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Intervertebral Disc Transplantation: Treatment in Motion
Abstract & Commentary
By Justin F. Fraser, MD, and John Boockvar, MD, Department of Neurological Surgery, Weill Medical College of Cornell University, New York, NY. Drs. Fraser and Boockvar report no financial relationships relevant to this field of study.
Synopsis: A pilot study of human cervical disc transplantation has been shown to be surgically feasible, but requires further investigation.
Source: Ruan D, et al. Intervertebral disc transplantation in the treatment of degenerative spine disease: a preliminary study. Lancet 2007; 369:993-999.
Anterior cervical discectomy and fusion is a standard procedure for the treatment of cervical herniated intervertebral discs and cervical spondylosis. However, while the procedure directly decompresses nerve roots and/or the spinal cord, it permanently alters spinal anatomy. In particular, cervical fusion reduces motion in at least one spinal segment. Traditionally considered benign, this modification to natural movement has been shown to accelerate adjacent disc degeneration. In an effort to reduce this effect, some investigators have studied the possibility of intervertebral disc transplantation to retain segmental motion while treating pathological discs in the cervical spine. Given initial success in animal models, Ruan et al. now publish their results of a pilot series of patients using composite allograft intervertebral disc transplantations from human donors. The stated aims of this trial were to demonstrate graft viability and stability, preservation of segmental mobility, and satisfactory clinical outcome.
The authors report outcomes of 5 patients in whom single-level anterior cervical discectomy was performed, and who received allograft disc transplants from previously healthy 20-30 year-old female victims of trauma. Four patients presented with cervical spondylotic myelopathy, and one presented with incomplete paraplegia from a traumatic cervical disc herniation. The surgery involved an endplate-disc-endplate transplantation, without internal fixation. All patients wore cervical collars for at least 2 weeks postoperatively, and were examined two months postoperatively, and every 3 months thereafter, with flexion-extension radiographs, and, at last follow-up, with MRI. Mean follow-up was 66 months, with all patients showing individual improvement in neurological status per Japanese Orthopedic Association (JOA) scale or Frankel grade. Two patients reported worse neck pain at last follow-up compared to preoperative assessment, and 2 patients had complications — one reported a 'foreign body sensation' in the throat that lasted 18 months postoperatively, and the second developed recurrent upper extremity numbness and radiculopathy at 20 months postoperatively, that required posterior unilateral foraminotomy. No patient had signs or symptoms of graft rejection, and no patient demonstrated evidence of graft migration. One patient had autofusion at the transplanted segment just posterior to the grafted disc. Three patients had hypointensity noted in the transplanted discs at last MRI follow-up similar to adjacent discs (so-called 'dark discs'), often indicative of early disc degeneration. With these results, the authors claim that "the motion and stability of the spinal unit is preserved after transplantation of fresh-frozen allogeneic intervertebral discs in human beings, despite signs of mild disc degeneration."
In their pilot series of human recipients of cervical disc transplantations, Ruan et al are pioneers in the clinical application of a novel treatment for cervical disc disease. They analyzed both clinical and radiographic outcome variables, studying neurologic outcome as well as biomechanical graft persistence and maintenance of mobility. With a mean follow-up of 66 months, the authors followed this pilot group of patients for a significant period. The study was successful in demonstrating that intervertebral disc transplantation is feasible without significant autoimmune response in the postoperative period. It also demonstrated that segmental motion could be preserved while qualitative improvement in neurological status could be obtained through this methodology. As such, the results of the study support further clinical research to study the long-term safety and efficacy of this therapy in larger groups of patients.
However, some features of this study limit its clinical applicability. First, while the mean 66-month follow-up provided a significant interval to study clinical and postoperative radiographic outcome, it falls short of determining long-term transplant degeneration. The majority of patients (3 of 5) demonstrated early signs (loss of T2 hyperintensity within the nucleus of the disc transplant) of disc degeneration at last follow-up MRI. Given that the grafts were all obtained from previously healthy 20-30 year-olds, imaging reports that 3 of 5 transplants resembled the degenerative pattern of adjacent native discs in the recipients is a concerning finding. It suggests an accelerated pathway of degeneration in the grafts. Indeed, this finding requires more study.
A second limitation is the methodology for graft selection. While taken from previously-healthy 20-30 year-old females screened for transmissible diseases, and imaged with plain radiographs to "exclude bony abnormality and any obvious disc degeneration," the grafts were not visualized using MRI of their hosts. It would have been helpful to visualize the MR characteristics of the grafts prior to harvesting in order to have a baseline for future comparison and to rule-out grafts with early degenerative changes.
The third problem relates to the selection criteria for graft recipients. In a pilot study where the number will be small, minimization of controllable variables is important. The authors should not have included a patient with paraplegia from a traumatic disc herniation, as the pathophysiology is very different from that of chronic degenerative spondylotic myelopathy.
Finally, while the authors show technical success in performing disc transplantation safely, the results during follow-up are discouraging. One of five of the patients demonstrated autofusion at the transplanted level within 2 years of operation. Two of 5 patients reported worse neck pain at last follow-up compared to preoperative assessment.
In summary, Ruan et al. provide an intriguing pilot study that highlights a potential future modality for treating cervical disc disease while maintaining segmental motion. Disc transplantation may represent an alternative to artificial disc replacement, but raises important questions that must be addressed in future trials if disc transplantation is to become a tool in the armamentarium of physicians who treats spine disease.