J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from J. Neurol. Neurosurg. Psychiat., 1971, 34, 668-673 Analysis of L-dopa induced dyskinesias in 51 patients with Parkinsonism R. J. MONES, T. S. ELIZAN, AND G. J. SIEGEL From the Department of Neurology, Mount Sinai Medical School, New York, New York, U.S.A. SUMMARY An analysis of 51 patients with Parkinsonism who have developed L-dopa induced dyskinesias is presented. The cause has not been proven, although various hypotheses are discussed. One third of the total number of patients treated developed dyskinesia. These patients tend to re- spond better to L-dopa than the other group. There is a tendency for the older patient or the patient with long-standing disease to develop dyskinesias. There appears to be no way of predicting which patients will develop dyskinesia by analysis of the symptoms or the aetiology of the Parkinsonism syndrome. The unilateral characteristic of the dyskinesia in patients with hemi-Parkinsonism and patients with unilateral thalamotomies suggests that structural abnormalities are critical in deter-guest. Protected by copyright. mining the presence and localization of dyskinesias. This is supported by non-occurrence of similarly treated patients without Parkinsonism. L-dopa is now established as the treatment of choice and 45 started in the hospital. The protocol for the medical for Parkinsonism. Many articles have appeared in and neurological evaluation of these patients, the follow- the literature since the initial work of Cotzias, up care, and the laboratory data are included in a pre- Van vious paper (Mones, 1969). The dyskinesias were evaluated Woert, and Schiffer (1967), Cotzias, Papava- by clinical history, neurological examination and by siliou, and Gellene (1969) concerning the use of cin6 films of selected patients. The dosage of L-dopa chronic high dose oral treatment with L-dopa. was between 3 and 6 g per day and the longest treatment Most authors have found the drug of great help period in this series is 12 months. in approximately 50% of patients (Duvoisin, Barrett, Schear, Hoehn, and Yahr, 1969; Yahr, Duvoisin, RESULTS Schear, Barrett, and Hoehn, 1969; Mones and Elizan, 1969; Elizan and Siegel, 1970). These Involuntary irregular movements have been observed patients have a change in their life style and a during L-dopa therapy in 51 patients. These are definite improvement in their symptoms in the most commonly seen in the facial muscles, jaw, periods of at least one to three years of observation. tongue, and neck, and consist of irregular fast and It has not yet been established if the drug stops the slow movements which can be categorized as ahttp://jnnp.bmj.com/ progression of the disease on a long-term basis. combination of choreiform movements, athetosis, One of the most important and fascinating compli- and dystonia. These dyskinesias are irregular, occur cations of the drug is the induction of dyskinesias. at different times of the day, but most commonly This paper is an analysis of L-dopa induced dyskine- are decreased or absent in the morning hours. sias seen in 51 patients with Parkinsonism treated Other abnormalities have been noted, including at the Mount Sinai Medical Center. dystonic movements of the limbs and involuntary flexion of the toes. Other more bizarre movements METHODS of the trunk, with irregular hip or shoulder move- on October 2, 2021 by ments, have been seen. Less common are abnormal The patients in this series of 152 were treated at the Mount Sinai Medical Center, from 1 November 1968 respirations such as panting or sighing respiration to 31 October 1969. The initial 60 patients were all and forced inspiratory spasms and dyspnoea. first treated in the hospital and then followed as out- Involuntary eye movements have not been seen. patients on a monthly basis. Of the next 90 patients, 45 These patients are frequently not aware of early have had treatment started in the outpatient department minor facial dyskinesias, but later these movements 668 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from Analysis Of L-dopa induced dyskinesia in 51 patients with Parkinsonism 669 may become embarrassing and a severe disability. is also indicated. The majority of patients developed In 25 of the 51 cases, the dyskinesias limited the their dyskinesias while on a dosage of 3 to 6 g amount of L-dopa that could be given and decreased daily. Most ofthe patients developedtheir dyskinesias the efficacy of the drug. by the fifth month of therapy. A total of 152 patients were started on L-dopa Table 1 lists the relationship of the induction of at the Mount Sinai Medical Center up to 31 July dyskinesias to the improvement of the patient on 1969 (Table 1). These cases of Parkinson's disease L-dopa therapy. The criteria for improvement have have been evaluated for this study, as they had been relatively simple. Patients are considered to have been on the drug for at least three months. By (1) no improvement, (2) mild improvement, (3) good 31 October 1969, 51 cases had developed dyskinesias improvement, implying a change in life style so that at some time during their L-dopa therapy. None if the patient was unable to work he is now working, of 12 patients with various diseases of the nervous or if the patient was unable to care for himself, he is system other than Parkinsonism who have been now able to care for himself, or (4) dramatic im- started on L-dopa developed induced dyskinesias. provement. Of 152 cases, 13 patients had a dra- The dosage of the drug at the time of the onset matic improvement on the drug, and of these 13, 11 of dyskinesias is shown in Table 2. The month of had some type of dyskinesia (Table 1). Sixty-three L-dopa therapy in which the dyskinesias occurred cases had a good result with L-dopa therapy, and 28 of these had induced dyskinesias. Of 37 patients who had mild improvement on the drug, only 11 TABLE 1 had induced dyskinesias. Of 22 patients who had no help from L-dopa, only one patient developed PATIENTS WITH PARKINSONISM EVALUATED (152) dyskinesias. It appears that patients who do well guest. Protected by copyright. A. Improved with L-dopa Induced dvskinesias with L-dopa have a high percentage of induced dyskinesias. This may imply that the improvement Dramatic 13 11 of a patient on L-dopa therapy is related in some way Good 63 28 Mild 37 11 to the induction of dyskinesias. It must be noted, however, that many patients with dramatic improve- B. No help 22 1 ment or good improvement in their Parkinson's C. Stopped L-dopa 17 0 disease did not develop dyskinesias. Died 6 The cause of Parkinsonism was analysed in this Cardiac problems 2 Psychiatric problems 3 series. Seven patients had post-encephalitic Parkin- Rash I sonism and of these, five showed significant clinical Fever 1 Other causes 4 improvement and two developed dyskinesias. Of the idiopathic type represented by 145 cases, 71 152 51 improved significantly and 49 developed dyskinesias. No conclusion can be drawn relating type of Parkinsonism to induction of dyskinesias. Nine patients in this series had bilateral thala- TABLE 2 motomies and only one patient developed dyskine- DEVELOPMENT OF L-DOPA INDUCED DYSKINESIA RELATED sias, which is a figure much lower than the general TO MONTH AND DRUG AND DOSAGE LEVEL AT TIME OF ON- overall percentage (Table 3). This patient developed SET OF DYSKINESIAS bilateral facial grimacing and respiratory abnormali- http://jnnp.bmj.com/ Months on L-dopa L-dopa dose (glday) at onset of dyskinesias ties. Thirteen patients had previous unilateral thala- motomies, and of these seven developed dyskinesias. 1-2 2-3 3-4 4-5 5-6 6-7 Totals 1 2 1 7 1 2 11 TABLE 3 3 1 7 1 3 12 4 1 4 4 4 13 EFFECT OF PREVIOUS THALAMOTOMY FOR PARKINSONISM 5 2 1 3 1 7 6 1 2 3 Patients Significant L-dopa 7 3 1 4 (no.) clinical induced on October 2, 2021 by 8 1 1 improvement dyskinesia 9 (L-dopa) 10 11 Bilateral operation 9 6 l 12 Unilateral operation 13 5 7 Non-operated Totals 3 25 8 14 1 patients 130 65 43 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.34.6.668 on 1 December 1971. Downloaded from 670 R. J. Mones, T. S. Elizan, and G. J. Siegel There were no unilateral limb dyskinesias seen TABLE 6 contralateral to the thalamotomy. Five patients who did PREDOMINANT ABNORMALITIES IN THE PATIENTS WITH have unilateral limb dyskinesias all had PARKINSONISM WHO DEVELOPED L-DOPA INDUCED DYSKIN- their movements ipsilateral to -the thalamotomy. ESIAS Table 4-shows that there-is-no definite statistical correlation between dyskinesia and duration of Tremor 13 Akinesia 10 Parkinson's disease before L-dopa. However, it Gait 17 appears that the longer the disease has been present, Face and speech 2 Rigidity 4 the greater the incidence of L-dopa induced dys- Fine movements 4 kinesias. Posture 1 The relationship of dyskinesias to severity of the Total 51 Parkinson's disease was analysed (Table 5). Patients graded as having a mild disease have evidence of extrapyramidal syndrome but are not disabled and can do their normal work or housework; moderate Table 7 analyses the relationship with age on Parkinsonisni implies difficulty in working, but starting L-dopa therapy. No conclusion is possible, some ability to care for themselves in their every- although it is noted that the percentage of dyskinesias day living activities; severe Parkinsonism implies in the oldest age group is low.