The first cases of independent stepping by people who had complete lower limb paralysis after spinal cord injury were reported in two journal articles Monday.
In a study published in , a 29-year-old man with complete sensorimotor lower limb paralysis after an accident was able to step independently on a treadmill -- and walk over ground with a front-wheeled walker while trainers provided occasional assistance -- when an implanted epidural electrical stimulator was activated, said Kendall Lee, MD, PhD, and Kristin Zhao, PhD, both of the Mayo Clinic in Rochester, Minnesota, and co-authors.
And two of four young patients who had epidural stimulators implanted after they were paralyzed by traumatic, motor-complete spinal injuries could walk over ground independently using a walker or horizontal poles, according to Susan Harkema, PhD, of the University of Louisville in Kentucky, and colleagues in the .
"What this is teaching us is that those networks of neurons below a spinal cord injury still can function after paralysis," Lee said in statement.
In all cases, patients had complete spinal cord injury, meaning they had no voluntary movement below the level of their injury, according to (ASIA) criteria. (The patients' spinal cords had not been totally severed, however.)
The Mayo patient had no sensory or motor lower limb function below the level of injury (grade A impairment on the ASIA Impairment Scale). Two Louisville patients had no motor function but had some spared sensation (grade B impairment) below the level of injury; the other two had grade A impairment.
All patients had epidural electrical stimulators implanted surgically at least 2 years post-injury, and all underwent intensive physical rehabilitation therapy and training. Patients were able to move their limbs only when the stimulator was activated. (A video comparing the Mayo patient's abilities with and without the stimulator can be viewed .)
The Mayo patient had 113 multimodal training sessions over 43 weeks to engage sensorimotor networks with the stimulator. In some sessions, he reached milestones like walking the length of a football field with occasional assistance. By week 43, two interleaved epidural electrical stimulation programs improved his ability to control each leg to achieve independent stepping on a treadmill without trainer assistance. At week 43, he also could step independently over ground using a front-wheeled walker, with trainer assistance at the hips to maintain balance (a video showing that can be seen ).
The four Louisville patients had daily locomotor training and recovered the ability to stand independently, improve their trunk stability during sitting, and perform components of independent stepping on a treadmill. The two patients with grade B impairment also were able to walk independently over ground with assistive devices -- one after 278 training sessions, the other after 81 sessions. "A key component of our training was the integration of 'intent' during every training session, meaning that the research participants attempted to actively take every step," co-author Claudia Angeli, PhD, of the University of Louisville, told 鶹ý. Whether the difference in outcomes among the four patients was due to sensory sparing or other variables is being studied.
The mechanism that allows a paralyzed patient to move intentionally when stimulated is unknown, Lee said. Additional research is needed to learn how electrical stimulation and rehabilitation interact and whether this approach could help others.
Both studies stemmed from earlier research by Harkema and V. Reggie Edgerton, PhD, of the University of California Los Angeles, and colleagues showing that a paralyzed patient who underwent epidural stimulation could recover a number of motor functions.
Disclosures
The Mayo Clinic research was funded by the Grainger Foundation, Regenerative Medicine Minnesota, Jack Jablonski BEL13VE in Miracles Foundation, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Rehabilitation Medicine Research Center, Mayo Clinic Transform the Practice, Minnesota Office of Higher Education Spinal Cord Injury and Traumatic Brain Injury Research Grant Program, Craig H. Neilsen Foundation, Dana and Albert R. Broccoli Charitable Foundation, Christopher and Dana Reeve Foundation, and Walkabout Foundation.
Mayo researchers Lee and Zhao reported no conflicts, but other co-authors reported relationships with NeuroRecovery Technologies and Medtronic.
The University of Louisville study was funded by the Leona M. and Harry B. Helmsley Charitable Trust, University of Louisville Hospital, and Medtronic.
The authors of this study reported receiving no other support.
Primary Source
Nature Medicine
Gill M, et al "Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia" Nature Med 2018; DOI: https://doi.org/10.1038/s41591-018-0175-7.
Secondary Source
New England Journal of Medicine
Angeli C, et al "Recovery of over-ground walking after chronic motor complete spinal cord injury" New Engl J Med 2018; DOI: 10.1056/NEJMoa1803588.