The Technology Behind Optimizing Parkinson Disease Management

October 23, 2020
Linda Peckel

Volume 3, Issue 5

Advances in wearables and virtual reality present an opportunity to maximize rehabilitative efforts and improve outcomes.

Technological developments over the past decade are now leading to long-awaited advances in the management of Parkinson disease (PD). These tech-driven approaches—including exergaming, virtual reality, and the use of wearable devices—have not only helped improve rehabilitation but may also provide more accurate measures of therapeutic efficacy for new treatments undergoing clinical trials.

The role of virtual reality and exergaming in PD physiotherapy

Virtual reality has been used to drive purposeful, targeted exercise therapy for a number of progressive disorders affecting muscular function, including traumatic brain injury, cerebral palsy, stroke, and PD.1 Virtual reality–based games are available on widely available gaming systems and have demonstrated specific benefits for improving balance, gait, functional mobility, and overall quality of life for individuals with PD.2,3 Results of a recent study from Brazil showed that the weekly addition of Nintendo Wii exercises significantly magnified the therapeutic effects of conventional exercise therapy alone.2

Exergaming, virtual reality, augmented reality, and their variants come in many shapes and sizes, said Jeffrey Hausdorff, PhD, director at the Center for the Study of Movement, Cognition, and Mobility at the Neurology Institute at the Sourasky Medical Center in Tel Aviv, Israel, who has been involved in many of the trials of digital technologies for PD. “In general, interventions based on these technologies can be very helpful as ways of enhancing and augmenting the impact of other, more conventional behavioral interventions for Parkinson disease. Engaging ‘games’ can heighten motivation and increase [adherence]; this in turn leads to a stronger impact of the therapy. They can also provide specific aspects of therapy that may be difficult to deliver otherwise,” he told NeurologyLive®.

In one multicenter, randomized, controlled study (RCT) designed to examine the added value of a relatively simple virtual reality system, Hausdorff explained that subjects walk on a treadmill with a screen attached to it that allows them to envision themselves walking through an environment with obstacles and challenging conditions where they have to learn implicitly, in a game-like fashion, how to walk and do other things at the same time, including dual tasks such as motor and cognitive challenges.4 In another study that included older adults as well as patients with PD, Hausdorff and colleagues found a significant reduction in falls among the participants who trained with a treadmill and virtual reality system compared with an active control group who performed treadmill training alone.5 “With this type of system, we can target certain aspects of cognitive function that are important to daily walking and cannot be targeted with treadmill training alone,” he said.

Managing progression in Parkinson disease

Long-term management of PD presents many clinical challenges as the status of the patient deteriorates over time. “In the early phases of the disease, typically patients respond well to pharmacotherapies,” explained Paolo Bonato, PhD, director of the Motion Analysis Laboratory at Spaulding Rehabilitation Hospital in Boston, Massachusetts, “but unfortunately, as the disease progresses, it becomes more difficult to control their symptoms.” Patients often report experiencing a roller coaster of parkinsonian symptoms, recognized clinically as motor fluctuations. Bradykinesia might respond well to treatment, but patients might experience severe dyskinesia as a result.

“A significant portion of patients with Parkinson disease experience motor fluctuations, meaning their symptoms are not constant over time,” Bonato said. The severity of dyskinesia often varies within the interval between medication intakes; patients might experience episodes within the first hour of taking their medication (onset dyskinesia), at the peak of the medication’s effects, or at the end, as the effects are wearing off. These symptoms are quite disruptive to their ability to perform activities of daily living, Bonato noted, and they are a significant focus of clinical attention during the later years of the disease.

Uses for wearable technology

Motor fluctuations

Although levodopa-induced dyskinesia is a common complication in PD, recent research indicates that dyskinesias develop as a function of disease duration rather than accumulation of levodopa. This has led to recommendations to initiate levodopa therapy without delay early in the disease course, but the problem with motor fluctuations remains once the disease progresses.6

Bonato observed that as neurologists titrate the patients’ medications to better manage their symptoms, a major challenge is that patients do not have an objective perception of their motor status, in part because of the cognitive effects of their disease. Patients are simply not able to report reliably on the effects of changes in the medication regimen. But more than that, Bonato pointed out that proper assessment of the severity of symptoms is very challenging, even to clinicians. “In fact, clinical researchers undergo training to administer the MDS-UPDRS [International Parkinson and Movement Disorder Society Parkinson’s disease rating scale], which is the clinical scale to assess the severity of parkinsonian symptoms that is most commonly used,” he said.

Wearable technology has been able to detect fluctuations occurring in increments of as little as 5 minutes compared with patient-reported symptoms in diaries, which monitor changes at only 30-minute intervals at best, according to Bonato, who plans to publish these data soon.

"We used to think that walking was primarily a motor ability that required intact muscle and skeletal function and sensory function for feedback. Those abilities are certainly critical components of safe ambulation. However, there’s a key ingredient that’s missing in that view, and that’s cognitive function," Hausdorff stated.

Falling

Falling is a complex type of dysfunction that involves multiple aspects of cognition. “Safe ambulation also involves executive function, a set of higher-level cognitive functions that include the ability to walk and multitask and the ability to plan and adapt to one’s environment,” Hausdorff explained. “We used to think that walking was primarily a motor ability that required intact muscle and skeletal function and sensory function for feedback,” he said. “Those abilities are certainly critical components of safe ambulation. However, there’s a key ingredient that’s missing in that view, and that’s cognitive function.”

Some of his studies looked at the role of cognition in helping the patient maintain attention to tasks of mobility.7 “The virtual reality technology that we evaluated in the RCT mirrors many real-world walking situations, such as walking outdoors, which requires being able to do multiple things while walking, such as listening to head- sets, talking to companions, thinking about what we’re going to be doing next, and negotiating obstacles. If you just walk on a treadmill alone without that added virtual reality component, it’s training just for the motor part while not focusing at all on the cognitive aspects of walking that are needed for safe ambulation,” Hausdorff said.

Freezing

Freezing gait is a significant problem in advanced PD, in which motion advancement is very small or does not occur at all. Results of recent studies have indicated that freezing is not limited to gait but can also significantly hinder upper limb movements and speech.8 Digital technologies have been extensively studied as cueing modalities to recover attention to specific motor tasks, to rescue the patient from a freezing episode.8

Hausdorff and Alice Nieuwboer, PhD, of the University of Leuven in Belgium, are currently collaborating on a study funded by the Michael J. Fox Foundation for Parkinson’s Research designed to detect a freezing event. In this study, subjects wear a sensor on their shoes that measures the movement of their feet and any freezing events as they conduct their daily activities. The sensor’s information is wirelessly transmitted to a smartphone that measures walking in real time. The system is designed to detect when a freezing event occurs and then give a cue back to the user, helping the user to quickly become free from the event. “In the future, it’s hoped that it will also be able to warn of a freezing event before it occurs to further ameliorate the problem,” Hausdorff said.

One of the unique aspects of this study is that all the assessments are conducted in the patient’s home and the intervention takes place throughout the day, wherever and whenever the patient walks. “Testing and treating in the home is especially advantageous at this time, when it is often increasingly difficult for people to make their way to a clinic or hospital,” Hausdorff said.

Data collection

A primary obstacle to many clinical trials of the 1980s and 1990s that may have contributed to negative results, according to Bonato, was the inaccuracy of the self-reported data being collected from patients. He and colleagues9 published a study early in 2020 that made a strong case for the use of wearable technologies to replace patient diaries in making treatment decisions as well as in clinical trials.

"There are 2 problems with the use of patient diaries,” Bonato stated. “The first and more obvious one is that patients display poor [adherence] with the use of diaries. We know that because we track when patients log on to fill out electronic diaries, and hence we know that they are not doing that on a regular basis. The second and perhaps even more important issue is that we have discovered that motor fluctuations evolve more rapidly than we originally thought. Therefore, gathering data at intervals of 30 minutes, as we do by using patient diaries, is not enough to properly capture the characteristics of the motor fluctuations that patients experience.”

Because clinical trials have relied heavily on patient diaries as measurements for outcomes, this new finding is highly significant. Bonato observed that pharmaceutical companies have started wondering whether the negative results of past clinical trials were the by-product of not having access to the right technology to capture the effects of medications on motor fluctuations. “I anticipate that the large body of work in this area will result in important advances in the field and better treatments for patients with Parkinson disease,” he added.

Where Parkinson disease tech is headed

A multinational task force on technology from the MDS convened in 2018 to produce a set of objectives for the use of digital technologies to obtain more usable data to inform treatment decisions.10 They reported that development of mobile digital devices has reached sufficient levels of “sophistication, versatility, and wearability” to warrant recommending their implementation in routine care for patients with PD.10 With different technologies offering opportunities to improve quality of life and outcomes for patients as they begin to develop advanced symptoms, these tools are increasingly being recognized as necessary supportive therapies over the long term.

"Clinicians, researchers, and pharmaceutical companies are very interested in using wearable technology,” Bonato said. “Clinicians are hoping that this technology may lead to significant improvements in the clinical management of symptoms experienced by patients, and researchers are adopting the technology to collect more reliable data and hence improve their ability to study the effects of new therapies.”

References
1. Barry G, Galna B, Rochester L. The role of exergaming in Parkinson’s disease rehabilitation: a systematic review of the evidence. J Neuroeng Rehabil. 2014;11:33. doi:10.1186/1743-0003-11-33.
2. Santos P, Machado T, Santos L, Ribeiro N, Melo A. Efficacy of the Nintendo Wii combination with conven- tional exercises in the rehabilitation of individuals with Parkinson’s disease: a randomized clinical trial. NeuroRehabilitation. 2019;45(2):255-263. doi:10.3233/NRE-192771
3. Garcia-Agundez A, Folkerts AK, Konrad R, et al. Recent advances in rehabilitation for Parkinson’s disease with exergames: a systematic review. J Neuroeng Rehabil. 2019;16(1):17. doi:10.1186/s12984-019-0492-1
4. Mirelman A, Maidan I, Herman T, Deutsch JE, Giladi N, Hausdorff JM. Virtual reality for gait training: can it induce motor learning to enhance complex walking and reduce fall risk in patients with Parkinson’s disease? J Gerontol A Biol Sci Med Sci. 2011;66(2):234-240. doi:10.1093/gerona/glq201
5. Mirelman A, Rochester L, Reelick M, et al. V-TIME: a treadmill training program augmented by virtual reality to decrease fall risk in older adults: study design of a randomized controlled trial. BMC Neurol. 2013;13:15. doi:10.1186/1471-2377-13-15
6. Espay AJ, Morgante F, Merola A, et al. Levodopa-induced dyskinesia in Parkinson disease: current and evolving concepts. Ann Neurol. 2018;84(6):797-811. doi:10.1002/ana.25364
7. Maidan I, Nieuwhof F, Bernad-Elazari H, et al. Evidence for differential effects of 2 forms of exer- cise on prefrontal plasticity during walking in Parkinson’s disease. Neurorehabil Neural Repair. 2018;32(3):200-208. doi:10.1177/1545968318763750
8. Ginis P, Nackaerts E, Nieuwboer A, Heremans E. Cueing for people with Parkinson’s disease with freezing of gait: a narrative review of the state-of-the-art and novel perspectives. Ann Phys Rehabil Med. 2018;61(6):407-413. doi:10.1016/j.rehab.2017.08.002
9. Erb MK, Karlin DR, Ho BK, et al. mHealth and wearable technology should replace motor diaries to track motor fluctuations in Parkinson’s disease. NPJ Digit Med. 2020;3:6. doi:10.1038/s41746-019-0214-x
10. Espay AJ, Hausdorff JM, Sánchez-Ferro Á, et al. A roadmap for implementation of patient-centered digital outcome measures in Parkinson’s disease obtained using mobile health technologies. Mov Disord. 2019;34(5):657-663. doi:10.1002/mds.27671
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