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Background and Objectives: To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD., Methods: We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD-) probable RBD preoperatively., Results: At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] III "off": 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire-39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD- patients. Both pre-opRBD+ and pre-opRBD- patients had significant MDS-UPDRS IV score decrease (-37% and -33%, respectively), MDS-UPDRS III "med 'off'/stim 'on'" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes., Conclusions: In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery., Trial Registration Information: NCT02360683., Classification of Evidence: This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery., (© 2021 American Academy of Neurology.)

Objective: To investigate the acute effect of subthalamic nuclei deep brain stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients with Parkinson disease. We hypothesized that a modification of pain threshold after STN-DBS would suggest a central modification of pain perception, whereas the absence of pain threshold change after STN-DBS would correspond to a peripheral mechanism via a decrease of painful stimuli., Methods: Nineteen patients with Parkinson disease were included in this double-blind, randomized, crossover study. Postoperatively, we evaluated pain thresholds (thermal and mechanical) and motor symptoms under 3 acute conditions: stimulation on/medication off; stimulation off/medication on; and stimulation off/medication off. We also conducted a retrospective analysis of the data prospectively recorded during the follow-up of the cohort pre- and postoperatively (Unified Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent levodopa daily dose, and tapping test score)., Results: We found a significant increase of pain and tolerance mechanical thresholds not only after acute STN-DBS but also after acute levodopa administration. We did not find any significant correlation between postoperative clinical pain improvement and UPDRS-III improvement after acute levodopa or STN-DBS, nor with motor complications improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was found between postoperative clinical pain improvement and mechanical pain threshold modification., Conclusion: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.

Objective: To assess the role of age in the results of bilateral deep brain stimulation in the subthalamic nucleus (DBS-STN), we carried out a study of two groups of patients regarding age at time of surgery., Methods: We compared, up to 2 years after surgery, the clinical effects, safety, and quality of life in parkinsonian patients younger than 65 years old (young patients) vs parkinsonian patients 65 years old or older (old patients)., Results: The mean age was 57.4 +/- 4.9 years (n = 53) in young patients and 68.8 +/- 2.8 years (n = 34) in old patients. A dramatic improvement in motor complications was equally observed in both groups of patients. There was no significant difference between the groups regarding acute effects of DBS-STN on the motor score of the Unified Parkinson's Disease Rating Scale part III (UPDRS III). Time course evolution of UPDRS the motor score (p < 0.0001) and axial score (p = 0.0001) assessed postoperatively in "on" medication and "on" stimulation conditions appeared worse in old patients as compared to young patients. Improvement in the Schwab and England Scale score was better in young patients in "on" (p < 0.0003) and "off" state (p < 0.001). Quality of life assessed with the 39-item Parkinson's Disease Questionnaire showed an improvement in subscales evaluating mobility (p < 0.0001), activities of daily life (p < 0.0001), emotion and stigma (p = 0.0004), cognition (p < 0.0074), and communication (p = 0.0029) in young patients as compared to old patients. Side effects were similar in the two groups., Conclusions: Although deep brain stimulation in the subthalamic nucleus reduces motor complications equally in both groups of patients, postoperative quality of life improved only in young patients.

Objective: To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD)., Methods: Fifty patients were randomized to treatment in this 10-week, double-blind, parallel-group, placebo-controlled, multicenter trial. The principal measure of outcome was the diurnal change in the "on" time with LID assessed using a self-evaluation of the motor performance fluctuations performed every 2 weeks. An acute levodopa challenge was also performed at the beginning and end of the study., Results: A reduction in the duration of "on" periods with LID was noted in favor of the clozapine group at the end of the study (placebo group day 0: 4.54 +/- 0.53 hours, end: 5.28 +/- 0.70 hours; clozapine group day 0: 5.68 +/- 0.66 hours, end: 3.98 +/- 0.57 hours; p = 0.003). The mean clozapine dosage was 39.4 +/- 4.5 (SEM) mg/day. The maximal LID score at rest during the levodopa challenge was significantly decreased under clozapine treatment, with a variation from day 0 to day 70 in the placebo group of +0.15 +/- 1.01 and in the clozapine group of -2.22 +/- 0.52 (p < 0.05). Five patients receiving clozapine and seven receiving placebo discontinued on account of adverse events. Among them, three patients in the clozapine group developed eosinophilia, which rapidly resolved after withdrawal of the drug., Conclusion: Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.