Wellness in a Heartbeat

Patients with essential tremor—a neurological disorder that causes involuntary rhythmic shaking during intentional movement—often have difficulty with everyday tasks such as writing, eating, and drinking. Currently, many patients with essential tremor are treated with Deep Brain Stimulation (DBS), a therapy that requires a surgeon to implant an electrode in the thalamus of a patient's brain that is wired down the neck to another implanted device—that contains a battery and other electronic components—housed under the clavicle. This type of system, referred to as ‘open-loop,’ delivers constant DBS at levels set by a doctor. While this DBS system can be effective for patients with essential tremor, the constant stimulation it delivers isn’t necessary and comes with several disadvantages, explained Andrew Ko, M.D., a neurosurgeon and researcher at the University of Washington Medicine Neurosciences Institute.

The symptoms of movement disorders such as Parkinson’s disease or essential tremor do not stay constant,” said Ko in an interview with reporters. “They can vary throughout the day, with different medication regimens, or even emotional state. Current DBS therapy does not take that into account. Patients may receive more or less stimulation than their symptoms require.”

Involuntary shaking only tends to occur during movement for patients with essential tremor, said Ko. When resting, patients do not have much tremor, which means that the constant stimulation delivered by current DBS devices is unnecessary if someone is relaxed and not performing any tasks.

Too much stimulation can cause side effects, while too little could mean symptoms are not well managed. In addition, extra stimulation uses up battery life unnecessarily. Batteries implanted for DBS only last three to five years before requiring a surgical replacement procedure, so wasting their limited power is not ideal. 

A team of electrical engineers, UW Medicine researchers and ethicists at the Center for Sensorimotor Neural Engineering (CSNE) at UW, has developed a novel approach to DBS that solves these issues. Their work is described in a paper to be published in a forthcoming issue of IEEE Transactions on Neural Systems and Rehabilitation Engineering, co-authored by Ko.

Their DBS paradigm uses brain signals to turn the stimulator on and off based on whether a patient requires stimulation at that time. During the implantation surgery, an extra set of electrodes is placed on top of the part of the brain that controls arm movements. These electrodes can detect movement onset, and turn stimulation on, and when the patient relaxes, the stimulation is turned down.

 

This sort of treatment paradigm is referred to as ‘closed-loop’ DBS. The feedback loop is based on a constant assessment of the patient’s state, rather than “open-loop,” where a clinician manually adjusts the stimulation at given clinic visits, said Ko.

The project originated in a partnership between the CSNE and medical device manufacturer Medtronic to test new ways of activating Medtronic's Activa PC+S Deep Brain Stimulation system with essential tremor patients. This system delivers electrical stimulation like traditional DBS systems, but also has the capability to sense and respond to electrical signals generated by the brain itself. The UW team received an investigational device exemption from the U.S. Food and Drug Administration (FDA) for these tests.

 

 

So far, UW Medicine surgeons implanted a small strip of electrodes on top of the brain's motor cortex, the part of the brain that controls movement, in three patients who received the Medtronic Activa PC+S Deep Brain Stimulation system. The electrode strip can be used to sense when a hand or other extremity affected by essential tremor is moving. The team developed machine learning algorithms to "decode" neural signals coming from the brain and correlate them with essential tremor symptoms that warrant treatment by stimulation.

This is the first time neural signals have been used to selectively treat essential tremor.

To test how well the systems work, the research team asked the patients to perform simple motor tasks— such as drawing a spiral shape with a pen, writing sentences or trying to hold their hands steady—with their Medtronic implanted deep brain stimulator turned off, with the system that delivered constant stimulation, and with the new system that only delivered stimulation as needed. In the experiments, the computational tasks were performed on an external laptop next to the patient.

“So far, they see no difference in how well open-loop versus closed-loop stimulation controls tremor. In fact, there is a trend toward the closed-loop trials being rated better than open loop stimulation,” said Ko. “Obviously we need more data before we can say whether this is the case. But the key finding is that so far, on these standardized tasks, patients with our system respond just as well as the older system–with about a 50 percent savings in battery life.”

 

 

As their next step, the team plans to transfer that computational power to the device implanted in the patient's chest wall and create a fully-implanted, closed-loop DBS system. They will then gather data on how this system works with essential tremor patients at home in order to characterize shortcomings in the system, and better evaluate the benefits with a fully implanted system. The team has received FDA approval to move onto real-world testing. After that, they hope to achieve a wider application of this technology through additional trials.

“In a relatively short time, we foresee being able to treat essential tremor with a fully implanted, closed-loop system, in what would be a head-to-head comparison in a larger group of patients,” said Ko. “At least for essential tremor, we are on the cusp of having a fully implanted system.”

A closed-loop system may also be beneficial to patients with other disorders, such as Parkinson’s disease, but more research is needed before this can be addressed, said Ko. Parkinson’s disease is more complex, involving a larger variety and variability of symptoms that can be troublesome both at rest and while the patient is moving. In addition, some symptoms come and go based on medication levels, while yet other symptoms do not respond at all to DBS.

“In general, our research has revealed many interesting issues that will need to be addressed to treat this and other disorders with closed-loop DBS,” said Ko. “I think to effectively treat PD with closed-loop DBS, it will be necessary to very specifically characterize symptoms in patients. On the other hand, the very variability of the symptoms means that treatments that respond to the disease state, as well as the treatments we implement, have the potential to really benefit patients.”