VISUAL-EVOKED RESPONSE D I F F E R E N T I A T I O N O F I S C H E M I C OPTIC NEURITIS FROM T H E OPTIC NEURITIS O F M U L T I P L E SCLEROSIS W. B R U C E W I L S O N , Denver,
Ischemic optic neuritis is the most common type of optic neuritis in people over 60 years of age. A diagnosis of ische mic optic neuritis is strongly suggested when recovery of vision is minimal and a vascular disease is present, for example, in temporal arteritis, diabetes mellitus, or hypertension. The optic neuritis of multi ple sclerosis is the most common type of optic neuritis in patients 20 to 40 years of age. Return of vision to a near normal level in the absence of vascular disease is indicative of this entity. However, in any given patient in the fifth or sixth decade of life, the differentiation between the two types of optic neuritis may be diffi cult. Because of the diagnostic value of the visual-evoked response in multiple scle rosis, we studied it in 15 patients with ischemic optic neuritis. The most reliable change in the visual-evoked response in the optic neuritis of multiple sclerosis seems to be an increase in the latent period. This is most consistently recog nized in the first negative wave and the major positive wave. 1 - 6 The latent period is the period of time between stimulus to the retina (for example, a flash of light) and the response (potential change) of the occipital cortex. An increase in the latent period may be seen in multiple sclerosis even without symptoms or signs of optic neuritis. 5 To my knowledge, no study has been published defining the visualevoked response findings in ischemic optic neuritis. From the Division of Ophthalmology, Denver General Hospital, and Division of Ophthalmology, University of Colorado Medical Center, Denver, Colorado. Reprint requests to W. Bruce Wilson, M.D., Divi sion of Ophthalmology, Denver General Hospital, West 8th Ave. and Cherokee St., Denver, CO 80204. 530
M.D.
Colorado S U B J E C T S AND M E T H O D S
I studied 15 patients with unilateral ischemic optic neuritis to determine if characteristic changes had occurred in the visual-evoked response. The age range was 52 to 79 years. Each patient had had a sudden loss of vision in one eye and had not shown significant visual improve ment. Excluded from the study were those patients who had more than one line of improvement in Snellen vision or a field defect that disappeared with time and all patients with clinically suspected strokes. Each patient had a loss of central vision, some mild (6/7.5 [20/25]), some severe (6/120 [20/400]). Each had a de fect in the field of vision consistent with ischemic disease, namely, altitudinal de fect or nerve fiber bundle defect. Twelve of the 15 patients showed acute changes at the disk head. These changes were edema, hemorrhage, dilated tortuous veins, and nerve fiber layer microinfarcts. All had a diagnosis suggesting an ischemic etiology for the acute optic nerve damage: tempor al arteritis, diabetes mellitus, collagen vascular disease, or hypertension. Fifty individuals who were free of dis ease served as control subjects. Both groups were examined in the same way. The patients were seated in a semidarkened room (background light intensi ty of approximately one foot candle), with their eyes open and pupils dilated (tropicamide 1%). Gold-plated electrodes were affixed to the scalp with electrode paste. The visual-evoked response was recorded from the active 0i and 0 2 electrodes; link ed ears served as reference (10-20 inter national nomenclature). The forehead served as ground. The resistance between the active and reference electrodes was kept under 3,000 ohms.
AMERICAN JOURNAL O F OPHTHALMOLOGY 86:530-535, 1978
VOL. 86, NO. 4
ISCHEMIC VISUAL-EVOKED RESPONSE
Two methods of stimulation were used: a diffused flash of light and a reversing checkerboard pattern. The diffused light was delivered by a Grass PS 22 photostimulator of 13-cm diameter, fitted with a diffusing screen that delivered approxi mately 250,000 candles/m 2 . The diffused flash of light was displayed at 0.33 meter and the checkerboard pattern at 1 m. In both cases a small, nonluminous fixation target was used. One hundred stimuli (1/sec) were given with each method. The checkerboard pattern was displayed over a field of 30 degrees on a side using large checks, 1 degree on a side. The black and white checks were displayed continuous ly, reversed on stimulus, produced a con stant luminance background, and had values of 50 and 750 candles/m 2 , respec tively. The cortical evoked responses were am plified by a Grass Model VIII electroencephalograph (band width, 1 to 70 Hz) coupled to a buffer amplifier. A signal averager was used to accumulate the am plified cortical responses. The final aver aged wave was displayed on a Tektronic scope and photographed with a Polaroid camera. Analysis time was 250 msec. Au ditory masking was used. The first five peaks were analyzed for three factors: latency, amplitude, and amplitude-latency ratio. Each patient had a complete neuroophthalmic examination. This included best corrected Snellen vision; Hardy, Rand, and Rittler color vision; Pulfrich phenomenon; formal field of vision; pupil examination; and a dilated exami nation of the posterior pole. Laboratory examination included a complete blood cell count, an erythrocyte sedimentation rate, rheumatoid arthritis factor, antinuclear antibody test, serology test for syph ilis, glucose tolerance, triglycerides, cho lesterol, and coagulopathy profile in all patients. Whole retina and macular electroretin-
531
ograms were done in each patient to dem onstrate that the retina was not the cause of the abnormality in the visual-evoked response. Results of normative data, diffused light—Values were similar to those re ported by Kooi 7 and Richey. 8 Measure ments for latency were always made from the beginning of stimulation to a positive or negative peak on the wave. The first peak in our laboratory was negative. The following peaks were positive, negative, positive (major positive), and negative, respectively. The upper limit of normal for each peak (mean + 3 SD) was: first negative, 60 msec; first positive, 85 msec; second negative, 100 msec; second or major positive, 120 msec; and the third negative, 150 msec. The first negative and major positive wave peaks were chosen for data reporting; they were thought to be representative. The range of amplitude for the first negative peak was 3 to 15 |xV (mean, 8 |xV), and 8 to 40 |xV (mean, 24 (xV) for the major positive peak. The ampli tude for the first negative peak was mea sured from the baseline to the top of the peak. For the major positive peak, ampli tude was measured from the previous highest point on the wave. Results of normative data, checker board pattern—Data for pattern stimula tion was similar to those of Halliday 3 ' 4 and Asselman. 1 The upper limit of normal (mean + 3 SD) was 60 msec for the first negative peak and 95 msec for the major positive peak. The range of amplitude was 4 to 12 (JLV (mean, 7 n-V) and 10 to 30 |j,V(mean, 18 JJLV), respectively. Amplitude was measured as it was when diffused light was used. Most patients displayed a five-peak wave (Fig. 1) when stimulated by the diffused light method, but a three-peak wave (Fig. 2) when stimulated by the checkerboard pattern method. We includ ed data only on those patients with a five-component wave on diffused light
532
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 1 (Wilson). A normal five-peak visual-evoked response wave obtained by stimulating the eye with a diffused flash of light. All figures have the same recording format; negative is up, each x-axis major division represents 30 msec time, each y-axis major division represents 10-JJLV amplitude, and the stim ulus is at the beginning of the trace pattern. " L " indicates latent period of major positive peak. The five peaks are numbered 1 (first negative), 2 (first positive), 3 (second negative), 4 (major positive), and 5 (third negative).
stimulation and a three-component wave on pattern stimulation. Results in ischemic optic neuritis pa tients—The first negative peak was pres-
M
OCTOBER, 1978
ent in 14 of the 15 patients. It increased in the latent period (diffused light and pattern) in four of the 15 patients, but was only slightly delayed in two of the four. The major positive peak (diffused light and pattern) also showed minor increases in the latent period in four of 15 patients, namely, above the mean + 3 SD (Table). In 13 of 15 patients, the amplitude was less than 50% of the mean for the normal subjects. This was seen in the first nega tive peak and in the major positive peak (Table). Amplitude was inversely propor tional to two factors: as the degree of involvement of central vision increased, amplitude decreased; as the area of in volvement of the field of vision increased, amplitude decreased (Table). Next, the amplitude:latency ratio was determined. Normal calculated values were 9 (JLV/60 msec = 0.15 for the first negative peak (diffused light and pattern), 24 u.V/120 msec = 0.2 for the major posi tive peak (diffused light), and 18 |xV/95 msec = 0.19 for the major positive peak (checkerboard pattern). Small values were consistently seen in our patients with ischemic optic nerve disease. Eight of 15 had values of 0.1 or lower for both the first negative and major positive peaks (Table). In contrast, only 10% of our
|
Fig. 2 (Wilson). Left, A normal three-peak visual-evoked response wave obtained by stimulating with a checkerboard pattern of 30 degrees field and checks of 1 degree on a side. The three peaks are lettered A (first negative), B (major positive), C (second negative). Right, A delayed response, as seen in multiple sclerosis, is shown for comparison. " L " indicates latent period of major positive peak.
Normal nerve Major positive peak Diseased nerve . Major positive peak (20/25) All had (20/30) altitudinal (20/25) d e f e c t (20/40) (20/25) (20/40) (20/30) (20/100) (20/200) (20/400)
6/12 6/7.5 6/9 6/7.5 6/12 6/7.5 6/12 6/9 6/30 6/60 6/120 6/12 (20/40) All had 6/30 (20/100) depressed, 6/120 (20/400) c o n t r a c t e d
3 4 5 6 7 8 9 10 11 12
13 14 15
field
(20/30) Both had nerve (20/40) fiber defect
6/9
1
All 6/6 (20/20) All full field of vision
Visual Status
2
15 control eyes
Case No.
TABLE
8.5 7.5 8.0 5.0 7.0 8.5 8.0 8.0 7.0 6.0 3.0 2.5 Not seen
9.5 8.5 9.5 5.5 9.5 7.5 9.5 9.0 7.5 7.5 4.0 3.5 Not seen
95 95 95 100 94 93 95 95 95 102 105 104 Not seen
117 118 120 124 120 117 116 120 120 130 135 132 Not seen
0.03 0.03 Not seen
0.03 0.02 Not seen
0.09 0.08 0.07 0.04 0.06 0.09 0.07 0.08 0.07 0.06
0.13 0.13 0.08 0.07 0.08 0.04 0.08 0.06 0.08 0.08 0.06 0.06
0.14 0.14 13.0 12.3
16.1 15.5
117
94
Mean 0.19 Mean 0.20
Mean 18
Mean 24
Large Field Pattern
Amplitude: Latency Diffused Flash
Large Field Pattern
Amplitude (u-V) Diffused Flash
93
A1K95
Large Field Pattern
118
A I R 120
Diffused Flash
Latency (msec)
ANALYSIS OF 15 PATIENTS WITH UNILATERAL ISCHEMIC OPTIC NEURITIS
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Ischemic optic neuritis is the most common type of optic neuritis in people over 60 years of age. A diagnosis of ische mic optic neuritis is strongly suggested when recovery of vision is minimal and a vascular disease is present, for example, in temporal arteritis, diabetes mellitus, or hypertension. The optic neuritis of multi ple sclerosis is the most common type of optic neuritis in patients 20 to 40 years of age. Return of vision to a near normal level in the absence of vascular disease is indicative of this entity. However, in any given patient in the fifth or sixth decade of life, the differentiation between the two types of optic neuritis may be diffi cult. Because of the diagnostic value of the visual-evoked response in multiple scle rosis, we studied it in 15 patients with ischemic optic neuritis. The most reliable change in the visual-evoked response in the optic neuritis of multiple sclerosis seems to be an increase in the latent period. This is most consistently recog nized in the first negative wave and the major positive wave. 1 - 6 The latent period is the period of time between stimulus to the retina (for example, a flash of light) and the response (potential change) of the occipital cortex. An increase in the latent period may be seen in multiple sclerosis even without symptoms or signs of optic neuritis. 5 To my knowledge, no study has been published defining the visualevoked response findings in ischemic optic neuritis. From the Division of Ophthalmology, Denver General Hospital, and Division of Ophthalmology, University of Colorado Medical Center, Denver, Colorado. Reprint requests to W. Bruce Wilson, M.D., Divi sion of Ophthalmology, Denver General Hospital, West 8th Ave. and Cherokee St., Denver, CO 80204. 530
M.D.
Colorado S U B J E C T S AND M E T H O D S
I studied 15 patients with unilateral ischemic optic neuritis to determine if characteristic changes had occurred in the visual-evoked response. The age range was 52 to 79 years. Each patient had had a sudden loss of vision in one eye and had not shown significant visual improve ment. Excluded from the study were those patients who had more than one line of improvement in Snellen vision or a field defect that disappeared with time and all patients with clinically suspected strokes. Each patient had a loss of central vision, some mild (6/7.5 [20/25]), some severe (6/120 [20/400]). Each had a de fect in the field of vision consistent with ischemic disease, namely, altitudinal de fect or nerve fiber bundle defect. Twelve of the 15 patients showed acute changes at the disk head. These changes were edema, hemorrhage, dilated tortuous veins, and nerve fiber layer microinfarcts. All had a diagnosis suggesting an ischemic etiology for the acute optic nerve damage: tempor al arteritis, diabetes mellitus, collagen vascular disease, or hypertension. Fifty individuals who were free of dis ease served as control subjects. Both groups were examined in the same way. The patients were seated in a semidarkened room (background light intensi ty of approximately one foot candle), with their eyes open and pupils dilated (tropicamide 1%). Gold-plated electrodes were affixed to the scalp with electrode paste. The visual-evoked response was recorded from the active 0i and 0 2 electrodes; link ed ears served as reference (10-20 inter national nomenclature). The forehead served as ground. The resistance between the active and reference electrodes was kept under 3,000 ohms.
AMERICAN JOURNAL O F OPHTHALMOLOGY 86:530-535, 1978
VOL. 86, NO. 4
ISCHEMIC VISUAL-EVOKED RESPONSE
Two methods of stimulation were used: a diffused flash of light and a reversing checkerboard pattern. The diffused light was delivered by a Grass PS 22 photostimulator of 13-cm diameter, fitted with a diffusing screen that delivered approxi mately 250,000 candles/m 2 . The diffused flash of light was displayed at 0.33 meter and the checkerboard pattern at 1 m. In both cases a small, nonluminous fixation target was used. One hundred stimuli (1/sec) were given with each method. The checkerboard pattern was displayed over a field of 30 degrees on a side using large checks, 1 degree on a side. The black and white checks were displayed continuous ly, reversed on stimulus, produced a con stant luminance background, and had values of 50 and 750 candles/m 2 , respec tively. The cortical evoked responses were am plified by a Grass Model VIII electroencephalograph (band width, 1 to 70 Hz) coupled to a buffer amplifier. A signal averager was used to accumulate the am plified cortical responses. The final aver aged wave was displayed on a Tektronic scope and photographed with a Polaroid camera. Analysis time was 250 msec. Au ditory masking was used. The first five peaks were analyzed for three factors: latency, amplitude, and amplitude-latency ratio. Each patient had a complete neuroophthalmic examination. This included best corrected Snellen vision; Hardy, Rand, and Rittler color vision; Pulfrich phenomenon; formal field of vision; pupil examination; and a dilated exami nation of the posterior pole. Laboratory examination included a complete blood cell count, an erythrocyte sedimentation rate, rheumatoid arthritis factor, antinuclear antibody test, serology test for syph ilis, glucose tolerance, triglycerides, cho lesterol, and coagulopathy profile in all patients. Whole retina and macular electroretin-
531
ograms were done in each patient to dem onstrate that the retina was not the cause of the abnormality in the visual-evoked response. Results of normative data, diffused light—Values were similar to those re ported by Kooi 7 and Richey. 8 Measure ments for latency were always made from the beginning of stimulation to a positive or negative peak on the wave. The first peak in our laboratory was negative. The following peaks were positive, negative, positive (major positive), and negative, respectively. The upper limit of normal for each peak (mean + 3 SD) was: first negative, 60 msec; first positive, 85 msec; second negative, 100 msec; second or major positive, 120 msec; and the third negative, 150 msec. The first negative and major positive wave peaks were chosen for data reporting; they were thought to be representative. The range of amplitude for the first negative peak was 3 to 15 |xV (mean, 8 |xV), and 8 to 40 |xV (mean, 24 (xV) for the major positive peak. The ampli tude for the first negative peak was mea sured from the baseline to the top of the peak. For the major positive peak, ampli tude was measured from the previous highest point on the wave. Results of normative data, checker board pattern—Data for pattern stimula tion was similar to those of Halliday 3 ' 4 and Asselman. 1 The upper limit of normal (mean + 3 SD) was 60 msec for the first negative peak and 95 msec for the major positive peak. The range of amplitude was 4 to 12 (JLV (mean, 7 n-V) and 10 to 30 |j,V(mean, 18 JJLV), respectively. Amplitude was measured as it was when diffused light was used. Most patients displayed a five-peak wave (Fig. 1) when stimulated by the diffused light method, but a three-peak wave (Fig. 2) when stimulated by the checkerboard pattern method. We includ ed data only on those patients with a five-component wave on diffused light
532
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 1 (Wilson). A normal five-peak visual-evoked response wave obtained by stimulating the eye with a diffused flash of light. All figures have the same recording format; negative is up, each x-axis major division represents 30 msec time, each y-axis major division represents 10-JJLV amplitude, and the stim ulus is at the beginning of the trace pattern. " L " indicates latent period of major positive peak. The five peaks are numbered 1 (first negative), 2 (first positive), 3 (second negative), 4 (major positive), and 5 (third negative).
stimulation and a three-component wave on pattern stimulation. Results in ischemic optic neuritis pa tients—The first negative peak was pres-
M
OCTOBER, 1978
ent in 14 of the 15 patients. It increased in the latent period (diffused light and pattern) in four of the 15 patients, but was only slightly delayed in two of the four. The major positive peak (diffused light and pattern) also showed minor increases in the latent period in four of 15 patients, namely, above the mean + 3 SD (Table). In 13 of 15 patients, the amplitude was less than 50% of the mean for the normal subjects. This was seen in the first nega tive peak and in the major positive peak (Table). Amplitude was inversely propor tional to two factors: as the degree of involvement of central vision increased, amplitude decreased; as the area of in volvement of the field of vision increased, amplitude decreased (Table). Next, the amplitude:latency ratio was determined. Normal calculated values were 9 (JLV/60 msec = 0.15 for the first negative peak (diffused light and pattern), 24 u.V/120 msec = 0.2 for the major posi tive peak (diffused light), and 18 |xV/95 msec = 0.19 for the major positive peak (checkerboard pattern). Small values were consistently seen in our patients with ischemic optic nerve disease. Eight of 15 had values of 0.1 or lower for both the first negative and major positive peaks (Table). In contrast, only 10% of our
|
Fig. 2 (Wilson). Left, A normal three-peak visual-evoked response wave obtained by stimulating with a checkerboard pattern of 30 degrees field and checks of 1 degree on a side. The three peaks are lettered A (first negative), B (major positive), C (second negative). Right, A delayed response, as seen in multiple sclerosis, is shown for comparison. " L " indicates latent period of major positive peak.
Normal nerve Major positive peak Diseased nerve . Major positive peak (20/25) All had (20/30) altitudinal (20/25) d e f e c t (20/40) (20/25) (20/40) (20/30) (20/100) (20/200) (20/400)
6/12 6/7.5 6/9 6/7.5 6/12 6/7.5 6/12 6/9 6/30 6/60 6/120 6/12 (20/40) All had 6/30 (20/100) depressed, 6/120 (20/400) c o n t r a c t e d
3 4 5 6 7 8 9 10 11 12
13 14 15
field
(20/30) Both had nerve (20/40) fiber defect
6/9
1
All 6/6 (20/20) All full field of vision
Visual Status
2
15 control eyes
Case No.
TABLE
8.5 7.5 8.0 5.0 7.0 8.5 8.0 8.0 7.0 6.0 3.0 2.5 Not seen
9.5 8.5 9.5 5.5 9.5 7.5 9.5 9.0 7.5 7.5 4.0 3.5 Not seen
95 95 95 100 94 93 95 95 95 102 105 104 Not seen
117 118 120 124 120 117 116 120 120 130 135 132 Not seen
0.03 0.03 Not seen
0.03 0.02 Not seen
0.09 0.08 0.07 0.04 0.06 0.09 0.07 0.08 0.07 0.06
0.13 0.13 0.08 0.07 0.08 0.04 0.08 0.06 0.08 0.08 0.06 0.06
0.14 0.14 13.0 12.3
16.1 15.5
117
94
Mean 0.19 Mean 0.20
Mean 18
Mean 24
Large Field Pattern
Amplitude: Latency Diffused Flash
Large Field Pattern
Amplitude (u-V) Diffused Flash
93
A1K95
Large Field Pattern
118
A I R 120
Diffused Flash
Latency (msec)
ANALYSIS OF 15 PATIENTS WITH UNILATERAL ISCHEMIC OPTIC NEURITIS
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