Review
Impulse control and related disorders in Parkinson’s disease patients treated with bilateral subthalamic nucleus stimulation: A review

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Abstract

Recently, impulse control and related disorders including punding and the dopamine dysregulation syndrome (DDS) have been increasingly recognized in treated patients with Parkinson’s disease (PD). Especially the impulse control disorders (ICD) such as pathological gambling, hypersexuality, compulsive eating and buying may have dramatic repercussions on family, personal and professional life. Drug replacement therapy (DRT) is believed to play an important role in the onset of these behavioral disturbances. Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) might be a therapeutic option for those patients with DRT-related behavior, it may also induce ICD. So far, little is known about the relationship between STN DBS and impulse control and related disorders. Our aim was to review the current knowledge on this relationship in PD patients. The available studies showed that stimulation of the STN is associated with both favorable and negative outcome in terms of impulse control and related disorders. Preoperative disorders may resolve or improve after STN DBS, but these can also worsen or show no change at all. Moreover, STN DBS can also reveal or even induce ICD. Possible explanations for this variability are proposed and suggestions for clinical management are given.

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder, which affects 0.2% of the population, although its prevalence increases with age [1]. PD prominently affects motor function, resulting in bradykinesia, rigidity, postural instability, and resting tremor. However, PD also causes non-motor manifestations, including problems with cognition, mood and behavior [2], [3], [4]. Recently, the impulse control disorders (ICD) have received special attention in PD patients. ICD are characterized by a failure to resist an impulse, drive or temptation to perform an act that is harmful to the person and others, and supposed to represent the severe end of a spectrum of related disorders in PD sharing poorly or uncontrolled repetitive behaviors, including dopamine dysregulation syndrome (DDS) and punding [5]. Based on case reporting and cross-sectional studies, prevalence estimates for ICD may be higher in PD than in the general population or in healthy control subjects, and patients may have multiple ICD [5]. Preliminary prevalence estimates for ICD in PD are 1.7–6% for pathological gambling (PG), 2–10% for hypersexuality, 0.4–5.7% for compulsive buying and 4.3% for compulsive eating, and 3.9% for 2 or more ICD [5], [6]. ICD may result in considerable distress to the patient and caregiver. In addition, it may have disastrous relational and financial consequences. Underreporting due to embarrassment or lack of insight may aggravate these consequences.

It is increasingly recognized that drug replacement therapy (DRT) may trigger ICD by inducing dysfunction in the meso(cortical)-limbic pathway involving the nucleus accumbens, ventral tegmental and prefrontal cortical areas [2], [7], [8], [9], [10], [11]. DRT with especially dopamine agonists is believed to play another important role in the onset of the behavior disturbances together with mutations of dopaminergic function-related genes, which provide a first contribution to the susceptibility to develop ICD [2], [12], [13], [14], [15]. A recent cross-sectional study in 3090 patients with DRT showed that ICD were more common in patients treated with dopamine agonists than in those without. Additional associations were found between ICD and levodopa use, younger age, being unmarried, current cigarette smoking and a history of gambling problems [6]. There is a significant overlap in risk factors for ICD, punding and DDS, but the duration of DRT may be longer for DDS or punding [16]. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has shown substantial improvement of motor complications in PD and may allow significant reductions in dopaminergic drug therapy (up to 50%) [17]. While STN DBS might be a therapeutic option for those patients with DRT-related behavior, it has been increasingly recognized that STN DBS might also induce ICD. So far, there is little information about the relationship between ICD, punding, DDS and STN DBS in patients with PD. Therefore our aim was to review the literature to address the current knowledge on this specific relationship.

Section snippets

Search strategy

The literature search was carried out using a PubMed search query covering a time period from 1999 until October 2010. The following key words were used: Parkinson’s disease, PD, Parkinson, behavioral disorders, impulse control disorder, ICD, excessive shopping, hypersexuality, compulsive eating, pathological gambling, PG, punding, dopamine dysregulation syndrome, DDS, in combination with deep brain stimulation, DBS, subthalamic nucleus, STN, surgery, neurosurgery and stereotactic surgery.

Results

In total 12 articles were found, however 5 studies mentioned ICD or DDS and STN DBS without providing a clear description of study and patient characteristics and therefore were excluded [18], [19], [20], [21], [22]. As such only seven studies were included, involving one clinical trial, one case series, one cross-sectional study and four case reports [9], [11], [23], [24], [25], [26], [27].

Four [9], [11], [23], [24] studies described improvement or resolving of impulse control and related

Discussion

In line with our expectation, analysis of the included studies showed that DBS of the STN is associated with both good and poor outcome in terms of impulse control and related disorders, including ICD, punding and DDS. While preoperative disorders may resolve or improve after stimulation of the STN, these can also worsen or show no change at all. Moreover, STN DBS can also reveal or even induce [26] ICD.

The results of this review are based on only case series and case reports and the evidence

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    The review of this paper was entirely handled by the Co-Editor-in-Chief, Z.K. Wszolek.

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