Old problems, new solutions: harnessing technology and innovation in Parkinson's disease-evidence and experiences from Thailand.

The prevalence of Parkinson's disease (PD) is increasing rapidly worldwide, but there are notable inequalities in its distribution and in the availability of healthcare resources across different world regions. Low- and middle-income countries (LMICs), including Thailand, bear the highest burden of PD so there is an urgent need to develop effective solutions that can overcome the many regional challenges associated with delivering high-quality, and equitable care to a diverse population with limited resources. This article describes the evolution of healthcare delivery for PD in Thailand, as a case example of a LMIC. The discussions reflect the author's presentation at the Yoshikuni Mizuno Lectureship Award given during the 8th Asian and Oceanian Parkinson's Disease and Movement Disorders Congress in March 2023 for which he was the 2023 recipient. The specific challenges faced in Thailand are reviewed along with new solutions that have been implemented to improve the knowledge and skills of healthcare professionals nationally, the delivery of care, and the outcomes for PD patients. Technology and innovation have played an important role in this process with many new tools and devices being implemented in clinical practice. Without any realistic prospect of a curative therapy in the near future that could halt the current PD pandemic, it will be necessary to focus on preventative lifestyle strategies that can help reduce the risk of developing PD such as good nutrition (EAT), exercise (MOVE), good sleep hygiene (SLEEP), and minimizing environmental risks (PROTECT), which should be initiated and continued (REPEAT) as early as possible.

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.

Scales for Antipsychotic-Associated Movement Disorders: Systematic Review, Critique, and Recommendations.

BACKGROUND: Antipsychotic-associated movement disorders remain common and disabling. Their screening and assessment are challenging due to clinical heterogeneity and different use of nomenclature between psychiatrists and neurologists. OBJECTIVE: An International Parkinson and Movement Disorder Society subcommittee aimed to rate psychometric quality of severity and screening instruments for antipsychotic-associated movement disorders. METHODS: Following the methodology adopted by previous International Parkinson and Movement Disorders Society subcommittee papers, instruments for antipsychotic-associated movement disorders were reviewed, applying a classification as "recommended," "recommended with caveats," "suggested," or "listed." RESULTS: Our review identified 23 instruments. The highest grade of recommendation reached is "recommended with caveats," assigned to seven severity rating instruments (Extrapyramidal Symptoms Rating Scale, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre involuntary movements scale, Simpson Angus Scale, and Matson Evaluation of Drug Side effects). Only three of these seven (Drug-Induced Extra-Pyramidal Symptoms Scale, Maryland Psychiatric Research Centre, Matson Evaluation of Drug Side effects) were also screening instruments. Their main caveats are insufficient demonstration of psychometric properties (internal consistency, skewing, responsiveness to change) and long duration of administration. Eight "suggested" instruments did not meet requirements for the "recommended" grade also because of insufficient psychometric validation. Other limitations shared by several instruments are lack of comprehensiveness in assessing the spectrum of antipsychotic-associated movement disorders and ambiguous nomenclature. CONCLUSIONS: The high number of instruments "recommended with caveats" does not support the need for developing new instruments for antipsychotic-associated movement disorders. However, addressing the caveats with new psychometric studies and revising existing instruments to improve the clarity of their nomenclature are recommended next steps. © 2023 International Parkinson and Movement Disorder Society.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Practical use of apomorphine infusion in Parkinson's disease: lessons from the TOLEDO study and clinical experience.

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.

Homocysteine, vitamin B metabolites, dopamine-substituting compounds, and symptomatology in Parkinson's disease: clinical and therapeutic considerations.

Emerging studies suggest a correlation between elevated plasma homocysteine (hcy) levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases, including Parkinson's disease (PD). This narrative review delves into the intricate relationships between Hcy, vitamin B metabolites, dopamine-substituting compounds, and various symptoms of PD. Patients undergoing a long-term L-dopa/dopa-decarboxylase inhibitor (DDI) regimen, especially without a concurrent catechol-O-methyl transferase (COMT) inhibitor or methyl group-donating vitamin supplementation, such as vitamins B6 and B12, exhibit an elevation in Hcy and a decline in vitamin B metabolites. These altered concentrations appear to be associated with heightened risks of developing non-motor symptoms, including peripheral neuropathy and cognitive disturbances. The review underscores the impact of levodopa metabolism via COMT on homocysteine levels. In light of these findings, we advocate for the supplementation of methyl group-donating vitamins, notably B6 and B12, in patients undergoing a high-dose L-dopa/DDI regimen, particularly those treated with L-dopa/carbidopa intestinal gel (LCIG) infusion.

Adopting the Rumsfeld approach to understanding the action of levodopa and apomorphine in Parkinson's disease.

Dopaminergic therapies dominate the treatment of the motor and non-motor symptoms of Parkinson's disease (PD) but there have been no major advances in therapy in many decades. Two of the oldest drugs used appear more effective than others-levodopa and apomorphine-but the reasons for this are seldom discussed and this may be one cause for a lack of progress. This short review questions current thinking on drug action and looks at whether adopting the philosophy of ex-US Secretary of State Donald Rumsfeld reveals 'unknown' aspects of the actions of levodopa and apomorphine that provide clues for a way forward. It appears that both levodopa and apomorphine have a more complex pharmacology than classical views would suggest. In addition, there are unexpected facets to the mechanisms through which levodopa acts that are either forgotten as 'known unknowns' or ignored as 'unknown unknowns'. The conclusion reached is that we may not know as much as we think about drug action in PD and there is a case for looking beyond the obvious.

Movement disorders in Indochina: Resource challenges and future solutions.

Movement disorders are a major cause of disability worldwide and their increasing prevalence predicts a substantial future burden of care. Impactful patient care requires availability of, and accessibility to, effective medications, knowledge, and disease awareness among both medical professionals and patients, driven by skilled personnel to harness and manage resources. The highest burden of movement disorders is in low-to-middle income countries where resources are often limited and infrastructure is insufficient to meet growing demands. This article focuses on the specific challenges faced in the management and delivery of care for movement disorders in Indochina, the mainland region of Southeast Asia comprising the neighboring countries of Cambodia, Laos, Malaysia, Myanmar, Thailand, and Vietnam. The first Indochina Movement Disorders Conference was held in August 2022 in Ho Chi Minh City, Vietnam, to provide a platform to better understand the situation in the region. Future management of movement disorders in Indochina will require progressive adaptation of existing practices to reflect modern approaches to care delivery. Digital technologies offer an opportunity to strengthen these processes and address the challenges identified in the region. Ultimately, a long-term collaborative approach by regional healthcare providers is key.

Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease.

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

Access and Attitudes Toward Palliative Care Among Movement Disorders Clinicians.

BACKGROUND: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited. OBJECTIVE: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care. METHODS: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated. RESULTS: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills. CONCLUSIONS: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.

Modernizing Daily Function Assessment in Parkinson's Disease Using Capacity, Perception, and Performance Measures.

Many disease symptoms restrict the quality of life of the affected. This usually occurs indirectly, at least in most neurological diseases. Here, impaired daily function is interposed between the symptoms and the reduced quality of life. This is reflected in the International Classification of Function, Disability and Health model published by the World Health Organization in 2001. This correlation between symptom, daily function, and quality of life makes it clear that to evaluate the success of a therapy and develop new therapies, daily function must also be evaluated as accurately as possible. However, daily function is a complex construct and therefore difficult to quantify. To date, daily function has been measured primarily by capacity (clinical assessments) and perception (surveys and patient-reported outcomes) assessment approaches. Now, daily function can be captured in a new dimension, that is, performance, through new digital technologies that can be used in the home environment of patients. This viewpoint discusses the differences and interdependencies of capacity, perception, and performance assessment types using the example of Parkinson's disease. Options regarding how future study protocols should be designed to get the most comprehensive and validated picture of daily function in patients are presented. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Mastering nocturnal jigsaws in Parkinson's disease: a dusk-to-dawn review of night-time symptoms.

Finding out about night-time symptoms from Parkinson's disease (PD) patients can be a challenge as many patients and their carers cannot recall many symptoms that occur during the night, resulting in an under-recognition or a large variability of responses from clinical interviews and scales. Moreover, technology-based assessments for most night-time symptoms are still not universally available for use in a patient's home environment. Therefore, most physicians rely on their clinical acumen to capture these night-time symptoms based on pieces of patients' history, bedpartner's reports, clinical features, associated symptoms or conditions. To capture more night-time symptoms, the authors identified common nocturnal symptoms based on how they manifest from dusk to dawn with selected features relevant to PD. While some symptoms occur in healthy individuals, in PD patients, they may impact differently. The authors intend this narrative review to provide a practical guide on how these common night-time symptoms manifest and highlight pertinent issues by focusing on prevalence, clinical symptomatology, and specific relationships to PD. It is also important to recognise that PD-specific sleep disturbances increase with advancing disease with additional contributions from ageing, comorbidities, and medication side effects. However, the relative contribution of each factor to individual symptom may be different in individual patient, necessitating clinical expertise for individual interpretation. While there are debatable issues in certain areas, they underlie the complexity of night-time symptoms. Understanding night-time symptoms in PD is like re-arranging jigsaw pieces of clinical information to create, but never complete, a picture for physicians to instigate appropriate management.

Addressing knowledge gaps in Parkinson's disease: a report on the Movement Disorder Society's Centre-to-Centre initiative to improve Parkinson's disease services in Lao People's Democratic Republic.

BACKGROUND: Lao People's Democratic Republic (Lao PDR) has only nine neurologists for seven million people; none have formal training in Parkinson's disease (PD). Medical specialists require sufficient PD knowledge to provide high-quality care. METHODS: This study outlines a Centre-to-Centre programme for developing PD expertise in underserved regions through a tailored two-year educational enterprise between an established movement disorder mentor centre at Chulalongkorn University in Thailand and mentee centres in Lao PDR. Background knowledge of 80 Laotian physicians was assessed using a validated PD knowledge questionnaire containing 26 questions divided into 3 sections (diagnosis, therapeutic options, disease course) before and immediately after one-day kick-start training. Responses were compared across physicians' demographic groups. RESULTS: Of 80 respondents, 50 (62.5%) were board-certified physicians, of which 27 (54%) specialised in internal medicine. Apparent knowledge gaps were shown by a 51.2% correct response rate for total score, 52.8% for diagnosis, 50.6% for therapeutic options, and 48.2% for disease course. No significant differences in total score or any domain sub-scores between neurologists and other specialties were found. Many did not know which non-motor symptoms could occur as prodromal symptoms or late in course of PD. Incorrect responses mainly reflected a lack of knowledge of the impact of medication on disease. Total and domain sub-scores significantly improved after the course (p < 0.05, each). The size of difference of the means was significant for the total score (d = 0.82), therapeutic option (d = 0.56), and disease course (d = 0.68) sub-scores. CONCLUSIONS: Significant improvement of PD knowledge amongst Laotian physicians is demonstrated after a training course, focusing on practical management of PD. Our findings highlight the importance of continued medical education, especially PD-specific training.

Objective Monitoring of Driving Behavior in Parkinson's Disease: The Utility of the Chula Parkinson Car®.

INTRODUCTION: Driving competency is important to evaluate among individuals with Parkinson's disease (PD). Driving in natural situations is the preferred assessment method; thus, we used a naturalistic driving environment to identify driving competency among individuals with PD in comparison to healthy age-matched controls. METHODS: Based on a power analysis, we recruited 20 participants (10 with PD and 10 healthy age-matched controls). Each participant completed 3 tasks while driving the ChulaPD car, a 4-door sedan installed with computerized monitoring systems. The tasks were forward and backward vehicle movement, reversing into a parking space, and parking parallel to a sidewalk. Trip start and end times, vehicle speed, and acceleration and deceleration times were logged using steering wheel motion, location parking sensors, and dashboard cameras and compared between groups. RESULTS: Age, gender, possession of a driver's license, present driving conditions, Thai Mini-Mental State Examination score, and driving experience did not significantly differ between groups. However, the PD group took longer to complete the driving tests (p = 0.002), had slower vehicle speeds (p = 0.002), longer brake times (p = 0.007), and decreased brake pressure ability (p = 0.009). Under normalized conditions, the ratio of failed driver's license tests was also higher among the PD group than in the control group (70 vs. 10%, p = 0.006). CONCLUSIONS: Individuals with PD had less-than-adequate driving ability based on our naturalistic setting. Our assessment method may be useful in other populations with chronic illnesses or for older adults. We discuss how naturalistic assessments could become the standard for evaluating driving ability in Thailand and elsewhere.

Association between Sleep Disturbances and Daytime Somnolence in Parkinson's Disease.

BACKGROUND: Sleep disturbance is a common problem among patients with Parkinson's disease (PD). OBJECTIVES: To investigate the prevalence of daytime somnolence and night-time sleep disturbances; to characterise the night-time sleep disturbance in patients with daytime somnolence; and to determine the correlation between daytime somnolence and night-time sleep disturbances. METHODS: One hundred and sixty patients with PD were included in the study. Each patient completed the Thai version of the Epworth Sleepiness Scale (ESS) questionnaire to evaluate excessive daytime sleepiness (EDS), and the PD Sleep Scale version-2 (PDSS-2) questionnaire to evaluate night-time sleep disturbance. Subjective sleep information and details about the presence or absence of sleep attack (SA) were also obtained from the patients. RESULTS: The types of daytime somnolence found in this study were EDS, SA, and combination of EDS and SA (EDS + SA) with the prevalence rates of 22.5, 3.1 and 6.3%, respectively. The prevalence of night-time sleep disturbance was 46.9%. The most common nocturnal disturbance (82.5%) was "get up at night to pass urine". There was a significant positive correlation between the ESS score and PDSS-2 total score with a correlation coefficient of 0.16 (p = 0.043). Patients with "EDS + SA" were the most affected by nocturnal disturbances, as they represented the largest group among those patients with night-time disturbances and had the highest PDSS-2 total score (p < 0.05). CONCLUSION: There are differences in nocturnal sleep disturbances among PD patients with different types of daytime somnolence. The significant positive correlation between the ESS and the PDSS-2 total scores suggests that night-time sleep disturbance may influence daytime somnolence.

Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations.

BACKGROUND: Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson's disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. SUMMARY: We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apathy were most prevalent when applying the health-professional completed NMSS. Key Messages: NMS are generally prevalent and highly burdensome within selected Asian PD populations living in countries included in this review. Our review suggests that NMS-driven phenotypic heterogeneity is present in Asian patients, and compared to Western PD populations there might be variations in assessed NMS.