Claudia Angeli, PhD, is an assistant professor with the Department of Bioengineering at the University of Louisville and the Kentucky Spinal Cord Injury Research Center. She talks about use of programmed electrical stimulation on spinal cord injuries in quadriplegics.
Interview conducted by Ivanhoe Broadcast News in October 2021.
I want to start by asking you a little bit about spinal stimulation, especially for spinal cord injury. Our viewers may not be familiar with what the theory of what’s happening in the body.
PROF ANGELI: Epidural stimulation was introduced through the animal model several years ago and what they were testing was the ability of the injured spinal cord to show patterns of locomotion in the rats and the mice. So, they implant an electrode, stimulate it, and then, would train the mice and the rats to see if they could generate stepping again. It was just a theory of how the circuitry in the spinal cord could generate those patterns. Back in 2009, there was enough evidence in the animal model that the circuitry would show those patterns. So, we moved that to the human model. Our initial assessment was just to show the proof of principle that the human spinal cord would behave similarly to what was shown in the animal models. We used the same theory of stimulation of the spinal circuitry to see if the spinal cord that was injured at different levels would be able to generate function, and then we saw that we were able to restore functions such as standing and stepping. We also saw other secondary improvements, what would be secondary consequences of spinal cord injury, received benefits from the stimulation itself. The blood pressure regulation was one example. Individuals that suffer a spinal cord injury at the cervical level typically have a hard time regulating blood pressure, so they suffer from very low blood pressures that they have to tilt back to regulate. We saw that epidural stimulation would resolve some of those issues and help maintain the blood pressure within a normal range. Other benefits we saw was with the bladder; individuals with spinal cord injury suffer from not being able to empty their bladders. There were improvements that were noted as a result of the stimulation, and then, we took the information that was learned from animal models and expanded it into a wide variety of improvements that we saw with the human physiology.
Where are you now? I understand that this research continues and there are still new avenues that you’re looking at.
PROF ANGELI: Yes, we started with four individuals back in 2009, and now we’re starting clinical trials, more of the randomized trials that are required to show evidence for moving this technology into clinical applications. We’re asking more mechanistic questions, trying to understand how this is happening. Development in the trials is more specific to cardiovascular as well as bladder, just because those give faster returns. If you look at just the application of epidural stimulation, the blood pressure can be regulated immediately and the bladder changes seem to match, as well, in terms of not needing long-term training. So, we’re looking at using epidural stimulation for restoration of the autonomic system versus the motor system. But we’re still exploring all avenues.
What would be the dangers of having your autonomic system out of whack? For example, the blood pressure. Over time, having that so low, what would the health risk be for a patient?
PROF ANGELI: I think it’s just overall quality of life. Living with a constant low blood pressure, you just have no energy, you’re down, you have to tilt and adjust. You also have to worry about passing out. Individuals that have significantly low blood pressures can just pass out and that can be of a high risk. So, just the ability to raise that to normal levels, it’s an immediate improvement in their quality of life.
What is the stimulation doing that’s allowing the system to regulate, especially when it comes to blood pressure and some of the bladder control?
PROF ANGELI: The key point is that when we’re implanting the electrode, it’s in the same place regardless of if we’re targeting the bladder or the cardiovascular system or motor function. We always implant the electrode on the same place, regardless of level of injury or what system we’re targeting. The difference is how we apply that stimulation, what parameters we use. Now, the question of how this is working, that’s what we’re trying to answer in terms of how this is mechanistically influencing the system. The ability of the spinal cord to have a certain level of excitability and receive all the sensory information that used to receive prior to injury and integrate that is also something we’re concerned about. So, what we’re learning is that the spinal cord is smart and can integrate multiple systems and decide in terms of regulation of blood pressure or generating activity or sending a signal to generate activity throughout muscle to generate movement. So, the spinal cord doesn’t need the brain to send all commands down; it’s just a single do, and then the spinal cord will organize and generate that.
Where are the implants done? Is the stimulation constant or is it periodic? How is that controlled?
PROF ANGELI: The electrode is a 16-electrode array, it contains 16 contacts. It is implanted in what’s called the lumbar sacral spinal cord, which is around the L1, lumbar level one for the spinal cord, all the way down to S1, the sacral level. That is where all that animal research has shown that the spinal cord circuitry for locomotion exists. But what we’re finding is that there’s also circuitry for other systems. It is constant. One of the big questions about how we’re stimulated, particularly for motion, is about movement. We’re not inducing the movement, we’re just generating a constant stimulation, so we’re raising the level of excitability and raising the volume of the spinal cord. It’s listening and allowing the integration of all those systems, and then, the brain can just send the signal of extending the knee and then the spinal cord organizes that and generates extension. We’re not inducing that extension. If the command from the brain doesn’t say “extension,” then nothing happens. So, the same way with the cardiovascular as well as the bladder, it’s just raising that excitability for integration. It is a constant stimulation and we’re just using different parameters.
What are the implications for being able to push the needle that much further?
PROF ANGELI: I think the main one is quality of life. Individuals that have lived with paralysis for an extended period don’t understand how bad things are until they’re good again. So, the impact in quality of life and the comments that we get from individuals just from a single session is helping us try to investigate how we can impact more systems. One of the things we’re working towards is not much about movement, although we are looking at standing and stepping, but how we can integrate motion, cardiovascular control, and bladder control into a single location of how we’re implanting. We are also looking at developing programs that can be used by these individuals to improve quality of life. We just want to be more involved in the home and community.
Are you able to speak to Jared’s case at all?
PROF ANGELI: Yes. So, Jared was a research participant in the randomized clinical trials. It’s a trial of 36 individuals and he was initially randomized to voluntary movement only and then moved on to voluntary and stand. The trial is focused on cardiovascular control. The voluntary group is our control group. Jared was able to regain independent standing as part of the trial. He still needs assistance getting up to the standing position and there are things that we’re developing with new technology. But he is pretty much able to stand without having somebody assisting at the knees for a prolonged period. After his participation in the initial portion of the trial, he has moved to the cardiovascular side to have his cardiovascular programs adjusted.
With the extent of Jared’s injury, would he have been able to progress this far without the spinal stimulation?
PROF ANGELI: No, he has always been an extremely active individual in regards rehabilitation options. I think he had exhausted all those options from inn regards to how much recovery he was seeking from standard rehabilitation, and the ability to regain standing and voluntary movement, I think he’s able to translate that now into his gym practice, and I think he’s training for a marathon. So, the things that he was doing in the past, he’s potentially doing now, but it takes a lot of effort to do. It’s just like an athlete training for an event. So, it has helped him. He had a lot of spasticity, just movement that he couldn’t control, and now he can use the stimulator to control that spasticity and move when he wants to move instead of when the spasms would kick in.
Is there anything that you would want to make sure that people know?
PROF ANGELI: I think our current goal is to improve the technology. We are using a clinical simulator that is implanted for pain and we’re finding some restrictions in terms of how we’re applying the stimulation. It was developed for pain, so we’re pushing the limits as to how we’re using the current system. Our goal is to develop a spinal cord specific system, not necessarily the stimulator itself, but at least the programming, and how we can arrange the programs to make it useful for those individuals. We’re also seeing how we can recover function and integrate that into the individual that with lives with spinal cord injuries.
END OF INTERVIEW
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