Spinal Cord Fusion Research Articles

Developing preclinical dog models for reconstructive severed spinal cord continuity via spinal cord fusion technique

BackgroundSpinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. MethodsSeven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. ResultsThe results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. ConclusionThe study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

Chitosan/PEG-mediated spinal cord fusion after complete dorsal transection in rabbits – functional results at 30 days

Background: The aim was to study functional recovery in experimental animals (rabbits) with transected spinal cords treated with a combination of photo-cross-linked chitosan in a homogeneous mixture with polyethylene glycol (PEG-chitosan). Methods: 20 rabbits (n = 10 experimental and n = 10 controls) were submitted to complete spinal cord transection at T9. The experimental group received an intraoperative injection of PEG-chitosan. Neurological recovery was assessed using the modified Basso, Beattie, and Bresnahan scale. Results: In the experimental group, partial recovery of movements, sensory function, and sphincter control were all observed by postoperative day 30. Paraplegia and anesthesia persisted in the control group; 4 controls died versus none in the test group. Conclusion: PEG-chitosan is a candidate for neurological restoration after spinal paralysis.

Partial restoration of spinal cord neural continuity via vascular pedicle hemisected spinal cord transplantation using spinal cord fusion technique.

AimsOur team tested spinal cord fusion (SCF) using the neuroprotective agent polyethylene glycol (PEG) in different animal (mice, rats, and beagles) models with complete spinal cord transection. To further explore the application of SCF for the treatment of paraplegic patients, we developed a new clinical procedure for SCF called vascular pedicle hemisected spinal cord transplantation (vSCT) and tested this procedure in eight paraplegic participants.MethodsEight paraplegic participants (American Spinal Injury Association, ASIA: A) were enrolled and treated with vSCT (PEG was applied to the sites of spinal cord transplantation). Pre‐ and postoperative pain intensities, neurologic assessments, electrophysiologic monitoring, and neuroimaging examinations were recorded.ResultsOf the eight paraplegic participants who completed vSCT, objective improvements occurred in motor function for one participant, in electrophysiologic motor‐evoked potentials for another participant, in re‐establishment of white matter continuity in three participants, in autonomic nerve function in seven participants, and in symptoms of cord central pain for seven participants.ConclusionsThe postoperative recovery of paraplegic participants demonstrated the clinical feasibility and efficacy of vSCT in re‐establishing the continuity of spinal nerve fibers. vSCT could provide the anatomic, morphologic, and histologic foundations to potentially restore the motor, sensory, and autonomic nervous functions in paraplegic patients. More future clinical trials are warranted.

Partial Restoration of Spinal Cord Neural Continuity via Sural Nerve Transplantation Using a Technique of Spinal Cord Fusion.

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].

Non-fusion palliative spine surgery without reconstruction is safe and effective in spinal metastasis patients: retrospective study

Considering the shorter life expectancy and poorer prognosis of metastatic epidural spinal cord compression patients, anterior reconstruction and fusion may be unnecessary. This study aimed to investigate the outcomes of palliative surgery for metastatic epidural spinal cord compression with neurological deficit among patients who underwent posterior decompression and instrumentation without fusion or anterior reconstruction. This single-center retrospective review included all patients aged > 18 years with thoracic or lumbar spinal metastasis who were surgically treated for metastatic spinal cord compression without fusion or anterior reconstruction at the Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during July 2015 to December 2017. Data from preoperation to the 1-year follow-up, including demographic and clinical data, Frankel classification, pain scores, complication, revision surgery, health-related quality-of-life scores, and survival data, were collected and analyzed. A total of 30 patients were included. The mean age was 59.83 ± 11.73 years, and 20 (66.7%) patients were female. The mean operative time was 208.17 ± 58.41 min. At least one Frankel grade improvement was reported in 53.33% of patients. The pain visual analog scale, the EuroQOL five-dimension five-level utility score, and the Oswestry Disability Index were all significantly improved at a minimum of 3 months after surgery. No intraoperative mortality or instrument-related complication was reported. The mean survival duration was 11.4 ± 8.97 months. Palliative non-fusion surgery without anterior reconstruction may be considered as a preferable choice for treating spinal metastasis patients with spinal cord compression with neurological deficits.

Bridging the gap: Spinal cord fusion as a treatment of chronic spinal cord injury.

Despite decades of animal experimentation, human translation with cell grafts, conduits, and other strategies has failed to cure patients with chronic spinal cord injury (SCI). Recent data show that motor deficits due to spinal cord transection in animal models can be reversed by local application of fusogens, such as Polyethylene glycol (PEG). Results proved superior at short term over all other treatments deployed in animal studies, opening the way to human trials. In particular, removal of the injured spinal cord segment followed by PEG fusion of the two ends along with vertebral osteotomy to shorten the spine holds the promise for a cure in many cases.

Full Body Transplantation, Is it Allowed?

Introduction In May 2016, an international medical team announced plans to perform the first full body transplantation (sometimes controversially designated as “head transplantation”) before the end of 2017. In their eagerness to cross what they call “the final frontier in transplant surgery”, team leaders Sergio Canavero and Xiaoping Ren brush aside all ethical and legal concerns, emphasising instead the (alleged) medical prospects for hitherto incurable diseases, such as progressive muscular disease and intractable cancer without brain metastases. In recent interviews they indicate that, although the estimated timeline will not be met, their project is going according to plan. Materials and Methods We conducted an extensive Internet search of the popular media and academic journals, collecting news items and articles that have been published on the topic, since Canavero first outlined his idea of spinal cord fusion in 2013. In addition, we consulted leading handbooks on the medical and criminal liability of medical professionals, examined relevant international guidelines, and analysed the few academic articles discussing medical experimentation in organ transplantation. Finally, we applied the relevant insights that emerged from this research to the topic of full body transplantation and investigated the legality of the procedure under the current state of medical knowledge. Results and Discussion We found that full body transplantation currently does not conform to the conditions that allow experimental and high-risk medical interventions to be legitimately performed under international and national law. Similarly, we discovered that full body transplantation, where this would be characterised as a research project instead of as a medical experiment, currently fails the conditions set out in international and national regulations. We concluded that it is very unlikely that prior ethics approval would be obtained, and that physicians who engage in full body transplantation are very likely to be found liable for medical malpractice. If this procedure would result in the death of the patient, the physicians involved would run a considerable risk of being held criminally liable for negligent homicide. The participating physicians will also risk severe disciplinary sanctions for professional misconduct, with a real possibility that they will be suspended or even banned from medical practice for life. Conclusion Under the current state of medical knowledge full body transplantation cannot legally be performed. Physicians attempting the procedure are very likely to be found civilly liable and to face severe disciplinary sanctions. In addition, they may under certain circumstances even be held criminally liable. Before an attempt to perform full body transplantation would be acceptable, the formidable surgical challenges first need to be resolved and the major ethical issues addressed.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model

BackgroundCephalosomatic anastomosis or what has been called a “head transplantation” requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. MethodsWe conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. ResultsA total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0–19), canine, Basso-Beattie-Bresnahan rating scale (P < .006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P < .02). ConclusionA sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.)

Multisystemic anomalies in conjoined twins: The role of imaging in management

Conjoined twins (CT) represent one of the rarest and most challenging congenital malformations arising as an unfortunate complication of monozygous twinning, with an estimated incidence ranging from 1 in 50,000 to 100,000 pregnancies, with an overall true incidence of about 1 in 200,000 live births with around 60% of them being stillborn. The types of the twins may differ depending on the site of fusion or nonseparation. The most commonly encountered types are thoraco-omphalopagus (28%), thoracopagus (18%), omphalopagus (10%), parasitic twins (10%), pygopagus (6-19%), and craniopagus (6%), with the pygopagus twins having the highest survival rate. Because of the highly variable and complex anatomy and associated malformations, skilled clinical assessments aided by detailed radiological studies, appropriate planning, and teamwork are required for the successful separation of the CT. The role of imaging in the diagnosis and management of missed diagnosed intrauterine case of pygopagus type CT was presented. At delivery, they were found to have sacral fusion on radiography with distal, rectal fusion on limited barium enema. Magnetic resonance imaging demonstrated distal spinal cord fusion with vascular anomaly found on computed tomography angiography. The surgical separation of the patients was successful with satisfactory postoperative lives.

Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration.

Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules.

Neurologic foundations of spinal cord fusion (GEMINI)

Cephalosomatic anastomosis has been carried out in both monkeys and mice with preservation of brain function. Nonetheless the spinal cord was not reconstructed, leaving the animals unable to move voluntarily. Here we review the details of the GEMINI spinal cord fusion protocol, which aims at restoring electrophysiologic conduction across an acutely transected spinal cord. The existence of the cortico-truncoreticulo-propriospinal pathway, a little-known anatomic entity, is described, and its importance concerning spinal cord fusion emphasized. The use of fusogens and electrical stimulation as adjuvants for nerve fusion is addressed. The possibility of achieving cephalosomatic anastomosis in humans has become reality in principle.

Human head transplantation. Where do we stand and a call to arms.

Human head transplantation. Where do we stand and a call to arms.

Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats.

Background:The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons.Methods:Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery.Results:While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery.Conclusion:In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.

GEMINI: Initial behavioral results after full severance of the cervical spinal cord in mice.

Background:The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord.Methods:Cervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera.Results:The PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity.Conclusion:In this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection.

The "Gemini" spinal cord fusion protocol: Reloaded.

Sir, Cephalosomatic anastomosis (CSA), that is, the surgical transference of a healthy head on a surgically beheaded body under deep hypothermic conditions, as conceived by Robert White,[39] hinges on the reconnection of the severed stumps of two heterologous spinal cords (reviewed in reference).[7] On the occasion of the first CSA between primates in 1970, Dr White hewed to the view that a severed spinal cord could not be reconnected, thus leaving the animal paralyzed.[7,39] In 1902, Stewart and Harte reported on CN, aged 26 years, who had her spinal cord severed by a 0.32 caliber gunshot. The distance between the segments of the cord was 0.75 inch, as verified by all five attending physicians: “The ends of the cord were then approximated with 3 chromicized catgut sutures passed by means of a small staphylorraphy needle, one suture being passed anteroposteriorly through the entire thickness of the cord and the other two being passed transversely. This part of the operation was attended with unusual difficulties because of…the wide interval between the fragments, the catgut frequently tearing out before the ends were finally brought together.” Sixteen months later, “the patient slides out of bed into her chair by her own efforts and is able to stand with either hand on the back of a chair, thus supporting much of the weight of the body.”[36] Importantly, they reviewed several cases of patients with sharp wounds to the cord that spontaneously recovered from initial paraplegia. Their conclusion was that “the operation of myelorrhaphy will be specially indicated in cases in which the cord has been cut by a sharp instrument or severed by a projectile.”[36] Whereas myelorrhaphy was not effective at 15 months in a young paraplegic patient after a self-inflicted 0.38 caliber gunshot,[16,35] nonetheless, a huge body of evidence accrued over the past decades made the first part of Stewart and Harte's prediction highly relevant.[33] In fact, had White attempted to reattach the sharply severed cord stumps in the monkey, the possibility exists that the animal might have recovered at least partial motricity. In this paper, I will detail the recently proposed GEMINI spinal cord fusion (SCF) protocol in view of the first human CSA,[7] giving new meaning to Stewart and Harte's prediction. The recent study by Estrada et al.,[14] in which rats whose spinal cords were sharply transected recovered ambulation, confirms that CSA (HEAVEN: 7) is feasible. Two key principles underlie the GEMINI SCF: A sharp severance of the cords is not as damaging as clinical spinal cord injury The gray matter “motor highway” is more important than the pyramidal tract in human motor processing.

Cervical myelopathy due to ossification of the transverse atlantal ligament: A Caucasian case report operated on and literature analysis

One case of cervical myelopathy associated to ossification of transverse atlantal ligament (OTAL) and C1 posterior arch hypoplasia in a Caucasian adult female is reported. A 53-year-old female affected by cervical myelopathy was treated with C1 laminectomy and posterior arthrodesis. CT scan demonstrated that the distance between ossification of the ligament and anterior cortex of the posterior arch of atlas was 6,2mm leading to consistent space reduction for spinal cord at this level. Patient underwent spinal cord decompression and fixation with C1 poliaxial screws in lateral masses and two bilateral crossing C2 laminar screws with an improvement of neurological functions at 4-years follow-up. The association between OTAL and C1 hypoplasia was reported in very few cases. The treatment with C1 laminectomy without fusion is reported in medical literature with good clinical outcome. Our patient obtained a neurological improvement at midterm follow-up with spinal cord decompression and fusion.

Occipitocervicothoracic fixation using a hook and rod system for patients with rheumatoid cervical spine

We retrospectively examined the outcomes of occipitocervicothoracic fixation using a hook and rod system for rheumatoid patients with cervical myelopathy in which decompression of the spinal cord and spinal fusion were performed simultaneously at multiple levels. There were 10 female patients with rheumatoid arthritis (ages 51–77 years, average 62.8 years; follow-up period 6 months to 3 years and 9 months, average 2 years and 8 months). Atlantoaxial subluxation was found in 5 patients, vertical subluxation in 4 patients, and subaxial subluxation in 8 patients. The progression of the disorder was assessed as class 4 stage 4 in 3 patients and class 3 stage 4 in 7 patients. The average time taken for surgery was 4 h 41 min, and the average volume of blood loss was 729 ml. There were no complications during surgery. One patient died of malignant lymphoma 1 month after surgery, and one patient died of heart failure 2 years and 3 months after surgery. The average Japanese Orthopaedic Association (JOA) score improved from 7.0 preoperatively to 9.5 postoperatively. Preoperative nuchal pain in 3 patients and difficulty in breathing on flexion of the cervical spine in 2 patients were improved after surgery. Good bony union was obtained in 9 patients. The exception being one patient who died of a disease unrelated to the surgery 1 month postoperatively. Occipitocervicothoracic fixation using a hook and rod system is an easy and safe procedure, and can facilitate not only good bony union, but also adequate decompression of the spinal cord with simultaneous laminoplasty because of the secure long fixation extending to the upper thoracic level and bilateral grafting of a considerable volume of bone.

MEDIATION OF DESCENDING LONG SPINAL REFLEX ACTIVITY

MEDIATION OF DESCENDING LONG SPINAL REFLEX ACTIVITY

ACTIVITY IN NEURONS OF THE BULBOSPINAL CORRELATION SYSTEM

ACTIVITY IN NEURONS OF THE BULBOSPINAL CORRELATION SYSTEM