Implantable direct current stimulation in para-axial cervical arthrodesis

Advances In Therapy®

Volume 21 No. 6 November/December 2004

Implantable Direct Current Stimulation in Para-Axial Cervical Arthrodesis William C. Welch, MD, FACS Shari L. Willis, RN, BSN Peter C. Gerszten, MD, MPH Department of Neurological and Orthopaedic Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

ABSTRACT This retrospective, case-controlled pilot study was designed to examine the efficacy and safety of an implantable direct current bone growth stimulator (IDCBGS) as an adjunct to cervical arthrodesis in patients at high risk for nonunion after undergoing cervical fusion in region from the occiput to C3. Twenty patients underwent para-axial cervical arthrodesis (involving posterior spine fusion and instrumentation using standard surgical techniques) for the correction of instability. All were at high risk for nonunion due to advanced age, rheumatoid arthritis, prior failed fusion attempts, infection, or immunosuppressive drug use. An IDCBGS was used to augment the surgical procedure. The mean follow-up period was 19 months, and 16 patients were available for follow-up. Radiographic evidence of fusion was demonstrated in 15 of 16 patients (94%). After surgery, all patients demonstrated clinical stabilization, a resolution of symptoms in combination with an improvement in neurologic status, or both. The mean elapsed time before fusion occurred was 4.6 months. No neurologic complications related to cathode or generator placement were observed. The use of the stimulator as an adjunct to instrument- or non-instrument-assisted surgical fusion of the para-axial region in these high-risk patients appeared both safe and efficacious. Further investigation is warranted to define the possible role and clinical utility of the IDCBGS in selected patients requiring cervical fusion, particularly those at high risk for nonunion.

Keywords: cervical vertebrae; arthrodesis; pseudoarthrosis; cervical pain; cervical instability; cervical fusion; implantable stimulator

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Address reprint requests to William C. Welch, MD, FACS Department of Neurological Surgery Presbyterian University Hospital 200 Lothrop Street, Suite B-400 Pittsburgh, PA 15213

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INTRODUCTION The unique anatomy of the para-axial region of the spine provides excellent sagittal mobility and rotation.1,2 This area of the spine, however, often becomes unstable in response to trauma, congenital anomalies, infection, os odontoideum, rheumatoid arthritis, and cancer. This instability can lead to neck and shoulder pain and potentially severe neurologic deficits. Ligamentous instability can also occur in rheumatoid arthritis and Down syndrome3 and lead to further weakening. If conservative treatment fails to resolve or stabilize symptoms, posterior arthrodesis is indicated to correct cervical instability. A number of surgical techniques involving instrumentation have been developed to provide immediate postoperative stability and promote solid bony arthrodesis.4-8 External immobilization and internal fixation are commonly used as adjuncts to these procedures. Unfortunately, even when these surgical and immobilization techniques are used, the development of pseudarthrosis leads to surgical failure in as many as 50% of patients undergoing cervical fusion in the para-axial region.9 This failure rate is attributed to the extensive anatomic mobility in the para-axial region, technical factors, and an inability to achieve adequate stabilization and immobilization.10 Patients who have rheumatoid arthritis, Down syndrome, or type II odontoid fractures represent an even greater challenge to surgeons.10 In bone graft surgery, the fusion of 2 or more vertebral bodies is dependent on the successful interplay of a number of biologic processes that must occur within a stable environment. When these processes are interrupted, delayed union or nonunion may occur. Electrical stimulation in the appendicular skeleton has been used for many years to promote bone growth during the repair of fractures, delayed union, and pseudarthrosis. The use of electrical stimulation in spinal fusions began in the early 1970s, first in small clinical studies and later in large multicenter clinical trials.11-19 Commercially available electrical stimulation devices did not become available to spine surgeons until the late 1980s. Electrical bone growth stimulation techniques have demonstrated efficacy in the lumbar spine.20-27 The purpose of this study was to both describe the technique of direct current (DC) bone growth stimulation and examine the safety and efficacy of the implantable direct current bone growth stimulator (IDCBGS) as an adjunct to occiput to C3 cervical arthrodesis in patients who were at high risk for nonunion.

METHODS Patient Selection This prospective pilot study initially included a total of 55 patients at the University of Pittsburgh/UPMC Health System, in Pittsburgh, Pa, who underwent para-axial cervical arthrodesis. Twenty of these patients were considered to be at high-risk for fusion failure. All study patients required posterior cervical arthrodesis in the region from the occiput to C3 to correct instability of congenital, traumatic, inflammatory, infectious, postsurgical, or degenerative etiology (Table). Each patient was at an increased risk of nonunion due to advanced age (age >65), rheumatoid arthritis, prior failed fusion attempts, infection, immunosuppressive drug use, or a combination of these.

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Age

54

50

47

16

79

11

63

31

Sex

M

F

F

F

F

M

M

M

Failed C1–C2 fusion with broken transarticular screws

Os odontoideum, synovial cyst, severe myelopathy, cervical instability C1–2 S/P transoral resection of dens

Os odontoideum, failed Brooks C1–C2 fusion

Left C2 root pain, severe facet arthropathy

Failed prior Gallie fusion for os odontoideum

Rheumatoid arthritis, C1–C2 instability, failed prior fusion attempts

C1–2 instability, S/P* transoral odontoid resection

Type II odontoid fracture, failed halo vest

Preoperative Diagnosis

Repeat C1–2 Brooks fusion, autograft, removal of broken right C1–2 screw

Occiput–C2 fusion using Luque rectangle, autograft

Occiput–C3 fusion using Luque rectangle, autograft

C1–2 fusion using Brooks technique, allograft

Takedown of previous C1–2 fusion, C1–2 instrumented Brooks fusion using transarticular screws, autograft

Suboccipital–C2 fusion, C1–2 transarticular screw placement, autograft, halo vest postoperatively

Suboccipital–C2 fusion using Luque rectangle, autograft

C1–2 transarticular screw placement, Brooks fusion, autograft

Surgical Procedure (All procedures were augmented with an implantable bone growth stimulator)

cont’d

Wound revision 9/18/97 due to infection at battery site; battery placed in new subcutaneous pocket; battery removed 4/98; fusion solid at 7 months

Fusion solid at 5 months

Fusion solid at 3 months

Stimulator removed at 6 months; fusion solid at 6 months

Fusion solid at 6 months; stimulator removed at 9 months

Solid fusion at 2 months

Fusion solid at 2 months

Fusion solid at 13 months; generator removed at 1 year

Postsurgical Results

Clinical Data of Patients Who Underwent Cervical Fusion With an Implantable Bone Growth Stimulator

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64

60

63

42

52

52

37

12

M

M

M

M

M

F

F

F

Status post

*

Age

Sex

Occipitocervical instability following transoral odontoid decompression

S/P transoral odontoid decompression, cervical pseudoarthrosis

Rheumatoid arthritis, C1–2 instability

Rheumatoid arthritis, C1–2 instability

Cervical instability s/p transoral odontoid decompression C1–2

C2 fracture

C1–2 instability due to rheumatoid arthritis

Failed C1–2 Brooks fusion

Preoperative Diagnosis

Occiput–C4 non-instrumented fusion, autograft and allograft, halo vest postoperatively

Occiput–C3 noninstrumented fusion, halo vest postoperatively

C1–2 Brooks fusion, autograft, halo vest postoperatively

Posterior C1–2 transarticular screws

Occiput–C4 fusion using Luque rectangle, halo vest postoperatively

C1–2 Brooks fusion using right transarticular screw

C1–2 Brooks fusion using right transarticular screw, autograft

C1–2 transarticular screw placement, allograft

Surgical Procedure (All procedures were augmented with an implantable bone growth stimulator)

Fusion solid at 6 months

Nonsolid fusion at 6 months; stimulator removed at 6 months

Fusion solid at 3 months

Fusion solid at 4 months

Fusion solid at 6 months

Fusion solid at 3 months

Fusion solid at approximately 1.5 months; stimulator removed at 2 years

Fusion solid at 2 months

Postsurgical Results

Clinical Data of Patients Who Underwent Cervical Fusion With an Implantable Bone Growth Stimulator (cont’d)

Surgical Procedure All patients underwent posterior spine exposure performed with the standard surgical techniques.1,28 In each patient, the posterior and lateral aspect of appropriate bone was exposed and any prior instrumentation was removed. Intraoperative somatosensory evoked potential monitoring was used in each case.5,29 Fibrotic tissue from previous fusion attempts and pseudarthrosis material was removed as necessary. Internal fixation was performed in each patient to increase biomechanical stability and promote solid arthrodesis. The placement of a transarticular C1–2 screw was performed preferentially for patients requiring atlantoaxial fusion only. When possible, this screw instrumentation was supplemented with Brooks fusion, using autograft bone. Those patients requiring occipital fusion underwent Luque-type construct placement in which multistrand wire was used to fix the rods to the occiput and cervical lamina.30 Autograft bone was used primarily, although it was supplemented with allograft in some cases. The bone was placed in the facet joints and on the remaining lamina and then secured with sublaminar wires. An SpF-2T® Implantable Spinal Fusion Stimulator (EBI, LP, Parsippany, NJ) was used to provide DC stimulation in each patient. The 2 cathode leads were placed laterally in the facet line, avoiding contact with the instrumentation. In cases in which occipital fusion was necessary, the leads were placed against the occiput. The bone graft was then placed directly on the leads. The fascia was closed and the generator was placed in a subcutaneous pocket created laterally to the skin incision (Fig 1). Monopolar electrocautery was avoided after the generator was placed into the pocket. The skin was closed in the usual fashion and all patients were maintained in a rigid collar or halo vest for 6 weeks to 3 months.

Fig 1. DCBGS placement on the cervical spine.

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Fusion Assessment The confirmation of solid fusion was determined both clinically and radiographically. Clinical confirmation was indicated by the resolution of the preoperative neurologic signs or symptoms associated with cervical spine movement. Radiographs, obtained in the immediate postoperative period and at 3-month intervals until solid fusion occurred, confirmed bone fusion by revealing the incorporation of osteosynthetic bone into the lateral masses, facet joints and lamina, the absence of movement between fused segments on dynamic studies, and the preservation of implant integrity (Fig 2).

Fig 2. Postoperative radiographic evidence of solid atlantoaxial arthrodesis.

RESULTS The mean follow-up period was 19 months (range, 2–60 months). One patient died in the early postoperative period from an underlying medical illness. There was no relationship between the death and the implantation of the IDCBGS. Three patients were lost to follow-up, although they had undergone successful IDCBGS placement without complications. Sixteen patients were available for follow-up, of which 94% demonstrated radiographic evidence of fusion and clinical demonstration of stabilization or of resolution of symptoms in combination with an improved

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neurologic status. The mean elapsed time before fusion occurred was 4.6 months (range, 1.5–13.0 months). Clinical data were obtained from 15 of the 16 patients. Of these, 67% reported a significant reduction in neck pain and 33% reported complete resolution of their pain. Patients who had arm or hand paresthesias and pain also reported a significant improvement following surgery. One of the 16 patients did not demonstrate radiographic evidence of solid fusion but had evidence of Chiari malformation and basilar invagination. The patient underwent transoral odontoid decompression and anterior, unilateral C1–2 transarticular screw placement, followed by occiput and C1 decompression, duraplasty, and Luque-type instrument-assisted fusion from the occiput to C3. An iliac crest autograft was used but an IDCBGS was not placed initially. The posterior instrumentation was removed 4 months later, owing to neck pain and a possible loosening of the instrumentation. At the time the instrumentation was removed, pseudarthrosis was suspected. An additional allograft was added and an IDCBGS was placed. The patient was maintained in a halo vest for 3 months. Follow-up radiographs did not demonstrate complete osteosynthetic incorporation of the bone graft at all levels. Mild clinical improvement was noted and the patient declined further surgery. There were no neurologic complications related to the placement of the cathode leads or generator, but a superficial wound infection did develop in 1 patient. Although the wound had initially responded to débridement and oral antibiotics, purulent material was still present at the generator site upon removal of the unit at 6 months. The patient underwent further surgical exploration and the cathode wires were removed from the bone fusion site. No subfascial infection was noted. A muscle flap was used to cover the surgical site and healing occurred without further incident. Local discomfort led 4 additional patients to have the device removed (2 patients at 6 months, 1 at 1 year, and 1 at 2 years), which was performed under local anesthesia with sedation. The lower aspect of the prior skin incision was opened and the generator was dissected free from surrounding scar tissue. The cathode leads were cut at the level of the fascia and the wound was closed.

DISCUSSION Cervical instability in the para-axial area can have devastating neurologic consequences, and in certain cases, nonunion is highly likely unless surgical intervention occurs.31,32 Posterior spinal fusion procedures are performed to obtain immediate biomechanical stability and to increase the likelihood of solid bony arthrodesis. Fusion procedures in the in C1-2 area, including those performed with instrumentation, have failure rates ranging from 3% to 50%.33-41 Successful fusion success depends both on the health and particular characteristics of the host and on the surgical techniques used. Some obstacles relating to the host, such as anatomic constraints, cannot be altered directly by the surgeon but can be overcome by proper surgical technique and immobilization.36,42,43 Other conditions involving the host that have been shown to reduce the likelihood of successful arthrodesis, such as a catabolic state or a history tobacco use, may be corrected by medical treatment and lifestyle adjustment.44

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Electrical stimulation has been studied for years as a method to mimic or enhance the biology of bone healing.45-63 Modern research into electrical stimulation began with Fukada and Yasuda when they observed the electrical potential produced by bone in response to mechanical forces.63,64 In their research, mechanical dynamic strain resulted in a negatively charged electrical potential on the side of the bone under compression. Hence, bone remodels itself to minimize the strain of compressive forces. The investigators hypothesized that negative potentials function as the body’s signal to initiate osteogenesis. Based on this hypothesis, Yasuda conducted an experiment in rabbits in which DC electrical stimulation of bone showed enhanced bone formation at the cathode.62,63 Bassett et al46 were the first to attempt a dose-response study with DC electrical stimulation. They noted a positive correlation between the magnitude of the osteogenic response and the amplitude of the current. Friedenberg et al,52 utilizing a constant current electronic circuit, found a dose-response relationship in the healing of transcortical drill holes in a rabbit femur exposed to current levels between 1 and 100 µA. In a later study, they observed a similar dose-response relationship in a rabbit model in which constant direct currents between 5 and 100 µA were introduced into the tibial medullary canal by an insulated 1-cm stainless steel bare wire cathode.53,54 Subsequent studies involving platinum cathodes have produced similar results.54 There have been many animal and cellular studies that have demonstrated that externally applied electric fields modify the cellular mechanisms involved in bone growth and repair.47,58,59,65-69 The effectiveness of electromagnetic fields in treating nonunion of the tibia was shown in dogs by Bassett.47 Beginning in the 1950s, the basic research in the use of electrical stimulation in clinical applications set the stage for the development of several types of medical devices used today to promote bone growth. Presently there are 4 distinct methods for delivering or inducing electrical current in tissue: (1) IDCBGS, (2) pulsing electromagnetic fields (PEMF), (3) capacitive coupled stimulation (CC), and (4) ultrasound. Of these, 3 are commercially available specifically for spinal fusion: IDCBGS, PEMF, and CC. IDCBGS was the modality chosen for this study because it does not depend on patient compliance to deliver its beneficial effect. The 10 µA produced by the generator exerts a 5- to 8-mm field of influence around each cathode.49 This field of influence is large enough to provide bone growth stimulation to the lateral masses, facet joints, and lamina of the cervical spine. When craniocervical fusion is necessary, the catheters are placed against occipital bone.70 Direct current implantable stimulators consist of a hermetically sealed generator that delivers a constant current of 20 µA to the fusion site for a minimum of 26 weeks through two 12-cm-long titanium cathodes. The mechanism by which DC stimulates osteogenesis at the fusion site includes electrophoresis (the attraction of charged proteins and growth factors), galvanotaxis (the movement of bone, cartilage, and endothelial cells), polarization of cell membrane (the voltage-gated channels initiating second messenger cascade), and faradic reactions (the formation of OH- and H2O2 at the cathode surface, reducing oxygen tension and slightly increasing pH).45 The electric field and the faradic products together and separately stimulate calcium uptake.48,50 An elevated pH is known to stimulate osteoblast bone formation and mineralization and inhibit osteoclast bone resorption; thus, new bone formation exceeds bone resorption, resulting in bone growth.50

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The physical size, configuration, and stimulation characteristics of the IDCBGS unit used in this study were appropriate for use in the cervical spine. The generator was sufficiently small to allow its placement in the subcutaneous space while producing minimum discomfort to the patient. The generator can be placed deeper in the neck tissues if the patient’s skin is too thin, prolonged cervical immobility with a rigid collar is required, or the device’s removal under local anesthesia is not anticipated. The cathode wires were of adequate length to provide coverage in the upper cervical spine and could have been shortened if necessary. The only complication directly attributable to the EBI unit was an infection at the generator site. Such infections, whether they occur in the lumbar spine or cervical spine, always necessitate the removal of the generator and the plastic coating on the proximal aspect of the cathodes. Although, the remaining titanium cathodes can be left in place if they are incorporated with the bone, this case suggests the prudent approach is to remove both the generator and the plastic-coated cathodes whenever infection occurs. Only 1 patient did not demonstrate complete, multilevel, osteosynthetic bone incorporation after undergoing the implantation surgery. The cause of this failure was likely due to a combination of technical errors (such as the failure to remove previous scar tissue or to replace internal instrumentation) and problems involving the host (such as poor bone healing or nutritional deficiency). The surgical technique for the placement of the IDCBGS in this pilot study was technically straightforward and resulted in a solid arthrodesis in 15 of the 16 patients evaluated. The use of the stimulator as an adjunct to instrument- or non–instrumentassisted surgical fusion of the para-axial region in these high-risk patients appeared to be both safe and efficacious. Further investigation is warranted to define the possible role and clinical utility of the IDCBGS in selected patients requiring cervical fusion, particularly those at high risk for nonunion.

ACKNOWLEDGMENTS William C. Welch, MD, FACS, is a consultant for EBI, L.P. The authors would like to thank Bruce Simon, PhD, and Steven M. Czop, RPh, for their review of the manuscript and useful comments. They would also like to thank Barbara Longo, RN, for retrieving the data and Pat Karausky, RN, for assistance in manuscript preparation.

REFERENCES 1. Dickman CA, Sonntag VKH. Surgical management of atlantoaxial nonunions. J Neurosurg. 1995; 83:248-253. 2. White AA, Panjabi MM. The clinical biomechanics of the occiptoatlantoaxial complex. Orthop Clin North Am. 1978;9:867-878. 3. Grob D, Crisco JJ, Panjabi MM, Wang P, Dvorak J. Biomechanical evaluation of four different posterior atlantoaxial fixation techniques. Spine. 1992;17:480-490. 4. Apostolides PJ, Dickman CA, Golfinos JG, Papadopoulos SM, Sonntag VKH. Threaded Steinmann pin fusion of the craniovertebral junction. Spine. 1996;21:1630-1637. 5. Bauman S, Welch W, Bloom M. Intraoperative SSEP detection of ulnar nerve compression or ischemia in an obese patient: a unique complication associated with a specialized spinal retraction system. Arch Phys Med Rehab. 2000;81:130-132.

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6. Ellis PM, Findlay JM. Craniocervical fusion with contoured Luque rod and autogenic bone graft. Can J Surg. 1994;37:50-54. 7. Fehlings MG, Errico T, Cooper P, Benjamin V, DiBartolo T. Occipitocervical fusion with a five-millimeter malleable rod and segmental fixation. Neurosurgery. 1993;32:198-207. 8. Pait TG, Al-Mefty O, Boop FA, Arnautovic KI, Rahman S, Ceola W. Inside-outside technique for posterior occiptocervical spine instrumentation and stabilization: preliminary results. J Neurosurg Spine. 1999;90:1-7. 9. Doyle JS, Lauerman WC, Wood KB, Krause DR. Complications and long-term outcome of upper cervical spine arthrodesis in patients with Down syndrome. Spine. 1996;21:1223-1231. 10. Dickman CA, Crawford NR, Paramore CG. Biomechanical characteristics of C1-2 cable fixations. J Neurosurg. 1996;85:316-322. 11. Dwyer AF. Direct current stimulation in spinal fusion. Med J Aust. 1974;1:73-75. 12. Dwyer AF. The use of electrical current stimulation in spinal fusion. Ortho Clin North Am. 1975;6:265. 13. Kane WJ. Direct current electrical bone growth stimulation for spinal fusion. Spine. 1988;13: 363-365. 14. Lee K. Clinical investigation of the spinal stim system, open-trial phase: pseudarthrosis stratum. Presented at: 56th Annual Meeting of the AAOS; Las Vegas, Nevada; February 9–14, 1989. 15. Mammi GI, Rocchi R. Effect of electromagnetic fields on spinal fusion: a prospective study with a control group. In: Blank M, ed. Electricity and Magnetism in Biology and Medicine. San Francisco, Calif: San Francisco Press Inc; 1993:800-802. 16. Mooney V. A randomized double-blind prospective study of the efficacy of pulsed electromagnetic fields for interbody lumbar fusions. Spine. 1990;15:708-712. 17. Savini R, DiSilvestre M, Gargiulo G, Bettini N. The use of pulsing electromagnetic fields in posterolateral lumbosacral spinal fusions. Journal of Electricity. 1990;9:9-17. 18. Simmons JW. Treatment of failed posterior lumbar interbody fusion (PLIF) of the spine with pulsing electromagnetic fields. Clin Orthop. 1985;183:127-132. 19. Simmons JW, Hayes MA, Christensen KD, Dwyer AP, Koulisis CW. The effect of post-operative pulsing electromagnetic fields on lumbar fusion: an open trial phase. Presented at: 4th Annual Meeting of the North American Spine Society, Quebec, Canada; June 29–July 2, 1989. 20. Grottkau B, Lipson SJ. A controlled pilot study to determine the effect of direct current (DC) stimulation on fusion mass in lumbar spine fusion patients. Presented at: 10th Annual Meeting of the North American Spine Society; Washington, DC; October 18–21, 1995. 21. Guizzardi S, DiSilvestre M, Govoni P, Scandroglio R. Pulsed electromagnetic field stimulation on posterior spinal fusions. J Spinal Disord. 1994;7:36-40. 22. Kant AP. An analysis of the effect of electrical stimulation as an adjunct to lumbar spinal fusion: a retrospective controlled study of implantable direct current stimulation in lumbar spine fusion. Presented at: 10th Annual Meeting of the North American Spine Society; Washington, DC; October 18–21, 1995. 23. Kucharzyk DW. A controlled prospective outcome study of implantable electrical stimulation with spinal instrumentation in a high-risk spinal fusion population. Spine. 1999;24:465–469. 24. Meril AJ. Direct current stimulation of allograft in anterior and posterior lumbar interbody fusions. Spine. 1994;19:2393-2398. 25. Pettine KA. A retrospective controlled study of implantable direct current stimulation in lumbar spinal fusion. Presented at: 10th Annual Meeting of the North American Spine Society; Washington, DC; October 18–21, 1995. 26. Rogozinski A, Rogozinski C. Efficacy of implanted bone growth stimulation in instrumented lumbosacral spine fusion. Spine. 1996;21:2479-2483.

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W. C. Welch et al Para-Axial Cervical Arthrodesis

27. Tejano NA, Puno R, Ignacio JMF. The use of implantable direct current stimulation in multilevel spinal fusion without instrumentation. A prospective clinical and radiographic evaluation with long-term follow-up. Spine. 1996;21:1904-1908. 28. Smith MD. Surgical management of cervical spondylotic myelopathy, part 2: posterior cervical fixation. In: Welch WC, Jacobs GB, Jackson RP, eds. Operative Spinal Surgery. Stamford, Conn: Appleton & Lange; 1999:142-152. 29. Moller AR. Preoperative and intraoperative neurophysiologic recordings. In: Welch WC, Jacobs GB, Jackson RP, eds. Operative Spine Surgery. Stamford, Conn: Appleton & Lange; 1999:78-95. 30. MacKenzie AI, Uttley D, Marsh HT, Bell BA. Craniocervical stabilization using Luque/Hartshill rectangles. Neurosurgery. 1990;26:32-36. 31. Greene KA, Dickman CA, Marciano FF, Drabier JB, Hadley MN, Sonntag VKH. Acute axis fractures: analysis of management and outcome in 340 consecutive cases. Spine. 1997;22:1843-1852. 32. Polin RS, Szabo T, Bogaev CA, Replogle RE, Jane JA. Nonoperative management of types II and III odontoid fractures: the Philadelphia collar versus the halo vest. Neurosurgery. 1996;38: 450-457. 33. Brooks AL, Jenkins EB. Atlantoaxial arthrodedesis by the wedge compression method. J Bone Joint Surg Am. 1978;60:279-284. 34. Griswold DM, Albright JA, Schiffman E, Johnson R, Southwick WO. Atlantoaxial fusion for instability. J Bone Joint Surg Am. 1978;60:285-292. 35. Holmes JC, Hall JE. Fusion for instability and potential instability in children and adolescents. Orthop Clin North Am. 1978;9:923-943. 36. Madawi AA, Casey ATH, Solanki GA, Tuite G, Veres R, Crockard HA. Radiological and anatomic evaluation of the atlantoaxial transarticular screw fixation technique. J Neurosurg. 1997;86: 961-968. 37. McGraw RW, Rusch RM. Atlanto-axial arthrodesis. J Bone Joint Surg Br. 1973;55:482-489. 38. Roy L, Gibson DA. Cervical spine fusions in children. Clin Orthop. 1970;73:146-151. 39. Sherk HH, Snyder B. Posterior fusions of the upper cervical spine. Indications, techniques and prognosis. Orthop Clin North Am. 1978;9:1091-1099. 40. Smith MD, Phillips WA, Hensinger RN. Complications of fusions to the upper cervical spine. Spine. 1991;16:702-705. 41. Stillerman CB, Wilson JA. Atlanto-axial stabilization with posterior transarticular screw fixation: technical description and report of 22 cases. Neurosurgery. 1993:32:948-955. 42. Coyne TJ, Fehlings MG, Wallace MC, Bernstein M, Tator CH. C1-2 posterior cervical fusion: long-term evaluation of results and efficacy. Neurosurgery. 1995;37:688-693. 43. Paramore CG, Dickman CA, Sonntag VKH. The anatomic suitability of the C1-2 complex for transarticular screw fixation. J Neurosurg. 1996;85:221-224. 44. Brown CW, Orme TJ, Richardson HD. The rate of pseudarthrosis (surgical nonunion) in patients who are smokers and patients who are non-smokers: a comparison study. Spine. 1986;11:942-943. 45. Baranowski TJ, Black J. The mechanism of faradic stimulation of osteogenesis. In: Blank M, Findl E, eds. Mechanistic Approaches to Interactions of Electric and Electromagnetic Fields with Living Systems. New York, NY: Plenum Press; 1987:399. 46. Bassett CAL, Pawluk RJ, Becker R. Effects of electric current on bone in vivo. Nature. 1964; 204:652. 47. Bassett CAL, Pawlik RJ, Pilla AA. Augmentation of bone repair by inductively coupled electromagnetic fields (PEMF). Science. 1974;184:575-577. 48. Black J, Baranowski TJ Jr, Brighton CT. Electrochemical aspects of DC stimulation of osteogenesis. Bioelectrochem Bioenerg. 1984;12:323.

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49. Black J, Brighton CT. Mechanisms of stimulation of osteogenesis by direct current. In: Brighton CT, Black J, Pollock SR, eds. Electrical Properties of Bone and Cartilage: Experimental Effects and Clinical Applications. New York, NY: Grune & Stratton; 1979:215. 50. Brighton CT, Adler S, Black J, Itada N, Friedenberg ZB. Cathodic oxygen consumption and electrically induced osteogenesis. Clin Orthop. 1975;107:277. 51. Brighton CT, Friedenberg ZB. Electrical stimulation and oxygen tension. Annals NY Acad Sci. 1974;238:314. 52. Brighton CT, Friedenberg ZB, Black J, Esterhai JL, Mitchel JE, Montique F. Electrically induced osteogenesis: relationship between charge, current density, and the amount of bone formed. Clin Orthop. 1981;161:122-132. 53. Friedenberg ZB, Andrews ET, Smolenski B, Perl BW, Brighton CT. Bone reactions to varying amounts of direct current. Surg Gyn Obstet. 1970;131:894. 54. Friedenberg ZB, Zemsky LM, Pollis RP, Brighton CT. The response of non-traumatized bone to direct current. J Bone Joint Surg. 1974;56A:1023. 55. Hotta SS. Electrical bone-growth stimulation and spinal fusion. Health Technology Review. Agency for Health Care Policy and Research, Office of Health Technology Assessment. January 1994:8. AHCPR Publication 94-0014. 56. Ito M, Fay Y, Edwards WT, Huan HA. The effect of pulsed electromagnetic fields on posterolateral fusions and device related osteopenia. Presented at: 21st Annual Meeting of the International Society for the Study of the Lumbar Spine; Seattle, Washington; June 21–25, 1994. 57. Kahanovitz N, Arnoczky S. The efficacy of direct current electrical stimulation to enhance canine spinal fusions. Clin Orthop. 1990;251:295-299. 58. Kahanovitz N, Arnoczky SP, Hulse D, Shires PK. The effect of postoperative electromagnetic pulsing on canine posterior spinal fusions. Spine. 1984;9:273-279. 59. Kahanovitz N, Arnoczky SP, Nemzek J, Shores A. The effect of electromagnetic pulsing on posterior lumbar spinal fusions in dogs. Spine. 1994;19:705-709. 60. Kahanovitz N, Pashos CL. The role of implantable direct current stimulation in the critical pathway for lumbar spinal fusion. Presented at: 11th Annual Meeting of the North American Spine Society; Vancouver, Canada; October 23–26, 1996. 61. Urban MA, Brighton CT and Black J. Dose response relationship for faradic stimulation of osteogenesis in the rabbit tibia by use of a single-strand platinum cathode. In: Brighton CT, Pollock SR, eds. Electromagnetics in Biology and Medicine. San Francisco, Calif: San Francisco Press Inc; 1991:199. 62. Yasuda I. Electrical callus and callus formation by electret. Clin Orthop. 1977;124:53-56. 63. Yasuda I, Noguchi K, Sata T. Dynamic callus and electric callus. J Bone Joint Surg. 1955;37A:1292. 64. Fukada E, Yasuda I. On the piezoelectric effect of bone. J Phy Soc Japan. 1957;12:1158. 65. Luben RA. Effects of low energy electromagnetic fields (EMF) on signal transduction by G protein-linked receptors. In: Blank M, ed. Electricity and Magnetism in Biology and Medicine. San Francisco, Calif: San Francisco Press Inc; 1993:57-62. 66. Nerubay J, Marganit B, Bubis J, Tadmor A, Katznelson A. Stimulation of bone formation by electrical current on spinal fusion. Spine. 1986;11:167-169. 67. Polk C. Electric and magnetic fields for bone and soft tissue repair. In: Polk C, Poston E, eds. Handbook of Biological Effects of Electromagnetic Fields. 2nd ed. New York, NY: CRC Press; 1996: 231-246. 68. Simon SR. Bone injury, regeneration, and repair. In: Simon SR, ed. Orthopedic Basic Science. Rosemont, Ill: American Academy of Orthopedic Surgeons; 1994:312-316. 69. Zichner L. Repair of nonunions by electrically pulsed current stimulation. Clin Orthop. 1981; 161:115-121. 70. Oishi M, Onesti ST. Electrical bone graft stimulation for spinal fusion: a review. Neurosurgery. 2000;47:1041-1056.

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