Abstract

BackgroundSpinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. Based on our previous experimental results of spinal cord fusion (SCF) in mice, rats, beagles, and monkeys, we developed a surgical protocol of SCF for paraplegic human patients. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction.MethodsWe conducted a clinical trial (ChiCTR2000030788) and performed SNT in 12 fully paraplegic patients due to SCI between T1 and T12. We assessed pre- and postoperative central nerve pain, motor function, sensory function, and autonomic nerve function. Conduction of action potentials across the sural nerve transplant was evaluated. Neural continuity was also examined by diffusion tensor imaging (DTI).ResultsAmong the 12 paraplegic patients enrolled in this clinical trial, seven patients demonstrated improved autonomic nerve functions. Seven patients had clinically significant relief of their symptoms of cord central pain. One patient, however, developed postoperative cord central pain (VAS: 4). Five patients had varying degrees of recovered sensory and/or motor functions below the single neurologic level 1 month after surgery. One patient showed recovery of electrophysiologic, motor-evoked potentials 6 months after the operation. At 6 months after surgery, DTI indicated fusion and nerve connections of white cord and sural nerves in seven patients.ConclusionSNT was able to fuse the axonal stumps of white cord and sural nerve and at least partially improve the cord central pain in most patients. Although SNT did not restore the spinal cord continuity in white matter in some patients, SNT could restore spinal cord continuity in the cortico-trunco-reticulo-propriospinal pathway, thereby restoring in part some motor and sensory functions. SNT may therefore be a safe, feasible, and effective method to treat paraplegic patients with SCI. Future clinical trials should be performed to optimize the type/technique of nerve transplantation, reduce surgical damage, and minimize postoperative scar formation and adhesion, to avoid postoperative cord central pain.Clinical Trial Registration[http://www.chictr.org.cn/showproj.aspx?proj=50526], identifier [ChiCTR2000030788].

Highlights

  • Spinal cord injury (SCI) is one of the most devastating diseases in the world

  • During the subsequent clinical recruitment process, we found that some patients had a SCI in the lower thoracic area or had marked distal spinal cord atrophy

  • Cutting half of the spinal cord tissue from the proximal spinal cord tissue site would lead to ascent of the single neurologic level. These patients were not suitable for the vascular pedicle hemisected spinal cord transplantation (vSCT) treatment. To treat these paraplegic patients, based on a clinical trial of peripheral nerves for SCI reported in 2014 (Tabakow et al, 2014), we developed a second clinical translational model of spinal cord fusion (SCF) (Model II), sural nerve transplantation (SNT)

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Summary

Introduction

Spinal cord injury (SCI) is one of the most devastating diseases in the world. About 27 million people worldwide have been chronically disabled as a result of SCI (James et al, 2019). There could be 10,000–20,000 new SCI patients in the United States and 60,000 new SCI patients in China every year (Qiu, 2009; National Spinal Cord Injury Statistical Center, 2014). It is estimated that the direct lifetime cost of care ranged from $1.1 million to $4.7 million per person for more than one million SCI people in North America. For SCI patients in North America alone, the total direct cost of acute treatment and chronic care in the United States exceeded $7 billion per year (Badhiwala et al, 2018). Spinal cord injury (SCI) can cause paralysis and serious chronic morbidity, and there is no effective treatment. We designed a novel surgical procedure of SCF, called sural nerve transplantation (SNT), for human patients with lower thoracic SCI and distal cord dysfunction

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