Treating spinal cord injury with implanted spinal cord stimulators

Spinal cord injury

Spinal cord injury (SCI), which literally means damage to the spinal cord, is a devastating and debilitating neurological condition, affecting millions of people worldwide. Traumatic SCI caused by external impacts accounts for the majority of all SCI cases and always accompanies a secondary injury that causes the further death of neurons and glial cells, leading to long-term neurological defects and paralysis. It can significantly harm the spinal cord’s functions and burden patients, their families, and friends with substantial personal and socio-economic pressures. According to the 2020 SCI datasheet reported by the National Spinal Cord Injury Statistical Center, approximately 294,000 persons are living with SCI in the United States, with about 17,810 new cases every year, while the World Health Organization (WHO) had estimated that 250,000–500,000 people suffer an SCI each year around the world ( ; ). Clearly, SCI has caused a significant burden on the healthcare system all over the globe.

Etiologically, SCI can be categorized into two types: traumatic SCI and non-traumatic SCI. Traumatic SCI is caused by external physical impacts such as vehicle accidents, sports injuries, violence, or falls. In a traumatic SCI, the external impact firstly causes bone, blood vessel, and ligament damage of the spine, then the debris and dislocation subsequently hurt and rip the spinal cord tissue, initiating the primary injury. After that, it leads to a secondary injury cascade ( Fig. 1 ), resulting in the death of glial cells and neurons, and a long-term neurological defect ( ). Differently, non-traumatic SCI is usually caused by other chronic or degenerative disorders such as tumors or infection, which however can induce a similar level of neurological deficit to a traumatic one. Despite its existence, non-traumatic SCI rarely happens compared with the traumatic SCI that accounts for over 90% of all SCI cases ( ).

With the improvement in emergency healthcare and medical services, many patients can survive from traumatic SCI and usually live up to a very optimistic life expectancy, however, frequently accompanied by terribly devastating disabilities. The injury cascade leads to complications such as inflammation, ischemia, and subsequently ruin in organization and structure of the spinal cord. Indeed, the clinical outcome is also heavily subject to the location and severity of the injury, since the patients may be partially or wholly paralyzed—depending on the lesion intensity—lose the sensory and motor functions below the level of the lesion, resulting in different extents of disability such as paraplegia and quadriplegia. If the sensory and motor function is totally lost below the injury level, it is clinically defined as a complete SCI; but if there is still any spare function left, it is called an incomplete SCI ( ). Regardless of different levels of disability, the loss of independence and ability returning to a job and daily life causes immense difficulties, extra works, and costs in caring for SCI patient’s daily living. The lifetime cost for each SCI patient is estimated to be US$2.35 million ( ), which is definitely a considerable amount for many families, especially under the circumstance that the patient themselves cannot often work in their regular jobs anymore. Besides the loss of sensorimotor functions, chronic pain is another common problem, which frequently happens after SCI, with a rate of about 30%–80% and strikingly one third of which suffer from severe pain ( ; ). Consequently, understanding SCI’s pathophysiological mechanism and developing effective treatment to this condition is critical and highly significant.

Treatments for SCI

Over the years, although substantial research and efforts have been contributed to study the SCI, there is still no known method to reverse or cure the damage of SCI at present. Fortunately, different strategies have been found to improve the lost sensorimotor functions, self-independence, and life quality of SCI patients; and other promising treatments are also in progress. Currently, available treatments for SCI are mainly in three aspects: intervention shortly after the injury happens (acute stage), compensatory strategies, and functional recovery in sub-acute and chronic stages ( ). The primary purpose of interventions after acute SCI is to decompress the spinal cord and minimize secondary injury. The typical early intervention approach includes surgical and pharmacological interventions. Though applications on animal models had suggested beneficial outcomes of surgical interventions, its effect on human trials remains unclear ( ). Also, despite some successful cases, the ability of pharmacological interventions to improve neurological function remains controversial at present and requires more demonstrations in patients ( ). The compensatory strategies usually help improve functions by utilizing assistive devices or training modalities to shift the tasks to unaffected body parts. Compensatory strategies are commonly employed to complete SCI, which has relatively limited restoring capability of the spinal cord functions ( ; ). On the other hand, functional recovery strategies attempt to restore the functions after SCI by means such as stimulations or neurorehabilitation training. These strategies normally show better outcomes for less severe SCI since incomplete SCI has a higher chance of functional recovery; however, stimulation-induced motor function recovery after complete SCI is also heavily investigated ( ; ). A promising rehabilitative strategy to SCI in recent years is spinal cord stimulation (SCS), which has shown encouraging outcomes in not only functional recovery but also SCI pain relief even in patients who did not expect to improve any function with classical interventions ( ). In this chapter, we have discussed the principles behind the SCS-mediated rehabilitation of sensorimotor functions after SCI, introduced several notable spinal cord stimulators, and illustrated the procedures of their clinical application.

Principles of SCS

SCS has been used to treat neuropathic pains for over 50 years. It is often applied to alleviate chronic pain for which conventional treatments have failed, such as congenital or acquired chronic low back and leg pains, complex regional pain syndrome (CRPS), failed back surgery syndrome (FBSS), and post-SCI pains, etc. ( ). SCS blocks pain but not cures it. SCS relieves pain by generating electric pulses at the spinal cord. Its working principle to block pain is the gate control theory of pain ( Fig. 2 ). Gate control theory indicates that other inputs will shut the “nerve gate” for the painful input in the spinal cord, preventing pain signals from reaching the brain so that one does not feel the pain ( ). Based on this theory, the stimulator produces electrical pulses on the spinal cord’s dorsal surface, which closes the “nerve gate” to pain signals, prevents them from being received by the brain, thus masks the neuropathic pains ( ).

Besides, SCS starts to serve as a promising tool for movement restoration after SCI. Both invasive and non-invasive SCS could be a powerful tool. The exact principle underlying the motor function improvement by SCS is largely unknown at present. Some findings suggest that even isolated from the brain the spinal circuitry is still able to generate locomotor activity driven by the externally applied stimulation ( ; ; ). According to this principle, the SCS replaces the brain to generate stimuli for triggering locomotor-like activity for the paralyzed. So SCS with different patterns, amplitudes, frequencies, pulse widths at different locations may result in different locomotor activities. Theoretically, these motion activities could happen only if SCS is applied to the patient sustainedly. However, another explanation suggests that instead of replacing the brain, the SCS enables the brain to recruit the spared and functionally silent nerves residue in SCI, so the reorganization of the residual neural pathway by the SCS promotes and improves locomotor functions ( ). In this theory, the brain is still the command center of the limb movement, and the role of SCS is just to activate the residual neural pathway important for locomotion. So, it is possible that after a period of SCS, the locomotor improvement became long-term and sustained even after the SCS is removed.