Image source @ Visual China
Text | Chen Gen
Spinal cord injury is the most serious complication of spinal injury, and when an injury severs the spinal cord or disrupts nerve pathways in the spinal cord, the damaged nerve fibers may no longer be able to transmit signals between the brain and muscles, and this regenerative failure often leads to severe and permanent paralysis. Worse still, these axons cannot regenerate.
According to the National Center for Spinal Cord Injury Statistics, nearly 300,000 people in the United States currently have spinal cord injuries. Life in these patients can be unusually difficult, with less than 3% of patients with complete spinal cord injury able to restore basic physical function. About 30 percent are re-hospitalized at least once in any year after the initial injury, spending an average of millions of dollars in medical expenses per patient's lifetime.
Moreover, life expectancy for people with spinal cord injury is significantly lower than that of people without spinal cord injury, which has not improved since the 1980s. At present, the treatment of paralysis caused by spinal cord injury is still limited, and the prevention, treatment and rehabilitation of spinal cord injury is still a major problem in today's medical community.
Treatable hope for spinal cord injury
The spinal cord and brain are the central nervous system of humans, and any instructions of the brain are transmitted to the limbs through the spinal cord, and similarly, the limbs' perception of the outside world is also transmitted to the brain by the spinal cord and analyzed and determined to respond. It can be said that the spinal cord is equivalent to a cable in a communication system. The importance of the spinal cord also makes the spinal cord one of the most closely protected organs in the human body structure – hidden deep in the spine behind the body.
Still, illness and accidents can lead to spinal cord injuries. To put it simply, spinal cord injury is due to diseases and accidents that cause nerves to cut off contact with the outside world, so that any sensations and movements in the areas below the spinal cord injury will disappear. To make matters worse, spinal cord injuries are often irreversible.
As early as an Egyptian medical book from 1700 BC, spinal cord injury was considered an incurable disease. Today, 4,000 years later, many ancient diseases have been treated under the rapid development of modern medicine, and the treatment of spinal cord injury has not progressed so far. In the face of spinal cord injury, people may only be able to use large doses of hormones to reduce the secondary damage of spinal cord injury and help patients adapt to paraplegic life.
The reason is because, in general, many tissues and organs of the human body, such as skin and bones, once damaged, it will stimulate the body to form a microenvironment suitable for regeneration, which will help the human body to repair the skin and integrate bones. For example, if you remove a small piece of the human body's tissues and organs and look at it under a microscope, you will find that the skeleton formed by the outer matrix outside, mainly scaffolds such as collagen, and various tissue cells are arranged in space, and there are many soluble, specific distributions, including gradient distribution of signaling molecules that can help these cells survive. However, after spinal cord injury, the central nervous system will form a microenvironment that inhibits regeneration, and stem cells cannot differentiate into neurons.
In the face of the current limited treatments for spinal cord injury, scientists have been trying new ways to help patients get back on their feet, and one of the treatment paths is to develop a applicable therapeutic neurotechnology to improve patient mobility. After all, in most cases, there are still some connections between the brains of some paralyzed patients and the motor neurons in the spinal cord after injury. Although they can no longer walk normally, these patients still have some simple mobility.
Scientists have long hoped to restore the motor neuron signal connection of these patients through electrical nerve stimulation, so as to achieve patients' walking rehabilitation. Based on this, extradural electrical stimulation (EES) on the lumbosacral spinal cord has become one of the most widely studied techniques.
Typically, EES is the recruitment of afferent fibers at the entrance to the spinal cord through the dorsal root, leading to the activation of motor neurons that are embedded in segments of the spinal cord innervated by the root nerves where these fibers are located. Thus, specific motor neurons can be regulated for a single dorsal root.
In fact, as early as 30 years ago, there were preclinical and clinical studies showing that epidural electrical stimulation (ESS) can restore the ability to walk in patients with spinal cord injury. But this requires the assistance of several physiotherapists, months of intensive training, and extremely limited success stories. It is a huge challenge to translate these complex, rare cases into a universally applicable treatment.
And, even if stimulation methods provide a patient with continuous electrical stimulation of the spinal cord by using neural techniques originally designed to treat pain for repurposing, these reused electrical stimulation devices fail to stimulate all nerves in the spinal cord associated with leg and trunk movements, and may limit the recovery of all motor functions.
EES technology update after four years
In 2018, Dr Grégoire Courtine of the Swiss Federal Institute of Technology in Lausanne and Jocelyne Bloch, a neurosurgeon at the University Hospital of Lausanne, reactivated spinal cord neurons using electrical stimulation based on targeted neurotechnology, allowing three chronic paraplegic patients to regain the ability to walk.
At that time, in order to better enhance the signal between the remaining motor neurons and the brain through electrical stimulation, the researchers first conducted a deeper study of human motor neurons, and they identified the spinal cord area involved in regular human exercises, such as bending the hip or stretching the ankle. The researchers then implanted an electrical stimulator in 3 patients. All 3 patients developed spinal cord injuries, but the degree of sports injuries in the legs varied. By identifying where the spinal cord is involved in walking, the researchers were able to stimulate the target area of the spinal cord at the right time and place by programming a series of electrical impulses.
In fact, this external electrical nerve stimulation does not cause the body to move, and the electrical stimulation is more to enhance the nerve signals that the patient himself is trying to exercise. The subjects gradually adapted to electrical stimulation after 2 days and achieved a certain degree of walking assisted by sports equipment within a week.
After more than five months of rehabilitation training and electrical stimulation treatment, the participants' recovery effect was further improved. Importantly, even after the stimulation treatment was stopped, all participants maintained some improvement in muscle movement, two participants were able to walk independently with crutches, and the most injured subjects were able to move their previously paralyzed legs while lying down. The study was published as a cover paper in the journal Nature.
Now, on February 8, 2022, a new research paper has once again been published by the same researchers in the top international medical journal Nature Medicine. This time, the researchers developed a personalized spinal cord electrical stimulation electrode controlled by artificial intelligence software, which activates the spinal cord area of the trunk and leg muscles through electrical stimulation after implantation, and three completely paralyzed spinal cord injury patients regained independent motor ability within hours of receiving treatment, able to stand, walk, ride bicycles, swim and control trunk movements.
Specifically, the researchers developed a personalized implantation system controlled by artificial intelligence called the STIMO-BSI system. The system includes a computational model that combines high-resolution structural and functional imaging, electrodes, and software that can quickly support device-specific stimulation of neurons.
Among them, the computational model is equivalent to a film, which provides guidance for electrode arrangement and surgical implantation position, the electrode is responsible for regulating the site of the control leg and torso, and the software can be used to adjust and optimize the position of the target dorsal root. The software is integrated with the tablet, and the user can choose the mode of action they want through the tablet. Subsequently, the researchers stimulated the lower back and coccyx of the spinal cord by placing a device embedded in the electrodes directly at the base of the spinal cord, aligning the electrodes with the nerve roots.
In addition, in the new study, the spin-off company Onward Medical will also engineer the electrodes, which are longer and wider, so that they can cover and activate more and more critical neurons. Now, 16 electrodes are implanted in each device, and the team plans to implant 32 electrodes. In fact, compared to previous studies, the core of the fundamental improvement of the efficacy of this device lies in the arrangement of electrodes and the combination of software.
It is worth mentioning that compared to the EES method that trained for months to resume walking, this new technology allowed 3 participants who exhibited complete sensorimotor paralysis to walk independently on the treadmill on the first day alone. After another 1-3 days, gait was optimized and 3 participants were able to walk independently on the ground with the support of the multidirectional weight support system, and 2 participants could even adjust the amplitude of their leg movements.
According to the principle of EES resuming walking, it seems that it can also be generalized to other types of exercise. The researchers configured an activity-specific stimulation program that enabled the 3 participants to swim in the water with their legs or actively pedal on an e-bike, or even squat and leg push.
After a rehabilitation program of up to 5 months, all 3 participants gradually regained their full weight-bearing capacity, allowing for a 6-minute walking test without any help, and one of them even regained the ability to climb stairs and walk on complex terrain. These improvements all coincided with a significant increase in muscle mass in the legs and trunk.
Overall, in this latest study, the researchers recombined dormant spinal nerves that control movements in the legs and upper body with personalized, customized devices. This widely used therapeutic neurotechnology undoubtedly further enhances the patient's mobility.
Clinical path to spinal cord treatment
No matter how cutting-edge the technology, only when it is truly used in the clinic will it be given universal significance, and from this point of view, although spinal cord electrical stimulation still faces many obstacles, it is not without hope.
In fact, back in 2015, the FDA approved a 10KHz high-frequency spinal cord stimulator for the treatment of pain. At present, spinal cord electrical stimulation has been widely used in clinical practice to treat pain and other diseases, and its effectiveness and safety have been verified by many parties.
For the results of the research, Grégoire Courtine said that it will start from the initial use and then expand other disease treatment areas on this basis. Appropriate spinal cord target sites are determined by adjusting the generic modules of the stimulation device according to the patient's disease and specific condition. Jocelyne Bloch also said that after the spinal cord stimulator is implanted, the device is tested and adjusted based on spinal cord length, nerve location and other factors.
Grégoire Courtine also noted that the next step will be to advance large-scale clinical trials in the United States and Europe to verify whether this spinal cord stimulation implant can become an accessible treatment. The researchers' ultimate goal is to build a library of electrodes that allow surgeons to choose the right electrodes based on the extent and length of spinal cord injury a patient has. In this way, for different diseases, the doctor can select the appropriate electrode, that is, the choice is ready to use.
Of course, this progress is an important milestone in the process of paralysis treatment, but the study needs to solve a series of problems to really go clinical. For now, this implant does not cure spinal injuries, and the current technology is still too complex to be used routinely in daily life, but patients can use it to exercise muscles and practice walking, thereby improving the quality of life. The technology has also taken an important step in the research of restoring the mobility of paralyzed patients.
Until now, spinal cord injury has been called "undead cancer", but it is gratifying that although the current treatment methods for spinal cord injury are limited, there are many potential new treatments, including new injection therapies, stem cell therapy, brain-computer interfaces and stimulation therapy for implants in vivo. Paralyzed patients are embracing more treatment options, perhaps regaining mobility in the not-too-distant future.