Clinical StudyDopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson’s disease
Introduction
Parkinson’s disease (PD) may be complicated by the dopamine dysregulation syndrome (DDS), in which patients compulsively overuse dopaminergic drug therapy, taking doses in excess of those required to treat motor symptoms.1 This typically results in significant physical, emotional and social dysfunction. Other dopaminergic drug-related behaviours often seen in these patients include punding and impulse control disorders (ICDs), such as pathological gambling, hypersexuality, compulsive shopping and binge eating.1 Treatment of these disorders is often difficult, with reduction of anti-parkinsonian drugs being the most important management approach. However, this is often limited by deterioration of parkinsonian symptoms. Deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) or globus pallidus internus (GPi) may markedly improve “off”-medication motor symptoms, and STN DBS has the potential to allow significant reductions in drug dose (on average by about 50%).2 Therefore, STN DBS is potentially a treatment option for patients with dopaminergic drug-related behaviours.
However, data regarding the impact of DBS surgery on these pathologic behaviours are limited, with conflicting results. In 12/17 patients undergoing bilateral STN DBS, DDS resolved or was dramatically improved post-operatively,[3], [4], [5], [6], [7], [8] but failed to improve or worsened in five other patients.[9], [10] A relationship between ICDs and DBS has also been reported. In nine patients, pathological gambling improved or disappeared after bilateral STN DBS.[11], [12] However, in 18 other patients who underwent STN DBS (11 bilateral, one unilateral, six not specified), ICDs or punding were reported to have developed or decompensated post-operatively (eight pathological gambling, seven hypersexuality, one intermittent explosive disorder and kleptomania and two punding).[13], [14], [15], [16], [17], [18], [19], [20], [21] A few patients have developed hypersexuality (one also with cravings for 3,4-dihydroxy-l-phenylalanine [l-dopa]) after GPi DBS.[22], [23]
We present a series of patients exhibiting DDS, ICDs or punding before and/or after DBS, and examined factors that could potentially predict outcome.
Section snippets
Methods
Neurologists at centres providing DBS surgery in Australia and the UK were sent a semi-structured questionnaire. They were asked to provide case histories of PD patients who had undergone STN or GPi DBS, and had exhibited DDS, ICDs or punding at some stage during the course of their disease. The following data were obtained: age, gender, age at PD diagnosis, pre-morbid history of alcohol abuse or illicit drug use, pre-operative history of depression or other psychiatric disorders and
Results
Neurologists at five out of seven invited centres participated. A total of 21 patients fulfilling criteria for DDS, ICDs or punding were identified (Table 1). Mean age at PD diagnosis was 42 ± 9 (range 17–57) years and time to surgery after PD diagnosis was 11 ± 5 years (range 4–24) years. At some point before surgery, 48% of patients had been depressed, 24% had abused alcohol, and 14% (patients 1, 19 and 20) had regularly used illicit drugs, which included cannabis, amphetamine, lysergic acid
Discussion
Patients with DDS, ICDs and punding represent a major management challenge and DBS does not appear to be a universally successful treatment for these disorders. In the present study, 71% of patients with pre-operative DDS remained unimproved or worsened post-operatively. Lack of recognition of these behaviours pre-operatively, poor or moderate motor benefit and higher dopaminergic medication intake post-operatively were associated with persistence or a new development of DDS, ICDs and punding
References (38)
- et al.
Compulsive use of dopamine replacement therapy in Parkinson’s disease: reward systems gone awry?
Lancet Neurol
(2003) - et al.
Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson’s disease
Parkinsonism Relat Disord
(2007) - et al.
Explosive-aggressive behaviour related to bilateral subthalamic stimulation
Parkinsonism Relat Disord
(2004) - et al.
Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies
Neurosci Biobehav Rev
(2008) - et al.
Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease
N Engl J Med
(1998) - et al.
Addiction in Parkinson’s disease: impact of subthalamic nucleus deep brain stimulation
Mov Disord
(2005) - et al.
Dopamine dysregulation syndrome: impact of subthalamic chronic stimulation
Mov Disord
(2007) - et al.
Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease
N Engl J Med
(2003) - et al.
Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s Disease
J Neurol Neurosurg Psychiatry
(2004) - et al.
Rapid resolution of dopamine dysregulation syndrome (DDS) after subthalamic DBS for Parkinson disease (PD): a case report
Cogn Behav Neurol
(2008)
Behavioural disorders, Parkinson’s disease and subthalamic stimulation
J Neurol Neurosurg Psychiatry
Stimulation of the subthalamic nucleus in Parkinson’s disease: a 5 year follow up
J Neurol Neurosurg Psychiatry
Pathologic gambling in Parkinson’s disease: a behavioural manifestation of pharmacologic treatment?
Mov Disord
Pathological gambling in Parkinson’s disease improves on chronic subthalamic nucleus stimulation
Mov Disord
Transient mania with hypersexuality after surgery for high-frequency stimulation of the subthalamic nucleus in Parkinson’s disease
Mov Disord
Long-term follow up of bilateral deep brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease
J Neurosurg
Fracture of subthalamic nucleus deep brain stimulation hardware as a result of compulsive manipulation: a case report
Neurosurgery
Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a controlled study
Neurology
Gambling and Parkinson disease
Arch Neurol
Cited by (208)
Effects of deep brain stimulation target on the activation and suppression of action impulses
2022, Clinical NeurophysiologyEffect of deep brain stimulation on impulse control behaviors of Parkinson's disease patients: A systematic review and meta-analysis
2021, Interdisciplinary Neurosurgery: Advanced Techniques and Case ManagementDBS imaging methods IV: Group analyses
2021, Connectomic Deep Brain StimulationNeuropsychiatric effects of subthalamic deep brain stimulation
2021, Handbook of Clinical Neurology
- †
S Tisch is now with the Department of Neurology, St Vincent’s Hospital, University of New South Wales, Sydney, Australia.