Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome.

OBJECTIVE: Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome. METHODS: In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005-2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded. RESULTS: Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment. CONCLUSIONS: Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.

A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation.

Prospective comparative long-term data on the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and continuous subcutaneous infusion of apomorphine (CSAI) in patients with advanced Parkinson disease (PD) are lacking. We report 5-year follow-up of 25 PD patients treated with either STN-DBS (n = 13) or CSAI (n = 12) who fulfilled CAPSIT-PD criteria. Cohorts were matched for disease duration and severity of motor complications. Baseline clinical and neuropsychological status did not differ among cohorts. Patients were assessed with the UPDRS, MMSE, HAMD-17 and Neuropsychiatric Inventory (NPI).Twelve subjects reached the 5-year follow-up with STN-DBS (one was lost at follow-up) versus two in the CSAI cohort. Drop-outs with CSAI were due to subcutaneous nodules (n = 2), insufficient control of motor fluctuations and dyskinesia (n = 4), death for unrelated reasons (n = 3) and one was lost at follow-up. Average apomorphine dose at last visit was 83.4 ± 19.2 mg/day and average treatment duration was 30 months. At 1-year as well as at last follow-up (intention-to-treat analysis), both therapies decreased daily off-time but only STN-DBS reduced dyskinesia duration and severity. Decrement of medications was greater with STN-DBS. There was a significant worsening of NPI after STN-DBS, primarily because four subjects developed apathy.