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.

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.

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.

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.

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.

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.

Early factors for predicting discontinuation to subcutaneous Apomorphine infusion in Parkinson's disease: A prospective analysis of the Thai Apomorphine Registry.

INTRODUCTION: Although continuous subcutaneous apomorphine infusion (CSAI) is an effective therapy for Parkinson's disease (PD) with motor fluctuations, data from Asian cohorts is limited. The therapy is often discontinued due to the complexity of its delivery. METHODS: Fifty-one PD patients undergoing CSAI as an add-on therapy were enrolled in the Thai Apomorphine Registry, an electronic database that recorded clinical characteristics and parameters during the 14-consecutive-day titration and long-term follow-up. Factors at the time of titration were documented in order to identify predictors of long-term discontinuation. RESULTS: Following initiation, PD patients were administered a mean CSAI dose of 5.89 mg/h (SD 1.36) over a mean time of 12.28 h (SD 1.90) each day. The mean follow-up period was 626.2 days (SD 619.17). Significant reductions in UPDRS-I, II, III, and IV scores, total NMSQ score, PDQ-8 score, daily off and dyskinesia hours, Timed Up and Go test, walking step test, levodopa-equivalent daily dose, number of times a day the levodopa was taken versus pre-CSAI values were observed (p < 0.05, each). Thirty-five (68.6%) patients discontinued during the follow-up period. Relative risks of variables recorded at the time of titration that determined discontinuation of CSAI therapy were an absence of full-time caregivers, achieving a daily off hours reduction <3.5 h, and NMSQ scores at the time of CSAI titration ≥9.5 points. CONCLUSION: Identifying factors that predict discontinuation of CSAI at the time of its initiation may help physicians to better understand the patient's drug response and how to manage them long-term.

Using Machine Learning for Predicting the Best Outcomes With Electrical Muscle Stimulation for Tremors in Parkinson's Disease.

Recent studies have identified that peripheral stimulation in Parkinson's disease (PD) is effective in tremor reduction, indicating that a peripheral feedback loop plays an important role in the tremor reset mechanism. This was an open-label, quasi-experimental, pre- and post-test design, single-blind, single-group study involving 20 tremor-dominant PD patients. The objective of this study is to explore the effect of electrical muscle stimulation (EMS) as an adjunctive treatment for resting tremor during "on" period and to identify the best machine learning model to predict the suitable stimulation level that will yield the longest period of tremor reduction or tremor reset time. In this study, we used a Parkinson's glove to evaluate, stimulate, and quantify the tremors of PD patients. This adjustable glove incorporates a 3-axis gyroscope to measure tremor signals and an EMS to provide an on-demand muscle stimulation to suppress tremors. Machine learning models were applied to identify the suitable pulse amplitude (stimulation level) in five classes that led to the longest tremor reset time. The study was registered at the www.clinicaltrials.gov under the name "The Study of Rest Tremor Suppression by Using Electrical Muscle Stimulation" (NCT02370108). Twenty tremor-dominant PD patients were recruited. After applying an average pulse amplitude of 6.25 (SD 2.84) mA and stimulation period of 440.7 (SD 560.82) seconds, the total time of tremor reduction, or tremor reset time, was 329.90 (SD 340.91) seconds. A significant reduction in tremor parameters during stimulation was demonstrated by a reduction of Unified Parkinson's Disease Rating Scale (UPDRS) scores, and objectively, with a reduction of gyroscopic data (p < 0.05, each). None of the subjects reported any serious adverse events. We also compared gyroscopic data with five machine learning techniques: Logistic Regression, Random Forest, Support Vector Machine (SVM), Neural Network (NN), and Long-Short-Term-Memory (LSTM). The machine learning model that gave the highest accuracy was LSTM, which obtained: accuracy = 0.865 and macro-F1 = 0.736. This study confirms the efficacy of EMS in the reduction of resting tremors in PD. LSTM was identified as the most effective model for predicting pulse amplitude that would elicit the longest tremor reset time. Our study provides further insight on the tremor reset mechanism in PD.

Impaired ability to turn in bed in parkinson's disease as a potential rare cause of positional asphyxia: a sensor-based analysis.

BACKGROUND: Nocturnal hypokinesia commonly affects Parkinson's disease (PD) patients, manifesting primarily as an impaired ability to turn in bed and sleeping in specific positions, such as prone that potentially poses the risk of positional asphyxia. OBJECTIVE: To objectively evaluate, using axial inertial sensors (the NIGHT-Recorder), the ability of PD patients and controls to turn in bed from prone to supine position and to correlate these parameters with disease severity scores. PATIENTS AND METHODS: Turning in bed from prone to supine position was assessed in 16 PD patients with a moderate disease stage and 16 age-matched controls using the NIGHT-Recorder. Successful turning was defined as a full 180 ° turn from prone to supine position as evidenced by the NIGHT-Recorder. Objective parameters included duration, velocity, and acceleration of turn. The ability to turn in bed was determined by torque per kilogram body weight (T/kg). RESULTS: Two out of 16 PD patients (12.5%) could not initiate their turns. PD patients turned with a significant longer duration (p = 0.04), slower velocity (p = 0.04), and acceleration (p = 0.04) compared to controls. Although PD patients had lower T/kg than controls, the difference was not significant. Several significant correlations were demonstrated between turning parameters and clinical rating scales (Duration vs. UPDRS axial: r=0.51, p = 0.04; T/kg vs. PDSS-2: r=0.53, p = 0.03; T/kg vs. NHQ: r=0.52, p = 0.03). CONCLUSION: Our study provides objective evidence of impaired turning in bed from prone to supine position in PD patients with nocturnal hypokinesia. Appropriate measures should be taken to improve nocturnal mobility in those at risk.

Posturographic abnormalities in ambulatory atypical parkinsonian disorders: Differentiating characteristics.

BACKGROUND: Postural instability is a common complaint in patients with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). However, objective evaluation to identify posturographic characteristics to enable clinical differentiation is limited. METHOD: Postural sway abnormalities in 35 atypical parkinsonian patients (19 PSP, 16 MSA), 35 matched PD patients, and healthy subjects were assessed under static posturography with eyes-open (EO) and eyes-closed (EC). RESULTS: With EO, MSA patients showed a significantly greater mean ML sway than PD patients (p = 0.03), but with EC even more parameters were significantly different, including mean sway in both ML (p = 0.02) and AP directions (p = 0.01), sway area (p = 0.001), and sway path length (p = 0.003). While differences between MSA and PD were seen in both ML and AP directions, significant differences between PD and PSP were limited to greater mean ML sway (p = 0.01) with EO, greater mean (p = 0.002) and maximal AP sway (p = 0.02) amongst PSP patient with EC. Moderate and significant correlation was demonstrated between HY stage and mean AP sway amongst APD patients (r = 0.56, p < 0.01) and in PSP patients (r = 0.62, p < 0.01). CONCLUSION: Our study identifies a number of objective sway measures assessed with EC that are potentially useful for clinical differentiation between APDs and PD. In comparison to PD, MSA showed greater sway area and a mean sway distance in both AP and ML directions, while the difference was limited to AP in PSP. Significant correlation between HY stage and sway parameters further supports postural sway as a potential disease progression marker in APDs.

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.

Evaluation of nocturnal hypokinesia in Parkinson's disease using a novel patient/proxy questionnaire and correlations with objective monitoring.

BACKGROUND: Nocturnal hypokinesia is a decreased ability to perform sufficient axial rotation and/or trunk flexion to turn in or get out of bed. Currently, there are no validated questionnaires specifically to assess nocturnal hypokinesia in PD patients. OBJECTIVE: To develop and validate a questionnaire to assess PD patients' problems associated with turning or getting out of bed. METHODS: The nocturnal hypokinesia questionnaire (NHQ) consists of 10 items, completed independently by patients and their caregivers. For validation, 76 patient-caregiver pairs completed the questionnaire and validity, agreement levels, and internal consistency assessed. In addition, 76 healthy couples served as controls. The NHQ and Modified Parkinson's Disease Sleep Scale (PDSS-2) were compared and 25 random patients-caregiver pairs were also assessed with objective night-time monitoring. RESULTS: Patient and caregiver scores showed a high level of agreement (Intra-class correlation: 0.84) with high internal consistency (KR-20 coefficient of 0.73 for patients and 0.69 for caregivers). No significant difference between the mean total NHQ scores as rated by patients and caregivers was observed. Mean NHQ scores from patients and caregivers were significantly higher than healthy controls (p < 0.001). Moderate correlations were found between the NHQ and PDSS-2 (r = 0.32, p = 0.004), and with objective monitoring (Number of turns: r = -0.41, p = 0.04, Degree of turn: r = -0.44, p = 0.02). CONCLUSION: The NHQ is a reliable instrument to identify symptoms of nocturnal hypokinesia amongst PD patients. Strong patient-caregiver agreement supports the use of proxy evaluation by caregivers when patient's information is unobtainable.

Tremor's glove-an innovative electrical muscle stimulation therapy for intractable tremor in Parkinson's disease: A randomized sham-controlled trial.

BACKGROUND: Medically refractory resting tremor is a debilitating symptom of Parkinson's disease (PD) patients. In our pilot study, modulation of peripheral reflex mechanism by electrical muscle stimulation (EMS) temporarily suppressed tremor. OBJECTIVES: To investigate the efficacy of EMS, delivered using Tremor's glove, as a treatment of resting hand tremor. PATIENTS AND METHODS: Thirty PD patients with medically refractory resting tremor were randomly allocated to a Tremor's glove group (n=15) or a sham glove group (n=15). Gloves were placed on the most tremulous hand for 30min per testing session. Demographics, clinical rating scales, and tremor parameters (RMS of angular velocity and angular displacement, peak magnitude, and frequency) were assessed before and during stimulation. Correlations with validated clinical rating scales were performed. RESULTS: There were no statistically significant differences between groups in demographics, rating scales, or tremor parameters. During stimulation, significant reduction in RMS angular velocity (as percentage) in every axis and peak magnitude in axis (x-, y-) and UPDRS tremor score, were found with Tremor's glove compared to the sham groups (p<0.05, each). Significant moderate correlations were observed between a percentage reduction of RMS angular velocity in every axis and UPDRS tremor scores. Mean duration of tremor reduction after stimulation was 107.78±104.15s. No serious adverse events were observed. CONCLUSION: In this study, EMS-based Tremor's glove was effective in suppressing resting hand tremor in PD patients. Tremor's glove is light-weight with a good safety profile, making it a future potential therapeutic option for PD patients with medically refractory tremor.

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.

Time for a strategy in night-time dopaminergic therapy? An objective sensor-based analysis of nocturnal hypokinesia and sleeping positions in Parkinson's disease.

BACKGROUND: Nocturnal hypokinesia is a common night-time symptom in patients with Parkinson's disease (PD). However, there is still little understanding of the nature, and variations of severity of this symptom. OBJECTIVES: To evaluate the severity of nocturnal hypokinesia and sleep positions in PD patients using multisite wearable sensors. METHODS: Nocturnal parameters and sleep positions in 18 PD couples were assessed and compared using wearable sensors (limbs and trunk) for one night in their homes. Nocturnal parameters included number, velocity, acceleration, degree, limb movements and the number of times they got out of bed. RESULTS: PD patients had significantly fewer episodes of turns in bed than their spouses (p=0.043), which was associated with significantly slower speed (p=0.005), acceleration (p=0.005) and fewer degrees (p=0.017). When we split the night into the first and second half, significant findings were mainly demonstrated in the second half of the night, including significantly fewer turns (p=0.02) with smaller degrees (p=0.017), slower speed (p=0.005) and acceleration (p=0.007). No significant differences in these parameters were shown in the first half of the night except for smaller degrees of turn in bed in PD patients (p=0.028) and slower acceleration (p=0.037). In addition, PD patients spent significantly more time in a supine position compared to their spouses (p=0.031) with significantly less time in a prone position (p=0.041). CONCLUSION: Nocturnal hypokinesia gets worse as the night progresses. Treatment of nocturnal hypokinesia should aim at providing a continuous dopaminergic delivery that can achieve a sustained therapeutic level of dopamine throughout the night.

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.

Support vector machine classification of Parkinson's disease and essential tremor subjects based on temporal fluctuation.

Tremor is a common symptom shared in both Parkinson's disease (PD) and Essential tremor (ET) subjects. The differential diagnosis of PD and ET tremor is important since the realization of treatment depends on specific medication. A novel feature is developed based on a hypothesis that tremor of PD subject has a larger fluctuation during resting than action task. Tremor signal is collected using a triaxial gyroscope sensor attached to subject's finger during kinetic and resting task. The angular velocity signal is analyzed by transforming a one-dimensional to two-dimensional signal using a relation of signal and its delay versions. Tremor fluctuation is defined as the area of 95% confidence ellipse covering the two-dimensional signal. The tremor fluctuation during kinetic and resting task is used as classification features. The support vector machine is used as a classifier and tested with 10-fold cross-validation. This novel feature provides a perfect PD/ET classification with 100% accuracy, sensitivity and specificity.

Temporal fluctuations of tremor signals from inertial sensor: a preliminary study in differentiating Parkinson's disease from essential tremor.

BACKGROUND: Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders but the rate of misdiagnosis rate in these disorders is high due to similar characteristics of tremor. The purpose of the study is to present: (a) a solution to identify PD and ET patients by using the novel measurement of tremor signal variations while performing the resting task, (b) the improvement of the differentiation of PD from ET patients can be obtained by using the ratio of the novel measurement while performing two specific tasks. METHODS: 35 PD and 22 ET patients were asked to participate in the study. They were asked to wear a 6-axis inertial sensor on his/her index finger of the tremor dominant hand and perform three tasks including kinetic, postural and resting tasks. Each task required 10 s to complete. The angular rate signal measured during the performance of these tasks was band-pass filtered and transformed into a two-dimensional representation. The ratio of the ellipse area covering 95 % of this two-dimensional representation of different tasks was investigated and the two best tasks were selected for the purpose of differentiation. RESULTS: The ellipse area of two-dimensional representation of the resting task of PD and ET subjects are statistically significantly different (p < 0.05). Furthermore, the fluctuation ratio, defined as a ratio of the ellipse area of two-dimensional representation of resting to kinetic tremor, of PD subjects were statistically significantly higher than ET subjects in all axes (p = 0.0014, 0.0011 and 0.0001 for x, y and z-axis, respectively). The validation shows that the proposed method provides 100 % sensitivity, specificity and accuracy of the discrimination in the 5 subjects in the validation group. While the method would have to be validated with a larger number of subjects, these preliminary results show the feasibility of the approach. CONCLUSIONS: This study provides the novel measurement of tremor variation in time domain termed 'temporal fluctuation'. The temporal fluctuation of the resting task can be used to discriminate PD from ET subjects. The ratio of the temporal fluctuation of the resting task to the kinetic task improves the reliability of the discrimination. While the method is powerful, it is also simple so it could be applied on low resource platforms such as smart phones and watches which are commonly equipped with inertial sensors.

Exploring the effect of electrical muscle stimulation as a novel treatment of intractable tremor in Parkinson's disease.

BACKGROUND: As the pathophysiology of tremor in Parkinson disease (PD) involves a complex interaction between central and peripheral mechanisms, we propose that modulation of peripheral reflex mechanism by electrical muscle stimulation (EMS) may improve tremor temporarily. OBJECTIVES: To determine the efficacy of EMS as a treatment for drug resistant tremor in PD patients. METHODS: This study was a single-blinded, quasi-experimental study involving 34 PD patients with classic resting tremor as confirmed by tremor analysis. The EMS was given at 50Hz over the abductor pollicis brevis and interrosseus muscles for 10s with identified tremor parameters before and during stimulation as primary outcomes. RESULTS: Compared to before stimulation, we observed a significant reduction in the root mean square (RMS) of the angular velocity (p<0.001) and peak magnitude (p<0.001) of resting tremor while tremor frequency (p=0.126) and dispersion (p=0.284) remained unchanged during stimulation. The UPDRS tremor score decreased from 10.59 (SD=1.74) before stimulation to 8.85 (SD=2.19) during stimulation (p<0.001). The average percentage of improvement of the peak magnitude and RMS angular velocity was 49.57% (SD=38.89) and 43.81% (SD=33.15) respectively. 70.6% and 61.8% of patients experienced at least 30% tremor attenuation as calculated from the peak magnitude and RMS angular velocity respectively. CONCLUSIONS: Our study demonstrated the efficacy of EMS in temporarily improving resting tremor in medically intractable PD patients. Although tremor severity decreased, they were not completely eliminated and continued with a similar frequency, thus demonstrating the role of peripheral reflex mechanism in the modulation of tremor, but not as a generator. EMS should be further explored as a possible therapeutic intervention for tremor in PD.

Visual deprivation elicits subclinical postural inflexibilities in early Parkinson's disease.

BACKGROUND: Postural instability is often experienced in the late stages of PD and is a marker of disease progression. Little information is available on the role of visual inputs as an adaptive strategy to compensate for postural instability in PD. The purpose of this study was to determine visual dependency for postural control in early PD. METHODS: Thirty early PD subjects without postural complaints and 30 matched controls were evaluated for subtle postural instability using static posturography under eyes opened and eyes closed conditions. RESULTS: No significant differences between groups were observed under eyes opened condition. In eyes closed condition, there was significantly greater mean sway in the mediolateral direction (p=0.01), mean sway velocity (p=0.03), lateral sway velocity (p=0.04), and sway area (p=0.04) in PD than in the control subjects. 95% confidence ellipse of mean sway was largest in PD patients with eyes closed. A strong and significant correlation was observed between disease duration and mean mediolateral sway, sway area, mean sway and lateral sway velocity, and a moderate correlation was shown between Hoehn & Yahr stage and mean mediolateral sway, and sway area. CONCLUSION: Our findings suggest that visual dependency exists in early PD and visual deprivation task can help identify subclinical postural instability.