Continuous Subcutaneous Apomorphine Infusion Research Articles

Nocturnal continuous subcutaneous infusion of apomorphine in advanced Parkinson's disease: a series of 37 cases

Multiple factors can cause sleep disturbances in Parkinson's disease. The quality of sleep and therefore of life is usually improved with continuous dopaminergic stimulation therapies, such as continuous subcutaneous infusion of apomorphine. We present an observational retrospective study of patients at our centre with advanced Parkinson's disease, treated with continuous infusion of apomorphine, with treatment extended to nights, between 2011 and 2022. We collected data from 37 patients, and evaluated the indication for nocturnal treatment, efficacy, safety and reasons for withdrawal. Fifty percent of patients began nocturnal treatment for motor complications, 19% for non-motor complications and 31% for both. The most common non-motor symptoms were sleep fragmentation and disturbances, neuropathic pain, psychiatric symptoms and intense nocturia. Twenty of the 37 patients (54%) were continuing treatment at the end of the study follow-up, 16 (43%) discontinued the infusion, and one (3%) was lost to follow-up. The adverse reactions that led to termination of the infusion were severe nodules (two), dopaminergic psychosis (one) and a positive Coombs test with/without anaemia (one). Four patients terminated the nocturnal infusions while continuing the daytime infusions due to suboptimal adaptation to the device. Patients whose symptoms improved without any significant adverse effects continued the treatment. Continuous infusion of apomorphine during the night was an effective and safe treatment in our series.

Gender disparity in access to advanced therapies for patients with Parkinson's disease: a retrospective real-word study.

Gender differences in the access to advanced therapies for Parkinson's disease (PD) are poorly investigated. The objective of this study was to investigate the presence of any gender disparity in the access to advanced therapies for PD. Retrospective study. Data from patients with consistent access to the Parkinson's and Movement Disorder Center of L'Aquila over the last 10-year period were screened. Patients selected for advanced therapies were included. Out of 1,252 patients, 200 (mean age ± SD 71.02 ± 9.70; 72% males; median Hoen Yahr level: 3, minimum 1 maximum 5) were selected for advanced therapies: 133 for Magnetic Resonance guided Focused Ultrasound (MRgFUS) thalamotomy (mean age ± SD 70.0 ± 8.9; 77% males), 49 for Levodopa/Carbidopa Intestinal Gel (LCIG) infusion (mean age ± SD 74.3 ± 11.4; 59% males), 12 for Deep Brain Stimulation (DBS) (mean age ± SD 71.2 ± 6.3; 75% males), and 7 for Continuous Subcutaneous Apomorphine Infusion (CSAI) (mean age ± SD 69.7 ± 5.5; 43% males). No sex differences were found in relation to age (MRgFUS group: males vs. females 70.2 ± 8.9 vs. 70.8 ± 8.9, p-value = 0.809; LCIG group: males vs. females 73.5 ± 13.0 vs. 75.5 ± 8.5, p-value = 0.557; DBS group: males vs. females 77.2 ± 8.1 vs. 67.3 ± 8.6, p-value = 0.843; CSAI group: males vs. females 73.3 ± 4.0 vs. 67.0 ± 5.2, p-value = 0.144) and disease duration (MRgFUS group: males vs. females 8.3 ± 4.4 vs. 9.6 ± 6.7, p-value = 0.419; LCIG group: males vs. females 14.5 ± 5.81 vs. 17.3 ± 5.5; p-value = 0.205; DBS group: males vs. females 15.0 ± 9.6 vs. 15.5 ± 7.7, p-value = 0.796; CSAI group: males vs. females 11.7 ± 3.7 vs. 10.3 ± 3.7, p-value = 0.505). The predominance of males is higher than that expected based on the higher prevalence of PD in men. Women are less confident in selecting advanced therapies during the natural progression of their disease. Factors accounting for this discrepancy deserve further investigation.

Personality and quality-of-life improvement after apomorphine infusion in Parkinson’s disease

Abstract People with Parkinson’s disease with motor fluctuations can be treated by Continuous Subcutaneous Apomorphine Infusion (CSAI) to reduce their symptoms. Nonetheless, factors are lacking to predict patients’ quality-of-life amelioration after CSAI. This pilot study aimed to evaluate associations between personality dimensions and quality-of-life improvement after six months of CSAI. Thirty-nine people with Parkinson’s disease awaiting CSAI were included. Linear regression models between “Temperament and Character Inventory” personality dimensions at baseline and percentage of change in PDQ-39 (Parkinson’s Disease Questionnaire-39) scores after six months of CSAI were realized (n = 35). Temperament and Character Inventory was also compared between patients awaiting CSAI and patients awaiting deep brain stimulation of the sub-thalamic nucleus (n = 39 from the PREDI-STIM study). Higher Reward Dependence scores were associated with a better quality-of-life outcome after six months of CSAI, while Self-Directedness scores were associated with a better quality of life before CSAI (as opposed to Harm Avoidance, Reward Dependence, and Self-Transcendence scores associated with a worse quality of life). Moreover, people with Parkinson’s disease awaiting deep brain stimulation of the sub-thalamic nucleus had similar Temperament and Character Inventory dimensions compared to patients awaiting CSAI. People with Parkinson’s disease with higher Reward Dependence scores at baseline had the best quality-of-life improvement after six months of CSAI. This finding could be used to better prepare and accompany people with Parkinson’s disease during CSAI establishment. Moreover, this result could serve as an orientation factor to second-line treatments.

What was first and what is next in selecting device-aided therapy in Parkinson's disease? Balancing evidence and experience.

Parkinson's disease (PD) progresses with motor fluctuations emerging several years after treatment initiation. Initially managed with oral medications, these fluctuations may later necessitate device-aided therapy (DATs). Globally, various DATs options are available, including continuous subcutaneous apomorphine infusion, deep brain stimulation, levodopa-carbidopa intestinal gel, levodopa-entacapone-carbidopa intestinal gel, and subcutaneous foslevodopa/foscarbidopa infusion, each with its complexities. Hence, matching complex patients with suitable therapy is critical. This review offers practical insights for physicians managing complex PD cases. Balancing evidence and experience is vital to select the most suitable DATs, considering factors like disease stage and patient preferences. Comparative analysis of DATs benefits and risks provides essential insights for clinicians and patients. Treatment sequences vary based on availability, patient needs, and disease progression. Less invasive options like apomorphine are often preferred initially, followed by other DATs if needed. Patient selection requires comprehensive evaluations, including motor function and cognitive status. Follow-up care involves symptom monitoring and adjusting medications. Customized treatment plans are essential for optimizing PD management with DATs.

Terminal Care in Parkinson's Disease: Real-Life Use of Continuous Subcutaneous Apomorphine Infusion to Improve Patient Comfort.

There are currently no recommendations on the therapeutic management of Parkinson's disease (PD) patients at the end of life. To describe a cohort of patients with PD who benefited from continuous subcutaneous apomorphine infusion (CSAI) initiation at the end of their life as comfort care. This real-life cohort includes 14 PD patients, who benefited from 24-h, low-dose CSAI (0.5-3 mg/h) in the context of terminal care. Patient's comfort (pain, rigidity, and/or ability to communicate) and occurrence of CSAI-related side-effects (nausea/vomiting, cutaneous and behavioral manifestations) were evaluated based on medical records. All patients (age 62-94 years, disease duration 2-32 years) presented with late-stage PD and a compromised oral route. Treatment lasted from a few hours to 39 days. CSAI led to substantial functional improvement, with a good safety profile. Overall clinical comfort was deemed improved by the medical team, the patient, and/or caregivers. CSAI might be a promising approach in PD terminal care, as it reduces motor symptoms and overall discomfort, with an apparent good safety profile. Use of the apomorphine pen, sublingual film or a classic syringe pump might be considered when apomorphine pumps are not available. Larger observational cohorts and randomized controlled trials are needed to establish the efficacy and tolerability of apomorphine in the context of terminal care and more broadly, in an advance care planning perspective.

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Safety and tolerability of long-term apomorphine infusion in advanced Parkinson's disease: an Indian multi-center (APO-IND) experience

Advanced Parkinson’s Disease (APD) is complicated by the emergence of motor and non-motor fluctuations, which are initially predictable and eventually become unpredictable, in part due to erratic gastric absorption and short half of oral levodopa. Attempts to manage such fluctuations with oral dopaminergic drugs often lead to disabling dyskinesias. Continuous Subcutaneous Apomorphine Infusion (CSAI), despite being approved for the treatment of APD since 1993, was approved in India only in 2019. We studied the safety, tolerability and efficacy of CSAI in Indian patients with APD in a registry design to raise local awareness of this important treatment. We conducted a prospective registry-based observational audit at 10 centers across different states of India. Patients with APD, not responding to or with significant side effects from oral dopaminergic therapy, were assessed at baseline and at month 6 and 12 following CSAI infusion. Fifty-one patients completed the study, CSAI significantly reduced the functional impact of dyskinesia (p < 0.01 at 6 months and p < 0.001 at 12 months). There was a significant improvement in the OFF-state from baseline (p < 0.01 at 6 months and p < 0.001 at 12 months) No discernible side effects were observed apart from mild site reaction (n = 7), nausea (n = 7) skin nodules (n = 2). CSAI demonstrated safety, efficacy, tolerability and improved quality of life in patients with APD, as shown in previous studies. Our study highlighted current existing inequalities in treatment availability, lack of awareness, knowledge gap, affordability and cost remains a concern regarding apomorphine use in Indian PD population.

Infusion Therapies in the Treatment of Parkinson's Disease.

Oral levodopa is the gold-standard therapy for treating Parkinson's disease (PD) but after a few years of treatment the therapeutic window narrows, and patients often experience various treatment-related complications. Patients in this advanced PD stage may benefit from alternative therapy, such as continuous intrajejunal delivery of levodopa-carbidopa intestinal gel (LCIG; or carbidopa-levodopa enteral suspension), continuous intrajejunal delivery of levodopa-carbidopa-entacapone intestinal gel, or continuous subcutaneous apomorphine infusion. Consideration and initiation of infusion therapies in advanced PD are suggested before the onset of major disability. The present review summarizes clinical evidence for infusion therapy in advanced PD management, discusses available screening tools for advanced PD, and provides considerations around optimal use of infusion therapy.

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

An update on advanced therapies for Parkinson's disease: From gene therapy to neuromodulation.

Advanced Parkinson's disease (PD) is characterized by increasingly debilitating impaired movements that include motor fluctuations and dyskinesias. At this stage of the disease, pharmacological management can result in unsatisfactory clinical benefits and increase the occurrence of adverse effects, leading to the consideration of advanced therapies. The scope of this review is to provide an overview of currently available therapies for advanced PD, specifically levodopa–carbidopa intestinal gel, continuous subcutaneous apomorphine infusion, radiofrequency ablation, stereotactic radiosurgery, MRI-guided focused ultrasound, and deep brain stimulation. Therapies in clinical trials are also discussed, including novel formulations of subcutaneous carbidopa/levodopa, gene-implantation therapies, and cell-based therapies. This review focuses on the clinical outcomes and adverse effects of the various therapies and also considers patient-specific characteristics that may influence treatment choice. This review can equip providers with updated information on advanced therapies in PD to better counsel patients on the available options.

A Review on Response to Device-Aided Therapies Used in Monogenic Parkinsonism and GBA Variants Carriers: A Need for Guidelines and Comparative Studies.

Parkinson’s disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring.

Device-Assisted and Neuromodulatory Therapies for Parkinson's Disease: A Network Meta-Analysis.

Device-assisted and neuromodulatory therapies are the standard of care for Parkinson's disease (PD) with disabling motor complications. We aimed to compare and rank the currently available advanced therapies for PD on patient relevant outcomes. We searched various databases for randomized controlled trials that studied subthalamic nucleus deep brain stimulation (STN-DBS), globus pallidus interna (GPi) DBS, pallidotomy, subthalamotomy, continuous subcutaneous apomorphine infusion (CSAI), or intrajejunal levodopa infusion (IJLI), in patients with PD and motor complications. Primary outcome was the quality of life (QOL) at 6 months. Secondary outcomes included Unified Parkinson's Disease Rating Scale III and II, ON time, OFF time, levodopa equivalent daily doses, and adverse events (AE). Data were pooled using a Bayesian network meta-analysis, summarized as mean difference (MD) with 95% credibility intervals (CrI) and visualized in forest plots/league tables. Surface under the cumulative ranking curve plots determined the ranking probability. We identified 6745 citations and included 26 trials. STN-DBS (MD, -8.0; 95% CrI, -11, -5.8), GPi-DBS (MD, -7.1; 95% CrI, -11, -2.9), and IJLI (MD, -7.0; 95% CrI, -12, -1.8) led to better QOL than medical therapy alone, without significant differences among them. STN-DBS had the highest probability of being ranked the best treatment for QOL (79.6%), followed by IJLI (63.5%) and GPi-DBS (62.8%). In advanced PD, STN-DBS alleviates more patient and clinician relevant outcomes, followed by GPi-DBS and IJLI. In resource limited settings, unilateral pallidotomy may improve motor symptoms and activities of daily living, although overall QOL may not be improved. © 2022 International Parkinson and Movement Disorder Society.

Continuous subcutaneous apomorphine infusion for the management of Parkinson’s disease at the end-of-life: two preliminary case reports (P1-4.011)

Continuous subcutaneous apomorphine infusion for the management of Parkinson’s disease at the end-of-life: two preliminary case reports (P1-4.011)

Long-Term Persistence and Monotherapy with Device-Aided Therapies: A Retrospective Analysis of an Israeli Cohort of Patients with Advanced Parkinson's Disease.

IntroductionPatients with advanced Parkinson’s disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG). The study also aims to describe patient profiles, treatment discontinuation rates, co-medication patterns, monotherapy rates, and rates of healthcare visits and their associated costs for patients receiving all forms of DAT (deep brain stimulation [DBS], continuous subcutaneous apomorphine infusion [CSAI], or LCIG).MethodsIn this retrospective analysis of the Israeli Maccabi Healthcare Services database, adult patients with PD were analyzed in three cohorts, based on DAT (DBS, CSAI, or LCIG). The primary endpoint was LCIG treatment persistence 12 months after initiation.ResultsThis analysis included 161 DAT-treated patients (LCIG, n = 62; DBS, n = 76; CSAI, n = 23). Among those who discontinued, the mean time to discontinuation was 86.4 months for LCIG and 42.4 months for CSAI (p = 0.046). Twelve months after initiation, 14.3% LCIG, 10.7% DBS, and 5.9% CSAI patients were not receiving any additional anti-parkinsonian therapy. At the last recorded visit, 28.6% LCIG, 13.3% DBS, and 5.9% CSAI patients received DAT as monotherapy. During the first 12 months after initiation, 45.2% LCIG, 65.2% CSAI, and 1.3% DBS patients had no reported hospitalization days. Annual healthcare visit costs decreased following LCIG initiation (US$9491 vs. $8146) and increased following DBS ($4113 vs. $7677) and CSAI ($6378 vs. $8277).ConclusionDAT are well maintained in patients with advanced PD. These retrospective data suggest that patients receiving LCIG may have higher long-term persistence rates compared with patients receiving CSAI. A subgroup of patients was treated with DAT as monotherapy without additional oral anti-parkinsonian therapy, with LCIG showing the highest rates.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02072-x.

Switching and Combining Device-Aided Therapies in Advanced Parkinson's Disease: A Double Centre Retrospective Study.

Background: Device-aided therapies (DAT), such as continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS), have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). In some patients, it is necessary to switch or combine DATs for various reasons. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons, adverse events for switching/combining, and their frequency were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale, Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III, Mini Mental State Examination, and Parkinson’s Disease Questionnaire 39. Descriptive statistics and non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in a total of 30 patients (6%) who either switched DAT (n = 24: 7 LCIG-to-STN−DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN−DBS, 8 CSAI-to-LCIG, 1 STN−DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN−DBS, and 1 STN−DBS-to-CSAI-to-LCIG) or combined DATs (n = 6:5 STN−DBS+LCIG and 1 STN−DBS+CSAI-to-STN−DBS+LCIG). In most of these patients, an inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT-related complications.

Apomorphine and frontal dysfunction in Parkinson's disease

Dysexecutive disorder and apathy are characteristic symptoms of frontal dysfunction linked to Parkinson's disease. The effect of continuous subcutaneous apomorphine infusion is not known in detail. A search for the most relevant studies published to date in this field was carried out, along with their analysis. Apomorphine achieves improvements in tests that measure tasks such as planning, attention, verbal fluency and apathy. Due to its distinctive pharmacological profile, with enhanced activity on D1-type dopaminergic receptors, apomorphine may have beneficial effects on the frontal dysfunction produced by the disease.

Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson’s disease: A prospective study of 22 patients

IntroductionParkinson’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. MethodsWe 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. ResultsAt 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. ConclusionIn 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.

Continuous Subcutaneous Apomorphine Infusion before Subthalamic Deep Brain Stimulation: A Prospective, Comparative Study in 20 Patients.

ABSTRACTBackgroundStudies 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.ObjectiveTo 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.MethodsWe 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.ResultsCompared 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).ConclusionsBoth 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.

Early factors for predicting discontinuation to subcutaneous Apomorphine infusion in Parkinson's disease: A prospective analysis of the Thai Apomorphine Registry

IntroductionAlthough continuous subcutaneous apomorphine infusion (CSAI) is an effective therapy for Parkinson's disease (PD) with motor fluctuations, data from Asian cohorts is limited. The therapy is often discontinued due to the complexity of its delivery. MethodsFifty-one PD patients undergoing CSAI as an add-on therapy were enrolled in the Thai Apomorphine Registry, an electronic database that recorded clinical characteristics and parameters during the 14-consecutive-day titration and long-term follow-up. Factors at the time of titration were documented in order to identify predictors of long-term discontinuation. ResultsFollowing initiation, PD patients were administered a mean CSAI dose of 5.89 mg/h (SD 1.36) over a mean time of 12.28 h (SD 1.90) each day. The mean follow-up period was 626.2 days (SD 619.17). Significant reductions in UPDRS-I, II, III, and IV scores, total NMSQ score, PDQ-8 score, daily off and dyskinesia hours, Timed Up and Go test, walking step test, levodopa-equivalent daily dose, number of times a day the levodopa was taken versus pre-CSAI values were observed (p < 0.05, each). Thirty-five (68.6%) patients discontinued during the follow-up period. Relative risks of variables recorded at the time of titration that determined discontinuation of CSAI therapy were an absence of full-time caregivers, achieving a daily off hours reduction <3.5 h, and NMSQ scores at the time of CSAI titration ≥9.5 points. ConclusionIdentifying factors that predict discontinuation of CSAI at the time of its initiation may help physicians to better understand the patient's drug response and how to manage them long-term.