Treatment of subcutaneous nodules after infusion of apomorphine:a biopsy-controlled study comparing 4 frequently used therapies

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology

Graphical Tasks to Measure Upper Limb Function in Patients With Parkinson's Disease:Validity and Response to Dopaminergic Medication

The most widely used method to assess motor functioning in Parkinson's disease (PD) patients is the unified Parkinson's disease rating scale-III (UPDRS-III). The UPDRS-III has limited ability to detect subtle changes in motor symptoms. Alternatively, graphical tasks can be used to provide objective measures of upper limb motor dysfunction. This study investigated the validity of such graphical tasks to assess upper limb function in PD patients and their ability to detect subtle changes in performance. Fourteen PD patients performed graphical tasks before and after taking dopaminergic medication. Graphical tasks included figure tracing, writing, and a modified Fitts' task. The Purdue pegboard test was performed to validate these graphical tasks. Movement time (MT), writing size, and the presence of tremor were assessed. MT on the graphical tasks correlated significantly with performance on the Purdue pegboard test (Spearman's rho > 0.65; p <0.05). MT decreased significantly after the intake of dopaminergic medication. Tremor power decreased after taking dopaminergic medication in most PD patients who suffered from tremor. Writing size did not correlate with performance on the Purdue pegboard test, nor did it change after taking medication. Our set of graphical tasks is valid to assess upper limb function in PD patients. MT proved to be the most useful measure for this purpose. The response on dopaminergic medication was optimally reflected by an improved MT on the graphical tasks in combination with a decreased tremor power, whereas writing size did not respond to dopaminergic treatment

Continuous subcutaneous apomorphine infusion in Parkinson's disease patients with cognitive dysfunction:A retrospective long-term follow-up study

INTRODUCTION: Continuous apomorphine infusion (CAI) is an advanced therapy in fluctuating Parkinson's disease (PD). The use of CAI is controversial in PD patients with cognitive dysfunction including visual hallucinations (VHs), and orthostatic hypotension (OH). This study was set-up to analyze the effectiveness and safety of CAI in elderly PD patients with cognitive dysfunction. METHODS: This new-user cohort study identified fluctuating PD patients who started CAI treatment at the rehabilitation unit of Parkinson Expertise Center (RU-PEC) Groningen, from November 2004 until 2016. Efficacy and safety data included motor function, cognitive status, OH and VHs, and was analyzed retrospectively. Pre-existent non-motor symptoms were treated optimally before starting CAI. RESULTS: Forty-five fluctuating PD patients (age: 70.9 ± 8.1 yrs, disease duration: 10.8 ± 4.8 yrs) were identified, with pre-existing cognitive dysfunction, VHs (71%), and OH (26%). During the stay at RU-PEC (median 52 days) apomorphine was successfully titrated without worsening of pre-existing VHs and OH. The mean daily apomorphine dose was 66 ± 28 mg, accompanied by a reduction of levodopa-equivalent daily dose (LEDD) with 17%. The duration of ON-time and OFF-time significantly improved with +2.36 h (25%) and -1.66 h (-45%), respectively, while dyskinesia duration did not change. During long-term follow-up (median of 26 months) VHs and OH worsened in 9 and 4 patients, which necessitated discontinuation in 4 cases. CONCLUSION: This study demonstrates that CAI is also an effective treatment in advanced PD patients with concomitant cognitive dysfunction including VHs and OH, provided that these comorbidities are treated adequately as well

Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson's disease patients

Introduction: Continuous apomorphine infusion (CAI) is an effective treatment in fluctuating Parkinson's disease (PD). However, long-term efficacy and safety data of CAI are scarce. Methods: We retrospectively reviewed long-term outcomes of CAI on motor and non-motor symptoms in a Dutch cohort of 125 PD patients. Results: Our cohort (age: 65.8 +/- 9.8 years, disease duration: 11.9 +/- 5.7 years) had a mean daily dose of apomorphine of 66 +/- 30 mg, thereby reducing the levodopa-equivalent daily dose (LEDD) by 20%. The mean duration of treatment with apomorphine was 32.3 +/- 31.9 months, ranging up to 139 months. Three-quarters of patients discontinued within the first four years. The main reason for discontinuation was a decreasing therapeutic effect. Patients who stopped apomorphine within four years had a lower LEDD reduction at hospital discharge and at last follow-up compared to patients who continued for a longer period. CAI showed good effects on motor fluctuations and dyskinesia, with better outcomes in patients with more pronounced LEDD reduction. CAI could be safely applied in patients with pre-existing visual hallucinations (30%). Conclusion: CAI showed beneficial effects on motor and several non-motor symptoms, whereas the magnitude of LEDD reduction seems to be a positive predictive factor on the duration of CAI. (C) 2015 Published by Elsevier Ltd

Parkinson's disease, visual hallucinations and apomorphine:A review of the available evidence

BACKGROUND: Visual hallucinations (VH) occur in the clinical course of Parkinson's disease (PD) and are predictive for PD dementia. The genesis of VH is related to impaired bottom-up and/or top-down visual processing which can be linked to cholinergic dysfunction and mono-amine imbalance. The risk of developing VH with oral dopamine agonists seems to increase with advancing disease, while in contrast some clinical studies suggest that apomorphine does not worsen VH, or might even improve VH. METHODS: The aim of this study is to review the current evidence of apomorphine and its effects on VH in PD patients. RESULTS: Apomorphine is well-tolerated in PD patients with VH, also in long-term follow-up studies. Apomorphine is also suggested to have the potential to alleviate VH. Some data suggest that the positive effect of apomorphine on VH is related to its piperidine moiety, part of many anti-psychotics. Irrespective this piperidine moiety, apomorphine has a high D1-like receptor affinity, and acts as a serotonin 5-HT2A receptor antagonist, which might explain the potential anti-hallucinogenic properties as well. CONCLUSION: The anecdotal evidence suggesting that apomorphine has a relatively low proclivity to induce VH in PD may be due to its capacity to reduce serotonergic activity in particular. Therefore apomorphine is still an option to consider in fluctuating PD patients with VH, if they are treated properly with respect to their cholinergic deficits and existing VH

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease

Objective Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). Methods In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. Results In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome. Conclusions This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. (c) 2019 International Parkinson and Movement Disorder Societ