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 ( À 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 4 0.001) and reduction in on-euphoria (P 4 0.001). There was an inversion in the number of patients functioning in an overall appetitive mode (29 before versus 2 after surgery, P 4 0.0001) to an overall apathetic mode (3 before versus 13 after surgery, P 5 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.

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

“…Patients with Parkinson's disease who are exposed to non-physiological dopaminergic stimulation are at high risk of developing a range of behavioural addictions or impulse control disorders. 88,89,91,122,154 By contrast, patients are at risk of developing apathy-an…”

“…102 All patients were completely withdrawn from dopamine agonists immediately after surgery and levodopa was greatly reduced to the minimally required dose, with a parallel increase in stimulation parameters. 91 Half of the patients developed apathy in the course of the fi rst year of followup, and half of those also developed depression at the same time. The full dopamine withdrawal syndrome consisted of a triad of apathy, anxiety, and depression, with apathy being the most common symptom.…”

“…[87][88][89] These fi ndings provide evidence of a behavioural spectrum disorder, ranging from a hyperdopaminergic syn drome (including impulse control disorders) to hypodopaminergic levels associated with apathy, anxiety, and depression, as described in the withdrawal dopaminergic syndromes. 83,[90][91][92][93] Besides the emotional-aff ective syndrome, apathy might also be associated with a disruption of cognitive func tions. This form of apathy is generally associated with an impairment in those executive functions (selection, planning, working memory, and set-shifting) needed to elaborate an action plan.…”

“…120 This process can at least partly be reversed after a careful titration of the dose of the dopamine agonist. 120 Prospective systematic assessment 91 of behaviours before and after STN-DBS in Parkinson's disease has shown that these observations apply not only to creativity and hobbies, but also to the full range of motivated human behaviours.…”

“…Review opposite motivational state-in untreated de-novo Parkinson's disease, 155 in more advanced stages of Parkinson's disease during non-motor off -periods, 91,92 in parallel with progressive cognitive deterioration, or in the context of a rapid decrease in dopaminergic drugs after deep brain stimulation, leading to a hypodopaminergic withdrawal syndrome or Parkinson's disease-related apathy. 83,90,91,93 Impairments of motivation therefore appear in Parkinson's disease as a continuum of abnormal behaviours that range from the syndrome of apathy to impulse control disorders and other behavioural addictions.…”