I'm sure these exact same sensors could be repurposed to tell us exact objective gait disabilities in stroke. But that won't occur, we have no stroke leadership.
A method for measuring time spent in bradykinesia and dyskinesia in people with Parkinson’s disease using an ambulatory monitor
Journal of NeuroEngineering and Rehabilitation volume 18, Article number: 116 (2021)
Abstract
Background
Fluctuations in motor function in Parkinson’s Disease (PD) are frequent and cause significant disability. Frequently device assisted therapies are required to treat them. Currently, fluctuations are self-reported through diaries and history yet frequently people with PD do not accurately identify and report fluctuations. As the management of fluctuations and the outcomes of many clinical trials depend on accurately measuring fluctuations a means of objectively measuring time spent with bradykinesia or dyskinesia would be important. The aim of this study was to present a system that uses wearable sensors to measure the percentage of time that bradykinesia or dyskinesia scores are above a target as a means for assessing levels of treatment and fluctuations in PD.
Methods
Data in a database of 228 people with Parkinson’s Disease and 157 control subjects, who had worn the Parkinson’s Kinetigraph ((PKG, Global Kinetics Corporation™, Australia) and scores from the Unified Parkinson’s Disease Rating Scale (UPDRS) and other clinic scales were used. The PKG’s provided score for bradykinesia and dyskinesia every two minutes and these were compared to a previously established target range representing a UPDRS III score of 35. The proportion of these scores above target over the 6 days that the PKG was worn were used to derive the percent time in bradykinesia (PTB) and percent time in dyskinesia (PTD). As well, a previously describe algorithm for estimating the amplitude of the levodopa response was used to determine whether a subject was a fluctuator or non-fluctuator.
Results
Using this approach, a normal range of PTB and PTD based on Control subject was developed. The level of PTB and PTD experienced by people with PD was compared with their levels of fluctuation. There was a correlation (Pearson’s ρ = 0.4) between UPDRS II scores and PTB: the correlation between Parkinson Disease Questionnaire scores and UPDRS Total scores and PTB and slightly lower. PTB and PTD fell in response to treatment for bradykinesia or dyskinesia (respectively) with greater sensitivity than clinical scales.
Conclusions
This approach provides an objective assessment of the severity of fluctuations in Parkinson’s Disease that could be used in in clinical trials and routine care.
Introduction
The first few years of Parkinson’s Disease (PD) respond well to levodopa and other dopaminergic medications [1, 2]. However, the duration of symptomatic benefit derived from each dose of levodopa gradually shortens, plateauing at about 3 h. After 2 years of disease, ~ 50% of people with PD (PwP) are symptomatically aware of this shortening of benefit and ~ 70% of PwP eventually experience this effect [3]. Historically, this phenomenon was considered a transition from mobility (“on”) to bradykinesia (“off”) and referred to as “wearing-off” [4]. However treating clinicians are frequently unaware of the presence of “wearing-off”, [5, 6] because PwP do not always recognise the accompanying symptomatology as re-emergence of bradykinesia [7,8,9] and may perceive them as a transitions to non-motor symptomologies [9,10,11].
Implicitly, “wearing-off” is preceded by a response to levodopa and typically occurs 3–4 h after that response. These “off–on–off” transitions will be referred to as fluctuations and dyskinesia will be considered as a separate entity, despite similar underlying mechanisms and frequent co-occurrence [3]. Specifically, the term fluctuator will apply when there is a significant levodopa response and thus the potential for significant “wearing-off”.
In PD, routine clinical care and clinical trials depend on self-reporting of fluctuations [8, 12, 13], but as noted above, fluctuations are often not recognised by the PwP. However, objective measurement of PD using wearable devices is now possible [14] and may be superior to motor diaries in detecting the presence and timing of fluctuations and dyskinesia [6] and leads to better outcomes when used in the management of PD [15, 16]. There are, however, important conceptual differences between self-reporting (such as by diary) and objective measurement of fluctuations and dyskinesia.
To report fluctuations, PwP must implicitly be aware of fluctuations. The diary or history report the symptoms or conscious experience of the PwP, whereas objective measures of bradykinesia, including the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, measure the signs of bradykinesia. There are many examples in medicine, such as asthma [17], where patient’s assessment of function may differ from an objective measurement of function. Diaries require recognition of three states: “off”, “on”, and “dyskinesia”. PwP who can recognise these states vary in the level of bradykinesia that they recognise as transitioning from “off” to “on” [11]. Similarly, the level that PwP recognise as the transition to dyskinesia varies from subject to subject. A previous study comparing diaries and objective measurement showed that patients whose levels of bradykinesia were habitually high, tended to identify “off” at higher objective scores [18], possibly due to an altered self-awareness of motor states in PD [19]. Objective measurements provide a continuous range of bradykinesia, with “off” referenced to a specific point on the scale, marking the boundary between acceptable and unacceptable or treatable bradykinesia. Thus, “off” time measured by diary records the hours the subject perceived medications to have failed, whereas objective measurement records the amount of time that scores were above an objective target. A diary records a symptom whereas objective measurement records a sign: these may be similar, but they are not identical.
It is difficult to find an example in medicine where objective measurement and effective therapy exist, without there being defined targets for control. Marsden and Parkes noted similarities between PD and diabetes [20], a condition where measurement is routine and terms such as “targets” and “controlled” are used. Targets are derived from physiological norms, improved outcomes and health economics. Achieving these targets comes with improved clinical outcomes, recognising that it is not always possible to achieve the target. Targets help avoid unnecessary treatments of those already “well controlled” and focus attention on those who would benefit from change in therapy. A bradykinesia target would be a score on a bradykinesia scale marking the boundary between acceptable bradykinesia and bradykinesia that requires an intervention.
The use of wearable sensors to objectively measure PD has received increasing attention and has been comprehensively reviewed elsewhere [14, 21, 22]. Several studies have demonstrated that fluctuations in bradykinesia following a dose of levodopa can be measured using wearable sensors [23, 24]. While not explicitly measuring time in bradykinesia or dyskinesia, one study showed that the use of wearable technology led to increased referral for advanced therapy, suggesting that their measurement system allowed greater detection of fluctuations [25]. However, a challenge facing wearable technologies is the intrinsic variability of PD. One approach is to remotely monitor several days, so that the response to a particular dose can be averaged to reveal the duration of benefit and wearing off [26]. While averaging reveals the usual pattern of response, it obscures variability in the pattern, such as that caused by dose failure. Reporting the response pattern’s interquartile range is one approach to measuring variability but another approach, reported in this present study, is to report the amount of time a subject’s bradykinesia or dyskinesia scores are above target. This is in effect a quantified version of the diary, notwithstanding the differences and caveats described above.
This method of objective measurement system requires continuous, remote monitoring over several days and requiring minimal attention from the PwP, to ensure naturalistic movements and patient fatigue. The system requires sampling at a frequency that captures fluctuations and dyskinesia following levodopa doses. At therapeutic target, indicating satisfactory levels of bradykinesia and dyskinesia is required. The PKG system was used in this study, because to our knowledge the PKG is the only system that meets these criteria. The Parkinson’s KinetiGraph (PKG, Global Kinetics Corporation™, Australia) is an objective measurement system where targets have been based on physiological norms [27, 28], expert opinion and the efficacy of these targets to guide therapy and improve outcomes [15, 16].
This is a report of a method that measures “time in bradykinesia” and “time in dyskinesia” using data from ambulatory monitoring of PwP. These parameters, along with a recently described method for measuring a levodopa response [29] were used to identify fluctuations. A boundary between these values from PwP and controls was then established and used to describe a means for categorising fluctuators. Credible measures for time in bradykinesia and dyskinesia should have meaningful correlations with clinical scales and be at least as sensitive as these scales in measuring the effect of clinical interventions: on this basis these comparisons were then carried out and reported. The findings of this study suggest that this approach shows promise as an outcome measure in clinical trials of PD therapies and further studies will establish their place in guiding the management of PD.
More at link.
No comments:
Post a Comment