Botulinum toxin treatment for hemifacial spasm: harmonising neurological and aesthetic outcomes.

Hemifacial spasm (HFS) represents a challenging cranial movement disorder primarily affecting the facial nerve innervated muscles, with significant prevalence among Asians. Botulinum toxin type A (BoNT/A) injections, established as a primary therapeutic intervention since FDA approval, offer considerable effectiveness in alleviating spasms, albeit accompanied by challenges such as temporary effects and potential adverse events including facial asymmetry. This comprehensive review underscores the crucial need for harmonising neurological benefits and aesthetic outcomes in HFS management. The discussion delves into the interplay between facial aesthetics and neurological objectives in BoNT/A injections, emphasising precise techniques, dosages, and site considerations. Distinct aspects in neurological and aesthetic domains are also examined, including detailing the targeted muscles and injection methodologies for optimal therapeutic and aesthetic results. Importantly, evidence regarding various BoNT/A formulations, recommendations, and reconstitution guidelines in both neurology and aesthetics contexts are provided, along with a schematic approach outlining the stepwise process for BoNT/A injection in HFS treatment, addressing critical areas such as orbicularis oculi muscle sites, eyebrow correction strategies, mid- and lower-face considerations, contralateral injection sites, and post-injection follow-up and complication management. By highlighting the culmination of neurological efficacy and facial esthetics in BoNT/A treatment for HFS patients, this review proposes a holistic paradigm to achieve balanced symptomatic relief and natural aesthetic expression, ultimately enhancing quality of life for individuals grappling with HFS.

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.

Empowering the management of early-onset Parkinsons' disease: The role of technology.

Early-onset Parkinson's disease (EOPD) is defined as PD with an age of onset after 21 years of age but before 50 years. It displays many important differences to late-onset PD in terms of its pathology, phenotype, presentation and disease course, all of which have consequences for achieving a definitive diagnosis, the choice of therapy and approach to management. Studies show that this younger population is keen to embrace digital technologies as part of PD care, being familiar with using digital tools in their daily lives. Although most of the literature relating to the use of technology in PD applies to the broad population, this review focuses on evidence and potential benefits of the use of digital technologies to support clinical management in EOPD as well as its value in empowering patients to achieve self-management and in improving their quality of life. Digital technologies also have important and increasing roles in providing telehealth, including rehabilitation strategies for motor and non-motor PD symptoms. EOPD is known to be associated with a higher risk of motor fluctuations, so technologies such as wearable sensors have a valuable role for monitoring symptoms, providing timely feedback, and informing treatment decisions. In addition, digital technologies allow easy provision and equitable access to education and networking opportunities that will enable patients to have a better understanding of their condition.

Small Particles, Big Potential: Polymeric Nanoparticles for Drug Delivery in Parkinson's Disease.

Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood-brain barrier. © 2024 International Parkinson and Movement Disorder Society.

Too little or too much nocturnal movements in Parkinson's disease: A practical guide to managing the unseen.

Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.

User-centred design, validation and clinical testing of an anti-choking mug for people with Parkinson's disease.

Oropharyngeal dysphagia, or difficulty initiating swallowing, is a frequent problem in people with Parkinson's disease (PD) and can lead to aspiration pneumonia. The efficacy of pharmacological options is limited. Postural strategies, such as a chin-down manoeuvre when drinking, have had some degree of success but may be difficult for people who have other limitations such as dementia or neck rigidity, to reproduce consistently. Using a user-centred design approach and a multidisciplinary team, we developed and tested an anti-choking mug for people with PD that helps angle the head in the optimum position for drinking. The design reflected anthropometric and ergonomic aspects of user needs with features including regulation of water flow rate and sip volume, an inner slope, a thickened handle and a wide base, which promoted a chin-down posture when used. Prototype testing using digital technology to compare neck flexion angles (the primary outcome), plus clinical outcomes assessed using standard tools (Swallowing Clinical Assessment Score in Parkinson's Disease (SCAS-PD) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III), found significant improvements in a range of parameters related to efficient swallowing and safe drinking when using the anti-choking mug versus a sham mug.

Bedside clinical assessment of patients with common upper limb tremor and algorithmic approach.

The diagnostic approach for patients with tremor is challenging due to the complex and overlapping phenotypes among tremor syndromes. The first step in the evaluation of tremor is to identify the tremulous movement and exclude the tremor mimics. The second step is to classify the tremor syndrome based on the characteristics of tremor from historical clues and focused examination (Axis 1). Comprehensive tremor examinations involve the assessment of tremor in different conditions (rest, action or mixed, position or task-specific), distribution of tremor (upper limb, lower limb, head, jaw), positive signs for functional tremor (FT) if suspected (distractibility, entrainment, co-contraction), and associated neurological signs including parkinsonism, dystonic posture, cerebellar/brainstem signs, neuropathy, and cognitive impairment. A pivotal feature in this step is to determine any distinct feature of a specific isolated or combined tremor syndrome. In this review, we propose an algorithm to assess upper limb tremors. Ancillary testing should be performed if clinical evaluation is unclear. The choice of investigation depends on the types of tremors considered to narrow down the spectrum of etiology (Axis 2). Laboratory blood tests are considered for acute onset and acute worsening of tremors, while structural neuroimaging is indicated in unilateral tremors with acute onset, nonclassical presentations, and a combination of neurological symptoms. Neurophysiological study is an important tool that aids in distinguishing between tremor and myoclonus, etiology of tremor and document specific signs of FT. Treatment is mainly symptomatic based depending on the etiology of the tremor and the patient's disabilities.

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.

Self-treatment of freezing of gait in Parkinson's disease patients using silicone pads to apply Thai acupressure to plantar acupoints: A randomised, controlled trial.

Introduction: Freezing of gait (FOG) involves dysfunction of the motor and sensory systems. Peripheral sensory stimuli, including Thai acupressure, can improve proprioceptive function and decrease FOG episodes. Here, we sought to determine the efficacy of acupressure as a self-treatment to alleviate FOG in patients with Parkinson's disease (PD). Methods: We conducted an open-label, controlled trial of 60 PD patients with FOG while medicated, randomised into two groups: an active-treatment group using silicone pads to apply pressure to plantar acupoints on the head of the big toe and the base of the first metatarsal bone on each foot for 6 s using patient body weight while seated, repeated four times for each acupoint bilaterally, and a sham-treatment group using a similar protocol without the silicone pads. The primary outcome was stride length. Secondary outcomes included FOG episodes, FOG duration, percent duration of FOG to total gait time (%FOG), and gait parameters. A baseline-adjusted analysis of covariance was used to compare outcomes between the two groups. Results: Compared with the sham treatment, the active treatment increased stride length, gait velocity, and cadence (all p < 0.001), and decreased FOG episodes and duration (both p < 0.001), %FOG (p = 0.011), and double-support time (p < 0.001). No adverse effects were noted. Conclusions: Acupressure using silicone pads to stimulate plantar acupoints for self-treatment is a noninvasive, simple, safe way to improve gait and alleviate FOG in patients with PD. Clinical Trial Registration: We registered the study prospectively in the Thai Clinical Trial Registry No. TCTR20200317001.

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.

Integrating technology into a successful apomorphine delivery program in Thailand: a 10-year journey of achievements with a five-motto concept.

Introduction: Apomorphine, a potent dopamine agonist, is a therapeutic option for patients with Parkinson's disease and motor fluctuations. However, the adoption of and adherence to this therapy have been limited by the need for complex delivery devices and specialized care as well as resource consumption, posing challenges for new physicians. Thailand is a unique example of a developing nation that has successfully implemented and continued the use of this therapy by employing cooperative technology that has dramatically enhanced apomorphine delivery services. Methods: Establishing apomorphine delivery services requires significant resources and step-by-step solutions. We began our services by implementing various strategies in three chronological stages: the initial stage (2013-2015), intermediate stage (2016-2019), and current stage (2020-present), each presenting unique challenges. Together, we also implemented a proposed set of five mottos to strengthen our apomorphine delivery service. Using additive technology, we developed a patient registry platform that combined electronic data acquisition, video and remote monitoring using wearable sensors, and in-house mobile applications to support our service. Results: At the initial stage, we assembled a team to enhance the efficacy and confirm the safety of apomorphine treatment in our hospital. At the intermediate stage, we expanded our apomorphine delivery services beyond just the patients at our hospital. We supported other hospitals in Thailand in setting up their own apomorphine services by educating both physicians and nurses regarding apomorphine therapy. With this educational undertaking, increased apomorphine-related knowledge among medical professionals, and a greater number of hospitals providing apomorphine services, an increasing number of patients were administered apomorphine in subsequent years. Currently, we are providing effective apomorphine delivery to improve patient outcomes and are seamlessly integrating technology into clinical practice. Incorporating integrative technologies in our apomorphine delivery program yielded positive results in data collection and support throughout patient care, in tracking patients' statuses, in the long-term use of this treatment, and in increasing medication adherence rates. Conclusion: This perspective paper describes how technology can help provide supportive healthcare services in resource-constrained environments, such as in Thailand, offering a step-by-step approach to overcoming several limitations. The valuable insights from our 10-year journey in successfully integrating technology into apomorphine delivery services can benefit new physicians seeking to replicate our success.

Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway.

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.

Comparing the efficacy of therapeutic Thai acupressure on plantar acupoints and laser cane therapy on freezing of gait in Parkinson's disease: a randomized non-inferiority trial.

Background: ON-freezing of gait (ON-FOG) in Parkinson's disease (PD), often resistant to medication, is linked to sensory deficits and proprioceptive impairment, and results in falls and reduced life quality. While visual cues from a laser cane (LC), which rapidly accesses the motor cortex, are commonly used to compensate for proprioceptive impairment, increased visual reliance may be affected by disease progression. Emerging evidence suggests that modulation of peripheral sensory processing may alleviate ON-FOG, and therapeutic Thai acupressure (TTA) may be a solution. This study aims to evaluate the effect of TTA in alleviating ON-FOG and compare its effectiveness to LC in patients with PD. Methods: This open-label, non-inferiority trial randomized 90 PD patients with ON-FOG equally into three arms: TTA for plantar nerve stimulation for 96 s, LC for visual cueing, and sham control (SC). Stride length was the primary non-inferiority endpoint [non-inferiority margin: lower limit of 95% confidence interval (CI) above -10 cm in mean change difference in pre- and immediately post-intervention in TTA versus LC (one-sided)]. Secondary outcomes included FOG episodes, double support time, velocity, cadence, step length, timed up and go (TUG) test, and visual analog scale (VAS) score. Results: TTA showed non-inferiority to LC in stride length (mean = -0.7 cm; 95% CI: -6.55; 5.15) (one-sided). The improvements with TTA and LC versus SC were comparable between (mean = 13.11 cm; 95% CI: 7.26; 18.96) and (mean = 13.8 cm; 95% CI: 7.96; 19.65) (one-sided). Secondary outcomes favored TTA and LC over SC with improved FOG, velocity, step length, and VAS scores, while only TTA resulted in improved double support time, cadence, and TUG test results. No complications occurred. Conclusion: The efficacy of TTA, which improves stride length, is non-inferior to that of LC and consequently alleviates FOG comparable to LC. TTA might enhance proprioceptive function and reduce visual dependence. Therefore, TTA, characterized by its non-invasive, simple, and safe techniques, is a potential non-pharmacological alternative for ON-FOG treatment and might enhance overall quality of life. However, further research into the mechanism, efficacy, and utilization of TTA is essential. Clinical trial registration: https://www.thaiclinicaltrials.org/show/TCTR20200317001, identifier TCTR20200317001.

Identifying Subtle Motor Deficits Before Parkinson's Disease is Diagnosed: What to Look for?

Motor deficits typical of Parkinson's disease (PD), such as gait and balance disturbances, tremor, reduced arm swing and finger movement, and voice and breathing changes, are believed to manifest several years prior to clinical diagnosis. Here we describe the evidence for the presence and progression of motor deficits in this pre-diagnostic phase in order to provide suggestions for the design of future observational studies for an effective, quantitatively oriented investigation. On the one hand, these future studies must detect these motor deficits in as large (potentially, population-based) cohorts as possible with high sensitivity and specificity. On the other hand, they must describe the progression of these motor deficits in the pre-diagnostic phase as accurately as possible, to support the testing of the effect of pharmacological and non-pharmacological interventions. Digital technologies and artificial intelligence can substantially accelerate this process.

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.