Measures Of Bradykinesia Research Articles

Sustained Clinical Benefit of Adaptive Deep Brain Stimulation in Parkinson's Disease Using Gamma Oscillations: A Case Report.

Adaptive deep brain stimulation (aDBS) dynamically adjusts stimulation parameters according to patient needs. We recently showed that chronic aDBS utilizing invasive neural signals for feedback control is superior to conventional DBS (cDBS) during normal daily life in a 2-month trial. The stability of aDBS over longer periods remains unclear. To assess the effects of aDBS on motor symptoms and quality of life (QoL) in one individual with Parkinson's disease over 8 months. We used stimulation-entrained cortical gamma oscillations as a control signal for aDBS in the subthalamic nucleus and quantified benefits using motor diary ratings, QoL scales, and wearable metrics. We found that aDBS delivered superior and consistent benefits compared with baseline cDBS in measures of bradykinesia and QoL. aDBS can achieve prolonged, stable improvement over clinically optimized cDBS. The neural signal remains stable, and aDBS parameters remain appropriate over extended periods. © 2024 International Parkinson and Movement Disorder Society.

Validation of computer vision technology for analyzing bradykinesia in outpatient clinic videos of people with Parkinson's disease

BackgroundCurrent diagnosis and monitoring of Parkinson's disease (PD) is based on subjective clinical assessments. Objective measures of motor functioning could support clinical acumen. Computer vision (CV) technology is a promising contactless technique but requires further validation. AimTo investigate the performance of CV analysis of clinic-based videos of finger-tapping. Our goals were (i) to distinguish PD from healthy controls (HC), when compared to human raters, (ii) to measure the severity of bradykinesia, and (iii) detect ON/OFF medication state. MethodsVideos of thirty-one persons with PD and forty-nine HC were collected during clinical outpatient visits. Videos were analysed using CV to produce speed, amplitude, rhythm and composite bradykinesia measures. All videos were independently rated by three raters using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Modified Bradykinesia Rating Scale (MBRS). Twenty video pairs were conducted in ON and OFF states. Classification accuracy for PD/HC state and ON/OFF state were measured using the Area under Receiver Operating characteristic curve and a confusion matrix. CV and clinical measures were correlated using Spearman coefficients. ResultsCV classified disease state with higher accuracy than clinical raters (91 % sensitivity; 97 % specificity). CV measures of bradykinesia correlated significantly with clinical ratings: R = 0.740 for MDS-UPDRS, 0.715 for MBRS speed, 0.714 for amplitude and 0.504 for rhythm. CV classified ON/OFF state as accurately as clinical raters. DiscussionCV can provide a valid, objective and contactless bradykinesia assessment based on clinically collected videos, which offers promise as a new clinical outcome, including in remote settings.

Beta Burst-Driven Adaptive Deep Brain Stimulation Improves Gait Impairment and Freezing of Gait in Parkinson's Disease.

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD. Seven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS). Beta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia. Beta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.

Assessment of Virtual Reality Devices as a Means of Objectively Monitoring Parkinson’s Disease (P10-11.014)

<h3>Objective:</h3> To show that consumer virtual reality (VR) devices are capable of providing statistically reliable and replicable data on treatment response in Parkinson Disease (PD). <h3>Background:</h3> Parkinson’s disease results in motor dysfunction with varying response to exogenous levodopa. Response to treatment is monitored with ratings scale such as the Unified Parkinson Disease Rating Scale (UPDRS). However, this paradigm of care results in slow response times and limited reliability. The development of technologies to assist with clinical assessments is essential to improving care. Mass market VR devices with their ability to measure movement and generate testing environments may be able to increase objectivity, validity, and monitoring frequency. <h3>Design/Methods:</h3> Individuals with levodopa responsive PD without other complicating conditions were selected (n=20). Participants were first evaluated in their off-state using the UPDRS motor scale and participated in a virtual reality assessment which mirrored the clinical exam. Hand positioning was recorded. Afterwards, levodopa was administered and individuals were reassessed clinically and with the VR device. <h3>Results:</h3> Severity of tremor decreased after levodopa administration in all assessed states with statistical significance achieved reliably in two of three states (p&lt;0.05). Bradykinesia measures improved in all three states, though statistical significance was only achieved reliably in one state. For tremor, strong correlations between various device and physician measures of tremor severity were present (r = 0.5–0.8). For bradykinesia, moderate correlations existed between the state which had achieved statistical significance in the on-off state comparison (r ~ 0.5). Patient perception surveys noted most individuals were willing to incorporate similar devices into their care. <h3>Conclusions:</h3> VR devices are can detect patient responsiveness to levodopa and device generated metrics correlate with validated physician metrics. Device use is accepted and essentially side-effect free. This study argues for the further evaluation of PD by VR devices with future focus on complex tasks. <b>Disclosure:</b> An immediate family member of Dr. Hirczy has received personal compensation for serving as an employee of Meta. Dr. Hirczy has received personal compensation in the range of $500-$4,999 for serving as a Author with Slack Enterprises. The institution of Dr. Salinas has received research support from North Texas VA Health Care System New Investigator Award.

Measurement of bradykinesia and chorea in Huntington's Disease using ambulatory monitoring

ObjectivesThe feasibility of measuring bradykinesia and chorea in Huntington's Disease using a wearable sensor system (Parkinson’s Kinetigraph: PKG) developed for measuring bradykinesia and dyskinesia in Parkinson’s Disease was assessed. MethodsUnified Huntington’s Disease Rating Scales (UHDRS) and a PKG were obtained for 25 people with Huntington's Disease. Bradykinesia and Chorea Score were derived from relevant sub-scores of the UHDRS and compared with the PKG’s bradykinesia and dyskinesia scores. The PKG’s daytime sleepiness score was also used. ResultsThere was good correlation between Chorea Scores and the PKG’s dyskinesia score (Pearson’s ρ = 0.66). Correlation between the Bradykinesia Scores and the PKG’s bradykinesia score was also good (Pearson’s ρ = 0.51) in cases whose PKG scores were in the normal or bradykinetic range. The PKG’s bradykinesia score of 23, which is in the higher range of control subjects, separated participants into those with Independence Score ≥ 80 or < 80 and a Functional Assessment (FAS) score ≥ 18 or < 18. The PKG’s daytime sleep score was high in 44 % of participants, whose average time asleep was 21 % compared to 1.6 % in participants with a normal sleep index. Participants with high sleep scores were significantly more likely to have low Independence and TFC scores. ConclusionsMeasures of bradykinesia and dyskinesia from clinical scales have acceptable correlations with those from the PKG. Continuous monitoring provides information about daytime sleep, which was associated with lower functional status. Further studies and larger sample sizes are required to confirm these findings and the utility of this measure in Huntington's Disease.

Movement disorders in COVID-19 times: impact on care in movement disorders and Parkinson disease.

The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP). As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine. COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.

Transcranial Direct Current Stimulation Over Motor Areas Improves Reaction Time in Parkinson's Disease.

BackgroundTranscranial direct current stimulation (tDCS) has been shown to modulate cortical motor excitability and improve bradykinesia symptoms in Parkinson's disease. It is unclear how targeting different cortical motor areas with tDCS may differentially influence upper limb function for individuals diagnosed with PD.ObjectiveThis study investigated whether anodal tDCS applied separately to the primary motor cortex and the supplementary motor area would improve upper limb function for individuals with Parkinson's disease. In addition, a startling acoustic stimulus was used to differentiate between the effect of stimulation on motor preparatory and initiation processes associated with upper limb movements.MethodsEleven participants with idiopathic Parkinson's disease performed two upper limb simple reaction time tasks, involving elbow extension or a button press before and after either anodal tDCS or sham tDCS was applied over the primary motor cortex or supplementary motor area. A loud, startling stimulus was presented on a selection of trials to involuntarily trigger the prepared action.ResultsAnodal tDCS led to improved premotor reaction time in both tasks, but this was moderated by reaction time in pre-tDCS testing, such that individuals with slower pre-tDCS reaction time showed the greatest reaction time improvements. Startle-trial reaction time was not modified following tDCS, suggesting that the stimulation primarily modulated response initiation processes.ConclusionAnodal tDCS improved response initiation speed, but only in slower reacting individuals with PD. However, no differences attributable to tDCS were observed in clinical measures of bradykinesia or kinematic variables, suggesting that reaction time may represent a more sensitive measure of some components of bradykinesia.

249 Slow motion analysis of repetitive tapping (SMART) test: a new measurement of bradykinesia

ObjectivesTo develop a quantitative and objective tool to track repetitive tapping movements (RTM) using a slow motion capture and and compare patients with Parkinson’s disease (PD), REM-sleep behaviour disorder (RBD) and healthy controls (HC).MethodsWe assessed 48 participants (PD=20, RBD=5, HC=23). For each participant, RTM was recorded during 20s by a smartphone at 240 frames/s and then analysed using novel Python scripts. Two kinetic parameters were extracted: amplitude between fingers and frequency (number of taps/s). Linear regres- sion was used to determine the trend of movement over time.ResultsAlthough HC and RBD group (64.8±8.7yo and 68.4±8.2yo respectively) were older than PD group (58.1±12.8yo), the PD group performed the task significantly slower (p=0.0003) and with greater, but not significant, amplitude decrement than HC (p=0.5). RBD group was similar to PD group with significant slower RTM (p&lt;0.0001) and non-significant amplitude decrement (p=0.3). SMART test was able to differentiate between all three groups, with a positive goodness of fit between PD and HC. The frequency parameter displayed 92.8% and 100% of sensibility (for 60.8% and 13% specificity with respective AUC=0.84 and 0.92) when comparing PD vs HC and RBD vs HC respectively.ConclusionsWe present an accurate way to quantify motor dysfunction in PD. Despite the small number of subjects, the fact that RBD group presented objective motor impairment could help with the early diagnosis at the prodromal phase of PD.15c6.simonet@qmul.ac.uk

A Smartphone Application as an Exploratory Endpoint in a Phase 3 Parkinson’s Disease Clinical Trial: A Pilot Study

Background: Smartphones can generate objective measures of Parkinson’s disease (PD) and supplement traditional in-person rating scales. However, smartphone use in clinical trials has been limited. Objective: This study aimed to determine the feasibility of introducing a smartphone research application into a PD clinical trial and to evaluate the resulting measures. Methods: A smartphone application was introduced part-way into a phase 3 randomized clinical trial of inosine. The application included finger tapping, gait, and cognition tests, and participants were asked to complete an assessment battery at home and in clinic alongside the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Results: Of 236 eligible participants in the parent study, 88 (37%) consented to participate, and 59 (27 randomized to inosine and 32 to placebo) completed a baseline smartphone assessment. These 59 participants collectively completed 1,292 batteries of assessments. The proportion of participants who completed at least one smartphone assessment was 61% at 3, 54% at 6, and 35% at 12 months. Finger tapping speed correlated weakly with the part III motor portion (r = −0.16, left hand; r = −0.04, right hand) and total (r = −0.14) MDS-UPDRS. Gait speed correlated better with the same measures (r = −0.25, part III motor; r = −0.34, total). Over 6 months, finger tapping speed, gait speed, and memory scores did not differ between those randomized to active drug or placebo. Conclusions: Introducing a smartphone application midway into a phase 3 clinical trial was challenging. Measures of bradykinesia and gait speed correlated modestly with traditional outcomes and were consistent with the study’s overall findings, which found no benefit of the active drug.

Detection of Parkinsonian Motor Symptoms Using Non-Invasive Motion Sensing Technology

Parkinson’s Disease (PD) is characterized by impaired movement, resting tremor, and muscle rigidity. The Unified PD Rating Scale (UPDRS) is a standardized protocol used by neurologists to measure progression of disease as well as evaluation of treatments. However, this examination is subjective, time consuming, and results can be affected by stress, diet, or sleep. Our goal is to develop a non-invasive device that can record objective clinically-relevant measurements during subtasks of the UPDRS to allow for remote evaluations, which would be beneficial considering the frequency of clinical visits for medication adjustments. Five healthy individuals (ages 21-59) completed UPDRS tasks 3.6 (pronation/supination of hands) and 3.17 (rest tremor amplitude). Participants performed these tasks twice, first normally and second simulating PD patients (tremor, bradykinesia, reduction of movement amplitude) after viewing example videos. Motion data including linear and angular accelerations in 3 dimensions was acquired using a lightweight wrist-mounted motion sensor. Three features were extracted: (1) Power of higher frequency components of the linear acceleration signal (rest task), as a measure of resting tremor amplitude. (2) Power of higher frequency components of the rotational acceleration signal (pronation/supination task), as a measure of bradykinesia. (3) Standard deviation of the local maxima of the rotational acceleration (pronation/supination task), as a measure of reduction in movement speed and amplitude. These features were used to correctly differentiate trials completed with and without simulated PD symptoms, using an SVM classifier with leave-one-out cross validation accuracy of 95%. These findings suggest it is possible to capture clinical features of PD using motion sensors. Future work in PD patients will examine how these measures correlate with UPDRS evaluations and whether they will be helpful in providing a quick, objective telehealth measure of progression and treatment response that can supplement current tools.

Frequency-specific network activity predicts bradykinesia severity in Parkinson’s disease

ObjectiveBradykinesia has been associated with beta and gamma band interactions in the basal ganglia-thalamo-cortical circuit in Parkinson’s disease. In this present cross-sectional study, we aimed to search for neural networks with electroencephalography whose frequency-specific actions may predict bradykinesia. MethodsTwenty Parkinsonian patients treated with bilateral subthalamic stimulation were first prescreened while we selected four levels of contralateral stimulation (0: OFF, 1–3: decreasing symptoms to ON state) individually, based on kinematics. In the screening period, we performed 64-channel electroencephalography measurements simultaneously with electromyography and motion detection during a resting state, finger tapping, hand grasping tasks, and pronation-supination of the arm, with the four levels of contralateral stimulation. We analyzed spectral power at the low (13–20 Hz) and high (21–30 Hz) beta frequency bands and low (31–60 Hz) and high (61–100 Hz) gamma frequency bands using the dynamic imaging of coherent sources. Structural equation modelling estimated causal relationships between the slope of changes in network beta and gamma activities and the slope of changes in bradykinesia measures. ResultsActivity in different subnetworks, including predominantly the primary motor and premotor cortex, the subthalamic nucleus predicted the slopes in amplitude and speed while switching between stimulation levels. These subnetwork dynamics on their preferred frequencies predicted distinct types and parameters of the movement only on the contralateral side. DiscussionConcurrent subnetworks affected in bradykinesia and their activity changes in the different frequency bands are specific to the type and parameters of the movement; and the primary motor and premotor cortex are common nodes.

Tremorography in fragile X-associated tremor/ataxia syndrome, Parkinson's disease and essential tremor

BackgroundFragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease affecting carriers of a 55–200 CGG repeat in the fragile X mental retardation 1 gene, may receive an initial diagnosis of Parkinson's disease (PD) or essential tremor (ET) due to overlapping motor symptoms. Therefore, tremor and bradykinesia were compared in these disorders using quantitative tremorography. MethodsThe inertial sensor based Kinesia ™ system was used to quantify upper extremity tremor and bradykinesia in participants with FXTAS (n = 25), PD (n = 23), ET (n = 18) and controls (n = 20) and regression analysis was performed to determine whether tremorography measures distinguished between the groups. The FXTAS Rating scale (FXTAS-RS) was administered to determine whether sub-score items on the clinician rated scale correlated with tremorography variables. ResultsFXTAS participants had reduced finger tap speed compared to those with ET, and ET had increased kinetic tremor compared to PD. Higher kinetic tremor distinguished FXTAS from PD (p = .02), and lower finger tap speed distinguished FXTAS from ET (p = .004). FXTAS-RS tremor and bradykinesia items correlated with tremorography measures (p = .005 to <0.0001). ConclusionsThis is the first quantitative study to compare tremor and bradykinesia in FXTAS, PD and ET. Kinetic tremor and bradykinesia measures using a quantitative inertial sensor system distinguished FXTAS from PD and ET, respectively. Such technologies may be useful for detecting precise tremor and bradykinesia abnormalities and distinguishing the tremor and bradykinesia profiles in each of these disorders.

Non-motor correlates of wrist-worn wearable sensor use in Parkinson\u2019s disease: an exploratory analysis

Wearable sensors are becoming increasingly more available in Parkinson’s disease and are used to measure motor function. Whether non-motor symptoms (NMS) can also be measured with these wearable sensors remains unclear. We therefore performed a retrospective, exploratory, analysis of 108 patients with a diagnosis of idiopathic Parkinson’s disease enroled in the Non-motor Longitudinal International Study (UKCRN No. 10084) at King’s College Hospital, London, to determine the association between the range and nature of NMS and an accelerometer-based outcome measure of bradykinesia (BKS) and dyskinesia (DKS). NMS were assessed by the validated NMS Scale, and included, e.g., cognition, mood and sleep, and gastrointestinal, urinary and sexual problems. Multiple linear regression modelling was used to identify NMS associated with BKS and DKS. We found that BKS was associated with domains 6 (gastrointestinal tract; p = 0.006) and 8 (sexual function; p = 0.003) of the NMS scale. DKS was associated with domains 3 (mood/cognition; p = 0.016), 4 (perceptual problems; p = 0.025), 6 (gastrointestinal tract; p = 0.029) and 9 (miscellaneous, p = 0.003). In the separate domains, constipation was significantly associated with BKS. Delusions, dysphagia, hyposmia, weight change and hyperhidrosis were identified as significantly associated with DKS. None of the NMSS domains were associated with disease duration (p ≥ 0.08). In conclusion, measures of BKS and DKS were mainly associated with gastrointestinal problems, independent of disease duration, showing the potential for wearable devices to pick up on these symptoms. These exploratory results deserve further exploration, and more research on this topic in the form of comprehensive large-scale studies is needed.

The BRadykinesia Akinesia INcoordination (BRAIN) Tap Test: Capturing the Sequence Effect.

The BRadykinesia Akinesia INcoordination (BRAIN) tap test is an online keyboard tapping task that has been previously validated to assess upper limb motor function in Parkinson's disease (PD). To develop a new parameter that detects a sequence effect and to reliably distinguish between PD patients on and off medication. In addition, we sought to validate a mobile version of the test for use on smartphones and tablet devices. The BRAIN test scores in 61 patients with PD and 93 healthy controls were compared. A range of established parameters captured number and accuracy of alternate taps. The new velocity score recorded the intertap speed. Decrement in the velocity score was used as a marker for the sequence effect. In the validation phase, 19 PD patients and 19 controls were tested using different hardware including mobile devices. Quantified slopes from the velocity score demonstrated bradykinesia (sequence effect) in PD patients (slope cut-off -0.002) with 58% sensitivity and 81% specificity (discovery phase of the study) and 65% sensitivity and 88% specificity (validation phase). All BRAIN test parameters differentiated between on and off medication states in PD. Differentiation between PD patients and controls was possible on all hardware versions of the test. The BRAIN tap test is a simple, user-friendly, and free-to-use tool for the assessment of upper limb motor dysfunction in PD, which now includes a measure of bradykinesia.

Using wearables to assess bradykinesia and rigidity in patients with Parkinson’s disease: a focused, narrative review of the literature

The potential of using wearable technologies for the objective assessment of motor symptoms in Parkinson's disease (PD) has gained prominence recently. Nonetheless, compared to tremor and gait impairment, less emphasis has been placed on the quantification of bradykinesia and rigidity. This review aimed to consolidate the existing research on objective measurement of bradykinesia and rigidity in PD through the use of wearables, focusing on the continuous monitoring of these two symptoms in free-living environments. A search of PubMed was conducted through a combination of keyword and MeSH searches. We also searched the IEEE, Google Scholar, Embase, and Scopus databases to ensure thorough results and to minimize the chances of missing relevant studies. Papers published after the year 2000 with sample sizes greater than five were included. Studies were assessed for quality and information was extracted regarding the devices used and their location on the body, the setting and duration of the study, the "gold standard" used as a reference for validation, the metrics used, and the results of each paper. Thirty-one and eight studies met the search criteria and evaluated bradykinesia and rigidity, respectively. Several studies reported strong associations between wearable-based measures and the gold-standard references for bradykinesia, and, to a lesser extent, rigidity. Only a few, pilot studies investigated the measurement of bradykinesia and rigidity in the home and free-living settings. While the current results are promising for the future of wearables, additional work is needed on their validation and adaptation in ecological, free-living settings. Doing so has the potential to improve the assessment and treatment of motor fluctuations and symptoms of PD more generally through real-time objective monitoring of bradykinesia and rigidity.

Evaluation of D1/D5 Partial Agonist PF-06412562 in Parkinson’s Disease following Oral Administration

Background: PF-06412562 is a moderately potent, highly selective oral D₁/D₅ dopamine receptor partial agonist. Objective: To study the efficacy and safety of a single, oral, split dose of PF-06412562 in patients with Parkinson’s disease. Methods: Following overnight levodopa (L-dopa, Sinemet®) washout, subjects received a single dose of levodopa in open-label period 1. Periods 2 and 3 had a double-blinded, sponsor-open, randomized, 2-way cross-over, placebo-controlled design, during which subjects were randomized to PF-06412562 30 mg (+ 20 mg 4 h later) or placebo. Maximum percent improvement from baseline in finger-tapping speed (measure of bradykinesia) measured using Kinesia^TM technology (as the primary end point) and change from baseline in the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III) motor section scores (the preferred exploratory end point) were evaluated. Results: Nineteen subjects received levodopa; 13 met the period 2/3 entry criteria and received PF-06412562, 30 + 20 mg, or placebo. The prespecified primary efficacy criterion for significant improvement in finger-tapping was not met due to inconsistencies in the task leading to large between-period fluctuations of within-patient baseline values. Change from baseline in MDS-UPDRS-III score with PF-06412562 resulted in a placebo-adjusted point estimate of –10.59 with a one-sided 90% upper CI of PF-06412562 versus placebo model-based contrast of (–inf, –7.44) at 1.5–2.5 h after the dose (p < 0.0001). All adverse events were mild-to-moderate. Conclusions: We report the first evidence of potential anti-parkinsonian efficacy of the oral selective D₁/D₅ partial agonist PF-06412562 without the significant acute changes in cardiovascular parameters reported with previous D₁ agonists.

Neurophysiological correlates of bradykinesia in Parkinson's disease.

Many neurophysiological abnormalities have been described in the primary motor cortex of patients with Parkinson's disease. However, it is unclear whether there is any relationship between them and bradykinesia, one of the cardinal motor features of the condition. In the present study we aimed to investigate whether objective measures of bradykinesia in Parkinson's disease have any relationship with neurophysiological measures in primary motor cortex as assessed by means of transcranial magnetic stimulation techniques. Twenty-two patients with Parkinson's disease and 18 healthy subjects were enrolled. Objective measurements of repetitive finger tapping (amplitude, speed and decrement) were obtained using a motion analysis system. The excitability of primary motor cortex was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and facilitation. Plasticity-like mechanisms in primary motor cortex were indexed according to the amplitude changes in motor-evoked potentials after the paired associative stimulation protocol. Patients were assessed in two sessions, i.e. OFF and ON medication. A canonical correlation analysis was used to test for relationships between the kinematic and neurophysiological variables. Patients with Parkinson's disease tapped more slowly and with smaller amplitude than normal, and displayed decrement as tapping progressed. They also had steeper input/output curves, reduced short-interval intracortical inhibition and a reduced response to the paired associative stimulation protocol. Within the patient group, bradykinesia features correlated with the slope of the input/output curve and the after-effects of the paired associative stimulation protocol. Although dopaminergic therapy improved movement kinematics as well as neurophysiological measures, there was no relationship between them. In conclusion, neurophysiological changes in primary motor cortex relate to bradykinesia in patients with Parkinson's disease, although other mechanisms sensitive to dopamine levels must also play a role.

Quantification of whole-body bradykinesia in Parkinson's disease participants using multiple inertial sensors

Bradykinesia (slowness of movement) is a common motor symptom of Parkinson's disease (PD) that can severely affect quality of life for those living with the disease. Assessment and treatment of PD motor symptoms largely depends on clinical scales such as the Unified Parkinson's Disease Rating Scale (UPDRS). However, such clinical scales rely on the visual assessment by a human observer, naturally resulting in inter-rater variability. Although previous studies have developed objective means for measuring bradykinesia in PD patients, their evaluation was restricted by the type of movement and number of joints assessed. These studies failed to provide a more comprehensive, whole-body evaluation capable of measuring multiple joints simultaneously.This study utilizes wearable inertial measurement units (IMUs) to quantify whole-body movements, providing novel bradykinesia indices for walking (WBI) and standing up from a chair (sit-to-stand; SBI). The proposed bradykinesia indices include the joint angles at both upper and lower limbs and trunk motion to compute a complete, objective score for whole body bradykinesia.Thirty PD and 11 age-matched healthy control participants were recruited for the study. The participants performed two standard walking tasks that involved multiple body joints in the upper and lower limbs. The WBI and SBI successfully identified differences between control and PD participants. The indices also effectively identified differences within the PD population, distinguishing participants assessed with (ON) and without (OFF) levodopa; the gold-standard of treatment for PD.The goal of this study is to provide health professionals with an objective score for whole body bradykinesia by simultaneously measuring the upper and lower extremities along with truncal movement. This method demonstrates potential to be used in conjunction with current clinical standards for motor symptom assessment, and may also be promising for the remote assessment of PD patients and in cases where experienced clinicians may not be available. In conclusion, the intelligent use of this technology for the measurement of bradykinesia (among other symptoms) has vast implications for optimizing treatment in Parkinson's disease, ultimately leading to an improvement in quality of life.

Subthalamic beta dynamics mirror Parkinsonian bradykinesia months after neurostimulator implantation.

ABSTRACTBackgroundExaggerated oscillatory activity in the beta frequency band in the subthalamic nucleus has been suggested to be related to bradykinesia in Parkinson's disease (PD). However, studies seeking correlations between such activity in the local field potential and motor performance have been limited to the immediate postoperative period, which may be confounded by a stun effect that leads to the temporary alleviation of PD deficits.MethodsLocal field potentials were recorded simultaneously with motor performance in PD patients several months after neurostimulator implantation. This was enabled by the chronic implantation of a pulse generator with the capacity to record and transmit local field potentials from deep brain stimulation electrodes. Specifically, we investigated oscillatory beta power dynamics and objective measures of bradykinesia during an upper limb alternating pronation and supination task in 9 patients.ResultsAlthough beta power was suppressed during continuously repeated movements, this suppression progressively diminished over time in tandem with a progressive decrement in the frequency and amplitude of movements. The relationship between changes within local field potentials and movement parameters was significant across patients, and not present for theta/alpha frequencies (5‐12 Hz). Change in movement frequency furthermore related to beta power dynamics within patients.ConclusionsChanges in beta power are linked to changes in movement performance and the sequence effect of bradykinesia months after neurostimulator implantation. These findings provide further evidence that beta power may serve as a biomarker for bradykinesia and provide a suitable substrate for feedback control in chronic adaptive deep brain stimulation. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Objective measure of bradykinesia in parkinsonism by the maximal frequency of standardized, large pronation/supination movements

Bradykinesia in Parkinson's disease (PD) predominates in large movements. Traditional assessments use the UPDRS, a subjective and ordinal tool that does not rate movement scaling (hypometria). We have measured the maximum frequency of standardized large alternating elbow pronation/supination movements in patients with PD, hypothesizing a negative correlation with the UPDRS III score and with the delay since diagnosis. We carried out a retrospective study on a convenience sample of 30 patients with idiopathic PD from Henri Mondor University Hospitals (Créteil, France), all assessed in the clinically defined OFF state by a single rater. Assessment included the maximal frequency of large (180°C) elbow pronation/supination movements (FLM), bilaterally, using a portable tool. Patients were also assessed on UPDRS III and bradykinesia sub-scores (UPDRS IIIb). We explored correlations (Pearson) between FLM and UPDRS III, UPDRS IIIb and time since diagnosis (TSD). UPDRS III was 20.08 ± 10.0 (mean ± SD), TSD was 9.9 ± 5.2 years and FLM were 0.75 ± 0.27 Hz and 0.94 ± 0.25 on the more and less affected side respectively (strongly correlated with each other, r = 0.80, p < 0.0001). Correlations with UPDRS III scores and time since diagnosis for the more affected arm (resp less affected arm) were as follows FLM-UPDRSIII: r = –0.28; p = 0.15 ( r = –0.40; p = 0.04); RLM-UPDRSIIIB, r = –0.48; p = 0.01 ( r = –0.36; p = 0.06); FLM-TSD, r = –0.36; p = 0.07 ( r = –0.51; p = 0.007). These findings validate the maximal frequency of standardized 180°C pronation/supination movements as a clinical marker of the severity of parkinsonism. Intra- and inter-rater reliability and sensitivity to change of FLM still need to be investigated. FLM is easily usable in the clinic setting and might become a useful tool to optimize the monitoring of treatment effects and patient evolution.