Electroencephalographic studies in workers exposed to solvents or pesticides

Electroencephalography and clinical Neurophysiology, 82 (1992) 438-444 © 1992 Elsevier Scientific Publishers Ireland, Ltd. 0013-4649/92/$05.00

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E l e c t r o e n c e p h a l o g r a p h i c studies in workers e x p o s e d to solvents or pesticides E.J. Jonkman a, A.V~. De Weerd a, D.C.J. Poortvliet a, R.J. Veldhuizen

a

and H. Emmen b

Westeinde Hospital, The Hague (The Netherlands), and b Medical Biological Laboratory TNO, Rijswijk (The Netherlands (Accepted for publication: 9 November 1991)

Summary The qEEG was studied in groups of young and old workers exposed to solvents (house and industrial painters) and m a group of workers exposed to pesticides. Three methods were used: a quantified visual scoring system, the neurometrics method and a multivariate analysis of mean frequencies. Using the visual assessment as well as the neurometrics method, the older painters showed more abnormalities than the younger painters and the pesticide exposed workers. The "profile" of abnormalities differed in all 3 groups. Changes of the mean spectral frequencies were mainly found in the subjects exposed to pesticides. In this study we concluded that the neurometrics method can be useful in neurotoxicological studies. With this technique minor changes in electrocortical function can be detected in seemingly normal workers. However, frequency parameters should be added to the power measures which are usually studied. Key words: qEEG; Solvents; Pesticides; Neurometrics

The possible neurotoxic effect of exposure to chemicals used in various production processes is an area of growing concern. Due to legal regulations, cases with severe symptoms as a result of heavy exposure are relatively scarce in most Western countries. Nowadays, the main research potential has to be focused on the influence of chronic low-dose exposure on the nervous system. It must be emphasized that for many commonly used chemicals there are no or insufficient data on neurotoxicity in humans while clinical studies are hampered by the fact that the subjective signs resulting from low-dose exposure are often non-specific (e.g., the "organo-psychosyndrome" resulting from exposure to solvents as described by Arlien-Soborg et al. in 1979). Neurological symptoms are sometimes only evident after many years of exposure, at which time the neurotoxic damage may be irreversible. This implies that the development and evaluation of objective noninvasive methods which can detect central nervous system dysfunction at an early stage can be rather important for preventing further neurotoxic damage in the individual worker, for the development of hygienic measures and ultimately for the banning of certain chemicals. Well-known techniques are the application of validated questionnaires and the use of neuropsychological test batteries. In the neurophysiological field the quantitative electroencephalogram (qEEG) and the

Correspondence to: Dr. E.J. Jonkman, Westeinde Hospital, Lijnbaan 32, 2501 CK The Hague (The Netherlands). Tel.: 70-3302005; Fax: 70-3809459.

registration of cortical evoked potentials seem to offer interesting possibilities. In the studies reported here, all methods mentioned above were used but only the results of the qEEG results will be described. Two different groups of neurotoxic agents will be evaluated: organic solvents to which painters are exposed and pesticides used by bulb-growers. According to the literature, results of EEG studies in workers exposed to solvents are not equivocal (Discussion) and E E G data on workers exposed to pesticides are scarce. Therefore, we decided to use the "neurometrics" method (John et al. 1987) for quantification of the E E G (apart from the visual assessment), since in our experience this method is rather sensitive in detecting minor cerebral disturbances (Jonkman et al. 1985). Usually only power and coherence values are used in the neurometric matrix. Since even small frequency changes in the EEG can be of clinical value (Van Huffelen et al. 1984) frequency matrices were constructed in addition to the power/coherence matrices.

Methods

Subjects For this study the qEEG results from 5 groups of subjects were evaluated. From the data of a group of normal Dutch controls (NC; N = 66), equally divided over the age span 20-70 years, the normative values necessary for the neurometric analysis were calculated. The validity of the control group was checked in an

EEG CHANGES DUE TO SOLVENTS OR PESTICIDES independent sample of 28 normals; in this latter group none of the methods decribed below revealed more abnormalities than could be expected by chance. T h e effect of solvents on the q E E G was evaluated in a group of young painters (PY; N = 40) and a group of old painters (PO; N = 42). The effect of pesticides was studied in the q E E G of 62 bulb-growers (BG). The details of these studies, including the epidemiological and neuropsychological data, will be published elsewhere. The exclusion criteria were the same for all 5 groups: a history of epilepsy, cerebral concussion, migraine, any other known CNS affection not related to the neurotoxic substances under study, daily intake of more than 5 units of alcoholic beverages and use of any medication with a known effect on the CNS. All subjects underwent a neurological examination according to a standard protocol. The examination focussed on visual acuity, function of the eye muscles, nystagmus and other signs of cranial nerve dysfunction, dysarthria and aphasia, paresis, gait, coordination and tremor. Included in the young painters group were painters between 30 and 40 years of age. The group of old painters consisted of subjects between 55 and 72 years of age who had been working as house or industrial painters at least from 1965 to 1975. This group included retired as well as still active painters. The bulb-growers (age 30-55) had been working for more than 10 years as such, using pesticides (probably mainly maneb, zineb and captan 1 over this period (Discussion). Because small differences between the q E E G data of men and w o m e n were found in our data base of normal controls, only data from m e n were used in the study and control groups. The m e a n age of the 3 study groups was as follows: PY group 35.9 ___3.0, PO group 63.7 +_ 4.9, B G group 44.6 +_ 6.8. However, since the neurometric analysis takes into account the age regression functions of all calculated parameters, the age differences between the groups are not relevant for the final q E E G findings.

Recording and visual assessment of the EEG E E G recording was done during at least 25 min from all electrodes of the 10-20 system with the subject lying awake in a semi-darkened room (eyes closed). The reactivity to opening of the eyes and sensori-motor stimulation was studied. For computer analysis at least 2 epochs of 60 sec E E G were selected. All parts of the record containing artefacts or any sign of drowsiness were excluded from the computer analysis. Visual scor-

Maneb: maganese-ethylenebisdithiocarbamate; zineb: zinc ethylenebisdithiocarbamate; captan: N-(trichloromethylthio)-4-cyclohexeen-l,2-dicarboximide.

439 ing was done by two experienced electroencephalographers independently, unaware whether an E E G belonged to one of the study groups or to the reference group. The scoring was done for the following items: frequency of the alpha rhythm, reactivity of the alpha rhythm, diffuse amount of continuous slow activity, paroxysmal slow activity, focal slow activity and other transients (sharp waves etc). Each item was scored on a 6-point scale (De W e e r d et al. 1990), ranging from 0 (completely normal) to 5 (very abnormal). Each E E G in which the investigators did not arrive at the same summated value ( T V A = total visual assessment, ranging from 0 to 30), was reviewed by a third investigator and discussed until a common opinion was reached. In the NC group there was no significant correlation between the value of T V A and the age of the subject.

qEEG analysis From the artefact-free E E G samples mentioned above the following derivations were constructed: F 7T 3, Fs-T 4, T3-T5, T4-T6, C3-C z, C4-C z, P3-O1, P4-O2. The power in delta, theta, alpha and beta bands was calculated relative to m e a n total power in all derivations mentioned above excepting the anterior temporal leads. Relative power values were preferred over absolute power values because absolute power values show a rather large interindividual variability. However, when relative power values are calculated as a percentage of the total power in the same derivation a decrease in power in one frequency band necessitates an increase in the other bands. Therefore the power was calculated relative to the total m e a n power because in this way the band values in one derivation are more independent measures than when the band values are expressed as a percentage of the total power in one location, The neurometric approach has been described elsewhere in detail (John et al. 1983, 1987). Briefly: after appropriate transformations, z values are calculated for the relative band power values and coherence values of each subject, using the age-regression equations and standard deviations obtained from the normal controls. Multivariate features (e.g., composites of z values across different p a r a m e t e r s for one lead or composites of the same p a r a m e t e r across different leads) can be computed, taking into account the intercorrelation among the features in each set. The resulting "matrix" consists of 168 values of multivariate and univariate features presented as z values. The same procedure as used for the relative power values was also used for the m e a n frequency measures. For each derivation the mean frequency of the total spectrum was determined as well as the mean frequency for each band separately. The asymmetries of the mean frequencies were also determined. All these frequency measures were z transformed in the same way as the p o w e r / c o h e r e n c e values. Multivariates were

440

E.J. J O N K M A N ET AL.

_

calculated. The resulting matrix of the frequency measures contained 133 "cells." For the power parameters as well as for the frequency parameters the t-test for independent observations was used to evaluate the differences between the mean cell values of the different groups. For the visual assessment score differences with P < 0.05 were considered as significant. Taking into account the number of cells in the neurometrics matrices (168 and 133 for the power and frequency matrix) the mean neurometrics values were only considered as being different from the control values when the z values indicated a significance level of P < 0.01.

Exposure indices For the painters exposure indices were calculated according to Mikkelsen et al. (1988) using data from questionnaires which, if necessary, had been completed on interview. The exposure index was calculated over the last 5 years before the q E E G study as well as over the whole working lives. For the bulb-growers an exposure index was calculated which included factors related to the planting area, the frequency of pesticide application, the different application methods and a correction for protective measurements during the use of pesticides.

,( >

2 -

1 .~3 I I i

i

1 -

PO

PY

8G

Fig. 1. Mean values and S.E.M. of the "total visual assessment score" TVA (the sum of 6 E E G features, each scored on a scale from 0 to 5, see text). PO: old painters; PY: young painters; BG: bulb-growers. Only the TVA value of the PO group is significantly higher (P < 0.05) than the mean value of the normal controls (0.86).

Results

14sual scoring of the EEG and neurological examination The mean values of the TVA scoring for the different groups are depicted in Fig. 1. In the exposed groups the score was highest in the PO group followed by the PY group and the B G group successively. The mean T V A score of the PO group (1.93) was significantly different ( P < 0.05) from the mean score of the NC group (0.81). The increase in mean TVA value in the PO group was almost completely caused by slowing of the dominant occipital rhythmic activity and the occurrence of focal slow activity, mainly in temporal regions. However, this difference between the NC group and the PO group was not reflected in the results of the neurological examination, which were within normal limits for all subjects of all groups. The mean TVA values of the PY and BG group were not significantly different from the NC group. Neurometric measures In previous studies (Jonkman et al. 1985; Veering et al. 1986) of patients with cerebral ischaemia it appeared that some multivariate measures were of special interest. These were: (1) the multivariate value of all relative bandpower values in all frequency bands of all locations (OAF), (2) the multivariate composed of all asymmetry values (OAA), and (3) the multivariate

composed of all coherence values (OAC). The mean group values of these 3 measures and the significance of the differences from the NC group are given in Table I (the multivariate measures of the normal control group having by definition a mean value of 0 and an S.D. of 1). From Table I it appears that, compared to the NC group, only the mean OAF value in the PO group reached the required level of significance. In the groups of young painters and bulb-growers no significant differences from the controls were found. When all the ceils in the matrix were considered (168) it appeared that in the PO group 38 abnormal TABLE I The multivariates O A F ("overall all frequencies"), O A A ("overall all asymmetries") and OAC ("overall all coherences"): mean values and level of significance of the differences with the normal control group. For abbreviations see text. OAF

OAA

OAC

PO

0.53 < 0.005

0.11 ns

0.39 < 0.05

PY

0.12 as

- 0.05 ns

- 0.07 ns

BG

- 0.17 ns

- 0.29 ns

- 0.09 ns

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T A B L E II Overview of the abnormal m e a n values in the groups of old painters (PO), young painters (PY) and bulb-growers (BG). Only differences from the normal controls with a significance of P < 0.01 are indicated. A capital letter is used when the m e a n value is significantly higher than in the controls, lower case when the m e a n value is lower than in the controls. C3-C z Relative delta power Relative theta power Relative alpha power Relative beta power Relative theta + delta All frequencies

PO

C4-C z

T3-Ts

T4-T6

PO

PO po

PO, BG PO PO, BG

PO, BG PO PO, BG

Total power Total power asymmetry

PO

PO

Asymmetry delta power Asymmetry theta power Asymmetry alpha power Asymmetry beta power All asymmetries

bg

Coherence delta band Coherence theta band Coherence alpha band Coherence beta band All coherences

PO

P3-OI

po PO, BG PO PO, PY

po

P4-O2 PO po PO, BG

F7-T 3

Fs-T4

py

py

po

po

PO, PY, BG

PO

Overall

Left

Right

Back

PO

PO PO PO

PO PO PO PO

PO PO

po

BG PO

PY PY

BG PY, BG po PY

PO, BG

mean values (23%) were present. The numbers of abnormal mean values in the PY group and BG group were lower, respectively 8 (5%) and 12 (7%). All measures which were abnormal ( P < 0.01; tested 2-sided for the monovariates, 1-sided for the multivariates) are depicted in Table II. It appears that the old painters group showed in several leads less alpha power and more theta and beta power than the normal controls. It was remarkable that a higher degree of abnormality was detected over the right than over the left hemisphere. The young painters showed another profile: less delta in fronto-temporal leads and in some derivations higher coherences than the normal control group. Apart from a few coherence values, the bulb-growers group differed from the normal controls in the (increased) amount of beta activity in the central and parieto-occipital leads.

Mean frequency measures In the "frequency matrix" the monovariates are the mean frequencies in all power bands and the mean frequencies of the whole spectrum, both determined in all derivations. Composite values (of all measures in one derivation or of the same measure in all derivations) were calculated as described for the "normal" neurometric matrix. A total of 133 frequency measures was obtained for each subject. Using a 1% criterion, 27 abnormal mean values (20%) were found in the PO group as well as in the BG group. Only a small percentage of abnormalities was found in the PY group

(3%). The results of one monovariate measure (the mean frequency of the total spectlum) in all derivations is given in Table III, while a detail of this table is depicted in Fig. 2. The chosen measure is the mean

T A B L E III Differences between the m e a n frequencies of the total spectra of the exposed groups and the normal control group expressed in Hertz. All values are positive, indicating higher m e a n frequencies in the study groups than in the control group. C 3-C z

C 4-C z

T3 "T5

T4-T6

P3-O 1

P4-O 2

PO

0.66 < 0.02

0.66 < 0.01

0.51 ns

0.38 ns

0.05 ns

0.15 ns

F7-T3 0.32 ns

Fs-T4 0.27 ns

PY

0.39 ns

0.23 ns

0.07 as

0.25 ns

0.16 ns

0.13 as

0.47 ns

0.57 ns

BG

0.92 < 0.001

0.75 < 0.001

0.26 ns

0.40 ns

0.58 < 0.001

0.69 < 0.001

0.52 ns

0.57 < 0.05

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E.J. J O N K M A N E T AL. 1.00

-

0.90

-

0.80

-

0.70

-

0.60

-

0.50

-

0.69

Z

0.40 0.30

-

0.20

-

0.10

-

0.00

-

0.15

0.13

PO

PY

BG

Fig. 2. Difference of the m e a n frequency of the exposed groups and the control group in the derivation P4-Oz. In all study groups the m e a n frequency is increased but the difference from the controls is only significant for the BG group ( P < 0.001).

deviation of the mean frequency of the total spectrum from the same measure of the NC group (the z values are recalculated in Hz). The older painters show an increase in the mean frequency ( P < 0.01) in the right central derivation while the left side just failed to reach the required level of significance. The bulb-growers showed a more pronounced increased mean frequency, not only in the central derivations but also in the parieto-occipital derivations.

qEEG and exposure In the young painters group there were no significant correlations between the exposure indices and the qEEG data. In the older painters most correlation coefficients were also very low and not significant ( P > 0.01). Only the relative beta power in the central derivations was correlated with the exposure index calculated over the last 5 years (r = 0.41; P = 0.007). In the bulb-growers a preliminary investigation did not reveal significant correlations between the calculated exposure index and the qEEG variables.

Discussion

There are many publications on the subject of E E G changes due to exposure to solvents, mainly from Scandinavian authors. However, the majority of these reports deal with studies in which computer analysis was not used. The scoring of the E E G abnormalities is often not very strictly defined. Sometimes high percentages of abnormal EEGs are reported in the study as well as in the control groups (Seppiiliiinen et al. 1978). Although a dose-response relationship is almost impossible to prove in retrospective studies of long-term low-dose exposure, such a relationship seems to emerge when different studies are combined. Sepp~il/iinen (1981) found an increase in percentage of abnormal

EEGs when low-dose exposure groups were compared with high-dose exposure groups. Quantitative E E G studies were done as part of a large cross-sectional investigation on occupationally exposed car and industrial spray painters (Elofsson et al. 1980). Differences between the qEEGs of painters and controls could not be demonstrated. However, Orb~ek et al. (1985; and ~rb~ek 1987) found small but significant differences in the qEEG when comparing solvent exposed workers with matched controls. In exposed subjects the beta power over the posterior part of the skull was higher than in the controls. More delta activity was found in the painters group (but only over the left hemisphere) and the antero-posterior ratio of absolute power values was lower in the exposed than in the non-exposed group. In our study abnormalities of the qEEG were mostly found in the older painters group. This was demonstrated by all 3 methods: visual assessment, neurometrics and frequency measurements. The young painters group showed hardly any differences from the NC group: only the number of abnormal mean values in the neurometric matrix was higher than could be expected by chance (Table II). This difference between the PO and PY groups cannot be explained by the difference in mean age of the groups because all qEEG data were age-corrected (Methods). (0rb~ek (1987) found an increase in absolute beta power whereas we found an increase in relative beta power; nevertheless it might be presumed that both studies point to the same phenomenon. A direct effect of exposure on the qEEG would be rather plausible when a significant correlation could be proved between the degree of exposure and the amount of qEEG changes. In our study we found only a significant correlation between central beta activity and exposure in the older painters group. However, exposure indices in long-term low-dose exposures are extremely difficult to calculate (Mikkelsen et al. 1988). Not only the exposed time (years) but also the daily consumption of solvents, the use of protective measures, the type of work and the type of painting tools should be taken into consideration. The inherent uncertainties are such that an exposure index based on questionnaires always remains disputable. Moreover, it should be pointed out that the results presented here apply only to painters with a long-term low-level exposure. The results of other groups with high-level exposure risks (e.g., spray-gun painters) might be quite different. It might be mentioned that the differences between younger and older painters cannot be explained by differences in alcohol habits since the mean daily alcohol consumption was less in the older than in the younger painters (respectively 1.4 and 2.4 units daily). Instead of organophosphate compounds and chlorinated hydrocarbons, Dutch bulb-growers nowadays

EEG CHANGES DUE TO SOLVENTS OR PESTICIDES

mainly use dithiocarbamates such as maneb and zineb. The literature on clinical signs resulting from exposure to these substances is limited (Miller 1982; Ferraz et al. 1988) and literature on concomitant neurophysiological disturbances virtually non-existent. Also the effects of the metabolites of zineb and maneb are unknown. Visual assessment of the E E G showed no differences between our BG group and the NC group. Neurometric analysis revealed some changes in the BG group, mainly an increase in beta power in central and parieto-occipital derivations (Table II). The changes in mean frequencies were highly significant. It might be argued that the mean frequency changes expressed in hertz were rather small (Table III). However, in clinical practice even minimal frequency changes can be of importance. Van Huffelen et al. (1984), e.g., showed that a frequency asymmetry of 0.3 Hz could be of importance for the detection of ischaemic lesions. Although for the neurometrics a non-linear age regression is used, the age regression function of the alpha peak frequency in our NC group could also be approximated by Y(Hz)= -0"025X(age)+ 10.52 ( r = 0.42; P = 0.002), which means that a change of 1 Hz is comparable to the normal aging process over a period of 40 years. We failed to find a correlation between the exposure index and the q E E G measures but, as in the solvent exposed workers, these exposure indices are often imprecise and can only be considered a crude estimate of absorbed dose and target organ exposure. Moreover, the majority of pesticide workers indicated having used other pesticides in the past (such as organic mercury compounds which are nowadays banned in The Netherlands). In group studies like those described here,, it is rather difficult to rule out all confounding factors. Natural toxins, e.g., are known to occur in some types of bulb flowers. Their effect ~n the human skin is well known but no information is available on the effect of these toxins on the human central nervous system. One should realize that the q E E G changes reported here are rather small. In a group .of renal patients on chronic hemodialysis, e.g. (for details of this group, see Rozeman 1990) the percentage of abnormal values in the neurometric matrix was twice as high as in the PO group. Moreover, the clinical relevance of these small q E E G changes is disputable and these changes cannot be accepted as a sign of unacceptable neurotoxicological risk. It should be emphasized that we could not detect any clinical abnormalities in the exposed groups, even in those subjects who showed on visual assessment focal slowing in the EEG. However, each deviation from the normal, be it clinical or electroencephalographical caused by exposure should be considered as an unwanted effect until proven otherwise. Summarizing, we come to the conclusion that the neurometrics method can be of interest in neurotoxico-

443

logical studies. It seems worthwhile, however, to add frequency parameters to the "classical" neurometric matrix measures: the abnormalities in the qEEGs of the bulb-growers were more spectacular with the frequency parameters, while abnormalities in the painters became more obvious when the power values were used. It remains difficult to prove a direct relationship between exposure and q E E G changes. The only observation we can make is that q E E G changes do occur in the groups of painters and bulb-growers. Whether these changes could be due to unknown group properties (not directly connected to exposure) remains to be seen. In the case of the bulb-growers this problem may be solved by monitoring the q E E G during acute exposure. Studies with ambulatory E E G equipment make such observations feasible.

References Arlien-Soborg, P., Bruhn, P., Gyldensted, C. and Melgaard, B. Chronic painters' syndrome. Chronic toxic encephalopathy in house painters. Acta Neurol. Scand., 1979, 60: 149-156. De Weerd, A.W., Perquin, W.V.M. and Jonkman, E.J. Role of the EEG in the prediction of dementia in Parkinson's disease. Dementia, 1990, 1: 115-118. Elofsson, S.A., Gamberale, F., Hindmarsh, Y., Iregren, A., Isaksson, A., Johnsson, I., Knave, B., Lydahl, E., Mindus, P., Persson, H.E., Philipson, B., Steby, M., Struwe, G., S6derman, E., Wenberg, A. and Widen, L. Exposure to organic solvents. A cross-sectional epidemiologic investigation on occupationally exposed car and industrial spray painters with special reference to the nervous system. Scand. J. Work Environ. Hlth, 1980, 6: 239-273. Ferraz, H.B., Bertolucci, P.H.F., Pereira, J.S., Lima, J.G.C. and Andrade, L.A.F. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology, 1988, 38: 550-553. John, E.R., Prichep, L., Ahn, H., Easton, P., Fridman, J. and Kaye, H. Neurometric evaluation of cognitive dysfunctions and neurological disorders in children. Prog. Neurobiol., 1983, 21: 239-290. John, E.R., Prichep, L.S. and Easton, P. Normative data banks and neurometrics. In: A.S. Gevins and A. R~mond (Eds.), Handbook of Electroencephalography and Clinical Neurophysiology. Vol. I. Methods of Analysis of Brain Electrical and Magnetic Signals. Elsevier, Amsterdam, 1987: 449-495. Jonkman, E.J., Poortvliet, D.C.J., Veering, M.M., De Weerd, A.W. and John, E.R. The use of neurometrics in the study of patients with cerebral ischaemia. Electroenceph. clin. Neurophysiol., 1985, 61: 333-341. Mikkelsen, S., J0rgesen, M., Browne, E. and Gyldensted, C. Mixed solvent exposure and organic brain damage. Acta Neurol. Scand., 1988, 78 (Suppl. 118). Miller, D.B. Neurotoxicity of pesticidal carbamates. Neurobehav. Toxicol. Teratol., 1982, 4: 779-787. Orb~ek, P. Effects of long-term exposure to organic solvents on the nervous system. Chronic toxic encephalopathy and the prognosis following cessation of exposure. Thesis, Lund, 1987. Orb~ek, P., Risberg, J., Ros~n, I., H~eger-Aronson, B., Hagstadius, S., Hjortsberg, U., Regnell, G., Rehnstr6m, S., Svensson, K. and Welinder, H. Effects of long-term exposure to solvents in the paint industry. A cross-sectional epidemiologic study with clinical and laboratory methods. Scand. J. Work Environ. Hlth, 1985, 11 (Suppl. 2): 28P.

444 Rozeman, C.A.M. Terminale nierinsuffici~ntie en het zenuwstelsel. Uraemische encephalopathie en neuropathie. Thesis. Free University, Amsterdam, 1990. Sepp~il/iinen, A.M. Neurophysiological findings among workers exposed to organic solvents. Scand. J. Work Environ. Hlth, 1981, 7 (Suppl. 4): 131-135. Seppiil~iinen, A.M., Husman, K.A.J. and Martenson, C. Neurophysiological effects of longterm exposure to a mixture of organic solvents. Scand. J. Work Environ. Hlth, 1978, 4: 304-314. Van Huffelen, A.C., Poortvliet, D.C.J. and Van der Wulp, C.J.M. Quantitative electroencephalography in cerebral ischemia. Detec-

E.J. JONKMAN ET AL. tion of abnormalities in "normal" EEGs. In: G. Pfurtscheller, E.J. Jonkman and F.H. Lopes da Silva (Eds.), Brain Ischemia: Quantitative EEG and Imaging Techniques. Elsevier, Amsterdam, 1984: 3-28. Veering, M.M., Jonkman, E.J., Poortvliet, D.C.J., De Weerd, A.W., Tans, J.Th.J. and John, E.R. The effect of reconstructive vascular surgery on clinical status, quantitative EEG and cerebral blood flow in patients with cerebral ischaemia. A three month follow-up study in operated and unoperated stroke patients. Electroenceph. clin. Neurophysiol., 1986, 64: 383-393.