Levodopa Equivalent Daily Dosage: Geographical Variations and Real-Life Modules in Parkinson's Disease.

BACKGROUND: The Levodopa Equivalent Daily Dosage (LEDD) calculation algorithms help in capturing and harmonization of Parkinson's Disease (PD) therapies. Analyzing these updates is essential for validating their effectiveness. OBJECTIVE: To assess updated LEDD conversion factors in capturing the newer therapies in PD and therapy modules in different geographical cohorts. METHODS: Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al and Jost et al, alongside investigating demographic disparities. RESULTS: The analysis involved 2943 subjects; 87% (n = 2577) met the UK Brain Bank criteria for PD. The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598 mg vs 610 mg, P < 0.0001). Geographical disparities highlighted variations in PD onset age (P < 0.0001). Jost and Tomlinson's calculations demonstrated consistency within but significant differences across countries (P < 0.0001).Age at onset revealed statistically significant differences in LEDD requirements (P < 0.0001), which were particularly higher in 21-50 years (718 mg vs 566 mg). This subgroup also demonstrated increased usage of non-Levodopa therapies (P < 0.0001). Men exhibited higher total LEDD (P = 0.001). 34% reported dyskinesia, associated with higher LEDD (756 mg, P < 0.0001). Surgically treated patients also had higher LEDD (P < 0.0001) and a significant difference between Jost and Tomlinson dosages (761 mg vs716mg) reflecting the incorporation of newer therapeutic molecules. CONCLUSION: This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age-related, and gender-specific variations, in real-life management scenarios.

Exercise Habits in People with Parkinson's: A Multinational Survey.

BACKGROUND: Exercise has been demonstrated to result in improvements in physical function, cognition, and quality of life in People with Parkinson's (PwP) but its adoption is variable. OBJECTIVES: To investigate exercise preferences, levels, influencing factors among a diverse Parkinson's disease (PD) population, to understand exercise adoption patterns and plan informed interventions. METHODS: A cross-sectional survey collected data through online platforms and paper-based methods. The Exercise Index (ExI) calculated exercise level based on frequency and duration. RESULTS: Of 2976 PwP, 40.6% exercised regularly, 38.3% occasionally, and 21.2% did not exercise. The overall mean ExI was 18.99 ± 12.37. Factors associated with high exercise levels included exercising in groups (ExI 24-26), weightlifting (ExI 27 (highest)), using muscle-building equipment (ExI 25-26), and exercising at home following an app (ExI 26). A positive trend between ExI and varied exercise groups, locations, types, and equipment was observed. No expected benefit from exercise achieved the lowest ExI (8). Having at least two exercise-promoting factors, a bachelor's degree or higher, receiving exercise advice at initial visits, and aged ≤40 years at PD onset were strong predictors of exercise (adjust OR = 7.814; 6.981; 4.170; 3.565). Falls and "other" most troublesome PD symptoms were negative predictors (aOR = 0.359; 0.466). Barriers to exercise did not predict the odds of exercise. CONCLUSIONS: The study shows that PwP's exercise behavior is influenced by their exercise belief, age at PD onset, doctor's advice at initial visits, education level, symptoms, and exercise-promoting factors. High exercise levels were associated with certain types of exercises and exercising in groups.

The rise of Parkinson's disease is a global challenge, but efforts to tackle this must begin at a national level: a protocol for national digital screening and "eat, move, sleep" lifestyle interventions to prevent or slow the rise of non-communicable diseases in Thailand.

The rising prevalence of Parkinson's disease (PD) globally presents a significant public health challenge for national healthcare systems, particularly in low-to-middle income countries, such as Thailand, which may have insufficient resources to meet these escalating healthcare needs. There are also many undiagnosed cases of early-stage PD, a period when therapeutic interventions would have the most value and least cost. The traditional "passive" approach, whereby clinicians wait for patients with symptomatic PD to seek treatment, is inadequate. Proactive, early identification of PD will allow timely therapeutic interventions, and digital health technologies can be scaled up in the identification and early diagnosis of cases. The Parkinson's disease risk survey (TCTR20231025005) aims to evaluate a digital population screening platform to identify undiagnosed PD cases in the Thai population. Recognizing the long prodromal phase of PD, the target demographic for screening is people aged ≥ 40 years, approximately 20 years before the usual emergence of motor symptoms. Thailand has a highly rated healthcare system with an established universal healthcare program for citizens, making it ideal for deploying a national screening program using digital technology. Designed by a multidisciplinary group of PD experts, the digital platform comprises a 20-item questionnaire about PD symptoms along with objective tests of eight digital markers: voice vowel, voice sentences, resting and postural tremor, alternate finger tapping, a "pinch-to-size" test, gait and balance, with performance recorded using a mobile application and smartphone's sensors. Machine learning tools use the collected data to identify subjects at risk of developing, or with early signs of, PD. This article describes the selection and validation of questionnaire items and digital markers, with results showing the chosen parameters and data analysis methods to be robust, reliable, and reproducible. This digital platform could serve as a model for similar screening strategies for other non-communicable diseases in Thailand.

Genetic Movement Disorders Commonly Seen in Asians.

The increasing availability of molecular genetic testing has changed the landscape of both genetic research and clinical practice. Not only is the pace of discovery of novel disease-causing genes accelerating but also the phenotypic spectra associated with previously known genes are expanding. These advancements lead to the awareness that some genetic movement disorders may cluster in certain ethnic populations and genetic pleiotropy may result in unique clinical presentations in specific ethnic groups. Thus, the characteristics, genetics and risk factors of movement disorders may differ between populations. Recognition of a particular clinical phenotype, combined with information about the ethnic origin of patients could lead to early and correct diagnosis and assist the development of future personalized medicine for patients with these disorders. Here, the Movement Disorders in Asia Task Force sought to review genetic movement disorders that are commonly seen in Asia, including Wilson's disease, spinocerebellar ataxias (SCA) types 12, 31, and 36, Gerstmann-Sträussler-Scheinker disease, PLA2G6-related parkinsonism, adult-onset neuronal intranuclear inclusion disease (NIID), and paroxysmal kinesigenic dyskinesia. We also review common disorders seen worldwide with specific mutations or presentations that occur frequently in Asians.

Historical and More Common Nongenetic Movement Disorders From Asia.

Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and ß-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution.

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

Clinical trials for cognition in Parkinson's disease: Where are we and how can we do better?

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and has a substantial impact on quality of life. Despite numerous trials targeting various PD features, we still lack effective treatments for cognition beyond cholinesterase inhibitors. OBJECTIVE: To identify the gaps in recent clinical trials with cognitive outcomes in PD and consider areas for improvement. METHODS: We examined recent clinical trials with cognitive outcomes in PD registered on ClinicalTrials.gov, excluding trials without cognitive outcomes, non-interventional studies, and in atypical Parkinsonian disorders. Included trials were categorized by treatment approach (investigational medicinal product, behavioral, physical activity, device-based). Details of trial design and outcomes were collected. RESULTS: 178 trials at different stages of trial completion were considered. 46 trials were completed, 25 had available results. Mean follow-up duration was 29.9 weeks. Most common cognitive measure was Montreal Cognitive Assessment. Most were performed in North America or Europe. Majority of the participants identified as non-Hispanic and White. Only eight trials showed improvement in cognition, none showed improvement beyond four months. These included trials of international medicinal products, cognitive and physical interventions and devices. GRADE certainty levels ranged from Moderate to Very Low. Only mevidalen had a Moderate certainty for potential clinical effectiveness. CONCLUSIONS: Amongst a large number of trials for cognition in PD, only a small proportion were completed. Few showed significant improvement, with no proven long-lasting effects. Trial design, lack of enrichment for at-risk groups, short follow-up duration, insensitive outcome measures likely contribute to lack of detectable benefit and should be considered in future trials.

Health-related quality of life of daily-life-affected benign essential blepharospasm: Multi-center observational study.

PURPOSE: To compare Thais' health-related quality of life (HRQOL) and severity grading, efficacy and safety in daily-life-affected benign essential blepharospasm (BEB) patients at baseline and after Botulinum toxin type A (BTX-A) treatment. DESIGN: Prospective-observational study. PARTICIPANTS: BEB patients with Jankovic rating scale (JRS) at least 3 in both severity and frequency graded from 14 institutes nationwide were included from August 2020 to June 2021. METHODS: Demographic data, HRQOL evaluated by the Thai version of EQ-5D-5L and NEI-VFQ-25 questionnaires, and severity grading score evaluated by Jankovic rating scale (JRS) at baseline, 1, and 3 months after the treatment were collected. The impact of the BTX-A injections and their complications were recorded. RESULTS: 184 daily-life-affected BEB patients were enrolled; 159 patients (86.4%) had complete data with a mean age of 61.40±10.09 years. About 88.05% were female, and 10.1% were newly diagnosed. Most of the patients had bilateral involvement (96.9%) and 12.6% had history of BEB-related accident. After BTX-A treatment, HRQOL improved significantly in 4 dimensions of EQ-5D-5L, except self-care. The EQ_VAS (mean±SD) was 64.54±19.27, 75.13±15.37, 73.8±15.85 (p<0.001) and EQ-5D-5L utility score was 0.748±0.23, 0.824±0.19 and 0.807±0.19 at baseline, 1, 3 months after treatment, respectively. From NEI-VFQ-25, HRQOL also improved in all dimensions, except eye pain. The JRS improved in all patients. Self-reported minor adverse events were 22.6%, which mostly resolved within the first month. CONCLUSION: Daily-life-affected BEB impacted HRQOL in most dimensions from both generic and visual-specific questionnaires. BTX-A treatment not only decreased disease severity, but also improved quality of life.

Umami and Other Taste Perceptions in Patients With Parkinson's Disease.

OBJECTIVE: Studies of taste perceptions in Parkinson's disease (PD) patients have been controversial, and none of these studies have assessed umami taste. This study aimed to assess umami, along with the other 4 taste functions in PD patients. METHODS: Participants were tested for gustation using the modified filter paper disc method and olfaction using the modified Sniffin' Stick-16 (mSS-16) test (only 14 culturally suitable items were used). A questionnaire evaluated patients' subjective olfactory and gustatory dysfunction, taste preference, appetite, and food habits. RESULTS: A total of 105 PD patients and 101 age- and sex-matched controls were included. The body mass index (BMI) of PD patients was lower than that of controls (PD = 22.62, controls = 23.86, p = 0.028). The mSS-16 score was 10.7 for controls and 6.4 for PD patients (p < 0.001) (normal ≥ 9). Taste recognition thresholds (RTs) for sweet, salty, sour, bitter and umami tastes were significantly higher in PD, indicating poorer gustation. All taste RTs correlated with each other, except for umami. Most patients were unaware of their dysfunction. Patients preferred sweet, salty and umami tastes more than the controls. Dysgeusia of different tastes in patients was differentially associated with poorer discrimination of tastes, an inability to identify the dish and adding extra seasoning to food. BMI and mSS-16 scores showed no correlation in either patients or controls. CONCLUSION: PD patients have dysgeusia for all five tastes, including umami, which affects their appetite and diet. Patients preferred sweet, salty and umami tastes. This information can help adjust patients' diets to improve their nutritional status.

Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale.

OBJECTIVE: This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). METHODS: The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing. RESULTS: The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions. CONCLUSION: The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.

Correction: Impact of disease stage and age at Parkinson's onset on patients' primary concerns: Insights for targeted management.

[This corrects the article DOI: 10.1371/journal.pone.0243051.].

Impact of disease stage and age at Parkinson's onset on patients' primary concerns: Insights for targeted management.

BACKGROUND: The concerns of people with Parkinson's disease (PD) about their disease are often different from the objective clinical picture and subject to various influencing factors, including disease progression. Currently our understanding of these concerns is limited, particularly in Asian countries. METHODS: A 50-item survey on Parkinson's Disease Patients' Concerns (PDPC Survey) was developed by a multidisciplinary care team. The subjective greatest concerns (most commonly concerning symptoms) of patients at a specialist centre in Bangkok, Thailand, were explored and categorised according to disease stage and age at onset of PD. RESULTS: Data for 222 patients showed concerns varied widely. Motor symptoms giving the greatest concern were problems with walking and/or balance (40.5% of patients), while the most commonly concerning non-motor symptom (NMS) was constipation (41.0%). Patterns were observed amongst different patient subgroups. Early PD patients (H&Y stage 1) were more concerned about NMS than motor symptoms, while the reverse was true for advanced PD patients. Young-onset PD patients showed significantly greater concerns than typical-onset patients about motor symptoms relating to social functioning, working and stigmatisation, such as speech (p = 0.003). CONCLUSIONS: This study, in an Asian patient cohort, provides an assessment of a wide range of PD patients' concerns, encompassing not only motor symptoms and NMS, but also treatment-related adverse events, care in the advanced stage, and the need for assistive devices. Identifying the concerns of individual PD patients and implementing a patient-centred approach to care is critical to their wellbeing and optimal outcomes. The PDPC survey can help healthcare teams build a more accurate picture of patients' experiences to inform clinical management.

If Your Patients Were Too Embarrassed to Go Out in Public, What Would You Do? - Public Education to Break the Stigma on Parkinson's Disease Using Integrated Media.

PURPOSE: People with Parkinson's (PwP) often feel stigmatized, especially when their symptoms are visually prominent. In some countries, public awareness of Parkinson's disease can be minimal, leading to social challenges for PwP. PATIENTS AND METHODS: A public educational campaign using videos (VDO) showing 5 PwP in different social situations that their symptoms could be a source of inconvenience to others were launched on Facebook (FB) and television (TV). We describe the process and report the impact of the campaign on patients and the public. Number of shares and likes and the first 100 comments on FB were analyzed. RESULTS: There were almost 1 million views, 680,000 likes, and 256,000 shares in the Center's and popular Facebook Pages within 24 hours, subsequently reaching 4.4 million views, 138,000 likes, and 78,000 shares. Patients reported changed behavior and demeanor by the public towards them. The public's comments ranged from stating that they have seen PwP without knowing what it was to requests for more information about PD to thanks for the informative VDO. People also shared their experiences with PwP. CONCLUSION: The campaign was impactful in creating awareness about PD. Creating appealing content with appropriate video length and collaborating with community groups that have relevant skills can help in creating and disseminating an educational video which creates a significant impact on society as a whole. This can be emulated to educate the public about other diseases.

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.

Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel.

An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.

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.

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.

Postural instability, the absence of sexual intercourse in the past month, and loss of libido are predictors of sexual dysfunction in Parkinson's disease.

OBJECTIVE: To determine the prevalence and predictors of sexual dysfunction (SD) in Parkinson's disease (PD) patients. BACKGROUND: Assessments of SD in the professional literature is limited. Understanding the predictors of SD can help physicians focus on this problem in vulnerable patients. METHOD: A total of 60 PD patients and 60 controls answered the Arizona Sexual Experiences Scale-Thai Version (ASEX-Thai) and the Hamilton Depression Rating Scale (HAMD) questionnaires, and were asked on 3 additional sets of questions about premature ejaculation (PE), dyspareunia, and hypersexual disorders. RESULT: The prevalence of SD in PD patients and controls was 81.6% and 48.3% respectively (p < 0.05). PD patients had lower BMI, lower uric acid level, higher HAMD score and had sexual intercourse (SI) less frequently. SD correlated with greater disease severity and depression. The most distressing problem in male patients was PE (51.4%) and orgasmic dissatisfaction (76%) for female patients. Logistic regression analysis found 3 factors were related to SD: no SI in the past month (p < 0.001), postural instability (PI) (p = 0.028), and HAMD item 14 (p = 0.021), predicting SD with the OR of 12.2, 5.5, and 5.0 respectively. CONCLUSIONS: SD in PD is common and usually occurs with depression. Absence of SI in the past month, PI, and loss of libido are predictors of SD in PD. A simple and quick screening of SD can be routinely performed by inquiring patients about the frequency of SI and the examination of the pull test. Detailed assessment of sexual functioning and depression may guide physicians in proper management.