title: Subthalamic stimulation in Parkinson's disease: restoring the balance of motivated behaviours.
abstract: Addictions to dopaminergic drugs or to pleasant behaviours are frequent and potentially devastating neuropsychiatric disorders observed in Parkinson's disease. They encompass impulse control disorders, punding and dopamine dysregulation syndrome. A relationship with dopaminergic treatment is strongly suggested. Subthalamic stimulation improves motor complications and allows for drastic reductions in medication. This treatment might, therefore, be considered for patients with behavioural addictions, when attempts to reduce dopaminergic medication have failed. However, conflicting data have reported suppression, alleviation, worsening or new onset of behavioural addictions after subthalamic stimulation. Non-motor fluctuations are also a disabling feature of the disease. We prospectively investigated behaviour in a cohort of 63 patients with Parkinson's disease, before and 1 year after subthalamic stimulation using the Ardouin scale, with systematic evaluation of functioning in overall appetitive or apathetic modes, non-motor fluctuations, dopaminergic dysregulation syndrome, as well as behavioural addictions (including impulse control disorders and punding) and compulsive use of dopaminergic medication. Defined drug management included immediate postoperative discontinuation of dopamine agonists and reduction in levodopa. Motor and cognitive statuses were controlled (Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, frontal score). After surgery, the OFF medication motor score improved (-45.2%), allowing for a 73% reduction in dopaminergic treatment, while overall cognitive evaluation was unchanged. Preoperative dopamine dysregulation syndrome had disappeared in 4/4, behavioural addictions in 17/17 and compulsive dopaminergic medication use in 9/9 patients. New onset of levodopa abuse occurred in one patient with surgical failure. Non-motor fluctuations were significantly reduced with improvements in off-dysphoria (P ≤ 0.001) and reduction in on-euphoria (P ≤ 0.001). There was an inversion in the number of patients functioning in an overall appetitive mode (29 before versus 2 after surgery, P ≤ 0.0001) to an overall apathetic mode (3 before versus 13 after surgery, P < 0.05). Two patients attempted suicide. Improvement in motor fluctuations is linked to the direct effect of stimulation on the sensory-motor subthalamic territory, while improvement in dyskinesias is mainly explained by an indirect effect related to the decrease in dopaminergic drugs. Our data suggest that non-motor fluctuations could similarly be directly alleviated through stimulation of the non-motor subthalamic territories, and hyperdopaminergic side effects might improve mainly due to the decrease in dopaminergic medication. We show an overall improvement in neuropsychiatric symptomatology and propose that disabling non-motor fluctuations, dopaminergic treatment abuse and drug-induced behavioural addictions in Parkinson's disease may be considered as new indications for subthalamic stimulation.
authors.affiliation: CHU de Grenoble, Pavillon de neurology, Grenoble Cedex 9, France. ELhommee@chu-grenoble.fr
authors.forename: Eugénie
authors.initials: E
authors.lastname: Lhommée
authors.forename: Hélène
authors.initials: H
authors.lastname: Klinger
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Schmitt
authors.forename: Claire
authors.initials: C
authors.lastname: Ardouin
authors.forename: Amélie
authors.initials: A
authors.lastname: Bichon
authors.forename: Andrea
authors.initials: A
authors.lastname: Kistner
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraix
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.forename: Magaly
authors.initials: M
authors.lastname: Aya Kombo
authors.forename: Stephan
authors.initials: S
authors.lastname: Chabardès
authors.forename: Eric
authors.initials: E
authors.lastname: Seigneuret
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
authors.forename: Patrick
authors.initials: P
authors.lastname: Mertens
authors.forename: Gustavo
authors.initials: G
authors.lastname: Polo
authors.forename: Sebastien
authors.initials: S
authors.lastname: Carnicella
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Quesada
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bosson
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects; D015331:Cohort Studies; D046690:Deep Brain Stimulation / Q000379:methods*; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000209:etiology / Q000628:therapy*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000628:therapy*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D020531:Subthalamic Nucleus / Q000502:physiology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa