1979VOL 10.NO 1

CLINICAL ELECTROENCEPHALOGRAPHY

Electroencephalographic Change in Parkinsonian Patients Treated with Levodopa-Carbidopa R. Stephens, J. Green, W. Haycook, and M. Kilgore

Introduction

ResuIt s

It is the purpose of this report to analyze the electroencephalographic changes, other than those due to chance, that occurred in a group of patients initially treated with Levodopa who were switched to Levodopa-Carbidopa combination therapy.

Table 1 compares the interpretations of electroencephalograms of patients on Levodopa with EEGs of the same patients on Levodopa-Carbidopa therapy. These results demonstrate no improvement o n the combination therapy. Table 2 shows an increase but an insignificant change in the basic background frequencies on combination therapy (P = 0.71). These data strongly suggest that the effectiveness of Levodopa on EEG activity is not sign if icant Iy improved.

Materials and Methods The 21 patient group treated with the Levodopa-Carbidopa combination included both men and women with ages ranging from 49 t o 82 years (a mean age of 75). Variabilities in the length of time of pre-treatment with Levodopa alone was from 1 t o 7 years before they were switched to the new combination therapy. A detailed review of electroencephalograms included an analysis of posterior background frequencies from the last available EEG while on Levodopa alone and when the patient had been switched to Levodopa-Carbidopa combination fora period of time ranging from 2 t o 6 months. All electroencephalograms were recorded in the wakeful state on an 8 channel instrument, utilizing the International 10-20 System electrode placement with both monopolar and bipolar techniques. “Abnormal” records included tracings showing a marked excess background slowing in all areas, focal slow waves, paroxysmal bursts like sharp wave and/ or slow-sharp wave combinations. “Borderline” tracings were those in which the basic background was slightly slower than normal and/or in which relatively excess “theta” slow waves of a generalized or of a semi-focal character were identified. These tracings were read at random and on several occasions by at least two of theauthors who then classified the EEGs as normal, borderline, and abnormal.

Discussion In 1817 James Parkinson first described in detail the syndrome now commonly known as “parkinsonism”’. The effective use of Levodopa in the amelioration of parkinsonism was well documented by Cotzias et al. in 1967 and thereafteP3. Further improvement in the therapy in parkinsonism included a noticeable decrease in nausea and vomiting and a reduced dose of Levodopa when it was used in combination with the new compound Carbidopa4. The use of the new compound suggested further testing in clinical and electroencephalographic areas which is the purpose of this investigation. There is little debate that electroencephalographic abnormalities occur in patients with Parkinson’s disease. The percentage of abnormal EEGs recorded in patients with Parkinson’s disease is still quite variable from series to series (Table 3). Diverse opinions as to the results of treatment have been reported both in the clinical Requests for reprints should be sent to Jacob Green, M.D., 2550 Park Street, Jacksonville, FL 32204.

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1979VOL 10,NO 1

Patients taking Levodopa-Carbidopa

Patients taking Levodopa Total Patients

EEG Classification

EEG Classification

Total Patients

9

Normal

8

Normal

8

Borderline

9

Borderline

4

Abnormal

4

Abnormal

TABLE 2 Patients treated with L-Dopa

Patients treated with L-Dopa/C-Dopa

Background Rhythm of EEG

Background Rhythm of EEG

Mean Frequency 8.78

Mean Frequency 9.40

and the EEG literature, in large numbers of patients treated with Levodopa. It is of interest to note that two authors suggest clinical wor~ e n i n g ~ Four , ~ . series suggest no changes other than those probably due to chance7-10. Three other authors suggest both clinical and electrographic i r n p r ~ v e r n e n t ~ These, ~ - ~ ~ . of course, are representative of relatively large groups of patients with Parkinson’s disease treated with Levodopa and/or other medications for varying periods of time and under various circumstances such as hospitalization, etc.14. In those reports suggestive of electroencephalographic improvement there is general agreement in that acceleration of background rhythm and normalization of accelerated “alpha” rhythm was the primary finding with treatment13-15.The fact that there is no clearcut correlation of the severity of clinical symptomatology and electroencephalographic abnormalities has been documented16. Improvement with Levodopa therapy (on the EEG) was suggested with a series in which as much as twenty-three percent of records returned to normaIl4. It was also suggested that if the patient had a pre-existing dementia and no EEG improvement occurred incident to early therapy with Levodopa this could be a reliable predictor of lack of future response to Levodopa therapy in what regard-motor, mental, etc.14. The deleterious effects of Levodopa medication have also been suggested in that EEG

disorganization could occur and that seizures might be precipitated by the m e d i c a t i o n ~ l ~ . Another study refutes this finding, reporting another group with clearcut epileptogenic EEG abnormalities, which did not worsen during the course of treatment with Levodopa18. In a related disease “progressive supranuclear palsy”, no apparent clinical improvement or EEG improvement was noted with Levodopa therapy. (It is of interest to note that 11 out of the 12 original EEGs were normal to begin with in this series of patients)lg. The effect of Levodopa on the electroencephalogram and clinical condition in patients with hepatic-encephalopathy has been studied by a number of authors. Most suggested both

TABLE 3 ~

Author Bengesser

No. of Patients 53

Abnormal EEGs 43%

McDowell

334

48%

McPherson

60

75%

Pikelny

34

88Yo

Rajput

125

66%

Rudkowska

44

54%

su

12

75%

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1979 VOL 10.NO 1

CLINICAL ELECTROENCEPHALOGRAPHY

clinical and EEG improvement with treatment20-22 and other authors suggested no impro~ernent.~~,~O Increasing clinical difficulty in managing patients on Levodopa medication (the on-off phenomena") suggests that further investigations need to be done and that pathological studies may in the future yield some of the solutions to the problems of clinical and EEG correlation with Levodopa therapy. Newer medications including Brorno~riptine~ may also cause electroencephalographic and clinical changes in the patients so treated.

patients with Parkinson's disease. There appears to be a slight increase in basic background frequency which was one of the earlier findings when Levodopa was first used clinically.13 From the literature surveyed there appears to be a definite lack of consistency in the effects of Levodopa therapy on the electroencephalogram and on the clinical status of the patients followed. We think this well may be explainable by the fact that no large study15 has been accomplished in which a neuroanatomical (pathological) correlation has been done with both the clinical and the EEG data. Neurological examination and the electroenSummary cephalogram are both clinical tools and have Our findings in a relatively small series of yet to be closely reviewed with the added cases seem to confirm a lack of statistically parameter of neuro-pathologic investigation significant EEG changes when Carbidopa is in this new day of therapy for Parkinson's combined with Levodopa in the therapy of disease.

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2. COTZIAS, G.C., VAN WOERT. M.H.. and SCHIF-

9. SELBY, G., Levodopa in Parkinson's disease-

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374-379,1967. 3. COTZIAS, G.C.. PAPAVASILIOU, P.S.. and GELLENE, R.. Modification of parkinsonism-Chronic Treatment with L-Dopa, New Eng. J. Med.. 280,

Australian collaborative trial, Med. J. Aust.. 1:

577-585,1973. 10. LUNZER, M., JAMES, I.M., WEINMAN, J., and SHERLOCK, S., Treatment of chronic hepatic encephalopathy with Levodopa, GUT, 15555-

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1 1 . MARJERRISON, G., BOULTON, A.A., and RAJPUT, A.H., EEG and urinary non-catecholic treatment with L-Dopa plus Benzerazide in Parkamine changes during L-Dopa therapy of Parkinson's disease, Dis. Nerv. Syst., 33:164-169, inson's disease. Neurology, 26:399-404,1976.

4. BARBEAU, A,, and ROY M., Six year results of

1972.

5. HERMAN, M.N.. ROWAN, A.J.. and GOLDENSOHN. E.S., Changes in the human electroen- 12. HICKS, E.P.. and RISCHBIETH. B.H. C.. An outpatient programme for L-Dopa therapy in Parcephalogram during L-Dopa Treatment, Paper 1971. kinson's disease, Med. J. Aust., 2:701-706, presented at American Neurological Association, 96th annual meeting, Washington, D.C.. 13. GREEN, and HAYCOOK, M.. ElectroencephaJune 14-16,1971,Program Abstr. No. 25,p. 78. lographic changes in parkinsonism patients treated with Levodopa and Levodopa-Amantadine 6. McPHERSON, A., Convulsive seizures and elecin combination, Clin. Electroenceph.. 2:28-34. troencephalogram changes in three patients 1971. during Levodopa therapy, Neurology, 20:41-45.

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14. RAJPUT, A.H. and ROZDILSKY, B., Parkinson-

7. PIKELNY, R.T.. The influence of L-dopa on the EEG in parkinsonism. Neurology, 21:453,1971.

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supranuclear palsy, Electroencephalographic studies, Arch. Neurol.. Chicago, 19:183-186, 1973.

15. RUDKOWSKA, A,. and MISZTAL, S., WPLYW L-Dopa NA ZAPlS EEG U OSOB DOTNIETYCH CHOROBA Parkinsona (The effect of L-Dopa on EEG tracings in patients with parkinsonism). POL. TYG. LEK. 30.593-595, 1975.

20. PARKES. J.D., SHARPSTONE. P., and WILLIAMS, R., Levodopa in Hepatic Coma, Lancet, 211341-1343, 1970.

16. BENGESSER, G.. Vergleigh Zwischen EEGBefund und Klinischem BlLD BE1 ParkinsonPatienten under L-Dopa (Comparison of EEG findings and clinical picture in Parkinson patients treated with L-Dopa). Wien. Med. Wochenschr.. 125:120-121, 1975.

21. SARRAZIN, A,. EMERIT. J.. OLIVER, L., REBELO. F.. and BOUSQUET, 0.. Traitement du coma hepatique par la L-Dopa. Premiers resultats Treatment of hepatic coma with L-Dopa: preliminary findings), Presse Med.. 79:2226-2227, 1971

17. MENA, I..COURT, J.. FUENZALIDA, S., PAPAVASILIOU. P.S., and COTZIAS. G.G., Modification of chronic manganese poisoning: Treatment with L-Dopa or 5-OH Tryptophane, N. Engl. J. Med., 181:5-10, 1970.

22. LUNZER, M., JAMES, I.M., and SHERLOCK, S., Treatment of chronic hepatic encephalopathy with Levodopa digestion, 6:291, 1972 Levo23. LANZINGER, G., and KOMMERELL, 8.. dopa-Therapie Beim Hepatisdhen Koma/Unter Desonderer Berucksightingung des EEG-Verlaufs/(Levodopa treatment in hepatic coma/with special consideration of serial EEG changes), Deut. Med. Wochenschr.. 99:700-705, 1974.

18. NEWMAN. S.E., TUCKER, R.P., and K001, K.A., Lack of Levodopa effect on pre-existing temporal lobe focus, Arch. Neurol.. Chicago, 29:122123, 1973. 19. SU, P.D., and GOLDENSOHN, E.S.. Progressive

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