Objective: We aimed to analyze the real-world use of COMT inhibitors associated with levodopa in patients with Parkinson’s disease (PD) who present early fluctuations and to explore whether early COMT inhibition optimizes treatment outcomes. Methods: REONPARK is an ongoing 2-year prospective observational study. We included patients diagnosed with PD who presented signs of end-of-dose motor fluctuations for <2 years and started COMT inhibitors according to clinical practice. Outcomes included the clinician and patient global impression of change (CGI-C, PGI-C), the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Parkinson’s Disease Questionnaire-8 (PDQ-8), Non-Motor Symptoms Scale (NMSS), 19-Symptom Wearing-off Questionnaire (WOQ-19), and safety. We present a pre-planned interim analysis (cut-off date 3 July 2023) of patients who completed the first 3 months of follow-up. Results: Seventy patients were analyzed (mean levodopa dose at inclusion 484.8 mg; duration of motor fluctuations 0.6 years). In all cases, COMT inhibition was initiated with opicapone, and 81% maintained a stable levodopa dose at 3 months. After 3 months of treatment with opicapone, 73.5% and 62.8% of patients improved on CGI-C and PGI-C, respectively. MDS-UPDRS scores improved significantly with a mean change from baseline of −3.3 ± 7.7 (p < 0.001) for Part III and −1.3 ± 1.7 (p < 0.001) for Part IV. The mean OFF time decreased from 3.7 ± 2.6 h at baseline to 2.2 ± 2.3 h, and 20.6% of patients no longer experienced OFF periods. Patients experiencing no impact of fluctuations increased from 10% to 45.6%. Conclusions: In PD patients with early fluctuations, three months of opicapone reduced the OFF time and improved functional outcomes, suggesting potential benefits in the early stages.

Non-motor symptoms (NMS) in Parkinson’s disease (PD), including neuropsychiatric or dysautonomic complaints, fatigue, or pain, are frequent and have a high impact on the patient’s quality of life. They are often poorly recognized and inadequately treated. In the recent years, the growing awareness of NMS has favored the development of techniques that complement the clinician’s diagnosis. This review provides an overview of the most important ultrasonographic findings related to the presence of various NMS. Literature research was conducted in PubMed, Scopus, and Web of Science from inception until January 2021, retrieving 23 prospective observational studies evaluating transcranial and cervical ultrasound in depression, dementia, dysautonomic symptoms, psychosis, and restless leg syndrome. Overall, the eligible articles showed good or fair quality according to the QUADAS-2 assessment. Brainstem raphe hypoechogenicity was related to the presence of depression in PD and also in depressed patients without PD, as well as to overactive bladder. Substantia nigra hyperechogenicity was frequent in patients with visual hallucinations, and larger intracranial ventricles correlated with dementia. Evaluation of the vagus nerve showed contradictory findings. The results of this systematic review demonstrated that transcranial ultrasound can be a useful complementary tool in the evaluation of NMS in PD.

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson’s disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, “Off” time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD.

Objective: To evaluate the sustained real-world effectiveness and safety of catechol-O-methyltransferase (COMT) inhibitors added to levodopa in patients with Parkinson’s disease (PD) presenting early motor fluctuations. Methods: REONPARK is an ongoing, multicenter, prospective observational study conducted in Spain. Adult patients with PD and end-of-dose motor fluctuations for <2 years initiating a COMT inhibitor were included. Outcomes assessed at 3, 6, and 12 months included Clinician and Patient Global Impression of Change (CGI-C, PGI-C), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Wearing-off Questionnaire (WOQ-19), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Questionnaire-8 (PDQ-8), and safety. This article presents the 3-, 6-, and 12-month planned interim analysis of the study. Results: A total of 143 patients were included (99.3% treated with opicapone), of whom 138, 131, and 89 patients completed the 3, 6, and 12 months of follow-up, respectively. Levodopa doses remained stable in most patients (73% at 12 months). Significant and sustained improvements were observed in MDS-UPDRS Parts III and IV scores, as well as the total MDS-UPDRS score over 12 months, with greater likelihood of Part IV improvement in patients receiving <4.5 mg/kg/day of levodopa. OFF time decreased by 1.6–2.0 h from baseline. ON-time quality was maintained over time with 97.7% of patients reporting no or minimal functional impact from dyskinesia, while 47.7% of patients had no impact from motor fluctuations and 36.4% of patients no longer experienced OFF periods at 12 months. PDQ-8 scores remained stable and no overall benefit on total non-motor symptoms burden was demonstrated, despite improvements in selected domains among patients with a higher baseline non-motor symptoms burden. WOQ-19 scores improved significantly. Conclusions: In PD patients with early motor fluctuations, opicapone initiation was associated with sustained improvements in motor outcomes and reduced OFF time, and maintained the ON-time quality over 12 months, with stable levodopa dosing.