Hands-feet wireless devices: Test-retest reliability and discriminant validity of motor measures in Parkinson's disease telemonitoring

Background Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. Objective To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands-SensFeet (SH-SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH-SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). Methods Altogether, 64 patients with mild-to-moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH-SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. Results Fifty-eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test-retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). Conclusion In a supervised environment, the SH-SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH-SF measurements should be evaluated in an unsupervised home setting in future studies

Wearable Platform for Automatic Recognition of Parkinson Disease by Muscular Implication Monitoring

The need for diagnostic tools for the characterization of progressive movement disorders - as the Parkinson Disease (PD) - aiming to early detect and monitor the pathology is getting more and more impelling. The parallel request of wearable and wireless solutions, for the real-time monitoring in a non-controlled environment, has led to the implementation of a Quantitative Gait Analysis platform for the extraction of muscular implications features in ordinary motor action, such as gait. The here proposed platform is used for the quantification of PD symptoms. Addressing the wearable trend, the proposed architecture is able to define the real-time modulation of the muscular indexes by using 8 EMG wireless nodes positioned on lower limbs. The implemented system “translates” the acquisition in a 1-bit signal, exploiting a dynamic thresholding algorithm. The resulting 1-bit signals are used both to define muscular indexes both to drastically reduce the amount of data to be analyzed, preserving at the same time the muscular information. The overall architecture has been fully implemented on Altera Cyclone V FPGA. The system has been tested on 4 subjects: 2 affected by PD and 2 healthy subjects (control group). The experimental results highlight the validity of the proposed solution in Disease recognition and the outcomes match the clinical literature results

Modulation of the 5-HT3 Receptor as a Novel Anti-Dyskinetic Target in Parkinson’s Disease

La L-3,4-dihydroxyphénylalanine (L-DOPA) est le traitement le plus efficace de la maladie de Parkinson. Cependant, avec une administration chronique de L-DOPA, les patients développent des complications motrices telles que les dyskinésies. Des études antérieures ont montré que le blocage des récepteurs type 3 de la sérotonine (5-HT3) réduit les niveaux de dopamine dans les ganglions de la base, suggérant qu'il pourrait atténuer la libération de dopamine qui caractérise l'état dyskinétique. Ici, nous avons étudié les effets de l’ondansétron, un antagoniste hautement sélectif du récepteur 5-HT3 à diminuer et à prévenir le développement des dyskinésies induites par L-DOPA chez le rat lésé a la 6-hydroxydopamine. Dans la première expérience, les rats sensibilisés avec L-DOPA pour induire des mouvements involontaires anormaux (AIMs), ont reçu L-DOPA en combinaison avec l'ondansétron ou un véhicule. Dans la seconde expérience, les doses efficaces d'ondansétron ont été administrées simultanément avec L-DOPA pendant 22 jours, et la sévérité des dyskinésies a été évaluée. Après 3 jours d’élimination, L-DOPA a été administré en aigu et la sévérité des dyskinésies évaluée. Nous avons trouvé que l'ondansétron 0,0001 mg/kg en combinaison avec L-DOPA, a significativement diminué la sévérité des dyskinésies par rapport à L-DOPA seul. Ondansétron 0,0001 mg/kg, administré en même temps que L-DOPA, a retardé le développement des dyskinésies. L'action anti-dyskinétique de l'ondansétron n'a pas compromis le bénéfice thérapeutique conféré par la L-DOPA. Ces résultats suggèrent que l'antagonisme des récepteurs 5-HT3 est une stratégie thérapeutique potentiellement nouvelle et efficace pour soulager la sévérité et prévenir le développement des dyskinésies.L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson’s disease However, with chronic administration of L-DOPA, patients develop motor complications such as dyskinesia. Previous studies have shown that 5-HT3 receptor blockade reduces dopamine levels within the basal ganglia, suggesting that it could mitigate the aberrant dopamine release that characterises the dyskinetic state. Here, we investigated the effects of the highly-selective 5-HT3 antagonist ondansetron at diminishing the expression of established, and preventing the development of L-DOPA-induced dyskinesia in the 6-hydroxydopamine-lesioned rat. In the first set of experiments, rats were primed with L-DOPA to induce abnormal involuntary movements (AIMs), after which L-DOPA was administered, in combination with ondansetron or vehicle. The effect of ondansetron on L-DOPA anti-parkinsonian action was subsequently determined by the cylinder test. In the second set of experiments, rats were administered effective doses of ondansetron, started concurrently with L-DOPA for 22 days, during which dyskinesia severity was monitored. After a 3-day washout period, an acute challenge of L-DOPA was administered and AIMs severity was assessed. We found that acute challenges of ondansetron 0.0001 mg/kg in combination with L-DOPA, significantly diminished the severity of AIMs compared to L-DOPA alone. Ondansetron 0.0001 mg/kg, when started concurrently with L-DOPA, attenuated the priming process leading to the development of dyskinesia. The anti-dyskinetic action of ondansetron did not compromise the therapeutic benefit conferred by L-DOPA. These results suggest that 5-HT3 receptor antagonism is a potentially new and effective therapeutic strategy to alleviate the severity, and prevent the development of dyskinesia

Unsupervised home monitoring of Parkinson's disease motor symptoms using body-worn accelerometers

IntroductionCurrent PD assessment methods have inherent limitations. There is need for an objective method to assist clinical decisions and to facilitate evaluation of treatments. Accelerometers, and analysis using artificial neural networks (ANN), have shown potential as a method of motor symptom evaluation. This work describes the development of a novel PD disease state detection system informed by algorithms based on data collected in an unsupervised, home environment. We evaluated whether this approach can reproduce patient-completed symptom diaries and clinical assessment of disease state.Methods34 participants with PD wore bilateral wrist-worn accelerometers for 4 h in a research facility (phase 1) and for 7 days at home whilst completing symptom diaries (phase 2). An ANN to predict disease state was developed based on home-derived accelerometer data. Using a leave-one-out approach, ANN performance was evaluated against patient-completed symptom diaries and against clinician rating of disease state.ResultsIn the clinical setting, specificity for dyskinesia detection was extremely high (0.99); high specificity was also demonstrated for home-derived data (0.93), but with low sensitivity (0.38). In both settings, sensitivity for on/off detection was sub-optimal. ANN-derived values of the proportions of time in each disease state showed strong, significant correlations with patient-completed symptom diaries.ConclusionAccurate, real-time evaluation of symptoms in an unsupervised, home environment, with this sensor system, is not yet achievable. In terms of the amounts of time spent in each disease state, ANN-derived results were comparable to those of symptom diaries, suggesting this method may provide a valuable outcome measure for medication trials

The use of current steering during subthalamic deep brain stimulation to alleviate upper limb symptoms of Parkinson\u27s disease

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson\u27s Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best symptom improvement based on kinematic data detected by a motion capture system and the Unified Parkinson\u27s Disease Rating Scale. Results assessing right and left upper limb symptoms gave 14 optimal settings in seven patients, of which eight settings employed current steering either unilaterally or bilaterally, and six settings employed bilateral monopolar stimulation. Thus, the use of current steering was patient-dependent and limb-dependent; factors contributing to this finding include differences in lead placement, symptom heterogeneity, and possible differences in STN functionality

Dopaminergic-induced dyskinesia assessment based on a single belt-worn accelerometer

Background After several years of treatment, patients with Parkinson's disease (PD) tend to have, as a side effect of the medication, dyskinesias. Close monitoring may benefit patients by enabling doctors to tailor a personalised medication regimen. Moreover, dyskinesia monitoring can help neurologists make more informed decisions in patient's care. Objective To design and validate an algorithm able to be embedded into a system that PD patients could wear during their activities of daily living with the purpose of registering the occurrence of dyskinesia in real conditions. Materials and methods Data from an accelerometer positioned in the waist are collected at the patient's home and are annotated by experienced clinicians. Data collection is divided into two parts: a main database gathered from 92 patients used to partially train and to evaluate the algorithms based on a leave-one-out approach and, on the other hand, a second database from 10 patients which have been used to also train a part of the detection algorithm. Results Results show that, depending on the severity and location of dyskinesia, specificities and sensitivities higher than 90% are achieved using a leave-one-out methodology. Although mild dyskinesias presented on the limbs are detected with 95% specificity and 39% sensitivity, the most important types of dyskinesia (any strong dyskinesia and trunk mild dyskinesia) are assessed with 95% specificity and 93% sensitivity. Conclusion The presented algorithmic method and wearable device have been successfully validated in monitoring the occurrence of strong dyskinesias and mild trunk dyskinesias during activities of daily living.Postprint (published version

Postural Control in Individuals with Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disorder in the elderly population. It is a complex, progressive, multisystem disease associated with motor and nonmotor impairments. Postural instability is a crucial component of functional mobility, often overlooked by both clinicians and patients with Parkinson’s disease. It is a refractory drug complication for which rehabilitation is the most effective nonpharmacological aid. However, many interventions are based on empirical experience. Improving knowledge on the pathophysiology of postural control disorders is crucial to understand the multifaceted components affected and thus design specific rehabilitation protocols. This chapter intends to offer a comprehensive overview of the current knowledge on this topic starting from the pathophysiology of postural control disorders occurring in various ecological conditions to the most innovative multidisciplinary rehabilitation approaches

Ambulatory monitoring of motor functions in patients with Parkinson's disease using kinematic sensors

Parkinson's disease (PD) is the second most common neurodegenerative disease in the general population. Cardinal symptoms of Parkinson's disease are resting tremor, rigidity, akinesia and bradykinesia and in advanced stages, gait impairments, postural instability and complications of chronic treatment with levodopa such as motor dysfunctions and dyskinesia. Multitude and complexity of these motor symptoms and their variability over the time have made assessment of them a difficult task. Moreover, following the fluctuations of motor performance (ON/OFF fluctuations) of the PD patients throughout their daily activities by quantifying their motor symptoms is a major challenge. The aim of this thesis was to design and validate a portable ambulatory movement analysis system for long-term monitoring and qualitative and quantitative assessment of motor abnormalities of PD patients during daily activities. We have designed a new measurement system consisting of five independent, lightweight, autonomous sensing units based on kinematic sensors that can continuously record body movements during daily life. Using this system and by performing several clinical studies, both in controlled conditions and on free moving patients, we have prepared a database of different movement patterns of PD patients. This database was the basis to design several new algorithms for the analysis of tremor, bradykinesia, gait and posture. An accurate algorithm based on spectral estimation has been proposed to detect and quantify tremor during daily activities of PD patients with a resolution down to three seconds using gyroscopes attached to the forearms. By quantifying the speed, range and the frequency of the movements, we have proposed a new method to assess the bradykinesia and tested it both in controlled and free conditions. We found out that in the free moving patients, the outcomes of this algorithm show significant and good correlation to the established clinical scores. Regarding the detection and analysis of gait, we have developed and tested a method based on four sensors attached to the lower limbs that provided spatio-temporal parameters of gait with good accuracy. We further improved our method using a new biomechanical model that could predict the movements of thighs from the movements of shanks during walking. This way we could reduce the number of sensor sites on the body while keeping the same accuracy in estimation of the spatio-temporal parameters of gait. By combining a statistical classifier, to detect transitions between sitting and standing postures, and a fuzzy classifier, to detect the basic body postures, we have developed an algorithm to classify basic body posture allocations both in PD patients and aged matched healthy subjects. Finally, while currently no other objective ambulatory method exists to accurately detect the periods of ON and OFF in PD patients, by combining the outcomes of the above algorithms (tremor, gait, bradykinesia and posture) using a statistical approach, we have proposed a method to detect periods of these two states with a resolution of 10 minutes in free moving patients. We believe that the proposed system has a high potential both for the clinical applications and research purposes related to the patient with Parkinson's disease and possibly other neurological movement disorders

The Influence of Dopamine Replacement on Movement Impairments During Bimanual Coordination in Parkinson’s Disease (PD)

The purpose of the current thesis was to investigate the influence of dopamine replacement on performance during bimanual coordination in individuals with Parkinson’s disease (PD) There has been conflicting research on the cause of movement impairments such as coordination deficits, slowed switching and upper limb freezing that occur during coordinated movements It is unclear whether decreased function of the dopaminergic system after withdrawal from dopamine replacement is responsible for these deficits Healthy age-matched control participants were compared to PD participants in two experiments to determine the movement impairments that occurred during three-dimensional wrist flexion-extension bimanual coordination as a result of PD. In addition, individuals with PD were compared without (‘off’) and with (‘on’) dopamine replacement in both experiments to determine whether modulation of the dopaminergic system influenced coordinated movements. In Experiment 1, continuous bimanual coordination was performed in m-phase (simultaneous wrist flexion and extension) and anti-phase (flexion of one wrist while extending other wrist) with movements externally paced with increasing across seven cycle frequencies (0.75 to 2 Hz). Visual feedback was also manipulated in one of three sensory conditions no vision, normal vision or augmented vision. Visual feedback, phase and cycle frequency manipulation was performed to determine whether other deficits (e.g. sensory and/or attentional deficits) may influence coordinated movements Despite reduced amplitude of movements in both limbs of individuals with PD (PD ‘off’), coordination deficits were not observed in PD compared to healthy control participants. In addition, there was an increased occurrence of upper limb freezing (ULF) when cycle frequency demand was greater Dopamine replacement did increase the amplitude of movements in individuals with PD but did not influence coordination performance or the occurrence of ULF. In Experiment 2, coordinated movements were initiated in either m-phase or antiphase and participants were required to voluntarily switch to the other phase pattern when an auditory cue was presented Trials were performed at one of two cycle frequencies (1 or 2 Hz) and one of two sensory conditions (no vision or normal vision) to determine whether other deficits (e.g. sensory and/or attentional deficits) may influence coordinated movement. In addition, a separate block of trials were performed in anti-phase coordination with an auditory cue that did not require a switch Non-switching trials were included to investigate whether the presence of a distracting cue could evoke ULF comparable to when switching between movements was required PD ‘off’ participants demonstrated slower switching, more delayed responses and deficits in coordination performance when compared to healthy control participants. The increased demand of cycle frequency particularly when initiating anti-phase coordination, after voluntary switching and with the presence of the auditory cue without switching contributed to a large occurrence of ULF in individuals with PD. Dopamine replacement improved the ability to switch between phase patterns but had no overall influence on coordination performance or the occurrence of ULF. Overall, the results of the current thesis demonstrated that dopamine replacement can improve motor symptoms during coordinated movements (e g hypometna and bradykinesia) but does not contribute to coordination performance or ULF in individuals with PD. As a consequence, it was concluded that coordination deficits and ULF are not caused by the dysfunctional dopaminergic system but rather associated to secondary impairment caused by PD. The movement impairments caused by secondary dysfunction of PD were proposed to be associated with increased attentional demands and possible executive dysfunction related to fronto-stnatal pathways that cannot be modulated by dopamine replacement. Thus, treatment of complex movement impairments such as coordination deficits and ULF may benefit from rehabilitation or non-dopamine therapies that focus on the global dysfunction caused by PD

Identification of Motor Symptoms Related to Parkinson Disease Using Motion-Tracking Sensors at Home (KAVELI) : Protocol for an Observational Case-Control Study

Background: Clinical characterization of motion in patients with Parkinson disease (PD) is challenging: symptom progression, suitability of medication, and level of independence in the home environment can vary across time and patients. Appointments at the neurological outpatient clinic provide a limited understanding of the overall situation. In order to follow up these variations, longer-term measurements performed outside of the clinic setting could help optimize and personalize therapies. Several wearable sensors have been used to estimate the severity of symptoms in PD; however, longitudinal recordings, even for a short duration of a few days, are rare. Home recordings have the potential benefit of providing a more thorough and objective follow-up of the disease while providing more information about the possible need to change medications or consider invasive treatments. Objective: The primary objective of this study is to collect a dataset for developing methods to detect PD-related symptoms that are visible in walking patterns at home. The movement data are collected continuously and remotely at home during the normal lives of patients with PD as well as controls. The secondary objective is to use the dataset to study whether the registered medication intakes can be identified from the collected movement data by looking for and analyzing short-term changes in walking patterns. Methods: This paper described the protocol for an observational case-control study that measures activity using three different devices: (1) a smartphone with a built-in accelerometer, gyroscope, and phone orientation sensor, (2) a Movesense smart sensor to measure movement data from the wrist, and (3) a Forciot smart insole to measure the forces applied on the feet. The measurements are first collected during the appointment at the clinic conducted by a trained clinical physiotherapist. Subsequently, the subjects wear the smartphone at home for 3 consecutive days. Wrist and insole sensors are not used in the home recordings. Results: Data collection began in March 2018. Subject recruitment and data collection will continue in spring 2019. The intended sample size was 150 subjects. In 2018, we collected a sample of 103 subjects, 66 of whom were diagnosed with PD. Conclusions: This study aims to produce an extensive movement-sensor dataset recorded from patients with PD in various phases of the disease as well as from a group of control subjects for effective and impactful comparison studies. The study also aims to develop data analysis methods to monitor PD symptoms and the effects of medication intake during normal life and outside of the clinic setting. Further applications of these methods may include using them as tools for health care professionals to monitor PD remotely and applying them to other movement disorders.Peer reviewe