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New Insights About Impulse Control Disorders in Parkinson's Disease
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports that she has consulted for Biovail.
Synopsis: Impulse control disorders in Parkinson's disease are associated with a unique pattern of electrophysiological activity in the ventral subthalamic nucleus.
Source: Rodriguez-Oroz MC, et al. Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease. Brain 2011;134:36-49.
Levodopa and dopamine agonists are highly effective treatment for Parkinson's disease (PD) and alleviate many of the disabling motor and non-motor disease manifestations. Over time, however, patients begin to develop motor and behavioral complications of chronic dopaminergic therapy. Motor complications such as end-of-dose wearing off and dyskinesias are most closely associated with the use of levodopa. In contrast, behavioral complications such as impulse control disorders (ICDs) are predominantly related to use of dopamine agonists such as pramipexole and ropinorole. There are a number of similarities between levodopa-induced dyskinesias (LID) and ICDs, including potential improvement after deep brain stimulation (DBS), either as a direct effect of DBS and/or due to concomitant reduction of dopaminergic medications.
Prior studies have identified a distinct pattern of electrophysiological activity in the motor portion of the subthalamic nucleus (STN) that occurs in subjects with a history of LID. In the current study, the authors examined whether a comparable electrophysiological pattern occurs in subjects with ICDs. Subjects who underwent STN DBS within the past five years were divided into three groups based on clinical presentation those with ICDs and no significant LID (PD-ICD; n = 10), those with LID but no ICDs (PD-LID; n = 9), and those with neither ICDs nor LID (PD controls; n = 9). Subjects with ICDs were instructed to discontinue dopamine agonist treatment and add a selective serotonin reuptake inhibitor and/or atypical antipsychotic medication 1-2 months prior to DBS surgery, but all reported ongoing ICDs. The power spectrum of subthalamic activity and subthalamo-cortical coherence patterns were examined in each of the study subjects. All subjects were examined in the medication "off" and "on" states.
The three groups of subjects had comparable oscillatory activity in the STN when they were in the medication "off" state, but distinct patterns of oscillatory activity when in the medication "on" state. PD-ICD subjects had theta-alpha (4-10 Hz) activity (mean peak = 6.71 Hz) in a relatively ventral portion of the STN (2-8 mm below the intercommissural line). In contrast, PD-LID subjects had theta-alpha activity that peaked at a higher mean frequency (8.38 Hz) in a more dorsal portion of the STN (0-2 mm below the intercommissural line). Neither of these patterns was present in PD control subjects. In PD-ICD subjects, cortico-subthalamic coherence (as evaluated with scalp electrodes) was more frequent in the 4-7.5 Hz range in the region of the premotor/dorsolateral prefrontal cortex. In contrast, in PD-LID subjects, it was more frequent in the 7.5-10 Hz range in leads overlying the primary motor and supplementary motor areas. Together, these findings implicate the ventral (associative limbic) portion of the STN in the pathophysiology of ICDs, and confirm the role of the dorsal (motor) portion of the STN in that of LID.
Impulse control disorders such as compulsive eating, pathological gambling, hypersexuality, and compulsive buying are common, potentially devastating side effects of dopaminergic therapy, affecting 17% of PD patients treated with dopamine agonists. Discontinuation of the offending medication(s) is not always practical, due to exacerbation of motor symptoms or the development of dopamine agonist withdrawal syndrome (DAWS). Accordingly, there has been increasing interest in determining the biological underpinnings and potential treatments for ICDs in PD. There has been considerable controversy about the effects of STN DBS on ICDs, with some studies showing that the procedure can reduce ICDs (either directly or due to concomitant medication reduction) and others suggesting that the procedure may itself trigger impulsive/compulsive behaviors, particularly with stimulation of the ventral STN.
In this study, the authors identify a distinct pattern of oscillatory pattern in the ventral (associative-limbic) STN that correlated with the presence of ICDs and differed from the pattern observed in the more dorsal (motor) STN in subjects with LID. This is an elegant study, with novel, biologically plausible findings that implicate the ventral STN in the pathophysiology of ICDs. Moreover, these observations provide further support for the conceptualization of ICDs and LID as distinct but parallel phenomena.
Study strengths include the use of two different comparison groups (PD-LID and PD controls), and the fact that subjects were studied in both the "off" and "on" medication state. Limitations include the fact that subjects with ICDs recently had tapered or discontinued dopamine agonist treatment, raising the possibility that the observed findings may have been attributable to DAWS. Therefore, future studies should examine whether similar findings also occur in PD-ICD subjects who are still on their maintenance dose of dopamine agonist. It also would be of interest to evaluate subjects with concomitant ICDs and LID to see whether both of the observed electrophysiological patterns can coexist with an individual patient.