Every parkie is interested in knowing the answer to the question: “how am I doing?” We know we have a progressive disease and we really want some objective feedback on how our condition is different from say a year ago. What symptoms are worse, what’s better, what’s the same? But it’s difficult to get an informative answer. Friends and family tend to be encouraging but vague…“You’re looking great!” And clinicians… well, they aren’t really all that much help, either. They drop into our lives every six months or so and take a clinical snap shot with the Unified Parkinson’s Disease Rating Scale (UPDRS).
The UPDRS has many critics. The widely used motor component of the test, which takes about 15 minutes, covers fourteen categories where muscles on both sides of the body may be behaving badly, including speech, facial expression, tremor, rigidity, finger tapping, hand movements, hand pronation/supination, foot tapping, ability to rise from a chair, posture, gait, and balance. The aggregate score (between 0 and 108) is supposed to quantify a patient’s motor deterioration. While some neurologists and researchers defend the scale, patients privately mock it. The patients are right. As a means of diagnosing Parkinson’s disease it’s not very accurate — studies show from 10% to 25% of patients turn out at post mortem not to have the condition. As a way of rating the severity of Parkinson’s, it also falls short. It’s highly subjective. Two neurologists will often give a different score for the same patient on the same subtest. Results vary dramatically depending on how recently patients have taken L-dopa and the time of day. The UPDRS scale is not linear, so a score of 40 is not "twice as bad" as 20. Likewise, dropping from a score of 20 to 25 is different from deteriorating from 30 to 35 — something that can impact clinical trials that follow a heterogeneous patient group.
There’s more. Many parts of the test, according to University of Tuebingen’s Walter Maetzler, “have almost nothing to do with daily life.” His favorite example is the test where a patient stretches out her arm with hand facing down and rotates it through 180 degrees back and forth as fast as the patient can manage. “You have to think of when really you need this in your everyday life,” says Maetzler drily. “Perhaps, if you put in a light bulb for example.” If we now add the distorting effect of the placebo response — that patients perform up to 30% better just by entering the clinic (some kind of Pavlovian response) — it really is hard to avoid the idea that patients and researchers deserve something better.
About a decade ago, individuals began speculating about capturing a more authentic picture of Parkinson’s, one that measured the ups and downs of Parkinson’s patients in their daily life. A technology, designed to work 24/7, with the potential to document the Parkinson’s experience. One of these individuals was Intel founder Andy Grove, who developed Parkinson’s in 1999. In an article for Forbes, Groves bluntly dismissed the UPDRS as “a piece of crap”. Grove used his money, technical knowledge and connections to develop a machine (the Home Box) that objectively measure a patient’s state. It turned out to be a hard problem to solve, even for a microchip engineer. But, in the early 2000’s, Rush University’s Christopher Goetz tested an early version of the Home Box and found that it could detect a decline in the UPDRS and see it earlier than a regular office visit.
Since then, objective Parkinson’s disease monitoring technology has got smaller faster and cheaper. Three projects with radically different philosophical approaches appear to be at the forefront. One is centered in Europe and has emerged from a patient driven process. The other two are US based and are built around a more conventional notion, where data is gathered at home, processed, and sent to a clinician for interpretation.
The European system, SENSE PARK, is a collaboration between the UK charity Cure Parkinson’s Trust, the University of Tuebingen, the Institut für Mikro- und Informationstechnik of the Hahn-Schickard-Gesellschaft (HSG-IMIT), Hasomed and others. Project leader, neurologist Walther Maetzler wasn’t interested in producing a digital version of the UPDRS, he wanted “to put patients in the driver’s seat... to include from the beginning people who have the condition and let them develop basically what they want to have at the end of the day.” So, Cure Parkinson’s Trust carried out surveys and patients and researchers together decided they wanted to track six domains (bradykinesia, tremor, walking, gait, balance, and cognition). Then researchers and technologists developed wearable sensors (for wrist, waist, and ankle), and fashioned algorithms to extract meaningful metrics from the data. According to Maetzler, “it's entirely different from the UPDRS, because the measurement occurs during the day and night. The data is then analyzed automatically and sent as a readable number to the user… the user is the owner of the data, and she can do with that data whatever she wants. No one else has access to the data unit unless the user decides they want to share it with the doctor for example.” The project plans a 16-week validation study in March 2014.
A competing team at a US company, Great Lakes Technologies, has developed a digital version of an enhanced UPDRS. This company already has FDA approved devices (see a recent JPD article) that can distinguish dyskinesia from tremor and discriminate changes in speed (bradykinesia), amplitude (hypokinesia) and rhythm (akinesia).
The devices (worn on the finger or ankle) have accelerometers and gyroscopes capable of tracking patients’ bodily movements (displacements and rotations) 24/7. Researcher Dustin Heldman says “it's really cool, we’re able to actually see the fluctuations… to see the tremor and bradykinesia scores changes as the medications wear off. “The devices they have built are already more sensitive than the UPDRS.” Says Heldman, “in the clinic, it often takes months to years to detect a significant change, but with this device we can detect changes much sooner by monitoring people at home.”
Unlike SENSE PARK, Great Lakes Technologies’ Kinesia Homeview is currently intended to be used by clinicians in either a telemedicine mode, where the patient performs standardized tests at home, which are sent to a clinician, or in a data-gathering mode, where data is collected over time and sent via 3G broadband for processing an analysis.
Heldman says the business model for these devices is still emerging. “Right now it's being used principally in clinical studies for drugs… but Great Lakes Technologies wants to find a way ‘to get insurance reimbursement for this technology.’”
A third exciting idea has emerged from Stanford researchers performing deep brain stimulation (DBS) surgery. On October 30, neurosurgeon Jamie Henderson implanted a new kind of neurostimulator into Parkinson’s patient Frank Donobedian, a 72-year-old retired schoolteacher from Seaside, California. The Medtronic device not only transmitted signals to Donobedian’s subthalamic nucleus — something that all such stimulators do — it also accessed the subthalamic nucleus’ electrical output. By capturing information about Donobedian’s brain-firing patterns and matching them to his symptoms, the team hopes to better understand the disease’s variability and progression outside the OR. There are also therapeutic possibilities, whereby the device might recognize certain firing patterns and adjust its output to a more appropriate level.
Says Helen Bronte-Stewart, director of Stanford’s Comprehensive Movement Disorders Center, “with this ‘brain radio’, we can study the brain’s signaling patterns at the same time that we’re observing a patient’s precise movements... we have high hopes that discoveries made possible by this new DBS system will fuel the development of new, personalized treatments for a range of neurological disorders.”
Of course, as Rush University’s Christopher Goetz puts it “the big question is whether all this data will be clinically pertinent and clinically useful… you have to show that good clinical decisions come from data of this sort otherwise it may not fly.” My hunch, however, is that such objective monitoring systems will not only make the UPDRS obsolete. By breaking the “tyranny of the clinic” they also have the potential to revolutionize medical research and clinical practice — and not just in Parkinson’s disease but throughout health care.