Curing Paralysis: Epidural Stimulation
The Reeve foundation reports that there are over a million people who are paralyzed due to spinal cord injuries in the United States. According to surveys done by the Spinal Cord Center, the function they desire the most to recover is walking. Enter epidural stimulation.
Why The Current State of Movement Rehabilitation is Not Enough
The most popular approach used to restore motor function in paralyzed patients is Functional Electrical Stimulation(FES). In FES, a neuroprosthetic device is placed over or inside the muscle and forces muscle contraction by using an electrical current to stimulate peripheral nerves. FES has been used to successfully treat foot drop in multiple sclerosis and stroke patients, and increase muscle mass, strength, balance, walking speed, and range of motion in cerebral palsy patients.
However, FES cannot restore standing and stepping for spinal cord injury patients, especially in patients with no clinically detectable control of their lower extremities. This is because FES is not precise enough. When humans move naturally, smaller muscles tend to get activated first. But in FES, as electricity spreads through peripheral nerves, larger muscles get activated before smaller muscles. This is because larger muscles have larger axons, and axon diameter is proportional to excitability in neurons. Furthermore, as the current is dispersed through the nerves, it can activate muscles that are antagonistic to the intended movement, while deeper, harder-to-reach muscle groups that are used in the natural movement are left unstimulated. All of these factors cause patients undergoing FES to experience high levels of muscle fatigue and have jerky, uncoordinated movements.
Another disadvantage is that FES requires constant electrical stimulation. Ideally, spinal cord injury patients would eventually not need any devices to help them walk. On a high level, a spinal injury disconnects the neural circuitry below it from the brain. If patients want to walk without the help of any devices, their disconnected nerves have to become rewired to the central nervous systems. FES stimulates peripheral nerves to induce movement, it does not try to reconnect them with the central nervous system. Patients become dependent on FES. Even if independence was not a desired outcome, in many cases the high levels of fatigue and unnatural movement patterns mean that even with FES, they cannot walk.
Epidural Stimulation
In the search for a more precise, penetrating, and permanent solution, researchers have found epidural stimulation. Epidural stimulation works by invasively applying electrical current to the lower part of the spinal cord through a chip implanted over the outermost protective layer of the spine. Instead of stimulating muscles directly through FES, epidural stimulation attempts to mimic the signals sent by the spine. While this stimulation is applied, the patient is given standing and stepping training, and over time is able to recover some control of their lower body. Epidural stimulation solves the problems of muscle fatigue and unnatural movement. The nerves are stimulated directly, so deep muscle groups are activated, and natural movement patterns are enabled.
Research has shown epidural stimulation to be promising. A study done by Victor Edgerton and Susan Harkema implemented epidural stimulation in conjunction with stand-step training to a patient who had lost all control of his legs in a motor accident. This allowed the patient to regain the ability to stand within weeks, and the patient continued to see improvements in standing ability years after the therapy. The patient was able to take steps while the device was on, but not enough to walk without assistance. Surprisingly, the patient was also able to recover or see improvements in bladder control, temperature regulation, muscle mass, and sexual function. In a study done at the University of Louisville, all patients were able to recover standing ability, with half also recovering walking ability after a period of four months. None of the patients in either study had any detectable control of their lower limbs before beginning epidural stimulation.
Why This Changes the Game
There are two plausible explanations of why epidural stimulation is so effective, and the methodology and results of the two papers point us in different directions.
In the Louisville study, various configurations of stimulation were tested, and combinations that enhanced standing and stepping for each individual patient were selected. In order to walk, patients needed this device to be on. The basic idea behind this approach is that neurons reach a higher level of excitability when they are electrically stimulated. For the patients in question, there may have been some surviving connections between the neurons above and below the lesion. These connections were too weak to cause movement, but when epidurally stimulated, the weakened signals sent by the brain were able to excite the previously disconnected neurons and allow the patient to walk. These results indicate that epidural stimulation is simply a more precise, invasive version of FES. Instead of stimulating peripheral nerves like in FES, epidural stimulation goes straight to the source, which leads to more natural movement patterns.
This theory seems completely reasonable, but it doesn’t explain the improvements in autonomous processes like bladder control and temperature regulation. In fact, even after the therapy concluded, the patient in the Edgerton paper was able to see continued improvements in bladder function. One possible explanation is that the repeated stimulation and training caused axons to grow through or around the injury. This would cause a reorganization of the spinal circuitry, and the resulting connections would explain the improvement in autonomic function. Since autonomic nervous control comes from the central nervous system (the brain and spinal cord), new connections to the central nervous system would better these functions, even when epidural stimulation ends. This would also explain why standing ability improved years after the therapy concluded for the patient in the Edgerton study. If this result is true, then it means that epidural stimulation solves the root cause of paralysis by reconnecting the spine with peripheral nerves, and would enable patients to no longer require epidural stimulation therapy after the motor function was restored.
These two explanations are not mutually exclusive. It is possible that during epidural stimulation motor neurons are more excitable, and that new connections are formed as a result of epidural stimulation. Either way, the bottom line is that epidural stimulation has the potential to cure paralysis.
So, What’s Next?
But in order to see widespread adoption, certain technological advancements must be made.
- A stimulating device that has sufficient flexibility and control of the parameters is needed to fine-tune motor responses is necessary to map stimulation configurations to intentions. The Louisville study shows significant progress toward this end, as it tested various configurations and picked the optimal one. However, in order to see better results when a patient wants to walk, the device must stimulate the appropriate circuits in real-time.
- Different people have different injuries and the type of stimulation they need may be different. Instead of trying to create a general model of what should be stimulated when for all patients, it would be advantageous to allow the device to learn what works for the patient it is implanted within. This can be done with machine learning.
- So far, only 16 electrode devices have been used. Given the complicated nature of neural circuitry, electrode arrays with higher resolutions could lead to better results, because they can take advantage of the localization of select clusters of interneurons that control specific motor pools and their respective muscles. This would allow for fine control over muscles and lead to better control.
- If the patient cannot walk without assistance even in the presence of epidural stimulation, assistive robotics with the ability to interface with the stimulation device will give the patient greater independence.
- Epidural stimulation has shown results in patients with spinal injuries, but it may be able to help people who have lost motor control due to other reasons as well. Research into applying epidural stimulation for other diseases can galvanize the medical community to allocate more resources towards studying and developing epidural stimulation.
- Rehabilitative devices that can be used at home so interventions can be incorporated into one’s daily life are necessary for epidural stimulation to become economically viable. This can lower the cost of therapy and speed up by allowing patients to practice certain exercises without a trained professional present.
Epidural stimulation is still in its infancy, but because it can potentially rewire neurons across lesions, it holds the potential to fundamentally better the lives of spinal cord patients.
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