1 Development, in vitro and in vivo evaluation of a new artificial disc prosthesis (Kineflex/Centurion disc) and the relevant insertion instrumentation for the human lumbar spine Ulrich Reinhard H?hnle A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy Johannesburg, 1st November 2008 2 DECLARATION I, Ulrich H?hnle, declare that this thesis is my own work. It is being submitted for the degree of Doctor of Philosophy at the University of the Witwatersrand, Johannesburg. It has not been submitted before for any degree or examination at this or any other university. Ulrich H?hnle 27 October 2008 I certify that the studies contained in this thesis have the approval of the Human Research Ethics Committee of the University of the Witwatersrand, Johannesburg. Human Research Ethics Committee protocol number: Protocol M03-06-13 Investigator: Dr U.R. H?hnle Protocol M080557 Investigator: Dr U.R. H?hnle Hospital approval: Nedcare Linksfield Hospital, signed by the Hospital General Manager, B Bedford Dr Ulrich R. H?hnle (Candidate) 27 October 2008 Prof. Barry M.B.E. Sweet (Supervisor) 27 October 2008 Geoffrey P. Candy (PhD) (Co-supervisor) 27 October 2008 3 DEDICATION First of all I want to thank my wife, (Prof.) Karen Sliwa, for her emotional and professional support. Without her, I would not have started this project, never mind bring it to an end. Secondly, I want to thank my children, Lina and Julia, for being so understanding when their dad was working on the PC over many weekends and in the evenings. 4 PUBLICATIONS AND PRESENTATIONS ARISING FROM THIS STUDY NATIONAL + INTERNATIONAL PATENTS: 1. United States of America - Patent Application Number 60/473.802 - date of filing 27 May 2003 2. United States of America - Patent Application Number 60/473.803 - date of filing 27 May 2003 3. Intervertebral Prosthesis - PCT/IB03/01529 - filing date 24 April 2003 4. Intervertebral Prosthesis - PCT/IB03/00781 - filing date 3 March 2003 5. Arthroplasty Implant- 2002/7516- filing date 19 September 2002 6. Intervertebral Prosthesis Placement Instrument - 2003/0875 - filing date 31 January 2003 7. Spinal Midline Indicator - 2003/0874 - filing date 31 January 2003 8. Arthroplasty Implant - PCT/IB03/04051- filing date 19 September 2003 9. United States Patent ? Intervertebral Prosthetic Disc ? Patent Nr: 7,442,211 ? Date of Patent: 28 October 2008. 5 PUBLICATIONS: Peer reviewed: Ulrich R. H?hnle, Ian R. Weinberg, Karen Sliwa, Barry M.B.E. Sweet, Malan de Villiers. Kineflex (Centurion) lumbar disc prosthesis: Insertion technique and 2-year clinical results. SAS Journal, Winter 2007;1;28-35. DOI:SASJ-2006-0005-RR. Ulrich R. H?hnle, Karen Sliwa, Ian R. Weinberg, Barry M.B.E .Sweet, Malan de Villiers, Geoffrey P. Candy. Lumbar Disc Replacement for Junctional Decompensation After Fusion Surgery: Clinical and Radiological Outcome at an Average Follow-Up of 33 Months. SAS Journal, Summer 2007;1:85-92. DOI:SASJ- 2007-0006-RR. Ulrich R. H?hnle, Karen Sliwa, Malan de Villiers, Ian R. Weinberg, Barry M.B.E. Sweet, Geoffrey P. Candy. Is degenerative spondylolisthesis a contraindication for total disc replacement? Kineflex lumbar disc replacement in 7 patients with 24-month follow-up. SAS Journal, Spring 2008;2:92-100. DOI:SASJ-2007-0125-NT. Non-Peer reviewed: U.R. H?hnle. Unconstrained metal TDR device indicated for advanced DDD: Of 96 patients treated at a center in South Africa, 87.1% had good or excellent scores at one-year follow-up. Orthopaedics Today July 2005; 25:58. Book chapter: Ulrich R. H?hnle, Malan De Villiers, Ian R. Weinberg. Chapter 42: Kineflex, in Yue J.J., Bertagnoli .R, McAfee P.C. and An H.S. (eds): Motion Preservation Surgery of the Spine: Advanced techniques and controversies. Philadelphia, Elsevier 2008, pp 338-345. 6 PUBLISHED CONFERENCE PROCEEDINGS Congress presentations 2003: H?hnle UR, Weinberg IR and De Villiers M. A new articulated lumbar disc prosthesis. Spinal Arthroplasty Society 3 (SAS 3), Scottsdale Arizona, USA, May 1- 3, 2003. H?hnle UR and Weinberg IR Charit? Disc Prosthesis- short term follow-up. SA Spine Society Congress, Johannesburg, June 12-14, 2003. H?hnle UR and Weinberg IR. Lumbar disc prosthesis as salvage procedure for failed adjacent level surgery. SA Spine Society Congress, Johannesburg, June 12-14, 2003. H?hnle UR and Weinberg IR. Short-term results with a mechanical lumbar disc prosthesis. Spine across the Sea 2003, NASS + JSRS, Maui, Hawaii USA, July 27- 31, 2003. H?hnle UR and Weinberg IR. Charit? Disc Prosthesis- short term results. 49th SAOA Congress, Cape Town, September 1-5, 2003. H?hnle UR and Weinberg IR. Lumbar disc replacement as salvage procedure for failed posterolateral fusion surgery. 49th SAOA Congress, Cape Town, September 1- 5, 2003. H?hnle UR and Weinberg IR and De Villiers M. Centurion Disc ? a new mechanical lumbar disc prosthesis. 49th SAOA Congress, Cape Town, September 1-5, 2003. Poster. 7 Congress presentations 2004: H?hnle UR and Weinberg IR and De Villiers M. Short term results with the Centurion Lumbar Disc. Spinal Arthroplasty Society 4 (SAS 4), Vienna, Austria, May 3-5, 2004. H?hnle UR and Weinberg IR and De Villiers M. Charit? Disc Prosthesis- short term follow-up. Eurospine 2004, Porto, May 30- June 5 2004. Poster H?hnle UR and Weinberg IR and De Villiers M. One year follow-up on the Centurion Lumbar Disc Prosthesis. SA Spine Society Congress, Windhoek, June 17- 19, 2004. H?hnle UR and Weinberg IR. Lumbar disc replacement as salvage procedure for fusion surgery. SA Spine Society Congress, Windhoek, June 17-19, 2004. H?hnle U.R. and Weinberg, IR Charit? Disc Prosthesis- short intermediate term results. 50th SAOA Congress, Pretoria, September 6-10, 2004. Poster H?hnle UR and Weinberg IR. Lumbar disc replacement as salvage procedure for fusion surgery. 50th SAOA Congress, Pretoria, September 6-10, 2004. H?hnle UR and Weinberg IR and De Villiers M. Short term results with the Centurion Lumbar Disc. 50th SAOA Congress, Pretoria, September 6-10, 2004. Congress presentations 2005: H?hnle UR and Weinberg IR and De Villiers M. One to two year results with the Kineflex (Centurion) lumbar disc. Spinal Arthroplasty Society (SAS 5), New York, May 3-7, 2005. H?hnle UR and Weinberg IR. Lumbar disc replacement for junctional decompensation after fusion surgery. 116:World Spine III, Rio de Janeiro, Brazil, 31 July- 3 August 2005. 8 H?hnle UR and Weinberg IR and De Villiers M. One to two year results with the Kineflex (Centurion) lumbar disc prosthesis. P70: World Spine III, Rio de Janeiro, Brazil, 31 July- 3 August 2005. Congress presentations 2006: H?hnle UR, De Villiers M, Weinberg IR. Kineflex (Centurion) lumbar disc prosthesis: two year results. Spinal Arthroplasty Society (SAS 6), Montreal, Canada, May 9-13, 2006. H?hnle UR and Weinberg IR. Disc replacement after fusion surgery: correlation between clinical outcome and spinal/pelvic alignment. P036: Spinal Arthroplasty Society (SAS 6), Montreal, Canada, May 9-13, 2006. H?hnle UR and Weinberg IR. Disc replacement after fusion surgery. SA Spine Society Congress, Somerset West, South Africa, May 31- June 3, 2006. H?hnle UR, De Villiers M and Weinberg IR. Kineflex lumbar disc prosthesis: two year results. SA Spine Society Congress, Somerset West, South Africa, May 31- June 3, 2006. Congress presentations 2007: H?hnle UR, Sliwa K, Weinberg IR and Candy GP. Disc replacement after fusion surgery: Correlation between clinical outcome and spinal/pelvic alignment. Spinal Arthroplasty Society (SAS 7), Berlin, Germany, May 1-4, 2007 (Prize for best Poster Presentation). H?hnle UR, Weinberg IR, Sliwa K, Sweet MBE and De Villiers M. Kineflex (Centurion) lumbar disc prosthesis: Two year clinical results and radiological placement accuracy in 100 patients. Spinal Arthroplasty Society (SAS 7), Berlin, Germany, May 1-4, 2007. 9 H?hnle UR, Weinberg IR and Candy GP. Juxta-fusional lumbar disc replacement: Correlation between clinical outcome and Spinal/Pelvic alignment. SA Spine Society Congress, Durban, South Africa, June 7-9, 2007. H?hnle UR, De Villiers M, Weinberg IR and Candy GP. Kineflex lumbar disc prosthesis: Two year clinical results and radiological placement accuracy in 100 patients. SA Spine Society Congress, Durban, South Africa, June 7-9, 2007. H?hnle UR, Weinberg IR and Candy GP Disc replacement pos lumbar fusion surgery: Correlation between clinical outcome and Spinal/Pelvic alignment. P18. World Spine IV, Istanbul, Turkey, 29 July- 1 August 2007. H?hnle UR, De Villiers M, Weinberg IR and Candy GP. Kineflex lumbar disc prosthesis: Two year clinical results and radiological placement accuracy in 100 patients. 83. World Spine IV, Istanbul, Turkey, 29 July- 1 August 2007. H?hnle UR, Weinberg IR, Sliwa K and Candy GP. Juxta-fusional lumbar disc replacement: Correlation between clinical outcome and Spinal/Pelvic alignment. 61. Eurospine, Brussels, Belgium, October 3-6 2007. H?hnle UR, Weinberg IR, Sliwa K, Sweet MBE. and De Villiers M. Kineflex lumbar disc prosthesis: Two year clinical results and radiological placement accuracy in 100 patients. 62. Eurospine, Brussels, Belgium, October 3-6 2007. Congress presentations 2008: H?hnle UR, Sliwa K, Weinberg IR and De Villiers M. Kineflex Cervical Disc Prosthesis: Disc development, clinical and radiological results at 27 months follow up. P119 Spinal Arthroplasty Society (SAS 8), Miami, USA, May 6-9, 2008. H?hnle UR, Sliwa K, Weinberg IR, De Villiers M and Candy GP. Is degenerative spondylolisthesis a contra-indication for total disc replacement? Kineflex Lumbar Disc in seven patients with 24 months follow up. P62 Spinal Arthroplasty Society (SAS 8), Miami, USA, May 6-9, 2008. 10 ABSTRACT Background: Lumbar disc replacement is a rapidly expanding surgical treatment modality for long- standing back and leg pain due to intervertebral disc degeneration. Compared to fusion surgery, it has the advantage of preserving segmental mobility, but convincing evidence of superiority over fusion surgery is missing. As part of this research project, I participated in the development of a new intervertebral disc prosthesis, with several international patents attached to the design of the prosthesis, the instrumentation and the insertion technique. The Kineflex (Centurion) lumbar disc is a mechanical, un-constrained, re-centering disc prosthesis developed in South Africa. After the development and manufacturing of the disc, prototype test racks were custom-made at the premises of the manufacturer and the disc was extensively tested for mechanical wear and fatigue. The first implantation took place in October 2002. I prospectively captured all cases performed by our centre, with documentation including demographic data, co-morbidities, clinical history, symptoms and signs. The completed consent forms were filed. The outcome was monitored, pre-operatively and in follow-up, with complete radiological documentation of all radiographs on JPEG files. Clinical outcome results were documented using two different internationally validated questionnaires as well as our own questionnaire, which expands further on work and demographic details, previous operative and conservative treatment, and satisfaction with the treatment outcome. The aim of the this project was to develop a disc prosthesis that is suitable and safe for human implantation into the lumbar spine disc space, even in severely advanced disc degeneration and to verify this in the outcome studies presented in this thesis. Existing indications and contra-indications for artificial disc replacement were critically evaluated regarding their validity for this particular implant. Results: Chapter 3 elaborates on the extensive pre-clinical mechanical wear and fatigue testing protocol to which the Centurion (Kineflex) lumbar disc prosthesis was 11 subjected. The results of this testing protocol, together with our early clinical outcome results, formed the basis for the awarding of the European quality recognition (CE-Mark). In these extensive in vitro studies, we were able to show the durability of the Kineflex disc prosthesis in the long term. This, together with our initial clinical outcome results, formed the basis for the acceptance into a ?prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the KINEFLEX Lumbar Artificial Disc versus the CHARIT?? Artificial Disc?. Chapter 4 is compiled from an invited submission to a new book on motion preservation surgery in the human spine, edited by leading spine surgeons in the field (James J. Yue, Rudolf Bertagnoli, Paul McAfee, and Howard An) and published by Elsevier Publishers: Chapter 42: Kineflex. In this chapter, an overview is given of the ideas behind the Kineflex disc development, as well as of the insertion instrumentation used for disc implantation. It further reports on early clinical outcome results of the first patients implanted with the device in our centre (the first 40 implantations worldwide were all performed by me). Chapter 5, our first peer reviewed international publication, reports on clinical and radiological 2-year outcome results of our first 100 patients. With the Kineflex implant, we could demonstrate equally good radiological placement accuracy in patients with severe and less severe disc degeneration of the index level, rendering the implant suitable even in severe degeneration of a spinal motion segment. Chapter 6 and Chapter 7 of this thesis consist of two further peer-reviewed publications. They both report on so-called ?off-label? patient sub-groups in our disc replacement series. In Chapter 6 we present the second published series on a larger group of patients presenting with adjacent segment disease after previous lumbar fusion surgery as well as the first publication, which investigated the radiological changes in alignment parameters secondary to the disc replacement surgery in this patient group. 12 Chapter 7 consists of the first published series on patients with ?degenerative spondylolisthesis? treated with disc replacement surgery. A detailed description of the operative reduction technique is provided, which is unique to the Kineflex disc and its insertion instrumentation. In this pilot study, two-year results on a limited patient group are presented. This thesis concludes with the overall discussion in Chapter 8. It outlines the current knowledge on artificial disc replacement and places my results into perspective with recent discoveries published in the literature. It finishes with my assessment of what future research should concentrate on. 13 ACKNOWLEDGEMENTS My sincere gratitude is extended to the following people: ? The patients at the Nedcare Linksfield Hospital, for their confidence and compliance. ? My supervisor, Prof. Barry Sweet, for his unconditional support during a very difficult time of his life. ? My supervisor, Dr Geoffrey Candy for his guidance and encouragement and for his help with statistical analysis. ? My colleague, Dr Ian Weinberg, co-developer of the Kineflex disc, for his positive spirit even during endless hours in theatre during some of the complex procedures, his input into the project and his help in patient care and management. ? Dr Malan De Villiers, co-developer and manufacturer of the Kineflex disc, chief engineer and CEO of Southern Medical for his professional collaboration and his input into this thesis, especially with regard to Chapter 3, which comprises the material studies of the Kineflex prosthesis. ? Our anaesthetists, Dr Mike Hachet and Dr Lesley Kolling, for their brilliant work with patient care and for being extremely accommodating when I went away to congresses or on holiday while they stayed behind without a theatre list. And it goes without saying, for adjusting the lights and tables and patiently answering the cell phones. ? Aldorin Gehring, our matron and the soul of the theatre complex, for her enthusiastic commitment to the running of the hospital. With her positive attitude, she kept staff motivated and the operating theatres running during what were often quite difficult circumstances. ? Stephanie Hanekom, for her friendly perseverance in encouraging patients to appear for their follow-ups. I?m grateful for her commitment to the running of our (Dr Weinberg and my) practice. ? Shaun Higgins and Ryan Voster, for their excellent assistance with surgery and servicing of equipment. They certainly have the greatest surgical experience with the Kineflex disc prosthesis. 14 ? Cindy Swart, for her help and enthusiasm in the pioneering phase of the Kineflex/Centurion disc implantation. ? The ward sisters in Ward G, especially Linda Pretorius and Sarah Modikane, for their dedication to patient care, their constant endaevour to help the patients on the front line and to assist the doctors in doing their work. ? Dr. Demetri (Jimmy) Revelas, vascular surgeon at Nedcare Linksfield Hospital, for his expert help with difficult approaches and in emergency situations. Without him I could not conscientiously have performed the surgical procedures. ? The doctors and staff of the radiology department at Nedcare Linksfield Hospital, for their help in patient care and diagnosis by means of image-guided interventions and for producing good quality radiographs. ? Barbara Speyer for her efforts to save our patient?s own blood. ? David Hovda, CEO of Spinal Motion, for his continuous efforts in the development and marketing of the Kineflex disc. ? The staff of our High Care Unit, for their excellent post-operative patient care. ? David Bedford, the Nedcare Linksfield Hospital administration, and the Nedcare Head Office for the help with Hospital approval of the research. ? Tania Van Leeve for her help with the registration and submission of the PhD. 15 TABLE OF CONTENTS Page No TITLE PAGE 1 CANDIDATE?S DECLARATION 2 DEDICATION 3 PUBLICATIONS AND PRESENTATIONS 4 PUBLISHED CONFERENCE PROCEEDINGS 6 ABSTRACT 10 ACKNOWLEDGEMENTS 13 TABLE OF CONTENTS 15 LIST OF FIGURES 19 LIST OF TABLES 20 NOMENCLATURE 21 1. INTRODUCTION AND LITERATURE REVIEW: 22 SURGERY FOR LOW BACK PAIN 1.1. Aetiology and treatment for low back pain 22 1.1.1. Epidemiology and social impact of low back pain 22 1.1.2. Aetiology of low back pain 23 1.1.3. Benefits of fusion surgery 25 1.1.4. Long term problems with lumbar fusion 26 1.1.4.1. Adjacent Segment Degeneration (ASD) 26 1.1.4.2. Sagittal imbalance 28 1.1.5. Summary on fusion surgery 29 1.2. Development of the Kineflex disc prosthesis 30 1.2.1. History of spinal disc replacement 30 1.2.2. Indications for lumbar disc replacement 31 1.2.3. Development of the Kineflex disc prosthesis 33 1.3. Framework for how the various chapters of the thesis contribute to the overall integrated argument of the thesis 39 1.4. References: Introduction 42 16 2. METHODS 47 2.1. Study objectives 47 2.2. Informed consent 48 2.3. Clinical study design and patient enrolment 49 2.3.1. Recruitment of patients and therapeutic work-up 49 2.3.2. Inclusion criteria 50 2.3.3. Exclusion criteria 50 2.3.4. Study visits 50 2.3.5. Clinical outcome measures 50 2.3.6. Radiological examination 51 2.3.7. Surgery 52 2.3.8. Post-operative mobilization 53 2.4. References: Methods 54 3. RESULTS: PRE-CLINICAL TESTING OF THE KINEFLEX 55 LUMBAR DISC PROSTHESIS 3.1. Kineflex M lumbar intervertebral disc prosthesis: Development 55 of wear protocol and protocol for static compression testing 3.1.1. Description of the Kineflex M intervertebral lumbar disc 55 prosthesis: Development of in vitro test protocol 3.1.2. Rationale of load condition imposed for wear studies: 56 Flexion/Extension, Lateral Bending and Rotation 3.1.3. Rationale of loading cycles imposed: wear test 56 3.1.4. Rationale of articulating limits imposed: Flexion/Extension, Lateral bending and Rotation 57 3.1.5. Rationale for the analysis of testing 58 3.2. Methods: Kineflex Disc: Set-up of wear and compression testing 59 3.2.1. Test bench set-up ? wear testing (gait simulator) 59 3.2.2. Test criteria ? wear testing 62 3.2.2.1. Pre-test set-up 62 3.2.2.2. Gait simulation wear test set-up 62 3.2.2.3. Test 64 3.2.2.4. Test result assessment 64 3.2.3. Static tests 65 17 3.2.3.1. Normal load 65 3.2.3.2. Shear load 65 3.2.4. Rationale for mono-axial fatigue tests 66 3.2.5. Torsion test 67 3.3. Results of accelerated wear test 67 3.3.1. Wear test protocol 67 3.3.2. Description of the test equipment 67 3.3.3. Weight verification 69 3.3.4. Results of wear testing 69 3.3.5. Discussion of wear test results 73 3.4. Result of static compression testing 75 3.4.1. Introduction 75 3.4.2. Rationale of load condition imposed 76 3.4.3. Test bench set-up 77 3.4.4. Test results 79 3.4.5. Discussion 81 3.4.6. Conclusion 81 3.5. References: Pre-clinical testing 82 4. RESULTS: BOOK CHAPTER (ELSEVIER): Motion Preservation Surgery of the Spine: Advanced Techniques and Controversies: CHAPTER 42: KINEFLEX 84 4.1. Introduction 84 4.2. Book Chapter 85 5. RESULTS: FIRST PUBLICATION Kineflex (Centurion) lumbar disc prosthesis: Insertion technique and two year clinical result in 100 patients. SAS Journal. Winter 2007;1:28?35. DOI: SASJ-2006-0005-RR. 93 5.1. Introduction 94 5.2. First publication 94 6. RESULTS: SECOND PUBLICATION Lumbar Disc Replacement for Junctional Decompensation 18 After Fusion Surgery: Clinical and Radiological Outcome at an Average Follow-Up of 33 Months. SAS Journal. Summer 2007; 1:85?92. DOI: SASJ-2007-0006-RR. 103 6.1. Introduction 103 6.2. Second publication 104 7. RESULTS: THIRD PUBLICATION Is Degenerative Spondylolisthesis a Contraindication for Total Disc Replacement? Kineflex Lumbar Disc Replacement in 7 Patients With 24-Month Follow-up. SAS Journal. Spring 2008; 2:92?100. DOI: SASJ-2007-0125-NT 112 7.1. Introduction 112 7.2. Third publication 113 8. OVERALL DISCUSSION 123 8.1. Motion preservation surgery history 123 8.2. Motion preservation surgery - what?s different in the spine? 124 8.3. Disc arthroplasty ? what do we know? 125 8.4. Disc arthroplasty ? the way forward 128 8.5. Summary of this research project 130 8.6. References: Overall discussion 131 9. APPENDIX 135 9.1. Ethical clearance 135 9.2. Questionaires 137 9.2.1. VAS 137 9.2.2. ODI 138 9.2.3. Own questionnaire: Pre-Op 139 9.2.4. Own questionnaire: Post-Op 142 9.3. Lumbar disc prosthesis- Patient consent 144 10. REFERENCE LIST- COMPLETE 147 19 LIST OF FIGURES Page No Figure 1.2.3 a-c: Illustration of Kineflex core motion 34-35 Figure 3.2.1.a-c: Spinal wear load simulation 60-61 Figure 3.2.2: Gait simulation wear test ? set-up 63 Figure 3.2.2.1: Compressive fatigue test 66 Figure 3.2.2.2: Shear fatigue test 66 Figure 3.3.2: Lumbar Spinal Fatigue Simulator Illustration 68 Figure 3.3.5.a: Cumulative mass loss in mg of core when subjected to 1200N loading 73 Figure 3.3.5.b: Cumulative mass loss in mg of disc prosthesis when subjected to 1200N loading 74 Figure 3.4.3.a: Test 2- Compressive load: Assembled prosthesis in the Instron machine 3.4.3.a: Schematic 77 3.4.3.a: Picture 77 Figure 3.4.3.b: Test 2- Shear load: Assembled prosthesis in the Instron machine at 100 3.4.3.b: Schematic 78 3.4.3.b: Picture 78 Figure 3.4.4.a: Load vs displacement for CCM disc and CCM core 79 Figure 3.4.4.b: Load vs displacement for CCM and CCM core at 10? 80 20 LIST OF TABLES Page No Table 1.2.2: Inclusion and exclusion criteria of lumbar TDR 32 Table 1.2.3: Limitations of available mechanical disc implants 37-38 Table 3.1.4: Summary of combined segmental motion (ROM) during gait 58 Tables 3.3.4.a-k Results of accelerated wear testing 69-72 21 NOMENCLATURE ALIF Anterior Lumbar Interbody Fusion ASD Adjacent Segment Disease ASTM American Standard for Testing and Material CCM Cobalt Chrome Molybdenum CE Conformit Europeane DDD Degenerative Disc Disease DHR Disc Height Reduction DPQ Dallas Pain Questionnaire DSPL Degenerative Spondylolisthesis FDA Food and Drug Administration FSU Functional Spinal Unit HREC Human Research Ethics Committee Kineflex Disc Centurion Disc KPD Kineflex Prosthetic Disc LBP Low Back Pain LL Lumbar Lordosis MRI Magnetic Resonance Investigation ODI Oswestry Disability Index OT Osteotomy PI Pelvic Incidence PLIF Posterior Lumbar Interbody Fusion PT Pelvic Tilt ROM Range Of Motion SF 36 Quality of life score SMS Spinal Motion Segment SLL Segmental Lumbar Lordosis SS Sacral Slope = Sacral Tilt (ST) ST Sacral Tilt = Sacral Slope (SS) TDR Total Disc Prosthesis TDP Total Disc Replacement TLIF Transforaminal Lumbar Interbody Fusion VAS Visualized Analog Score 22 1. INTRODUCTION AND LITERATURE REVIEW: SURGERY FOR LOW BACK PAIN 1.1. Aetiology and treatment of low back pain 1.1.1. Epidemiology and social impact of low back pain During their lifetime, 70 - 85% of people have back pain at some stage. Low Back Pain (LBP) is the major cause for absenteeism from work in western societies. In Sweden, 11 - 19% of all annual sickness leave is taken by people with back pain. In the USA, back pain is the most common cause of activity limitation in people younger than 45 years, the second most frequent reason for visits to a physician, the fifth ranking cause for admission to hospital, and the third most common cause for surgical procedures. About 2% of the US workforce is compensated for back pain each year (Andersson, et al., 1999). Sixty to seventy percent of back pain patients recover by six weeks and 80 - 90 % by 12 weeks. Recovery after 12 weeks is slow and uncertain. Fewer than half of those individuals disabled for longer than six months return to work; after two years of absence from work, the return-to-work ratio is close to zero. Compensation has a negative influence on the length of disability. Patients with lumbar sprains and strains recover within 14.9 months from injuries that occur on-duty, but within 3.6 months from injuries that happen off-duty. Patients, who had an operation, returned to work at 9.3 and 4.4 months respectively (Andersson, et al., 1999). A recent systematic review on LBP costs in different reported data from Australia, Belgium, Japan, Korea, the Netherlands, Sweden, the UK and the United States (Dagenais, et al. 20082) showed that the largest portion of direct medical cost was spent on physical therapy and in-patient services, followed by pharmacy and primary care. The yearly per capita cost of LBP is substantial in these countries (Australia - 474 AUD; Netherlands - 399 Euro; Sweden - 381 Euro; UK - 209 Pounds; US - 335 USD) (only direct costs), but the separation into direct and indirect costs varied widely between studies and countries. In 1998, the direct health care expenditure in 23 the United States for individuals with back pain was estimated to be over 90 billion US $ (Luo, et al. 20043). 1.1.2. Aetiology of low back pain The cause and therefore the treatment of ?mechanical? low back pain remains unsolved, despite almost a century of endeavour. It is now generally accepted that some kind of failure of the intervertebral disc is central to causation (Mulholland RC, 20084). In 1950, Barr suggested in a review article that backache was often associated with mechanical instability of a degenerative disk lesion (Barr JS, 19505). In 1954, Harris and MacNab fully addressed the central role of the disc in causing low back pain and sciatica. Although the term instability was used in the paper, it did not suggest that excessive movement is present - indeed translational movement is deemed to be unusual. The term ?unstable? was used to indicate a disc whose movement was irregular (Harris & McNab, 1954). In 1964, Harmon (1964) described the clinical triad of spinal instability including: low back, gluteal and thigh pain as follows: ?Spinal instability refers to a low back- gluteal-thigh clinical triad of symptoms that may be accompanied (overt cases) by incapacitating regional weakness and pain. This was the effect of disc degeneration with or without disc hernia. Some could be asymptomatic or slightly symptomatic when instability was compensated by muscle and ligament control. It does not refer to spinous process or laminal hypermobility, which some surgeons like to demonstrate on the operating table; nor does this clinical concept parallel the common spinal hypermobility, which was the product of spinal intervertebral disc degeneration, demonstrable in flexion-extension filming of the region, since the anatomic hypermobility is not always productive of symptoms.? Influenced by the increasing influence of basic science and mechanical engineering, Pope and Panjabi developed a biomechanical concept of spinal instability developing as a consequence of failure of spinal restraining structures resulting in a loss of 24 stiffness (Pope & Panjabi, 19858). Panjabi later concluded that increased movement was not necessarily a feature of what he termed instability, but a reduction of the neutral zone was (Panjabi MM, 19929). However, in a more recent paper, he has abandoned the concept of instability altogether and ascribes chronic back pain as being caused by ligamentous sub-failure injuries leading to muscle control dysfunction (Panjabi MM, 200610). The term instability is still widely used in degenerative disc disorders, indicating the fact that disc degeneration leads to decreased, rather than increased movement, as the term instability would imply. Despite the introduction of pedicle screw into fusion surgery, with significantly increased rigidity and decreased non-union rates, clinical results of fusion surgery in low back pain has not improved. It was well recognized that clinical success was unrelated to the success of the fusion. Pseudarthrosis was as common in successful patients as it was in those who had failed (Mulholland RC, 20084). In his review article, Mulholland (20084) further elaborates on the mechanism by which pain was generated in the intervertebral disc. He mentions that although there was no correlation between the degree of degeneration and the severity of back pain, it was well recognized that changes in the disc play a major role in low back pain. The disc has two biomechanical roles: it must transmit load and it must allow a controlled range of movement, so that such movement does not compromise the adjacent neural elements. The normal disc behaves like a fluid filled bag and transmits load uniformly across the surface of the disc and to the end-plate. In any position of the spine, load is transmitted uniformly over the end-plates. In any diathrodial joint (hip, knee, etc.), high spot loading is avoided by the design of a joint that guarantees an even pattern of load transmission. Disturbance of the anatomy of the joint, such as meniscectomy in the knee, or destruction of the cartilage by disease (arthritis, infection) in other joints, leads to disturbance in normal weight transmission, and produces pain. An appropriately planned osteotomy, which alters the weight transmission, might result in pain relief. If we accept that in load- 25 bearing joints overall an altered load bearing pattern produces pain, then we can more easily accept that this concept also applies to the disc. This load transfer is to the underlying vertebra. The vertebrae are well innervated and sensitive to excessive pressure. Another important consequence of the uniformity of distribution of load transmission across the surface of the disc is that it transmits load to the annulus, producing a tension in the annulus and converting it into a load bearing structure. It is established that disc degeneration alters the isotropic nature of the disc and, as a consequence, load transmission over the end-plates becomes irregular, leading to high spot-loading, particularly when associated with certain positions (Mulholland RC, 20084). In the 1990s, Mcnally et al (1992 & 1996) developed a technique of performing a profilometry immediately before routine discography on all patients undergoing fusion surgery. They could demonstrate that discs with missing nuclear support (annular loading) or discs with very focal areas of high load were the painful discs. (Mcnally & Adams, 199211; Mcnally, et al.199612). 1.1.3. Benefits of fusion surgery Spinal fusion as a treatment for back pain was in vogue from the beginning of the last century, with little thought given to what the source of the pain might be. None of the papers dealing with fusion mention abnormal movement (instability) as a cause of pain until the nineteen-fifties (Mulholland RC, 20084). Fusion surgery has been accepted as the ?Golden Standard? for treatment of disabling low back pain, but scientific evidence to support this is still scarce. Spinal fusion emerged early in the last century as a means of dealing with spinal infection, later being extended to fractures and tumors, and then to cases of spinal deformity. The intention was to restore segmental stability and spinal alignment. Spinal fusion for degenerative disease is a more recent extension of the indication. Nonetheless, it is one that became established by default and in the absence of any viable alternative. One might argue that if ethics approval for this procedure were sought now, this would be unlikely to be forthcoming (Turner, et al. 199213). 26 Recuperation is lengthy and slow, and return to work is considerably delayed. The posterior approach to the spine inevitably causes damage to the paravertebral muscles, which are so important for subsequent functional recovery. Harvesting autologous bone from the pelvis, for which there is no scientifically proven, satisfactory substitute, can cause chronic donor site pain. The reported incidence of these complications varies (Boeree, N. 200714). Two randomized studies have failed to detect a definite, significant advantage of spinal fusion surgery over state of the art, conservative treatment, including aggressive exercise and cognitive therapy. (Brox, et al. 200315) (Fairbank, et al. 200516). Nevertheless, both studies suffered from severe limitations. The follow-up was short, being one and two years respectively. The first study had only 64 patients randomized to the two groups. In the Fairbank study, the crossover of 28%, from the ?Intensive Rehabilitation Group? to the Spinal Stabilisation Group, was unacceptably high. Recently, Anderson et al (200817) published a long term follow up (11-13 years) of patients who originally had been randomised to two groups: one had undergone uninstrumented posterolateral fusion, the other had undergone instrumented posterolateral fusion with pedicle screw instrumentation. They managed to follow-up results on 83% (107 patients) of their original study cohort. Patients maintained significant improvement in Dallas Pain Questionnaire (DPQ), Oswestry Disability Index (ODI) and SF36 - quality of life score. About 70% of patients in both groups answered positively to the global outcome question. This was despite a high percentage of patients having undergone previous decompression surgery. Furthermore, there was no significant difference between the two groups (Andersen, et al. 200817). 1.1.4. Long term problems with lumbar fusion 1.1.4.1. Adjacent Segment Degeneration (ASD) ASD means the degeneration of the intervertebral disc next to a spinal fusion. It was first described in the 1950s, but it was only in the 1980s and 1990s that it became a major consideration (Leong, et al 198318; Lehmann, et al. 198719; Penta, et al. 199520; 27 Hambly, et al 199821; Kumar, et al. 2001a22; Gillet, et al. 200323; Park, et al. 200424). With the increase in fusion surgery, surgeons realized that ASD might pose a serious problem in the long term. Lehmann (Lehmann, et al. 198719) presented a cohort of 62 patients with an average follow-up of 33 years after a posterior lumbar fusion. Fifteen percent had undergone repeat lumbar surgery, 42% had spinal stenosis, and segmental instability was present in 45%. In many patients, the ASD was not clinically symptomatic. Kumar et al. published a matched control study in 2001 with patients undergoing surgery for DDD; one group with fusion, the other without fusion. At 30 years mean follow up, using validated outcome questionnaires, they found similar clinical outcomes in patients in the two groups (fusion group and non-fusion group), despite an incidence of ASD twice as high in the fusion group as in the non-fusion group (Kumar, et al. 2001a22). In a literature review of 22 retrospective studies on ASD after lumbar spinal fusion, Park et al. (2004) detected a wide range of radiolocical ASD reported (5 - 100%). In contrast, the reported incidence of symptomatic ASD is only 5 - 19%). Suggested risk factors for ASD were: instrumentation, fusion length, sagittal mal-alignment, facet injury during surgery, age and pre-existing degenerative changes. (Park, et al. 200424) In two studies, the patients were treated with Anterior Lumbar Interbody Fusion (ALIF) surgery (Leong, et al. 198318; Penta, et al. 199520). At 13 and 10 years post- operatively, the fusion rate was 55% and 84% and ASD was present in 52% and 32% of patients, respectively, with no difference in single and multiple level fusions. No cases of impotence occurred in Leong?s study and non-union did not jeopardize the clinical outcome (Leong, et al. 198318). Nevertheless, spinal stenosis at the adjacent level was rare (Penta, et al. 199520). Schulte et al., after an almost 10 year follow-up, re-examined a group of 40 patients who had undergone a 360 degree fusion (2/3 for Degenerative Disc Disease (DDD) - Group 1); 1/3 for lytic spondylolisthesis - Group 2). Clinical outcome showed an improvement of 44.6% in ODI and 43.8% in VAS, with a tendency towards better 28 results in Group 2. Fusion rate was 95%. Disc height of the first cephalad adjacent segment in all patients was reduced by an average 20% (second cephalad level 15%). A tendency towards more Disc Height Reduction (DHR) in the degenerative group was observed. Advanced age correlated with advanced DHR. Multiple-level fusion led to a more pronounced DHR than 1-level fusion. There was no correlation between the clinical outcome and DHR (Schulte TJ, et al. 200725). Jun Young Yang (2008) determined the impact of ASD on clinical outcome in patients who had undergone 1, 2 or 3 level posterolateral fusion for degenerative spondylolisthesis, spinal stenosis or degenerative lumbar kyphoscoliosis. He graded ASD according to the UCLA grading scale for intervertebral disc degeneration. After short follow-up they found that ASD is more severe in multi-level fusion surgery and clinical outcome deteriorated with the severity of change in ASD (Yang JY, et al. 200826). 1.1.4.2. Sagittal imbalance There is increasing evidence that loss of lumbar lordosis or sagittal imbalance are contributing factors in the development of low back pain (Lazennec, et al. 200027; Kumar, et al. 2001b28; Jang, et al. 200729; Soegaard, et al. 200730); but it was only recently that Roussouly presented a classification of sagittal lumbar alignment (Roussouly, et al. 200531). TDR, as the ALIF procedure, by restoration of anterior disc height, more than posterolateral fusion, has a stronger potential than posterolateral fusion procedures to normalise sagittal imbalance through a single approach (H?hnle, et al. 200732). 29 1.1.5. Summary on fusion surgery Whereas a successful fusion reliably protects the neural structures at the fused levels and abolishes the pain originating from abnormal motion at that particular FSU, there are considerable drawbacks associated with fusion, viz.: ? By abolishing motion in one FSU, the other lumbar FSUs have to compensate for the loss of motion, leading to ASD. ? An inadequate restoration of the sagittal spinal balance during fusion surgery may promote the early onset of ASD. ? Posterior fusion surgery, unless performed in conjunction with posterior OT surgery, has a limited potential of treating the flat back deformity that is often associated with DDD. ? Posterolateral fusion surgery causes significant damage to the spinal muscles and it carries considerable risk of developing non-union. ? Posterior spinal fusion surgery has the potential for spinal nerve root injury. This risk increases in cases where extensive recess decompression is required or when instrumentation is added. ? Anterior fusion surgery is very powerful in restoring lumbar lordosis. The non- union rate is considerable, especially in multilevel anterior fusion surgery. ? Combined anterior and posterior fusion surgery can achieve good spinal balance with high fusion rates, but it is large surgery, with the combination of risks for complications resulting from the anterior and posterior surgery. Therefore, the potential short and long term morbidity arising from fusion surgery is significant and other treatment modalities will need to be explored. It is due to this associated morbidity, that motion preserving spinal surgery is currently experiencing a revival. 30 1.2. Development of the Kineflex disc prosthesis 1.2.1. History of spinal disc replacement As described earlier, adjacent level degeneration is a major concern in lumbar fusion operations (Lehman, et al. 198719; Lazennec, et al. 200029; Kumar, et al. 2000a22; Gillet P, 200323; Park, et al. 2004). Artificial lumbar discs are an alternative to arthrodesis. The purpose of Total Disc Replacement (TDR) is to restore the intervertebral segment and protect the adjacent levels against non-physiological loading conditions. The first description of surgical insertion of a lumbar prosthetic nucleus replacement, using a steel ball, was published by Fernstr?m (Fernstr?m U, 196633). It failed clinically, essentially because of subsidence of the implant into the bony end-plate. Modern types of total lumbar disc replacement commenced in 1984 with the insertion of the first generation Charit? disc prosthesis (Charit? SB I) developed by B?ttner-Janz and Schnellnack (B?ttner-Janz, et al. 198734). The ingenious ?sliding core? articular mechanism of this device was interposed between two bottle-cap shaped disc end-plates. The first results on 16 patients were published in 1987 (B?ttner-Janz, et al. 198734; B?ttner-Janz & Schnellnack, 199035). The subsidence at the bone end-plate interface led to the second (Charit? SB II) and third (Charit? SB III) generation articulated lumbar disc prosthesis. The second generation disc had wings added to increase the bearing surface and avoid subsidence into the bony end-plate. Breakage through these wings and subsidence still occurred in this model (Charit? SB I). The mechanism of the prosthesis was carried through to the third generation device that is still being used today (Charit? SB III: De Puy, Raynham. Mass, US). This third generation disc has been used since 1987 and intermediate and long term results are available (Griffith, et al. 199436; David, 199937; Lemaire, et al. 200538). Final (two year) results of randomized FDA (Food and Drug Administration) trials in North America have been published (Blumenthal, et al. 200539; McAfee, et al.200540). Subsequently, more constrained lumbar disc prostheses were developed. One of these prostheses was recently approved (Prodisc: Synthes, West Chester, PA, US) and others are currently being evaluated in FDA studies, (Maverick disc: Medtronic, Memphis, Tenn, US; Flexicore disc: Stryker Spine, Allendale, New Yersey). The only other disc with long term follow up currently available is the lumbar Prodisc 31 (Marnay T, 200241). Despite improvement in the disc insertion techniques and designs, difficulties persist with the correct midline and posterior placement of the prostheses within the disc spaces, even in experienced hands (McAfee, et al. 200540). 1.2.2. Indications for lumbar disc replacement Despite 20 years of experience with TDR, no general consensus exists about indications and contra-indications of TDR (Huang, et al. 200442; McAfee PC, 200443; Wong, et al. 200544). Strict guidelines were laid down in the US-FDA trials regarding indications and contra-indications for total disc replacement (Blumenthal, et al. 200539) (Table 1.2.2.). Multiple European centres have used total disc replacement for a much wider range of indications. In terms of these so-called ?off-label? indications, only a limited number of outcome results have been published in recent years (Bertagnoli, et al. 200645). 32 Table 1.2.2: Inclusion and exclusion criteria of lumbar TDR (adapted from Blumenthal et al., 2005) Inclusion criteria Exclusion criteria -Age 18 to 60 yrs -Previous thoracic or lumbar fusion -Symptomatic DDD confirmed by discography -Current or prior fracture at L4, L5, or S1 -Single-level DDD at L4?L5 or L5-S1 -Symptomatic multi-level degeneration. -Oswestry score > 30 -Non-contained herniated nucleus pulposus -VAS score > 40 (of 100) -Spondylosis -Failed > 6 mos of appropriate non-operative care -Spondylolisthesis > 3 mm -Back and/or leg pain with no nerve root compression -Scoliosis > 11? -Able to tolerate anterior approach -Mid-sagittal stenosis < 8 mm -Able and willing to comply with follow-up schedule -Positive straight leg raise -Willing to give written informed consent -Spinal tumor -Osteoporosis, osteopenia -Metabolic bone disease -Infection -Facet joint arthrosis -Psychosocial disorder -Morbid obesity -Metal allergy -Use of a bone growth stimulator -Participation in another study -Arachnoiditis -Chronic steroid use -Autoimmune disorder -Pregnancy -Other spinal surgery at the affected level (except discectomy, laminotomy/ectomy, without accompanying facetotomy or nucleolysis at the level to be treated) 33 1.2.3. Development of the Kineflex disc prosthesis The aim in designing the Kineflex disc was to develop a wear-resistant prosthesis with motion properties close to a human FSU. A simple, non-traumatic insertion technique should facilitate its use, even in severely degenerated and collapsed disc spaces. The Kineflex Disc Prosthesis represents a Chrome-Cobalt Molybdenum (CCM- Carpenter Technologies, Biodur Plus; USA), un-constrained but re-centering disc prosthesis with a mobile centre of rotation. The mechanism comprises two metal end- plates articulating over a sliding core that is positioned between the end-plates. It allows 12 degrees of movement into flexion, extension and left and right side bending. The inferior end-plate has a retaining ring that limits the excursion in the inferior articulation to 2 mm in all directions and prevents dislodgement of the sliding core. The mechanism therefore only allows around 3.5 mm of translation before, by distraction of the disc space, a re-centering force is produced which counteracts further translation (Figure 1.2.3 a-c). The disc is inserted as a single unit, with a freely mobile articular mechanism during the final insertion process, to facilitate posterior placement within the disc space (Figure 42?1. in Chapter 4.2.). 34 Figure 1.2.3. a-c: Illustration of Kineflex core motion Illustrate the core motion of the Kineflex prosthetic disc (KPD). (Note: As the KPD arthroplasty is symmetrical, the following analysis is equally applicable to flexion and extension) Figure 1.2.3.a: Cross - section of the KPD in neutral position The core motion is limited in the inferior articulation by the retaining ring of the inferior endplate. The superior articulation has no retaining ring. Line 1 shows the assembly center: Point 1 is the core center while Point 2 is the point on the lower disc endplate where the lower disc articulation cuts the assembly center and contacts the core. 35 Figure 1.2.3.b: KPD at 10? right sided inclination shows the Kineflex lumbar disc with a 10? articulation towards the right. It is shown that the core moves, from the disc assembly center, 1.24 mm away from the inclination side while point 2 moves 0.59 mm towards the inclination side. There is contact between the core and the lower endplate on the left side of the assembly. In contrast to this, analysis of Figure 1.2.3.c shows the assembly with a right side core contact. Figure 1.2.3.c: KPD at 10? right sided inclination and translation shows the Kineflex lumbar disc with a 10? articulation and additional maximal translation of the top endplate towards the right. It is shown that the center of the core 36 and Point 2 on the inferior endplate both move away from the disc assembly center, 3.1 mm away from the side of inclination. The contact between the core and the lower endplate on the right side of the assembly prevents further translation unless the inclination increases. Karin B?ttner-Janz (200846), the pioneer of modern type total disc replacement (TDR), recently sub-categorized TDR into 3 groups, viz.: i. Functional three-component prostheses ii. Functional two-component prostheses iii. Functional one-component prostheses classified The Kineflex lumbar disc prosthesis (Spinal Motion; CA; USA) falls into group A. It was, after the Charit? Artificial Disc Prosthesis (De Puy Spine, Inc., Raynham, MA), only the second functional three-component prosthesis design. Later designs in this sub-category are the Mobidisc (LDR, Troyes, France), the Activ-L (Aesculap spine, Tuttlingen, Germany), the Dynardi (Zimmer Spine, Minneapolis, MN), the Secure-C (Globus Medical, Inc., Audubon, PA) and the Baguera (International Center Cointrin, Geneva, Switzerland). Before engaging in the development of the Kineflex (Centurion) lumbar disc prosthesis, I had considerable surgical experience with anterior and posterior lumbar fusion surgery for DDD and with the Charite SB III Disc prosthesis. The Charite prosthesis comprises an ingenious, sliding core mechanism as articulation. Despite my satisfaction with the basic mechanism of the prosthesis, I found several design features of the Charite disc considerably limited the potential indications for the prosthesis in DDD and jeopardized the exact placement of the prosthesis, viz.: 1) The anchoring spikes on the prosthetic end-plates made midline, as well as posterior placement within the disc space, close to the natural centre of rotation, difficult to achieve. In stiffer and more collapsed disc spaces, this could lead to sub-optimal placement or end-plate fractures during insertion. 2) The insertion instrumentation was relatively bulky and wider than the actual implant, which significantly impeded visualisation when inserted through minimal invasive surgical approaches. 3) The insertion instrumentation held the implant end-plates rigidly and parallel throughout 37 the entire insertion process, therefore creating difficulties in narrow and stiff disc spaces in preserving the integrity of the bony end-plates of the disc space during the insertion process. At the onset of the development of the Kineflex disc prosthesis, there existed two further mechanical discs with wider distribution, i.e. the lumbar ProDisc (Synthes, West Chester, PA, US) and the Maverick Disc prostheses (Medtronic, Memphis, Tenn, US). Both comprised of a ?ball and socket? articular mechanism. The mechanism allowed translation within the joint only when coupled with flexion, extension or side-bending within the joint or by partial disengagement between the articular surfaces (semi-constrained). Their pattern of motion is, therefore, significantly different to the natural motion pattern of a human spinal motion segment (SMS) (Moumene M, Geisler FH, 200747). Table 1.2.3 below reflects the limitations I encountered with the available mechanical lumbar disc implants, available at the onset of the development of the Kineflex (Centurion) lumbar disc prosthesis. It describes the changes incorporated in the design of the Kineflex lumbar disc prosthesis in order to improve on these limitations. Table 1.2.3: Limitations of available mechanical disc implants Prosthesis model Feature Resulting limitation Solution Charite SBIII V- shaped anchoring teeth Teeth restrict posterior placement within the disc space Multiple small, machined teeth V- shaped anchoring teeth Teeth don?t always follow the pre-cut grooves, resulting in difficulties in maintaining coronal plane direction during insertion process Midline fin 38 Sharp leading edge of the prosthetic end-plate Danger of bony end-plate violation during insertion process Bevelled leading edge of the prosthesis Rigid fixation of prosthesis by insertion instrumentation Danger of bony end-plate violation during insertion process Modular fixation of prosthetic end-plates during the insertion process ProDisc L +Maverick Disc Fixed centre of rotation Motion pattern of prosthesis differs from natural SMS Sliding core ProDisc L +Maverick Disc Large midline fin Danger of vertebral splitting in double level disc replacement Small, narrow midline fin ProDisc L +Maverick Disc Large midline fin Restriction in seating the prosthesis fully into disc space Small, narrow midline fin ProDisc L Clip-in polyethylene core Danger of disengagement Sliding core dislodgement avoided by retaining ring +Maverick Disc Very posterior articulating mechanism Need of osteotomy in wedged, narrow disc spaces in order to seat the prosthesis Less back-seated articular mechanism and freed prosthetic end-plates during insertion process 39 1.3. Framework for how the various chapters of the thesis contribute to the overall integrated argument of the thesis After initial planning of a new prosthesis, together with my neurological colleague, Dr Ian Weinberg, we approached Dr Malan De Villiers (PhD), an engineer and CEO of Southern Medical (Centurion, Gauteng), which is South Africa?s leading designer and manufacturer of medical implants. Together we designed the ?Centurion disc prosthesis? (later re-named the ?Kineflex disc prosthesis?), as well as the insertion instrumentation (8 patents in my name). The aim in the development of this prosthesis was: a motion pattern close to the natural disc motion; an insertion technique that allows accurate placement within the disc space, even in patients with very advanced disc degeneration; and to explore the use of disc replacement in problems that are often considered as contra-indications to total disc replacement (disc height narrowing to less than 5 mm, previous fusion surgery and degenerative spondylolisthesis). A portion of the pre-clinical in vitro studies have been published in the book chapter on the Kineflex disc published with Elseviers. (H?hnle, et al. 200848) Chapter 3 expands on the extensive pre-clinical testing, which is the portion of the results that has not been published. Due to the results of this testing protocol, together with our early clinical outcome results, the Kineflex disc is currently Conformit Europeane (CE) certified. These results also formed the foundation for the inclusion of the Kineflex into a prospective, randomized, multi-center ?Food and Drug Administration Investigational Device Exemptions Study? of lumbar total disc replacement comparing KINEFLEX Artificial Disc versus CHARIT?? Artificial Disc. The recruitment phase of the study has been completed and the two-year results of two US centres have recently been presented (Guyer, 2008 49). Chapter 4 features the book chapter that we published with Elsevier (H?hnle, et al. 200848). It describes the development of the prosthesis and instrumentation, outlines 40 the material testing and presents early results of the first patient treated with the Kineflex lumbar disc. Chapter 5 consists of the first (H?hnle, et al. Winter 200732) of three publications in the SAS Journal, the official publication of the Spine Arthroplasty Society (SAS). It describes discs and the implantation technique of the Kineflex disc, which differs significantly from the insertion technique of earlier implants. A detailed description of the insertion procedure with intra-operative, radiological imaging is given and the two-year clinical and radiological results of the first 100 patients are presented. As with artificial implants in other joints, outcome depends on the accuracy of placement within the disc space (McAfee, et al. 2005). Ideal positioning within the disc space is difficult to achieve, especially in very collapsed and rigid disc spaces. In our publication, therefore, a comparison is done in terms of the prosthetic placement accuracy in cases with advanced disc space collapse and cases with lesser disc space narrowing. We further compare our placement accuracy achieved to the placement accuracy published in terms of another implant (McAfee, et al. 2005). Our clinical outcome was compared to the outcome of other disc prostheses, mostly in patients with significantly less advanced disc degeneration (Siepe, et al. 2006). Chapter 6 and 7 incorporate two of our publications, both of which were so called off-?label indications? for lumbar TDR. Chapter 6 reports on the results of TDR in patients who had previously undergone lumbar fusion surgery of other lumbo-sacral spinal levels (H?hnle, et al. Summer 200750). Although TDR has been used by other surgeons for this indication, little was previously published. Chapter 7 consists of the second publication of an ?off-label? indication. It explains the insertion and reduction technique used to treat patients with lower grade Degenerative Spondylolisthesis (DSPL) (H?hnle, et al. Summer 200852). It comprises a pilot study with a small number of patients enrolled. 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A prospective, randomized, multicenter Food and Drug Administration Investigational Device Exemption Study of lumbar total disc replacement with the Charit? artificial disc versus lumbar fusion: Part II: Evaluation of radiographic outcomes and correlation of surgical technique accuracy with clinical outcomes. Spine. 2005;30(14):1576-1583. 41. Marnay T. Lumbar disc replacement: 7-10 year results with the Prodisc. Eur Spine J. 2002;11:S19. 42. Huang R, Lim MR, Girardi FP et al. The prevalence of contraindications to total disc replacement in a cohort of lumbar surgical patients. Spine. 2004;29:2538-2541. 43. McAfee PC. The indication for lumbar and cervical disc replacement. Spine J. 2004;4;Suppl 1:177-181. 44. Wong D, Annesser B, Birney T, et al. Incidence of contraindications to total disc arthroplasty. World Spine 3 2005 (Rio de Janeiro, Brazil 111). 45. Bertagnoli R, Yue JJ, Fenk-Mayer A, et al. Treatment of symptomatic adjacent-segment degeneration after lumbar fusion with total disc arthroplasty by using the prodisc prosthesis: a prospective study with 2-year minimum follow up. J Neurosurg Spine. 2006;4:91-97. 46. B?ttner-Janz K: Classification of Spine Arthroplasty Devices in Yue JJ, Bertagnoli R, McAfee PC, An HS (eds): Motion preservation surgery of the spine: Advanced techniques and controversies. Philadelphia, Elsevier 2008, pp 21-35. 47. Moumene M, Geisler FH.Comparison of biomechanical function at ideal and varied surgical placement for two lumbar artificial disc implant designs: mobile-core versus fixed-core. Spine. 2007;32:1840-1851. 48. H?hnle UR, De Villiers M, Weinberg IR. Chapter 42: Kineflex. in Yue JJ, Bertagnoli R, McAfee PC, An HS (eds): Motion Preservation Surgery of the Spine: Advanced techniques and controversies. Philadelphia, Elsevier 2008, pp 338-345. 46 49. Guyer R, Cappuccino A, Blumenthal S. A prospective randomised comparison of two lumbar total disc replacement devices. SAS Congress, 6-9 May 2008, Miami, US: Abstract 51. 50. H?hnle UR, Sliwa K, Weinberg IR, Sweet MBE, De Villiers M, Candy GP. Lumbar disc replacement for junctional decompensation after fusion surgery: Clinical and radiological outcome at an average follow-up of 33 months. SAS Journal, Summer 2007; 1:85-92. DOI:SASJ-2007-0006-RR. 51. H?hnle UR, Sliwa K, Weinberg IR, Sweet MBE, De Villiers M, Candy GP. Is degenerative spondylolisthesis a contra-indication for total disc replacement? Kineflex lumbar disc replacement in seven patients with 24 months follow-up. SAS Journal, Summer 2008. 52. Siepe CJ, Mayer HM, Wiechert K, et al. Clinical results of lumbar disc replacement with ProDisc II: three-year results for different indications. Spine. 2006;31:1923-1932. 47 2. METHODS 2.1. Study objectives In this chapter, the overall design idea of the prosthesis and the design of the clinical study are outlined. I further elaborate on aspects that are only superficially covered in the different publications referred to in Chapter 3. I have already described the intellectual background leading to the development of the Kineflex disc prosthesis (Chapter 1, Sections 1.2 and 1.3). A detailed description of the material and methods applicable to the specific aspects of this work will follow in the remaining chapters, as outlined in Chapter 1, Section 1.3. I therefore limit myself in the present chapter to an outline of the research, with further detail presented in the subsequent chapters. My intellectual ownership in the design of the Kineflex disc prosthesis is documented in the patents relating to the prosthesis and its insertion instrumentation and a brief description of the final product follows. The Kineflex (Centurion) Disc Prosthesis (Spinal Motion; CA; USA) represents a Chrome-Cobalt Molybdenum (CCM- Carpenter Technologies, Biodur Plus; USA), un-constrained but re-centering disc prosthesis with a mobile centre of rotation (see Figure 42?1. in Chapter 4). The mechanism comprises two metal end-plates articulating over a sliding core that is positioned between the end-plates. It allows 12 degrees of movement into flexion, extension and left and right side bending. The inferior end-plate has a retaining ring that limits the excursion in the inferior articulation to 2 mm in all directions and prevents dislodgement of the sliding core. The mechanism therefore only allows 4 mm of translation before, by distraction of the disc space, a re-centering force is produced that counteracts further translation. The disc is inserted as a single unit with a freely mobile mechanism during the final insertion process to facilitate posterior placement within the disc space. The disc was originally named ?Centurion?, as it was developed in Centurion (between Pretoria and Johannesburg, in South Africa). 48 The objective in the design of this implant was to develop a lasting, wear-resistant prosthesis. The design of the implant and the insertion instrumentation ought to facilitate reliable midline and posterior placement of the implant within the disc space, even in severely degenerative disc spaces. This placement should be easily achieved through a minimally invasive approach. The objectives of this study were: to investigate the properties of the implant; to evaluate the insertion technique; and to assess the clinical and radiological outcome in patients with degenerative disc disease as well as the relevant sub-groups within this patient group. As most aspects of the Material and Methods are described in the results section that contains the various publications, I will follow with a description of the aspects that have been neglected in the result chapters (Chapters 3 - 7) and only summarize the other parts (Sections 2.2 and 2.3). 2.2. Informed consent Ethical clearance for the study was obtained from the University of the Witwatersrand (WITS) Ethics Committee on 27 March 2003 (protocol number: M03- 06-13 & Protocol M080557). It was amended on 5 April 2004 by the Internal Review Board of the Nedcare Linksfield Hospital; this is the hospital at which all procedures have been performed. A second, revised, ethical clearance was obtained from the WITS Ethics Committee on 19 June 2008. The study has been conducted in accordance with the ethical standards laid down in an appropriate version of the 1964 declaration of Helsinki. All patients received written information and signed a consent form. Before engaging in surgical treatment, patients were informed about the lack of experience with this particular disc implant (Kineflex disc) and about the limited world-wide long term results (over 10 years) of lumbar total disc replacement as a treatment for back and/or leg pain. The alternative surgical treatment options were 49 discussed (fusion, decompression and disc replacement with an alternative prosthesis). 2.3. Clinical study design and patient enrolment This study was a single centre, prospective, observational study. The primary clinical outcome measures for this study were pain relief and functional improvement, as assessed by the Oswestry Disability Index (ODI) (Fairbank & Pynsent, 20001), the Visual Analoque Pain Score (VAS) and our own questionnaire. The primary radiological outcome measures are outlined in Chapter 2, Section 2.3.6. 2.3.1. Recruitment of patients and therapeutic work-up Patients were recruited from in and out-patients seen for purposes of consultation by myself or Dr Ian R. Weinberg. During clinical examination, the patients had to physically indicate the painful areas of the back and lower limbs. This was followed by palpation of the inter-spinous spaces in both standing and prone positions to determine the pain levels. Routine spinal examinations followed. Before the surgical index procedure, all patients had experienced severe, disabling low back pain (LBP) of at least one year duration and/or leg pain of over 6 months duration. When patients had significant neurological deficits or neurological deterioration during the course of conservative treatment, the conservative treatment might have been shortened. All patients underwent at least six weeks of an active, physiotherapeutically supervised, exercise orientated, treatment program Diagnostic and therapeutic cortisone injections into the facet joint, sacro-iliac joints, the disc or the epidural space were performed when indicated. 50 2.3.2. Inclusion criteria Inclusion criteria for the study were: age of 18 - 65 years; symptomatic single or multi-level degenerative disc disease at the L2/L3, L3/L4, L4-L5 or L5-S1 levels confirmed on x-rays, magnetic resonance imaging and provocative discography in selected cases. Further inclusion criteria included: mechanical back and leg pain, recurrent disc herniation, broad based central disc herniation without sequestration; and junctional failure after previous fusion. All patients had failed conservative treatment of at least 6 months. Only the symptomatic levels on clinical examination and/or discography were replaced. 2.3.3. Exclusion criteria Exclusion criteria were: osteoporosis, tumor, infection, spondylolisis of the level, bony spinal stenosis, sequestrated disc prolapse tracking up or down behind the vertebral body, severe obesity, structural deformity, previous retroperitoneal surgery, vascular pathology and previous wide laminectomy with destabilization of the facet complex. Advanced facet arthritis was not an exclusion criterion unless osteophyte formation from the facet resulted in bony canal or recess stenosis. Spinal or lateral recess stenosis caused by soft tissue (disc, ligamentum flavum or joint capsule) was not considered a contra-indication for disc replacement if proper decompression during surgery, by means of direct or indirect decompression, could be anticipated on pre-operative imaging. 2.3.4. Study visits Patients were seen; pre-operatively, at 6 weeks, at 3 months, 6 months, at one and two years in conjunction with the regular follow-up examinations. In addition to the outcome data, general demographic information and operative data, as well as data pertaining to radiological examination, were collected. The follow-ups formed part of our routine, standard-of-care and follow-up visits. 2.3.5. Clinical outcome measures The primary clinical outcome measures for this study were pain relief and functional improvement as assessed by the Oswestry Disability Index (ODI) (Fairbank JC, 51 Pynsent PB. 20001), the Visual Analoque Pain Score (VAS) and our own questionnaire. The questionnaires were completed by patients pre-operatively, at 6 weeks, at 3 months, at 6 months, and yearly in conjunction with regular follow-up examinations. The questionnaire was our own, designed by myself and Dr I. Weinberg, and has not been validated. It captured general demographic information regarding marital status, number of children, work status, recreational sport activities, the reason for stopping sport activities, intake of alcohol and cigarettes as well as drugs and medicine. Pre- operatively, the questionnaire screens for previous conservative treatment, pain duration and pressure experienced in the work process. Pre-operatively and post- operatively (follow-up) it incorporates a detailed scoring of pains and weaknesses (see appendix). During follow?up, the patient is asked about satisfaction with the treatment outcome (options: excellent, good, fair, poor) and whether he or she would undergo the same operation again or recommend it to friends (options: yes; don't know; no). 2.3.6. Radiological examination All patients had a pre-operative magnetic resonance investigation (MRI) or lumbar myelography followed by computer tomography (Myelo-CT) or both. Pre-operative, at 3 months, at one year, and yearly the following radiographs were taken: Antero- posterior (AP), a lateral standing radiographs (which included the bottom end-plate of the T12 vertebra and the top half of both femoral heads), lateral flexion/extension radiographs and a lateral whole-spine standing radiograph (kyphosis X-ray). At all other follow-ups (2 weeks, 6 weeks and 6 months), only standing AP side-bending and lateral flexion/extension radiographs of the lumbar spine were performed. Oblique standing radiographs were only done pre-operatively. Pre-operative discography was only performed in cases when, after clinical examination and radiographic evaluation, doubt persisted about inclusion or exclusion of a lumbar level in the operation. The amount of disc space narrowing, the presence or absence of spondylolisis, the mobility of the motion segment, and the 52 radiological stability of the relevant spinal level were carefully assessed on the plain radiographs. The disc quality, the amount of canal and recess encroachment by the disc, the facet joints and the ligamentum flavum were determined on MRI. The degree of facet arthritis and modic changes were also assessed. Pre-operative disc height at the operated level was measured by 2 different observers on lateral standing radiographs at 3 points (anterior, middle and posterior) and averaged and corrected by the magnification error (McAfee PC et al. 20052). Radiographic placement accuracy: The exact central placement of all disc implants in the coronal and mid-sagittal plane was determined and categorized, as described by McAfee (McAfee PC et al. 20052), into ideal, sub-optimal and poor placement. The mid-sagittal plane on lateral radiograph is defined as 2 mm posterior to the middle of the vertebral body in the sagittal plane. The coronal plane on anteroposterior radiographs is the exact center line of the vertebral body (McAfee PC et al. 2005) or interpedicular midpoint (Mistry & Robertson, 20063). The center of the core of the artificial disc was placed: within 3 mm of exact central placement in both the coronal and midsagittal planes in Group I (ideal placement); from 3-5 mm from exact central placement in Group II (sub-optimal placement); and over 5 mm from exact central placement in Group 3 (poor placement). If the two axes are rated in different groups, the rating of the placement was determined by the poorer rating. The measurements were checked by two different observers, then averaged and corrected by the magnification error (McAfee PC et al. 20052). 2.3.7. Surgery All surgery was performed in Nedcare Linksfield Hospital. I personally performed or directly assisted Dr Ian Weinberg in all surgical procedures. Two anaesthesists and two scrub sisters formed part of the operative team. All operations were performed on a translucent electrical table under radiographic image control. Intra-operative cell-saving was used in all patients. After a transverse midline incision of between 5 and 9 cm, depending on patient size and number of levels to be exposed, the rectus sheet was opened parallel to the linea alba and the rectus muscle was retracted laterally. The spine was approached retroperitoneally, partially incising the transversus abdominis fascia from the arcade ligament cranially. 53 After mobilization of the major vessels, Hohman retractors, attached to a frame retractor, were used to maintain exposure throughout the procedure. After a midline anuloplasty (a trap-door-like opening of the annulus of the disc), the disc nucleus, the inner layer of the annulus and any sequestrated disc material were removed. The end-plates were prepared using a Cobbs instrument and curettes to remove the cartilaginous end-plates and to prepare the bony end-plates. Osteotomes and burrs were occasionally used to remove big osteophytes or to prepare the end- plates in cases of significant end-plate sclerosis. This was followed by sequential distraction of the disc spaces using wedge distracters of increasing sizes. The midline was determined on AP radiographs using a specially designed and patented midline finder. The insertion of the disc followed the principle described in the relevant publications, as the technique varies slightly with the indication for the surgery (see Material and methods in the result section (Section 3.2-3.5)). 2.3.8. Post-operative mobilization Patients were routinely allowed to ambulate the day after surgery without bracing, initially under supervision of a qualified physiotherapist. Patients started supervised gait training, isometric muscle strengthening and stretching exercises as from day 1 post-operatively. At discharge, patients were instructed to walk every day and they were allowed to sit as long as they felt comfortable. Cycling on a stationary bike was encouraged after removal of stitches at 12 days after the operation. Low-impact sport was allowed at 6 weeks and impact sport at 3 - 4 months. All employed office workers were allowed to return to work at 4 weeks, provided they could sit for prolonged periods without additional discomfort. Manual workers were kept off work for 6 weeks post surgery and were then allowed to go back onto light duty (no lifting of objects weighing more than 10 kg, no vibration, only limited bending and no running) for the next 6 weeks. 54 2.4. References: Methods 1. Fairbank JC, Pynsent PB. The Oswestry Disability Index. Spine. 2000;25:2940-2952. 2. McAfee PC, Cunningham BW, Holtsapple G, et al. A prospective, randomized, multicenter Food and Drug Administration Investigational Device Exemption Study of lumbar total disc replacement with the Charit? artificial disc versus lumbar fusion: Part II: Evaluation of radiographic outcomes and correlation of surgical technique accuracy with clinical outcomes. Spine. 2005;30:1576-1583. 3. Mistry DN, Robertson PA. Radiological landmark accuracy for optimum coronal placement of total disc arthroplasty. J Spinal Disord Tech. 2006;19:231-236. 55 3. Results: Pre-clinical, in vitro testing of the Kineflex lumbar disc prosthesis 3.1. Kineflex M lumbar intervertebral disc prosthesis: Development of wear protocol and protocol for static compression testing 3.1.1. Description of the Kineflex M intervertebral lumbar disc prosthesis: Development of in vitro test protocol The Centurion intervertebral prosthesis consists of two cobalt chrome molybdenum (CCM) end-plates positioned on either side of a cobalt-chrome-molybdenum core. The articulating surfaces are polished CCM against polished CCM; the bone integrating surfaces are plasma sprayed with titanium. The goal of the tests was to simulate the load and movement to which the prosthesis would be exposed under in vivo conditions and to verify the prosthesis? ability to withstand static and fatigue load conditions as well as determine the wear characteristics of the prosthesis. Custom equipment was used to test the prosthesis under a simultaneous combination of flexion/extension, lateral bending and rotational movement (wear tests). Further custom test benches were used to perform compression under a Z-axis load (fatigue tests). Fatigue tests included mono-axial cyclical testing for compressive and compressive-shear modes. Five test samples were tested for the wear test; five test samples were tested for the compressive fatigue test under each load condition. The tests were conducted over 10 million cycles at a constant frequency of 5 Hz - well within the frequency range of previous metal on metal prosthesis testing. Test samples, with respect to the articulating surfaces, were faithful replicas of production discs. The non-articulating surfaces were modified to allow fixtures to be attached for testing purposes. 56 Since all Kineflex discs utilized the same core, variations in thickness to match the dimensions of the anatomic space were achieved by varying the end-plate thickness. Thus, there was not a distinct difference amongst the cores regarding thickness for different disc heights and sizes. Additionally, while end-plate sizes varied to accommodate different sized vertebrae, the articulating surface area (i.e. the part of the articulating surface that is in direct contact with the core) remained constant. Thus, because there is only one articulating surface size across all end-plate-core combinations, and the articulating surface was the critical design parameter for purposes of mechanical performance in dynamic testing, the core end-plate combination in this test provided the smallest available articulating surface. It should be noted that the end-plates had to be modified on the non-articulating sides to accommodate fixation to the spinal simulation equipment, consistent with applicable draft ASTM standards (ASTM F04.25.05.011). 3.1.2. Rationale of load condition imposed for wear studies: lexion/Extension, Lateral Bending and Rotation The prostheses were tested under a constant Z-axis load of 1200N. A maximum load condition of the lower lumber discs has been defined as being that load exerted when a person is in a hunch-back position and lifting an additional load of 20kg. This condition results in a force of 2700N on the FSU (Functional Spinal Unit) according to Nachemson (Nachemson A, 19662) and 4140N according to Wilke (Wilke et al 19983). According to Wilke, the standing position is defined as a 100% load condition; other body-positions are a percentage in relation to the 100%. The 100% or standing position represents the normal load. This load was determined to be approximately 22% of the maximum load of 4140 N (911 N); 22% of the maximum load of 4140 N is 911 N. A vertical load of 1200N was chosen as the test rig load. The 1200N load condition was well in excess of the in vivo condition when viewed in terms of an average load over 10 years, but was applied to gain experience as to the disc wear under excess loading. Due to the angle of articulation a shear, load is generated concurrently in the prosthesis during the cycle of articulation. 57 The disc is symmetrical in the X-X and Y-Y directions. The test was carried out in combined flexion-extension (X-X) and lateral bending (Y-Y), combined with simultaneous rotation around the axis of symmetry (Figure 3.2.1.a-c). The disc combinations all utilized the same core. The articulating geometry of all discs was, therefore, constant across the range of disc sizes and hence only one combination required evaluation. Wear debris was collected and analyzed to give an indication of debris load and particle geometry for comparison to debris loads found in other arthroplasties. 3.1.3. Rationale of loading cycles imposed: wear test According to Eijkelkamp (20014), the number of walking cycles of an average person is 2,000,000 per year and the number of lifting cycles is 125,000 per year. A compromise for a wear test should lie somewhere between the former figure, at a low degree of articulation, and the latter figure, at a high degree of articulation. The proposed test is to be carried out for 10 million cycles, which is deemed to represent a minimum of 10 years of in vivo use. Analysis of the test specimens was performed at every 1,000,000 cycles. This included a dimensional check with specific reference to meniscal height and diameter to comment on possible creep deformation of the meniscus. 3.1.4. Rationale of articulating limits imposed: Flexion/Extension, Lateral bending and Rotation The range of motion limits of the normal spinal motion segment (SMS) have been studied by various researchers (Dvorak , et al. 19915; Pearcy, et al. 19846; Putto, Tallroth K. 19907; Hayes, et al. 19898). From these studies, it can be seen that the range of motion at the disc level reduces after arthroplasty (De Kleuver M, et al. 20039). In the case of a walking cycle (gait), the motion is less than 2 in total (see table below) in any of the three planes, namely flexion-extension, lateral bending and axial rotation (Table 3.4.1). 58 Table 3.1.4: Summary of combined segmental motion (ROM) during gait, as found by various researchers (in degrees) Study Flexion/extension Lateral b ending Axial rotation Vogt, et al. 200110 0.5 0.8 1.0 Cromwell, et al. 198911 1.2 2 2.7 Callaghan, et al 199612 1.9 1.2 2.45 Taylor, et al 199613 1.0 3.0 1.6 Average Total ROM 1.15 1.75 1.94 Gait is the predominant cyclical load condition and a range of motion to simulate this condition is, therefore, appropriate for implant wear assessment. To simulate a worst- case gait load condition, a movement in excess of the published data was therefore applied. A total cyclical ROM of 14.2 of lateral bending, combined with a cyclical ROM of 14.2 of flexion/extension bending and 8 of rotation, were applied simultaneously. The relative phase of the flexion/extension, lateral bending and axial rotation movements were based on human gait studies ? see Figure 2 below. These represent movement in the 3 planes for the full spinal lumbar region during fast walking. The proposed wear test would emulate the phasing, whereby F-E and rotation is in phase and lateral bending out of phase. Because the amount of wear debris generated is a product of the applied load and the sliding distance, combining the high load with maximal simultaneous motion in flexion-extension and rotation in this manner was believed to substantially exaggerate the amount of wear that would be generated under actual in vivo conditions. A gait simulator had been constructed to replicate this movement. 3.1.5. Rationale for the analysis of testing Results were analyzed to establish whether the implants? intended physical performance would be compromised by cyclic loading. It was established whether dimensional changes were such that the intended ROM could be sustained, or implant 59 stability lost. Further, the wear rate and wear particle size distribution were compared to published data to establish whether any adverse biologic reaction should be anticipated. 3.2. Methods: Kineflex Disc: Set-up of wear and compression testing 3.2.1. Test bench set-up (gait simulator) The gait simulator consisted of a loaded vertical arm that pivots on the assembled artificial disc (Figure 3.3.2.). The articulating motion for the flexion/extension test was introduced by means of a horizontal arm connected to an eccentric pin on a wheel that was rotationally driven by an electric motor. The lateral bending motion was introduced by means of the same drive chain, but was applied to the inferior end-plate. The phasing of the 3 desired motions could be adjusted and remained synchronized for the duration of the wear test (Figure 3.2.1.a-c). The loads were imposed on the prosthesis via a combination of 20kg and 15kg weights combined with the load of the vertical arm. The test specimens were tested in a physiologically buffered 0.9% saline held at 37oC ? 3oC to simulate the body fluids such that the implant would function under in vivo conditions. The following components were used in the test set-ups: ? AC electric motor ? Electronic speed controller ? Electric fluid heater ? Filter with in-line pump A VVVF speed controller was used to bring down the frequency to 5Hz. 60 SPINAL DISC WEAR LOAD SIMULATION F A A B B CC Figure 3.2.1.a: Flexion/Extension and lateral bending combined with rotation Lateral Bending Flexion-Extension Rotation Figure 3.2.1.b: Side and top views of motion generation 61 Figure 3.2.1.c: Concurrent (a) F-E, (b) Lateral Bend and (c) Rotation of Lumbar Spine for the sum of all 6 lumbar levels during gait (Cromwell et al. 198911), with phasing of lumbar spine gait simulator superimposed. Indicates phasing of motion imposed by gait simulator 62 3.2.2. Test criteria 3.2.2.1. Pre-test Set-up 1. Receipt of two CCM disc end-plates: ? 40mm x 5mm with articulating surfaces finished as per normal manufacturing procedure, inclusive of sterilization. 2. Receipt of CCM menisci finished as per normal manufacturing procedure, inclusive of sterilization. 3. Removal from packaging and weighing of the discs x 2 per test rig to three decimal places (Sartorius TE313S). 4. Weighing of the menisci x 1 per test rig to three decimal places. 5. Dimensional check of height and diameter of meniscus. 3.2.2.2. Gait simulation wear test set-up Five spinal motion simulators were utilized in the testing of the disc prosthesis and a sixth static load soak control was subjected to the applied load for the corresponding testing times. The test prostheses were evaluated in reservoirs of physiologically buffered saline, which were maintained at 37 ? 2 C by means of thermostatically controlled submersed heaters. Electronic cycle counters confirmed the number of cycles to which test prostheses were subjected. The test frequency was maintained at 5Hz by adjustment of electronic speed controllers. At every 1 million cycles, the following data was determined or collected: 1. Weight loss of prosthesis components. 2. Dimensional checks of the core, being the total height and the overall diameter. 3. One 60ml sample of physiologically buffered saline per simulator reservoir. At intervals of 2, 5, 8 and 10 million cycles, one sample per simulator was subjected to particle isolation and wear debris analysis. 63 Figure 3.2.2: Gait simulation wear test ? set-up Saline bath preparation Water temperature 37 ? 3oC Place prosthesis in the test bench Load the test bench with the load (1200N) Cover test bench to prevent dust and other particles from contaminating the saline bath Re-set counters on respective test rig 64 3.2.2.3. Test After every 1,000,000 cycles, the following procedures were followed on each of the test benches: 1. Cleaning of discs and meniscus ultrasonically. 2. Weighing of discs x 2 to three decimal places (g). 3. Weighing of meniscus x 1 to three decimal places (g). 4. Dimensional check of height and diameter to three decimal places (mm). The difference in weight was utilized to correctly determine weight loss due to wear. A visual inspection of the test specimens was carried out and recorded to ascertain the extent of visual damage. A photographic record was compiled for reference. The saline medium was filtered at 2 million, 5 million, 8 million and 10 million cycles through sequential filters of 10 micron, 1 micron and 0.1 micron (Endo, et al. 200114; Tipper, et al. 200115; Tipper, et al. 200016) Analysis of wear debris quantum, size and geometry was carried out. 3.2.2.4. Test result assessment Upon each completion of the tests (i.e. after the 10 million cycles were completed) the following parameters were calculated for each test: The weight of test samples at all intervals of wear and fatigue testing were verified on a Sartorius CP4235 validated scale to an accuracy of ?0.001g. This took place in a temperature-controlled room. 1. Mass reduction [mg] 2. Percentage mass reduction [%] 4. Wear Rate = Volume loss due to wear/Sliding distance [mm3/m] 5. Wear Factor = Volume loss due to wear/(Sliding distance x Load) [mm3/Nm] 6. Dimensional changes (creep indication) [mm] The results were analyzed to establish whether the implants? intended physical performance was compromised by cyclic loading. It had to be established whether dimensional changes were such that the intended ROM could be sustained, or implant stability was lost. Further, the wear rate and wear particle size distribution had to be 65 compared to published data to establish whether any adverse biological reaction was anticipated. 3.2.3. Static tests Static tests were carried out in 2 configurations (Figure 3.2.3.1 & Figure 3.2.3.2), as described below. 3.2.3.1. Normal load A normally loaded disc mechanism was at 90 degrees to disc end-plates, with the end-plates parallel to each other. 3.2.3.2. Shear load The disc mechanism in an extreme lordotic position of 10 degrees, with axial loading applied to simulate the worst in vivo shear condition. This is the in vivo position in which shear resistance is required. The tests carried out had to include a pre-determination of the test fixture stiffness. The actual device configuration had to then be loaded at a rate not exceeding 25mm/min until functional failure was attained. Load and displacement data were recorded. The following parameters were determined as an average of 5 test samples for each condition, as per 3.2.3.1. and 3.2.3.2.: ? Load-displacement curves; ? Yield displacement; ? Yield load; ? Ultimate displacement; ? Ultimate load; ? Device stiffness; The ultimate load was recorded as input for fatigue test loading purposes. 66 F Normal Loading Figure 3.2.3.1: Compressive fatigue F 10o Lordotic Loading Figure 3.2.3.2: Shear fatigue 3.2.4. Rationale for mono-axial fatigue tests Cyclical compression tests for the case of a normally loaded disc as well as a disc in a lordotic position (see paragraphs 3.2.3.1 and 3.2.3.2 above) were carried out. This gave an indication of the fatigue properties in a correctly implanted disc as well as for 67 instances where a pronounced lordosis were encountered and the meniscal spacer position would therefore not lie horizontally. The test medium was physiologically buffered saline (0.9%) and a test frequency of 5Hz was applied. The purpose of this test was to confirm a load-cycle to failure plot and to comment on the suitability of the fatigue resistance of the device for in vivo use. Five samples in each configuration were tested. The fatigue tests were carried out under a cyclic load condition of 200N to 2000N over 10,000,000 cycles. The condition of the prosthesis was recorded for every 1 million cycles. This included a visual integrity check as well as a dimensional verification. For the purposes of this test, a failure mode was defined as a visible deterioration of the meniscal spacer or end-plates evidenced by cracking, spalling or creep of magnitude that prevents the prosthesis from articulating freely or maintaining its structural integrity. 3.2.5. Torsion test This device was unconstrained in axial rotation and therefore no torsion test was required (ASTM1). 3.3. Results of accelerated wear test 3.3.1. Wear test protocol The wear tests described herein were carried out in accordance with the protocol: Methods: Kineflex Disc: Set-up of wear and compression testing (Chapter 3.2). 3.3.2. Description of the test equipment Spinal simulators were constructed, which enable a variety of loading conditions and ranges of motion to be applied to the prosthesis. The simulator design has been illustrated in drawings appended hereto as Figure 3.3.2. It allows for cyclical motion to be applied under a constant load in the three degrees of freedom of the Functional Spinal Unit (FSU). 68 Figure 3.3.2: Lumbar Spinal Fatigue Simulator Illustration The load was accurately applied by means of weights that were loaded onto the articulating arm of the simulator. The parameters applied were: Loading : 1200N F-E Range : +7.1 to -7.1 Lateral Bending Range : +7.1 to -7.1 Rotation : +4 to -4 69 3.3.3. Weight verification The weight of test samples at all intervals of wear and fatigue testing was verified on a Sartorius CP4235 validated scale to an accuracy of ?0.001g. This took place in a temperature-controlled room. 3.3.4. Results of wear testing The following tables (3.3.4.a-k) summarize results achieved for the accelerated wear testing. Table 3.3.4. a-k: Results of accelerated wear testing a) COMMENCEMENT OF TEST: 3 AUGUST 2004 Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.483 - 27.203 - 29.044 - 10.48 - 19.41 - 2 16.497 - 27.403 - 29.323 - 10.49 - 19.39 - 3 16.222 - 27.542 - 29.075 - 10.49 - 19.40 - 4 16.368 - 27.694 - 29.314 - 10.50 - 19.40 - 5 16.448 - 27.223 - 29.035 - 10.51 - 19.43 - Average 16.404 27.413 29.158 10.49 19.41 b) ONE MILLION CYCLE PARAMETERS: 5 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.474 0.009 27.197 0.006 29.038 0.006 10.44 0.04 19.41 0.00 2 16.492 0.005 27.399 0.004 29.319 0.004 10.47 0.02 19.39 0.00 3 16.210 0.012 27.538 0.004 29.070 0.005 10.43 0.06 19.40 0.00 4 16.361 0.007 27.691 0.003 29.308 0.006 10.46 0.04 19.40 0.00 5 16.439 0.009 27.219 0.004 29.031 0.004 10.46 0.05 19.43 0.00 Average 16.395 0.008 27.409 0.004 29.153 0.005 10.45 0.04 19.41 0.00 70 c) TWO MILLION CYCLE PARAMETERS: 8 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.466 0.008 27.194 0.003 29.034 0.004 10.40 0.04 19.41 0.00 2 16.483 0.009 27.394 0.005 29.315 0.004 10.42 0.05 19.39 0.00 3 16.204 0.006 27.534 0.004 29.067 0.003 10.40 0.03 19.40 0.00 4 16.355 0.006 27.686 0.005 29.303 0.005 10.42 0.04 19.40 0.00 5 16.432 0.007 27.217 0.002 29.027 0.004 10.41 0.05 19.43 0.00 Average 16.388 0.007 27.405 0.004 29.149 0.004 10.41 0.04 19.41 0.00 d) THREE MILLION CYCLE PARAMETERS: 10 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.461 0.005 27.191 0.003 29.029 0.005 10.37 0.03 19.41 0.00 2 16.479 0.004 27.391 0.003 29.310 0.005 10.39 0.03 19.39 0.00 3 16.200 0.004 27.530 0.004 29.065 0.002 10.37 0.03 19.40 0.00 4 16.350 0.005 27.683 0.003 29.299 0.004 10.38 0.04 19.40 0.00 5 16.427 0.005 27.213 0.004 29.024 0.003 10.38 0.03 19.43 0.00 Average 16.383 0.005 27.402 0.003 29.145 0.004 10.38 0.03 19.41 0.00 e) FOUR MILLION CYCLE PARAMETERS: 13 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.458 0.003 27.189 0.002 29.027 0.002 10.35 0.02 19.41 0.00 2 16.477 0.002 27.388 0.003 29.306 0.004 10.38 0.01 19.39 0.00 3 16.196 0.004 27.530 0.000 29.060 0.005 10.35 0.02 19.40 0.00 4 16.344 0.006 27.681 0.002 29.296 0.003 10.36 0.02 19.40 0.00 5 16.422 0.005 27.209 0.004 29.022 0.002 10.35 0.03 19.43 0.00 Average 16.3794 0.004 27.399 0.002 29.142 0.003 10.36 0.02 19.41 0.00 71 f) FIVE MILLION CYCLE PARAMETERS: 15 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.455 0.003 27.186 0.003 29.025 0.002 10.33 0.02 19.41 0.00 2 16.472 0.005 27.383 0.005 29.304 0.002 10.35 0.03 19.39 0.00 3 16.192 0.004 27.528 0.002 29.058 0.002 10.32 0.03 19.40 0.00 4 16.342 0.002 27.680 0.001 29.292 0.004 10.32 0.04 19.40 0.00 5 16.418 0.004 27.207 0.002 29.017 0.005 10.32 0.03 19.43 0.00 Average 16.376 0.004 27.397 0.003 29.139 0.003 10.33 0.03 19.41 0.00 g) SIX MILLION CYCLE PARAMETERS: 17 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.453 0.002 27.182 0.004 29.020 0.005 10.30 0.03 19.41 0.00 2 16.469 0.003 27.379 0.004 29.302 0.002 10.33 0.02 19.39 0.00 3 16.185 0.007 27.527 0.001 29.056 0.002 10.28 0.04 19.40 0.00 4 16.338 0.004 27.678 0.002 29.291 0.001 10.29 0.03 19.40 0.00 5 16.415 0.003 27.206 0.001 29.013 0.004 10.30 0.02 19.43 0.00 Average 16.372 0.004 27.394 0.002 29.136 0.003 10.30 0.03 19.41 0.00 h) SEVEN MILLION CYCLE PARAMETERS: 20 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.448 0.005 27.180 0.002 29.016 0.004 10.27 0.03 19.41 0.00 2 16.462 0.007 27.377 0.002 29.301 0.001 10.29 0.04 19.39 0.00 3 16.183 0.002 27.524 0.003 29.055 0.001 10.28 0.00 19.40 0.00 4 16.333 0.005 27.676 0.002 29.288 0.003 10.25 0.04 19.40 0.00 5 16.411 0.004 27.204 0.002 29.008 0.005 10.27 0.03 19.43 0.00 Average 16.367 0.005 27.392 0.002 29.134 0.003 10.27 0.03 19.41 0.00 72 i) EIGHT MILLION CYCLE PARAMETERS: 22 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actua LOSS 1 16.444 0.004 27.175 0.005 29.013 0.003 10.25 0.02 19.41 0.00 2 16.456 0.006 27.372 0.005 29.299 0.002 10.25 0.04 19.39 0.00 3 16.177 0.006 27.522 0.002 29.051 0.004 10.25 0.03 19.40 0.00 4 16.330 0.003 27.673 0.003 29.284 0.004 10.24 0.01 19.40 0.00 5 16.402 0.009 27.202 0.002 29.006 0.002 10.22 0.05 19.43 0.00 Average 16.362 0.006 27.389 0.003 29.131 0.003 10.24 0.03 19.41 0.00 j) NINE MILLION CYCLE PARAMETERS: 25 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.438 0.006 27.172 0.003 29.010 0.003 10.22 0.03 19.41 0.00 2 16.450 0.006 27.370 0.002 29.297 0.002 10.23 0.02 19.39 0.00 3 16.170 0.007 27.519 0.003 29.049 0.002 10.21 0.04 19.40 0.00 4 16.325 0.005 27.668 0.005 29.283 0.001 10.22 0.02 19.40 0.00 5 16.396 0.006 27.198 0.004 29.003 0.003 10.19 0.03 19.43 0.00 Average 16.356 0.006 27.385 0.003 29.128 0.002 10.21 0.03 19.41 0.00 k) TEN MILLION CYCLE PARAMETERS: 28 AUGUST Simulator MASS (g) DIMENSIONS (mm) CORE SUPERIOR END-PLATE INFERIOR END-PLATE CORE HEIGHT CORE DIAMETER Actual LOSS Actual LOSS Actual LOSS Actual LOSS Actual LOSS 1 16.431 0.007 27.168 0.004 29.008 0.002 10.19 0.03 19.41 0.00 2 16.446 0.004 27.367 0.003 29.294 0.003 10.20 0.03 19.39 0.00 3 16.169 0.001 27.516 0.003 29.046 0.003 10.21 0.00 19.40 0.00 4 16.318 0.007 27.666 0.002 29.279 0.004 10.20 0.02 19.40 0.00 5 16.392 0.004 27.196 0.002 29.002 0.001 10.16 0.03 19.43 0.00 Average 16.351 0.005 27.383 0.003 29.126 0.003 10.19 0.02 19.41 0.00 73 3.3.5. Discussion of wear test results Figure 3.3.5.a summarizes the average mass loss of the core over 10 million cycles. The mass loss of the core over 10 million cycles was 52 mg, or an average of 5.2 mg/M cycles. This equates to a loss of 0.3% of the entire core over 10 million cycles. The volumetric loss after 10 million cycles was 6.28mm3, or an average of 0.628mm3/M cycles. Cum Mass Loss of CCM Cores Subjected to 1200N Loading 8 15 20 24 28 32 37 43 49 52 0 10 20 30 40 50 60 1 2 3 4 5 6 7 8 9 10 Million cycles M as s Lo ss o f C CM C or e (m g) Figure 3.3.5.a: Cumulative mass loss in mg of core when subjected to 1200N loading Figure 3.3.5.b summarizes the average mass loss for the full disc construct over 10 million cycles.The volumetric loss after 10 million cycles was 13.88mm3. The mass loss after 10 million cycles was 115 mg, for an average of 11.5 mg/M cycles. This equates to a loss of 0.1% of the entire disc over 10 million cycles. The volumetric loss after 10 million cycles was 13.88mm3, for an average volumetric loss rate of 1.388mm3/M cycles. 74 Cum Mass Loss of CCM Disc Subjected to 1200N Loading 17 32 44 53 63 72 82 94 105 115 0 20 40 60 80 100 120 140 1 2 3 4 5 6 7 8 9 10 Million Cycles M as s Lo ss o f C CM D is c (m g) Figure 3.3.5.b: Cumulative mass loss of disc prosthesis when subjected to 1200N loading The wear particle generation shows a decrease over the first 3 million cycles, followed by a relatively linear wear trend over subsequent cycles. The mass loss equates to 0.3% of the entire core and 0.1% of the entire disc over 10 million cycles. Factors that may have contributed to this trend are: 1. Magnitude of applied loading conditions. 2. Spinal simulator constructs of different test facilities would vary from facility to facility and to this extent comparative testing of different prostheses in future in the same facility would be informative. 3. The use of buffered saline in comparison to bovine serum is known to increase wear rates. 75 Wear particles fall within reported results for wear tests of other metal on metal (M- O-M) prostheses, with specific reference to M-O-M hip prostheses, for which the most literature is available. A mass balance calculation (weight loss calculated from wear debris versus weight loss physically measured) shows good correlation and this comparison is included in the wear particle analysis report. 3.4. Result of static compression testing 3.4.1. Introduction The test was performed in accordance with ASTM F-04.25.05.01 Draft I (February 2003) Item Z8924Z. The inter-vertebral prosthesis consists of two end-plates positioned on either side of a meniscal core. Tests were conducted on Cobalt Chrome Molybdenum (CCM) end- plates with a CCM core. The goal of this test was to determine the mechanical performance of the inter- vertebral prosthesis under compression. Two tests were performed on the materials configuration. The first test was conducted with the end-plates parallel throughout the test. In the second test, the bottom end-plate with retention was rotated to a 10? angle in relation to the top end-plate. The top end-plate was unconstrained in the horizontal plane. All samples were previously unused parts and of standard production quality. The assembled lumbar prosthesis was placed in an Instron machine with a 0-100kN compression load capacity. In test one, the assembly was compressed until the end- plates touch; 25kN is achieved or mechanical failure occurs on any of the three components i.e. the two end-plates or the meniscal core. In test two, the assembly was compressed to a minimum of 10kN or until mechanical failure occurs. Mechanical failure was defined as a permanent deformation or breakage of any of the 76 three components. A total of five assembled samples were tested in each of the two tests. The results reported in this report were load vs displacement results and the deformation of the samples at various intervals of the tests. The height of every meniscus was measured before and after the test for the five samples in test 1. 3.4.2. Rationale of load condition imposed The test was conducted in an Instron machine capable of compressing the assembled prosthesis to 100kN. The load carrying capacity of the vertebral bone had been estimated to be approximately 5000N ? 8200N17. Any load borne by the prosthesis in excess of this value would, under in vivo conditions, entail damage to the vertebrae. Compression of the discs was to increase until mechanical failure or a pre-set ultimate load was reached. During the test, the load was constantly monitored and plotted against the displacement. 77 3.4.3. Test bench set-up Figure 3.4.3.a: Test 1 - Compressive load The assembled artificial disc is placed between the metal blocks in the Instron machine with the end-plates parallel to another as indicated in the schematic below. Schematic 3.4.3.a: Assembled prosthesis in the Instron machine The load was imposed vertically on the prosthesis. The force was increased at a displacement rate of 25mm/min. Picture 3.4.3.a: Assembled prosthesis in the Instron machine Metal blocks End plates Meniscus 78 Figure 3.4.3.b: Test 2 - Shear load The assembled artificial disc was placed between the metal blocks in the Instron machine with the end-plates at a 10? angle to one another, as indicated in the schematic below. Schematic 3.4.3.b: Assembled prosthesis in the Instron machine at 10? The load was imposed vertically on the prosthesis. The force was increased at a displacement rate of 25mm/min. Picture 3.4.3.b: Assembled prosthesis in the Instron machine at 10? Metal blocks End plates Meniscus 10? 79 3.4.4. Test results 3.4.4.a: Test 1 - compressive load Figure 3.4.4.a: Average displacement of the device under compression Force vs. Displacement: Test 1 0 5 10 15 20 25 30 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Displacement (mm) Fo rc e (k N ) A Figure 3.4.4.a: Load vs displacement for CCM disc and CCM core The height of the assemblies was measured before the test commenced and within 5 minutes upon completion of compression. In Test 1, no height reduction occurred on any of the five samples. 80 3.4.4.b: Test 1- shear load Figure 3.4.4.b: Average displacement of the device under compression with a 10? angle between the end-plates. Force vs. Displacement: Test 2 0.00 2.00 4.00 6.00 8.00 10.00 12.00 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 Displacement (mm) Fo rc e (k N ) A Figure 3.4.4.b: Load vs displacement for CCM & CCM core at 10? The results of Test 2 are shown in Figure 3.4.4.b. This graph is divided into two regions, each representing a phase through which the test samples went. The regions represent the following: ? Region A: On average, the first 0.31mm of vertical displacement of the test, the core rotated within the bottom end-plate up to an average applied load of 1.36kN (highest result is 1.74kN at 0.36mm and the lowest result 1.3kN at 0.3mm). ? Region B: Due to the angled assembly, the core rotated within the cup of the end- plate until the final position was found where the meniscus could not rotate any further. A linear elastic region was evident thereafter. The test was restrained to a maximum of 10 kN and no mechanical failure of the CCM end-plates or CCM cores was noted. 81 3.4.5. Discussion Test 1 - Compressive load In Figure 3.4.4.a, it can be seen that the samples remain within the elastic region of the materials. Recoverable strain occurs in this region. All loads applied on the assembled samples were in excess of 25kN. The average displacement at 25kN load is 1.29mm. Test 2 - Shear load The graph in Figure 3.4.4.a: is divided into two regions, each representing a phase through which the test samples went. Region A represents the rotation of the core within the bottom end-plate until the final position; Region B represents the linear elastic displacement. No mechanical failure occurred. 3.4.6. Conclusion The cumulative mass loss of the disc was 0.3 % for the core and 0.1 % for the entire disc prosthesis at the end of the 10 million cycles. This had no impact on the integrity or function of the disc prosthesis. The results of the static testing showed that the assembled CCM end-plate with CCM core prosthesis recovered within the elastic region after a load of 25kN was imposed axially. No visible or measurable deformation or deterioration was recorded. The shear test result was carried out with a 10o inclination between the two end- plates. No constraint was placed on the top end-plate without the retention. The test showed an elastic region of the CCM core up to the tested10kN. Under the maximum load, reported by Wilke H-J3 (1998), of 4140N when lifting 20kg in a hunch-backed posture, the Kineflex-M lumbar prosthesis will not permanently deform, nor will any temporary deformation result in constraint of movement of the prosthesis. 82 3.5. References: Results: Pre-clinical, in vitro testing of the Kineflex lumbar disc prosthesis 1. ASTM F04.25.05.01: Standard test methods for static and dynamic characterization of spinal artificial discs. Z8924Z Draft I, February, 2003. 2. Nachemson A: The load on lumbar disks in different positions of the body. Clin Orthop and Relat Res. 1966;45:107-122. 3. Wilke H-J: Workshop: Pr?fkriterien f?r Wirbels?ulenimplantate, 1998. 4. Eijkelkamp MF, van Donkelaar CC, Veldhuizen AG, et al. Requirements for an artificial intervertebral disc. Int J Artif Organs. 2001;24:311-321. 5. Dvorak J, Punjabi MM, Chang DG, et al. Functional radiographic diagnosis of the lumbar spine. Flexion-extension and lateral bending. Spine. 1991;16:562- 571. 6. Pearcy M, Portek I, Shepherd J. Three-dimensional X-ray analysis of normal movement in the lumbar spine. Spine. 1984:9;294-297. 7. Putto E, Tallroth K. Extension-flexion radiographs for motion studies of the lumbar spine: A comparison of two methods. Spine. 1990;15:107-110. 8. Hayes MA, Howard TC, Gruel CR, et al. Roentgenographic evaluation of lumbar spine flexion-extension in asymptomatic individuals. Spine. 1989;14:327-331. 9. De Kleuver M, Oner FC, Jacobs WCH. Total disc replacement for chronic low back paid: background and systematic review of the literature. Eur Spine J. 2003;12:108-116. 10. Vogt L, Pfeifer K, Portscher M, et al. Influences of nonspecific low back pain on three-dimensional lumbar spine kinematics in locomotion. Spine. 2001;26:1910-1919. 11. Cromwell R, Schultz AB, Beck R, et al. Loads on the lumbar trunk during level walking. J Orthop Res. 1989;7:371?377. 12. Callaghan J P, Patla A E, McGill S M. An examination of rigid link segment models for gait analysis. In: Proceedings of the Ninth Biennial Conference and Symposia of the Canadian Society for Biomechanics. Vancouver: Simon Fraser University. 1996: 216-217. 83 13. Taylor NF, Evans OM, Goldie PA. Angular movements of the lumbar spine and pelvis can be reliably measured after four minutes of treadmill walking. Clin Biomech. 1996;11:484?486. 14. Endo MM, Barbour PSM, Barton DC, et al. Comparative wear and wear debris under three different counterface conditions of cross-linked and non- crosslinked ultra high molecular weight polyethylene. Bio-Med Mat Eng. 2001;11:23-35. 15. Tipper JL, Firkins PJ, Besong AA, et al. Characterization of wear debris from UHMWPE on zirconia ceramic, metal-on-metal and alumina ceramic-on- ceramic hip prostheses generated in a physiological anatomical hip joint simulator. Wear. 2001;250:120-128. 16. Tipper JL, Ingham E, Hailey JL, et al. Quantitative analysis of polyethylene wear debris, wear rate and head damage in retrieved Charnley hip prostheses. Journal of Materials Science, Materials in Medicine. 2000;11:117-124. 17. Cunningham B. presentation on Charit? PMA submission at FDA Orthopedic Device Panel meeting June 2, 2004. 84 4. RESULTS: BOOK CHAPTER (ELSEVIER): James J. Yue, Rudolf Bertagnoli, Paul McAfee, and Howard A. Motion Preservation Surgery of the Spine: Advanced Techniques and Controversies. CHAPTER 42: KINEFLEX: Ulrich R. H?hnle, Malan De Villiers, and Ian R. Weinberg 4.1. Introduction In the middle of 2006, I was approached to write the chapter of a new book on motion preservation surgery in the human spine, edited by leading spine surgeons in the field (James J. Yue, Rudolf Bertagnoli, Paul McAfee, and Howard An) and published by Elsevier Publishers. By then, I had presented extensively at national and international meetings (see Publications and Presentations) on surgical outcome with different lumbar disc prostheses, primarily with the lumbar Kineflex intervertebral disc prosthesis. The book chapter elaborates on the ideas behind the development of the prosthesis, the pre-clinical testing in the laboratory, the properties particular to the device and the insertion technique. It then follows with the clinical short-term outcome studies of the first patients, who had by then completed a 2-year follow-up. Co-authors are Malan de Villiers (PhD), who performed a large part of the pre- clinical testing and who is a co-developer of the prosthesis, and Dr Ian R. Weinberg, who is my partner in practice, co-developer of the prosthesis and co-investigator in the clinical trials. The book was published in June 2008 and I received a complimentary copy from the publisher, which can be reviewed. 85 86 87 88 89 90 91 92 93 5. RESULTS: FIRST PUBLICATION: Ulrich R. H?hnle, MD, FCS (Ortho), Ian R. Weinberg, MD, FCS (Neuro), Karen Sliwa MD, PhD, Barry M.B.E. Sweet, MD, PhD, and Malan de Villiers, PhD. Kineflex (Centurion) lumbar disc prosthesis: Insertion technique and two-year clinical results in 100 patients. SAS Journal. Winter 2007;1:28?35. DOI: SASJ-2006- 0005-RR. 5.1. Introduction Worldwide, this is the first peer-reviewed publication on the Kineflex lumbar disc prosthesis. It was published in the first volume of the SAS Journal, the official journal of the Spine Arthroplasty Society. The article presents the design and the insertion technique of the Kineflex lumbar disc prosthesis. It further investigates the radiological placement accuracy and two year clinical outcome of the first 100 patients treated. 94 95 96 97 98 99 100 101 102 103 6. RESULTS: SECOND PUBLICATION: Ulrich R. H?hnle, MD, FCS (Ortho), Karen Sliwa, MD, PhD, Ian R. Weinberg, MD, FCS (Neuro), Barry MBE Sweet, MD, PhD, Malan de Villiers, PhD, and Geoffrey P. Candy, PhD. Lumbar disc replacement for junctional decompensation after fusion surgery: Clinical and radiological outcome at an average follow-up of 33 months. SAS Journal. Summer 2007;1:85?92. DOI: SASJ-2007- 0006-RR. 6.1. Introduction This publication reports on our experience with the use of total disc replacement (TDR) in patients, who had previously undergone fusion surgery and had developed Adjacent Segment Disease (ASD). ASD is an ?off-label? indication for TDR and only one previous publication had dealt with this particular problem in a larger patient group (Bertagnoli, et al. 2006). Our patient sample was published in the SAS Journal, the official journal of the Spine Arthroplasty Society. 104 105 106 107 108 109 110 111 112 7. RESULTS: THIRD PUBLICATION Ulrich R. H?hnle, MD, FCS (Ortho), Karen Sliwa MD, PhD, Malan de Villiers, PhD, Ian R. Weinberg, MD, FCS (Neuro), Barry M.B.E. Sweet, MD, PhD, and Geoffrey P. Candy, PhD. Is degenerative spondylolisthesis a contraindication for total disc replacement? Kineflex lumbar disc replacement in 7 patients with 24-month follow-up. SAS Journal. Spring 2008;2:92?100. DOI: SASJ-2007- 0125-NT This publication summarizes our experience with the use of total disc replacement (TDR) in patients with degenerative spondylolisthesis (DSPL). DSPL is an ?off- label? indication for TDR and no articles had previously been published on this particular indication. The study comprises a pilot study with only a limited number of patients involved. It was published in the SAS Journal, the official journal of the Spine Arthroplasty Society. 113 114 115 116 117 118 119 120 121 122 123 8. OVERALL DISCUSSION 8.1. Motion preservation surgery history In the opening chapter of a recently published book on motion preservation, McKenzie (2008) compares the spine to a ?multi-pinned ship?s mast? with power, agility, endurance and grace to provide mobility with stability and freedom from pain. With damage to structure or rigging, it can still function after ?bracing the mast? or ?reefing the sails? and by careful, energetic sailing until it is ?re-stepped by fixing? or fusion. His lesson learned from the past is that the spine cannot function at full purpose or in longevity without the essential duality of ?stability and motion?. When damage, disorder or discectomy leaves excessive motion at one of the spine?s segments, it often spawns the corrosion of facet arthritis at the same level, with instability and breakdown at the next level or the levels beyond (McKenzie AH, 20081). Any form of decompression spinal surgery performed to a motion segment, without instrumentationis, at least in the short term, a motion preserving surgery, but fails to re-stabilize and to re-orientate the FSU. Motion preserving spine stabilisation forms a rapidly evolving, fascinating part of modern surgical spine treatment. Intervertebral disc replacement comprises currently the largest portion of motion preservation surgery. Disc prostheses, made out of a variety of materials, implants with a variety of fixation principles and degree of constraint of the mechanism, and which use a range of insertion techniques, may render different clinical outcomes in different indications. We are only at the very beginning of understanding the advantages and limitations of TDR in surgery for a failed FSU. There is also limited understanding of the influence of different types of prostheses on the outcome in different clinical conditions. Hip arthroplasty surgery has evolved from being highly experimental, in the form of tissue interposition arthroplasties at the change from the nineteenth to the twentieth century, to be a procedure considered as the ?golden standard for the treatment of the 124 arthritic hip?, with the highest patient satisfaction ratings of all orthopaedic procedures and with clear indication and acceptable complication rates (Learmonth, et al. 20072). We should not be discouraged by the upsets and setbacks of spinal arthroplasty, but rather try to learn from past failures. The purpose of total disc replacement is to restore the intervertebral segment and protect the adjacent FSUs against abnormal loading conditions. A first description of the surgical insertion of a lumbar prosthetic nucleus replacement with a steel ball was published in 1966 by Fernstr?m (Fernstr?m U, 19663). Despite some excellent results, it failed because of subsidence into the bony end-plate due to failure of weight distribution at the prosthesis/end-plate interphase. Modern total lumbar disc replacement procedures commenced in 1984, with the insertion of the first-generation Charit? disc prosthesis by Karin B?ttner-Janz. The prosthesis was later perfected, but the initial mechanism was carried through to the third-generation device, which is still in use today (Charit? SB III) (B?ttner-Janz, et al. 19874; B?ttner-Janz & Schellnack, 19905). Despite the 24-year history of modern type total lumbar disc replacement, which started with the development of the Charit? disc prosthesis, there remains considerable controversy about the value, the indications and contraindications, the materials used and the amount of constraint within the prosthetic mechanism. Considering the complex nature of the FSU, we should expect that it will be some time before there is full understanding of the best prosthetic articulation of this joint (Sakalkale, et al. 20036; Moumene & Geisler, 20077). 8.2. Motion preservation surgery - what?s different in the spine? The motion of the FSU, compared to other weight bearing joints in the body, only exerts limited motion (less than 10 degrees in all directions). It comprises 3 articulations, viz.: the disc articulation in the front, and the paired facet joints in the back. The disc is not a classical, synovial joint. Therefore, unlike the hip joint (which constitutes a ball and socket joint), but similar to the knee joint, the FSU involves 125 joints other than the disc itself (the knee cap in the knee; the facet joints in the FSU). The restraints of the knee joint and FSU are mainly ligamentous and capsular. In the FSU, the disc itself - with its complex fibrous architecture of the outer annulus and the more pliable core providing tensioning of the annulus under load - forms part of the restraint of the articulation. The motion mechanism incorporates a variable centre of rotation. The FSU differs from hip and knee joints by the greater shock-absorbing properties within the joint and the fact that the FSU forms part of a sequence of similar looking joints, which are aligned within the spinal column, like a chain. Through its ligamentous and muscular support structures, the lumbar spine acts like an elastic spring. It is the dependence on ligamentous restraints and the more complex motion patters that caused the knee joint replacement to lag behind the hip joint replacement before it became a reliable and lasting new joint. It involved going from more constraining prostheses to implants with lesser constraint and placing more emphasis on so-called soft tissue balancing. TDR is only one motion preserving surgical approach used to try to resolve chronic LBP. Other procedures, like a large variety of pedicle screw based posterior shock- absorbing devices or interspinous spacer devices, address primarily the posterior elements of the motion segment. They all aim to reduce the mobility in the FSU, allowing motion through a limited and ideally painless range of movement. The advantage of posterior motion preserving surgery is the familiarity of most surgeons with the posterior approach; the disadvantage is the inability to address failure of the FSU close to the centre of motion and the inability to improve the sagittal balance (flat back deformity), which is one of the consequences of disc height loss in DDD. 8.3. Disc arthroplasty ? what do we know? Most lumbar fusions, today, are performed for degenerative conditions. There is an increasing focus on the disc as the source of lumbar pain. This provides many challenges as all discs degenerate with age, yet only a few cause significant debilitating pain. Strict adherence to mainstream indications and proper surgical techniques is essential. (Dunn RN, 20088). 126 There is increasing evidence in the literature that positive spinal balance in spinal deformity correlates with an increase in spinal symptoms (Glassman, et al. 20059; Kumar, et al. 200110). This may well be the primary reason why circumferential fusion renders superior long term results and is more cost effective when compared to postero-lateral fusion alone (Soegaard, et al. 200711). Failed spinal fusion surgery is a serious professional challenge for the treating physician. In a recent publication, Shipley expertly dealt with the problem when describing a practical and very clinical approach (Shipley JA, 200812). Sagittal imbalance seems to be a common cause of failed back syndrome; complex posterior osteotomy, or combined posterior and anterior surgery, is often required to achieve adequate correction (Jang, et al. 200713; Chang, et al. 200814). There is weak but increasing evidence that disc replacement, when compared to fusions, may be advantageous in protecting other lumbar levels from degeneration or at least in slowing down the incidence of ASD (Harrop, et al. 200815; Chun-Kun, et al. 200816). There are no publications on ASD, which provide a comparison of degeneration adjacent to disc replacement with the natural history of degeneration of this segment without surgery. Such studies would be useful in order to determine whether the added stiffness of the instrumented segment would lead to accelerated degeneration of the adjacent FSU or whether the change in spinal alignment to the adjacent segment might even be protective (Tournier, et al. 200717; H?hnle, et al. 200718). After primary disc replacement surgery, no significant changes in overall spinal alignment parameters were demonstrated (Le Huec, et al. 200518; Cakir, et al. 200520), although internal realignment within the lumbar spine occurred. TDR resulted in increased lordosis in the lower (instrumented) part of the lumbar spine and decreased lordosis of the upper, non-instrumented lumbar area (Tournier, et al. 200717). It is also my own experience, that patients with severe disc degeneration in only the two caudal lumbar motion segments, on lateral standing radiographs, often show a 127 localized flat-back deformity in the lower lumbar spine. In the upper lumbar spine, a compensatory hyperlordosis with retrolisthesis of the otherwise normal upper lumbar levels develops. After disc replacement surgery, the lower lumbar lordosis increases, whereas the upper lumbar lordosis and the retrolisthesis decrease. The result is a reorientation within the lumbar spine with no or very small changes in the total lumbar lordosis. In patients with ?disc replacement after previous fusion surgery?, we were able to show a significant change in spinal and pelvic alignment parameters after surgery (H?hnle, et al. Summer 200721). The use of TDR in failed fusion surgery as cranial top-up, above an existing fusion, is a logical treatment in ASD. Apart from absorbing part of the stresses being transmitted to the cranial lumbar levels, TDR is able to improve the sagittal alignment by increasing anterior column height. Careful consideration of the overall sagittal spinal balance is of paramount importance in the planning of this procedure. The disc prosthesis comprises a mobile spacer that will passively adjust to a certain position by the restrained surrounding soft tissue structures in order to achieve a balanced position. Due to a flat back deformity within the fusion, the spinal balance is often significantly disturbed after previous fusion surgery. Lumbar TDR still has considerable drawbacks. TDR can only approximate the natural motion of an intact SMS. The prostheses presently in use, in their material properties, differ significantly from the properties of the natural disc. The only prostheses with successful long term follow-up are mechanical discs (Lemaire, et al. 200522 ;Tropiano, et al. 200523), which offer no elastic properties. Visco-elastic discs have, thus far, not rendered good sustainable long term results. Anterior revision surgery, after previous anterior spine surgery for fusion or TDR purposes, presents a significant challenge to the access surgeon. Re-exposure of the spine requires mobilisation of the peritoneal sac as well as mobilisation of the major vessels and ureter, which are now strongly encased in fibrous tissue and firmly adherent to each other and the surface of the spine. Complications reported in the literature have varied widely, with vascular incidences ranging from 5% to 89%. The difference in complications results from the experience of the access surgeon, the pre- 128 operative planning and the inclusion of cases with lesser risk (as anterior revision of other levels than the index levels) (Brau, et al. 200824; Nguyen, et al. 200625; Punt, et al. 200826; Wagner, et al. 200627). The L4/5 disc space is the most difficult to revise; the L5/S1 is generally the easiest, except in patients with caudally situated venous confluents. A pre-revision venogram with contrast injected simultaneously into both femoral veins has greatly helped me to obtain an exact image of the venous vascular configuration in revision surgery. The future use of adhesion barriers in primary anterior spine surgery may reduce the dangers of anterior revision surgery (Patel, et al. 200828). Revision surgery should only be undertaken by highly experienced vascular and arthroplasty surgeons. From the onset of modern disc arthroplasty, the recommended patient age ranged from 18 - 50 (60) years. This recommendation includes considerably younger patients than recommended in any other arthroplasty; hip and knee arthroplasty is primarily performed in patients past the recommended age range for spinal arthroplasty. Considering the dangers of anterior revision surgery, this needs to be reconsidered. 8.4. Disc arthroplasty ? the way forward There is evidence in the literature that positive sagital balance is associated with an increase in lower back symptoms (Glassman S, et al. 20059) and surgical flat back correction during fusion surgery positively correlates with improved clinical outcome of fusion surgery (Kumar, et al. 200110). Only recently have classification systems been published for assessing sagital plane deformities (Roussouly, et al. 200529; Jang, et al. 200730). Jang et al. (2007) found that kyphosis at the T-L junction was particularly detrimental to the overall sagittal balance. There are no publications investigating the influence of pre-existing thoracic deformities on outcome of TDR. Total disc replacement, by increasing the anterior column height can improve sagittal imbalance. Only a limited correction of flat back deformity within a FSU can be achieved. Where there is a need for stronger flat back correction, the insertion of a TDP will lead to hyper-extended disc prosthesis during upright standing posture. Over time, this will lead to over-stretching of the anterior soft tissue restraint structures and overloading of the posterior spinal elements. Recurrence of symptoms 129 (LBP and SS) will be the consequence. With increasing experience with the lumbar disc prostheses, I became more aware of the overall importance of the sagittal spinal balance in failed fusion surgery (H?hnle, et al. Summer 200721). Long, whole-spine lateral standing radiographs should be performed on all patients undergoing lumbar TDR. Research is urgently needed into the influence of pre-existing thoracic and thoraco-lumbar kyphosis on the clinical and radiological outcome of disc replacement surgery. Siepe et al. (2007) retrospectively analyzed their patient cohort after pro-disc insertion. With the pro-disc, they found a better outcome in L4/5 disc replacement when compared to L5/S1 disc replacement; the outcome was poorer with double level replacements when compared to single level replacements. They further investigated clinical outcome in relation to the initial clinical diagnosis and had the best outcome in patients with DDD and associated soft disc herniation (Siepe, et al. 200632). These are important first steps towards the comprehension of what might determine the success of TDR. More research into indication related outcome will be required and the results need to be compared to conventional (fusion) treatment. The clinical outcome has been shown to depend on the accuracy of placement of the disc prosthesis (McAfee, et al. 200533; Moumene, Geisler. 20077). Using the Kineflex lumbar disc prosthesis, we could achieve excellent placement accuracy in our patient cohort. The placement accuracy was equally good in patients with more advanced disc space collapse (H?hnle UR, et al. 200734). We are of the opinion that the amount of disc space collapse should not necessarily influence the decision whether TDR can be performed. Significant facet arthrosis is considered as contraindication for total disc replacement. There is no consensus on whether artificial disc replacement, or which type of disc prosthesis, increases or decreases facet loading. Fixed core implants seem to produce more facet joint incongruence during motion and they seem to be less tolerant towards slight misplacement within the disc space (Rousseau, et al. 200635; Moumene, Geisler. 20077). 130 Although it may be likely and logical, to date there is no proof that the amount of facet arthrosis has any influence on the clinical results of TDR. As described in our publication in Chapter 7, we implanted disc prostheses in seven selected patients with Grade 2 spondylolisthes and/or localised kyphosis - a condition widely considered as a contraindication for TDR. The condition is associated with significant facet arthritis, incongruence of the facet joint and a segmental kyphosis. The very particular insertion technique of the Kineflex disc prosthesis allowed an almost complete reduction of the deformity through a single access anterior approach and rendered excellent two year clinical and radiological results (H?hnle, et al. Winter 200718). Further controlled studies will be required to confirm the viability of this procedure for DSPL. A recent publication investigated the existing literature for factors that might affect the outcome of lumbar TDR. The authors concluded that there is only limited, lower level data available on most factors determining outcome and they found only weak evidence that TDR might prevent ASD (Zindrick, et al. 200836). 8.5. Summary of this research project As part of this research project, we developed a new intervertebral disc prosthesis with several international patents attached to the design of the prosthesis, the instrumentation as well as the insertion technique. In extensive in vitro studies, we could show the durability of the Kineflex disc prosthesis over the long term. This, together with our initial clinical outcome results, formed the basis for the acceptance into a ?prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the KINEFLEX Lumbar Artificial Disc versus the CHARIT?? Artificial Disc?. As lumbar total disc replacement traditionally carried restrictive indications, our initial aim was to develop a prosthesis that could be used in a wider range of indications. In our studies we could demonstrate accurate placement even in severely collapsed disc spaces (Chapter 5). We successfully applied the Kineflex disc 131 prosthesis in patients with ASD who had undergone previous fusion surgery (Chapter 6) and in patients with DSPL, which both constitute contraindications for the insertion of artificial disc prosthesis. The successful outcome in these off-label indications will have to hold up in long term follow-up and requires confirmation in larger, controlled trials, in order to determine what part of the traditional fusion surgery will finally be replaced by motion preserving surgery. 8.6. References: Overall discussion 1. McKenzie Alvin H. The basis for motion preservation surgery: Lesson learned from the past. in Yue JJ, Bertagnoli R, McAfee PC, An HS (eds): Motion Preservation Surgery of the Spine: Advanced techniques and controversies. Philadelphia, Elsevier 2008, pp 3-10. 2. Learmonth ID, Young C, Rorabeck C. The operation of the century; total hip replacement. Lancet 2007. 370;1508?1519. 3. Fernstr?m U. Arthroplasty with intercorporal endoprosthesis in herniated disc and in painful disc. Acta Chir Scand. 1966;355:154?159. 4. B?ttner-Janz K, Schellnack K, Zippel H. Eine alternative Behandlungsstrategie beim lumbalen Bandscheibenschaden mit der Bandscheiben-endoprothese Modulartyp SB Charit?. Z Othop. 1987;125:1?6. 5. B?ttner-Janz K, Schellnack K. Bandscheibenendoprothetik.Entwicklungsweg und gegenw?rtiger Stand. Beitr OthopTraumatol. 1990;37:137?147. 6. Sakalkale DP, Bhagia SA, Slipman CW. A Historical Review and Current Perspective on the Intervertebral Disc Prosthesis. Pain Physician 2003.6;195- 198. 7. Moumene M, Geisler FH. Comparison of biomechanical function at ideal and varied surgical placement for two lumbar artificial disc implant designs. Mobile core versus fixed core. Spine 2007;32;1840-1851. 8. Dunn, Robert N. Lumbar fusion- indications and surgical options. SAOS Journal. 2008;7(2):8-12. 132 9. Glassman S, Bridwell K, Dimar J, et al The Impact of Positive Sagittal Balance in Adult Spinal Deformity. Spine. 2005;30;2024-2029. 10. Kumar MN, Baklanov A, Chopin D. Correlation between sagittal plane changes and adjacent segment degeneration following lumbar spine fusion. Eur Spine J 2001;10 314?319. 11. Soegaard R, Bunger C, Christiansen T et al. Circumferential Fusion Over Posterolateral Fusion in Cost-Utility Evaluation of a RCT in Chronic Low Back Pain. Spine 2007;32;2405-2414. 12. Shipley John A. An approach to failed lumbar fusion surgery SAOS Journal. 2008;7(2):13-16+58. 13. Jang JS, Lee SH, Min JH et al. Surgical treatment of failed back surgery syndrome due to sagittal imbalance. Spine. 2007;32;3081-3087. 14. Chang K-W, Cheng C-W, Chen H-C, et al.Closing-opening wedge osteotomy for the treatment of sagittal imbalance. Spine. 2008. 33:1470-1477. 15. Harrop JS, Youssef JA, Maltenfort M et al. Lumbar adjacent Segment degeneration and disease after arthrodesis and total disc arthroplasty. Spine 2008.33;1701?1707. 16. Chun-Kun P, Kyeo0ng-Sik R, Won-Hee J. Degenerative changes of discs and facet joints in lumbar total disc replacement using ProDisc II. Spine. 2008.33;1755?1761. 17. Tournier C, Aunoble S, Le Huec JC. Total disc arthroplasty; consequences for sagittal balance and lumbar spine movement. Europ Spine J. 2007.16;411- 421. 18. H?hnle UR, Sliwa K, De Villiers M, et al. Is degenerative spondylolisthesis a contraindication for total disc replacement? Kineflex lumbar disc replacement in 7 patients with 24-month follow-up. SAS Journal, Spring 2008;2:92-100. 19. Le Huec JC, Basso Y, Mathews H, et al. The effect of single-level, total disc arthroplasty on sagittal balance parameters: a prospective study. Eur Spine J. 2005;14:480?486. 20. Cakir B, Richter M, Kafer W, et al. The impact of total lumbar disc replacement on segmental and total lumbar lordosis. Clin Biomech. 2005;20:357?364. 21. H?hnle UR, Sliwa K, Weinberg IR, et al. Lumbar disc replacement for junctional decompensation after fusion surgery: Clinical and radiological 133 outcome at an average follow-up of 33 months. SAS Journal. Summer 2007;1:85-92. 22. Lemaire JP, Carrier H, Ali E-H S. clinical and radiological outcomes with the charit?? artificial disc a 10-year minimum follow-up. J Spinal Disord Tech. 2005;18:353-359. 23. Tropiano P, Huang RC, Girardi FP et al. Lumbar total disc replacement: Seven to eleven-year follow-up. J Bone Joint Surg [Am]. 2005;87:490?496. 24. Brau, SA, Delamarter RB, Kropf MA, et al. Access strategies for revision in anterior lumbar surgery. Spine 2008.33;662?1667. 25. Nguyen HV, Akbarnia BA, Van Dam BE, et al. 2006. Anterior exposure of the spine for removal of lumbar interbody devices and implants. Spine 2006, 31(21); 2449-2453. 26. Punt IM, Visser VM, Van Rhijn LW, et al. Complications and reoperations of the SB Charite lumbar disc prosthesis; Experience with 75 patients. Eur Spine J 2008.17;36?43. 27. Wagner WH, Regan JJ, Leary SP, et al. Access strategies for revision or explantation of the Charite lumbar artificial disc replacement. J Vasc Surg 2006;44:1266?1272. 28. Patel AA, Brodke DS, Pimienta L, et al. Revision strategies in lumbar total disc arthroplasty. Spine. 2008;33:1276-1283 29. Roussouly P, Gollogly S, Berthonnaud E, et al. Classification of the Normal Variation in the Sagittal Alignment of the Human Lumbar Spine and Pelvis in the Standing Position. Spine 2005;30:346-353. 30. Jang JS, Lee SH, Min JH, et al. Lumbar degenerative kyphosis: radiologic analysis and classifications. Spine 2007;32:2694-2699. 31. Siepe CJ, Meyer MH, Heinz-Leisenheimer M, Korge A. Lumbar total disc replacement; different results for different levels. Spine. 2007;32;782-790. 32. Siepe CJ, MayerHM, Wiechert K, et al. Clinical results of lumbar disc replacement with Pro-Disc II; three-year results for different indications. Spine. 2006;31:1923-1932. 33. McAfee PC, Cunningham B, Holsapple G, et al. A prospective, randomized, multicenter Food and Drug Administration Investigational Device Exemption Study of lumbar total disc replacement with the CHARIT?? artificial disc versus lumbar fusion: Part II: Evaluation of radiographic outcomes and 134 correlation of surgical technique accuracy with clinical outcomes. Spine 2005;30;1576-1583. 34. H?hnle UR, Weinberg IR, Sliwa K, et al. Kineflex (Centurion) lumbar disc prothesis: Insertion technique and 2-year clinical results in 100 patients. SAS Journal. Winter 2007;1:28-35. 35. Rousseau MA, Bradford DS, Bertagnoli R et al. Disc arthroplasty design influences intervertebral kinematics and facet forces. Spine j. 2006;6;258-266. 36. Zindrick MR, Zermiadianos MN, Voronov LI, et al.An evidence-based medicine approach in determining factors that may affect outcome in lumbar total disc replacement. Spine. 2008;33:1262-1269. 135 9. APPENDICES 9.1. Ethical clearances 136 137 9.2. Questionnaires 9.2.1. VAS Pain Intensity Worksheet (VAS) Lumbar Subject Initials ___________________ Date of Birth: Date of office visit Visit Type: pre-op, post-op, 6 wks, 3 mo, 6 mo, 12 mo, 24 mo Directions for Subject Below is a scale with the left end of the scale indicating no pain and the right end of the scale indicating the worst pain possible. Please use this scale to record the average amount of back pain and leg (sciatica) pain you have had since your last visit (or for the past six months if this is the first time you are completing this scale) while you were at rest. Make a circle around the number that corresponds to the level of pain. 0 ? 10 scale (0= No pain, 10 = Worst pain) 0 1 2 3 4 5 6 7 8 9 10 Subject Signature Date Study Coordinator Please note the value below Study Co-ordinator Signature Date 138 9.2.2. ODI Name Address Date Date of birth Age Occupation How long have you had back pain? Years Months Weeks How long have you had leg pain? Years Months Weeks THE OSWESTRY DISABILITY INDEX FOR BACK PAIN This questionnaire has been designed to give us information as to how your back pain has affected your ability to manage everyday life activities. Please answer every section, and mark in each section the one box that applies to you. We realize you may consider that two of the statements in any one section relate to you, but please just mark the box that most closely describes your present day situation. Section 1. Pain Intensity Section 6. Standing A. I can tolerate the pain I have without having to use pain killers. A. I can stand as long as I want without extra pain. B. The pain is bad, but I manage without taking pain killers. B. I can stand as long as I want, but it gives me extra pain. C. Pain killers give complete relief from pain. C. Pain prevents me from standing for more than 1 hour. D. Pain killers give moderate relief from pain. D. Pain prevents me from standing for more than 30 minutes. E. Pain killers give very little relief from pain. E. Pain prevents me from standing for more than 10 minutes. F. Pain killers have no effect on the pain and I do not use them. F. Pain prevents me from standing at all. Section 2. Personal Care (Washing, Dressing, etc) Section 7. Sleeping A. I can look after myself normally without causing extra pain. A. Pain does not prevent me from sleeping well. B. I can look after myself normally but it causes extra pain. B. I can sleep well only by using tablets. C. It is painful to look after myself and I am slow and careful. C. Even when I take tablets I have less than six hours sleep. D. I need some help but manage most of my personal care. D. Even when I take tablets I have less than four hours sleep. E. I need help every day in most aspects of self care. E. Even when I take tablets I have less than two hours sleep. F. I do not get dressed, wash with difficulty and stay in bed. F. Pain prevents me from sleeping at all. Section 3. Lifting Section 8. Sex Life A. I can lift heavy weights without extra pain. A. My sex life is normal and causes no extra pain. B. I can lift heavy weights but it gives extra pain. B. My sex life is normal but causes some extra pain. C. Pain prevents me from lifting heavy weights off the floor, but C. My sex life is nearly normal but is very painful. I can manage if they are conveniently positioned, eg on a table. D. Pain prevents me from lifting heavy weights, but I can manage D. My sex life is severely restricted by pain light to medium weights if they are conveniently positioned. E. I can lift only very light weights. E. My sex life is nearly absent because of pain. F. I cannot lift or carry anything at all. F. Pain prevents any sex life at all. Section 4. Walking Section 9. Social Life A Pain does not prevent me walking any distance. A. My social life is normal and gives me no extra pain. B. Pain prevents me walking more than 1 km. B. My social life is normal but increases the degree of pain. C. Pain prevents me walking more than ? km. C. Pain has no significant effect on my social life apart from limiting my more energetic interests, eg dancing, etc. D. Pain prevents me walking more than ? km. D. Pain has restricted my social life and I do not go out as often. E. I can only walk using a stick or crutches. E. Pain has restricted my social life to my home. F. I am in bed most of the time and have to crawl to the toilet. F. I have no social life because of pain. Section 5. Sitting Section 10. Traveling A. I can sit in any chair as long as I like. A. I can travel anywhere without extra pain. B. I can only sit in my favorite chair as long as I like. B. I can travel anywhere, but it gives me extra pain. C. Pain prevents me from sitting more than 1 hour. C. Pain is bad, but I manage journeys over two hours. D. Pain prevents me from sitting more than ? hour. D. Pain restricts me to journeys of less than one hour. E. Pain prevents me from sitting more than 10 minutes. E. Pain restricts me to short necessary journeys under 30 minutes F. Pain prevents me from sitting at all. F. Pain prevents me from traveling except to the doctor/hospital. Comments 139 9.2.3. Own questionnaire: Pre-Op (Dr Uli H?hnle / Dr Ian Weinberg) PRE-OP QUESTIONNAIRE - KINEFLEX DISC Lumbar To be completed by the patient (please ask when in doubt) Name (Mr/Ms) Date Date of birth Height (cm) Weight (kg) Single Married Divorced Widowed Other Children: Number Age Sex PROFESSION: Employed Self-employed Retired Specify: Manual Office Driving (hrs/day) PAST MEDICAL HISTORY Previous Spine Operations: Year Operation Surgeon Result (good/poor) 1) 2) 3) more Previous other Operations: Gynaecologic: Abdominal: Others: Other illnesses: Heart disease: High blood pressure: Diabetes: Other: HABITS: Smoking ? No Yes (cigarettes per day) 140 Alcohol ? No Yes (please specify) Who referred you? (please specify) Doctor Chiropractor Physiotherapist Patient Other What non-operative treatment did you have before? Doctor Chiropractor Physiotherapist Patients Other Treatment Duration Result? Medication: Name Dose times per day per week Painkillers Anti-inflammatories Others Pain score: Back: (please mark the severity of your back pain over the last two weeks from 0 - 10) 0 10 No pain Pain as bad as can be (please choose one number) Leg: left right (please mark the severity of your pain over the last two weeks from 0 - 10) 0 10 No pain Pain as bad as can be (please choose one number) Duration of pain: please insert numbers Years Months Weeks Pain Severity: rate your pain 1 ? 10 Lying 0 10 No pain Pain as bad as can be 141 Sitting 0 10 No pain Pain as bad as can be Standing 0 10 No pain Pain as bad as can be Walking 0 10 No pain Pain as bad as can be Weakness: Do you feel any weakness in your legs? No Yes left right If yes, please specify. When do you notice it most? Work: Are you currently working? Yes No Occupation If no: Did you stop working because of back problems? Yes No Do you feel pressurized at work? Yes No Sport: Are you playing sport? Yes No Which sports? How often? If not: Did you stop because of back problems? Yes No When? Would you return to sport if your pain would allow it? Yes No What do you expect from the treatment? (please describe in your own words) Anything you think it would be important for us to know? 142 9.2.4. Own questionnaire: Post-op (Doctors U H?hnle and I Weinberg) POST-OP QUESTIONNAIRE - Kineflex Disc Lumbar To be completed by the patient (please ask when in doubt) Name (Mr/Ms) Date Date of birth Height (cm) Weight (kg) Diagnosis Procedure performed Date of operation Time since operation 6w 3m 6m 1y 2y 3y 5y 7y QUESTIONNAIRE Satisfaction with outcome of treatment Excellent Good Fair Poor Would you undergo the same operation again or recommend it to friends? Yes Don?t know No Pain score (please grade your present pain) 0 = no pain 10 = Pain as bad as can be General Before operation Today Specific today Back pain 0 5 10 No pain Pain as bad as can be Leg pain 0 5 10 No pain Pain as bad as can be Stiffness 0 5 10 No pain Pain as bad as can be Others (please explain): 143 Medication: Name Dose times per day per week Painkillers Anti-inflammatories Others Work What work do (did) you do? Do you feel like going back to your previous occupation? Yes No If you are already back at work, when did you go back? Date What are the remaining restrictions at work? Sports What sports do (did) you do? none Do you feel like going back to your previous sport? Yes No If you are back at sport, when did you go back Date What are the remaining restrictions in sport? What are the remaining restrictions in daily life? ______ What did you not like about the treatment? What did you like about the treatment? ______ What would you improve in work up and treatment? Other comments: __________________________________________ ____________ 144 9.3. Lumbar disc prosthesis - Patient consent (Doctors U H?hnle and I Weinberg) KINEFLEX DISC REPLACEMENT- LUMBAR (GENERAL) You are about to undergo a disc replacement operation. This operation is performed through a cut made between the bellybutton and the panty line. The bowels are moved to one side (together with their covering membrane) in order to reach the spine. Once at the spine, the surgeon needs to move the big vessels (aorta and vena cava with its branches) temporarily out of the way in order to remove the disc and to insert the prosthesis (disc). There is the possibility of injury to the vessels and resultant significant bleeding. The nerves that supply temperature sensation to the legs, as well as the nerves to the sexual organs, also overlie the spine. They may be irritated or in rare cases permanently damaged during the operation. This may lead to a variety of neurological complications that might be permanent or transient (see neurological complications). Behind the disc lies the spinal cord enclosed in a fluid-filled membrane. Damage to the covering membrane or the nerves can occur during the operation. The prosthesis is placed within the disc space and will maintain the movement of the motion segment. The disc that will be inserted, the Kineflex disc, is a new development. Our team has implanted over 400 Kineflex prostheses since October 2002. There is limited experience as regards the implantation and no long term results of this disc in people. The materials are well established and tested. The disc has also been tested extensively in the laboratory for wear and tear. The Kineflex disc is currently used in the US as part of a Food and Drug Administration (FDA) trial but is not approved for general use. Disc replacements with similar discs have been performed in Europe for over 10 years with good results in follow up studies. 145 We believe that the Kineflex disc combines some advantages of the older disc prostheses while eliminating certain disadvantages. The alternative operation is usually an anterior and/or posterior fusion operation, which are both well established procedures but carry certain risks and disadvantages. On the following page you will find a summary of all the possible problems that can occur in relation to the operation. We well understand that you may be anxious and afraid regarding the planned procedure. Please feel free to discuss all issues relating to this procedure with the doctor. He will be happy to elaborate further on the operation. You are also welcome to discuss any other appropriate operation after discussion with your doctor. Possible complications: General: Death Neural (nerve) injuries with weakness of the legs Vascular injury with severe bleeding Need for blood transfusion DVT and emboli (blood clots in the legs with danger to circulation) Pulmonary embolism: blood clot in the lungs Bowel injury Infection Hernia through the wound Specific: Impotence (loss of virility) ? rare Paraplegia Urine and bowel incontinence Kidney, ureter or bowel injury Retrograde ejaculation (dry orgasm) in 2 - 7% of male patients Weakness or numbness of parts of the lower limbs 146 Warm feeling in left leg Dural leak (leak of spinal fluid) Implant loosening or breaking, non-union, with need for re- operation Subsidence: sinking of the implant into the bone Residual pain in the legs or back Development of additional back or leg pain Continuous back pain with the need for a later fusion operation Any kind of anterior re-operation (revision operation) carries a much higher risk of the abovementioned complications, especially ureteric injury, vascular injury and abdominal organ injury. I have read, understood and accept all relevant facts and possible complications relating to the Kineflex disc implant procedure. NAME (print please)??????????????????.. SIGNATURE ????????????????????? DATE ??????????????. WITNESS NAME ???????????????????????.. SIGNATURE????????????????????? 147 10. REFERENCE LIST Andersen T, Videb?k TS, Hansen ES, et al. The positive effect of posterolateral lumbar spinal fusion is preserved at long-term follow-up: a RCT with 11 ? 13 year follow-up. Eur Spine J.2008;17:272-280. Andersson, Gunnar BJ. Epinemiological features of chronic low-back pain. Lancet.1999;354:581-585. ASTM F04.25.05.01. February, 2003. Standard test methods for static and dynamic characterization of spinal artificial discs. Z8924Z Draft I. Barr JS. 1950. Editorial back pain. J Bone Joint Surg [Br].1950; 32:461?569. Barrey C, Jund J, Noseda O, et al. Sagittal balance of the pelvis-spine complex and lumbar degenerative diseases. A comparative study about 85 cases. 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