(1) Background: Subcutaneous apomorphine infusion (SCAI) is one of the three main treatment options for motor fluctuations in advanced Parkinson’s disease (PD). The adherence to SCAI is generally ...considered to be low due to adverse events and because it is perceived as a treatment option to be used for a limited period only. We evaluated the reasons for discontinuation of SCAI in relation to when patients stopped treatment. (2) Methods: We reviewed the medical records of PD patients treated with SCAI at a single center, capturing patient demographics and the reasons for cessation of SCAI. (3) Results: 101 patients were included in the analysis, with a median time on treatment of 6.34 years. The main reasons for stopping SCAI were adverse events, death, and dissatisfaction with treatment. In the first 6 years of treatment, the predominant side effects leading to discontinuation were somnolence and hallucinations. (4) Conclusions: We suggest that SCAI can be an effective long-term treatment option for advanced PD, but it requires careful patient selection, a high level of communication with the patient and carer, and rigorous monitoring of the effects of treatment and for any adverse events so they can be promptly managed.
Objectives
Deep brain stimulation, continuous subcutaneous apomorphine infusion, and levodopa–carbidopa intestinal gel infusion, together called device‐aided therapies (DAT), are introduced when oral ...and transdermal pharmacotherapy are not enough for a satisfactory control of Parkinson's disease (PD) symptoms. Solid relationships are central to an individual's well‐being, but the impact of close relationships in advanced PD remains underexplored. The aim of this study was to investigate the development of close relationships between PD patients and their partners following the initiation of DAT and to examine the relationship structures in these relationships.
Materials and Methods
This was a retrospective quantitative multicenter pilot study wherein 41 couples, patients with advanced PD and their partners, retrospectively rated their relationship satisfaction before the start of DAT, after one year of DAT and at the time of the interview. The couples also answered the Experiences in Close Relationships—Questionnaire of Relational Structures (ECR‐RS).
Results
Partners more often report changes in relationship satisfaction than patients between baseline and both 1 year after start of DAT (p = .049) and last evaluation (p = .041). The ECR‐RS data reported significantly higher avoidance score for partners (p = .005) and significantly higher anxiety score for patients (p = .024).
Conclusions
The close relationship wherein one part has PD and receives DAT has a high risk of being unequal. Prospective studies are needed for further clarification of the interplay between advanced PD, DAT, and close relationships, this in order to improve pre‐ and postinterventional support for PD patients receiving DAT, as well as their partners.
The close relationship wherein one part has PD and receives Device‐Aided Therapy has a high risk of being unequal. Partners more often report changes in relationship satisfaction and report significantly higher avoidance score on the ECR‐RS in contrast to patients who reports significantly higher anxiety scores.
Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) ...and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life). Defining cutoffs by consensus, which can be subsequently tested and refined, is the first step to optimizing OM in the management of PD. OM should be used by all clinicians that treat people with PD but the least experienced may find the most value, but this requires guidance from experts to allow non-experts to apply guidelines. While evidence is gained for devices that produce OM, expert opinion is needed to supplement the evidence base.
Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also ...influence non-motor symptoms. The aim of this study is to investigate how the cerebral 5-HT system associates to disturbances in cognition and mood in PD patients with DBS-STN turned on and off. We used psychological tests and questionnaires to evaluate cognitive function and the effects on mood from turning DBS-STN off. We applied a novel PET neuroimaging methodology to evaluate the integrity of the cerebral serotonin system. We measured 5-HT1BR binding in 13 DBS-STN-treated PD patients, at baseline and after turning DBS off. Thirteen age-matched volunteers served as controls. The measures for cognition and mood were correlated to the 5-HT1BR availability in temporal limbic cortex. 5-HT1BR binding was proportional to working memory performance and inverse proportional to affective bias for face recognition. When DBS is turned off, patients feel less vigorous; the higher the limbic and temporal 5-HT1BR binding, the more they are affected by DBS being turned off. Our study suggests that cerebral 5-HTR binding is associated with non-motor symptoms, and that preservation of serotonergic functions may be predictive of DBS-STN effects.
Key Clinical Message
Tardive dystonia is a risk factor in medical antipsychotic treatment. It often begins with repetitive involuntary jaw and tongue movements resulting in impaired chewing and ...detrimental effect on the dentition. The orofacial dysfunction may go unrecognized in a neurological setting. The diagnosis may be difficult so we suggest interdisciplinary collaboration.
Tardive dystonia is a risk factor in medical antipsychotic treatment. It often begins with repetitive involuntary jaw and tongue movements resulting in impaired chewing and detrimental effect on the dentition. The orofacial dysfunction may go unrecognized in a neurological setting. The diagnosis may be difficult so we suggest interdisciplinary collaboration.
IntroductionGait difficulties are common in Parkinson’s disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to ...improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and imaging study, we aim to shed light on the mechanism of action of SCS and collect data to inform development of a scientifically sound clinical trial protocol. We also aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysisA total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months.Ethics and disseminationThis study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numberNCT05110053; ClinicalTrials.gov Identifier.
Apomorphine was introduced before the era of levodopa as a treatment for idiopathic Parkinson's disease (iPD). A number of practical obstacles were to be solved before a wider use of the drug was ...possible. Today, however, the drug is probably still underutilized. Apomorphine is a strong nonergoline D1 and D2 receptor agonist with a dopaminergic effect comparable with levodopa. In this review motor and non-motor indications for intermittent injections and subcutaneous apomorphine infusions are listed. The reduction of 'off' periods is more than 50% on infusion therapy and if monotherapy is achieved a significant reduction of pre-existing levodopainduced dyskinesias is seen. The aim of this review is to give practical insight into apomorphine treatment, highlighting side effects, and complications and device-related problems are discussed with advice on how to prevent or handle these, should they occur. A number of practical points including the apomorphine test, requirements of the clinical setting, how to increase adherence and troubleshooting are added.
Subcutaneous apomorphine infusion is a clinically established therapy for patients with Parkinson's disease with motor fluctuations not optimally controlled by oral medication. Open-label studies ...have shown that apomorphine infusion is effective in reducing off time (periods when antiparkinsonian drugs have no effect), dyskinesias, and levodopa dose, but confirmatory evidence from double-blind, controlled studies is lacking. We aimed to investigate the efficacy and safety of apomorphine infusion compared with placebo in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal treatment.
In this randomised, placebo-controlled, double-blind, multicentre trial, we enrolled patients at 23 European hospitals who had been diagnosed with Parkinson's disease more than 3 years previously and had motor fluctuations not adequately controlled by medical treatment. Patients were randomly assigned (1:1) with a computer-generated randomisation code, stratified by site, to receive 3–8 mg/h apomorphine or placebo saline infusion during waking hours (16 h a day range 14–18 was acceptable) for 12 weeks. The flow rate of the study drug and other oral medications could be adjusted during the first 4 weeks on the basis of individual efficacy and tolerability, after which patients entered an 8-week maintenance period. The primary endpoint was the absolute change in daily off time based on patient's diaries, and was assessed in the full analysis set, which was defined as all patients who received at least one dose of allocated study drug and had efficacy data available at any timepoint post-baseline. Safety was assessed in all patients who received at least one dose of apomorphine or placebo. All study participants and investigators were masked to treatment assignment. Both the 12-week double-blind phase and the 52-week open-label phase of this study are now complete; this paper reports results for the double-blind phase only. This study is registered with ClinicalTrials.gov (NCT02006121).
Between March 3, 2014, and March 1, 2016, 128 patients were screened for eligibility and 107 were randomly assigned, of whom 106 were included in the full analysis set (n=53 in both groups). Apomorphine infusion (mean final dose 4·68 mg/h SD 1·50) significantly reduced off time compared with placebo (−2·47 h per day SD 3·70 in the apomorphine group vs −0·58 h per day 2·80 in the placebo group; difference −1·89 h per day, 95% CI −3·16 to −0·62; p=0·0025). Apomorphine was well tolerated without any unexpected safety signals. Six patients in the apomorphine group withdrew from the study because of treatment-related adverse events.
Apomorphine infusion results in a clinically meaningful reduction in off time in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal therapy.
Britannia Pharmaceuticals.
Subcutaneous apomorphine infusion is a device-aided therapy for Parkinson’s disease that can be considered when motor fluctuations become persistent and are no longer adequately controlled by ...oral/transdermal medication. Apomorphine infusion is less invasive than enteral levodopa, deep brain stimulation or focused ultrasound, and is often indicated even when neurosurgical approaches are contraindicated. This article aims to provide practical guidance for doctors and nurses initiating and treating patients with apomorphine infusion, and is based on both trial data and clinical experience from movement disorders specialists. A post hoc analysis of data from the TOLEDO randomized clinical trial of apomorphine infusion was conducted along with an analysis of ‘real world’ experience from 13 movement disorders specialists using a questionnaire that focused on starting patients on apomorphine infusion. Practical guidelines for starting treatment with apomorphine infusion are provided taking into consideration the regional disparities in healthcare. Apomorphine infusion is straightforward to administer but to be successful it requires concordance from the patient and family, and clinical support from an experienced team of doctors and nurses, particularly in the early months of treatment.