

Celesia: Steady-State a n d Transient VEP

WS d age 6months OD 0s

I Flosh/sec

299

u 02-Fz

24 Floshes/sec

52 Flashes/sec

0 msec 250

FIGURE 6. T-VEPs and S-VEPs in an infant suspected to be blind. Fundoscopic examination and pupillary reactions were normal. Note the excellent retinal responses with a retinal CFPD of 52 but the total absence of cortical responses from stimulation of either eye. This pattern is highly suggestive of bilateral retrochiasmatic dysfunction.

the responses was normal. In one subject, the latencies of both N, and PI were delayed whereas they were normal on the other two subjects. In every patient cortical CFPD was abnormally low with stimulation of either eye, but retinal CFPD was normal. CFPD has also been found useful in our laboratory to assess infants with suspected blindness. Although a normal response does not exclude impairment of visual perception” and/or moderate visual deficit, an abnormal cortical CFPD usually confirms the clinical suspicion. Severely impaired cortical CFPD to either eye or to binocular stimulation with preserved retinal CFPD were found in four of six newborns with suspected cortical blindness (FIGURE 6).

Delayed or absent T-VEPs have now been reported in optic and retrobulbar neuritis, optic atrophy, ischemic optic neuropathy, and compression of the optic nerve (FIGURES 7 & 8). A T-VEP is considered to have a delayed latency when the peak latency for wave N, and P, falls outside the boundary of normality (mean 2.5 S D according to age) or when the peak latency difference for both waves N , and PI between the stimulation of the right and left eyes is greater than 6 msec. Celesia** studied 74 multiplesclerosis patients and found delayed or absent T-VEPs in 55 (74%) of the cases. Every patient with a central or a paracentral scotoma had an abnormal T-VEP. Of 865 patients suffering from multiple sclerosis, 556 (65%) have so far been reported to have abnormal T-VEPs (TABLE 2). More important is the great sensitivity of the test and its ability to show abnormal pattern evoked responses in early optic nerve lesions when other clinical signs of visual impairment are lacking.

CelesiaZ8 demonstrated delayed T-VEPs in 16 (55%) of 29 multiple sclerosis patients who were without signs or symptoms of visual dysfunction. Delays were also

300 Annals N e w York Academy of Sciences

found in 6 out of 7 cases of multiple sclerosis who had normal visual acuity, visual fields, and no subjective visual complaints, but who had a past history of optic neuritis. Similarly, Halliday and co-workers6.” found delayed T-VEPs in 12 of 14 patients with normal optic discs and no history of optic neuritis. Asselman et al.” reported delayed VEPs in 28% of eyes assessed as normal by other criteria. Seven of 10 patients with a diagnosis of multiple sclerosis but no visual symptoms were similarly found to have abnormal VEPs to a sinusoidal grating pattern.26 Not only are T-VEPs useful in determining subclinical and/or early lesions of the optic nerves, but they can also be

GR dage42 OD 0s

102

250 maec 0

FIGURE 7. 42-year-old man with a diagnosis of definite multiple sclerosis. The patient had a history of right optic neuritis 10 years previously. At the time of these recordings, his visual acuity was 20/30 in both eya, and perimetry was normal. T-VEPs have normal amplitude but prolonged latencies suggestive of optic nerve dysfunction. Note the remarkable reliability of the responses, waveforms, and latencies during a period of 16 months.

used to monitor early compression of the optic nerve and chiasma by sellar and parasellar tumors. T-VEPs can also be utilized to quantify the effect of surgery and/or irradiation. Halliday et al.” showed marked improvement of VEP in the postoperative recordings of 9 parasellar neoplasms. The improvement of VEPs was associated with improved visual function. Craniopharyngiomas and pituitary tumors compressing the chiasma resulted in abnormal VEPs in both eyes in 9 out of 10 patients.

Critical frequency of photic driving was studied in 74 multiple sclerosis patients. It was abnormal in 44% of the cases. When compared to T-VEPs, CFPD was a less

KS d age 52

OD 0s

MARCH 4, f9BO

P97

SEPTEMBER 12,1980

Pf05 NWEMBER 28, f980

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FIGURE 8. T-VEPs to pattern reversal in a patient with ischemic optic neuropathy. The patient developed a sudden onset of visual blurring in February, 1980. Visual fields showed a central scotoma in the left eye (0s). T-VEPs in March showed absence of response to stimulation of 0s and normal response to stimulation of the right eye (OD). A follow-up 6 months later showed a change in the potential evoked from OD with broadened PI and a PI latency 8 msec longer on March 7, although still within the normal range of values for his age. At this time the patient was complaining of transient obscurations but Goldman’s peximetry of OD was normal. Worsening of vision was noted by the patient in November of the same year; at that time he had bilateral cortical scotoma and absent T-VEPs.

TABLE 2 PATTERN-REVERSAL VISUAL EVOKED RESFQNSES IN MULTIPLE SCLEROSIS

Number Check of Patients Abnormal VER

Reference Year (rninofarc) Studied Number 5% Size

Halliday er 01.” 1973 50 5 1 49 96 Asselman er 01.” 1975 30 51 34 67 Lowitzch et 01.’~ 1976 50 135 98 73 Zee~e’~ 1977 45 30 20 67 Hennerici er ~ 1 . l ~ 1977 45 57 50 88 CeIesia’* 1978 I5 74 55 74 Mastaglia er al.” 1977 102 52 51 Hoeppner & Lolas” 1978 50 104 49 47 Shahrokhi et ~ 1 . ’ ~ 1978 26 149 85 57 Bodis-Wolher el uLz6 1979 137 103 64 62

Totals 856 556 65

8

*Information not given. ?Gratings.

302 Annals New York Academy of Sciences

sensitive indicator of optic nerve pathology than T-VEPs but the two tests were not mutually exclusive because CFPD was the sole abnormality in 2 of the 74 patients2’ The effectiveness of CFPD for the diagnosis of optic nerve involvement in multiple sclerosis was confirmed by Cohen el al.” Similarly, Regan el u [ . ~ ’ identified a distinct group of multiple sclerosis patients having a defect to medium frequency flicker independently of the delay in pattern-reversal VEPs. The utilization of more than one test will enhance the reliability and the yield of the procedure.

There is considerable controversy about the effect of retrochiasmatic lesions on the amplitude of T - V E P S . ’ ~ ” . ~ ’ . ~ ~ . ~ ~ . ~ ~ Halliday’s group, using full- and half-field pattern stimulation, were able to demonstrate clear asymmetries of amplitude distribution in hemianopic patients. These findings were confirmed by Kuroiwa and Celesia.22 In a study of 14 hemianopic patients, the following amplitude distribution abnormalities were noted: ( I ) absent T-VEPs to stimulation of the affected half-field with normal amplitude distribution to stimulation of the normal half-field; (2) reversal of normal amplitude pattern to the half-field stimulated; and (3) lateral occipital ratios above 1.36. One or two of these abnormalities were present in 12 patients (FIGURE 9 & 10).

Another method that has shown promise for the detection of hemianopic fields is the visual evoked spectrum array (VESA). The following abnormalities were noted in 16 hemianopic patients: (1) Small spectral amplitude over the occipital region contralateral to the affected field; (2) visual evoked spectral ratio plot with high peaks and valleys; ( 3 ) spectral ratios above 2.5 (FIGURE 11). The major strength of VESA is

LT

LO

MO

RO

RT

0 MSEC. 256

5mm WHliE \

RIGHT MOR = 2.1 LOR TO RIGHT HALF-FIELD = 17.0

LT LO MO RO R 1

FIGURE 9. Patient with right homonymous hemianopsia from an infarct of the left occipital lobe. Note the pathological reversal of amplitude asymmetry with contralateral preponderance to stimulation of affected right hemifield. Amplitude of large positive wave is plotted in the lower part of the figure. LOR, lateral occipital ratio; LT, left temporal; LO, left occipital; MO, midoccipital; RO, right occipital; RT, right temporal.

Celesia: Steady-State and Transient VEP 303

M.C. 00

RO

= i 9 1

0 MSEC. 204

LT LO NO RO RT

FIGURE 10. Patient with left homonymous hemianopsia. Selective T-VEP to full field, right and left hemifield, are shown in the upper half of the figure. Note the lack of ipsilateral amplitude preponderance to the left hemifield (affected field) stimulation, that is a reversal of normal amplitude asymmetry.

its ability to be carried out in uncooperative patients. Visual stimulation a t each frequency lasts 8 sec and the test is over in less than 2 min. As promising as these tests appear for the objective determination of retrochiasmatic lesions, a note of caution is in order. While either T-VEP amplitude distribution of VESA is reliable, neither test has yet proved as sensitive as the visual field perimetry. Further testing of these methods is needed.

Transient visual evoked potentials have been used successfully to demonstrate disorganization of retinogeniculo striate projections in human albino^.^^*'^ Albinism is not only characterized by hypomelanosis but also by aberrant retinal projections. Guillery et ~ 1 . ’ ~ have verified these aberrant optic projections in several brains of human oculocutaneous albinos. In contrast to the normal pattern of decussation, albinos have crossing fibers arising from the temporal retina near the zero vertical meridian while the more peripheral temporal retina produces nondecussating projec- tions. This disorganization alters the orderly representation within the lateral genicu- late and the striate cortex. Coleman et found that their albino subjects had abnormal amplitude distribution of visual evoked responses suggesting aberrant visual pathways. The albinos showing abnormal VEP had defective stereopsis. These authors suggest that human albinos have separate representations of both the ipsilateral and abnormal contralateral visual fields in each hemisphere.

SUMMARY

The electrophysiological analysis of visual evoked responses is a powerful tool for the study of visual function. The combined application of pattern-reversal transient

304 Annals New York Academy of Sciences JC d RIGHT QUADRANTIANOPIA

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T - 250 ? mrec I I , I

25 Hz 4

FIGURE 11. Transient visual evoked responses to pattern reversal are shown in the right half of the illustration. Note the absence of T-VEPs with stimulation of the affected field. The visual evoked spectrum array to steady-state flash stimuli is displayed in the lower part of the right half and shows very small energy peaks over the left occipital region (O,-Fz). The ratio of the peak energy is a 0.5 Hz band for each of the six frequencies of stimulation. and is plotted in the upper part of the right half of the figure. The dominant energy side was the right occipital region with a mean ratio of 3.9.

visual evoked potentials, critical frequency of photic driving, and visual evoked spectrum array has enhanced the reliability and the yield of these tests for the diagnosis of visual dysfunctions. Prechiasmatic and retrochiasmatic lesions a re char- acterized by different abnormalities. Prechiasmatic lesions often can be further differentiated into retinal and optic nerve lesions by the simultaneous recording of retinal and cortical potentials.

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