Use of visually evoked responses in evaluation of visual blurring in brain-damaged patients

Electroencephalographv and clinical Neurophvsiolog~ , 1989, 74:394-398 Elsevier Scientific Publishers Ireland, Ltd.

394

EVOPOT 02356

Short communication

Use of visually evoked responses in evaluation of visual blurring in brain-damaged patients J. Zihl and C. Schmid Max-Planck-lnstitut fiir P~Tchiatrie, Munich (F.R.G.) (Accepted for publication: 11 April 1989)

Summa~ Pattern visual evoked potentials were recorded in brain-damaged patients who complained of fluctuation of vision causing visual blurring. Continuous prolonged pattern stimulation revealed marked variability of P100 amplitudes. In contrast, normal subjects and brain-damaged patients who did not complain of visual blurring showed stable P100 amplitudes. Fluctuation of vision thus seems to have an electrophysiological correlate in terms of P100 amplitude lability, which can be objectively assessed by prolonged continuous recording of pattern visual evoked potentials. Key words: Pattern visual evoked potential; Amplitude variability; Visual blurring; Brain damage

Most visual disturbances caused by brain damage can be assessed quantitatively by standardized neuro-ophthalmological and neuropsychological testing. However, there are patients who complain of visual disturbances which cannot be evaluated objectively because appropriate methods are not available. One visual disorder which is not uncommon for patients with brain damage is blurred vision, although pupillary responses, visual acuity, accommodation and convergence are not impaired. Patients with blurred vision either complain of persistent ' foggy' vision or fluctuation and even extinction of perception after prolonged inspection of a visual stimulus (Bender and Teuber 1946: Bodis-Wollner and Diamond 1976). Patients claim that they can no longer read because letters appear indistinct or merge into one another, and words are often obscured by shadows. In the case of fluctuation of vision, patients do not experience any difficulty at the beginning of reading. The print appears clear and distinct, then gradually deteriorates and letters become greyish so that the whole page appears 'foggy.' While persistent visual blurring can be explained by impaired spatial contrast sensitivity (Bodis-Wollner and Diamond 1976), fluctuation of vision is still an unsettled issue. Bender and Teuber (1946) suggested that marked lability of the threshold in impaired cortical tissue is responsible for the symptom. The question arises whether fluctuation of vision can be assessed objectively by recording visual evoked potentials (VEPs) during prolonged inspection of a pattern shift stimulus.

Corre,wondence to: J. Zihl, Max-Planck-lnstitut fiir Psychiatrie, Kraepelinstrasse 10, D-8000 Munich 40 (F.R.G.).

The pattern-generated VEP seems a reasonable tool for assessing temporal instability because in normal people both latency and amplitude of the first prominent positive wave (P100) show relatively small variability during continuous prolonged stimulation (Meienberg et al. 1979). Considering patients' reports of fluctuation of vision one may hypothesize that this symptom might correlate with unstable VEP responses. Our observations indicate that fluctuation of vision in fact correlates with marked instability of the amplitude of P100.

Methods Subjects Two groups of subjects participated in this study, 15 norreal subjects (9 females, 6 males) and 2 groups of 15 patients each (10 females, 20 males) with damage involving the posterior parts of the brain. Age range was from 19 to 61 years in normal subjects (mean: 40 years). All patients of the first group (group A) complained of visual blurring occurring shortly after they started reading, whereas no patient of the second group (group B) reported this visual symptom. Age ranges were from 21 to 68 years in group A (mean: 37 years), and from 17 to 70 years in group B (mean: 36 years). Aetiology of brain damage was closed head trauma in 10 cases in both groups A and B, unilateral cerebrovascular damage in 4 cases in group A, and in 3 cases in group B (4 left-sided, 3 right-sided), tumour (right-sided, operated) in 1 case in group A, and cerebral hypoxia in 2 cases in group B. Time since lesion varied between 2 and 60 months in group A

0168-5597/89/$03.50 ~ 1989 Elsevier Scientific Publishers Ireland, Ltd.

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(mean: 12 months), and between 3 and 12 months in group B (mean: 5 months). Eight cases showed homonymous hemianopia, 5 in group A, and 3 in group B. Visual field sparing ranged from 2 to 5 °. Snellen values for monocular visual acuity (corrected) for near vision were 3 0 / 3 0 in 13, and 3 0 / 5 0 in 2 patients in group A; for far vision 13 cases showed 6 / 6 , and 2 showed 6 / 9 . In group B, 11 patients showed near acuity of 30/30, 2 cases showed 3 0 / 4 0 and 2 cases 30/50. Far acuity values were 6 / 6 in 12 cases, and 6 / 9 in 3 cases. All normal subjects had full near and far Snellen acuity (corrected). No pupillary impairment was evident in patients; accommodation and convergence were within normal limits in all subjects. Furthermore, there was no evidence for a peripheral lesion affecting the eyes or the optic nerve (e.g., optic neuritis). Neuropsychological testing did not reveal any disorder which could interfere with VEP recording. There were especially no cases with aphasic disorders, memory impairment or deficits in attention.

Stimulatton and recording Pattern-reversed stimulation was obtained with a commercially available TV pattern generator (Medelec visual stimulator). A black and white checkerboard pattern was presented in front of the patient at a distance of 40 cm. The whole stimulating field corresponded to a visual angle of 42 ° horizontally

and 35 ° vertically and each square subtended a visual angle of 52 min of arc. The average luminance of the TV screen was 54 c d / m 2 with a contrast between squares of 80%. Pattern-reversal frequency was 2 Hz. The subjects were requested to fixate on a small black circle in the centre of the screen during the period of recording. VEPs were recorded between a mid-occipital electrode placed 3 cm above the inion (Oz) and a mid-frontal electrode (Fz), and were fed into a preamplifier with low and high frequency filters set at 0.16 and 500 Hz. Impedance was maintained below 5000 /2. Sampling rate was 1 kHz corresponding to I msec; analysis time was 400 msec. EOG was not controlled, but every single response was tested for artifacts before the summation procedure was performed. Artifact thresholds were set at >~100 /tV for amplitudes and at >/100 ktV/msec for differences between adjacent sampling points. If threshold values were exceeded because of, e.g., muscle artefacts, such as blinking, eye or head shifts, the response was not included for summation. Monocular and binocular VEPs to 32 reversals over a whole period of 15 trials were averaged using a PC-AT, which was triggered by the pattern reversal. Thus in each condition (right eye, left eye, both eyes), 480 individual responses were recorded and 15 averages were obtained. The whole period of stimulation lasted 4 min. The peak latency of the major positive wave of the VEPs

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ms ITIS Fig. 1. Pattern reversal evoked potentials (binocular stimulation) in a patient without visual blurring (A), and in a patient with blurring of vision (B). Both patients were 35-year-old females who had suffered cerebral hypoxia. Time since brain da ma ge was 3 months in A and 5 months in B. Numbers 1-15 refer to continuous averaged recordings (32 sweeps per trial); the black arrows indicate the first major positive potential (P100). Note stability of P100 amplitudes in A and, in contrast, pronounced variability in B.

396

J. ZIHL, C. S C H M I D report visual blurring, and in the group of patients who complained of visual blurring shortly after beginning their reading. While mean latencies were similar for the 3 groups, standard deviations were larger in the first 2 groups of patients, and coefficients of variability were largest in the group of patients with visual blurring. Mean amplitudes, standard deviations and coefficients of variability were similar in the 2 control groups. In contrast, patients with visual blurring showed smaller amplitudes, larger standard deviations and also larger coefficients of variability. Analysis of variance did not reveal statistically significant differences for latencies or amplitudes of P100 between monocular and binocular stimulation conditions in either group (highest F = 1.69, df = 2, P = 0.19), and no significant interactions between groups and stimulation conditions were found (largest F - 0.757, df = 4, P = 0.55). Therefore, only binocular data were included for further statistical analysis. P100 latencies did not significantly differ between groups (largest F - 1.90, df - 2; P - 0.16). Coefficients of variability also did not show statistically significant differences at the 0.05 level. In contrast, P100 amplitudes significantly differed between groups ( F = 3.37, df = 2; P - 0.04), but Duncan's test only revealed a significant difference between patients with visual blurring and normal subjects at the 0.05 level. Coefficients of variability differed highly significantly between groups

(PI00) was determined and its amplitude measured from the peak of the immediately preceding negativity. Data analysis and data plots were performed with a special software program on a PC-AT. Mean latencies and amplitudes were calculated from 15 trials carried out with each subject. The coefficient of variability (standard deviation divided by mean) was calculated for each trial, and used as index for the variability of latencies and amplitudes of PI00.

Results

Fig. 1 shows typical results of VEP recording in a patient without visual blurring (A) and in a patient who complained of visual blurring after about 1 min when reading (B). Both had normal visual acuity. While the first patient did not show any essential P100 amplitude variability, there was marked fluctuation in the second patient. Fig. 2 shows the course of amplitudes of P100 with monocular and binocular stimulation for the 2 patients shown in Fig. 1. While amplitudes of P100 did not show any essential fluctuation in either stimulation condition in the first patient, there was marked instability of amplitudes in all conditions in the second case. Table I summarizes the results of VEP recording in the group of normal subjects, in the group of patients who did not

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Fig. 2. Course of P100 amplitudes of continuously recorded pattern reversal VEP responses under monocular (RE, right eye; LE, left eye) and binocular stimulation conditions (BIN) in the 2 patients shown in Fig. 1. Each square represents the average of 32 responses. Note the stability of P100 amplitudes in patient A who did not complain of blurring of vision, and the lability of the amplitudes in patient B who reported pronounced blurring of vision. The values in the binocular condition (BIN) correspond to the averaged responses in Fig. 1. Coefficients of P100 variability are 0.19 (RE) and 0.13 (LE, BIN) for patient A. and 0.57 (RE), 0.74 (LE), and 0.36 for patient B.

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TABLE I Latencies (in msec) and amplitudes (in btV) of P100 in normal subjects (n = 15), in patients without visual blurring (n = 15), and in patients with visual blurring (n = 15) under monocular (RE, right eye; LE, left eye) and binocular (BIN) stimulation conditions. S.D., standard deviation; V, coefficient of variability; R, range. Mean

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1.81 1.80 1.88 2.41 2.59 2.35 3.68 3.68 3.86

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1.54 1.51 1.77 1.65 1.47 1.66 2.46 2.78 2.96

0.15 0.15 0.16 0.18 0.17 0.17 0.43 0.46 0.42

0.11 0.20 0.08 0.21 0.08-0.22 0.12 0.26 0.09 0.24 0.10 0.29 0.27-0.69 0.23-0.69 0.18-0.69

(A) Latencies Normal subjects

Patients without visual blurring Patients with visual blurring

(B) Amplitudes Normal subjects

Patients without visual blurring Patients with visual blurring

( F = 48.6, df = 2; P < 0.001). Duncan's test revealed significant differences at the 0.05 level between the group of patients with visual blurring and both control groups. Pattern evoked responses in Fig. 1B not only show systematic variability of the P100 amplitudes, but also more pronounced changes in the overall wave form of P100 and a higher baseline variability than responses in Fig. 1A. One may ask, therefore, whether the significantly larger fluctuation of P100 amplitudes in the group of patients complaining of visual blurring is the result of an increased overall variability in this group. To rule out this possibility we calculated for all 3 groups the mean variability for each sample, i.e., every millisecond, over the 15 trials. Statistical testing neither revealed significant differences between groups in either testing condition (left eye, right eye, binocular stimulation) (largest t: 0.95, df = 28, P > 0.10) nor within groups (largest t: 1.65, dr= 28, P > 0.05). Thus, the systematic fluctuation of the P100 amplitudes in the patient group complaining of visual blurring can hardly be attributed to a higher unspecific variability.

Discussion Our data on continuous prolonged recording of pattern reversal evoked responses suggest that complaints of visual blurring are associated with marked lability of the P100 amplitude. Normal subjects as well as brain-damaged patients who

did not report visual blurring did not show unstable PI00 amplitudes, it is unlikely, therefore, that the VEP fluctuation found in patients who did not complain of visual blurring is the result of deliberate alteration (cf., Tan et al. 1984), global visual fatigue due to prolonged inspection, or unspecific baseline variability. Although the EOG was not controlled, the absence of any significant difference in the baseline variability between the groups with an without visual blurring makes it very unlikely that the observed P100 fluctuation is caused by blinking, gaze shifts or other muscle artifacts. The observation that, in the absence of any prechiasmatic impairment, fluctuation was obtained under monocular as well as binocular conditions indicates that fluctuation most likely occurs at a postchiasmatic stage in the visual system. This assumption is also supported by other abnormal findings, for example, reduction of the amplitude of P100 and alterations of its form (cf., Fig. 1), which are known to result from post-chiasmatic dysfunction (Feinsod et al. 1976; Streletz et al. 1981; Gupta et al. 1986). Blurring of vision and fluctuation of the PI00 amplitude seem not to be associated with a specific aetiology of brain damage, as patients with cerebrovascular, traumatic and hypoxic damage suffered form this visual disorder. However, the small group of patients in this study does not allow any conclusion regarding the association between aetiology of brain damage and the frequency and severity of blurred vision and fluctuation of the amplitudes of P100. At the moment, one can only speculate as to the cause of fluctuation of vision in brain-damaged patients. With reference

398 to Bender and Teuber (1946) we would like to hypothesize that temporal instability in cortical visual processing is responsible for the fluctuation of vision. One m a y assume that VEP generators in the striate cortex or visual association areas are affected and are, thus, no longer capable of stable neuronal excitability. Alternatively, non-retinal modulation of visual cortical activity is altered so that the level of excitability cannot be maintained constantly over a longer period of time. It is well known that the pontine and mesencephalic reticular cores specifically influence activity in the post-chiasmatic visual system. Ascending reticular activation has been shown to influence both transmission of visual information and visual cortical excitability in a global but modality-specific way, that leads to striking variations in sensory thresholds (for review, see Singer 1977. 1979). The setting and maintenance of particular excitability levels in the visual cortex are two of the most important functions of reticular activation, because they guarantee high stability of visual functioning. Both lability of threshold in impaired cortical tissue and temporal instability of the level of neuronal excitability caused by impaired ascending reticular activation can lead to fluctuation of vision. As patients with visual field disorders in the control group neither complained of visual blurring nor showed altered VEP responses, it can be argued that damage to the optic radiation a n d / o r striate cortex as such is not sufficient to produce fluctuation of vision. Therefore, it seems likely that an alteration of the ascending reticular modulation is responsible for the observed temporal instability of vision. In conclusion, the results of this study show that fluctuation of vision in brain-damaged patients is correlated with PI00 amplitude variability in the pattern visual evoked responses during continuous prolonged stimulation. Although both amplitude and wave form of P100 responses undergo fluctuation, the variability of the amplitude seems sufficient to evaluate visual blurring as a result of temporal instability of vision. We are grateful to P. Z a h n for the development of the software used in this study, to Dr. G. Kerkhoff for his cooper-

J. ZIHL, C. S C H M I D ation in this investigation, and to Prof. D. Von Cramon, Department of Neuropsychology, Stfidt. Krankenhaus Miinchen-Bogenhausen, for permission to study our findings on patients under his care.

References

Bender, M.B. and Teuber, H.L. Phenomena of fluctuation, extinction and completion in visual perception. Arch. Neurol. Psychiat., 1946, 55: 627-658. Bodis-Wollner, I. and Diamond, S.P. The measurement of spatial contrast sensitivity in cases of blurred vision associated with cerebral lesions. Brain, 1976, 99:695 710. Feinsod, M., Hoyt, W.F., Wilson, B. and Spire. J.-P. Visually evoked response. Arch. Ophthalmol., 1976, 94:237 240. Gupta, N.K.. Verma, N.P., Guidice, M.A. and Kooi, K.A. Visual evoked response in head trauma: pattern-shift stimulus. Neurology, 1986, 36: 578-581. Meienberg, O., Kutak, L., Smolenski. C. and Ludin, H.P. Pattern reversal evoked cortical responses in normals. J. Neurol., 1979, 222: 81-93. Singer, W. Control of thalamic transmission by corticofugal and ascending reticular pathways in the visual system. Physiol. Rev., 1977.57: 386-420. Singer, W. Central-core control of visual-cortex functions. In: The Neurosciences, 4th Study Program. MIT Press, Cambridge, MA, 1979: 1093-1110. Streletz, L.J., Bae, S.H., Roeshman, R.M., Schatz, N.J. and Savino, P.J. Visual evoked potentials in occipital lobe lesions. Arch. Neurol., 1981, 38: 80-85. Tan, C.T., Murray, N.M.F., Sawyers, D. and l,eonard, T.J.K. Deliberate alteration of the visual evoked potential. J. Neurol. Neurosurg. Psychiat., 1984. 4 7 : 5 1 8 523.