606
Electroencephalography and Clinical Neurophysiology, 1978, 44:606--616
© Elsevier]North-Holland Scientific Publishers Ltd.
V I S U A L L Y E V O K E D C O R T I C A L P O T E N T I A L S IN R E N A L F A I L U R E : TRANSIENT POTENTIALS* B. HAMEL, J.R. BOURNE, J.W. WARD and P.E. TESCHAN School of Engineering, School of Medicine, Vanderbilt University, Nashville, Tenn 37235 (U.S.A.)
(Accepted for publication: October 10, 1977)
Although increased slow wave activity in the EEG is a well-known correlate of advancing renal failure (Locke et al. 1961; Kennedy et al. 1963; Kiley and Hines 1964, 1965; Bourne et al. 1975), there have been few investigations of how evoked activity in the EEG is modified by uremia. Evoked cortical potentials can be elicited by virtually all types of sensory stimuli ranging from tactile to visual. Of these, the visually evoked cortical potentials (VECPs) elicited by photic stimulation of uremic patients have been most frequently studied (Watson et al. 1958; Tyler 1965; 1968). These investigations have arisen naturally because photic stimulation is often a part of the full clinical EEG. Photic stimulation at slow rates (e.g., 1 flash/sec) produces evoked potentials c o m m o n l y referred to as transient VECPs. The relatively small amplitude of such potentials often necessitates the use of signal averaging techniques to extract the transient VECP from the background EEG (Regan 1972; Perry and Childers 1969). Two studies have reported changes in the transient VECP during renal failure. Klingler (1954), described exaggerated high amplitude VECPs elicited by photic stimulation of patients with severe uremic encephalopathy. As the stimulus rate was increased from 1 to * This work was supported, in part, by NSF Grant ENG 74-04188. Data used in the study were supplied from contractual work conducted under the aegis of NIH-NIAMDD Contract NO1-AM-22211.
5 flashes/sec the response amplitude decreased and above 10 flashes/sec no response could be observed. More recently, H y m a n and Kooi (1969) reported the results of random photic stimulation at low average frequencies on VECPs recorded from seven azotemic patients. For this population, the latencies of 5 major peaks in the averaged VECP were found to be significantly longer than those in a normal test population (Kooi and Bagchi, 1964) while there was no significant change in the amplitude of any peak.
Method Patients
A total of 129 patients have been studied over a 4-year period. Of these, data from 90 were collected for periods ranging from 6 months to 4 years. Patients in three main groups were studied: (1) Data were collected from 49 patients not on dialysis therapy (referred to as azotemic) with varying degrees of renal failure and serum creatinine concentrations ranging from 2 to 29 mg/100 ml. Of the 49 patients who were initially azotemic, 29 switched to routine dialysis therapy during the course of the study. (2) Thirty-six patients who were on dialysis treatment on entry into the program were studied and (3) data were recorded from 20 patients with kidney transplants of which 15 received the transplants during the study. Seven of these transplant patients were from the initially dialyzed group while 8 were from the initially azotemic
TRANSIENT VECPs IN RENAL FAILURE group. Patients were normally distributed in age and education. Ages ranged from 15 to 69 while the n u m b e r of years of education ranged from 3 to 18. For purposes of control, 41 normal subjects were tested using the same testing regimen as the patient population. Ages ranged from 13 to 65 and the number of years of education ranged from 6 to 20.
607 of the positive and negative peaks in the averaged waveforms were c o m p u t e d and printed out using standard programs (DECUS 1971). Each peak latency was identified by standard symbols, e.g., N1, N2, N3, etc., P1, P2, P3, etc. for negative and positive peak latencies respectively (Perry and Childers 1969).
Other variables recorded VECP recording and analysis procedures Transient evoked potentials were recorded as part of a battery of neurobehavioral tests which included the EEG (Bourne et al. 1975) and a number of reaction-time based tests (Ginn et al. 1975). For both the EEG and VECP recordings, scalp electrodes were located at F3, P3 and O1 of the International 10-20 system. Bipolar recordings between F3 and P3, P3 and O1 were obtained as well as monopolar recordings from each of the three electrodes referred to the left mastoid. The right ear was used as ground. VECP data described in this paper were recorded from the occipital bipolar channel P3 to O1. The 5 EEG channels were recorded on both an 8-channel Grass Model 6 electroencephalograph and a Honeywell 5600 magnetic tape recorder. A timing channel from the stimulus was recorded on a sixth channel. A Grass Model PS-22 x e n o n strobe was placed 12 inches in f r o n t of the closed eyes of the patient who was seated upright and instructed to avoid head or eye movements. Photic stimulation was delivered at an intensity of 16 for 100 sec at a rate of 1 flash/sec. Patients were not tested if they had less than 2/3 of their normal a m o u n t of sleep on the night prior to testing. Thus, in most cases, patient drowsiness did n o t influence VECP recordings. Records with visually evident artifacts were deleted from the data analyzed. Quantification of the VECPs elicited by the strobe stimulus was entirely conventional. Signal averaging of 500 msec. EEG epochs following each flash was accomplished using a Digital Equipment Corporation Lab 8/e minicomputer. The latencies and amplitudes
In addition to the VECP, three main groups of variables were collected: (1) blood chemistries, (2) cognitive function tests and (3) the a m o u n t of slow wave power in the resting EEG. Detailed descriptions of changes in these variables appear elsewhere (Ginn et al. 1975, Bourne et al. 1975). The blood chemistries measured were: blood urea nitrogen (BUN), creatinine, potassium, calcium and phosphates. An estimate of creatinine clearance was made by the formula: C R Clearance (ml/min)=
(140 --- Age in Years) X Weight in kg 72 X Serum Ca (ml/100 ml) attributed to Cockcroft and Gault (1976) who found an 82% correlation between estimated creatinine clearance and actual 24-h clearance measurements. While serum creatinine provides a simpler approximation of renal excretory failure, the estimate of clearance based on additional weight and age information may provide an even better index since the wide anthropometric attributes and ages of the patients studied may be taken into account. Two cognitive function measures, the choice reaction time (CRT) and the continuous m e m o r y test (CMT) were employed (Ginn et al. 1975). In brief, the CRT is a reaction time measure in which the patient presses buttons corresponding to the color of a series of randomly presented colored lights and the CMT is a m e m o r y task requiring the patient to indicate if words presented are contained in a previously presented list.
608 Slowing of the resting EEG was measured by a ratio of the power in the 3--7 c/sec bandwidth divided b y the p o w e r in the 3--13 c/sec bandwidth, {Bourne et al. 1975).
Analysis o f the data Intergroup analysis of VECP latencies was c o n d u c t e d b y use of analysis of variance (ANOVA) methods with Duncan's ~ posteriori multiple comparisons (Kirk 1968) to compare the significance of intergroup mean differences. Correlational analyses were carried o u t by two methods: (1) Pearson p r o d u c t m o m e n t (PPM) correlations in which test values obtained during each patient's azotemic period were averaged and (2) Pooled covariance analysis (Kirk 1968) in which the correlation was derived from the pooled covariance of all individuals. The latter method deemphasizes any irrelevant betweensubject-differences. While the first analysis shows correlation across the group, the second reveals correlation between changes in an individual's data as the disease progresses. Results
The data obtained in this study are described in five main sections: (1) Normative differences between VECP latencies recorded from (a) normals, (b) patients with high and low levels of creatinine concentration in the azotemic period, (c} dialyzed patients and (d) patients who received transplants are examined via an analysis of variance. (2) Variations in VECP latency and estimated creatinine clearance are described for patients with varying degrees of renal failure in their azotemic period. (3) Individual VECP changes during azotemia to dialysis and dialysis to transplant transitions are presented. (4) VECP latency changes in t w o patients are described. One patient moved from a regular dialysis schedule to a reduced dialysis regimen. The second patient received a transplant after progressing from azotemia to dialysis. (5) Finally, correlations of VECP latency changes
B. HAMEL ET AL. with other variables are presented. Variations in the latency of N2, the second negative peak in the VECP waveform obtained from P3-O1, were used as primary descriptors of VECP changes. Other latencies were measured and changes compared with N2. A general finding was that the latency values moved together, i.e., all would concomitantly increase or decrease as a function of the clinical progress of the patient. In most cases there were insignificant changes in amplitude. One case in which a small amplitude change did occur is discussed in the description of the effect of reduced dialysis.
Normative comparisons Fig. 1 displays the group differences between means of latencies recorded from normals, high and low azotemics, dialyzed patients and patients who received a transplant. The differences in latency values between the 5 groups closely mirror the clinical results one might expect as a patient progresses across the range of five possible clinical phases. Latencies become, on the average, longer than normal in low azotemia, increase to a maximum during high azotemia, decrease with the onset of dialysis therapy and return to more normal levels in the post transplant period. While the variation in latency is small and the variability moderately large because of individual differences, intergroup differences are statistically significant between the groups as shown in the table below the histogram in Fig. 1. Duncan's posteriori multiple comparisons (Kirk 1968) of the group data revealed significant differences between the normal, low azotemic, dialyzed and transplant groups with respect to the high azotemic population and between the dialyzed patients and the normal population. Azotemia As patients progress through the nondialyzed or azotemic period of renal disease, residual renal function gradually declines. Transition from the azotemic period to a
T R A N S I E N T VECPs IN R E N A L F A I L U R E
NORMALS
mean 59,87 s,d. I 1.08
n=16
NORMALS
NORMALS AZOTEMICS LOW
---
609
AZOTEMICS AZOTEMICS HIGH LOW mean 66.18 s.d. 16.97 n=9
mean 83,92 s.d. 22.94 n=ll
DIAL¥SED PATIENTS
POST "RANSPLAN PATIENTS
mean 72,39 s.d. 15.36 n=45
milan 67.46 s,d.
15.72 n=17
AZOTEMICS AZOTEMICS DIALYSED POST LOW HIGH PATIENTS TRANSPLAN1
N.S.
P < .01
P < .05
N.S.
P < .05
N.S.
N.S.
P < .05
P < .05
AZOTEMICS HIGH DIALYSED PATIENTS
N.S.
POST TRANSPLANTS
Fig. 1. Average Group VECP latencies for 4 patient categories and a normal group. Results of Duncan's a-posteriori multiple comparisons are shown below the histogram.
regular dialysis treatment regimen is usually dictated by appearance of clinical uremic symptoms, usually associated with serum creatinine concentration above 10 mg/ml and by inference, values of creatinine clearance below 10 and often below 5 ml/min. The continual long-term deterioration in a patient's clinical well-being (often months or years) during azotemia offers a unique opportunity to observe concomitant long term changes in objective measures. Fig. 2 displays increases in VECP latency values for 12 patients between the onset of VECP measurement in the azotemia period until just prior to changing to dialysis therapy. Estimates of the creatinine clearance are shown at the b o t t o m of this graph. The
visually evident general increases and decreases of the two measures were confirmed statistically by computing the trends on all data collected between the initial and final points shown in Fig. 2. Each of the patients contributed between 3 and 9 VECP latency and clearance values. A significant upward trend (P < 0.001) was found in the VECP latencies using regression analysis and a similar downward trend was observed (P < 0.001) in the estimated clearance measures. A z o t e m i a to dialysis and dialysis to transplant A--D. The azotemia-to-dialysis transition was investigated by selecting patients who had a minimum of three points in the azotemic
B. HAMEL ET AL.
610
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months Fig. 2. VECP latency and estimated creatinine clearance changes during azotemia. The numbers (//) shown correspond to individual patients.
(A) period and in the dialysis (D) period. Data collected from the five patients who provided this minimal n u m b e r of points in each period are shown in Fig. 3. Each point in the A period represents the average of the patient's last three measurements before he began dialysis therapy, and each point in the D period represents his average latency in the D period. The number of measurements in the D period is indicated in the figure. In addition to the
visual evidence of a decrease in latency from A to D, a two way least squares ANOVA revealed statistically significant differences (P < 0.001) between the t w o groups. The ANOVA also showed that the between-subject variation was as great as the between-treatment variation. D--T. A similar analysis was conducted for a dialysis to transplant group of patients with the results shown in Fig. 4. A clearly signifi-
TRANSIENT VECPs IN R E N A L F A I L U R E
611
Azotemia-dialysis-reduced dialysis
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~
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90'
_1
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n=8
~ n = = S
n=4
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n=5 50
A
D
Fig. 3. Azotemia (A) to dialysis (D) transition, n, number of measurements in the dialysis period.
cant decrease in latency (P < 0.001) was found for the 6 patients studied. As in the A--D group, significant interpatient differences were found. The next two sections describe changes in VECPs in two individual patients from whom data was collected in several different treatment regimens.
Averaged VECPs were recorded from a 59-year-old female patient with chronic renal failure during her azotemic and dialysis periods. During the first dialysis period she was on a 3 dialyses/week treatment regimen (D1). She was switched to a 2/week treatment program (D2) on February 14th, 1976 and on August 1st, 1976 the number of dialysis h/week was increased by 55.6% while retaining the 2/week frequency (D2+). During the 3/week dialysis period she had a total of 2711 ml/week/1 creatinine clearance, 1928 ml/week/1 during reduced dialysis and 3000 ml/week/1 during the increased time period (D2+). Twenty-nine VECPs were collected over a 2-year period at approximately monthly intervals with additional tests near treatment transition times. Fig. 5 displays VECPs selected
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Fig. 4. Dialysis (D) to Transplant (T) Transition. n, number of points in the dialysis and transplant periods.
25~uv[
4
I00 msec Fig. 5. VECPs during reduced dialysis. D1, 3 dialyses/
week; D2, 2 dialyses/week; D2*, 2 dialyses/week with increased dialysis time.
612
B. HAMEL ET AL.
from the mid-point of each period. Other VECPs during the same period were similar in waveshape. The notable features derived by observation of the temporal waveforms were: (1) There was a lengthening of the latency of N2 and P2 c o m p o n e n t s as the azotemic period came to an end. (2) Approximately 3 months were required for VECPs to assume a stable waveshape after changing from A to D1 and from D1 to D2. (3) During D1, amplitudes increased and an alpha-like 'ringing' was clearly observable in the last 250 msec of the 500 msec averaging period which was n o t seen in the A or D2 period. (4) In the 3 samples in the D2+ the VECP waveshapes assumed an unusual configuration, unlike any waveform observed in the other 26 VECPs recorded. Fig. 6 summarizes the latency and amplitude changes for averaged values in the first 3 treatment periods. Latency and amplitude values are n o t shown during D2 ÷ because of the difficulty of establishing recognizable wave components. Average latencies are longest in azotemia, reduced during D1 and increased in D2. Amplitudes varied inversely 220-
A
200
DI
02
P2
latency
MSec 180,
160
MSec I001
'5t I0
5
Azotemia-dialysis-transplant A unique set of data (n = 13) was recorded over a 1-year period from a 41-year-old female who made the transition from azotemia to dialysis and finally to a successful transplant. The period between D and T was, however, complicated by a rejection episode lasting approximately one week. After steroid treatment and immunosuppressive therapy the renal allograft was accepted and the patient's comparative clinical health dramatically improved. Fig. 7 shows the VECPs recorded across a 1-year period. The primary change in the waveforms is the increased latency during the rejection episode. Fig. 8 shows the latencies of N2 as a function of time. After acceptance of the kidney, a continual decrease in latency is clearly observable. The results obtained with the VECP for this patient closely mirror the results obtained by analysis of the EEG (Bourne et al. 1975). The most notable difference between EEG and VECP changes is that the time required for the VECP to normalize or reach a baseline is much longer than the EEG. Amounts of slow wave power in the EEG returned to baseline almost immediately after the patient's rejection episode was completed. In contrast, for the VECP, a stable baseline was not reached for a b o u t 3 months.
N2 latency
80 J
juv
with the latencies in the A-D1-D2 periods. Such variations in amplitude were rarely observed in most patients. An additional anomolous feature of this set of data is the disappearance of P2 during the D2 ÷ treatment period. The disappearance of components in the VECP waveform is observed infrequently in stable dialysis patients.
~--
N2 - P2
amplitude
Fig. 6. Latency and amplitude changes for A-D1-D2 treatment program.
Correlation with other variables in azotemia Twelve azotemic patients were studied who conformed to t w o criteria: (1) each patient had a minimum of three testing batteries (including blood chemistries, VECP, EEG and behavioral tests) during their azotemic period and (2) their clinical condition progressed toward the need for dialysis therapy as revealed
T R A N S I E N T VECPs IN R E N A L F A I L U R E
613
89
I,I 1.74 3 5.74 4..74
~
~
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TRANSPLANT
4.2,74 4.3,74 4.4.74 4,5.74
4.8.74 4.2:5.74
5,7.74 6,11.74 8.27.74 I. 16.75
Fig. 7. VECPs r e c o r d e d f r o m a p a t i e n t w h o received a k i d n e y t r a n s p l a n t .
95
85
80 _J
75 70.
.
.
OAN FEB-MAR APR
i
.
.
.
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.
MAY JUNE JULY AUG SEP
i
i
OCT NOV DEC
Fig. 8. Latency of N 2 of VECPs recorded from the transplant patient as a function of time.
614
B. H A M E L E T A L .
TABLE I PPM a n d PCC f o r N 2 l a t e n c i e s w i t h o t h e r m e a s u r e d v a r i a b l e s
PCC w i t h VECP latency
Correlation with VECP latency
BUN
Creat
K
Ca
PO4
N.S.
R = 0.33 d.f. = 30 P < 0.05
R = 0.37 d.f. = 27 P < 0.05
R = 0.26 d.f. = 23 P < 0.05
R = 0.26 d.f. = 24 P < 0.1 N.S.
R = 0.62 N = 12 P < 0.03
N.S.
N.S.
N.S.
N.S.
in reductions in their estimated creatinine clearances. Examination of correlations between variables in the azotemic period was selected as an analysis technique because of the continual progression of patients toward an eventual need for dialysis therapy. The fundamental hypothesis was that a concomitant progression in the measured variables could be more easily interrelated if intervening dialysis therapy, which would rapidly normalize the blood chemistries, was not a part of a patient's treatment program. Table I shows the results of correlation analysis between the latencies of N2 and each of the other variables measured by the two correlational techniques described earlier. Two variables, the BUN and the EEG percentage power 3--7/3--13 were significantly correlated with VECP latency using the PPM correlation but n o t significantly correlated using the pooled covariance correlation (PCC). Three chemistry measures, creatinine, calcium and potassium, positively correlated with VECP latency for the PCC but were insignificantly correlated using the PPM. One behavioral test, the CMT, negatively correlated with the VECP in the PCC calculation.
Discussion
As a renal patient's comparative clinical health deteriorates, the latencies of the major components of the VECP, elicited by a strobe stimulus, become longer. The relationship of
EEG
CRT
CMT
N.S.
N.S.
R = -0.37 d.f. = 22 P < 0.05
R = 0.67 N = 12 P < 0.02
N.S.
N.S.
this finding to clinical health is largely inferential since the only other available direct objective measures are the EEG, blood chemistries, behavioral tests and quantitative information about the time course of the patient's clinical history. However, the differences in these measures (1) between patients in different clinical groups and (2) the clear ipsative changes in data collected from patients who temporally progress across groups, offer compelling evidence that this retinocortical measure is indeed directly influenced by uremic toxicity. In agreement with other investigators (e.g., Hyman and Kooi 1969) our results rarely revealed significant amplitude changes and frequently showed significant latency variations. Presumably, increased latencies are an outward manifestation of, as yet, u n k n o w n neurotoxins affecting transsynaptic and axonal transmission of signals provoked at the retinal level by the strobe stimulus. Concomitance of amplitude invariance and latency variability may indicate that information c o n t e n t in signals in the retino-cortical pathway is simply delayed by neurotoxicity. If one considers the slowing of reaction times, mental sluggishness and other outward behavioral manifestations of renal encephalopathy (Teschan 1975), it is plausible to suggest the increased latency measures provide a similar parallel assessment. Slow-wave-related activity in the EEG (Bourne et al. 1975) increases as a patient's clinical condition deteriorates. It is not surprising that as this activity increases, longer
TRANSIENT VECPs IN RENAL FAILURE VECP latencies are also observed. However, one result that could n o t be predicted in advance was that there were differences in the rates of change of these t w o variables as patients moved from one treatment to another. After a change from one clinical state to another (e.g., A--D) the EEG would rapidly normalize within a few weeks. In contrast, the VECP latency required months to reach a baseline. The results of comparison of changes in VECP latency with other variables in the azotemic period reveal interesting intervariable characteristics. The pooled covariance correlation indicates that there is a significant interrelationship between latency values and creatinine, calcium and potassium measures which is insignificant using the Pearson p r o d u c t m o m e n t correlation. Also, BUN and EEG percentage p o w e r 3-7/3-13 are significantly correlated with latency using the PPM b u t n o t with the PCC. The significance of these findings lies in the character of the data that is interrelated. The three measures, creatinine, calcium and potassium move in a very restricted range for individual patients. Intersubject differences for VECP latencies are large and within subject variability is small. Thus, large intersubject differences tend to mask within subject changes and produce an insignificant PPM. Removing intersubject variability by use of the PCC reveals the overall correlation for the group based only on individual changes. In contrast to the variability of creatinine and potassium, BUN and EEG measures are relatively labile and vary much more rapidly than the VECP latency. Thus, individual correlations using the PCC are insignificant because of the vastly different time constants of these sets of variables. Yet, the gross characteristics of the group data taken together reveal a significant correlation. This result simply means that, for the group, when high values of BUN and EEG percent p o w e r are present, large latencies should be expected and that the time course of changes between variables across the azotemic period differ greatly resulting in an
615 insignificant pooled covariance correlation. Although the EEG and the VECP latency have been shown to correlate directly with renal failure, both measures have special attributes. For example, the EEG responds rapidly to clinical changes b u t is occasionally difficult to analyze correctly because of artifactual data and sleep-related slow-wave activity. In contrast, the VECP, although less labile than the EEG, is influenced only moderately by artifacts and sleep. EEGs with little organized activity of biological origin (so-called 'flat' EEGs) cannot be computer analyzed while VECPs recorded from patients without large amplitude EEGs are usually quite simple to analyze. Without severe clinical perturbation, the VECP latency remains almost completely stable over the course of many months and can be repeatedly measured with little variability. In contrast, EEG measures of slow-wave-related activity (e.g., 3--7 c/sec / 3--13 c/sec; Bourne et al. 1975) fluctuate modestly in stable patients and normal subjects. Thus, the EEG and VECP latency measures appear to provide overlapping yet complementary measures of nervous system function in renal failure. Perhaps neither by itself is entirely sufficient to provide a reliable estimate of the presence of nervous system dysfunction. Together, however, and in combination with other concomitantly measured variables, a more complete picture of the relationship of nervous system impairment to renal dysfunction can be obtained. On-going research is currently investigating such intervariable relationships. In summary, there is little d o u b t that renal insufficiency produces neurotoxins that, in turn, produce detectable manifestations of nervous system dysfunction in the evoked potential and in other nervous system and behavioral measures. The VECP is only one of a possible universe of measures that m a y provide quantitative information a b o u t the degree of renal insufficiency. It is, however, a reliable, repeatable, and accessible measure which is relatively simple to analyze. As such,
616
it m a y prove to be a useful tool for routine evaluation of nervous system function in patients with renal failure.
Summary Transient visually evoked cortical potentials (VECPs) were recorded from patients with renal disease. Changes in VECP latencies are described for undialyzed patients, patients receiving dialysis therapy, and patients who received kidney transplants. Characteristics of VECP latencies in these patient groups as well as examples of changes in latency values with respect to time for two individual patients are examined. The basic overall finding is that the VECP latencies increase as a patient's clinical condition deteriorates and normalize as the condition improves.
Rdsumd
Potentiels $voqu$s visuels corticaux dans la deficience r~nale: potentiels transitoires Des potentiels dvoquds visuels corticaux transitoires (VECPs) ont dtd enregistrds chez des malades prdsentant des affections rdnales. Des modifications de latences du V E C P sont ddcrites chez les malades non-dialysds, les malades sous thdrapeutique par dialyse et les malades qui reqoivent des greffes rdnales. Les caractdristiques des latences du V E C P chez ces groupes de malade ainsi que des exemples de modification des valeurs de latence en fonction du temps chez deux malades individuels sont dtudids. La donnde de base globale est que les latences du V E C P augmentent au fur et fi mesure que la condition clinique du malade se ddtdriore et se normalise lorsque la situation s'amdliore.
The authors wish to thank Mr. James Folk for his essential role in collection of the data.
B. HAMEL ET AL.
References Bourne, J.R., Ward, J.W., Teschan, P.E., Musso, M., Johnston, H.B. and Ginn, H.E. Quantitative assessment of the electroencephalogram in renal disease. Electroenceph. clin. Neurophysiol., 1975, 39: 377--388. Cockcroft, D.W. and Gault, M . H . Prediction of creatinine clearance from Serum Creatinine. Nephron, 1976, 16: 31--41. DECUS, Digital Equipment Corporation, Daquan user's manual, Maynard, Massachusetts, 1971. Ginn, H.E., Teschan, P.E., Walker, P.J., Bourne, J.R., Fristoe, M., Ward, J.W., McClain, L.W., Johnston, H.B. and Hamel, B. Neurotoxicity in Uremia. Kidney International, 1975, 7: $357--$360. Hyman, P.R. and Kooi, K.A. Visually evoked cortical responses in renal insufficiency. Univ. Mich. Med. Centr. J., 1969, 35: 177--179. Kennedy, A.C., Linton, A.I., Luke, R.G. and Renfrew, S. Electroencephalographic changes during hemodialysis, Lancet, 1963, 1: 408--411. Kiley, J.E. and Hines, O. EEG evaluation of uremia. Proc. 2nd Int'l Cong. of Nephrology, 1964, 745-747. Kiley, J.E. and Hines, O. Electroencephalographic evaluation of uremia: Wave frequency evaluation of 40 uremic patients. Arch. Int. Med., 1965, 116: 67--73. Kirk, E. Roger. Experimental Design: Procedures for the behavioral sciences. Brooks/Cole Publishing Company, Belmont, California, 1968. Klingler, M., EEG observations in uremia. Electroenceph, clin. Neurophysiol. 1954, 6: 519. Kooi, K.A. and Bagchi, B.K. Visual evoked responses in man: Normative data. Ann. N.Y. Acad. Sci., 1964, 112: 254--269. Locke, S., Merrill, J.P. and Tyler, H.R. Neurologic complications of acute uremia. Amer. Med. Assoc. Arch. Int. Med., 1961, 108: 519. Perry, N.W. and Childers, D.G. The human visual evoked response: Method and theory. Charles C. Thomas, Springfield, Ill., 1969. Regan, D. Evoked Potentials in Psychology. Sensory Psychology and Clinical Medicine, Wiley-Interscience, New York, 1972. Teschan, P.E. Electroencephalographic and other neurophysiological abnormalities in uremia. Kidney International 1975, 7: $210--216. Tyler, H.R. Neurological complications of dialysis, transplantation, and other forms of treatment in chronic uremia. Neurology, 1965 15: 1081. Tyler, H.R., Neurlogic disorders in renal failure. Amer. J. Med., 1968, 44: 734--738. Watson, C.W., Marcus, E., Bowker, R. and Davidson, S. The "Photomyoclonic Response" as one manifestation of Uremia, observations of uremic man and cat. Electroenceph. clin. Neurophysiol., 1958, 10: 364.
Electroencephalography and Clinical Neurophysiology, 1978, 44:606--616
© Elsevier]North-Holland Scientific Publishers Ltd.
V I S U A L L Y E V O K E D C O R T I C A L P O T E N T I A L S IN R E N A L F A I L U R E : TRANSIENT POTENTIALS* B. HAMEL, J.R. BOURNE, J.W. WARD and P.E. TESCHAN School of Engineering, School of Medicine, Vanderbilt University, Nashville, Tenn 37235 (U.S.A.)
(Accepted for publication: October 10, 1977)
Although increased slow wave activity in the EEG is a well-known correlate of advancing renal failure (Locke et al. 1961; Kennedy et al. 1963; Kiley and Hines 1964, 1965; Bourne et al. 1975), there have been few investigations of how evoked activity in the EEG is modified by uremia. Evoked cortical potentials can be elicited by virtually all types of sensory stimuli ranging from tactile to visual. Of these, the visually evoked cortical potentials (VECPs) elicited by photic stimulation of uremic patients have been most frequently studied (Watson et al. 1958; Tyler 1965; 1968). These investigations have arisen naturally because photic stimulation is often a part of the full clinical EEG. Photic stimulation at slow rates (e.g., 1 flash/sec) produces evoked potentials c o m m o n l y referred to as transient VECPs. The relatively small amplitude of such potentials often necessitates the use of signal averaging techniques to extract the transient VECP from the background EEG (Regan 1972; Perry and Childers 1969). Two studies have reported changes in the transient VECP during renal failure. Klingler (1954), described exaggerated high amplitude VECPs elicited by photic stimulation of patients with severe uremic encephalopathy. As the stimulus rate was increased from 1 to * This work was supported, in part, by NSF Grant ENG 74-04188. Data used in the study were supplied from contractual work conducted under the aegis of NIH-NIAMDD Contract NO1-AM-22211.
5 flashes/sec the response amplitude decreased and above 10 flashes/sec no response could be observed. More recently, H y m a n and Kooi (1969) reported the results of random photic stimulation at low average frequencies on VECPs recorded from seven azotemic patients. For this population, the latencies of 5 major peaks in the averaged VECP were found to be significantly longer than those in a normal test population (Kooi and Bagchi, 1964) while there was no significant change in the amplitude of any peak.
Method Patients
A total of 129 patients have been studied over a 4-year period. Of these, data from 90 were collected for periods ranging from 6 months to 4 years. Patients in three main groups were studied: (1) Data were collected from 49 patients not on dialysis therapy (referred to as azotemic) with varying degrees of renal failure and serum creatinine concentrations ranging from 2 to 29 mg/100 ml. Of the 49 patients who were initially azotemic, 29 switched to routine dialysis therapy during the course of the study. (2) Thirty-six patients who were on dialysis treatment on entry into the program were studied and (3) data were recorded from 20 patients with kidney transplants of which 15 received the transplants during the study. Seven of these transplant patients were from the initially dialyzed group while 8 were from the initially azotemic
TRANSIENT VECPs IN RENAL FAILURE group. Patients were normally distributed in age and education. Ages ranged from 15 to 69 while the n u m b e r of years of education ranged from 3 to 18. For purposes of control, 41 normal subjects were tested using the same testing regimen as the patient population. Ages ranged from 13 to 65 and the number of years of education ranged from 6 to 20.
607 of the positive and negative peaks in the averaged waveforms were c o m p u t e d and printed out using standard programs (DECUS 1971). Each peak latency was identified by standard symbols, e.g., N1, N2, N3, etc., P1, P2, P3, etc. for negative and positive peak latencies respectively (Perry and Childers 1969).
Other variables recorded VECP recording and analysis procedures Transient evoked potentials were recorded as part of a battery of neurobehavioral tests which included the EEG (Bourne et al. 1975) and a number of reaction-time based tests (Ginn et al. 1975). For both the EEG and VECP recordings, scalp electrodes were located at F3, P3 and O1 of the International 10-20 system. Bipolar recordings between F3 and P3, P3 and O1 were obtained as well as monopolar recordings from each of the three electrodes referred to the left mastoid. The right ear was used as ground. VECP data described in this paper were recorded from the occipital bipolar channel P3 to O1. The 5 EEG channels were recorded on both an 8-channel Grass Model 6 electroencephalograph and a Honeywell 5600 magnetic tape recorder. A timing channel from the stimulus was recorded on a sixth channel. A Grass Model PS-22 x e n o n strobe was placed 12 inches in f r o n t of the closed eyes of the patient who was seated upright and instructed to avoid head or eye movements. Photic stimulation was delivered at an intensity of 16 for 100 sec at a rate of 1 flash/sec. Patients were not tested if they had less than 2/3 of their normal a m o u n t of sleep on the night prior to testing. Thus, in most cases, patient drowsiness did n o t influence VECP recordings. Records with visually evident artifacts were deleted from the data analyzed. Quantification of the VECPs elicited by the strobe stimulus was entirely conventional. Signal averaging of 500 msec. EEG epochs following each flash was accomplished using a Digital Equipment Corporation Lab 8/e minicomputer. The latencies and amplitudes
In addition to the VECP, three main groups of variables were collected: (1) blood chemistries, (2) cognitive function tests and (3) the a m o u n t of slow wave power in the resting EEG. Detailed descriptions of changes in these variables appear elsewhere (Ginn et al. 1975, Bourne et al. 1975). The blood chemistries measured were: blood urea nitrogen (BUN), creatinine, potassium, calcium and phosphates. An estimate of creatinine clearance was made by the formula: C R Clearance (ml/min)=
(140 --- Age in Years) X Weight in kg 72 X Serum Ca (ml/100 ml) attributed to Cockcroft and Gault (1976) who found an 82% correlation between estimated creatinine clearance and actual 24-h clearance measurements. While serum creatinine provides a simpler approximation of renal excretory failure, the estimate of clearance based on additional weight and age information may provide an even better index since the wide anthropometric attributes and ages of the patients studied may be taken into account. Two cognitive function measures, the choice reaction time (CRT) and the continuous m e m o r y test (CMT) were employed (Ginn et al. 1975). In brief, the CRT is a reaction time measure in which the patient presses buttons corresponding to the color of a series of randomly presented colored lights and the CMT is a m e m o r y task requiring the patient to indicate if words presented are contained in a previously presented list.
608 Slowing of the resting EEG was measured by a ratio of the power in the 3--7 c/sec bandwidth divided b y the p o w e r in the 3--13 c/sec bandwidth, {Bourne et al. 1975).
Analysis o f the data Intergroup analysis of VECP latencies was c o n d u c t e d b y use of analysis of variance (ANOVA) methods with Duncan's ~ posteriori multiple comparisons (Kirk 1968) to compare the significance of intergroup mean differences. Correlational analyses were carried o u t by two methods: (1) Pearson p r o d u c t m o m e n t (PPM) correlations in which test values obtained during each patient's azotemic period were averaged and (2) Pooled covariance analysis (Kirk 1968) in which the correlation was derived from the pooled covariance of all individuals. The latter method deemphasizes any irrelevant betweensubject-differences. While the first analysis shows correlation across the group, the second reveals correlation between changes in an individual's data as the disease progresses. Results
The data obtained in this study are described in five main sections: (1) Normative differences between VECP latencies recorded from (a) normals, (b) patients with high and low levels of creatinine concentration in the azotemic period, (c} dialyzed patients and (d) patients who received transplants are examined via an analysis of variance. (2) Variations in VECP latency and estimated creatinine clearance are described for patients with varying degrees of renal failure in their azotemic period. (3) Individual VECP changes during azotemia to dialysis and dialysis to transplant transitions are presented. (4) VECP latency changes in t w o patients are described. One patient moved from a regular dialysis schedule to a reduced dialysis regimen. The second patient received a transplant after progressing from azotemia to dialysis. (5) Finally, correlations of VECP latency changes
B. HAMEL ET AL. with other variables are presented. Variations in the latency of N2, the second negative peak in the VECP waveform obtained from P3-O1, were used as primary descriptors of VECP changes. Other latencies were measured and changes compared with N2. A general finding was that the latency values moved together, i.e., all would concomitantly increase or decrease as a function of the clinical progress of the patient. In most cases there were insignificant changes in amplitude. One case in which a small amplitude change did occur is discussed in the description of the effect of reduced dialysis.
Normative comparisons Fig. 1 displays the group differences between means of latencies recorded from normals, high and low azotemics, dialyzed patients and patients who received a transplant. The differences in latency values between the 5 groups closely mirror the clinical results one might expect as a patient progresses across the range of five possible clinical phases. Latencies become, on the average, longer than normal in low azotemia, increase to a maximum during high azotemia, decrease with the onset of dialysis therapy and return to more normal levels in the post transplant period. While the variation in latency is small and the variability moderately large because of individual differences, intergroup differences are statistically significant between the groups as shown in the table below the histogram in Fig. 1. Duncan's posteriori multiple comparisons (Kirk 1968) of the group data revealed significant differences between the normal, low azotemic, dialyzed and transplant groups with respect to the high azotemic population and between the dialyzed patients and the normal population. Azotemia As patients progress through the nondialyzed or azotemic period of renal disease, residual renal function gradually declines. Transition from the azotemic period to a
T R A N S I E N T VECPs IN R E N A L F A I L U R E
NORMALS
mean 59,87 s,d. I 1.08
n=16
NORMALS
NORMALS AZOTEMICS LOW
---
609
AZOTEMICS AZOTEMICS HIGH LOW mean 66.18 s.d. 16.97 n=9
mean 83,92 s.d. 22.94 n=ll
DIAL¥SED PATIENTS
POST "RANSPLAN PATIENTS
mean 72,39 s.d. 15.36 n=45
milan 67.46 s,d.
15.72 n=17
AZOTEMICS AZOTEMICS DIALYSED POST LOW HIGH PATIENTS TRANSPLAN1
N.S.
P < .01
P < .05
N.S.
P < .05
N.S.
N.S.
P < .05
P < .05
AZOTEMICS HIGH DIALYSED PATIENTS
N.S.
POST TRANSPLANTS
Fig. 1. Average Group VECP latencies for 4 patient categories and a normal group. Results of Duncan's a-posteriori multiple comparisons are shown below the histogram.
regular dialysis treatment regimen is usually dictated by appearance of clinical uremic symptoms, usually associated with serum creatinine concentration above 10 mg/ml and by inference, values of creatinine clearance below 10 and often below 5 ml/min. The continual long-term deterioration in a patient's clinical well-being (often months or years) during azotemia offers a unique opportunity to observe concomitant long term changes in objective measures. Fig. 2 displays increases in VECP latency values for 12 patients between the onset of VECP measurement in the azotemia period until just prior to changing to dialysis therapy. Estimates of the creatinine clearance are shown at the b o t t o m of this graph. The
visually evident general increases and decreases of the two measures were confirmed statistically by computing the trends on all data collected between the initial and final points shown in Fig. 2. Each of the patients contributed between 3 and 9 VECP latency and clearance values. A significant upward trend (P < 0.001) was found in the VECP latencies using regression analysis and a similar downward trend was observed (P < 0.001) in the estimated clearance measures. A z o t e m i a to dialysis and dialysis to transplant A--D. The azotemia-to-dialysis transition was investigated by selecting patients who had a minimum of three points in the azotemic
B. HAMEL ET AL.
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(A) period and in the dialysis (D) period. Data collected from the five patients who provided this minimal n u m b e r of points in each period are shown in Fig. 3. Each point in the A period represents the average of the patient's last three measurements before he began dialysis therapy, and each point in the D period represents his average latency in the D period. The number of measurements in the D period is indicated in the figure. In addition to the
visual evidence of a decrease in latency from A to D, a two way least squares ANOVA revealed statistically significant differences (P < 0.001) between the t w o groups. The ANOVA also showed that the between-subject variation was as great as the between-treatment variation. D--T. A similar analysis was conducted for a dialysis to transplant group of patients with the results shown in Fig. 4. A clearly signifi-
TRANSIENT VECPs IN R E N A L F A I L U R E
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cant decrease in latency (P < 0.001) was found for the 6 patients studied. As in the A--D group, significant interpatient differences were found. The next two sections describe changes in VECPs in two individual patients from whom data was collected in several different treatment regimens.
Averaged VECPs were recorded from a 59-year-old female patient with chronic renal failure during her azotemic and dialysis periods. During the first dialysis period she was on a 3 dialyses/week treatment regimen (D1). She was switched to a 2/week treatment program (D2) on February 14th, 1976 and on August 1st, 1976 the number of dialysis h/week was increased by 55.6% while retaining the 2/week frequency (D2+). During the 3/week dialysis period she had a total of 2711 ml/week/1 creatinine clearance, 1928 ml/week/1 during reduced dialysis and 3000 ml/week/1 during the increased time period (D2+). Twenty-nine VECPs were collected over a 2-year period at approximately monthly intervals with additional tests near treatment transition times. Fig. 5 displays VECPs selected
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week; D2, 2 dialyses/week; D2*, 2 dialyses/week with increased dialysis time.
612
B. HAMEL ET AL.
from the mid-point of each period. Other VECPs during the same period were similar in waveshape. The notable features derived by observation of the temporal waveforms were: (1) There was a lengthening of the latency of N2 and P2 c o m p o n e n t s as the azotemic period came to an end. (2) Approximately 3 months were required for VECPs to assume a stable waveshape after changing from A to D1 and from D1 to D2. (3) During D1, amplitudes increased and an alpha-like 'ringing' was clearly observable in the last 250 msec of the 500 msec averaging period which was n o t seen in the A or D2 period. (4) In the 3 samples in the D2+ the VECP waveshapes assumed an unusual configuration, unlike any waveform observed in the other 26 VECPs recorded. Fig. 6 summarizes the latency and amplitude changes for averaged values in the first 3 treatment periods. Latency and amplitude values are n o t shown during D2 ÷ because of the difficulty of establishing recognizable wave components. Average latencies are longest in azotemia, reduced during D1 and increased in D2. Amplitudes varied inversely 220-
A
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DI
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latency
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160
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Azotemia-dialysis-transplant A unique set of data (n = 13) was recorded over a 1-year period from a 41-year-old female who made the transition from azotemia to dialysis and finally to a successful transplant. The period between D and T was, however, complicated by a rejection episode lasting approximately one week. After steroid treatment and immunosuppressive therapy the renal allograft was accepted and the patient's comparative clinical health dramatically improved. Fig. 7 shows the VECPs recorded across a 1-year period. The primary change in the waveforms is the increased latency during the rejection episode. Fig. 8 shows the latencies of N2 as a function of time. After acceptance of the kidney, a continual decrease in latency is clearly observable. The results obtained with the VECP for this patient closely mirror the results obtained by analysis of the EEG (Bourne et al. 1975). The most notable difference between EEG and VECP changes is that the time required for the VECP to normalize or reach a baseline is much longer than the EEG. Amounts of slow wave power in the EEG returned to baseline almost immediately after the patient's rejection episode was completed. In contrast, for the VECP, a stable baseline was not reached for a b o u t 3 months.
N2 latency
80 J
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with the latencies in the A-D1-D2 periods. Such variations in amplitude were rarely observed in most patients. An additional anomolous feature of this set of data is the disappearance of P2 during the D2 ÷ treatment period. The disappearance of components in the VECP waveform is observed infrequently in stable dialysis patients.
~--
N2 - P2
amplitude
Fig. 6. Latency and amplitude changes for A-D1-D2 treatment program.
Correlation with other variables in azotemia Twelve azotemic patients were studied who conformed to t w o criteria: (1) each patient had a minimum of three testing batteries (including blood chemistries, VECP, EEG and behavioral tests) during their azotemic period and (2) their clinical condition progressed toward the need for dialysis therapy as revealed
T R A N S I E N T VECPs IN R E N A L F A I L U R E
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Fig. 7. VECPs r e c o r d e d f r o m a p a t i e n t w h o received a k i d n e y t r a n s p l a n t .
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Fig. 8. Latency of N 2 of VECPs recorded from the transplant patient as a function of time.
614
B. H A M E L E T A L .
TABLE I PPM a n d PCC f o r N 2 l a t e n c i e s w i t h o t h e r m e a s u r e d v a r i a b l e s
PCC w i t h VECP latency
Correlation with VECP latency
BUN
Creat
K
Ca
PO4
N.S.
R = 0.33 d.f. = 30 P < 0.05
R = 0.37 d.f. = 27 P < 0.05
R = 0.26 d.f. = 23 P < 0.05
R = 0.26 d.f. = 24 P < 0.1 N.S.
R = 0.62 N = 12 P < 0.03
N.S.
N.S.
N.S.
N.S.
in reductions in their estimated creatinine clearances. Examination of correlations between variables in the azotemic period was selected as an analysis technique because of the continual progression of patients toward an eventual need for dialysis therapy. The fundamental hypothesis was that a concomitant progression in the measured variables could be more easily interrelated if intervening dialysis therapy, which would rapidly normalize the blood chemistries, was not a part of a patient's treatment program. Table I shows the results of correlation analysis between the latencies of N2 and each of the other variables measured by the two correlational techniques described earlier. Two variables, the BUN and the EEG percentage power 3--7/3--13 were significantly correlated with VECP latency using the PPM correlation but n o t significantly correlated using the pooled covariance correlation (PCC). Three chemistry measures, creatinine, calcium and potassium, positively correlated with VECP latency for the PCC but were insignificantly correlated using the PPM. One behavioral test, the CMT, negatively correlated with the VECP in the PCC calculation.
Discussion
As a renal patient's comparative clinical health deteriorates, the latencies of the major components of the VECP, elicited by a strobe stimulus, become longer. The relationship of
EEG
CRT
CMT
N.S.
N.S.
R = -0.37 d.f. = 22 P < 0.05
R = 0.67 N = 12 P < 0.02
N.S.
N.S.
this finding to clinical health is largely inferential since the only other available direct objective measures are the EEG, blood chemistries, behavioral tests and quantitative information about the time course of the patient's clinical history. However, the differences in these measures (1) between patients in different clinical groups and (2) the clear ipsative changes in data collected from patients who temporally progress across groups, offer compelling evidence that this retinocortical measure is indeed directly influenced by uremic toxicity. In agreement with other investigators (e.g., Hyman and Kooi 1969) our results rarely revealed significant amplitude changes and frequently showed significant latency variations. Presumably, increased latencies are an outward manifestation of, as yet, u n k n o w n neurotoxins affecting transsynaptic and axonal transmission of signals provoked at the retinal level by the strobe stimulus. Concomitance of amplitude invariance and latency variability may indicate that information c o n t e n t in signals in the retino-cortical pathway is simply delayed by neurotoxicity. If one considers the slowing of reaction times, mental sluggishness and other outward behavioral manifestations of renal encephalopathy (Teschan 1975), it is plausible to suggest the increased latency measures provide a similar parallel assessment. Slow-wave-related activity in the EEG (Bourne et al. 1975) increases as a patient's clinical condition deteriorates. It is not surprising that as this activity increases, longer
TRANSIENT VECPs IN RENAL FAILURE VECP latencies are also observed. However, one result that could n o t be predicted in advance was that there were differences in the rates of change of these t w o variables as patients moved from one treatment to another. After a change from one clinical state to another (e.g., A--D) the EEG would rapidly normalize within a few weeks. In contrast, the VECP latency required months to reach a baseline. The results of comparison of changes in VECP latency with other variables in the azotemic period reveal interesting intervariable characteristics. The pooled covariance correlation indicates that there is a significant interrelationship between latency values and creatinine, calcium and potassium measures which is insignificant using the Pearson p r o d u c t m o m e n t correlation. Also, BUN and EEG percentage p o w e r 3-7/3-13 are significantly correlated with latency using the PPM b u t n o t with the PCC. The significance of these findings lies in the character of the data that is interrelated. The three measures, creatinine, calcium and potassium move in a very restricted range for individual patients. Intersubject differences for VECP latencies are large and within subject variability is small. Thus, large intersubject differences tend to mask within subject changes and produce an insignificant PPM. Removing intersubject variability by use of the PCC reveals the overall correlation for the group based only on individual changes. In contrast to the variability of creatinine and potassium, BUN and EEG measures are relatively labile and vary much more rapidly than the VECP latency. Thus, individual correlations using the PCC are insignificant because of the vastly different time constants of these sets of variables. Yet, the gross characteristics of the group data taken together reveal a significant correlation. This result simply means that, for the group, when high values of BUN and EEG percent p o w e r are present, large latencies should be expected and that the time course of changes between variables across the azotemic period differ greatly resulting in an
615 insignificant pooled covariance correlation. Although the EEG and the VECP latency have been shown to correlate directly with renal failure, both measures have special attributes. For example, the EEG responds rapidly to clinical changes b u t is occasionally difficult to analyze correctly because of artifactual data and sleep-related slow-wave activity. In contrast, the VECP, although less labile than the EEG, is influenced only moderately by artifacts and sleep. EEGs with little organized activity of biological origin (so-called 'flat' EEGs) cannot be computer analyzed while VECPs recorded from patients without large amplitude EEGs are usually quite simple to analyze. Without severe clinical perturbation, the VECP latency remains almost completely stable over the course of many months and can be repeatedly measured with little variability. In contrast, EEG measures of slow-wave-related activity (e.g., 3--7 c/sec / 3--13 c/sec; Bourne et al. 1975) fluctuate modestly in stable patients and normal subjects. Thus, the EEG and VECP latency measures appear to provide overlapping yet complementary measures of nervous system function in renal failure. Perhaps neither by itself is entirely sufficient to provide a reliable estimate of the presence of nervous system dysfunction. Together, however, and in combination with other concomitantly measured variables, a more complete picture of the relationship of nervous system impairment to renal dysfunction can be obtained. On-going research is currently investigating such intervariable relationships. In summary, there is little d o u b t that renal insufficiency produces neurotoxins that, in turn, produce detectable manifestations of nervous system dysfunction in the evoked potential and in other nervous system and behavioral measures. The VECP is only one of a possible universe of measures that m a y provide quantitative information a b o u t the degree of renal insufficiency. It is, however, a reliable, repeatable, and accessible measure which is relatively simple to analyze. As such,
616
it m a y prove to be a useful tool for routine evaluation of nervous system function in patients with renal failure.
Summary Transient visually evoked cortical potentials (VECPs) were recorded from patients with renal disease. Changes in VECP latencies are described for undialyzed patients, patients receiving dialysis therapy, and patients who received kidney transplants. Characteristics of VECP latencies in these patient groups as well as examples of changes in latency values with respect to time for two individual patients are examined. The basic overall finding is that the VECP latencies increase as a patient's clinical condition deteriorates and normalize as the condition improves.
Rdsumd
Potentiels $voqu$s visuels corticaux dans la deficience r~nale: potentiels transitoires Des potentiels dvoquds visuels corticaux transitoires (VECPs) ont dtd enregistrds chez des malades prdsentant des affections rdnales. Des modifications de latences du V E C P sont ddcrites chez les malades non-dialysds, les malades sous thdrapeutique par dialyse et les malades qui reqoivent des greffes rdnales. Les caractdristiques des latences du V E C P chez ces groupes de malade ainsi que des exemples de modification des valeurs de latence en fonction du temps chez deux malades individuels sont dtudids. La donnde de base globale est que les latences du V E C P augmentent au fur et fi mesure que la condition clinique du malade se ddtdriore et se normalise lorsque la situation s'amdliore.
The authors wish to thank Mr. James Folk for his essential role in collection of the data.
B. HAMEL ET AL.
References Bourne, J.R., Ward, J.W., Teschan, P.E., Musso, M., Johnston, H.B. and Ginn, H.E. Quantitative assessment of the electroencephalogram in renal disease. Electroenceph. clin. Neurophysiol., 1975, 39: 377--388. Cockcroft, D.W. and Gault, M . H . Prediction of creatinine clearance from Serum Creatinine. Nephron, 1976, 16: 31--41. DECUS, Digital Equipment Corporation, Daquan user's manual, Maynard, Massachusetts, 1971. Ginn, H.E., Teschan, P.E., Walker, P.J., Bourne, J.R., Fristoe, M., Ward, J.W., McClain, L.W., Johnston, H.B. and Hamel, B. Neurotoxicity in Uremia. Kidney International, 1975, 7: $357--$360. Hyman, P.R. and Kooi, K.A. Visually evoked cortical responses in renal insufficiency. Univ. Mich. Med. Centr. J., 1969, 35: 177--179. Kennedy, A.C., Linton, A.I., Luke, R.G. and Renfrew, S. Electroencephalographic changes during hemodialysis, Lancet, 1963, 1: 408--411. Kiley, J.E. and Hines, O. EEG evaluation of uremia. Proc. 2nd Int'l Cong. of Nephrology, 1964, 745-747. Kiley, J.E. and Hines, O. Electroencephalographic evaluation of uremia: Wave frequency evaluation of 40 uremic patients. Arch. Int. Med., 1965, 116: 67--73. Kirk, E. Roger. Experimental Design: Procedures for the behavioral sciences. Brooks/Cole Publishing Company, Belmont, California, 1968. Klingler, M., EEG observations in uremia. Electroenceph, clin. Neurophysiol. 1954, 6: 519. Kooi, K.A. and Bagchi, B.K. Visual evoked responses in man: Normative data. Ann. N.Y. Acad. Sci., 1964, 112: 254--269. Locke, S., Merrill, J.P. and Tyler, H.R. Neurologic complications of acute uremia. Amer. Med. Assoc. Arch. Int. Med., 1961, 108: 519. Perry, N.W. and Childers, D.G. The human visual evoked response: Method and theory. Charles C. Thomas, Springfield, Ill., 1969. Regan, D. Evoked Potentials in Psychology. Sensory Psychology and Clinical Medicine, Wiley-Interscience, New York, 1972. Teschan, P.E. Electroencephalographic and other neurophysiological abnormalities in uremia. Kidney International 1975, 7: $210--216. Tyler, H.R. Neurological complications of dialysis, transplantation, and other forms of treatment in chronic uremia. Neurology, 1965 15: 1081. Tyler, H.R., Neurlogic disorders in renal failure. Amer. J. Med., 1968, 44: 734--738. Watson, C.W., Marcus, E., Bowker, R. and Davidson, S. The "Photomyoclonic Response" as one manifestation of Uremia, observations of uremic man and cat. Electroenceph. clin. Neurophysiol., 1958, 10: 364.
