- Turin Advanced Neuromodulation Group (TANG), Turin, Italy
Turin Advanced Neuromodulation Group (TANG), Turin, Italy
DOI:10.4103/2152-7806.150674Copyright: © 2015 Canavero S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Canavero S. The “Gemini” spinal cord fusion protocol: Reloaded. Surg Neurol Int 03-Feb-2015;6:18
How to cite this URL: Canavero S. The “Gemini” spinal cord fusion protocol: Reloaded. Surg Neurol Int 03-Feb-2015;6:18. Available from: http://sni.wpengine.com/surgicalint_articles/the-gemini-spinal-cord-fusion-protocol-reloaded/
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,[
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.”[
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.”[
In this paper, I will detail the recently proposed GEMINI spinal cord fusion (SCF) protocol in view of the first human CSA,[
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.
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.
The key to SCF is a sharp severance of the cords themselves, with its attendant minimal damage to both the axons in the white matter and the neurons in the gray laminae. This is a key point: A typical force generated by creating a sharp transection is less than 10 N versus approximately 26000 N experienced during spinal cord injury, a 2600× difference![
A specially fashioned diamond microtomic snare-blade is one option (unpublished); a nanoknife made of a thin layer of silicon nitride with a nanometer sharp cutting edge is another alternative.[
In man, motricity is only modestly subserved by long axonal systems coursing through the spinal white matter as taught in contemporary anatomical and neurology textbooks (parenthetically, “Subdivision of the (human) white matter…into tracts is…not feasible, because most of the tracts mix with one another and overlap”).[
In a recent case report, a subject with tetraplegia (ASIA A) recovered 15 months later to ASIA D, despite a 62% atrophy of the white matter tissue at the injury epicenter,[
In GEMINI, the gray matter neuropil will be restored by spontaneous regrowth of the severed axons/dendrites over very short distances at the point of contact between the apposed cords.
GEMINI exploits special substances (fusogens/sealants: Poly-ethylene glycol [PEG], Chitosan) that have the power to literally fuse together severed axons or seal injured leaky neurons.[
Notice that during CSA no gap is expected between the cord stumps. Should have this not been the case, transplantable miniature neurono-axonal constructs internalized within engineered tubes could have been used to fill the gap (e.g.[
Tangentially, collagen conduits containing autologous platelet-rich plasma have allowed successful axonal regeneration and neurological recovery in clinical peripheral nerve injury with gaps up to 12 cm (16 cm along with an added sensory nerve graft).[
In GEMINI, local sprouting between neurons in the gray matter (see above) will reestablish a functional bridge over days to weeks. This process is accelerated by electrical stimulation via application of a spinal cord stimulator (SCS) straddling the fusion point. For instance, 1 h of continuous electrical stimulation at 20 Hz applied right after suturing together the stumps of a transected peripheral nerve cut the regeneration time from 8–10 to 3 weeks; similar accelerations are seen in man.[
The role of electrical stimulation goes well beyond acceleration of axonal and dendritic regrowth. The spinal cord has the capacity to execute complex stereotyped motor tasks in response to rather unspecific stimuli even after chronic separation from supraspinal structures. However, being deprived of sufficient supraspinal drive, neural processing, and pattern generating networks caudal to a spinal cord lesion lose an adequate, sustainable state of excitability to be fully operational: SCS (15–60 Hz, 5–9 V) provides a multi-segmental tonic neural drive to these circuitries and “tune” their physiological state to a more functional level.[
In sum, the GEMINI SCF protocol hinges on the following steps [
(a) Longitudinal cut along a primate spinal cord depicting the internuncial system (gray matter motor highway) and the nano-size of the proposed severance (left). The red circle on the right side of this panel is the pyramidal tract, shown in two exploded views of a sharply transected cord (middle right) and of the cord in the vertebral canal (lower middle right). (b)Visualization of the severed pyramidal tract. The uppermost image depicts a motor neuron in the cortex sending forth the axonal prolongation. Middle panel: The pyramidal tract (red) and a portion of its severed axons. Lower panel: The sharply severed axonal extensions (adapted from Laruelle 1937 and several images in the public domain)
The sharp severance of the cervical cords (donor's and recipient's), with its attendant minimal tissue damage The exploitation of the gray matter internuncial sensori-motor “highway” rebridged by sprouting connections between the two reapposed cord stumps. This could also explain the partial motor recovery in a paraplegic patient submitted to implantation of olfactory ensheathing glia and peripheral nerve bridges: A 2-mm bridge of remaining cord matter might have allowed gray matter axons to reconnect the two ends[ The bridging as per point 2 above is accelerated by electrical SCS straddling the fusion point The application of “fusogens/sealants”: Sealants “seal” the thin layer of injured cells in the gray matter, both neuronal, glial and vascular, with little expected scarring; simultaneously they fuse a certain number of axons in the white matter.
The sharp severance of the cervical cords (donor's and recipient's), with its attendant minimal tissue damage
The exploitation of the gray matter internuncial sensori-motor “highway” rebridged by sprouting connections between the two reapposed cord stumps. This could also explain the partial motor recovery in a paraplegic patient submitted to implantation of olfactory ensheathing glia and peripheral nerve bridges: A 2-mm bridge of remaining cord matter might have allowed gray matter axons to reconnect the two ends[
The bridging as per point 2 above is accelerated by electrical SCS straddling the fusion point
The application of “fusogens/sealants”: Sealants “seal” the thin layer of injured cells in the gray matter, both neuronal, glial and vascular, with little expected scarring; simultaneously they fuse a certain number of axons in the white matter.
During CSA, microsutures (mini-myelorrhaphy) will be applied along the outer rim of the apposed stumps. A cephalosomatic anastomosee will thus be kept in induced coma for 3–4 weeks following CSA to give time to the stumps to refuse (and avoid movements of the neck) and will then undergo appropriate rehabilitation in the months following the procedure.
In addition, the immunosuppressant regime that will be instituted after CSA is expected to be pro-regenerative.[
The author wishes to thank the thousands of scientists and patients from around the world who benefited him with their encouragement and suggestions.
1. Alstermark B, Isa T. Circuits for skilled reaching and grasping. Annu Rev Neurosci. 2012. 35: 559-78
2. Amoozgar Z, Rickett T, Park J, Tuchek C, Shi R, Yeo Y. Semi-interpenetrating network of polyethylene glycol and photocrosslinkable chitosan as an in-situ-forming nerve adhesive. Acta Biomater. 2012. 8: 1849-58
3. Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014. 137: 1394-409
4. Basso DM. Neuroanatomical substrates of functional recovery after experimental spinal cord injury: Implications of basic science research for human spinal cord injury. Phys Ther. 2000. 80: 808-17
5. Bittner GD, Keating CP, Kane JR, Britt JM, Spaeth CS, Fan JD. Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves. J Neurosci Res. 2012. 90: 967-80
6. Bucy PC, Keplinger JE, Siqueira EB. Destruction of the “pyramidal tract” in man. J Neurosurg. 1964. 21: 285-98
7. Canavero S. HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg Neurol Int. 2013. 4: S335-42
8. Chang WC, Hawkes EA, Kliot M, Sretavan DW. In vivo use of a nanoknife for axon microsurgery. Neurosurgery. 2007. 61: 683-92
9. Chang WC, Kliot M, Sretavan DW. Microtechnology and nanotechnology in nerve repair. Neurol Res. 2008. 30: 1053-62
10. Chang WC, Hawkes E, Keller CG, Sretavan DW. Axon repair: Surgical application at a subcellular scale. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010. 2: 151-61
11. Chen B, Bohnert D, Borgens RB, Cho Y. Pushing the science forward: Chitosan nanoparticles and functional repair of CNS tissue after spinal cord injury. J Biol Eng. 2013. 7: 15-
12. Choe AS, Belegu V, Yoshida S, Joel S, Sadowsky CL, Smith SA. Extensive neurological recovery from a complete spinal cord injury: A case report and hypothesis on the role of cortical plasticity. Front Hum Neurosci. 2013. 7: 290-
13. Cullen DK, Tang-Schomer MD, Struzyna LA, Joel S, Sadowsky CL, Smith SA. Microtissue engineered constructs with living axons for targeted nervous system reconstruction. Tissue Eng Part A. 2012. 18: 2280-9
14. Estrada V, Brazda N, Schmitz C, Heller S, Blazyca H, Martini R. Long-lasting significant functional improvement in chronic severe spinal cord injury following scar resection and polyethylene glycol implantation. Neurobiol Dis. 2014. 67C: 165-79
15. Feringa ER, Johnson RD, Wendt JS. Spinal cord regeneration in rats after immunosuppressive treatment. Theoretic considerations and histologic results. Arch Neurol. 1975. 32: 676-83
16. Goodkin R, Budzilovich GN, Campbell JB. Myelorrhaphy: Part II. Spine. 1976. 1: 193-5
17. Gordon T, Chan KM, Sulaiman OA, Udina E, Amirjani N, Brushart TM. Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury. Neurosurgery. 2009. 65: A132-44
18. Gybels JM, Sweet WH.editors. Neurosurgical treatment of persistent pain. Basel: Karger; 1989. p.
19. Isa T, Nishimura Y. Plasticity for recovery after partial spinal cord injury – hierarchical organization. Neurosci Res. 2014. 78: 3-8
20. Jane JA, Yashon D, Becker DP, Beatty R, Sugar O. The effect of destruction of the corticospinal tract in the human cerebral peduncle upon motor function and involuntary movements. Report of 11 cases. J Neurosurg. 1968. 29: 581-5
21. Kouhzaei S, Rad I, Khodayari K, Mobasheri H. The neuroprotective ability of polyethylene glycol is affected by temperature in ex vivo spinal cord injury model. J Membr Biol. 2013. 246: 613-9
22. Kouhzaei S, Rad I, Mousavidoust S, Mobasheri H. Protective effect of low molecular weight polyethylene glycol on the repair of experimentally damaged neural membranes in rat's spinal cord. Neurol Res. 2013. 35: 415-23
23. Kuffler DP. An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma. Prog Neurobiol. 2014. 116C: 1-12
24. Laruelle L. La structure d la moelle epinière en coupes longitudinales. Rev Neurol. 1937. 67: 697-711
25. Minassian K, Hofstoetter US, Danner SM, Mayr W, McKay WB, Tansey K. Mechanisms of rhythm generation of the human lumbar spinal cord in response to tonic stimulation without and with step-related sensory feedback. Biomed Tech. 2013. 58:
26. Nathan PW, Smith MC. Fasciculi proprii of the spinal cord in man. Brain. 1959. 82: 610-68
27. Nathan PW, Smith M, Deacon P. Vestibulospinal, reticulospinal and descending propriospinal nerve fibres in man. Brain. 1996. 119: 1809-33
28. Putnam TJ. Treatment of unilateral paralysis agitans by section of the lateral pyramidal tract. Arch Neurol Psychiatry. 1940. 44: 950-76
29. Rad I, Khodayari K, Hadi Alijanvand S, Mobasheri H. Interaction of polyethylene glycol (PEG) with the membrane-binding domains following spinal cord injury (SCI): Introduction of a mechanism for SCI repair. J Drug Target. 2014. p. 1-10
30. Schlaeger R, Papinutto N, Panara V. Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann Neurol. 2014. 76: 568-80
31. Sexton KW, Pollins AC, Cardwell NL, Del Corral GA, Bittner GD, Shack RB. Hydrophilic polymers enhance early functional outcomes after nerve autografting. J Surg Res. 2012. 177: 392-400
32. Shi R. Polyethylene glycol repairs membrane damage and enhances functional recovery: A tissue engineering approach to spinal cord injury. Neurosci Bull. 2013. 29: 460-6
33. Sledge J, Graham WA, Westmoreland S, Sejdic E, Miller A, Hoggatt A. Spinal cord injury models in non human primates: Are lesions created by sharp instruments relevant to human injuries?. Med Hypotheses. 2013. 81: 747-8
34. Sretavan DW, Chang W, Hawkes E, Keller C, Kliot M. Microscale surgery on single axons. Neurosurgery. 2005. 57: 635-46
35. Stauffer ES, Goodman FG, Nickel VL. Myelorrhaphy: Part I. Spine. 1976. 1: 189-92
36. Stewart FT, Harte RH. A case of severed spinal cord in which myelorrhaphy was followed by partial return of function. Philadelphia Med J. 1902. 9: 1016-20
37. Sunshine MD, Cho FS, Lockwood DR, Fechko AS, Kasten MR, Moritz CT. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury. J Neural Eng. 2013. 10: 036001-
38. Tabakow P, Raisman G, Fortuna W, Czyz M, Huber J, Li D. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 2014. p.
39. White RJ. Head transplants. Sci Am. 1999. p. 24-6
40. Zhang J, Sheng L, Jin C, Liu J. Liquid metal as connecting or functional recovery channel for the transected sciatic nerve. 2014. p.