Pathological Gambling in Parkinson’s Disease Improves on Chronic Subthalamic Nucleus Stimulation Claire Ardouin, MA, 1 Valerie Voon, MD, 2 Yulia Worbe, MD, 3 Nehman Abouazar, MD, 1 Virginie Czernecki, MA, 3 Hassan Hosseini, MD, 4 Antoine Pelissolo, MD, 5 Elena Moro, MD, 2 Euge ´nie Lhomme ´e, MA, 1 Anthony E. Lang, MD, 2 Yves Agid, MD, 3 Alim-Louis Benabid, MD, 6 Pierre Pollak, MD, 1 Luc Mallet, MD, 3,5 and Paul Krack, MD 1 * 1 De ´partement de Neurologie, CHU Grenoble, INSERM U318, Universite ´ Joseph Fourier, Grenoble, France 2 Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada 3 Centre d’Investigation Clinique 9503, INSERM U679, CHU Pitie ´-Salpe ˆtrie `re, Universite ´ Pierre et Marie Curie, Paris, France 4 Service de Neurologie, Ho ˆpital Henri Mondor, Cre ´teil, France 5 Psychiatrie UMR7593, Pitie ´- Salpe ˆtrie `re, Paris, France 6 Service de Neurochirurgie, CHU Grenoble, INSERM U318, Universite ´ Joseph Fourier, Grenoble, France Abstract: Pathological gambling (PG) related to dopaminergic treatment in Parkinson’s disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syn- drome (DDS). We describe a series of PD patients with pre- operative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The pa- tients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54  9 years; levodopa equivalent dose, 1,390  350 mg/day) had preoper- ative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0 – 48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symp- toms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS- associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly at- tributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subtha- lamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment. © 2006 Move- ment Disorder Society Key words: Parkinson’s disease; deep brain stimulation; pathological gambling; dopamine; subthalamic nucleus Psychiatric symptoms related to Parkinson’s disease (PD) or dopaminergic treatment include mood disorders, psychotic symptoms, apathy, anxiety, 1 the recently recog- nized dopamine dysregulation syndrome, 2,3 and impulse control disorders. 4 –7 Dopamine dysregulation syndrome is defined as compulsive use of dopaminergic treatment with secondary cognitive and behavioral disturbances. 2,3 The range of reported impulse control behaviors includes patho- logical gambling (PG), hypersexuality, compulsive shop- ping, pathological overeating, hobbyism, and other repeti- tive, purposeless behaviors (“punding”). PG has been conceptualized within the impulsive– compulsive spectrum disorders and also as a behavioral addiction with overlaps with substance use disorders. 8 Subthalamic nucleus (STN) deep brain stimulation (DBS) is a treatment for advanced PD with demonstrated efficacy on levodopa-sensitive motor symptoms. 9 How- ever, there are limited data available on the effects of STN DBS on preoperative psychiatric symptoms in PD. Postoperative amplification or decompensation of previ- ously existing psychiatric disorders has been reported 10 and behavioral problems therefore are generally consid- ered as a contraindication for STN DBS. The objective of this study was to describe the outcomes of a series of PD patients with active preoperative medication-related PG who have undergone STN DBS. *Correspondence to: Dr. Paul Krack, De ´partement de Neurologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France. E-mail: paul.krack@ujf-grenoble.fr Received 30 January 2006; Revised 31 March, 9 and 16 May 2006; Accepted 20 May 2006 Published online 13 September 2006 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21098 Movement Disorders Vol. 21, No. 11, 2006, pp. 1941–1946 © 2006 Movement Disorder Society 1941