Background: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson’s disease (PD). Objective: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. Methods: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. Results: NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales ( p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. Conclusion: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

Patients with Parkinson’s disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson’s Disease) is a prospective open-label single-arm study conducted in 5 centers from Spain. The primary efficacy outcome was the change from baseline (V0) to the end of the observational period (6 months ± 30 days) (V2) in the Non-Motor Symptoms Scale (NMSS) total score. Different scales were used for analyzing the change in motor, NMS, quality of life (QoL), and disability. Thirty-three patients were included between JUL/2019 and JUN/2021 (age 63.3 ± 7.91; 60.6% males; 7.48 ± 4.22 years from symptoms onset). At 6 months, 30 patients completed the follow-up (90.9%). The NMSS total score was reduced by 27.3% (from 71.67 ± 37.12 at V0 to 52.1 ± 34.76 at V2; Cohen’s effect size = −0.97; p = 0.002). By domains, improvement was observed in sleep/fatigue (−40.1%; p < 0.0001), mood/apathy (−46.6%; p = 0.001), gastrointestinal symptoms (−20.7%; p = 0.029), and miscellaneous (−44.94%; p = 0.021). QoL also improved with a 18.4% reduction in the 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index (from 26.67 ± 17.61 at V0 to 21.75 ± 14.9 at V2; p = 0.001). A total of 13 adverse events in 11 patients (33.3%) were reported, 1 of which was severe (not related to opicapone). Dyskinesias and nausea were the most frequent (6.1%). Opicapone is well tolerated and improves global NMS burden and QoL in PD patients at 6 months.

Parkinson’s disease (PD) patients usually start treatment with apomorphine infusion (APO) in later stages of advanced PD (aPD). This timing limits the evaluation of its motor efficacy and other potential clinical benefits throughout the full course of aPD. We prospectively analyzed the effect of APO on motor and non-motor symptoms, cognitive function and quality of life (QoL) in 22 PD patients with early stage aPD, defined as: age < 71 years and diagnosis of aPD for < 3 years. At baseline, mean (±SD) age and disease duration were 59.4 ± 6.1 and 8.7 ± 3.5 years, respectively. After 6 months of APO treatment, daily off-time decreased from 4.98 ± 2.37 to 1.48 ± 1.47 h (p ≤ 0.001) and UPDRS IV scores from 7.00 ± 2.58 to 5.32 ± 2.48 (p = 0.018). Dyskinesia did not worsen with APO despite an overall increase in levodopa equivalent daily dose. Mean NMSS scores improved with APO, from 52.50 ± 27.24 to 38.68 ± 27.17 (p = 0.002), with particular improvements in apathy and sleep quality. Mean PDQ-39 score was reduced with APO from 31.96 ± 11.93 to 19.27 ± 11.86 (p ≤ 0.001). Overall, cognition did not change after APO, while slight improvements were observed in executive functioning (attention and planning). All but one patient eventually underwent subthalamic deep brain stimulation. In patients with early stage initial aPD, s substantial benefit of APO was observed on motor symptoms, driven by a 70% reduction in off-time versus baseline, superior to that observed in previous prospective studies. APO also improved frontal dysfunction in PD patients.

Background: Studies comparing the clinical efficacy of apomorphine infusion (APO) with subsequent subthalamic deep brain stimulation (STN‐DBS) in advanced Parkinson's disease (aPD) are currently lacking. Retrospective data have shown that patients treated with APO are usually older, have a more prolonged disease, and a more severe phenotype.Objective: To compare the benefit of APO with that of STN‐DBS on motor, non‐motor, cognitive, and quality of life in the same patient when given sequentially.Methods: We prospectively analyzed 20 aPD patients over 3 different treatment phases: baseline (optimized medical treatment), during APO treatment, and during subsequent STN‐DBS treatment. The APO and STN‐DBS phases were stable for 6 months, and evaluation of the different treatments was separated by 6 months.Results: Compared to baseline, APO, and STN‐DBS reduced mean daily off time by 70.5% and 89.3% (P = 0.012), respectively, and scores for Unified Parkinson's Disease Rating Scale (UPDRS) IV by 27.5% and 80.5% (P ≤ 0.001), Non‐motor symptoms scale (NMSS) by 24.6% and 49.3% (P ≤ 0.001), Montgomery Asberg depression scale (MADRS) by 7.4% and 39.0% (P = 0.27), Starkstein apathy scale (SAS) by 51.1% and 39.9% (P = 0.734), Parkinson's disease sleep scale 2 (PDSS‐2) by 25.7% and 56.7% (P ≤ 0.001), and Parkinson's disease questionnaire 39 item (PDQ‐39) by 39.6% and 64.9% (P ≤ 0.001). Global cognition did not change with either therapy, but phonetic fluency worsened after STN‐DBS compared to APO (P = 0.022).Conclusions: Both APO and STN‐DBS improved motor and non‐motor symptoms and quality of life compared to optimized medical treatment in aPD. Overall, STN‐DBS was the most effective treatment, but APO showed a pronounced benefit on motor symptoms. Effective treatment for aPD should not be delayed, even when waiting for surgery.