Establishing apomorphine treatment in Thailand: understanding the challenges and opportunities of Parkinson's disease management in developing countries.

INTRODUCTION: The increasing global burden of Parkinson's disease (PD) poses a particular challenge for developing countries, such as Thailand, when delivering care to a geographically diverse populace with limited resources, often compounded by a lack of expertise in the use of certain PD medications, such as device-aided therapies (DAT). AREAS COVERED: A panel of local, regional, and international PD experts convened to review the unmet needs of PD in Thailand and share insights into effective delivery of DAT, focusing on experience with apomorphine infusion. Despite its proven efficacy and safety, implementation of apomorphine infusion as a new option was not straightforward. This has prompted a range of health-care professional and patient-focused initiatives, led by the Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders in Bangkok, to help establish a more coordinated approach to PD management throughout the country and ensure patients have access to suitable treatments. EXPERT OPINION: Overcoming the challenges of education, proficiency, resource capacity and standard of care for PD patients in developing countries requires a coordinated effort both nationally and beyond. The best practices identified in Thailand following the introduction of apomorphine infusion might be helpful for other countries when implementing similar programs.

Long-term Apomorphine Infusion Users Versus Short-term Users: An International Dual-center Analysis of the Reasons for Discontinuing Therapy.

OBJECTIVES: A retrospective analysis at 2 specialist centers was undertaken to determine the long-term efficacy of subcutaneous apomorphine infusion (APO), rates and reasons for discontinuation, and factors that might contribute to discontinuation. METHODS: Demographics, clinical outcomes data, and reasons for discontinuation were collected for patients treated with APO at Chulalongkorn Centre of Excellence for Parkinson's Disease and Related Disorders, Bangkok, Thailand (n = 36) and Fundacion Jimemez Diaz Universidad Autonoma de Madrid, Spain (n = 16). RESULTS: There were 19 (52.7%) patients in the Thai cohort and 10 (62.5%) patients in the Spanish cohort who discontinued treatment within around 6 months of initiation, most commonly due to skin nodules (Thai cohort) and perceived lack of efficacy (Spanish cohort). Those who continued APO tended to stay on treatment. In both cohorts, APO resulted in significant reductions in Unified Parkinson's Disease Rating Scale 3 motor scores, daily OFF time, and levodopa-equivalent dose in patients who subsequently stopped therapy, suggesting APO is clinically effective even when "lack of efficacy" is stated as a reason for discontinuing. Daily OFF hours after APO therapy was found to be a significant predictive factor for APO discontinuation with an odds ratio of 5.952 (P = 0.040). The cutoff point that determined APO discontinuation was calculated to be 1.75 or more OFF hours (sensitivity, 84.6%; specificity, 63.2%). CONCLUSIONS: Apomorphine infusion is a minimally invasive therapy and therefore very easy to discontinue if difficulties arise. This fact might explain the high dropout rate of this technique. Successful long-term adherence to APO therapy requires a multidisciplinary health care team approach including regular patient follow-up and assessment and prompt resolution of queries and concerns.

Subthalamic deep brain stimulation aggravates speech problems in Parkinson's disease: Objective and subjective analysis of the influence of stimulation frequency and electrode contact location.

BACKGROUND: Speech disorders, including stuttering and hypophonia, have been reported in patients with Parkinson's disease (PD) after subthalamic deep brain stimulation (STN-DBS). OBJECTIVE: To evaluate the effect of stimulation frequency or electrode contact location on speech disorders in PD patients with STN-DBS. METHOD: In this case-controlled study, we enrolled 50 PD patients with, and 100 PD patients without STN-DBS to compare their vocal intensities, measured by a sound pressure meter, and perceptual speech ratings, obtained from the speech sections of the United Parkinson's Disease Rating Scale (UPDRS) and subjective ratings regarding the impediment of functional communication by stuttering. For patients with STN-DBS, comparisons were made between high-frequency (HFS; 130 Hz), low-frequency (LFS; 80 Hz), and off-stimulation. We also evaluated the effect of electrode contact locations on speech function. RESULTS: Patients with STN-DBS had decreased vocal intensities and UPDRS scores compared to those without (p < 0.05). Vocal intensity was significantly lower during HFS than during LFS and off-stimulation (both, p < 0.05). Stuttering impeded STN-DBS patients' communication to greater extent than for those without (p < 0.001). Vocal intensity was lower when active contacts were in the dorsal zone compared to those in the ventral zone (p < 0.05). Only STN-DBS treatment was a predictive factor for low vocal intensity (OR = 9.53, p = 0.04). CONCLUSION: High-frequency STN-DBS with dorsal zone contacts can aggravate certain speech problems in PD patients. Therefore, it is important to balance between motor control and speech impairments in these patients.

Exploring Bedroom Usability and Accessibility in Parkinson's Disease (PD): The Utility of a PD Home Safety Questionnaire and Implications for Adaptations.

BACKGROUND: Although bedrooms are identified as a major location for accidents among Parkinson's disease (PD) patients, there are no studies that specifically evaluate the bedroom environments of PD patients. OBJECTIVE: To examine the physical bedroom environment of patients with PD by generating a home safety questionnaire to rate bedroom accessibility and usability specifically for PD patients, and piloting it in a small set of PD patients, to identify environmental barriers and recommend adaptations to reduce accident risks. METHODS: Questionnaire development was based on the concept of Personal (P)-Environmental (E) fit. The P component covers five clinical domains that contribute to a patients' current state of health, including PD-related motor symptoms, PD-related non-motor symptoms, gait and balance impairments, comorbidities, and limitations on specific activities. The E component focuses on both indoor (bedroom, bathroom, living room, stairs, and kitchen), and outdoor (outdoor area and entrance) areas within a home where PD patients commonly get injured. Total score for the whole questionnaire is 171. A higher score indicates more P-E problems. RESULTS: Comprehension of questions was tested for content validity with an item-objective congruence index of above 0.6 for all items. High internal consistency (reliability) was confirmed by Cronbach's alpha coefficient of 0.828 (r). The pilot in five PD patients gave a mean total score of 48.2 ± 7.29 with a mean score on personal and environmental components of 16.8 ± 5.12 and 31.4 ± 4.51, respectively. CONCLUSION: This PD home safety questionnaire is a valid and reliable instrument for examining P-E problems by a multidisciplinary team during their home visits. More studies, involving a large number of PD patients, are needed to establish its utility as a screening instrument in PD patients to assess for home adaptations.

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized, placebo-controlled trial using an axial inertial sensor.

BACKGROUND: Nocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited. OBJECTIVE: To evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility. METHODS: 34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1-8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed. RESULTS: There was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo. CONCLUSION: We show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials.

Understanding the role of the Parkinson's disease nurse specialist in the delivery of apomorphine therpy.

Optimal care of Parkinson's disease (PD) patients should involve a multidisciplinary team (MDT) of which a PD nurse specialist (PDNS) is a key member. The role of a PDNS is particularly prominent in the care of advanced PD patients suitable for apomorphine because, in addition to nursing skills, apomorphine treatment requires liaison, training, interaction and coordination with patients, caregivers and other members of the MDT as well as the interface with primary care physicians. The therapeutic success of apomorphine therapy depends not only upon the pharmacologic drug response, but also on how well the patient understands his/her disease and how to handle the therapy. In this respect, a PDNS is a vital member of the MDT who provides education and training, support, and is available for consultation when problems arise. In this article, we review the literature on the contribution of PDNSs in both continuous subcutaneous apomorphine infusion and intermittent subcutaneous apomorphine injection and highlight the various beneficial aspects of PDNS care, supported by scientific evidence when available. Despite a low level of published evidence, there is strong clinical evidence that the impact of PDNSs on the management of apomorphine therapy is vital and indispensable for the success of this treatment.

Quantitative demonstration of the efficacy of night-time apomorphine infusion to treat nocturnal hypokinesia in Parkinson's disease using wearable sensors.

BACKGROUND: Nocturnal hypokinesia/akinesia is one of the common night-time symptoms in patients with Parkinson's disease (PD), negatively affecting quality of life of patients and caregivers. The recognition of this problem and treatment options are limited in clinical practice. OBJECTIVES: To evaluate the efficacy of nocturnal apomorphine infusion, using a wearable sensor, in patients who are already on daytime continuous subcutaneous apomorphine infusion and still suffer from nocturnal hypokinesia. METHODS: Nocturnal parameters in 10 PD patients before and during nocturnal infusion were assessed over two nights at their homes, using a wearable sensor (trunk). Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, and number of times they got out of bed. Correlations with validated clinical rating scales were performed. RESULTS: Following nocturnal apomorphine infusion (34.8 ± 6.5 mg per night), there were significant improvements in the number of turns in bed (p = 0.027), turning velocity (p = 0.046), and the degree of turning (p = 0.028) in PD patients. Significant improvements of Modified Parkinson's Disease Sleep Scale (p = 0.005), the axial score of Unified Parkinson's Disease Rating Scale (p = 0.013), and Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.014) were also observed. CONCLUSION: Our study was able to demonstrate quantitatively the efficacy of nocturnal apomorphine infusion in PD patients with nocturnal hypokinesia and demonstrated the feasibility of using wearable sensors to yield objective and quantifiable outcomes in a clinical trial setting. More studies are needed to determine the long-term efficacy of this treatment in a large prospective cohort of PD patients.

Impact of Neu-botulinumtoxinA on the Severity and Quality of Life of Cervical Dystonia Patients.

BACKGROUND: Cervical dystonia (CD) is a debilitating neurological disorder that may gravely affect a patient's quality of life (QoL). Botulinum toxin treatment has been approved as a first-line treatment for this condition. This study aims to look at the efficacy and impact on the QoL of neu-botulinumtoxinA, a newer and cheaper botulinum toxin type A, in patients with CD. METHODS: This is a prospective, open-label, single-arm study. CD patients were recruited and evaluated for severity of CD using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and for QoL using the Craniocervical Dystonia Questionnaire (CDQ-24), and the 36-item Short Form Health Survey questionnaire (SF-36) at baseline and 6 weeks after injection. RESULTS: Twenty patients were recruited. Significant improvement was shown in part 1 and total TWSTRS score and total CDQ-24 scores. Analysis of individual items of the TWSTRS scale showed significant improvement in rotation, duration of CD, and work ability. Significant improvements in the QoL were also seen in some items of the stigma, emotional wellbeing, and energy/fatigue domains of the CDQ-24 and SF-36 questionnaires. DISCUSSION: Neu-botulinumtoxinA is efficacious in treating CD symptoms and improving QoL of patients with CD. A larger, double-blinded study is needed to study the extent of improvements.

Effective delivery of apomorphine in the management of Parkinson disease: practical considerations for clinicians and Parkinson nurses.

The clinical utility of long-term oral levodopa therapy in Parkinson disease (PD) is often limited by the emergence of motor complications. Over time, many patients with PD experience regular and/or unpredictable "off" periods, despite taking optimized oral medication regimens, with a major negative impact on their ability to undertake routine activities of daily living and consequently on their overall quality of life. One established approach for treating patients experiencing off periods and controlling motor fluctuations refractory to conventional oral drug therapy is the subcutaneous administration of the dopaminergic agonist apomorphine. This article outlines how the pharmacokinetic properties of apomorphine underpin its efficacy for the treatment of PD and provides practical guidance for the 3 main approaches in which it is used: subcutaneous intermittent apomorphine injection as a "rescue" therapy for off states, subcutaneous continuous apomorphine infusion for PD patients with intractable motor fluctuations as an alternative to other dopaminergic treatment, and in the apomorphine response (or challenge) test for assessment of dopamine-induced motor response in patients thought to have PD, or in establishing the optimal tolerated dose of apomorphine in patients already known to have PD. Also discussed is the management of potential adverse events with subcutaneous administration of apomorphine, the majority of which are mild and easily managed in practice. The importance of a multidisciplinary PD team in the optimal management of PD patients is now recognized, in particular the role of the specialist PD nurse.