Reply: Dopamine agonist withdrawal syndrome and non-motor symptoms after Parkinson's disease surgery

We would like to thank Dr Nirenberg for her thoughtful comments on our prospective study reporting the occurrence of a delayed withdrawal syndrome in patients with Parkinson’s disease treated with bilateral subthalamic stimulation. This syndrome, which includes depression, apathy and anxiety, is the consequence of a marked decrease in dopaminergic treatment rendered possible by a major improvement in motor symptoms (Thobois et al ., 2010). This study identified preoperative non-motor fluctuations as predictors of post-operative apathy and demonstrated that non-motor psychic symptoms of Parkinson’s disease can be explained by mesolimbic dopaminergic denervation. In order to examine and discuss the points raised by Dr Nirenberg (2010), several aspects of our study need to be highlighted and clarified. The fact that Parkinson’s disease surgery that preferentially targets the sensorimotor rather than the limbic subthalamic nucleus deep brain stimulation produces better motor than non-motor effects provides an almost experimental model with which to study non-motor psychic symptoms of Parkinson’s disease. This study was designed to obtain a better understanding of post-operative non-motor withdrawal symptoms, their time course and mechanisms. In accordance with our study protocol, dopaminergic treatment was reduced drastically, with complete arrest of dopamine agonists at time of surgery and marked reduction of levodopa depending on patients’ motor state in the two weeks following surgery, when stimulation parameters were increased. Reduction of dopaminergic treatment after surgery is a normal procedure, which is necessary for the adjustment of subthalamic stimulation parameters and the establishment of satisfactory control of motor fluctuations and dyskinesias (Krack et al ., 2002; Thobois et al ., 2003). It is important to note that the management of medication in our study differs from routine practice, where medication is adapted more individually and where low-dosage dopamine agonists are often maintained in order to prevent the delayed appearance of …