In the last couple weeks lots of people have asked me about the “Parkinson’s glove.” Many had seen a report on the Today Show that made some extraordinary claims about reversal of Parkinson disease (PD) symptoms, and some read a much more muted report about the glove via the Michael J Fox Foundation. Many asked whether I had read the studies, and asked where they could get the glove. Although this was news to me also, because so many have asked, because it generated so much excitement, I have been looking into this and am responding with this short article, despite the fact that I am not a researcher. I just try to keep my eye on PD and will act as a science reporter here.
First, what are we talking about? A Stanford Medicine team led by Peter Tass, MD, PhD, is trialing a “vibrotactile” glove intended to lessen or alleviate motor symptoms caused by Parkinson’s disease (PD). Per the 12/14/2022 Research News article by the Fox Foundation “results from initial pilot studies in roughly a half-dozen participants suggest that it may ease tremors, slowness and stiffness… Participants wore a glove on each hand for several hours per day. The gloves deliver light vibration through the fingertips. Study researchers suggest that this stimulation can ‘reset’ abnormal electrical activity in the brain, which happens in Parkinson’s disease.” I will discuss the pilot studies below.
Before that however, and as interesting a concept as this is, let’s linger for a moment on the point that pilot studies are not adequate to make an assessment of how people will generally respond to some intervention. Pilot studies are typically small and preliminary, meant to see if a device or medication is feasible, and for example, to see if the design should be improved before launching into larger studies. Pilot studies occur before or at the beginning of the typical phase I-IV trials needed for FDA approval. Even if results are remarkable, we need to see how considerably more than a handful of patients will respond before we can make generalizations.
It is also a good idea to take into consideration that the lay press often unintentionally distorts what is being presented, in part because the reporters might not understand the science (or the scientific method in many cases). Much of what has been presented in lay press so far around this topic has been testimonial, not science. A lot of hyperbolic discussion has taken place in these reports: words such as “miraculous” or “transformative” that raise red flags. And, it is often problematic to present incomplete information via the media and generally not a good idea to have media coverage prior to completion of studies.
One more aside. Please don’t mistake my statements about the media reports for a lack of interest in, or a dismissal of this topic. That is not the case. We just don’t have have all of the information yet, even if the videos seem amazing. Looking at this from a different angle, it is also often true that revolutionary innovation is mocked or heckled prior to being understood. That is not my position either. I would guess a lot of big breakthroughs first suffered this way. And, I can only assume it is almost a rite of passage for any genius to first be called crazy. Considering those points, and given that we don’t want to be among those Einstein called “mediocre minds,” it is also a good idea to recall the words of Carl Sagan: “extraordinary claims require extraordinary evidence.” Let’s keep all of that in our thoughts as we evaluate this with our mental toolbox.
The Today Show December 13, 2022 presented clips of Kanwar Bhutani, a 58-year-old man who was diagnosed with PD at age 39. Mr. Bhutani was shown prior to treatment with the glove on a day in 2018. In that scene he was stuck in a doorway with freezing of gait. Per correspondent Jacob Soboroff, Mr. Bhutani had been “bound to a wheelchair and taking twenty-five medications to treat his symptoms. But, after his very first session wearing the gloves for just four hours, Kanwar saw remarkable results.” The monologue is superimposed over a video of the Mr. Bhutani walking upright with a seemingly normal pace and near-normal stride. The subject verified that this was “day one…I was in disbelief…the good news today is I only take two medicines.” Mr. Soboroff then said “You’ve gone from twenty-five to two.”
Point of clarification: It is likely that Mr. Bhutani was taking twenty-five tablets daily, not twenty-five different medicines for PD. And, it is more likely that he is taking “two” different medications with different dosing times, than two tablets daily, but that is only conjecture. The information is not given in the story. Perhaps he was able to reduce medications, but the representation is likely media distortion number one.
Next, there was a clip of Bhutani reportedly finishing the New York City Marathon “just three months after his first treatment.” To this day he was stated to have completed multiple 5K races. Mr. Bhutani said, “It has changed my life, totally transformed me.” It seems remarkable.
On the same Today Show segment a man was shown with “stiff steps”, and in the next clip it appeared the same man was working with gymnasts’ bars. Likewise, another man with a shuffling gait was shown performing “happy dances.” The Today Show stated that 20 patients were involved in the “first round of clinical trials…So far, they say everyone that’s used the gloves has seen some improvement…for Dr. Tass, and the team at Stanford Medicine, they say they’ve had thousands of people already apply for their next trial. They hope to have the gloves approved by the FDA and available for purchase in about two years.”
There is a lot to unpack there. We don’t know for example, whether these patients were examined (and filmed) on or off medications, which would of course make a huge difference for many people with PD. In the “on” state medications are working and movement is better. In the “off” state, medications are not working and movement is worse: stiffness of muscles, slowness of gait, for example. In the case of advanced PD fluctuation of symptoms throughout the day is common, whether or not medications have been taken. If you catch someone in an off fluctuation, they will look much worse than in an “on” state. I’m sure you know that walking is very different from gymnastics or dancing, and it would have been better to show efforts at any activities before and after use of the glove for a one-to-one comparison: here he is walking before the glove, here he is walking in the same location after the glove. There are also are numerous reports of preserved motor function in one task or another despite severe PD gait impairment. In other words, some abilities may be normal, even in a person with advanced disease. In 2010 for example, there was a widely distributed report of a man with severe gait impairment who appeared normal while riding a bicycle. As for the before and after of Mr. Bhutani walking through a doorway versus walking on a straightaway, that is also an uneven comparison. Doorways can be notoriously difficult for PD patients and a prime location for freezing of gait, even when gait may look relatively normal otherwise. Finally, PD is a clinical diagnosis and there can be mimicking conditions. We don’t have any information about these patients on the basis of this news report to know how the diagnosis was made. Certainly, other points could be made, but I will stop here. Suffice it to say, the program was not science, and if anything, leaned a little toward sensationalized reporting. Let’s not get swept up in that. This is not to say there is no science reporting on this topic, or that the efforts of the Dr. Tass team are not legitimate. There will be a little more on that below. I would also say that Stanford is known for cutting edge investigation. Still, a person’s or an institution’s standing alone is not enough. We should still apply all of our tools of critical analysis.
Where did this idea come from? It turns out vibration therapy is not new. French neurologist Jean-Martin Charcot (1825-1893) first reported that vibrations from a train or carriage ride might transiently make patients with PD more comfortable and sleep better. Charcot lectured multiple times about vibration therapy, and even developed an automated vibratory chair (fauteuil trépidant) to simulate the rhythm of train travel. I can say anecdotally that I have many times heard from caregivers or patients that gait has been better in the exam room than they expected after a long drive to my office. Maybe this is the same effect. However, I would also note that data has not been consistent in that area of investigation, and attempts to evaluate vibratory chairs have not always been positive. For example Christopher Goetz’s team at Rush University found no benefit in 2012. There have been many other investigations into vibration therapy, whether focal to a specific part, or whole body therapy.
Some patients have pointed me towards a 2022 Stanford Alumni presentation by Dr. Tass in which he explained the gloves. This was not a scientific, but more of an informational presentation. Nonetheless, he stated that he was relying on medicine, math, physics and “self-organization systems theories” that allow one to understand how complex systems generate order. Per Dr. Tass “the standard self-organization issue problem is synchronization.” Here he refers to synchronization of brain neurons.
I want to interject here to try to simplify this and say that the basic cell of the brain is the neuron. When one neuron “fires”, it sends a message to another neuron. That is the basis of thinking, moving, and feeling in the brain. When two or more neurons fire together, that is synchrony. Sometimes synchrony is good, and sometimes synchrony is bad, depending on several factors. Many diseases are known to have some degree of abnormal synchrony. For example, a seizure is a “hypersynchronous discharge” of multiple neurons. Instead of the back-and-forth communication of millions or billions of neurons, some begin to fire together, disrupting the normal background, and a seizure occurs. You can imagine, other dysfunction might also be possible.
I realize thinking about how brains work is not something most people do. Here is an analogy that might help to understand the synchrony issue. There is a crowded auditorium where you’ve gone to hear someone speak. Pretend the auditorium is the brain, and people inside (including you) are the neurons. Before the start of the evening there is a din of talk, laughter, and other sounds (the normal background activity). There is no obvious synchrony on the level of the floor, or if it is present, it is not overriding. Things change when the speaker walks on stage. First a few, then many, then the whole place begin to clap. That is synchrony. It is fine in short bursts but imagine if it did not stop. That would be a noisy evening and you probably would not be able to hear the speaker (abnormal synchrony). You would want to break up, or de-synchronize (ultimately stopping) the clapping so you could hear the speaker. That is idea.
Dr. Tass notes that where synchronization in the brain is concerned, “too much of it massively impairs brain functioning” because different neurons have to process different types of information. “If everybody does the same thing that’s not good and can cause massive impairment.” Thus, he states “we were able to design stimulation techniques that allow us to move systems from this pathological synchronized state to a better state, to physiological, desynchronized states…desynchronizing stimulation enables us to make networks unlearn the abnormal connectivity and hence make them unlearn to produce abnormal synchrony. ..that’s the core of what we are doing.”
So, why a glove? The fingertips have a huge cortical representation. This means the fingertips are very sensitive, with many, many nerve endings and a large area of the brain is devoted to deciphering information from them. The glove system reportedly uses what is called “coordinated reset,” which “means that if you have a large neuron population you do not stimulate everybody at the same time. What you do is you stimulate at different sites, different times, weakly. These are weak vibratory bursts. …in this way we disrupt synchrony and cause therapeutic effects.”
How does that work? The Stanford group uses vibrotactile coordinated reset (vCR) fingertip stimulation in hopes that it will affect neurons in the sensory cortex and thalamus of the brain, both of which are connected to the basal ganglia. Vibratory stimulation may affect brainwave rhythms which can be detected by EEG as well.
There are multiple scientific papers published in peer-reviewed journals by Dr. Tass and his team going back over several years. This brings us to the above-mentioned pilot studies. In 2021 the team reported on two clinical feasibility studies involving a total of eight patients in the journal Frontiers in Physiology. The article is free and can be read by anyone. If you want to delve into the science of this, to read a great deal more about the proposed mechanism, and observe the study design and results, take a look. The results of these trials were also published in the journal Neural Regeneration Research in July 2022. Briefly, in group one during the acute phase of treatment “five out of six patients showed a clinically significant acute reduction of MDS-UPDRS III scores.” The MDS-UPDRS III is a measure of motor function in PD. After three months of treatment “all patients showed a clinically significant cumulative reduction of MDS-UPDRS III scores.” I would point out that five of the six had only a 4 – 6 point change in the MDS-UPDRS III scores. This is not a big difference on a scale ranging from 0 – 137. In group two “all three patients showed sustained cumulative therapeutic effect as demonstrated by a significant linear decrease of the off medication MDS-UPDRS III scores as well as off medication tremor subscores.” The changes were overall more impressive than group one. Additionally, two of the three patients were able to lower dopaminergic medication use. The data is hopeful, but again, larger studies are needed. Even among this small group of patients the results varied a fair amount.
To summarize, the premise is that groups of neurons in the brain may begin to fire together in a way that is harmful and may cause symptoms of disease, and that is not a new concept. That is part of what deep brain stimulation intervenes upon. However, DBS does not typically improve gait or sense of smell; whereas these reports indicate the glove does. The hope is that by vCR with a glove that causes tiny vibrations in the fingertips, information will be carried to the brain, abnormally synchronized neurons will become desynchronized, and symptoms will improve. These are extraordinary claims, and the videos are compelling, but raise so many questions. It is potentially groundbreaking, but we need more evidence. I will be watching and waiting for publication of the clinical trials. I encourage you to do so also if this is something that interests you. As time goes on perhaps a trail will be available near you. That is what moves science forward.
URLs checked on date of publication, 12/31/2022
