Electrical stimulation is giving new hope to people with severe spinal cord injury. A recent study shows that four young men with paraplegia are now able to move their legs on their own with the help of electrical stimulation of the spine. Researchers believe the therapy has the potential to change the prognosis of people with paralysis even years after injury.
The men, who had been paralyzed for more than 2 years, were able to able flex their toes, ankles, and knees while using electric stimulation. An even greater improvement in movement was found when the men used the stimulation in combination with physical rehabilitation. Details on this groundbreaking discovery were published in the April 8 issue of Brain.
The discovery “offers a new outlook that the spinal cord, even after a severe injury, has great potential for functional recovery,” said lead investigator Claudia Angeli, Ph.D., senior researcher, Human Locomotor Research Center at Frazier Rehab Institute, and assant professor, University of Louisville’s Kentucky Spinal Cord Injury Research Center (KSCIRC).
How Electrical Stimulation Works
Electrical stimulation involves pulses of electricity that are sent down the spine to mimic the signals the brain normally sends to initiate movement. The electrical pulses are delivered through a stimulator that is surgically placed on the spinal cord.
Rob Summers, who is paralyzed below his chest, was the first person to benefit from this treatment. He received electrical pulses to his spinal cord just below the injury while undergoing daily training in which he was suspended in a harness over a treadmill while researchers helped him either stand or walk. Eventually, Rob could stand on his own for up to 4 minutes. Seven months into the trial, Rob regained some voluntary control of his legs.
Above: Kent Stephenson, the second person to undergo epidural stimulation of the spinal cord, voluntarily raises his leg while his stimulator is active. Photo courtesy of the University of Louisville.
All the men were able to synchronize leg, ankle, and toe movements in unison with a visual cue of the rise and fall of a wave shown on a computer screen, and three out of the four were able to change the force at which they flexed their leg, depending on the intensity of three different auditory cues.
“The fact that the brain is able to take advantage of the few connections that may be remaining, and then process this complicated visual, auditory, and perceptual information, is pretty amazing. It tells us that the information from the brain is getting to the right place in the spinal cord, so that the person can control, with fairly impressive accuracy, the nature of the movement,” said V. Reggie Edgerton, PhD, the researcher responsible for developing this approach to therapy. Dr. Edgerton is Distinguished Professor of Integrative Biology, Physiology, Neurobiology, and Neurosurgery at the University of California, Los Angeles.
Other Health Improvements
All four of the men were able to bear their own weight on their own and also showed other health improvements, such as increased muscle mass, less fatigue, and a greater sense of well-being. Rob, for example, Rob began to have better blood pressure control, body temperature regulation, bladder control, and sexual function.
The researchers are studying whether epidural stimulation can be used to help people with paralysis of the arms and developing a technology to deliver spinal stimulation through the skin rather than having to surgically implant the stimulator. In addition, researchers are working to advance electrical stimulator technology to help achieve greater control of movement in people with paralysis.
Recently, much attention has been directed at therapeutic strategies for spinal cord injury (SCI), including cell transplantation and/or drug administration. Clinical trials of neural precursor cells for SCI have already taken place1, as have trials of mesenchymal stem cells1, and medication such as sodium/glutamate antagonists2, and the antibiotic minocycline3. In this context, the work presented by Angeli and colleagues in a current issue of Brain presents a novel strategy for the treatment of SCI4. In their study, 4 patients with complete motor SCI were enrolled. More than 2 years had passed since the SCI in all patients, and the injury levels ranged from C7 to T5. Epidural spinal cord stimulation units were surgically implanted at the level of T11/12. Surprisingly, all 4 patients with chronic complete paralysis regained voluntary movement of their legs through the epidural stimulation soon after implantation of the device. Moreover, the patients could activate the motor movement of their legs according to visual and auditory cues. Repetitive standing and voluntary training using epidural stimulation promoted higher force generation and accuracy of movement of the leg muscles.
The striking point of this study is that the therapeutic strategy for SCI focused not on the lesion site itself, but below the level of the lesion site on the spinal cord. In cell transplantation therapy, the focus is on replacing the damaged neural cells and promotion of axon regeneration and remyelination at and across the lesion site. However, the results from this work demonstrate a new strategy of activating the spared spinal cord circuitry below the level of injury by epidural stimulation, without any direct treatment of the lesion site. In the lumbar spinal cord, central pattern generators (CPG) which control the locomotor behavior of the hindlimbs are known to exist5, and the epidural stimulation in this work could contribute to the reactivation of CPG neural circuitry. In contrast, the mechanism remains by which the visual and auditory inputs descended to the spinal circuitry through highly disrupted axons in the lesion site remains elusive. However, Courtine and colleagues demonstrated that, in the absence of any supraspinal input, use-dependent learning mechanisms can promote the recovery of full weight-bearing treadmill locomotion in rodent model of SCI6. Therefore, the stimulation of CPG neural circuitry in the lumbar spinal cord could be a novel therapeutic target for the SCI.
The main limitation of this work is the small number of the enrolled patients. Although the patients are relatively young (mean 26.9 years), prevalence of SCI tends to increase in geriatric patients7, and outcomes in this patient group should be examined. Future studies will be needed to investigate the functional effects of the epidural stimulation and training in larger clinical trials.
References
1. Tetzlaff W, et al. A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma. 28:1611-1682, doi:10.1089/neu.2009.1177 (2011).
2. Fehlings MG, et al. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial. J Neurosurg Spine. 17:151-156, doi:10.3171/2012.4.AOSPINE1259 (2012).
3. Casha S, et al. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 135:1224-1236, doi:10.1093/brain/aws072aws072 [pii] (2012).
4. Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. doi:awu038 [pii]10.1093/brain/awu038 (2014).
5. Kiehn O. Locomotor circuits in the mammalian spinal cord. Annu Rev Neurosci. 29:279-306, doi:10.1146/annurev.neuro.29.051605.112910 (2006).
6. Courtine G, et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 12:1333-1342, doi:10.1038/nn.2401nn.2401 [pii] (2009).
7. Martin ND, et al. The mortality inflection point for age and acute cervical spinal cord injury. J Trauma. 71:380-385;discussion 385-386, doi:10.1097/TA.0b013e318228221f00005373-201108000-00016 [pii] (2011).
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