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Risk Factors for Peak Dose Dyskinesia in 100 Levodopa-treated Parkinsonian Patients

Published online by Cambridge University Press:  18 September 2015

Pierre J. Blanchet ,
Pierre Allard ,
Laurent Grégoire ,
François Tardif  and
Paul J. Bédard
Pierre J. Blanchet
Affiliation:
Neurobiology Research Centre, Hôpital de l’Enfant-Jésus, Canada
Pierre Allard
Affiliation:
Epidemiology Research Unit. Hôpital du Saint-Sacrement, Québec City (Québec), Canada
Laurent Grégoire
Affiliation:
Neurobiology Research Centre, Hôpital de l’Enfant-Jésus, Canada
François Tardif
Affiliation:
Neurobiology Research Centre, Hôpital de l’Enfant-Jésus, Canada
Paul J. Bédard*
Affiliation:
Neurobiology Research Centre, Hôpital de l’Enfant-Jésus, Canada
*
Neurobiology Research Centre, Hôpital de l’Enfant-Jésus, 1401, 18e Rue, Québec City (Quebec), Canada GIJ 1Z4
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Abstract

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Background: No clinical parameter other than “sufficient” dopamine denervation and exposure to exogenous levodopa has been unquestionably linked to dyskinesia in levodopa-treated Parkinson’s disease patients. Methods: We retrospectively analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free survival probability in relation to levodopa therapy was assessed using the Kaplan-Meier method. Results: Overall, 56% of patients developed dyskinesia after a mean of 2.9 years, a figure similar to the average duration of levodopa treatment in the non-dyskinetic group. Dyskinetic patients were significantly younger at disease onset, but their mean latency to dyskinesia induction after levodopa initiation was not different from older dyskinetic individuals and the overall dyskinesia-free survival of younger subjects was not worse either. Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay in initiating levodopa therapy of more than three years after disease onset and levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients did not increase the probability of developing dyskinesia over time. Conclusions: Since withholding levodopa therapy did not increase the risk for dyskinesia in our patients and can delay the emergence of dyskinesia after onset of parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment appears logical.

Résumé

Résumé

Facteurs de risque de l’apparition de dyskinésies chez 100 patients parkinsoniens traités par la lévodopa. Introduction: Le profil clinique du parkinsonien à risque de développer des dyskinésies sous L-dopa demeure controversé. Une dénervation dopaminergique et une exposition à la L-dopa “suffisantes” ne peuvent identifier les sujets susceptibles. Méthode: Par une analyse rétrospective des dossiers de 100 patients traités par la L-dopa pendant au moins un an, nous avons tenté d’identifier des facteurs de risque favorisant l’apparitiende dyskinésies. La méthode de Kaplan-Meier a permis de comparer la probabilité de sous-groupes de sujets de demeurer sans dyskinésie en fonction de la durée de la dopalhérapie. Résultats: La proportion de sujets dyskinétiques dans cette population a atteint 56%. le délai moyen d’induction de dyskinésies après le début du traitement par la L-dopa a été de 2.9 années, une valeur non discriminante car semblable à la durée moyenne de traitement de nos sujets non dyskinétiques. Les patients dyskinétiques étaient statistiquement plus jeunes au moment de l’apparition des premiers signes parkinsoniens. Toutefois, le délai d’induction de dyskinésies et la survie globale sans dyskinésie chez les sujets jeunes n’étaient pas différents de ceux des sujets plus âgés. La dose quotidienne de L-dopa administrée au moment de l’apparition de dyskinésies était en moyenne plus élevée que celle des sujets non dyskinétiques mais la dose cumulative de L-dopa avant l’apparition de dyskinésies était semblable pour les deux groupes. L’introduction de la L-dopa plus de trois ans après le début des symptômes parkinsoniens ou au stade Hoehn-Yahr II plutôt que I n’a pas été associée à une probabilité accrue de développer des dyskinésies en cours de dopathérapie. La dyskinésie est un phénomène précoce dont le processus d’induction n’est pas accéléré par une dopathérapie introduite plus tardivement. Conclusion: Les auteurs concluent qu’il est souhaitable de tenter un traitement avec un agoniste dopaminergique dans les stades initiaux de la maladie de Parkinson afin de retarder l’apparition de dyskinésies après le début du syndrome parkinsonien, en particuler chez les sujets jeunes.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 23 , Issue 3 , August 1996 , pp. 189 - 193
Copyright
Copyright © Canadian Neurological Sciences Federation 1996

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