Objective: Dopamine dysregulation syndrome (DDS) is a phenomenon where Parkinson’s disease (PD) patients develop an addictive pattern of dopaminergic drug intake, mainly to avoid the motor and nonmotor aspects related to “OFF” state. Deep brain stimulation of subthalamic nucleus (STN-DBS) may improve motor disabilities in PD. Effects of STN-DBS on DDS are less clear, since evidence suggest that STN-DBS may improve, worsen, or have no effect on preoperative DDS. However, some reports described the onset of DDS after STN-DBS.

Background: We report two unusual cases of DBS-related DDS post STN-DBS, where a progressive increase in stimulation parameters are required to simply maintain motor performance.

Method: The first case is a 36 yo male who received bilateral STN-DBS after 8 years of PD. He exhibited a good response to DBS but the effects would wane within 3 weeks such that he required frequent DBS settings change to improve his OFF symptoms. In 18 months post-operatively, his DBS parameter was increased (TEED*1s: L-STN +1040%; R-STN +516%) and an escalation in his dopaminergic uptake was observed (LED 280 pre-op, 775 post-op). The second case is a 47 yo male who received bilateral STN-DBS after 9 years of PD. He exhibited good motor response to STN-DBS but effects would wane after 6 weeks when he would require further DBS parameters adjustments. Within a 12 months period, his DBS output was increased (L-STN +700%; R-STN +407%), without an equivalent reduction in his medications.

Results: Both of these patients exhibited genuine waning in the effects of DBS as evidenced by worsening motor symptoms which improved following DBS programming. Neither exhibited the typical L-dopa associated DDS behaviour where excessive treatment is sought at the expense of severe dyskinesia or harmful social behaviour. Both subjects had an history of pathological gambling, that subsided completely pre-DBS surgery following dopamine agonist withdrawal.

Conclusion: Most DDS studies have focused on the ventral/limbic striatal sensitisation following L-dopa treatment. Here we described an unusual motor sensitisation to the effects of STN-DBS in 2 patients with a history of ICD, but without the accompanying drug-seeking behavioural change. We suggest that a possible underlying mechanism relies on a neuroadaptation in basal ganglia dopaminergic motor circuities., therefore explaining the progressively higher amount of TEED and LED required to maintain the motor response.

References: Bhattacharjee S. Impulse control disorders in Parkinson’s disease: Review of pathophysiology, epidemiology, clinical features, management, and future challenges. Neurol India. 2018 Jul-Aug; 66 (4): 967-975. doi: 10.4103/0028-3886.237019. Merola A, Romagnolo A, Rizzi L, Rizzone MG, Zibetti M, Lanotte M, Mandybur G, Duker AP, Espay AJ, Lopiano L. Impulse control behaviors and subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2017 Jan; 264 (1): 40-48. doi: 10.1007/s00415-016-8314-x. Epub 2016 Oct 19. Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, Brooks DJ, Lees AJ, Piccini P. Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol. 2006 May; 59 (5): 852-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/motor-dds-is-motor-sensitization-underestimated-after-stn-dbs/