Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care

North American Spine Society Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care

Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis

NASS Evidence-Based Guideline Development Committee William C. Watters III, MD, Committee Chair Jamie Baisden, MD Christopher Bono, MD, John Easa, MD Surgical Treatment Chair Robert Fernand, MD Thomas Gilbert, MD, Gary Ghiselli, MD Diagnosis/Imaging Chair Michael Heggeness, MD, PhD D. Scott Kreiner, MD, Richard Mendel, MD Natural History Chair Conor O’Neill, MD Daniel Mazanec, MD, Charles Reitman, MD Medical/Interventional Treatment Chair Daniel Resnick, MD William O. Shaffer, MD, Jeffrey Summers, MD Outcome Measures Chair Reuben Timmons, MD John Toton, MD Financial Statement This clinical guideline was developed and funded in its entirety by the North American Spine Society (NASS). All participating authors have submitted a disclosure form relative to potential conflicts of interest which is kept on file at NASS.

Comments Comments regarding the guideline may be submitted to the North American Spine Society and will be considered in development of future revisions of the work.

North American Spine Society Clinical Guidelines for Multidisciplinary Spine Care Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis

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ISBN 1-929988-22-2 NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 3

I. Introduction ...... 4

II. Guideline Development Methodology ...... 5

III. Natural History of Degenerative Lumbar Spondylolisthesis...... 9

IV. Recommendations for Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis A. Diagnosis/Imaging ...... 13 B. Outcome Measures for Treatment ...... 24 C. Medical and Interventional Treatment ...... 34 D. Surgical Treatment ...... 36

V. Appendices A. Acronyms ...... 62 B. Levels of Evidence for Primary Research Questions ...... 63 C. Grades of Recommendations for Summaries or Reviews of Studies ...... 64 D. NASS Literature Search Protocol ...... 65 E. Literature Search Parameters ...... 67 F. Evidentiary Tables ...... 80

VI. References ...... 127

Objective The objective of the North American Spine Society for adult patients with a diagnosis of degenerative (NASS) Clinical Guideline for the Diagnosis and lumbar spondylolisthesis. Treatment of Degenerative Lumbar Spondylolis- thesis is to provide evidence-based recommenda- THIS GUIDELINE DOES NOT REPRESENT tions to address key clinical questions surrounding A “STANDARD OF CARE,” nor is it intended the diagnosis and treatment of degenerative lumbar as a fixed treatment protocol. It is anticipated that spondylolisthesis. The guideline is intended to there will be patients who will require less or more reflect contemporary treatment concepts for symp- treatment than the average. It is also acknowledged tomatic degenerative lumbar spondylolisthesis as that in atypical cases, treatment falling outside this reflected in the highest quality clinical literature guideline will sometimes be necessary. This guide- available on this subject as of June 2007. The goals line should not be seen as prescribing the type, of the guideline recommendations are to assist frequency or duration of intervention. Treatment in delivering optimum, efficacious treatment and should be based on the individual patient’s need functional recovery from this spinal disorder. and physician’s professional judgment. This document is designed to function as a guideline and Scope, Purpose and Intended User should not be used as the sole reason for denial of This document was developed by the North treatment and services. This guideline is not in- American Spine Society Evidence-Based Guide- tended to expand or restrict a health care provider’s line Development Committee as an educational scope of practice or to supersede applicable ethical tool to assist practitioners who treat patients with standards or provisions of law. degenerative lumbar spondylolisthesis. The goal is to provide a tool that assists practitioners in Patient Population improving the quality and efficiency of care deliv- The patient population for this guideline encom- ered to patients with degenerative lumbar spon- passes adults (18 years or older) with a chief com- dylolisthesis. The NASS Clinical Guideline for the plaint of low back pain and/or lower extremity Diagnosis and Treatment of Degenerative Lumbar symptoms related to spinal stenosis. In general, Spondylolisthesis provides a definition and explana- the nature of the pain and associated patient char- tion of the natural history of degenerative lumbar acteristics (eg, age) are more typical of a diagnosis spondylolisthesis, outlines a reasonable evaluation of spinal stenosis than discogenic low back pain, of patients suspected to have degenerative lumbar lumbar sprain/strain, or mechanical low back pain. spondylolisthesis and outlines treatment options

Through objective evaluation of the evidence and guideline development. All participants in guideline transparency in the process of making recom- development for NASS have completed the train- mendations, it is NASS’ goal to develop evidence- ing prior to participating in the guideline develop- based clinical practice guidelines for the diagnosis ment program at NASS. This training includes a and treatment of adult patients with various spinal series of readings and exercises, or interactivities, conditions. These guidelines are developed for to prepare guideline developers for systematically educational purposes to assist practitioners in their evaluating literature and developing evidence-based clinical decision-making processes. It is anticipated guidelines. The online course takes approximately that where evidence is very strong in support of 15-30 hours to complete, and participants have recommendations, these recommendations will be been awarded CME credit upon completion of the operationalized into performance measures. course.

Multidisciplinary Collaboration Disclosure of Potential Conflicts of With the goal of ensuring the best possible care Interest for adult patients suffering with back pain, NASS All participants involved in guideline development is committed to multidisciplinary involvement in have disclosed potential conflicts of interest to their the process of guideline and performance measure colleagues and their potential conflicts have been development. To this end, NASS has ensured that documented for future reference. They will not be representatives from medical, interventional and published in any guideline, but kept on file for ref- surgical spine specialties have participated in the erence, if needed. Participants have been asked to development and review of all NASS guidelines. update their disclosures regularly throughout the It is also important that primary care providers guideline development process. and musculoskeletal specialists who care for patients with spinal complaints are represented in the development and review of guidelines that address Levels of Evidence and Grades of treatment by first contact physicians, and NASS has involved these providers in the development Recommendation process as well. To ensure broad-based representa- NASS has adopted standardized levels of evidence tion, NASS has invited and welcomes input from (Appendix B) and grades of recommendation other societies and specialties. (Appendix C) to assist practitioners in easily un- derstanding the strength of the evidence and rec- Evidence Analysis Training of All ommendations within the guidelines. The levels of evidence range from Level I (high quality random- NASS Guideline Developers ized controlled trial) to Level V (expert consensus). NASS has initiated, in conjunction with the Uni- Grades of recommendation indicate the strength of versity of Alberta’s Centre for Health Evidence, an the recommendations made in the guideline based online training program geared toward educating on the quality of the literature. guideline developers about evidence analysis and

Grades of Recommendation: In addition, a number of studies were reviewed several times in answering different questions with- A: Good evidence (Level I studies with con- in this guideline. How a given question was asked sistent finding) for or against recommending might influence how a study was evaluated and intervention. interpreted as to its level of evidence in answering that particular question. For example, a random- B: Fair evidence (Level II or III studies with ized control trial reviewed to evaluate the differ- consistent findings) for or against recommend- ences between the outcomes of surgically treated ing intervention. versus untreated patients with lumbar spinal stenosis might be a well designed and implemented Level C: Poor quality evidence (Level IV or V stud- I therapeutic study. This same study, however, ies) for or against recommending intervention. might be classified as giving Level II prognostic evidence if the data for the untreated controls were I: Insufficient or conflicting evidence not al- extracted and evaluated prognostically. lowing a recommendation for or against intervention. Guideline Development Process  Step 1: Identification of Clinical Questions The levels of evidence and grades of recommenda- Trained guideline participants were asked to submit tion implemented in this guideline have also been a list of clinical questions that the guideline should adopted by the Journal of Bone and Joint Surgery, address. The lists were compiled into a master list, the American Academy of Orthopaedic Surgeons, which was then circulated to each member with Clinical Orthopaedics and Related Research, the a request that they independently rank the ques- journal Spine and the Pediatric Orthopaedic Soci- tions in order of importance for consideration in ety of North America. the guideline. The most highly ranked questions, as determined by the participants, served to focus the In evaluating studies as to levels of evidence for guideline. this guideline, the study design was interpreted as establishing only a potential level of evidence.  Step 2: Identification of Work Groups As an example, a therapeutic study designed as a Multidisciplinary teams were assigned to work randomized controlled trial would be considered groups and assigned specific clinical questions to a potential Level I study. The study would then be address. Because NASS is comprised of surgical, further analyzed as to how well the study design medical and interventional specialists, it is impera- was implemented and significant short comings in tive to the guideline development process that a the execution of the study would be used to down- cross-section of NASS membership is represented grade the levels of evidence for the study’s conclu- on each group. This also helps to ensure that the sions. In the example cited previously, reasons to potential for inadvertent biases in evaluating the downgrade the results of a potential Level I ran- literature and formulating recommendations is domized controlled trial to a Level II study would minimized. include, among other possibilities, an underpow- ered study (patient sample too small, variance too  Step 3: Identification of Search Terms and high), inadequate randomization or masking of the Parameters group assignments and lack of validated outcome One of the most crucial elements of evidence measures. analysis to support development of recommendations for appropriate clinical care is the compre-

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 7 hensive literature search. Thorough assessment of Members have independently developed eviden- the literature is the basis for the review of existing tiary tables summarizing study conclusions, identi- evidence and the formulation of evidence-based fying strengths and weaknesses and assigning levels recommendations. In order to ensure a thorough of evidence. In order to systematically control for literature search, NASS has instituted a Literature potential biases, at least two work group members Search Protocol (Appendix D) which has been fol- have reviewed each article selected and indepen- lowed to identify literature for evaluation in guide- dently assigned levels of evidence to the literature line development. In keeping with the Literature using the NASS levels of evidence. Any discrepan- Search Protocol, work group members have iden- cies in scoring have been addressed by two or more tified appropriate search terms and parameters to reviewers. The consensus level (the level upon direct the literature search. which two-thirds of reviewers were in agreement) was then assigned to the article. Specific search strategies, including search terms, parameters and databases searched, are documented As a final step in the evidence analysis process, in the appendices (Appendix E). members have identified and documented gaps in the evidence to educate guideline readers about  Step 4: Completion of the Literature Search where evidence is lacking and help guide further Once each work group identified search terms/ needed research by NASS and other societies. parameters, the literature search was implemented by a medical/research librarian, consistent with the  Step 7: Formulation of Evidence-Based Rec- Literature Search Protocol. ommendations and Incorporation of Expert Consensus Following these protocols ensures that NASS Work groups held face-to-face meetings to discuss recommendations (1) are based on a thorough the evidence-based answers to the clinical ques- review of relevant literature; (2) are truly based on tions, the grades of recommendations and the a uniform, comprehensive search strategy; and (3) incorporation of expert consensus. Expert con- represent the current best research evidence avail- sensus has been incorporated only where Level able. NASS maintains a search history in Endnote, I-IV evidence is insufficient and the work group for future use or reference. has deemed that a recommendation is warranted. Transparency in the incorporation of consensus  Step 5: Review of Search Results/Identifica- is crucial, and all consensus-based recommendation of Literature to Review tions made in this guideline very clearly indicate Work group members reviewed all abstracts yield- that Level I-IV evidence is insufficient to support ed from the literature search and identified the a recommendation and that the recommendation is literature they will review in order to address the based only on expert consensus. clinical questions, in accordance with the Literature Search Protocol. Members have identified the best Consensus Development Process research evidence available to answer the targeted Voting on guideline recommendations was con- clinical questions. That is, if Level I, II and or III ducted using a modification of the nominal group literature is available to answer specific questions, technique in which each work group member the work group was not required to review Level independently and anonymously ranked a recom- IV or V studies. mendation on a scale ranging from 1 (“extremely inappropriate”) to 9 (“extremely appropriate”).  Step 6: Evidence Analysis Consensus was obtained when at least 80% of

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 8 work group members ranked the recommendation  Step 11: Identification and Development of as 7, 8 or 9. When the 80% threshold was not at- Performance Measures tained, up to three rounds of discussion and voting The recommendations will be reviewed by a group were held to resolve disagreements. If disagree- experienced in performance measure development ments were not resolved after these rounds, no (eg, the AMA Physician’s Consortium for Per- recommendation was adopted. formance Improvement) to identify those recommendations rigorous enough for measure develop- After the recommendations were established, work ment. All relevant medical specialties involved in group members developed the guideline content, the guideline development and at the Consortium addressing the literature which supports the recom- will be invited to collaborate in the development mendations. of evidence-based performance measures related to spine care.  Step 8: Submission of the Draft Guidelines for Review/Comment This guideline will be pilot tested among spine Guidelines were submitted to the full Evidence- care specialists and primary care physicians for one Based Guideline Development Committee, the year following publication. Findings of the pilot Clinical Care Council Director and the Advisory test will be considered to inform future guideline Panel for review and comment. The Advisory development. Panel is comprised of representatives from physical medicine and rehab, pain medicine/management,  Step 12: Review and Revision Process orthopedic surgery, neurosurgery, anesthesiology, The guideline recommendations will be reviewed rheumatology, psychology/psychiatry and family every three years by an EBM-trained multidisci- practice. Revisions to recommendations were con- plinary team and revised as appropriate based on a sidered for incorporation only when substantiated thorough review and assessment of relevant litera- by a preponderance of appropriate level evidence. ture published since the development of this ver- sion of the guideline.  Step 9: Submission for Board Approval Once any evidence-based revisions were incorpo- Use of Acronyms rated, the drafts were prepared for NASS Board Throughout the guideline, readers will see many review and approval. Edits and revisions to recom- acronyms with which they may not be familiar. A mendations and any other content were considered glossary of acronyms is available in Appendix A. for incorporation only when substantiated by a preponderance of appropriate level evidence. Nomenclature for Medical/  Step 10: Submission for Endorsement, Pub- lication and National Guideline Clearinghouse Interventional Treatment (NGC) Inclusion Throughout the guideline, readers will see that Following NASS Board approval, the guidelines what has traditionally been referred to as “non- have been slated for publication, submitted for operative,” “nonsurgical” or “conservative” care endorsement to all appropriate societies and sub- is now referred to as “medical/interventional mitted for inclusion in the National Guidelines care.” The term medical/interventional is meant Clearinghouse (NGC). No revisions were made at to encompass pharmacological treatment, physi- this point in the process, but comments have been cal therapy, exercise therapy, manipulative therapy, and will be saved for the next iteration. modalities, various types of external stimulators and injections. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 9 III. Definition and Natural History of Degenerative Lumbar Spondylolisthesis What is the best working What is the natural history definition of degenerative lumbar of degenerative lumbar spondylolisthesis? spondylolisthesis?

An acquired anterior displacement of The majority of patients with symptomatic one vertebra over the subjacent vertebra, degenerative lumbar spondylolisthesis and an associated with degenerative changes, without absence of neurologic deficits will do well with an associated disruption or defect in the conservative care. Patients who present with vertebral ring. sensory changes, muscle weakness or cauda equina syndrome, are more likely to develop Work Group Consensus Statement progressive functional decline without surgery. Progression of slip correlates with jobs that The literature search has revealed several reports require repetitive anterior flexion of the spine. that describe variants of degenerative spondylolis- Slip progression is less likely to occur when thesis in which the degree of anterior displacement the disc has lost over 80% of its native height is measurably affected by the posture and posi- and intervertebral osteophytes have formed. tion of the patient. These observations on position Progression of clinical symptoms does not dependent deformities may have significant impli- correlate with progression of the slip. cations for the pathophysiology and natural history of degenerative spondylolisthesis; however, no In order to perform a systematic review of the liter- longitudinal studies have yet addressed this issue. ature regarding the natural history of patients with The position dependent variants of spondylolisthe- degenerative lumbar spondylolisthesis, a defini- sis are therefore not included in this guideline. tion of degenerative lumbar spondylolisthesis was developed by consensus, following a global review Degenerative spondylolisthesis is an anatomic of the literature and definitive texts, and used as the finding. The clinical symptoms of degenerative standard for comparison of treatment groups. In spondylolisthesis, however, are varied. Patients order for a study to be considered relevant to the with degenerative lumbar spondylolisthesis can discussion, the patient population needed to fit this be asymptomatic. They can also present with axial definition of degenerative lumbar spondylolisthesis back pain, or with neurogenic claudication and/ which includes both clinical and radiographic fea- or radicular pain, with or without axial back pain. tures. The Levels of Evidence for Primary Research Therefore, the work group agreed upon this ana- Questions grading scale (Appendix B) was used to tomic definition but also evaluated the relevant rate the level of evidence provided by each article literature inclusive of the variations of clinical with a relevant patient population. The diagnosis of presentation. degenerative lumbar spondylolisthesis was examined for its utility as a prognostic factor. The central question asked was: What happens to patients with degenerative lumbar spondylolisthesis who do not receive treatment?

Matsunaga et al12 reported a retrospective review of Matsunaga et al11 reported a prospective, compara- 40 patients with spondylolisthesis. Inclusion crite- tive, cohort study of 145 patients with degenerative ria were a slippage rate of at least 5% by Morgan anterolisthesis who were either determined not to and King’s compass method and at least five year need surgery (110 patients) or refused surgery (35 follow-up of medical/interventional care. Outcome patients). The patients were followed from 10-18 measures utilized included progression of slip- years, although only 46 were followed up longer page and Japanese Orthopaedic Association (JOA) than 10 years. Outcome measures utilized included score. Joint laxity was evaluated using Carter’s test progression of spondylolisthesis (5% or more on of knee, elbow and wrist hypermobility. General radiographs), frequency of transitory radicular joint laxity using Carter’s criteria was noted in 65% pain, improvement or worsening of symptoms and of these patients as compared with 8% of normal ability to walk without help. individuals. Progression of slip was observed in 49 (34%) Progression of slippage, defined as a slippage rate patients. Of the patients who were initially felt not of 5% or more during the observation period, to need surgery, 85 (77%) experienced improve- was observed in 12 (30%) of the 40 patients. The ment during follow-up and 25 remained the same. authors defined this to be the progressive group, Of these patients, 84 (76%) continued to show no and the other 28 patients to be the nonprogressive neurologic deficits on examination. Of the patients group. Comparison of these two groups showed no who refused surgery, 29 (83%) had worsened neu- difference in age at presentation, duration of ill- rologic deficit on examination, and this was noted ness or duration of follow-up. Further, whereas the not to correlate with the progression of slippage. lumbosacral angle, lamina angle and facet inclina- Fifteen of these patients were followed over 10 tion angle were greater in both groups, there were years and all of them required an assistive device to no significant differences between these groups. ambulate.

In critique, this was a relatively small study, but In critique of this study, no validated outcome did use a validated outcome measure. This poten- measures were used. The initial sample of patients tially Level II retrospective, comparative study was was not the group initially assigned to medical/ downgraded to Level III evidence because of the interventional treatment, rather it consisted of small sample size and incomplete documentation patients who remained medically/intervention- of patient information. This study provides Level ally treated at 10 years. This study provides Level III evidence that slip is more likely to progress II evidence that in patients who initially do not in laborers whose jobs require repetitive anterior have neurologic deficits, the majority will do well flexion of the spine. Progression of slip is less likely with conservative care. Patients who present with in the presence of a relative intervertebral height of sensory changes, muscle weakness or cauda equina 20% or less, intervertebral osteophyte formation, syndrome, are more likely to develop progressive subcartilagenous sclerosis or ligamentous ossifica- functional decline without surgery. Progression tion, suggesting that mechanisms of restabilization of the slip does not correlate with progression of prevent progression of the slip. Progression of the clinical symptoms. Radicular pain, accompanied by slip does not correlate with clinical symptoms. The neurologic deficits, forebodes a poor outcome. This authors also observed that general joint laxity us- study provides Level III evidence that low back ing Carter’s criteria correlates with the presence of pain can be expected to improve in patients with degenerative spondylolisthesis. narrowed intervertebral disc spaces.

Vogt et al17 described a cross sectional study of In critique of the study, unlike most other studies 788 white south central Pennsylvanian women in this area, a degenerative slip was defined as either over 65 years of age who were enrolled in a study a forward or backward slip. This paper offers Level intended to address osteoporotic fractures. Spine III prognostic evidence that in an elderly popula- radiographs were digitized to retrospectively as- tion, back pain is correlated with the olisthesis; sess prevalence of anterolisthesis. Subluxation of however, only one third with olistheses is symp- 3 mm or more at any level (L3-4, L4-5, or L5-S1) tomatic. Thus degenerative spondylolisthesis can was defined as a degenerative slip. Anterolisthesis be acquired in an asymptomatic population, with a was noted in 29% of this very specific population higher incidence in females (4:1). of white women over the age of 65. Of these patients, only a single level was involved in 90% of Mardjetko et al10 reported a meta-analysis of de- women with anterolisthesis. The incidence of slip generative lumbar spondylolisthesis literature from was not affected by smoking, diabetes mellitus or 1970-1993, primarily designed to study posterior oophorectomy. fusion with and without instrumentation. Howev- er, three studies included addressed natural history Anterolisthesis was not associated with presence with a total of 278 patients. Inclusion criteria were of back symptoms; however no validated outcome limited only to degenerative spondylolisthesis with measure was used. This study provides Level II radicular leg pain or neurogenic claudication. Of evidence that degenerative spondylolisthesis is the three studies, only the Matsunaga paper ad- found in 29% of this very specific population of dressed slippage and was considered by the work white women over the age of 65. Slip is most likely group to be a true natural history paper. Because to occur at a single level and does not necessarily of the limitations of this meta-analysis relative to correlate with back pain. the question of natural history, the reviewers chose to base recommendations on the Matsunaga paper Kauppila et al8 detailed a population-based, retro- directly and not include this article as a basis for spective, cohort study of 217 men and 400 women. the recommendations. Radiographs were taken at a mean age of 54 years and again at 79 years. Degenerative spondylolisthesis was defined as >3 mm of forward or backward Future Directions for Research slip. Twenty-three men (12%) and 100 women The work group identified the following potential (25%) developed some form of “slippage” either studies, which could generate meaningful evidence forward or backward. Forward slip occurred in to assist in further defining the natural history of eight men and 75 women, and backward slip oc- degenerative lumbar spondylolisthesis. curred in 16 men and 35 women. Forward slip was 18% +/- 5.5 and backward slip magnitude was Recommendation #1: 15% +/- 4.0. Olisthesis did predict back pain or A prospective study of untreated patients, all stiffness on most days (32% [39/123] in the de- with degenerative lumbar spondylolisthesis generative spondylolisthesis group compared with without neurologic compromise, would pro- 19% [90/484] in controls). Controlling for sclerosis vide Level I evidence regarding the natural still accounted for pain. Patients with acquired slips history of the disease. This study could include reported more daily back symptoms, but did not stratification as to type of spondylolisthesis and report more disability than controls. evaluate progression of radiographic severity and clinical severity over time.

Recommendation #2: 7. Gibson JN, Grant IC, Waddell G. The Cochrane review Any systematic study of patients with untreated of surgery for lumbar disc prolapse and degenerative spondylolisthesis who presented with varying lumbar spondylosis. Spine. 1999;24(17):1820-1832. 8. Kauppila LI, Eustace S, Kiel DP, Felson DT, Wright degrees of neurologic deficit would provide AM. Degenerative displacement of lumbar vertebrae. evidence regarding the natural history of the A 25-year follow-up study in Framingham. Spine. disease in this patient population. For example, 1998;23(17):1868-1873; discussion 1873-1864. defining and following a group of patients with 9. Kwon BK, Albert TJ. Adult low-grade acquired spon- lumbar spondylolisthesis and sensory deficits as dylolytic spondylolisthesis: evaluation and management. Spine. 2005;30(6 Suppl):S35-41. compared with those who present with motor 10. Mardjetko SM, Connolly PJ, Shott S. Degenerative deficits that have not been treated would yield lumbar spondylolisthesis. A meta-analysis of literature Level I evidence. 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S. 11. Matsunaga S, Ijiri K, Hayashi K. Nonsurgically man- aged patients with degenerative spondylolisthesis: a 10- to 18-year follow-up study. J Neurosurg. 2000;93(2 Natural History References Suppl):194-198. 1. Apel DM, Lorenz MA, Zindrick MR. Symptomatic 12. Matsunaga S, Sakou T, Morizono Y, Masuda A, Demirtas spondylolisthesis in adults: four decades later. Spine. AM. Natural history of degenerative spondylolisthesis. 1989;14(3):345-348. Pathogenesis and natural course of the slippage. Spine. 2. Ben-Galim P, Reitman CA. The distended facet sign: an 1990;15(11):1204-1210. indicator of position-dependent spinal stenosis and de- 13. Nizard RS, Wybier M, Laredo JD. Radiologic as- generative spondylolisthesis. Spine J. 2007;7(2):245-248. sessment of lumbar intervertebral instability and de- 3. Beutler WJ, Fredrickson BE, Murtland A, Sweeney CA, generative spondylolisthesis. Radiol Clin North Am. Grant WD, Baker D. The natural history of spondyloly- 2001;39(1):55-71, v-vi. sis and spondylolisthesis: 45-year follow-up evaluation. 14. Sinaki M, Lutness MP, Ilstrup DM, Chu CP, Gramse Spine. 2003;28(10):1027-1035; discussion 1035. RR. Lumbar spondylolisthesis: retrospective comparison 4. Cummins J, Lurie JD, Tosteson TD, et al. Descriptive and three-year follow-up of two conservative treatment epidemiology and prior healthcare utilization of pa- programs. Arch Phys Med Rehabil. 1989;70(8):594-598. tients in the Spine Patient Outcomes Research Trial’s 15. Soren A, Waugh TR. Spondylolisthesis and related dis- (SPORT) three observational cohorts: disc herniation, orders. A correlative study of 105 patients. Clin Orthop spinal stenosis, and degenerative spondylolisthesis. Spine. Relat Res. 1985(193):171-177. 2006;31(7):806-814. 16. Vibert BT, Sliva CD, Herkowitz HN. Treatment of insta- 5. DeWald CJ, Vartabedian JE, Rodts MF, Hammerberg bility and spondylolisthesis: surgical versus nonsurgical KW. Evaluation and management of high-grade spon- treatment. Clin Orthop Relat Res. 2006;443:222-227. dylolisthesis in adults. Spine. 2005;30(6 Suppl):S49-59. 17. Vogt MT, Rubin D, Valentin RS, et al. Lumbar olis- 6. Frymoyer JW, Selby DK. Segmental instability. Rationale thesis and lower back symptoms in elderly white for treatment. Spine. 1985;10(3):280-286. women. The Study of Osteoporotic Fractures. Spine. 1998;23(23):2640-2647.

Work Group Consensus Statement Degenerative lumbar spondylolisthesis represents an anatomic entity. There are no clinical symptoms Traditionally, the evaluation of a patient begins that are specific to degenerative lumbar spon- with the physician obtaining a history and per- dylolisthesis. Patients with symptomatic degenera- forming a focused physical examination related to tive lumbar spondylolisthesis complain primarily the patient’s presenting complaints. This forms the of radiculopathy or neurogenic intermittent clau- basis upon which the physician formulates an ini- dication with or without concomitant back pain. tial list of diagnoses to explain the patient’s symp- However, there is a variable rate of back pain in toms and signs. Additional testing subsequently patients with degenerative spondylolisthesis. The enables the physician to identify the most probable association between back pain and degenerative diagnosis and formulate a treatment plan. lumbar spondylolisthesis is inconsistent, as many patients with spondylolisthesis have no back pain. When evaluating the Levels of Evidence in support of appropriate history and physical exam findings, The signs and symptoms of mechanical instability the evidence is generally of a low level, as little con- associated with degenerative lumbar spondylolis- temporary research has been applied to the prog- thesis without neurological symptoms have not nostic value of the history and physical exam in been well characterized and are not addressed in clinical decision-making. Nonetheless, the history this guideline. and physical exam remain central to the practice of evidence-based medicine. An accurate history and In older patients presenting with radiculopathy physical examination forms the informational basis and neurogenic intermittent claudication, for the initiation of the evidence-based medicine with or without back pain, a diagnosis of process, namely asking meaningful, answerable degenerative lumbar spondylolisthesis should questions. be considered.

When assessing studies related to historical and Grade of Recommendation: B physical examination findings consistent with the

Cauchioux et al5 described a study in which the di- symptoms of degenerative spondylolisthesis. agnostic evaluation of 26 patients with degenerative spondylolisthesis included plain radiographs and Postacchini et al19 performed a retrospective study myelography. Specifically, the authors stated that which reported on the clinical features of 77 pa- they made the diagnosis based on the “presence of tients. Within these patients, 18% reported chronic a slip of one vertebra on the vertebra below in the low back pain as the only symptom; 12% had absence of a defect of the pars interarticularis.” The lower extremity symptoms felt to be nonvertebral study included 26 patients with nerve root com- in origin (eg, hip arthritis), and reported no low pression secondary to degenerative slip, with 80% back pain; 47% had radicular symptoms and low reporting back pain, 46% reporting primary chron- back pain; and 23% reported only radicular symp- ic sciatica and 54% reporting primary neurogenic toms. Radiculopathy presented as pain alone, pain claudication. Sciatica tended to occur in the older and sensory symptoms, or pain and sensorimotor patient and neurogenic claudication in the younger changes. Lasegue test was negative in almost all subjects. cases. The most common neurological signs were absent ankle jerks, weak extensor hallucis longus In critique of this study, this is a characterization of (EHL), weak anterior tibialis or loss of knee jerk a subset of patients with degenerative lumbar spon- reflex. dylolisthesis referred for evaluation of neurological symptoms. These data offer Level IV prognostic The authors reviewed five clinical patterns and evidence for the neurological symptoms associated three radiographic patterns as defined by Fitzgerald with degenerative lumbar spondylolisthesis. and MacNab. Clinical patterns included the following: (1) no symptoms, occasional back pain; (2) Fitzgerald et al8 conducted a study of 43 patients chronic low back pain with no radicular symptoms; with symptomatic spondylolisthesis which exam- (3) radicular symptoms with no root compression, ined various parameters. It is unclear if the patients with or without back pain; (4) radicular symptoms represented a consecutive or nonconsecutive series. with neurologic deficit; or (5) intermittent claudi- In addition to a description of plain radiographic cation. Radiological findings included slight central findings of the spine, as well as concomitant hip stenosis, lateral root canal stenosis or combined arthritis, the authors provided a detailed descrip- central and root canal stenosis. The authors con- tion of the presentation (symptom) pattern of the cluded that degenerative lumbar spondylolisthesis patients. In summary, they found that 34 patients is not always symptomatic. Patients may complain had back pain without leg pain and signs of nerve of low back pain, but the etiology is uncertain. root compression, five cases with leg pain with or Patients largely complain of radicular symptoms or without back pain with signs of nerve root com- intermittent claudication, which is secondary to an pression and four cases in which patients reported associated stenosis. neurogenic claudication. In critique of this study, data were collected ret- In critique of this study, one must presume that rospectively and tests were not uniformly applied the patients were enrolled nonconsecutively. As a across patients. Because of these weaknesses, this diagnostic history and physical examination study, potential Level II study was downgraded to Level the study presents a spectrum of symptoms and III. These data provide Level III prognostic evi- signs in patients with degenerative lumbar spon- dence of clinical signs and symptoms of degenera- dylolisthesis. This study offers Level IV prognos- tive lumbar spondylolisthesis. tic evidence of the clinical spectrum of signs and

Rosenberg et al20 conducted a retrospective study In critique of this study, data was collected retro- which characterized symptoms in 200 consecutive spectively from a study conducted for other epi- patients with degenerative lumbar spondylolisthe- demiological purposes. This study offers Level II sis. Back, buttock or thigh pain were the principal prognostic evidence that degenerative spondylolis- complaints in a large majority of patients and were thesis is relatively common in elderly Caucasian rarely severe. Of the 200 patients, 61 had leg symp- women and does not correlate with back pain. toms. Some patients described gait abnormalities. Seven patients had sacral nerve root symptoms. Acute radiculopathy occurred in 19 instances and Future Directions for Research a disc herniation was confirmed on myelography. The work group recommends a high quality, pro- Symptoms included aching, pulling, weakness, spective study identifying specific aspects of the heaviness, numbness or burning. Lower extremity history and physical examination and character- symptoms could be unilateral, bilateral or alternat- izing the subgroups of patients with degenerative ing. Neurogenic claudication was uncommon. Ex- spondylolisthesis. The study would enroll a large amination of the patients demonstrated that many number of patients, screen for symptomatic and as- were supple and able to touch toes, 10% had back ymptomatic degenerative lumbar spondylolisthesis, spasms and 42% had neurologic deficits, primarily and have greater than 80% follow-up. Subgroups L5 with decreased sensation in the lateral thigh or for evaluation could include patients with or with- inability to walk on heels. Atrophy occurred occa- out instability, radiculopathy, neurogenic intermit- sionally and 20% had altered deep tendon reflexes. tent claudication and back pain.

In critique of this study, data were collected retrospectively and tests were not uniformly applied History and Physical Exam Findings across patients. Because of these weaknesses, this potential Level II study was downgraded to Level References III. These data provide Level III prognostic evi- 1. Belfi LM, Ortiz AO, Katz DS. Computed tomography evaluation of spondylolysis and spondylolisthesis in dence of the typical clinical signs and symptoms asymptomatic patients. Spine. 2006;31(24):E907-910. which may be associated with degenerative lumbar 2. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. The spondylolisthesis. role of lumbar lordosis, vertebral end-plate inclination, disc height, and facet orientation in degenerative spon- Vogt et al26 described a retrospective, cross-sectional, dylolisthesis. J Spinal Disord. 1999;12(1):68-73. 3. Berven S, Tay BB, Colman W, Hu SS. The lumbar zy- prognostic study of 788 women greater than 65 gapophyseal (facet) joints: a role in the pathogenesis of years of age enrolled in the Study of Osteoporotic spinal pain syndromes and degenerative spondylolisthe- Fractures. The incidence of olisthesis (degenerative sis. Semin Neurol. 2002;22(2):187-196. spondylolisthesis and retrodisplacement) was 4. Bolesta MJ, Bohlman HH. Degenerative spondylolisthe- defined as greater than 3 mm of translational change. sis. Instr Course Lect. 1989;38:157-165. 5. Cauchoix J, Benoist M, Chassaing V. Degenerative spon- Of the women enrolled in the study, 29% had dylolisthesis. Clin Orthop Relat Res. 1976(115):122-129. anterior olisthesis (degenerative spondylolisthesis) 6. Dupuis PR, Yong-Hing K, Cassidy JD, Kirkaldy-Willis and 14% had retrolisthesis. Ninety percent WH. Radiologic diagnosis of degenerative lumbar spinal of degenerative spondylolisthesis and 88% of instability. Spine. 1985;10(3):262-276. retrolisthesis occurred at one level. Prevalence was 7. Elster AD, Jensen KM. Computed tomography of spondylolisthesis: patterns of associated pathology. J Comput not associated with smoking status, diabetes or Assist Tomogr. 1985;9(5):867-874. oophorectomy. Unlike retrolisthesis, degenerative 8. Fitzgerald JA, Newman PH. Degenerative spondylolis- spondylolisthesis was not associated with back pain. thesis. J Bone Joint Surg Br. 1976;58(2):184-192.

9. Herkowitz HN. Spine update. Degenerative lumbar global spinal motion? Spine. 2001;26(3):282-286. spondylolisthesis. Spine. 1995;20(9):1084-1090. 18. Okawa A, Shinomiya K, Komori H, Muneta T, Arai Y, 10. Hilibrand AS, Rand N. Degenerative lumbar stenosis: Nakai O. Dynamic motion study of the whole lumbar diagnosis and management. J Am Acad Orthop Surg. spine by videofluoroscopy. Spine. 1998;23(16):1743-1749. 1999;7(4):239-249. 19. Postacchini F, Perugia D. Degenerative lumbar spon- 11. Jaovisidha S, Techatipakorn S, Apiyasawat P, Laohacha- dylolisthesis. Part I: Etiology, pathogenesis, pathomor- roensombat W, Poramathikul M, Siriwongpairat P. phology, and clinical features. Ital J Orthop Traumatol. Degenerative disk disease at lumbosacral junction: plain 1991;17(2):165-173. film findings and related MRI abnormalities. J Med Assoc 20. Rosenberg NJ. Degenerative spondylolisthesis. Predis- Thai. 2000;83(8):865-871. posing factors. J Bone Joint Surg Am. 1975;57(4):467-474. 12. Jayakumar P, Nnadi C, Saifuddin A, Macsweeney E, 21. Rothman SL, Glenn WV, Jr., Kerber CW. Multiplanar Casey A. Dynamic degenerative lumbar spondylolis- CT in the evaluation of degenerative spondylolisthesis. A thesis: diagnosis with axial loaded magnetic resonance review of 150 cases. Comput Radiol. 1985;9(4):223-232. imaging. Spine. 2006;31(10):E298-301. 22. Takayanagi K, Takahashi K, Yamagata M, Moriya H, Ki- 13. Lefkowitz DM, Quencer RM. Vacuum facet phenom- tahara H, Tamaki T. Using cineradiography for continu- enon: a computed tomographic sign of degenerative ous dynamic-motion analysis of the lumbar spine. Spine. spondylolisthesis. Radiology. 1982;144(3):562. 2001;26(17):1858-1865. 14. Maheshwaran S, Davies AM, Evans N, Broadley P, 23. Teplick JG, Laffey PA, Berman A, Haskin ME. Di- Cassar-Pullicino VN. Sciatica in degenerative spon- agnosis and evaluation of spondylolisthesis and/or dylolisthesis of the lumbar spine. Ann Rheum Dis. spondylolysis on axial CT. AJNR Am J Neuroradiol. 1995;54(7):539-543. 1986;7(3):479-491. 15. McAfee PC, Ullrich CG, Yuan HA, Sherry RG, Lock- 24. Tokuhashi Y, Matsuzaki H, Sano S. Evaluation of wood RC. Computed tomography in degenerative spinal clinical lumbar instability using the treadmill. Spine. stenosis. Clin Orthop Relat Res. 1981(161):221-234. 1993;18(15):2321-2324. 16. McGregor AH, Anderton L, Gedroyc WM, Johnson J, 25. Vitzthum HE, Konig A, Seifert V. Dynamic examina- Hughes SP. The use of interventional open MRI to assess tion of the lumbar spine by using vertical, open magnetic the kinematics of the lumbar spine in patients with spon- resonance imaging. J Neurosurg. 2000;93(1 Suppl):58-64. dylolisthesis. Spine. 2002;27(14):1582-1586. 26. Vogt MT, Rubin D, Valentin RS, et al. Lumbar olis- 17. McGregor AH, Cattermole HR, Hughes SP. Global thesis and lower back symptoms in elderly white spinal motion in subjects with lumbar spondylolysis and women. The Study of Osteoporotic Fractures. Spine. spondylolisthesis: does the grade or type of slip affect 1998;23(23):2640-2647.

Diagnosing Spondylolisthesis with Imaging

What are the most appropriate which included plain radiographs and myelography. Specifically, the authors stated that they made diagnostic tests for degenerative the diagnosis based on the “presence of a slip of lumbar spondylolisthesis? one vertebra on the vertebra below in the absence of a defect of the pars interarticularis.” The study The most appropriate, noninvasive included 26 patients with nerve root compression test for detecting degenerative lumbar secondary to degenerative slip, with 80% reporting spondylolisthesis is the lateral radiograph. back pain, 46% reporting chronic sciatica and 54% reporting neurogenic claudication. Sciatica tended Grade of Recommendation: B to occur in the older patient and neurogenic claudication in the younger subjects. Myelography was Brown et al6 reported findings from a retrospective performed in 17 patients to detect nerve root/cauda study of patients with degenerative spondylolis- equina compression. Although not supported by thesis, which examined a number of different statistical analysis, the authors claimed that lateral parameters, including diagnostic features on plain recess stenosis was “most important.” radiographs. These patients were selected from a review of 2348 consecutive charts of patients with In critique of this study, the authors did not state low back pain; 132 (5.6%) had radiographic evi- whether patients were consecutively selected, thus dence of degenerative spondylolisthesis. Of pa- it was assumed that they were nonconsecutive tients included in the study, 88 were female and 44 patients. The study did not include comparison were male. The average age was 63.5 years for the of diagnostic modalities. Admittedly, in the mid female group and 65.2 years for the male group. to late 1970s, plain radiograph and myelography Seventy-eight percent had back pain with proximal were the most advanced imaging methods available. leg referral lasting between one week and 40 years; By default, they would have been considered gold 17% had instability symptoms (eg, catch in the standard diagnostic tests for degenerative spon- back, tiredness in back, inability to walk one hour, dylolisthesis and spinal stenosis. These data offer limitation of forward bend, inability to lift weights, Level III diagnostic evidence that plain radiographs back pain with coughing or sneezing, significant and myelography are useful diagnostic tests for this back pain with twisting). disorder.

In critique, this study does not present peer- Fitzgerald et al16 described a study of 43 patients reviewed data. There was no comparison of with symptomatic spondylolisthesis. It is unclear diagnostic tests. As the study was performed in if the patients represented a consecutive or non- the early 1980s, the primary radiographic modality consecutive series. In addition to a description of was plain radiographs. These data offer Level plain radiographic findings of the spine, as well as III diagnostic evidence that plain radiographs concomitant hip arthritis, the authors provided a are a useful test for identifying patients with detailed description of the presentation (symptom) degenerative spondylolisthesis. pattern of the patients. In summary, they found that 34 patients had back pain without leg pain and Cauchioux et al7 conducted a diagnostic evaluation signs of nerve root compression, five cases with leg on 26 patients with degenerative spondylolisthesis pain with or without back pain with signs of nerve This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 18

root compression, and four cases in which patients ing room. The authors concluded that disc angle in reported neurogenic claudication. As a diagnos- flexion and ROM were highly correlated with dis- tic study, the primary imaging method was plain traction stiffness. Patients with segmental kyphosis radiographs; however, plain myelography was also with flexion showed lower stiffness compared to performed in seven of the nine patients with neuro- those with lordosis in flexion. logical symptoms. In critique of this study, it assessed an intraopera- In critique of this study, one must presume that the tive and nonvalidated test. The clinical applica- patients were not consecutively enrolled. The only tion of such a test remains unknown. Although two imaging methods used were plain radiographs the study presents potential Level II diagnostic and myelography, which were not uniformly per- evidence, the authors failed to mention whether formed in all patients. This study provides Level the patients were consecutively assigned, thus the III diagnostic evidence that plain radiographs and study was downgraded to Level III evidence. The myelography are useful modalities with which to study provides Level III diagnostic evidence that diagnose and evaluate degenerative spondylolisthe- standing flexion and extension radiographs are pre- sis in the lumbar spine. dictive of instability.

While standing radiographs are commonly used, Postacchini et al44 described a study of 77 patients few studies assess the relative value of this tech- with degenerative spondylolisthesis in which nique compared with supine lateral radiographs. flexion-extension radiographs, CT and/or MRI, Limited data support the use of dynamic views and myelography were obtained. The various (flexion-extension or axially loaded) in the evalua- findings were reported. The authors found that tion of degenerative spondylolisthesis. Lowe et al32 radiographs used for imaging quantified the degree showed increased sagittal displacement with the use of slips observed. Dynamic radiographs “showed of standing rather than supine lateral radiographs. hypermobility of L4 in approximately half of the However, only one of 13 patients had degenera- cases.” Myelography revealed neural structure tive spondylolisthesis. Wood et al58 also found that compression in the spinal canal in all cases in which the degree of static spondylolisthesis was greater it was performed. (Note: myelography may have with the patient in the standing lateral rather than only been performed if patients had neurologic the supine position, however, they included post- symptoms.) CT was useful for assessing the facet laminectomy patients in the degenerative spon- joint. MRI, CT and myelography were useful in dylolisthesis group. Because the paper did not pres- identifying stenosis in patients with neurological ent a subgroup analysis specific to the degenerative symptoms. spondylolisthesis group, the work group was unable to use this paper to address this question. In critique, the diagnostic studies were applied inconsistently across patients. Not all patients re- Kanayama et al26 reviewed a case series of 19 pa- ceived all studies, preventing comparison between tients with symptomatic degenerative lumbar spon- diagnostic modalities. This article presented com- dylolisthesis who were candidates for instrumented prehensive descriptions of the findings with each of lumbar arthrodesis and decompression. Patients the diagnostic modalities. These data offer Level III were assessed according to radiographic parameters diagnostic evidence of the utility of dynamic radio- including disc angle, range of motion (ROM), per- graphs, CT, MRI and myelography for evaluation cent slip, percent posterior height, which were then of degenerative spondylolisthesis. compared with distraction stiffness in the operat-

The most appropriate, noninvasive test it was assumed that they were nonconsecutive for imaging the stenosis accompanying patients. There was no comparison of diagnostic degenerative lumbar spondylolisthesis is the modalities. Admittedly, in the mid to late 1970s, MRI. plain radiographs and myelography were the most advanced imaging methods available. By default, Work Group Consensus Statement they would have been considered gold standard diagnostic tests for degenerative spondylolisthesis Based on NASS’ Clinical Guideline for Diagno- and spinal stenosis. These data offer Level III diag- sis and Treatment of Degenerative Lumbar Spinal nostic evidence that plain radiographs and myelog- Stenosis (2007), MRI was demonstrated to be the raphy are useful diagnostic tests for this disorder. most effective noninvasive diagnostic tool to detect degenerative lumbar spinal stenosis. As many Fitzgerald et al16 described a study of 43 patients patients included in the review had degenerative with symptomatic spondylolisthesis. It is unclear spondylolisthesis, it is logical to conclude that MRI if the patients represented a consecutive or non- would be useful in this group as well. However, no consecutive series. In addition to a description of disease-specific studies were found to confirm this plain radiographic findings of the spine, as well as conclusion. concomitant hip arthritis, the authors provided a detailed description of the presentation (symptom) Plain myelography or CT myelography pattern of the patients. In summary, they found are useful studies to assess spinal stenosis that 34 patients had back pain without leg pain and in patients with degenerative lumbar signs of nerve root compression, five cases with leg spondylolisthesis. pain with or without back pain with signs of nerve root compression, and four cases in which patients Grade of Recommendation: B reported neurogenic claudication. As a diagnostic study, the primary imaging method was plain Cauchioux et al7 conducted a diagnostic evaluation radiographs. However, plain myelography was also of 26 patients with degenerative spondylolisthesis performed in seven of the nine patients with neuro- which included plain radiographs and myelogra- logical symptoms. phy. Specifically, the authors stated that they made the diagnosis based on the “presence of a slip of In critique of this study, one must presume that the one vertebra on the vertebra below in the absence patients were not consecutively enrolled. The only of a defect of the pars interarticularis.” The study two imaging methods used were plain radiographs included 26 patients with nerve root compression and myelography, which were not uniformly per- secondary to degenerative slip, with 80% reporting formed in all patients. This study provides Level back pain, 46% reporting chronic sciatica and 54% III diagnostic evidence that plain radiographs and reporting neurogenic claudication. Sciatica tended myelography are useful modalities with which to to occur in the older patient and neurogenic clau- diagnose and evaluate degenerative spondylolisthe- dication in the younger subject. Myelography was sis in the lumbar spine. performed in 17 patients to detect nerve root/cauda equina compression. Although not supported by Postacchini et al44 described a study of 77 patients statistical analysis, the authors claimed that lateral with degenerative spondylolisthesis in which recess stenosis was “most important.” flexion-extension radiographs, CT and/or MRI, and myelography were obtained. The various In critique of this study, the authors did not state findings were reported. The authors found that whether patients were consecutively selected, thus This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 20

radiographs used for imaging quantified the degree Satomi et al51 reported findings from a retro- of slips observed. Dynamic radiographs “showed spective case series of patients with degenerative hypermobility of L4 in approximately half of the spondylolisthesis who were evaluated with CT cases.” Myelography revealed neural structure myelography in order to plan the optimal surgical compression in the spinal canal in all cases in which procedure. CT myelograms were compared with it was performed. (Note: Myelography may have plain radiographic myelograms to evaluate the sites only been performed if patients had neurologic of dural compression. symptoms.) CT was useful for assessing the facet joint. MRI, CT and myelography were useful in Patients who underwent anterior lumbar interbody identifying stenosis in patients with neurological fusion (ALIF) were included in Group A. Patients symptoms. were selected for the posterior decompression group (Group B) if their imaging showed displace- In critique, the diagnostic studies were applied ment at two or more discs, had CT myelographic inconsistently across patients. Not all patients re- findings indicating lateral stenosis or were deemed ceived all studies, preventing comparison between inappropriate candidates for ALIF because of age. diagnostic modalities. This article presented com- Group A consisted of 27 patients; discography was prehensive descriptions of the findings with each of performed in 22. Based on the novel CT myelo- the diagnostic modalities. These data offer Level III gram classification used in the study, 38% of these diagnostic evidence of the utility of dynamic radio- patients had stage 3 stenotic changes. Group B graphs, CT, MRI and myelography for evaluation consisted of 14 patients, five of whom underwent of degenerative spondylolisthesis. fusion. Of these patients, four reported back pain; neurogenic intermittent claudication was more Rosenberg et al47 conducted a retrospective study severe in group B. Discography was performed in which characterized 200 consecutive patients with two patients. Based on myelogram classification degenerative lumbar spondylolisthesis. This cohort used in the study, 62% of these patients had stage 3 contained a subgroup of 39 patients with severe un- stenotic changes. Stenosis over two disc space levels remitting symptoms; 29 underwent myelography was present in 92% of these patients. The authors and showed an hourglass constriction of the dura at concluded that information on CTM was useful for the level of slippage. Seven patients also had a pro- identifying pathologic processes and for planning trusion. Surgical findings include absence of epidu- surgery. ral fat, pale pulseless dura and decreased capacity of the spinal canal. In critique of this study, the authors did not evaluate a list of diagnostic criteria a priori. The authors In critique of this study, data were collected ret- failed to indicate whether patients were selected rospectively and tests were not uniformly applied consecutively. These data offer Level III diagnostic across patients. However, from the diagnostic evidence that CT myelography is a useful imaging perspective, this small subgroup of 29 patients study for this disorder. provides a consecutive series of patients that was retrospectively analyzed. These subgroup data CT is a useful noninvasive study in patients provide Level II diagnostic evidence that myelogra- who have a contraindication to MRI, for whom phy is useful in identifying stenosis in patients with MRI findings are inconclusive or for whom degenerative spondylolisthesis and neurological there is a poor correlation between symptoms symptoms. and MRI findings, and in whom CT myelogram is deemed inappropriate.

Work Group Consensus Statement In critique, this was a study of nonconsecutive patients, radiological findings were not corre- Based on NASS’ Clinical Guideline for Diagnosis lated with clinical signs or symptoms, and no gold and Treatment of Degenerative Lumbar Spinal standard was employed. The data present Level IV Stenosis (2007), CT was demonstrated to be an ef- diagnostic evidence that CT is a useful modality in fective diagnostic tool to detect degenerative lum- the diagnosis of stenosis in patients with degenera- bar spinal stenosis. As many patients included in tive spondylolisthesis. the review had degenerative spondylolisthesis, it is logical to conclude that CT would be useful in this group as well. However, only one disease-specific Future Directions for Research study was found, necessitating reference to the The work group identified the following potential NASS Clinical Guideline on Lumbar Spinal Steno- studies that would generate meaningful evidence to sis to support this consensus statement. assist in further defining the appropriate diagnostic tests for degenerative lumbar spondylolisthesis. 48 Rothman et al conducted a retrospective review These studies should assess a set of diagnostic crite- of the CT findings of 150 patients with degenera- ria established a priori. tive spondylolisthesis. The authors described the pathological findings, which included canal steno- Recommendation #1: sis, facet overgrowth, joint-capsule hypertrophy, The work group recommends a prospective, ligamentum flavum enlargement and gas within the appropriately powered study assessing the facet joints. utility of supine (gold standard), standing and dynamic flexion-extension lateral radiographs All patients were examined on GE 8800 CT scan- in the evaluation of patients with degenerative ners using axial scans of 5 mm-thick sections at 3 spondylolisthesis. mm spacing, with sagittal and coronal reformats. The authors found only 19% had subluxation Recommendation #2: greater than 6 mm. Severe facet degeneration with The work group recommends a prospective, marked hypertrophy, erosive changes or gas within appropriately powered study assessing the util- an irregular joint was noted in 91 patients. Severe ity of supine recumbent (gold standard), axial canal stenosis was detected in 15 patients as a result loaded and positional MRI in the detection and of narrowing of the central canal secondary to a evaluation of stenosis via analysis of the dural combination of subluxation, facet boney over- sac area in patients with degenerative spon- growth, joint-capsule hypertrophy, ligamentous dylolisthesis. hypertrophy, bulging and end plate osteophyte formation. Foraminal stenosis was observed in 38 patients. Anterior soft tissue bulge/herniation Imaging References of greater than 5 mm was present in only three 1. Belfi LM, Ortiz AO, Katz DS. Computed tomography patients. The authors concluded that CT is use- evaluation of spondylolysis and spondylolisthesis in ful in evaluating the severity of stenosis in patients asymptomatic patients. Spine. 2006;31(24):E907-910. with symptomatic degenerative spondylolisthe- 2. Bendo JA, Ong B. Importance of correlating static and sis. Stenosis is frequently secondary to soft tis- dynamic imaging studies in diagnosing degenerative lumbar spondylolisthesis. Am J Orthop. 2001;30(3):247-250. sue changes and facet hypertrophy, and does not 3. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. always correlate with the severity of slip. Facet joint remodeling in degenerative spondylolisthesis: an investigation of joint orientation and tropism. Eur Spine J. 1998;7(5):376-380. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 22

4. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. The 19. Herkowitz HN. Spine update. Degenerative lumbar role of lumbar lordosis, vertebral end-plate inclination, spondylolisthesis. Spine. 1995;20(9):1084-1090. disc height, and facet orientation in degenerative spon- 20. Inoue S, Watanabe T, Goto S, Takahashi K, Takata K, dylolisthesis. J Spinal Disord. 1999;12(1):68-73. Sho E. Degenerative spondylolisthesis. Pathophysiology 5. Boden SD, Riew KD, Yamaguchi K, Branch TP, Schell- and results of anterior interbody fusion. Clin Orthop inger D, Wiesel SW. Orientation of the lumbar facet Relat Res. 1988;227:90-98. joints: association with degenerative disc disease. J Bone 21. Ito S, Yamada Y, Tuboi S, Muro T. Specific pattern of Joint Surg Am. 1996;78(3):403-411. ruptured annulus fibrosus in lumbar degenerative spon- 6. Brown MD, Lockwood JM. Degenerative spondylolis- dylolisthesis. Neuroradiology. 1990;32(6):460-463. thesis. Instr Course Lect. 1983;32:162-169. 22. Jackson A, Isherwood I. Does degenerative disease 7. Cauchoix J, Benoist M, Chassaing V. Degenerative spon- of the lumbar spine cause arachnoiditis? A magnetic dylolisthesis. Clin Orthop Relat Res. 1976(115):122-129. resonance study and review of the literature. Br J Radiol. 8. Cinotti G, Postacchini F, Fassari F, Urso S. Predisposing 1994;67(801):840-847. factors in degenerative spondylolisthesis. A radiographic 23. Jacobsen S, Sonne-Holm S, Rovsing H, Monrad H, and CT study. Int Orthop. 1997;21(5):337-342. Gebuhr P. Degenerative lumbar spondylolisthesis: an 9. Crawford NR, Cagli S, Sonntag VK, Dickman CA. Bio- epidemiological perspective: the Copenhagen Osteoar- mechanics of grade I degenerative lumbar spondylolis- thritis Study. Spine. 2007;32(1):120-125. thesis. Part 1: in vitro model. J Neurosurg. 2001;94(1 24. Jaovisidha S, Techatipakorn S, Apiyasawat P, Laohacha- Suppl):45-50. roensombat W, Poramathikul M, Siriwongpairat P. 10. Dai LY. Orientation and tropism of lumbar facet Degenerative disk disease at lumbosacral junction: plain joints in degenerative spondylolisthesis. Int Orthop. film findings and related MRI abnormalities. J Med Assoc 2001;25(1):40-42. Thai. 2000;83(8):865-871. 11. Dai LY, Jia LS, Yuan W, Ni B, Zhu HB. Direct repair of 25. Jayakumar P, Nnadi C, Saifuddin A, Macsweeney E, defect in lumbar spondylolysis and mild isthmic spon- Casey A. Dynamic degenerative lumbar spondylolis- dylolisthesis by bone grafting, with or without facet joint thesis: diagnosis with axial loaded magnetic resonance fusion. Eur Spine J. 2001;10(1):78-83. imaging. Spine. 2006;31(10):E298-301. 12. Elster AD, Jensen KM. Computed tomography of spon- 26. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Ishida dylolisthesis: patterns of associated pathology. J Comput T, Yamane S. Intraoperative biomechanical assessment Assist Tomogr. 1985;9(5):867-874. of lumbar spinal instability: validation of radiographic 13. Epstein BS, Epstein JA, Jones MD. Degenerative spon- parameters indicating anterior column support in lumbar dylolisthesis with an intact neural arch. Radiol Clin spinal fusion. Spine. 15 2003;28(20):2368-2372. North Am. Aug 1977;15(2):275-287. 27. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- 14. Epstein JA, Epstein BS, Lavine LS, Carras R, Rosenthal zume H, Yoshida M. Lumbar sagittal balance influences AD. Degenerative lumbar spondylolisthesis with an in- the clinical outcome after decompression and posterolat- tact neural arch (pseudospondylolisthesis). J Neurosurg. eral spinal fusion for degenerative lumbar spondylolis- 1976;44(2):139-147. thesis. Spine. 2002;27(1):59-64. 15. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, 28. Kim NH, Lee JW. The relationship between isth- Montgomery DM, Kurz LT. 1997 Volvo Award winner mic and degenerative spondylolisthesis and the con- in clinical studies. Degenerative lumbar spondylolisthesis figuration of the lamina and facet joints. Eur Spine J. with spinal stenosis: a prospective, randomized study 1995;4(3):139-144. comparing decompressive laminectomy and arthrod- 29. Kirkaldy-Willis WH, Wedge JH, Yong-Hing K, Reilly J. esis with and without spinal instrumentation. Spine. Pathology and pathogenesis of lumbar spondylosis and 1997;22(24):2807-2812. stenosis. Spine. 1978;3(4):319-328. 16. Fitzgerald JA, Newman PH. Degenerative spondylolis- 30. Knuttson F. The instability associated with disc degener- thesis. J Bone Joint Surg Br. 1976;58(2):184-192. ation in the lumbar spine. Acta Radiol. 1944;25:593-609. 17. Grobler LJ, Robertson PA, Novotny JE, Ahern JW. 31. Lefkowitz DM, Quencer RM. Vacuum facet phenom- Decompression for degenerative spondylolisthesis and enon: a computed tomographic sign of degenerative spinal stenosis at L4-5. The effects on facet joint mor- spondylolisthesis. Radiology. 1982;144(3):562. phology. Spine. 1993;18(11):1475-1482. 32. Lowe RW, Hayes TD, Kaye J, Bagg RJ, Luekens CA. 18. Grobler LJ, Robertson PA, Novotny JE, Pope MH. Standing roentgenograms in spondylolisthesis. Clin Or- Etiology of spondylolisthesis. Assessment of the thop Relat Res. 1976(117):80-84. role played by lumbar facet joint morphology. Spine. 33. Maheshwaran S, Davies AM, Evans N, Broadley P, 1993;18(1):80-91. Cassar-Pullicino VN. Sciatica in degenerative spon-

dylolisthesis of the lumbar spine. Ann Rheum Dis. 46. Robertson PA, Grobler LJ, Novotny JE, Katz JN. 1995;54(7):539-543. Postoperative spondylolisthesis at L4-5. The role of facet 34. Matsunaga S, Sakou T, Morizono Y, Masuda A, Demirtas joint morphology. Spine. 1993;18(11):1483-1490. AM. Natural history of degenerative spondylolisthesis. 47. Rosenberg NJ. Degenerative spondylolisthesis. Predis- Pathogenesis and natural course of the slippage. Spine. posing factors. J Bone Joint Surg Am. 1975;57(4):467-474. 1990;15(11):1204-1210. 48. Rothman SL, Glenn WV, Jr., Kerber CW. Multiplanar 35. McAfee PC, Ullrich CG, Yuan HA, Sherry RG, Lock- CT in the evaluation of degenerative spondylolisthesis. A wood RC. Computed tomography in degenerative spinal review of 150 cases. Comput Radiol. 1985;9(4):223-232. stenosis. Clin Orthop Relat Res. 1981(161):221-234. 49. Sanderson PL, Wood PL. Surgery for lumbar spi- 36. McGregor AH, Anderton L, Gedroyc WM, Johnson J, nal stenosis in old people. J Bone Joint Surg Br. Hughes SP. The use of interventional open MRI to assess 1993;75(3):393-397. the kinematics of the lumbar spine in patients with spon- 50. Sato K, Wakamatsu E, Yoshizumi A, Watanabe N, Irei dylolisthesis. Spine. 2002;27(14):1582-1586. O. The configuration of the laminas and facet joints in 37. McGregor AH, Cattermole HR, Hughes SP. Global degenerative spondylolisthesis. A clinicoradiologic study. spinal motion in subjects with lumbar spondylolysis and Spine. 1989;14(11):1265-1271. spondylolisthesis: does the grade or type of slip affect 51. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A global spinal motion? Spine. 2001;26(3):282-286. clinical study of degenerative spondylolisthesis. Ra- 38. Nizard RS, Wybier M, Laredo JD. Radiologic as- diographic analysis and choice of treatment. Spine. sessment of lumbar intervertebral instability and de- 1992;17(11):1329-1336. generative spondylolisthesis. Radiol Clin North Am. 52. Takayanagi K, Takahashi K, Yamagata M, Moriya H, Ki- 2001;39(1):55-71, v-vi. tahara H, Tamaki T. Using cineradiography for continu- 39. Nojiri K, Matsumoto M, Chiba K, Toyama Y, Momo- ous dynamic-motion analysis of the lumbar spine. Spine. shima S. Comparative assessment of pedicle morphology 2001;26(17):1858-1865. of the lumbar spine in various degenerative diseases. Surg 53. Teplick JG, Laffey PA, Berman A, Haskin ME. Di- Radiol Anat. 2005;27(4):317-321. agnosis and evaluation of spondylolisthesis and/or 40. Okawa A, Shinomiya K, Komori H, Muneta T, Arai Y, spondylolysis on axial CT. AJNR Am J Neuroradiol. Nakai O. Dynamic motion study of the whole lumbar 1986;7(3):479-491. spine by videofluoroscopy. Spine. 1998;23(16):1743-1749. 54. Tokuhashi Y, Matsuzaki H, Sano S. Evaluation of 41. Penning L, Blickman JR. Instability in lumbar spon- clinical lumbar instability using the treadmill. Spine. dylolisthesis: a radiologic study of several concepts. AJR 1993;18(15):2321-2324. Am J Roentgenol. 1980;134(2):293-301. 55. Tsai KH, Chang GL, Lin HT, Kuo DC, Chang LT, Lin 42. Ploumis A, Transfeldt EE, Gilbert TJ, Jr., Mehbod AA, RM. Differences of lumbosacral kinematics between Dykes DC, Perra JE. Degenerative lumbar scoliosis: ra- degenerative and induced spondylolisthetic spine. Clin diographic correlation of lateral rotatory olisthesis with Biomech (Bristol, Avon). 2003;18(6):S10-16. neural canal dimensions. Spine. 2006;31(20):2353-2358. 56. Vamvanij V, Ferrara LA, Hai Y, Zhao J, Kolata R, Yuan 43. Posner I, White AA, 3rd, Edwards WT, Hayes WC. A HA. Quantitative changes in spinal canal dimensions biomechanical analysis of the clinical stability of the using interbody distraction for spondylolisthesis. Spine. lumbar and lumbosacral spine. Spine. 1982;7(4):374-389. 2001;26(3):E13-18. 44. Postacchini F, Perugia D. Degenerative lumbar spon- 57. Vitzthum HE, Konig A, Seifert V. Dynamic examina- dylolisthesis. Part I: Etiology, pathogenesis, pathomor- tion of the lumbar spine by using vertical, open magnetic phology, and clinical features. Ital J Orthop Traumatol. resonance imaging. J Neurosurg. 2000;93(1 Suppl):58-64. 1991;17(2):165-173. 58. Wood KB, Popp CA, Transfeldt EE, Geissele AE. Ra- 45. Radu AS, Menkes CJ. Update on lumbar spinal steno- diographic evaluation of instability in spondylolisthesis. sis. Retrospective study of 62 patients and review of the Spine. 1994;19(15):1697-1703. literature. Rev Rhum Engl Ed. 1998;65(5):337-345.

B. Outcome Measures for Medical/Interventional and Surgical Treatment What are the appropriate (ZCQ) represents an evolution of Swiss Spinal Stenosis Questionnaire (SSS). Conclusions made outcome measures for the about either questionnaire have a high likelihood of treatment of degenerative being applicable to the other. lumbar spondylolisthesis? Anderson et al1 described a randomized (post hoc) controlled trial of patients with neurogenic claudi- Asking this question about the treatment of de- cation secondary to degenerative spondylolisthesis. generative lumbar spondylolisthesis is intrinsically Of the 75 spondylolisthesis patients included in the valuable. Our review of the literature on degenera- study, 42 received the X STOP device and 33 were tive lumbar spondylolisthesis with symptoms of included in the control group assigned to medical/ spinal stenosis confirmed that outcome studies are interventional treatment consisting of at least one valuable in determining the course of treatment. epidural steroid injection, drugs, analgesic agents and physical therapy as needed. Two-year follow- When evaluating studies in terms of the use of up data were obtained for 70 of the 75 patients. outcome measures, the work group evaluated this literature as prognostic in nature. Prognostic stud- The outcome measures implemented in the study ies investigate the effect of a patient characteristic included the Zurich Claudication Questionnaire on the outcome of a disease. Studies investigating (ZCQ), patient satisfaction on a scale from 0-5, outcome measures, by their design, are prognostic 36-Item Short Form Health Survey (SF-36) and studies. radiographic assessment. Successful treatment was defined as improvement in ZCQ of 15 points, An appropriate clinical outcome measure must patient satisfaction of greater than 2.5 and no ad- be validated. Further, the validated outcome mea- ditional surgery. The authors reported that success sure must be used in a high quality, prospective was noted in 63.4% of the surgically treated indi- outcome trial in order to be useful. The literature viduals, which was statistically significant between review yielded no validated outcome measures uti- preoperative and postoperative scores. Only 12.9% lized for the subset of patients with back pain and of medically/interventionally treated patients were degenerative lumbar spondylolisthesis. considered successes which was not statistically significant between pretreatment and posttreatment The Zurich Claudication Questionnaire patients. The authors concluded that the clinical (ZCQ)/Swiss Spinal Stenosis Questionnaire success for the X STOP surgically treated patients (SSS), Oswestry Disability Index (ODI), Likert compared with the medically/interventionally Five-Point Pain Scale and 36-Item Short treated controls was highly significant. Form Health Survey (SF-36) are appropriate measures for assessing treatment of In critique, this study was a cohort analysis of a degenerative lumbar spondylolisthesis. randomized prospective trial for spinal stenosis. The cohort studied consisted of patients who had Grade of Recommendation: A grade I spondylolisthesis as well as spinal stenosis. The outcome measures used included both validat- Note: The Zurich Claudication Questionnaire ed and nonvalidated outcome measures including

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 25 the validated Zurich Claudication Questionnaire but that fusion rationale may be questioned. (ZCQ) and an arbitrary patient satisfaction survey at follow-up visits. Although the authors obtained In critique, this study was not designed to validate SF-36 outcome data, these data were not used in the Walking Capacity Scale or the Five Point Likert the study to determine clinical success. Pain Scale as sensitive measures for degenerative spondylolisthesis. However, these measures have This study provides Level II prognostic evidence been previously validated by Stucki et al38 as the supporting use of the Zurich Claudication Ques- SSS, currently referred to as the ZCQ. tionnaire (ZCQ) and the SF-36 outcome measures as sensitive tools in distinguishing the outcome dif- This study offers Level II prognostic evidence that ferences between surgically treated (X STOP) and the ZCQ/SSS is sensitive enough to show differ- medically/interventionally treated individuals. ences between surgically and medically/interventionally treated patients with degenerative spon- Frazier et al7 reported a prospective, observational dylolisthesis and symptomatic spinal stenosis. study evaluating the prognostic factors affecting clinical outcomes as correlated to the presence or Gaetani et al8 described a prospective, prognostic absence of the deformities of degenerative scolio- study of 76 patients treated with decompression sis and spondylolisthesis. The outcome measure and bilateral instrumented fusion and followed implemented in the study included a question- for two years. There were 25 males and 51 females naire administered preoperatively, and at six and 24 with a mean age of 59.6 years (+/-12.2) and mean months postoperatively. Patients rated the severity duration of symptoms of 23.42 months. The out- of back pain, leg pain, overall pain and difficulty come measures used in the study included the ambulating using a Five Point Likert Pain Scale. Roland Morris Disability Questionnaire (RMDQ); A Walking Capacity Scale was calculated using Oswestry Disability Index (ODI) for quality of the average responses to five questions on walk- life patient centered outcomes; Visual Analog Scale ing difficulty in general, outdoor, indoor, shopping (VAS) for leg and back pain; preoperative dynamic and bedroom to bathroom walking. The patient X-ray studies, CT, and MRI; and postoperative X- satisfaction scale was generated by using the aver- ray studies. age for six questions concerning satisfaction with pain relief, functional improvement and other do- The authors reported a fusion rate of 85.5%, im- mains. The authors stated that these scales had been provement in ODI scores of less than 20 points shown to be reproducible, internally consistent and in 35.7% of patients and greater than 20 points in valid for patients with spinal stenosis. No statistical 55.7%. Scores on the RMDQ improved greater support for these statements was provided. than five points in 59.4% of patients, 2-4 points in 13.1%, and remained unchanged in 27.5%. There The authors reported that the spondylolisthesis was no difference between solid fusion and pseudo- subgroup showed no correlation of slip magni- arthrosis. The authors concluded that instrumented tude and patient outcomes. An increase in the slip fusion was effective in improving the quality of life, postoperatively was significantly correlated with as exhibited by the reduced disability scores. improved leg pain relief and borderline improvement in walking capacity. Satisfaction with the In critique of this study, this study provides only procedure and back pain relief was positively, but 24-month follow-up data. This time frame may not significantly, correlated with slip progression. not be long enough to fully evaluate the effect of The authors concluded that surgery was beneficial, pseudoarthrosis on patient outcomes. This study

provides Level I prognostic evidence suggesting from a prospective, randomized, controlled trial of correlation of RMDQ and ODI scores with symp- posterior decompression and fusion to determine toms and slippage. The RMDQ appears to be a the relationship of presence or absence of pseudo- sensitive tool to assess degenerative spondylolisthe- arthrosis to outcomes. Of the 118 patients original- sis outcome data. This study shows improvement ly randomized to decompression or decompression in the quality of life scores in both outcome tools. with a noninstrumented fusion, 58 patients under- The study also supports the conclusion that the went fusion, of which 47 were available for review. presence or absence of fusion was not a prognostic The outcome measures used in this study included indicator of patient outcome improvements. the Visual Analog Scale (VAS) (modified), a rudimentary outcome scale (excellent, good, fair, poor) Ghogowala et al10 conducted a prospective study and the Swiss Spinal Stenosis Questionnaire (SSS). assessing the outcomes of decompression alone in The authors reported that arthrodesis does result 20 patients and decompression with instrumented in better outcomes on the SSS at five to14 years as fusion in 14 patients with degenerative grade I opposed to earlier follow-up. lumbar spondylolisthesis. The outcome measures implemented included the ODI and the SF-36. In critique of this study, the bundling of these patients and subsequent evaluation at three year The authors reported that fusion occurred at a 93% follow-up represents a significant weakness of the rate in the arthrodesis group. The ODI improved study. The SSS was not applied preoperatively, but 27.5 points in the fusion group and 13.6 points in was only administered postoperatively. This study the decompression only group. The difference was provides Level I prognostic evidence suggesting statistically significant. The SF-36 data was also sig- that the SSS is a sensitive, validated instrument nificantly different between the two groups. Both which correlates well with patient outcome, and instruments, SF-36 and ODI, demonstrated poorer is appropriate for use in the assessment of clinical outcomes in older patients at 12 months. outcomes for degenerative lumbar spondylolisthesis. In critique of this study, this was a small pilot study demonstrating a clear need for future Level I ran- Pratt et al29 conducted a prospective, prognostic domized controlled trials utilizing these measures. study evaluating outcome instruments in all pa- This study provides Level II prognostic evidence tients who attended the Nuffield Orthopaedic supporting the use of the ODI and SF-36 as tools Center. These were patients with spinal stenosis, to assess outcomes after surgery for degenerative which included patients with degenerative spon- spondylolisthesis. These two outcome tools iden- dylolisthesis. tify similar and parallel changes in outcomes of the treatment groups, and this study supports the use Of the 52 patients approached to participate in the of these two outcome measures together to effec- study, 13 declined involvement and seven were tively assess outcomes in this population. Evidence excluded because of comorbidities, ie, limiting of the ability to discriminate between treatment walking distance. To determine reliability, the 32 outcomes using the ODI and SF-36 is supported clinic patients with lumbar spinal stenosis were as- by the findings in this study that older patients sessed twice, with one week between assessments. demonstrated poorer outcomes than younger pa- Retrospective data from 17 patients assessed before tients. surgery and 18 months after surgery for lumbar spinal stenosis were used to investigate the use of Kornblum et al20 reported on 58 patients extracted reliability in a clinical setting.

The patients were assessed using the Oswestry Dis- (0.80; P ≤0.001). ability Index (ODI) and three instruments designed specifically for use in patients with lumbar spinal In critique of this study, the subset of patients with stenosis: the Swiss Spinal Stenosis (SSS) Question- degenerative spondylolisthesis was not broken out naire, the Oxford Claudication Score (OCS) and and analyzed separately from the stenosis group. a functional test, the Shuttle Walk Test (SWT). Fluctuations in a patient’s symptoms resulted Patient outcomes were studied by the previously in wide individual confidence intervals. Perfor- validated outcome studies, the SSS and ODI. The mance on the SSS, OCS and ODI questionnaires OCS and SWT were studied in relation to these are broadly similar, the most precise being the previously validated outcome measures. condition-specific SSS. The SWT gives a snapshot of physical function, which is acceptable for group Data analysis included a test against normality analysis. Use of the SWT for individual assessment using the Komolgorov-Smirnov-Goodness-of-Fit after surgery is feasible. test. The test-retest reliability of the SSS, OCS, ODI and SWT were assessed with an internal cor- This study offers Level I prognostic evidence that relation coefficient test in which the reliability was the ODI, SSS, OCS and SWT tests reliably and the subject variability/ (subject variability + mea- validly evaluate patients with symptomatic spinal surement error). The 95% confidence intervals for stenosis within which a subgroup of degenerative each outcome instrument were reported. spondylolisthesis patients reside.

The internal consistency of the scales and their sub- Stucki et al38 described a prospective, prognostic sections was assessed using Cronbach’s coefficient study of the Zurich Claudication Questionnaire alpha, which summarizes interitem correlations. (ZCQ) or Swiss Spinal Stenosis (SSS) Question- The relationship between the four tests was as- naire, an outcome instrument specific to spinal sessed using scatter plots, according to the method stenosis. The measurement properties and valid- of Bland and Altmann, and the Pearson product– ity of this newly-developed patient questionnaire moment correlation coefficient (two-tailed). Bon- for the assessment of patients with lumbar spinal ferroni’s correction was used for multiple tests to stenosis was tested in an ongoing prospective mul- reduce the chance of Type 1 error. ticenter observational study of patients undergoing decompressive surgery in three teaching hospitals. Test–retest reliability in terms of the intraclass correlation coefficient (ICC) was 0.92 for the SWT, The internal consistency of the scales was assessed 0.92 for the SSS, 0.83 for the OCS and 0.89 for with Cronbach’s coefficient alpha on cross- the ODI. The mean percentage scores were 51 for sectional data from 193 patients before surgery. the SSS, 45 for the OCS, and 40 for the ODI. To The test-retest reliability was assessed on data from achieve 95% certainty of change between assess- a random sample of 23 patients using Spearman’s ments for a single patient, the SSS would need to rank correlation coefficient. The responsiveness change by 15, the OCS by 20 and the ODI by 16. was assessed on 130 patients with six-month follow-up data using the standardized response The mean SWT was 150 m, with a change of 76 m mean. The test-retest reliability of the scales required for 95% confidence. Cronbach’s alpha ranged from 0.82 to 0.96, the internal consistency was 0.91 for the SSS, 0.90 for the OCS, and 0.89 from 0.64 to 0.92, and the responsiveness from for the ODI. The change in ODI correlated most 0.96 to 1.07. The direction, statistical significance strongly with patient satisfaction after surgery and strength of hypothesized relationships with

external criteria were as expected. scores at one year. An 86% success rate was reported for the OP1 putty group, and a 73% success rate In critique, of the 193 patients included in this was reported for the patients receiving autograft. study, only 23 had pretest and posttest validation According to radiographic criteria, fusion was of the SSS. The follow-up on 130/193 patients for achieved in 74% of patients in the OP1 group and test responsiveness at six months is arguably short. 60% of patients in the autograft group. Of the 29 Because of these shortcomings, this potentially patients evaluated radiographically, 15 were defined Level I prospective study was downgraded to a as both radiographically and clinically successful, Level II study. Although the reproducibility, inter- while five were categorized as radiographically nal consistency, validity and responsiveness of this successful with clinical failure and eight were clas- test were established by comparison with known sified as radiographic failures, but achieved clinical validated outcome measurement instruments, these success. instruments are not necessarily specific to degenerative lumbar spondylolisthesis. In addition, the In critique of this study, clinical success was ar- extent of stenosis and associated pathology was not bitrarily defined as a 20% improvement in ODI clear. Patients with language barriers and cognitive scores. The authors failed to justify the choice difficulties were excluded. of this benchmark. The study does not correlate any outcome instruments to the ODI. This study This study provides Level II prognostic evidence provides Level II prognostic evidence that the ODI that the devised questionnaire scales of symtom se- can be used to assess clinical outcome after surgical verity, physical function and satisfaction are repro- treatment of degenerative spondylolisthesis. ducible, internally consistent, valid and responsive measures of outcome in patients with degenerative Weinstein et al42 conducted a prospective, random- lumbar spondylolisthesis with symptomatic spinal ized control trial evaluating the outcomes of sur- stenosis. This instrument is currently referred to as gical treatment of degenerative spondylolisthesis the Zurich Claudication Questionnaire (ZCQ) or compared with medical/interventional treatment Swiss Spinal Stenosis Questionnaire (SSS). in 304 patients. The study also included a second observational cohort of 303 patients who refused Vaccaro et al39 reported a prospective, random- randomization, but agreed to participate in the ized control trial comparing surgical outcomes in study. patients randomly assigned to receive either OP1 putty (24 patients) or autograft bone (12 patients) The primary outcome measures used in the study in conjunction with decompressive laminectomy included the Medical Outcomes Study SF-36 for the treatment of degenerative lumbar spon- bodily pain and physical function scores and the dylolisthesis. The outcome measures utilized in this modified Oswestry Disability Index. Data were study included the ODI, SF-36 and radiographic collected at six weeks, three months, six months, assessment. one year and two years. Secondary outcomes measures included patient reported improvement, sat- At one year, of the 36 patients studied, 32 were isfaction with current symptoms and care, Stenosis available for clinical follow-up (18 in the OP1 Bothersome Index and LBP Bothersome Index. group and eight in the autograft group) and 29 received radiographic assessment (14 in the OP1 Within the randomized arm of the study, the au- group and six in the autograft group). ODI success thors reported a 40% crossover in each direction. was defined by greater than 20% improvement in Intention-to-treat analysis showed no significant

differences in any outcome. As-treated analysis for LASD value and the changes in slippage during the both cohorts showed significant advantages at three follow-up period: the patients with LASD greater months that increased at one year and was durable than 35 mm (Group A) and those with LASD less at two years. Treatment effects at two years were than 35 mm (Group B). The patients in Group A 18.1 for bodily pain (95%, CI 14.5-21.7) 18.3 for were divided into two subgroups: the patients with physical function (95%, CI 14.6-21.9) and -16.7 in situ fusion (Group A1) and patients with re- for ODI (95%, CI -19.5 to -13.9). There is little duced slippage (Group A2). evidence suggesting harm with either surgical or medical treatment. The authors reported that the JOA scores were 12.6 points +/- 4.8 preoperatively and 21.7 points In critique of this study, the secondary outcome +/- 4.9 postoperatively, and the recovery rate was measures, Stenosis Bothersome Index and LBP 55.1% +/- 27.8%. There were no differences in the Bothersome Index, have not been specifically vali- prognostic factors of preoperative slip, lumbar lor- dated for degenerative lumbar spondylolisthesis. dosis, lordosis of fused segment and recovery rates. This study provides Level I prognostic evidence LASD and recovery rate were negatively corre- from both the randomization and observational co- lated. Patients in Group A1 had poorer JOA scores horts that the primary outcome measures, Medical and recovery rates than those in Groups A2 and B. Outcomes Study SF-36 bodily pain and physical function scores and the modified Oswestry Dis- In critique, this study utilized a validated out- ability Index, are appropriate instruments to use in come measure commonly used in Japan that has detecting treatment effects in patients with degen- not gained universal acceptance. The paper was erative lumbar spondylolisthesis. designed as a clinical outcome study, rather than a prognostic study evaluating the JOA outcome The Japanese Orthopedic Association (JOA) measure, specifically. This study provides Level III Score and the calculated Recovery Rate may prognostic evidence suggesting that the JOA score be useful in assessing outcome in degenerative and recovery rate may be sensitive outcome tools lumbar spondylolisthesis. in assessing treatment for degenerative lumbar spondylolisthesis. Grade of Recommendation: B Okuda et al24 conducted a comparative retrospec- Kawakami et al16 performed a retrospective case tive prognostic study including 101 elderly patients control study of 47 patients (15 males / 32 fe- with degenerative spondylolisthesis treated with males) who had undergone decompression and posterior lumbar interbody fusion (PLIF). Patients fusion with and without instrumentation. Pedicle were divided into two groups based upon age. screw fixation was used in those cases with a fixed Group 1 included patients aged 70 years and older, kyphosis at the involved segment. The outcome while Group 2 included patients from 55 years to measures used included the Japanese Orthopedic 69 years of age at the time of the index procedure. Association (JOA) score, VAS, recovery rate (Hi- The authors compared treatment outcomes be- rabayashi’s method), slippage, L1 axis S1 distance tween both groups to determine differences in out- (LASD), lumbar lordosis, lordosis at the fused seg- come based upon age. The outcome measures used ment, bony union and adjacent segment changes. in this study included the JOA score, VAS, complication rates, recovery rate (Hirabayashi method) Patients with degenerative lumbar spondylolisthe- and radiographic evaluation. sis were divided into two groups according to the

The authors reported that in Group 1, the JOA The patients were assessed using the Oswestry Dis- improved from 12 to 23; the recovery rate was ability Index (ODI) and three instruments designed 63%; and general complications, delirium and brain specifically for use in patients with lumbar spinal infarct occurred in 10% of patients. In Group 2, stenosis: the Swiss Spinal Stenosis (SSS) Question- the JOA improved from 12 to 24 and the recovery naire, the Oxford Claudication Score (OCS) and rate was 70%. a functional test, the Shuttle Walk Test (SWT). Patient outcomes were studied by the previously In critique of this study, 39% of the cases were validated outcome studies, the SSS and ODI. The not independently reviewed. This study provides OCS and SWT were studied in relation to these Level II prognostic evidence that the JOA shows previously validated outcome measures. improvement in functional outcome with surgical treatment regardless of age, but is not correlated Data analysis included a test against normality with other measures of functional outcomes. Older using the Komolgorov-Smirnov-Goodness-of-Fit patients, despite higher definable complication test. The test-retest reliability of the SSS, OCS, rates (approaching 10%) showed similar recovery ODI and SWT were assessed with an internal rates and JOA scores to younger patients. correlation coefficient test in which the R was the subject variability/ (subject variability + measure- The Shuttle Walking Test (SWT), Oxford ment error). The 95% confidence intervals for each Claudication Score (OCS), Low Back outcome instrument were reported. Pain Bothersome Index and Stenosis Bothersome Index are potential outcome The internal consistency of the scales and their sub- measures in studying degenerative lumbar sections was assessed using Cronbach’s coefficient spondylolisthesis. alpha, which summarizes inter-item correlations. The relationship between the four tests was as- Grade of Recommendation: I (Insufficient sessed using scatter plots, according to the method Evidence) of Bland and Altmann, and the Pearson product– moment correlation coefficient (two-tailed). Bon- Pratt et al29 conducted a prospective prognostic ferroni’s correction was used for multiple tests to study evaluating outcome instruments in all pa- reduce the chance of Type 1 error. tients who attended the Nuffield Orthopaedic Center. These were patients with spinal stenosis, Test–retest reliability in terms of the intraclass cor- which included patients with degenerative spon- relation coefficient (ICC) was 0.92 for the SWT, dylolisthesis. 0.92 for the SSS, 0.83 for the OCS and 0.89 for the ODI. The mean percentage scores were 51 for Of the 52 patients approached to participate in the the SSS, 45 for the OCS, and 40 for the ODI. To study, 13 declined involvement and seven were achieve 95% certainty of change between assess- excluded because of comorbidities limiting walk- ments for a single patient, the SSS would need to ing distance. To determine reliability, the 32 clinic change by 15, the OCS by 20 and the ODI by 16. patients with lumbar spinal stenosis were assessed twice, with one week between assessments. Ret- The mean SWT was 150 m, with a change of 76 m rospective data from 17 patients assessed before required for 95% confidence. Cronbach’s alpha surgery and 18 months after surgery for lumbar was 0.91 for the SSS, 0.90 for the OCS and 0.89 spinal stenosis were used to investigate the use of for the ODI. The change in ODI correlated most reliability in a clinical setting. strongly with patient satisfaction after surgery

(0.80; P 0.001). at two years. Treatment effects at two years were 18.1 for bodily pain (95%, CI 14.5-21.7) 18.3 for In critique of this study, the subset of patients with physical function (95%, CI 14.6-21.9) and -16.7 degenerative spondylolisthesis was not broken out for ODI (95%, CI -19.5 to -13.9). There is little and analyzed separately from the stenosis group. evidence suggesting harm with either surgical or Fluctuations in a patient’s symptoms result in wide medical treatment. individual confidence intervals. Performance on the SSS, OCS and ODI questionnaires are broadly In critique of this study, the secondary outcome similar, the most precise being the condition- measures, Stenosis Bothersome Index and LBP specific SSS. The SWT provides a snapshot of Bothersome Index, have not been specifically vali- physical function which is acceptable for group dated for degenerative lumbar spondylolisthesis. analysis. Use of the SWT for individual assessment This study provides Level I prognostic evidence after surgery is feasible. This study offers Level I from both the randomization and observational co- prognostic evidence that the ODI, SSS, OCS and horts that the primary outcome measures, Medical SWT tests reliably and validly evaluate patients Outcomes Study SF-36 bodily pain and physical with symptomatic spinal stenosis within which a function scores and the modified Oswestry Dis- subgroup of degenerative spondylolisthesis patients ability Index, are appropriate instruments to use in exist. detecting treatment effects in patients with degenerative lumbar spondylolisthesis. Weinstein et al42 conducted a prospective, randomized control trial evaluating the outcomes of surgical treatment of degenerative spondylolisthesis Future Directions for Research compared with medical/interventional treatment Further studies are needed to validate additional in 304 patients. The study also included a second outcome measures (Stenosis Bothersome Index, observational cohort of 303 patients who refused LBP Bothersome Index, Oxford Claudication randomization but agreed to participate in the Score, Shuttle Walking Test, JOA and Calculated study. Recovery Rate) for the treatment of degenerative lumbar spondylolisthesis. Currently, the best out- The primary outcome measures used in the study come measure for degenerative spondylolisthesis included the Medical Outcomes Study SF-36 with symptoms of spinal stenosis is the ZCQ/SSS bodily pain and physical function scores and the as a disease-specific outcome tool. General health modified Oswestry Disability Index. Data was col- outcome tools that are appropriate for degenerative lected at six weeks, three months, six months, one lumbar spondylolisthesis are the SF-36 and ODI. year and two years. Secondary outcomes measures included patient reported improvement, satisfac- Degenerative lumbar spondylolisthesis with back tion with current symptoms and care, Stenosis pain alone needs to be defined as a stand-alone Bothersome Index and LBP Bothersome Index. clinical entity by outcomes research. The use of these outcome measures in this subgroup of pa- Within the randomized arm of the study, the au- tients needs to be studied. thors reported a 40% crossover in each direction. Intention-to-treat analysis showed no significant Outcome Measures References differences in any outcome. As-treated analysis for 1. Anderson PA, Tribus CB, Kitchel SH. Treatment of both cohorts showed significant advantages at three neurogenic claudication by interspinous decompression: months that increased at one year and was durable application of the X STOP device in patients with lumbar degenerative spondylolisthesis. J Neurosurg Spine. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 32

2006;4(6):463-471. laminectomy. Spine. 1999;24(15):1533-1537. 2. Bednar DA. Surgical management of lumbar degenera- 14. Houten JK, Post NH, Dryer JW, Errico TJ. Clinical and tive spinal stenosis with spondylolisthesis via posterior radiographically/neuroimaging documented outcome reduction with minimal laminectomy. J Spinal Disord in transforaminal lumbar interbody fusion. Neurosurg Tech. 2002;15(2):105-109. Focus. 2006;20(3):E8. 3. Bono CM, Lee CK. The influence of subdiagnosis on ra- 15. Kanayama M, Hashimoto T, Shigenobu K, Yamane S, diographic and clinical outcomes after lumbar fusion for Bauer TW, Togawa D. A prospective randomized study degenerative disc disorders: an analysis of the literature of posterolateral lumbar fusion using osteogenic pro- from two decades. Spine. 2005;30(2):227-234. tein-1 (OP-1) versus local autograft with ceramic bone 4. Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, substitute: emphasis of surgical exploration and histo- Lenke LG. Minimum 5-year results of degenerative logic assessment. Spine. 2006;31(10):1067-1074. spondylolisthesis treated with decompression and instru- 16. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- mented posterior fusion. Spine. 1999;24(16):1721-1727. zume H, Yoshida M. Lumbar sagittal balance influences 5. Fernandez-Fairen M, Sala P, Ramirez H, Gil J. A pro- the clinical outcome after decompression and posterolat- spective randomized study of unilateral versus bilateral eral spinal fusion for degenerative lumbar spondylolis- instrumented posterolateral lumbar fusion in degenera- thesis. Spine. 2002;27(1):59-64. tive spondylolisthesis. Spine. 2007;32(4):395-401. 17. Kleeman TJ, Hiscoe AC, Berg EE. Patient out- 6. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, comes after minimally destabilizing lumbar stenosis Montgomery DM, Kurz LT. 1997 Volvo Award winner decompression: the “Port-Hole” technique. Spine. in clinical studies. Degenerative lumbar spondylolisthesis 2000;25(7):865-870. with spinal stenosis: a prospective, randomized study 18. Klopfenstein JD, Kim LJ, Feiz-Erfan I, Dickman CA. comparing decompressive laminectomy and arthrod- Retroperitoneal approach for lumbar interbody fusion esis with and without spinal instrumentation. Spine. with anterolateral instrumentation for treatment of spon- 1997;22(24):2807-2812. dylolisthesis and degenerative foraminal stenosis. Surg 7. Frazier DD, Lipson SJ, Fossel AH, Katz JN. As- Neurol. 2006;65(2):111-116; discussion 116. sociations between spinal deformity and outcomes 19. Konno S, Kikuchi S. Prospective study of surgical treat- after decompression for spinal stenosis. Spine. ment of degenerative spondylolisthesis: comparison 1997;22(17):2025-2029. between decompression alone and decompression with 8. Gaetani P, Aimar E, Panella L, et al. Functional disability graf system stabilization. Spine. 2000;25(12):1533-1537. after instrumented stabilization in lumbar degenera- 20. Kornblum MB, Fischgrund JS, Herkowitz HN, Abra- tive spondylolisthesis: a follow-up study. Funct Neurol. ham DA, Berkower DL, Ditkoff JS. Degenerative lumbar 2006;21(1):31-37. spondylolisthesis with spinal stenosis: a prospective 9. Gehrchen PM, Dahl B, Katonis P, Blyme P, Tondevold E, long-term study comparing fusion and pseudarthrosis. Kiaer T. No difference in clinical outcome after poste- Spine. 2004;29(7):726-733; discussion 733-724. rolateral lumbar fusion between patients with isthmic 21. Lauber S, Schulte TL, Liljenqvist U, Halm H, Hack- spondylolisthesis and those with degenerative disc enberg L. Clinical and radiologic 2-4-year results of disease using pedicle screw instrumentation: a compara- transforaminal lumbar interbody fusion in degenerative study of 112 patients with 4 years of follow-up. Eur tive and isthmic spondylolisthesis grades 1 and 2. Spine. Spine J. 2002;11(5):423-427. 2006;31(15):1693-1698. 10. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Pro- 22. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis spective outcomes evaluation after decompression with in grade I degenerative lumbar spondylolisthesis: a com- or without instrumented fusion for lumbar stenosis and parative study of outcomes following laminoplasty and degenerative Grade I spondylolisthesis. J Neurosurg laminectomy with instrumented spinal fusion. J Orthop Spine. 2004;1(3):267-272. Sci. 2005;10(3):270-276. 11. Gibson JN, Grant IC, Waddell G. The Cochrane review 23. McCulloch JA. Microdecompression and uninstru- of surgery for lumbar disc prolapse and degenerative mented single-level fusion for spinal canal steno- lumbar spondylosis. Spine. 1999;24(17):1820-1832. sis with degenerative spondylolisthesis. Spine. 12. Glaser JA, Bernhardt M, Found EM, McDowell GS, 1998;23(20):2243-2252. Wetzel FT. Lumbar arthrodesis for degenerative condi- 24. Okuda S, Oda T, Miyauchi A, Haku T, Yamamoto T, tions. Instr Course Lect. 2004;53:325-340. Iwasaki M. Surgical outcomes of posterior lumbar inter- 13. Herno A, Partanen K, Talaslahti T, et al. Long-term body fusion in elderly patients. J Bone Joint Surg Am. clinical and magnetic resonance imaging follow-up as- 2006;88(12):2714-2720. sessment of patients with lumbar spinal stenosis after 25. Okuyama K, Kido T, Unoki E, Chiba M. PLIF with a ti-

tanium cage and excised facet joint bone for degenerative diographic analysis and choice of treatment. Spine. spondylolisthesis-in augmentation with a pedicle screw. J 1992;17(11):1329-1336. Spinal Disord Tech. 2007;20(1):53-59. 35. Schnake KJ, Schaeren S, Jeanneret B. Dynamic stabili- 26. Onda A, Otani K, Konno S, Kikuchi S. Mid-term and zation in addition to decompression for lumbar spinal long-term follow-up data after placement of the Graf stenosis with degenerative spondylolisthesis. Spine. stabilization system for lumbar degenerative disorders. J 2006;31(4):442-449. Neurosurg Spine. 2006;5(1):26-32. 36. Schnee CL, Freese A, Ansell LV. Outcome analysis for 27. Panagiotis ZE, Athanasios K, Panagiotis D, Minos T, adults with spondylolisthesis treated with posterolateral Charis M, Elias L. Functional outcome of surgical treat- fusion and transpedicular screw fixation. J Neurosurg. ment for multilevel lumbar spinal stenosis. Acta Orthop. 1997;86(1):56-63. 2006;77(4):670-676. 37. Sengupta DK. Point of view: Dynamic stabiliza- 28. Podichetty VK, Spears J, Isaacs RE, Booher J, Biscup tion in addition to decompression for lumbar spinal RS. Complications associated with minimally invasive stenosis with degenerative spondylolisthesis. Spine. decompression for lumbar spinal stenosis. J Spinal Disord 2006;31(4):450. Tech. 2006;19(3):161-166. 38. Stucki G, Daltroy L, Liang MH, Lipson SJ, Fossel AH, 29. Pratt RK, Fairbank JC, Virr A. The reliability of the Katz JN. Measurement properties of a self-administered Shuttle Walking Test, the Swiss Spinal Stenosis Ques- outcome measure in lumbar spinal stenosis. Spine. tionnaire, the Oxford Spinal Stenosis Score, and the 1996;21(7):796-803. Oswestry Disability Index in the assessment of patients 39. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot safety with lumbar spinal stenosis. Spine. 2002;27(1):84-91. and efficacy study of OP-1 putty (rhBMP-7) as an 30. Prolo DJ, Oklund SA, Butcher M. Toward uniformity in adjunct to iliac crest autograft in posterolateral lumbar evaluating results of lumbar spine operations. A para- fusions. Eur Spine J. 2003;12(5):495-500. digm applied to posterior lumbar interbody fusions. 40. Vaccaro AR, Patel T, Fischgrund J, et al. A 2-year Spine. 1986;11(6):601-606. follow-up pilot study evaluating the safety and efficacy 31. Rechtine GR, Sutterlin CE, Wood GW, Boyd RJ, Mans- of op-1 putty (rhbmp-7) as an adjunct to iliac crest field FL. The efficacy of pedicle screw/plate fixation autograft in posterolateral lumbar fusions. Eur Spine J. on lumbar/lumbosacral autogenous bone graft fusion 2005;14(7):623-629. in adult patients with degenerative spondylolisthesis. J 41. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study Spinal Disord. 1996;9(5):382-391. evaluating the safety and efficacy of OP-1 Putty (rh- 32. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- BMP-7) as a replacement for iliac crest autograft in tors of outcomes after posterior decompression and posterolateral lumbar arthrodesis for degenerative spon- fusion in degenerative spondylolisthesis. Eur Spine J. dylolisthesis. Spine. 2004;29(17):1885-1892. 2005;14(1):55-60. 42. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ver- 33. Sato K, Kikuchi S. Clinical analysis of two-level com- sus nonsurgical treatment for lumbar degenerative spon- pression of the cauda equina and the nerve roots in lum- dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. bar spinal canal stenosis. Spine. 1997;22(16):1898-1903; 43. Zhao J, Hou T, Wang X, Ma S. Posterior lumbar discussion 1904. interbody fusion using one diagonal fusion cage 34. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A with transpedicular screw/rod fixation. Eur Spine J. clinical study of degenerative spondylolisthesis. Ra- 2003;12(2):173-177.

A systematic review of the literature yielded no a total of 47 articles related to medical/interven- studies to adequately address any of the medical/ tional treatment. Work group members reviewed interventional treatment questions posed below: all abstracts and identified nine articles to review in order to address the questions above and to iden- 1. Do medical/interventional treatments im- tify any other relevant articles cited in the reference prove outcomes in the treatment of degen- sections. erative lumbar spondylolisthesis compared to the natural history of the disease? An extensive review of all articles cited in the reference section found no direct comparison of 2. What is the role of pharmacological treat- active treatment (medical/interventional) to an ment in the management of degenerative untreated control group (natural history). Patients lumbar spondylolisthesis? with degenerative lumbar spondylolisthesis can be asymptomatic, present exclusively with axial back 3. What is the role of physical therapy/exer- pain or present with neurogenic claudication and/ cise in the treatment of degenerative lumbar or radicular pain with or without accompanying spondylolisthesis? axial back pain. Treatment for each of these patient populations will be different. Identifying relevant 4. What is the role of manipulation in the studies and formulating evidence-based treatment treatment of degenerative lumbar spon- recommendations for subpopulations of the de- dylolisthesis? generative lumbar spondylolytic patients (eg, axial back pain only, combination of axial back pain and 5. What is the role of epidural steroid injec- radiculopathy) was not feasible as none of the stud- tions for the treatment of degenerative ies presented results stratified by symptomatology. lumbar spondylolisthesis? Medical/interventional treatment for 6. What is the role of ancillary treatments such degenerative lumbar spondylolisthesis, as bracing, traction, electrical stimulation when the radicular symptoms of stenosis and transcutaneous electrical stimulation predominate, most logically should be similar (TENS) in the treatment of degenerative to treatment for symptomatic degenerative lumbar spondylolisthesis? lumbar spinal stenosis.

7. What is the long-term result of medical/ Work Group Consensus Statement interventional management of degenerative lumbar spondylolisthesis? Treatment recommendations and the supporting evidence are available in the NASS guideline Di- Unfortunately, a thorough literature search tar- agnosis and Treatment of Degenerative Lumbar geted at the subset of stenotic patients with degen- Spinal Stenosis (2007) available on the NASS Web erative lumbar spondylolisthesis yielded a paucity site at (www.spine.org). of evidence addressing medical/interventional treatment. A thorough literature search identified

Future Directions for Research that a randomized controlled study comparing The work group identified the following sug- the benefits of physical therapy with directional gestions for future studies which would generate preference versus nonpreferential therapy for meaningful evidence to assist in further defining the treatment of degenerative lumbar spon- the role of medical treatment for degenerative lum- dylolisthesis would be useful. bar spondylolisthesis.

Recommendation #1: Medical/Interventional Treatment Future studies of the effects of medical, non- References invasive interventions for degenerative lumbar 1. Atlas SJ, Delitto A. Spinal stenosis: surgical ver- spondylolisthesis should include an untreated sus nonsurgical treatment. Clin Orthop Relat Res. control group when ethically possible. 2006;443:198-207. 2. Bassewitz H, Herkowitz H. Lumbar stenosis with spon- Recommendation #2: dylolisthesis: current concepts of surgical treatment. Clin Orthop Relat Res. 2001(384):54-60. Future outcome studies of degenerative lumbar 3. Herkowitz HN. Spine update. Degenerative lumbar spondylolisthesis should include results specific spondylolisthesis. Spine. 1995;20(9):1084-1090. to each of the medical/interventional treatment 4. Radu AS, Menkes CJ. Update on lumbar spinal steno- methods, presenting results stratified by patient sis. Retrospective study of 62 patients and review of the symptomatology (eg, axial back pain only, com- literature. Rev Rhum Engl Ed. 1998;65(5):337-345. 5. Rosenberg NJ. Degenerative spondylolisthesis. Predis- bination of axial back pain and radiculopathy). posing factors. J Bone Joint Surg Am. 1975;57(4):467-474. 6. Soren A, Waugh TR. Spondylolisthesis and related dis- Recommendation #3: orders. A correlative study of 105 patients. Clin Orthop Although the review was devoid of studies Relat Res. 1985(193):171-177. examining the benefits of physical therapy with 7. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spon- a directional preference (eg, avoiding extension) dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. in patients with degenerative lumbar spon- 8. Yue WM, Tan SB. Distant skip level discitis and vertebral dylolisthesis, this appears to be an area of grow- osteomyelitis after caudal epidural injection: a case report ing interest. Accordingly, the group suggests of a rare complication of epidural injections. Spine. 2003;28(11):E209-211.

Do surgical treatments improve spinal stenosis (and not necessarily spondylolisthesis) that were randomized into the X STOP outcomes in the treatment treatment group and medical/interventional group. of degenerative lumbar However there were no significant baseline differences detected between the groups. Five patients in spondylolisthesis compared the X STOP group and four patients in the medi- to the natural history of the cal/interventional group subsequently underwent a laminectomy. It is unclear if the data from these disease? patients were included as an intention-to-treat analysis. Surgery is recommended for treatment of patients with symptomatic spinal stenosis If one were to equate medical/interventional treat- associated with low grade degenerative ment including injections, therapy and medica- spondylolisthesis whose symptoms have been tions with natural history, this study offers Level recalcitrant to a trial of medical/interventional III therapeutic evidence that surgical treatment in treatment. the form of an interspinous spacer improves upon the natural history of neurogenic claudication and Grade of Recommendation: B spinal stenosis with low grade degenerative spondylolisthesis. Anderson et al1 reported subgroup analysis data from a large, randomized controlled trial deal- Weinstein et al6 conducted a multicenter, pro- ing with spinal stenosis. As such, this represents spective, randomized controlled trial comparing a prospective, comparative study of 75 patients surgery and medical/interventional treatment for with neurogenic claudication from lumbar spinal neurogenic claudication from spinal stenosis and stenosis and low grade (less than 25% translation) degenerative spondylolisthesis. In addition, there spondylolisthesis who were treated either with the was a nonrandomized observational arm that com- X STOP device (an interspinous process spacer) or pared the two treatment options. Eligible patients with medical/interventional treatment. The medi- had symptoms for at least 12 weeks and could have cal/interventional (control) group did receive treat- had medical/interventional treatment prior to en- ment, which included at least one epidural steroid rollment. Surgical treatment included laminectomy injection, medications and physical therapy. Thus, with or without fusion; however, few patients this group was not truly representative of the natu- underwent laminectomy alone. Medical/interven- ral history of the disorder. At two-year follow-up, tional treatment included at least active physical there were statistically significant improvements therapy, education/counseling and medications. in the Zurich Claudication Questionnaire (ZCQ) In critique of this study, there was a high crossover score and patient satisfaction in those treated with rate between study groups. For instance, 49% of X STOP; there were no statistically significant im- those patients assigned to medical/interventional provements in the medical/interventional group. treatment had undergone surgery at two-year follow-up. Likewise, only 64% of those who were In critique of this study, the cohort of 75 patients assigned to the surgical group had undergone was derived from a larger pool of candidates with surgery by two years. Because of the high degree

Does surgical decompression of a decompressive laminoplasty results in better outcomes than the natural history of spinal stenosis alone improve surgical outcomes with grade I degenerative spondylolisthesis. in the treatment of degenerative Indirect surgical decompression is lumbar spondylolisthesis recommended for treatment of patients compared to medical/ with symptomatic spinal stenosis associated with low grade degenerative lumbar spondy- interventional treatment alone lolisthesis whose symptoms have been or the natural history of the recalcitrant to a trial of medical/interventional disease? treatment. Grade of Recommendation: I (Insufficient Direct surgical decompression is Evidence) recommended for treatment of patients with symptomatic spinal stenosis associated Anderson et al1 performed a subgroup analysis of with low grade degenerative lumbar 75 patients with grade I degenerative spondylolis- spondylolisthesis whose symptoms have been thesis who were originally included in the pivotal recalcitrant to a trial of medical/interventional randomized controlled trial comparing the X treatment. STOP device and medical/interventional treatment for spinal stenosis with neurogenic claudication Grade of Recommendation: I (Insufficient that was relieved by flexion and sitting. Although Evidence) examined prospectively, this subgroup was not ap- propriated to surgical and medical/interventional 17 Matsudaira et al conducted a retrospective com- treatment in a truly randomized fashion. parative study of 53 patients with spinal stenosis and grade I degenerative spondylolisthesis. Nine- Forty-two patients had the X STOP device placed, teen underwent decompression with instrumented while 33 had medical/interventional treatment fusion, 18 underwent decompressive laminoplasty that included at least one epidural steroid injec- without fusion, and 16 had medical/interventional tion, medications and physical therapy as needed. treatment. At a minimum of two years follow-up, Only 70 of 75 patients had a minimum of two year patients in both surgical treatment groups showed follow-up. Of patients in the X STOP group, 63% significantly better improvements in Japanese had significant improvements in the Zurich Clau- Orthopaedic Association (JOA) scores than the dication Questionnaire (ZCQ) score, while 12% medical/interventional group. in the medical/interventional group had significant improvements. In critique of this study, the sample was modest, particularly considering there were only 16 patients In critique of this study, although labeled by the in the medical/interventional group. To be used authors as a randomized controlled trial, it was not to answer the current question, one has to assume such for patients with degenerative spondylolisthe- that medical/interventional treatment is equivalent sis. Patient numbers were relatively low. In support to natural history. In support of the study, patients of their findings, there was a low attrition rate (7% uniformly had grade I degenerative spondylolisthe- at two year follow-up). Furthermore, the investiga- sis. This paper provides Level III therapeutic evi- tors utilized a validated outcome instrument, the dence that decompressive surgery alone in the form

ZCQ. This study offers Level III therapeutic evi- Masferrer R, Sonntag VK. Surgical treatment of lum- dence that an interspinous distraction device that bar spondylolisthesis. Adv Tech Stand Neurosurg. provides indirect decompression leads to better 2000;26:331-346. 6. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. outcomes in patients with spinal stenosis and grade Degenerative spondylolisthesis. To fuse or not to fuse. I degenerative spondylolisthesis than does medical/ Spine. 1985;10(3):287-289. interventional intervention. 7. France JC, Yaszemski MJ, Lauerman WC, et al. A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instru- Future Directions for Research mentation. Spine. 1999;24(6):553-560. Because of the lack of clarity of the ideal candidate 8. Gibson JN, Grant IC, Waddell G. The Cochrane review for decompression alone, a large scale randomized of surgery for lumbar disc prolapse and degenerative controlled trial may be logistically and ethically lumbar spondylosis. Spine. 1999;24(17):1820-1832. 9. Gibson JN, Waddell G. Surgery for degenerative difficult to perform. The work group acknowl- lumbar spondylosis. Cochrane Database Syst Rev. edges that recently published high profile studies 2005(4):CD001352. (SPORT trials) demonstrated the intrinsic dif- 10. Gibson JN, Waddell G, Grant IC. Surgery for degenera- ficulties in conducting RCTs comparing surgical tive lumbar spondylosis. Cochrane Database Syst Rev. to medical/interventional treatment in the North 2000(3):CD001352. 11. Herkowitz HN. Spine update. Degenerative lumbar American patient population. It is unlikely that spondylolisthesis. Spine. 1995;20(9):1084-1090. higher quality data are achievable for the compari- 12. Hilibrand AS, Rand N. Degenerative lumbar stenosis: son of surgical and medical/interventional treat- diagnosis and management. J Am Acad Orthop Surg. ment. 1999;7(4):239-249. 13. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- cer C, 3rd. Treatment of degenerative spondylolisthesis. A greater number of nonindustry-sponsored, Spine. 1985;10(9):821-827. independent, randomized controlled trials need to 14. Mardjetko SM, Connolly PJ, Shott S. Degenerative be done to validate what appears to be an effective lumbar spondylolisthesis. A meta-analysis of literature and minimally invasive means (interspinous spac- 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S. ers) of decompressing the spinal canal in patients 15. Mariconda M, Fava R, Gatto A, Longo C, Milano C. Unilateral laminectomy for bilateral decompression of with symptomatic spinal stenosis and degenerative lumbar spinal stenosis: a prospective comparative study lumbar spondylolisthesis. with conservatively treated patients. J Spinal Disord Tech. 2002;15(1):39-46. 16. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah Surgical Decompression Versus SM, O’Neil J, Wai EK. The surgical management of de- Natural History or Medical generative lumbar spondylolisthesis: a systematic review. Spine. 2007;32(16):1791-1798. Treatment References 17. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis 1. Anderson PA, Tribus CB, Kitchel SH. Treatment of in grade I degenerative lumbar spondylolisthesis: a com- neurogenic claudication by interspinous decompression: parative study of outcomes following laminoplasty and application of the X STOP device in patients with lum- laminectomy with instrumented spinal fusion. J Orthop bar degenerative spondylolisthesis. J Neurosurg Spine. Sci. 2005;10(3):270-276. 2006;4(6):463-471. 18. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A 2. Atlas SJ, Delitto A. Spinal stenosis: surgical ver- clinical study of degenerative spondylolisthesis. Ra- sus nonsurgical treatment. Clin Orthop Relat Res. diographic analysis and choice of treatment. Spine. 2006;443:198-207. 1992;17(11):1329-1336. 3. Bassewitz H, Herkowitz H. Lumbar stenosis with spon- 19. Sengupta DK, Herkowitz HN. Lumbar spinal stenosis. dylolisthesis: current concepts of surgical treatment. Clin Treatment strategies and indications for surgery. Orthop Orthop Relat Res. 2001(384):54-60. Clin North Am. 2003;34(2):281-295. 4. Benoist M. The natural history of lumbar degenerative 20. Soren A, Waugh TR. Spondylolisthesis and related dis- spinal stenosis. Joint Bone Spine. 2002;69(5):450-457. orders. A correlative study of 105 patients. Clin Orthop 5. Detwiler PW, Porter RW, Han PP, Karahalios DG,

Relat Res. 1985(193):171-177. dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. 21. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ver- 22. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. sus nonsurgical treatment for lumbar degenerative spon- Indication of fusion for lumbar spinal stenosis in elderly patients and its significance. Spine. 1996;21(2):242-248.

Does the addition of lumbar fu- gression reported that they were helped by the surgery than those whose slippage progressed post- sion, with or without instrumen- operatively (ρ<0.01). tation, to surgical decompression In critique, this was a small study in which selec- improve surgical outcomes in the tion bias entered into the randomization process, treatment of degenerative lum- reviewers were not masked to patient treatment and validated outcome measures were not utilized. bar spondylolisthesis compared Because of these weaknesses, this potential Level to treatment by decompression II study was downgraded to Level III. This study provides Level III therapeutic evidence that instru- alone? mented fusion patients had less chance of progressive slippage postoperatively than laminectomy Surgical decompression with fusion is alone or noninstrumented fusions and a higher recommended for the treatment of patients proportion of patients with stable or unchanged with symptomatic spinal stenosis and spondylolisthesis reported greater improvement degenerative lumbar spondylolisthesis to after surgery. improve clinical outcomes compared with decompression alone. Herkowitz et al15 conducted a prospective, comparative study of 50 patients with degenerative Grade of Recommendation: B lumbar spondylolisthesis who were studied clinically and radiographically to determine if concomi- 4 Bridwell et al described a prospective, comparative tant intertransverse process arthrodesis provided study of 44 surgically treated patients with degen- better results than decompression alone. Outcomes erative lumbar spondylolisthesis followed for a were assessed using a rudimentary outcome scale minimum of two years. Of the 44 patients, nine un- (excellent, good, fair, poor) with a mean follow-up derwent laminectomy alone, 10 had laminectomy of three years. and instrumented fusion and 24 had laminectomy and instrumented fusion (18 single level, six two- The authors reported that of the 25 patients treated level). Patients were radiographically assessed and with decompression and fusion, 11 reported excel- a functional assessment was conducted by asking lent results, 13 good, one fair and zero poor. Of the whether they felt their ability to walk distances was 25 patients treated with decompression alone, two worse (-), the same (0) or significantly better (+). reported excellent results, nine good, 12 fair and Of the 44 patients, 43 were followed for two years two poor. Improved results in the patients who had or more. an arthrodesis concomitantly with decompression were significant by the Fisher exact test (ρ=0.0001). The authors determined that instrumented fu- The authors concluded that in patients who had a sion had higher fusion rates than noninstrumented concomitant arthrodesis, the results were signifi- fusion (ρ=0.002). The authors further observed cantly better with respect to relief of low back pain greater progression of spondylolisthesis in patients and lower limb pain. treated with laminectomy alone (44%) and in laminectomy without instrumented fusion (70%) In critique, this was a small study which did not compared to patients who received laminectomy utilize validated clinical outcome measures or with instrumented fusion (4%,ρ=0.001). A higher describe baseline characteristics of the groups. proportion of the patients without slippage pro-

Because of these weaknesses, this potential Level II (JOA) score. Excellent and good results were study was downgraded to Level III. This study of- reassigned as satisfactory; poor results were fers Level III therapeutic evidence that decompres- classified as unsatisfactory. sion with arthrodesis in patients with degenerative lumbar spondylolisthesis provides significantly The authors reported that in the decompression better relief of low back pain and leg pain than alone category, 11 papers representing 216 patients decompression alone. were accepted. Sixty-nine percent of patients had a satisfactory outcome. The incidence of worsened Mardjetko et al23 performed a meta-analysis of postoperative slip was 31% but was not associ- primarily Level III studies. The objective of the ated with a poorer clinical result in the majority of study was to analyze the published data on degen- patients. erative spondylolisthesis to evaluate the feasibility of its use as a literature control to compare with the In the category of decompression with fusion and historical cohort pedicle screw study data. no instrumentation, six papers qualified for inclusion. In one paper, only fusion data were broken The authors conducted a comprehensive literature out for the diagnosis of degenerative spondylolis- search to identify studies published in English thesis and were used just for this outcome variable. peer-reviewed journals between 1970 and 1993 ad- Ninety percent of the patients in this category had dressing degenerative spondylolisthesis with radic- a satisfactory outcome; 86% achieved solid spinal ular leg pain or neurogenic claudication. Inclusion fusion. With regard to clinical outcome, the differ- criteria included a minimum of four cases reviewed ence between patients treated with decompression and reporting of the primary outcome variable of without fusion (69% satisfactory) and those treated fusion in articles in which this was part of the treat- with decompression and fusion without instrumen- ment. Clinical outcome variables of back pain, leg tation (90% satisfactory) was statistically signifi- pain, function, neurogenic claudication and global cant (P < 0.0001). outcome scores were recorded when available. A total of 25 papers representing 889 patients were In the decompression with fusion and pedicle accepted for inclusion. Twenty-one were retrospec- screws category, five studies met the inclusion tive, nonrandomized and uncontrolled. One paper criteria. Fusion status was analyzed in 101 patients. was retrospective and nonrandomized, but com- Eighty-five patients were analyzed with respect pared two different treatments. Three prospective, to clinical outcome. One paper did not separately randomized studies were included. analyze clinical data, but did so for fusion data; therefore, only fusion data were included. The The primary outcome variable, fusion, was proportionally weighted fusion rates for this group determined by each author. The most constant were 93%. When comparing the fusion without clinical outcome variable reported was pain with instrumentation group to the fusion with pedicle 16 papers reporting pain only, six papers reporting screw group, there was not a statistically significant pain and function, and two papers reporting increase in fusion rate (P = 0.08). Analysis of the patient-determined outcomes. Patient function was clinical outcomes reveals an 86% satisfactory rating reported in six papers and referred to the presence for the pedicle screw group. This compares favor- or absence of neurogenic claudication. In addition ably to the 69% satisfactory rate in the decompres- to these clinical outcomes, four papers reported a sion without fusion group (P <0.0001). global evaluation. Two used Kaneda’s rating system and two used the Japanese Orthopedic Association In the anterior spinal fusion category, three papers

presenting the results for 72 patients who received another included patient population or if it was not anterior spinal fusion for the treatment of degener- clearly a comparative study. ative spondylolisthesis were included. Pooling the data from these three studies yielded a 94% fusion Data from the included studies were extracted by rate with an 86% rate of patient satisfaction. two independent reviewers using a standard data abstraction sheet. The data abstraction sheet identi- The authors concluded that the meta-analysis fied the following information: (1) patient popula- results support the clinical impression that, in the tion’s age, gender, symptoms and degree of spon- surgical management of degenerative lumbar spondylolisthesis; (2) type of decompression, fusion, dylolisthesis, spinal fusion significantly improves instrumentation, bone graft material, and preopera- patient satisfaction. tive and postoperative treatment; (3) study design and methodological quality using the Cochrane In critique of this study, only three Level II studies RCT/CCT/Crossover Studies Checklist, modified were reviewed and data was very heterogeneous. by the additional criterion that observational stud- This paper offers Level III therapeutic evidence ies state the use of a consecutive series of patients; that the addition of fusion with or without in- and (4) study outcomes. strumentation to decompression improves clinical outcomes. The main abstracted outcomes were clinical outcome, reoperation rate and solid fusion status. An Martin et al24 conducted a systematic review de- attempt was made to compare patient-centered, signed to identify and analyze comparative studies validated and disease-specific outcomes, complica- that examined the surgical management of de- tions and spondylolisthesis progression, but be- generative lumbar spondylolisthesis, specifically cause of heterogeneity in reporting these outcomes the differences in outcomes between fusion and in the primary studies, no pooled analysis could be decompression alone, and between instrumented performed on these outcomes. When appropriate, a fusion and noninstrumented fusion. study’s clinical outcome rating scale was altered to match a dichotomous rating scale of “satisfactory” Relevant randomized controlled trials (RCTs) and or “unsatisfactory” clinical outcome, and results comparative observational studies were identified were entered into Review Manager 4.2 for weight- in a comprehensive literature search (1966 to June ed grouped analyses. 2005). The inclusion criteria required that a study be an RCT or comparative observational study that The authors reported that eight studies were in- investigated the surgical management of degenera- cluded in the fusion versus decompression alone tive lumbar spondylolisthesis by comparing: (1) analysis, including two RCTs. Limitations were fusion to decompression and/or (2) instrumented found in the methodologies of both RCTs and fusion to noninstrumented fusion. A minimum most of the observational studies. one-year follow-up was required. Studies also had to include at least five patients per treatment group. Grouped analysis detected a significantly higher A study was excluded if it included patients who probability of achieving a satisfactory clinical out- had received previous spine surgery or patients come with spinal fusion than with decompression with cervical injuries, spinal fractures, tumors or alone (relative risk, 1.40; 95% confidence interval, isthmic spondylolisthesis. A study was also exclud- 1.04–1.89; P < 0.05). The clinical benefit favoring ed if it was not possible to analyze patients with fusion decreased when analysis was limited to stud- degenerative spondylolisthesis separately from ies where the majority of patients were reported

to be experiencing neurologic symptoms such as Of the 55 patients, 20 underwent laminectomy intermittent claudication and/or leg pain. plus posterolateral fusion and pedicle screw instrumentation (Group 1), 19 underwent lamino- Six studies were included in the instrumented plasty alone (Group 2) and 16 refused surgery and fusion versus noninstrumented fusion analysis, received medical/interventional treatment (Group including three RCTs. The use of adjunctive instru- 3). One patient in each surgical group was lost to mentation significantly increased the probability follow-up. Outcomes were assessed by the Japa- of attaining solid fusion (relative risk, 1.37; 95% nese Orthopedic Association (JOA) score, along confidence interval, 1.07–1.75; P < 0.05), but no with radiographic evaluation at minimum two-year significant improvement in clinical outcome was follow-up. recorded (relative risk, 1.19; 95% confidence interval, 0.92–1.54). There was a nonsignificant trend The authors reported that alleviation of symptoms towards a lower repeat operation rate in the fusion was noted in the fusion and laminoplasty groups group compared with both decompression alone but not in the medical/interventional treatment and instrumented fusion. group. No statistically significant difference in clinical improvement was noted between the fu- The authors concluded there is moderate evidence sion and laminoplasty groups. The percent slip that fusion may lead to a better clinical outcome increased significantly in groups 2 and 3, whereas compared with decompression alone. Evidence that spondylolisthesis was stabilized in Group 1. The the use of adjunctive instrumentation leads to im- authors concluded that decompression with pres- proved fusion status and less risk of pseudoarthro- ervation of the posterior elements can be useful in sis is also moderate. No conclusion could be made treating patients with symptomatic lumbar spinal about the clinical effectiveness of instrumented stenosis resulting from grade I degenerative spon- fusion versus noninstrumented fusion. dylolisthesis.

In critique of this study, it was a systematic review In critique of this study, the numbers were small, of studies ranging down to Level III, and is thus patients were not randomized and no clearly de- classified as a Level III systematic review. Limita- fined indications for specific treatment selections tions were found in the methodologies of all RCTs, were included. This paper offers Level III thera- specifically in the pseudorandomization, absence peutic evidence that decompression with poste- of masking and/or the lack of validated outcome rolateral fusion and instrumentation, as well as measures to assess clinical outcomes. laminoplasty alone yield improved outcomes in the treatment of symptomatic lumbar spinal stenosis This paper offers Level III therapeutic evidence resulting from grade I degenerative spondylolisthe- that fusion leads to a better clinical outcome com- sis as compared with medical/interventional treat- pared with decompression alone and the use of ment alone. adjunctive instrumentation leads to improved fusion status and less risk of pseudoarthrosis. Their Future Directions for Research data does not demonstrate any difference in clinical Because of the lack of clarity of the ideal candidate outcomes between instrumented and noninstru- for decompression alone, a large scale randomized mented fusions. controlled trial may be logistically and ethically difficult to perform in comparison to decompres- 25 Matsudaira et al described a retrospective, com- sion and fusion. parative study of 55 patients with spinal stenosis in grade I degenerative lumbar spondylolisthesis. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 45

Fusion and Decompression 2000(3):CD001352. 15. Herkowitz HN, Kurz LT. Degenerative lumbar spon- References dylolisthesis with spinal stenosis. A prospective study 1. Atlas SJ, Delitto A. Spinal stenosis: surgical ver- comparing decompression with decompression and in- sus nonsurgical treatment. Clin Orthop Relat Res. tertransverse process arthrodesis. J Bone Joint Surg Am. 2006;443:198-207. 1991;73(6):802-808. 2. Bassewitz H, Herkowitz H. Lumbar stenosis with spon- 16. Herron LD, Trippi AC. L4-5 degenerative spondylolis- dylolisthesis: current concepts of surgical treatment. Clin thesis. The results of treatment by decompressive lamine- Orthop Relat Res. 2001(384):54-60. ctomy without fusion. Spine. 1989;14(5):534-538. 3. Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, 17. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- Lenke LG. Minimum 5-year results of degenerative zume H, Yoshida M. Lumbar sagittal balance influences spondylolisthesis treated with decompression and instru- the clinical outcome after decompression and posterolat- mented posterior fusion. Spine. 1999;24(16):1721-1727. eral spinal fusion for degenerative lumbar spondylolis- 4. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, thesis. Spine. 2002;27(1):59-64. Baldus C. The role of fusion and instrumentation in the 18. Kimura I, Shingu H, Murata M, Hashiguchi H. Lum- treatment of degenerative spondylolisthesis with spinal bar posterolateral fusion alone or with transpedicular stenosis. J Spinal Disord. 1993;6(6):461-472. instrumentation in L4-L5 degenerative spondylolisthesis. 5. Detwiler PW, Porter RW, Han PP, Karahalios DG, J Spinal Disord. 2001;14(4):301-310. Masferrer R, Sonntag VK. Surgical treatment of lum- 19. Kornblum MB, Fischgrund JS, Herkowitz HN, Abra- bar spondylolisthesis. Adv Tech Stand Neurosurg. ham DA, Berkower DL, Ditkoff JS. Degenerative lumbar 2000;26:331-346. spondylolisthesis with spinal stenosis: a prospective 6. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. long-term study comparing fusion and pseudarthrosis. Degenerative spondylolisthesis. To fuse or not to fuse. Spine. 2004;29(7):726-733; discussion 733-724. Spine. 1985;10(3):287-289. 20. Kuntz KM, Snider RK, Weinstein JN, Pope MH, Katz 7. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, JN. Cost-effectiveness of fusion with and without instru- Montgomery DM, Kurz LT. 1997 Volvo Award winner mentation for patients with degenerative spondylolisthe- in clinical studies. Degenerative lumbar spondylolisthesis sis and spinal stenosis. Spine. 2000;25(9):1132-1139. with spinal stenosis: a prospective, randomized study 21. Laus M, Tigani D, Alfonso C, Giunti A. Degenerative comparing decompressive laminectomy and arthrod- spondylolisthesis: lumbar stenosis and instability. Chir esis with and without spinal instrumentation. Spine. Organi Mov. 1992;77(1):39-49. 1997;22(24):2807-2812. 22. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- 8. Fitzgerald JA, Newman PH. Degenerative spondylolis- cer C, 3rd. Treatment of degenerative spondylolisthesis. thesis. J Bone Joint Surg Br. 1976;58(2):184-192. Spine. 1985;10(9):821-827. 9. France JC, Yaszemski MJ, Lauerman WC, et al. A 23. Mardjetko SM, Connolly PJ, Shott S. Degenerative randomized prospective study of posterolateral lumbar lumbar spondylolisthesis. A meta-analysis of literature fusion. Outcomes with and without pedicle screw instru- 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S. mentation. Spine. 1999;24(6):553-560. 24. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah 10. Frazier DD, Lipson SJ, Fossel AH, Katz JN. As- SM, O’Neil J, Wai EK. The surgical management of de- sociations between spinal deformity and outcomes generative lumbar spondylolisthesis: a systematic review. after decompression for spinal stenosis. Spine. Spine. 2007;32(16):1791-1798. 1997;22(17):2025-2029. 25. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis 11. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Pro- in grade I degenerative lumbar spondylolisthesis: a com- spective outcomes evaluation after decompression with parative study of outcomes following laminoplasty and or without instrumented fusion for lumbar stenosis and laminectomy with instrumented spinal fusion. J Orthop degenerative Grade I spondylolisthesis. J Neurosurg Sci. 2005;10(3):270-276. Spine. 2004;1(3):267-272. 26. McCulloch JA. Microdecompression and uninstru- 12. Gibson JN, Grant IC, Waddell G. The Cochrane review mented single-level fusion for spinal canal steno- of surgery for lumbar disc prolapse and degenerative sis with degenerative spondylolisthesis. Spine. lumbar spondylosis. Spine. 1999;24(17):1820-1832. 1998;23(20):2243-2252. 13. Gibson JN, Waddell G. Surgery for degenerative 27. Mochida J, Suzuki K, Chiba M. How to stabilize a single lumbar spondylosis. Cochrane Database Syst Rev. level lesion of degenerative lumbar spondylolisthesis. 2005(4):CD001352. Clin Orthop Relat Res. 1999(368):126-134. 14. Gibson JN, Waddell G, Grant IC. Surgery for degenera- 28. Nasca RJ. Rationale for spinal fusion in lumbar spinal tive lumbar spondylosis. Cochrane Database Syst Rev. This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 46

stenosis. Spine. 1989;14(4):451-454. 33. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A 29. Plotz GM, Benini A. Surgical treatment of degenera- clinical study of degenerative spondylolisthesis. Ra- tive spondylolisthesis in the lumbar spine: no reposition diographic analysis and choice of treatment. Spine. without prior decompression. Acta Neurochir (Wien). 1992;17(11):1329-1336. 1995;137(3-4):188-191. 34. Silvers HR, Lewis PJ, Asch HL. Decompressive lum- 30. Postacchini F, Cinotti G. Bone regrowth after surgical bar laminectomy for spinal stenosis. J Neurosurg. decompression for lumbar spinal stenosis. J Bone Joint 1993;78(5):695-701. Surg Br. 1992;74(6):862-869. 35. Soren A, Waugh TR. Spondylolisthesis and related dis- 31. Postacchini F, Cinotti G, Perugia D. Degenerative orders. A correlative study of 105 patients. Clin Orthop lumbar spondylolisthesis. II. Surgical treatment. Ital J Relat Res. 1985(193):171-177. Orthop Traumatol. 1991;17(4):467-477. 36. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ver- 32. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- sus nonsurgical treatment for lumbar degenerative spon- tors of outcomes after posterior decompression and dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. fusion in degenerative spondylolisthesis. Eur Spine J. 37. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. 2005;14(1):55-60. Indication of fusion for lumbar spinal stenosis in elderly patients and its significance. Spine. 1996;21(2):242-248.

Does the addition of ctomy alone and laminectomy without instrumented fusion compared to patients who received instrumentation to laminectomy with instrumented fusion (ρ=0.001). decompression and fusion A higher proportion of the patients without slippage progression reported that they were helped by for degenerative lumbar the surgery than those whose slippage progressed spondylolisthesis improve surgical postoperatively (ρ<0.01). outcomes compared with In critique, this was a small study in which selec- decompression and fusion alone? tion bias entered into the randomization process, reviewers were not masked to patient treatment The addition of instrumentation is and validated outcome measures were not utilized. recommended to improve fusion rates in Because of these weaknesses, this potential Level patients with symptomatic spinal stenosis and II study was downgraded to Level III. This study degenerative lumbar spondylolisthesis. provides Level III therapeutic evidence that addition of instrumentation to fusion results in higher Grade of Recommendation: B fusion rates and subjective improvement in walking distance when compared with fusion alone. The addition of instrumentation is not recommended to improve clinical Fischgrund et al9 conducted a prospective, random- outcomes for the treatment of patients with ized comparative study of 76 consecutive patients symptomatic spinal stenosis and degenerative with symptomatic spinal stenosis associated with lumbar spondylolisthesis. degenerative lumbar spondylolisthesis who underwent posterior decompression and posterolateral Grade of Recommendation: B fusion. Patients were randomized into a transpedicular fixation group or noninstrumented group. Bridwell et al4 described a prospective comparative Outcomes were assessed at two-year follow-up study of 44 surgically treated patients with degen- using a five-point visual analog scale (VAS) and an erative lumbar spondylolisthesis followed for a operative result rating (excellent, good, fair, poor) minimum of two years. Of the 44 patients, nine un- based on examiner assessment of pain and func- derwent laminectomy alone, 10 had laminectomy tional level. and noninstrumented fusion and 24 had laminectomy and instrumented fusion (18 single level, six The authors reported that of the 76 patients includ- two-level). Patients were radiographically assessed ed in the study, 68 (89%) were available for two- and a functional assessment was conducted by ask- year follow-up. Clinical outcome was excellent or ing whether they felt their ability to walk distances good in 76% of instrumented patients and 85% was worse (-), the same (0) or significantly better of noninstrumented patients (ρ=0.45). Successful (+). Of the 44 patients, 43 were followed for two arthrodesis occurred in 82% of instrumented ver- years or more. sus 45% of noninstrumented patients (ρ=0.0015). Overall, successful fusion did not correlate with The authors reported that instrumented fusion had patient outcome (ρ=0.435). The authors concluded higher fusion rates than noninstrumented fusion that for single-level degenerative lumbar spon- (ρ=0.002) and observed greater progression of dylolisthesis, use of instrumentation may lead to a spondylolisthesis in patients treated with lamine- higher fusion rate, but clinical outcome showed no

improvement in low back pain and lower limb pain fers Level III therapeutic evidence that although with their nonvalidated outcome measures. instrumentation improves the fusion rate, clinical outcome is probably only marginally improved at a In critique of this study, the follow-up may have potential risk of higher complication rates. been too short to detect the effects of pseudoarthrosis in this nonmasked study. Validated outcome Kimura et al19 described a retrospective, compara- measures were not utilized to assess clinical out- tive study of 57 patients with grade I or II L4-5 comes. Because of these weaknesses, this potential degenerative lumbar spondylolisthesis. Group A Level II study was downgraded to Level III. consisted of 28 patients who underwent decompression and posterolateral fusion without instru- This study offers Level III therapeutic evidence mentation. Group B was comprised of 29 patients that the addition of instrumentation to postero- who had decompression and posterolateral fusion lateral fusion for the treatment of degenerative with pedicle screw instrumentation. Following lumbar spondylolisthesis increases the likelihood surgery, Group A was immobilized with bed rest of obtaining a solid arthrodesis, but does not cor- and a cast for 4-6 weeks, whereas Group B was relate with improved clinical outcomes at two-year mobilized much more quickly. Outcomes were as- follow-up. sessed using the Japanese Orthopedic Association (JOA) scores and radiographs with mean follow-up Gibson et al14 performed a systematic review of in Group A of six years and in Group B of three 31 randomized controlled trials (RCT) looking years. at all forms of surgical treatment for degenerative lumbar spondylosis. The authors reported eight The authors indicated that patients in Group A trials showing that instrumented fusion produced a (noninstrumented) reported 72.4% satisfaction higher fusion rate, but any improvement in clini- rate, with an 82.8% fusion rate. Patients in Group cal outcomes is probably marginal. Other evidence B (instrumented) reported an 82.1% satisfaction suggests instrumentation may be associated with a rate, with a 92.8% fusion rate. The authors did not higher complication rate. The authors concluded find any significant differences in outcomes be- that although fusion rates improve with instrumen- tween the two groups, except that Group B (instru- tation, there does not appear to be any correlation mented) had less low back pain. with clinical outcomes. In critique of this study, patients were not random- In critique of this study, it was a systematic review ized and there was varying duration of follow-up of primarily Level II studies and is thus classified between groups. Although there was a trend to- as a Level II systematic review. Limitations were ward improved satisfaction and fusion rates with found in the methodologies of all RCTs, specifical- instrumentation, with the numbers available no ly in the randomization, absence of masking and/ significant difference was detected. This paper of- or the lack of validated outcome measures to assess fers Level III therapeutic evidence of no significant clinical outcomes. Studies were heterogeneous in benefit with the addition of instrumentation for nature and lacked long-term outcome studies. L4-5 degenerative lumbar spondylolisthesis.

In the work group’s review of the specific stud- Mardjetko et al23 performed a meta-analysis of ies cited in this paper, many were downgraded primarily Level III studies. The objective of the to Level III; therefore, the work group classified study was to analyze the published data on degen- this review as Level III evidence. This paper of- erative spondylolisthesis to evaluate the feasibility

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 49 of its use as a literature control to compare with the no instrumentation, six papers qualified for inclu- historical cohort pedicle screw study data. sion. In one paper, only fusion data were broken out for the diagnosis of degenerative spondylolis- The authors conducted a comprehensive literature thesis and were used just for this outcome variable. search to identify studies published in English peer- Ninety percent of the patients in this category had reviewed journals between 1970 and 1993 address- a satisfactory outcome; 86% achieved solid spinal ing degenerative spondylolisthesis with radicular fusion. With regard to clinical outcome, the differ- leg pain or neurogenic claudication. Inclusion crite- ence between patients treated with decompression ria included (1) a minimum of four cases reviewed without fusion (69% satisfactory) and those treated and (2) reporting of the primary outcome variable with decompression and fusion without instrumen- of fusion in articles in which this was part of the tation (90% satisfactory) was statistically signifi- treatment. Clinical outcome variables of back pain, cant (P < 0.0001). leg pain, function, neurogenic claudication and global outcome scores were recorded when avail- In the decompression with fusion and pedicle able. A total of 25 papers representing 889 patients screws category, five studies met the inclusion were accepted for inclusion. Twenty-one were ret- criteria. Fusion status was analyzed in a total of 101 rospective, nonrandomized and uncontrolled. One patients. Eighty-five patients were analyzed with paper was retrospective and nonrandomized, but respect to clinical outcome. One paper did not sep- compared two different treatments. Three prospec- arately analyze clinical data, but did so for fusion tive, randomized studies were included. data; therefore, only fusion data were included. The proportionally weighted fusion rates for this group The primary outcome variable, fusion, was were 93%. When comparing the fusion without determined by each author. The most constant instrumentation group to the fusion with pedicle clinical outcome variable reported was pain with screw group, there was not a statistically significant 16 papers reporting pain only, six papers reporting increase in fusion rate (P = 0.08). Analysis of the pain and function, and two papers reporting clinical outcomes reveals an 86% satisfactory rating patient-determined outcomes. Patient function was for the pedicle screw group. This compares favor- reported in six papers and referred to the presence ably to the 69% satisfactory rate in the decompres- or absence of neurogenic claudication. In addition sion without fusion group (P <0.0001). to these clinical outcomes, four papers reported a global evaluation. Two used Kaneda’s rating system In the anterior spinal fusion category, three papers and two used the Japanese Orthopedic Association presenting the results for 72 patients who received (JOA) score. Excellent and good results were anterior spinal fusion for the treatment of degener- reassigned as satisfactory; poor results were ative spondylolisthesis were included. Pooling the classified as unsatisfactory. data from these three studies yielded a 94% fusion rate with an 86% rate of patient satisfaction. In the decompression alone category, 11 papers representing 216 patients were accepted for inclu- The authors concluded that the meta-analysis sion. Sixty-nine percent of patients had a satisfac- results support the clinical impression that in the tory outcome. The incidence of worsened postop- surgical management of degenerative lumbar spon- erative slip was 31%, but was not associated with a dylolisthesis, spinal fusion significantly improves poorer clinical result in the majority of patients. patient satisfaction.

In the category of decompression with fusion and In critique of this study, only three Level II studies

were reviewed and data was very heterogeneous. outcomes. This paper offers Level III therapeutic evidence that addition of instrumentation to fusion does not The main abstracted outcomes were clinical out- result in improved clinical outcome or fusion rate. come, reoperation rate and solid fusion status. An Martin et al24 conducted a systematic review de- attempt was made to compare patient-centered, signed to identify and analyze comparative studies validated and disease-specific outcomes, complica- that examined the surgical management of de- tions and spondylolisthesis progression, but be- generative lumbar spondylolisthesis, specifically cause of heterogeneity in reporting these outcomes the differences in outcomes between fusion and in the primary studies, no pooled analysis could be decompression alone, and between instrumented performed on these outcomes. When appropriate, a fusion and noninstrumented fusion. study’s clinical outcome rating scale was altered to match a dichotomous rating scale of “satisfactory” Relevant randomized controlled trials (RCTs) and or “unsatisfactory” clinical outcome, and results comparative, observational studies were identified were entered into Review Manager 4.2 for weight- in a comprehensive literature search (1966 to June ed grouped analyses. 2005). The inclusion criteria required that a study be an RCT or comparative observational study that The authors reported that eight studies were in- investigated the surgical management of degenera- cluded in the fusion versus decompression alone tive lumbar spondylolisthesis by comparing: (1) analysis, including two RCTs. Limitations were fusion to decompression and/or (2) instrumented found in the methodologies of both RCTs and fusion to noninstrumented fusion. A minimum most of the observational studies. one-year follow-up was required. Studies also had to include at least five patients per treatment group. Grouped analysis detected a significantly higher A study was excluded if it included patients who probability of achieving a satisfactory clinical out- had received previous spine surgery, or patients come with spinal fusion than with decompression with cervical injuries, spinal fractures, tumors or alone (relative risk, 1.40; 95% confidence interval, isthmic spondylolisthesis. A study was also exclud- 1.04–1.89; P < 0.05). The clinical benefit favoring ed if it was not possible to analyze patients with fusion decreased when analysis was limited to stud- degenerative spondylolisthesis separately from an- ies where the majority of patients were reported other included patient population, or if it was not to be experiencing neurologic symptoms such as clearly a comparative study. intermittent claudication and/or leg pain.

Data from the included studies were extracted by Six studies were included in the instrumented two independent reviewers using a standard data fusion versus noninstrumented fusion analysis, abstraction sheet which identified the following including three RCTs. The use of adjunctive instru- information: (1) patient population’s age, gender, mentation significantly increased the probability symptoms and degree of spondylolisthesis; (2) type of attaining solid fusion (relative risk, 1.37; 95% of decompression, fusion, instrumentation, bone confidence interval, 1.07–1.75; P < 0.05), but no graft material, and preoperative and postoperative significant improvement in clinical outcome was treatment; (3) study design and methodological recorded (relative risk, 1.19; 95% confidence inter- quality using the Cochrane RCT/CCT/Cross- val, 0.92–1.54). There was a nonsignificant trend over Studies Checklist, modified by the additional towards a lower repeat operation rate in the fusion criterion that observational studies state the use group compared with both decompression alone of a consecutive series of patients; and (4) study and instrumented fusion.

3. Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, The authors concluded there is moderate evidence Lenke LG. Minimum 5-year results of degenerative that fusion may lead to a better clinical outcome spondylolisthesis treated with decompression and instrumented posterior fusion. Spine. 1999;24(16):1721-1727. compared with decompression alone. Evidence that 4. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, the use of adjunctive instrumentation leads to im- Baldus C. The role of fusion and instrumentation in the proved fusion status and less risk of pseudoarthro- treatment of degenerative spondylolisthesis with spinal sis is also moderate. No conclusion could be made stenosis. J Spinal Disord. 1993;6(6):461-472. about the clinical effectiveness of instrumented 5. Detwiler PW, Porter RW, Han PP, Karahalios DG, Masferrer R, Sonntag VK. Surgical treatment of lum- fusion versus noninstrumented fusion. bar spondylolisthesis. Adv Tech Stand Neurosurg. 2000;26:331-346. In critique of this study, it was a systematic review 6. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. of studies ranging down to Level III, and is thus Degenerative spondylolisthesis. To fuse or not to fuse. classified as a Level III systematic review. Limita- Spine. 1985;10(3):287-289. 7. Fernandez-Fairen M, Sala P, Ramirez H, Gil J. A pro- tions were found in the methodologies of all RCTs, spective randomized study of unilateral versus bilateral specifically in the pseudorandomization, absence instrumented posterolateral lumbar fusion in degenera- of masking and/or the lack of validated outcome tive spondylolisthesis. Spine. 2007;32(4):395-401. measures to assess clinical outcomes. This paper 8. Fischgrund JS. The argument for instrumented decom- offers Level III therapeutic evidence that the use of pressive posterolateral fusion for patients with degenerative spondylolisthesis and spinal stenosis. Spine. adjunctive instrumentation leads to improved fu- 2004;29(2):173-174. sion rates, but failed to show a statistically signifi- 9. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, cant improvement in clinical outcomes. Montgomery DM, Kurz LT. 1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrod- Future Directions for Research esis with and without spinal instrumentation. Spine. A high quality randomized controlled trial is 1997;22(24):2807-2812. recommended to provide meaningful informa- 10. France JC, Yaszemski MJ, Lauerman WC, et al. A randomized prospective study of posterolateral lumbar tion about the clinical benefits of achieving a solid fusion. Outcomes with and without pedicle screw instru- fusion in patients treated with instrumented and mentation. Spine. 1999;24(6):553-560. noninstrumented fusion for symptomatic spinal 11. Gaetani P, Aimar E, Panella L, et al. Functional disability stenosis and degenerative lumbar spondylolisthe- after instrumented stabilization in lumbar degenera- sis. This study should utilize validated, functional, tive spondylolisthesis: a follow-up study. Funct Neurol. 2006;21(1):31-37. disease-specific outcome measures with long-term 12. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Pro- follow-up of four years or more. spective outcomes evaluation after decompression with or without instrumented fusion for lumbar stenosis and degenerative Grade I spondylolisthesis. J Neurosurg Spine. 2004;1(3):267-272. Role of Instrumentation with Fusion 13. Gibson JN, Grant IC, Waddell G. The Cochrane review and Decompression References of surgery for lumbar disc prolapse and degenerative 1. Austin RC, Branch CL, Jr., Alexander JT. Novel bio- lumbar spondylosis. Spine. 1999;24(17):1820-1832. absorbable interbody fusion spacer-assisted fusion 14. Gibson JN, Waddell G. Surgery for degenerative for correction of spinal deformity. Neurosurg Focus. lumbar spondylosis. Cochrane Database Syst Rev. 2003;14(1):e11. 2005(4):CD001352. 2. Bednar DA. Surgical management of lumbar degenera- 15. Hansraj KK, O’Leary PF, Cammisa FP, Jr., et al. De- tive spinal stenosis with spondylolisthesis via posterior compression, fusion, and instrumentation surgery for reduction with minimal laminectomy. J Spinal Disord complex lumbar spinal stenosis. Clin Orthop Relat Res. Tech. 2002;15(2):105-109. 2001(384):18-25.

16. Houten JK, Post NH, Dryer JW, Errico TJ. Clinical and 27. Mochida J, Suzuki K, Chiba M. How to stabilize a single radiographically/neuroimaging documented outcome level lesion of degenerative lumbar spondylolisthesis. in transforaminal lumbar interbody fusion. Neurosurg Clin Orthop Relat Res. 1999(368):126-134. Focus. 2006;20(3):E8. 28. Park YK, Chung HS. Instrumented facet fusion for the 17. Jin J, Jianxiong S, Guixing Q, Hong Z, Xisheng W, degenerative lumbar disorders. Acta Neurochir (Wien). Yipeng W. Surgical treatment of spondylolisthe- 1999;141(9):915-920. sis with SOCON instrumentation. Chin Med Sci J. 29. Plotz GM, Benini A. Surgical treatment of degenera- 2000;15(2):111-114. tive spondylolisthesis in the lumbar spine: no reposition 18. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- without prior decompression. Acta Neurochir (Wien). zume H, Yoshida M. Lumbar sagittal balance influences 1995;137(3-4):188-191. the clinical outcome after decompression and posterolat- 30. Postacchini F, Cinotti G. Bone regrowth after surgical eral spinal fusion for degenerative lumbar spondylolis- decompression for lumbar spinal stenosis. J Bone Joint thesis. Spine. 2002;27(1):59-64. Surg Br. 1992;74(6):862-869. 19. Kimura I, Shingu H, Murata M, Hashiguchi H. Lum- 31. Postacchini F, Cinotti G, Perugia D. Degenerative bar posterolateral fusion alone or with transpedicular lumbar spondylolisthesis. II. Surgical treatment. Ital J instrumentation in L4-L5 degenerative spondylolisthesis. Orthop Traumatol. 1991;17(4):467-477. J Spinal Disord. 2001;14(4):301-310. 32. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- 20. Kornblum MB, Fischgrund JS, Herkowitz HN, Abra- tors of outcomes after posterior decompression and ham DA, Berkower DL, Ditkoff JS. Degenerative lumbar fusion in degenerative spondylolisthesis. Eur Spine J. spondylolisthesis with spinal stenosis: a prospective 2005;14(1):55-60. long-term study comparing fusion and pseudarthrosis. 33. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A Spine. 2004;29(7):726-733; discussion 733-724. clinical study of degenerative spondylolisthesis. Ra- 21. Kuntz KM, Snider RK, Weinstein JN, Pope MH, Katz diographic analysis and choice of treatment. Spine. JN. Cost-effectiveness of fusion with and without instru- 1992;17(11):1329-1336. mentation for patients with degenerative spondylolisthe- 34. Schnake KJ, Schaeren S, Jeanneret B. Dynamic stabili- sis and spinal stenosis. Spine. 2000;25(9):1132-1139. zation in addition to decompression for lumbar spinal 22. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- stenosis with degenerative spondylolisthesis. Spine. cer C, 3rd. Treatment of degenerative spondylolisthesis. 2006;31(4):442-449. Spine. 1985;10(9):821-827. 35. Schnee CL, Freese A, Ansell LV. Outcome analysis for 23. Mardjetko SM, Connolly PJ, Shott S. Degenerative adults with spondylolisthesis treated with posterolateral lumbar spondylolisthesis. A meta-analysis of literature fusion and transpedicular screw fixation. J Neurosurg. 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S. 1997;86(1):56-63. 24. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah 36. Sears W. Posterior lumbar interbody fusion for degen- SM, O’Neil J, Wai EK. The surgical management of de- erative spondylolisthesis: restoration of sagittal bal- generative lumbar spondylolisthesis: a systematic review. ance using insert-and-rotate interbody spacers. Spine J. Spine. 2007;32(16):1791-1798. 2005;5(2):170-179. 25. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis 37. Sengupta DK. Point of view: Dynamic stabiliza- in grade I degenerative lumbar spondylolisthesis: a com- tion in addition to decompression for lumbar spinal parative study of outcomes following laminoplasty and stenosis with degenerative spondylolisthesis. Spine. laminectomy with instrumented spinal fusion. J Orthop 2006;31(4):450. Sci. 2005;10(3):270-276. 38. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. 26. McAfee PC, DeVine JG, Chaput CD, et al. The indi- Indication of fusion for lumbar spinal stenosis in elderly cations for interbody fusion cages in the treatment of patients and its significance. Spine. 1996;21(2):242-248. spondylolisthesis: analysis of 120 cases. Spine. 2005;30(6 Suppl):S60-65.

How do outcomes of 7. Gibson JN, Waddell G. Surgery for degenerative lumbar spondylosis. Cochrane Database Syst Rev. decompression with 2005(4):CD001352. 8. Hansraj KK, O’Leary PF, Cammisa FP, Jr., et al. De- posterolateral fusion compare compression, fusion, and instrumentation surgery for complex lumbar spinal stenosis. Clin Orthop Relat Res. with those for 360° fusion in 2001(384):18-25. 9. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- the treatment of degenerative zume H, Yoshida M. Lumbar sagittal balance influences lumbar spondylolisthesis? the clinical outcome after decompression and posterolateral spinal fusion for degenerative lumbar spondylolisthesis. Spine. 2002;27(1):59-64. Because of the paucity of literature addressing this 10. Kimura I, Shingu H, Murata M, Hashiguchi H. Lum- question, the work group was unable to generate a bar posterolateral fusion alone or with transpedicular recommendation to answer this question. instrumentation in L4-L5 degenerative spondylolisthesis. J Spinal Disord. 2001;14(4):301-310. 11. Lee TC. Reduction and stabilization without lamine- Future Directions for Research ctomy for unstable degenerative spondylolisthesis: a A high quality RCT comparing decompression preliminary report. Neurosurgery. 1994;35(6):1072-1076. with instrumented posterolateral fusion to decom- 12. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- pression with 360° (circumferential) instrumented cer C, 3rd. Treatment of degenerative spondylolisthesis. Spine. 1985;10(9):821-827. fusion would generate meaningful evidence to ad- 13. Mardjetko SM, Connolly PJ, Shott S. Degenerative dress this question. lumbar spondylolisthesis. A meta-analysis of literature 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S. 14. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah Posterolateral Fusion Versus 360° SM, O’Neil J, Wai EK. The surgical management of de- Fusion References generative lumbar spondylolisthesis: a systematic review. 1. Austin RC, Branch CL, Jr., Alexander JT. Novel bio- Spine. 2007;32(16):1791-1798. absorbable interbody fusion spacer-assisted fusion 15. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis for correction of spinal deformity. Neurosurg Focus. in grade I degenerative lumbar spondylolisthesis: a com- 2003;14(1):e11. parative study of outcomes following laminoplasty and 2. Detwiler PW, Porter RW, Han PP, Karahalios DG, laminectomy with instrumented spinal fusion. J Orthop Masferrer R, Sonntag VK. Surgical treatment of lum- Sci. 2005;10(3):270-276. bar spondylolisthesis. Adv Tech Stand Neurosurg. 16. McAfee PC, DeVine JG, Chaput CD, et al. The indi- 2000;26:331-346. cations for interbody fusion cages in the treatment of 3. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. spondylolisthesis: analysis of 120 cases. Spine. 2005;30(6 Degenerative spondylolisthesis. To fuse or not to fuse. Suppl):S60-65. Spine. 1985;10(3):287-289. 17. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- 4. Fernandez-Fairen M, Sala P, Ramirez H, Gil J. A pro- tors of outcomes after posterior decompression and spective randomized study of unilateral versus bilateral fusion in degenerative spondylolisthesis. Eur Spine J. instrumented posterolateral lumbar fusion in degenera- 2005;14(1):55-60. tive spondylolisthesis. Spine. 2007;32(4):395-401. 18. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A 5. Fischgrund JS. The argument for instrumented decom- clinical study of degenerative spondylolisthesis. Ra- pressive posterolateral fusion for patients with degen- diographic analysis and choice of treatment. Spine. erative spondylolisthesis and spinal stenosis. Spine. 1992;17(11):1329-1336. 2004;29(2):173-174. 19. Schnee CL, Freese A, Ansell LV. Outcome analysis for 6. France JC, Yaszemski MJ, Lauerman WC, et al. A adults with spondylolisthesis treated with posterolateral randomized prospective study of posterolateral lumbar fusion and transpedicular screw fixation. J Neurosurg. fusion. Outcomes with and without pedicle screw instru- 1997;86(1):56-63. mentation. Spine. 1999;24(6):553-560.

20. Sears W. Posterior lumbar interbody fusion for degen- posterolateral lumbar arthrodesis for degenerative spon- erative spondylolisthesis: restoration of sagittal bal- dylolisthesis. Spine. 2004;29(17):1885-1892. ance using insert-and-rotate interbody spacers. Spine J. 22. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. 2005;5(2):170-179. Indication of fusion for lumbar spinal stenosis in elderly 21. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study patients and its significance. Spine. 1996;21(2):242-248. evaluating the safety and efficacy of OP-1 Putty (rh- BMP-7) as a replacement for iliac crest autograft in

What is the role of reduction perfect reduction.

(deliberate attempt to reduce via In critique, this is a moderately small, retrospec- surgical technique) with fusion tive review of a consecutive case series of surgical patients from one surgeon with no comparison in the treatment of degenerative group and with less than 80% follow-up. This lumbar spondylolisthesis? paper offers Level IV therapeutic evidence that limited bilateral foraminotomies with instrumented Reduction with fusion and internal fixation of reduction and fusion for symptomatic degenera- patients with low grade degenerative lumbar tive spondylolisthesis and stenosis is as effective as spondylolisthesis is not recommended to laminectomy and in situ fusion without as much improve clinical outcomes. operative exposure of neural structures.

Grade of Recommendation: I (Insufficient Lee et al14 reported on a prospective case series of Evidence) 52 consecutive patients with objectively defined unstable degenerative spondylolisthesis who un- Although reduction and fusion can be performed, derwent reduction and fusion without decom- the evidence reviewed does not substantiate any pression using the Fixater Interne pedicle fixation improvement in clinical outcomes and may increase device. Forty-seven patients had low back pain, the risk of neurological complications. 40 patients had radicular pain and 36 patients had intermittent claudication. Bednar et al1 described a retrospective consecutive case series of 56 patients with degenerative Follow-up was at a minimum of 12 months (range spondylolisthesis and symptoms of back pain and/ 12-16 months). Subjective measurement of success or stenosis treated with bilateral foraminotomies, was classified as excellent, good, fair and poor for reduction and instrumented fusion. The proce- pain. An excellent or good outcome was consid- dure had a 7% major complication rate. Outcomes ered satisfactory and a fair or poor outcome was measures were the Visual Analog Scale (VAS), Os- considered unsatisfactory. A satisfactory outcome westry Disability Index (ODI) and radiographs. Of (excellent and good results) occurred in 42 of 47 the 56 patients, 42 were available for follow-up at patients with complaints of back pain, 37 of 40 an average of 33 months (range 14-53 months). Of patients with radicular pain and 31of 36 patients the 42 patients, 82% experienced relief of leg pain, with claudication. The authors commented that 75% experienced improvement in low back pain, only two groups, based on their findings, are not and 77% experienced significant improvement in good candidates for this procedure: (1) those with their ODI scores (average preoperatively of 56% a positive Lasegue’s sign and (2) those with border- versus average of 26% postoperatively). line instability.

Only 38 patients were available for late review of In critique of this study, this was a prospective case X-ray studies at an average of 33 months. Average series of consecutive patients with degenerative preoperative slip was 16%, and of the 38 patients spondylolisthesis undergoing reduction, fixation available at late review, 75% had perfect reduction. and fusion which lacked a comparison group. Vali- Of the 38 patients, 16% had minor loss of reduc- dated outcome measures were not used. This paper tion. Outcome measures (VAS and ODI) were not presents Level IV therapeutic evidence that patients compared based on the presence or absence of a with degenerative spondylolisthesis who do not

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 56 have borderline instability or a positive Lasegue’s Future Directions for Research sign can undergo reduction, fixation and fusion The work group does not recommend any further without decompression. studies addressing reduction with fusion and internal fixation in patients with low grade degenerative Sears et al19 reviewed a prospective case series of lumbar spondylolisthesis. 34 patients with degenerative spondylolisthesis who underwent decompression, reduction, inter- Role of Reduction with Fusion nal fixation and fusion. Twenty-five patients had a one-level fusion and nine patients had a two-level References 1. Bednar DA. Surgical management of lumbar degenera- fusion. Of the 34 patients, 32 had surgery to relieve tive spinal stenosis with spondylolisthesis via posterior leg pain. Outcome measures included the VAS, reduction with minimal laminectomy. J Spinal Disord Low Back Pain Outcome Score (LBOS), SF-12 and Tech. 2002;15(2):105-109. patient satisfaction questionnaire. Preoperative and 2. Bendo JA, Ong B. Importance of correlating static and postoperative measurement of slips by radiograph dynamic imaging studies in diagnosing degenerative lumbar spondylolisthesis. Am J Orthop. 2001;30(3):247-250. were also recorded. Mean preoperative slip was 3. Benini A, Plotz G. Reduction and stabilization without 20% (range was12% to 33%). laminectomy for unstable degenerative spondylolisthesis: a preliminary report. Neurosurgery. 1995;37(4):843-844. Follow-up occurred at a mean of 21.2 months 4. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. (range 12 to 32 months), with no dropouts. Sig- Degenerative spondylolisthesis. To fuse or not to fuse. Spine. 1985;10(3):287-289. nificant improvements (p<.001) occurred in mean 5. France JC, Yaszemski MJ, Lauerman WC, et al. A VAS and LBOS scores. Ninety-one percent of the randomized prospective study of posterolateral lumbar patients considered their results excellent or good fusion. Outcomes with and without pedicle screw instru- on the subjective satisfaction rating. Radiograph mentation. Spine. 1999;24(6):553-560. analysis revealed mean slip reduction from 20.2% 6. Gaetani P, Aimar E, Panella L, et al. Functional disability after instrumented stabilization in lumbar degenera- to 1.7% and focal lordosis (available in only 17/34 tive spondylolisthesis: a follow-up study. Funct Neurol. patients) increased from 13.1 to 16.1 degrees. Both 2006;21(1):31-37. of these findings were clinically significant. Three 7. Grob D, Humke T, Dvorak J. Direct pediculo-body fixa- of the 34 patients had postoperative nerve root ir- tion in cases of spondylolisthesis with advanced interver- ritation, with two of these persisting up to the time tebral disc degeneration. Eur Spine J. 1996;5(4):281-285. 8. Hackenberg L, Halm H, Bullmann V, Vieth V, Schneider of final report. No procedure-related complications M, Liljenqvist U. Transforaminal lumbar interbody fu- were reported postoperatively, but one patient re- sion: a safe technique with satisfactory three to five year quired adjacent level decompression and fusion 12 results. Eur Spine J. 2005;14(6):551-558. months after surgery. 9. Hirabayashi S, Kumano K, Kuroki T. Cotrel-Dubousset pedicle screw system for various spinal disorders. Merits and problems. Spine. 1991;16(11):1298-1304. In critique, this is a small prospective case series on 10. Jin J, Jianxiong S, Guixing Q, Hong Z, Xisheng W, nonconsecutive patients with degenerative spon- Yipeng W. Surgical treatment of spondylolisthe- dylolisthesis with no comparison group. This paper sis with SOCON instrumentation. Chin Med Sci J. offers Level IV therapeutic evidence that reduction 2000;15(2):111-114. of a degenerative spondylolisthesis with internal 11. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- zume H, Yoshida M. Lumbar sagittal balance influences fixation and posterior lumbar interbody fusion can the clinical outcome after decompression and posterolat- provide good deformity correction with few com- eral spinal fusion for degenerative lumbar spondylolis- plications and good short-term patient outcomes thesis. Spine. 2002;27(1):59-64. on validated patient outcome measures. 12. Lauber S, Schulte TL, Liljenqvist U, Halm H, Hack- enberg L. Clinical and radiologic 2-4-year results of transforaminal lumbar interbody fusion in degenera-

tive and isthmic spondylolisthesis grades 1 and 2. Spine. cations for interbody fusion cages in the treatment of 2006;31(15):1693-1698. spondylolisthesis: analysis of 120 cases. Spine. 2005;30(6 13. Laus M, Tigani D, Pignatti G, et al. Posterolateral spinal Suppl):S60-65. fusion: a study of 123 cases with a long-term follow-up. 18. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A Chir Organi Mov. 1994;79(1):69-79. clinical study of degenerative spondylolisthesis. Ra- 14. Lee TC. Reduction and stabilization without lamine- diographic analysis and choice of treatment. Spine. ctomy for unstable degenerative spondylolisthesis: a 1992;17(11):1329-1336. preliminary report. Neurosurgery. 1994;35(6):1072-1076. 19. Sears W. Posterior lumbar interbody fusion for degen- 15. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- erative spondylolisthesis: restoration of sagittal bal- cer C, 3rd. Treatment of degenerative spondylolisthesis. ance using insert-and-rotate interbody spacers. Spine J. Spine. 1985;10(9):821-827. 2005;5(2):170-179. 16. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah 20. Stone AT, Tribus CB. Acute progression of spon- SM, O’Neil J, Wai EK. The surgical management of de- dylolysis to isthmic spondylolisthesis in an adult. Spine. generative lumbar spondylolisthesis: a systematic review. 2002;27(16):E370-372. Spine. 2007;32(16):1791-1798. 21. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. 17. McAfee PC, DeVine JG, Chaput CD, et al. The indi- Indication of fusion for lumbar spinal stenosis in elderly patients and its significance. Spine. 1996;21(2):242-248.

What is the long-term result Kornblum et al32 conducted a follow-up study on 47 of 58 patients who had originally been part of a (four+ years) of surgical randomized controlled trial comparing instrument- management of degenerative ed versus noninstrumented fusion for spinal stenosis and degenerative spondylolisthesis. This study’s lumbar spondylolisthesis? cohort consisted only of the noninstrumented cases, which were followed for a minimum of five Decompression and fusion is recommended years. Clinical outcomes were analyzed based as a means to provide satisfactory long-term on the presence of solid fusion (22 patients) or a results for the treatment of patients with pseudoarthrosis (25 patients). A statistically greater symptomatic spinal stenosis and degenerative percentage of patients had good or excellent results lumbar spondylolisthesis. in patients with solid fusion (86%) versus pseudoarthrosis (56%). Importantly, five of the pseudoar- Grade of Recommendation: C throsis patients and two of the fusion patients had undergone a second procedure. Booth et al1 described a presumably retrospective study of 41 patients with neurogenic claudication In critique of this study, the authors used a less from spinal stenosis and spondylolisthesis who frequently implemented outcomes instrument, the were followed for a minimum of five years after Swiss Spinal Stenosis (SSS) Questionnaire, making a laminectomy and instrumented fusion. At final it difficult to compare directly to other studies in follow-up, there were no new neurological deficits, which the ODI or ZCQ were used. Despite these no recurrent stenosis at the level of surgery and minor limitations, as a prospective case series, the no symptomatic pseudoarthroses. Three patients data offer Level IV therapeutic (>80% follow-up) underwent surgery for adjacent level stenosis, evidence that laminectomy and attempted fusion which took place four to 12 years after the index results in longstanding symptom improvement for procedure. Clinical outcomes were available in spinal stenosis from degenerative spondylolisthesis. 36 patients: 83% reported high satisfaction, 86% Furthermore, these data suggest that those patients reported reduced back and leg pain, and 46% had who achieved solid fusion have statistically better increased function at follow-up that ranged from long-term outcomes than those with pseudoar- five to 10.7 years. throses.

In critique of this study, it had small patient num- Postacchini et al48 performed a long-term follow-up bers and there was a considerable amount of attri- study evaluating the clinical outcomes and radio- tion (less than 80% follow-up). Of 49 consecutive graphic evidence of bone regrowth five to 19 years patients operated during the study interval, 41 were after laminectomy for spinal stenosis. Of the 40 available for follow-up (eight patients died) and patients included, 16 had degenerative spondylolis- only 36 had clinical outcomes measured. Attrition thesis, 10 of whom were treated with concomitant from death, however, is expected in the affected fusion. At final follow-up, three patients had excel- population. This retrospective case series provides lent results, seven patients had good results, three Level IV therapeutic evidence that laminectomy had fair results and three had poor results. The pro- and instrumented fusion for stenosis from degener- portion of satisfactory clinical results was higher ative spondylolisthesis provides a high rate of sat- in the patients who were fused compared to those isfaction and pain relief and moderately increased who underwent laminectomy alone. function at long-term follow-up. In critique of this study, clinical outcomes were

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 59 graded using a rudimentary four tier system (excel- 2. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, lent, good, fair, poor). Furthermore, there was a Baldus C. The role of fusion and instrumentation in the high attrition rate. Of 88 patients identified during treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord. 1993;6(6):461-472. the study period, 27 died or could not be located 3. Buttermann GR, Garvey TA, Hunt AF, et al. and 21 did not have adequate radiographs, leaving Lumbar fusion results related to diagnosis. Spine. the 40 study patients (45% follow-up). 1998;23(1):116-127. 4. Chang P, Seow KH, Tan SK. Comparison of the results Based on these limitations, this retrospective case of spinal fusion for spondylolisthesis in patients who are instrumented with patients who are not. Singapore Med series provides Level IV therapeutic evidence that J. 1993;34(6):511-514. laminectomy with fusion provides satisfactory 5. Dall BE, Rowe DE. Degenerative spondylolisthesis. Its long-term results. surgical management. Spine. 1985;10(7):668-672. 6. Epstein NE, Epstein JA, Carras R, Lavine LS. Degenera- tive spondylolisthesis with an intact neural arch: a review Future Directions for Research of 60 cases with an analysis of clinical findings and the The work group identified the following sugges- development of surgical management. Neurosurgery. tions for future studies, which would generate 1983;13(5):555-561. 7. Fernandez-Fairen M, Sala P, Ramirez H, Gil J. A pro- meaningful evidence to assist in further defining spective randomized study of unilateral versus bilateral the role of surgical treatment for degenerative lum- instrumented posterolateral lumbar fusion in degenera- bar spondylolisthesis. tive spondylolisthesis. Spine. 2007;32(4):395-401. 8. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Recommendation #1: Montgomery DM, Kurz LT. 1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis Future long-term studies of the effects of surgi- with spinal stenosis: a prospective, randomized study cal interventions for patients with symptomatic comparing decompressive laminectomy and arthrod- spinal stenosis and degenerative lumbar spon- esis with and without spinal instrumentation. Spine. dylolisthesis should include an untreated con- 1997;22(24):2807-2812. trol group, when ethically feasible. Continued 9. Fischgrund JS. The argument for instrumented decompressive posterolateral fusion for patients with degen- follow-up of patients already enrolled in ongo- erative spondylolisthesis and spinal stenosis. Spine. ing randomized controlled trials or prospective 2004;29(2):173-174. comparative studies will yield higher quality 10. Frazier DD, Lipson SJ, Fossel AH, Katz JN. As- data regarding the relative efficacy of surgery sociations between spinal deformity and outcomes compared to medical/interventional treatments. after decompression for spinal stenosis. Spine. 1997;22(17):2025-2029. 11. Fujiya M, Saita M, Kaneda K, Abumi K. Clinical study Recommendation #2: on stability of combined distraction and compres- Future long-term outcome studies are neces- sion rod instrumentation with posterolateral fusion sary to compare different surgical techniques for unstable degenerative spondylolisthesis. Spine. for the treatment of patients with symptomatic 1990;15(11):1216-1222. 12. Gaetani P, Aimar E, Panella L, et al. Functional disability spinal stenosis and degenerative lumbar spon- after instrumented stabilization in lumbar degenera- dylolisthesis. tive spondylolisthesis: a follow-up study. Funct Neurol. 2006;21(1):31-37. 13. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Pro- Surgical Long Term Outcome spective outcomes evaluation after decompression with References or without instrumented fusion for lumbar stenosis and 1. Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, degenerative Grade I spondylolisthesis. J Neurosurg Lenke LG. Minimum 5-year results of degenerative Spine. 2004;1(3):267-272. spondylolisthesis treated with decompression and instru- 14. Gibson JN, Waddell G. Surgery for degenerative mented posterior fusion. Spine. 1999;24(16):1721-1727. lumbar spondylosis. Cochrane Database Syst Rev.

2005(4):CD001352. 28. Kinoshita T, Ohki I, Roth KR, Amano K, Moriya H. 15. Hashimoto T, Oha F, Shigenobu K, et al. Mid-term Results of degenerative spondylolisthesis treated with clinical results of Graf stabilization for lumbar degenera- posterior decompression alone via a new surgical ap- tive pathologies. a minimum 2-year follow-up. Spine J. proach. J Neurosurg. 2001;95(1 Suppl):11-16. 2001;1(4):283-289. 29. Kleeman TJ, Hiscoe AC, Berg EE. Patient out- 16. Hee HT, Wong HK. The long-term results of surgical comes after minimally destabilizing lumbar stenosis treatment for spinal stenosis in the elderly. Singapore decompression: the “Port-Hole” technique. Spine. Med J. 2003;44(4):175-180. 2000;25(7):865-870. 17. Herkowitz HN, Kurz LT. Degenerative lumbar spon- 30. Knox BD, Harvell JC, Jr., Nelson PB, Hanley EN, Jr. dylolisthesis with spinal stenosis. A prospective study Decompression and luque rectangle fusion for degenera- comparing decompression with decompression and in- tive spondylolisthesis. J Spinal Disord. 1989;2(4):223-228. tertransverse process arthrodesis. J Bone Joint Surg Am. 31. Konno S, Kikuchi S. Prospective study of surgical treat- 1991;73(6):802-808. ment of degenerative spondylolisthesis: comparison 18. Herno A, Partanen K, Talaslahti T, et al. Long-term between decompression alone and decompression with clinical and magnetic resonance imaging follow-up as- graf system stabilization. Spine. 2000;25(12):1533-1537. sessment of patients with lumbar spinal stenosis after 32. Kornblum MB, Fischgrund JS, Herkowitz HN, Abra- laminectomy. Spine. 1999;24(15):1533-1537. ham DA, Berkower DL, Ditkoff JS. Degenerative lumbar 19. Herron LD, Trippi AC. L4-5 degenerative spondylolis- spondylolisthesis with spinal stenosis: a prospective thesis. The results of treatment by decompressive lamine- long-term study comparing fusion and pseudarthrosis. ctomy without fusion. Spine. 1989;14(5):534-538. Spine. 2004;29(7):726-733; discussion 733-724. 20. Houten JK, Post NH, Dryer JW, Errico TJ. Clinical and 33. Kuntz KM, Snider RK, Weinstein JN, Pope MH, Katz radiographically/neuroimaging documented outcome JN. Cost-effectiveness of fusion with and without in- in transforaminal lumbar interbody fusion. Neurosurg strumentation for patients with degenerative spondylolis- Focus. 2006;20(3):E8. thesis and spinal stenosis. Spine. 2000;25(9):1132-1139. 21. Huang KF, Chen TY. Clinical results of a single central 34. Lamberg T, Remes V, Helenius I, Schlenzka D, Seit- interbody fusion cage and transpedicle screws fixation salo S, Poussa M. Uninstrumented in situ fusion for for recurrent herniated lumbar disc and low-grade spon- high-grade childhood and adolescent isthmic spondylolisthesis. Chang Gung Med J. 2003;26(3):170-177. dylolisthesis: long-term outcome. J Bone Joint Surg Am. 22. Ido K, Urushidani H. Radiographic evaluation of 2007;89(3):512-518. posterolateral lumbar fusion for degenerative spon- 35. Lauber S, Schulte TL, Liljenqvist U, Halm H, Hack- dylolisthesis: long-term follow-up of more than 10 years enberg L. Clinical and radiologic 2-4-year results of vs. midterm follow-up of 2-5 years. Neurosurg Rev. transforaminal lumbar interbody fusion in degenera- 2001;24(4):195-199. tive and isthmic spondylolisthesis grades 1 and 2. Spine. 23. Inoue S, Watanabe T, Goto S, Takahashi K, Takata K, 2006;31(15):1693-1698. Sho E. Degenerative spondylolisthesis. Pathophysiology 36. Laus M, Tigani D, Alfonso C, Giunti A. Degenerative and results of anterior interbody fusion. Clin Orthop spondylolisthesis: lumbar stenosis and instability. Chir Relat Res. 1988;227:90-98. Organi Mov. 1992;77(1):39-49. 24. Jin J, Jianxiong S, Guixing Q, Hong Z, Xisheng W, 37. Laus M, Tigani D, Pignatti G, et al. Posterolateral spinal Yipeng W. Surgical treatment of spondylolisthe- fusion: a study of 123 cases with a long-term follow-up. sis with SOCON instrumentation. Chin Med Sci J. Chir Organi Mov. 1994;79(1):69-79. 2000;15(2):111-114. 38. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- 25. Johnson JR, Kirwan EO. The long-term results of fusion cer C, 3rd. Treatment of degenerative spondylolisthesis. in situ for severe spondylolisthesis. J Bone Joint Surg Br. Spine. 1985;10(9):821-827. 1983;65(1):43-46. 39. Lorenz R. Lumbar spondylolisthesis. Clinical syndrome 26. Kanayama M, Hashimoto T, Shigenobu K, et al. and operative experience with Cloward’s technique. Acta Adjacent-segment morbidity after Graf ligamentoplasty Neurochir (Wien). 1982;60(3-4):223-244. compared with posterolateral lumbar fusion. J 40. Markwalder TM. Surgical management of neurogenic Neurosurg. 2001;95(1 Suppl):5-10. claudication in 100 patients with lumbar spinal stenosis 27. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- due to degenerative spondylolisthesis. Acta Neurochir zume H, Yoshida M. Lumbar sagittal balance influences (Wien). 1993;120(3-4):136-142. the clinical outcome after decompression and posterolat- 41. McAfee PC, DeVine JG, Chaput CD, et al. The indi- eral spinal fusion for degenerative lumbar spondylolis- cations for interbody fusion cages in the treatment of thesis. Spine. 2002;27(1):59-64. spondylolisthesis: analysis of 120 cases. Spine. 2005;30(6

Suppl):S60-65. 55. Schnake KJ, Schaeren S, Jeanneret B. Dynamic stabili- 42. McCulloch JA. Microdecompression and uninstru- zation in addition to decompression for lumbar spinal mented single-level fusion for spinal canal steno- stenosis with degenerative spondylolisthesis. Spine. sis with degenerative spondylolisthesis. Spine. 2006;31(4):442-449. 1998;23(20):2243-2252. 56. Schnee CL, Freese A, Ansell LV. Outcome analysis for 43. Nasca RJ. Rationale for spinal fusion in lumbar spinal adults with spondylolisthesis treated with posterolateral stenosis. Spine. 1989;14(4):451-454. fusion and transpedicular screw fixation. J Neurosurg. 44. Okuyama K, Kido T, Unoki E, Chiba M. PLIF with a ti- 1997;86(1):56-63. tanium cage and excised facet joint bone for degenerative 57. Stoll TM, Dubois G, Schwarzenbach O. The dynamic spondylolisthesis-in augmentation with a pedicle screw. J neutralization system for the spine: a multi-center study Spinal Disord Tech. 2007;20(1):53-59. of a novel non-fusion system. Eur Spine J. 2002;11 Suppl 45. Onda A, Otani K, Konno S, Kikuchi S. Mid-term and 2:S170-178. long-term follow-up data after placement of the Graf 58. Takahashi K, Kitahara H, Yamagata M, et al. Long- stabilization system for lumbar degenerative disorders. J term results of anterior interbody fusion for treat- Neurosurg Spine. 2006;5(1):26-32. ment of degenerative spondylolisthesis. Spine. 46. Palmer S, Turner R, Palmer R. Bilateral decompression 1990;15(11):1211-1215. of lumbar spinal stenosis involving a unilateral approach 59. Unnanantana A. Posterolateral lumbar fusion for de- with microscope and tubular retractor system. J Neuro- generative spondylolisthesis: experiences of a modi-fied surg. 2002;97(2 Suppl):213-217. technique without instrumentation. J Med Assoc Thai. 47. Panagiotis ZE, Athanasios K, Panagiotis D, Minos T, 1997;80(9):570-574. Charis M, Elias L. Functional outcome of surgical treat- 60. Vaccaro AR, Garfin SR. Degenerative lumbar spon- ment for multilevel lumbar spinal stenosis. Acta Orthop. dylolisthesis with spinal stenosis, a prospective study 2006;77(4):670-676. comparing decompression with decompression and 48. Postacchini F, Cinotti G. Bone regrowth after surgical intertransverse process arthrodesis: a critical analysis. decompression for lumbar spinal stenosis. J Bone Joint Spine. 1997;22(4):368-369. Surg Br. 1992;74(6):862-869. 61. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ver- 49. Potter BK, Freedman BA, Verwiebe EG, Hall JM, Polly sus nonsurgical treatment for lumbar degenerative spon- DW, Jr., Kuklo TR. Transforaminal lumbar inter-body dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. fusion: clinical and radiographic results and complica- 62. Zdeblick TA. A prospective, randomized study of lum- tions in 100 consecutive patients. J Spinal Disord Tech. bar fusion. Preliminary results. Spine. 1993;18(8):983-991. 2005;18(4):337-346. 63. Zhao J, Wang X, Hou T, He S. One versus two BAK fu- 50. Rechtine GR, Sutterlin CE, Wood GW, Boyd RJ, Mans- sion cages in posterior lumbar interbody fusion to L4-L5 field FL. The efficacy of pedicle screw/plate fixation degenerative spondylolisthesis: a randomized, controlled on lumbar/lumbosacral autogenous bone graft fusion prospective study in 25 patients with minimum two-year in adult patients with degenerative spondylolisthesis. J follow-up. Spine. 2002;27(24):2753-2757 Spinal Disord. 1996;9(5):382-391. 51. Remes V, Lamberg T, Tervahartiala P, et al. Long-term outcome after posterolateral, anterior, and circumferential fusion for high-grade isthmic spondylolisthesis in children and adolescents: magnetic resonance imaging findings after average of 17-year follow-up. Spine. 2006;31(21):2491-2499. 52. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- tors of outcomes after posterior decompression and fusion in degenerative spondylolisthesis. Eur Spine J. 2005;14(1):55-60. 53. Sanderson PL, Wood PL. Surgery for lumbar spinal stenosis in old people. J Bone Joint Surg Br. 1993;75(3):393-397. 54. Sato K, Kikuchi S. Clinical analysis of two-level compression of the cauda equina and the nerve roots in lumbar spinal canal stenosis. Spine. 1997;22(16):1898-1903; discussion 1904.

Appendix A: Acronyms

ALIF anterior lumbar interbody fusion CT computed tomography CTM computed tomography myelography EBM evidence-based medicine EHL extensor hallucis longus JOA Japanese Orthopaedic Association LASD L1 axis S1 distance LBOS low back outcome score LBP low back pain MR magnetic resonance MRI magnetic resonance imaging NASS North American Spine Society NSAIDs nonsteroidal anti-inflammatory drugs OCS Oxford Claudication Score ODI Oswestry Disability Index PLIF posterior lumbar interbody fusion RCT randomized clinical trial RMDQ Roland Morris Disability Questionnaire SF-12 12-Item Short Form Health Survey SF-36 36-Item Short Form Health Survey SSS Swiss Spinal Stenosis Questionnaire SWT shuttle walking test TENS transcutaneous electrical nerve stimulation VAS Visual Analog Scale ZCQ Zurich Claudication Questionnaire

Appendix B: Levels of Evidence for Primary Research Question1

Appendix C: Grades of Recommendationfor Summaries or Reviews of Studies

A: Good evidence (Level I Studies with consistent findings) for or against recommending intervention.

B: Fair evidence (Level II or III Studies with consistent findings) for or against recommending intervention.

C: Poor quality evidence (Level IV or V Studies) for or against recommending intervention.

I: Insufficient or conflicting evidence not allowing a recommendation for or against intervention.

Appendix D: Protocol for NASS Literature Searches

One of the most crucial elements of evidence Protocol for NASS Literature Searches analysis to support development of recommenda- The NASS Research Department has a relation- tions for appropriate clinical care or use of new ship with Northwestern University’s Galter Health technologies is the comprehensive literature search. Sciences Library. When it is determined that a Thorough assessment of the literature is the basis literature search is needed, NASS research staff will for the review of existing evidence, which will be work with the requesting parties and Galter to run instrumental to these activities. a comprehensive search employing at a minimum the following search techniques: Background It has become apparent that the number of litera- 1. A preliminary search of the evidence will ture searches being conducted at NASS is increas- be conducted using the following clearly ing and that they are not necessarily conducted in defined search parameters (as determined by a consistent manner between committees/projects. the content experts). The following param- Because the quality of a literature search directly eters are to be provided to research staff to affects the quality of recommendations made, a facilitate this search. comparative literature search was undertaken to • Time frames for search help NASS refine the process and make recom- • Foreign and/or English language mendations about how to conduct future literature • Order of results (chronological, by jour- searches on a NASS-wide basis. nal, etc.) • Key search terms and connectors, with In November-December 2004, NASS conducted a or without MeSH terms to be employed trial run at new technology assessment. As part of • Age range the analysis of that pilot process, the same litera- • Answers to the following questions: ture searches were conducted by both an experi- o Should duplicates be eliminated be- enced NASS member and a medical librarian for tween searches? comparison purposes. After reviewing the results o Should searches be separated by term of that experiment and the different strategies or as one large package? employed for both searches, it was the recommen- o Should human studies, animal studies dation of NASS Research Staff that a protocol be or cadaver studies be included? developed to ensure that all future NASS searches be conducted consistently to yield the most com- This preliminary search should encompass prehensive results. While it is recognized that some a search of the Cochrane database when ac- searches occur outside the Research and Clinical cess is available. Care Councils, it is important that all searches conducted at NASS employ a solid search strategy, 2. Search results with abstracts will be com- regardless of the source of the request. To this end, piled by Galter in Endnote software. Galter this protocol has been developed and NASS-wide typically responds to requests and com- implementation is recommended. pletes the searches within two to five days. Results will be forwarded to the research

staff, who will share it with the appro- 7. NASS research staff will work with Galter priate NASS staff member or requesting library to obtain the 2nd related articles party(ies). (Research staff hasve access to search results and any necessary full-text EndNote software and will maintain a da- articles for review. tabase of search results for future use/documentation.) 8. NASS members reviewing full-text articles should also review the references at the end 3. NASS staff shares the search results with an of each article to identify additional articles appropriate content expert (NASS Com- which should be reviewed, but may have mittee member or other) to assess relevance been missed in the search. of articles and identify appropriate articles to review and on which to run a “related Protocol for Expedited Searches articles” search. At a minimum, numbers 1, 2 and 3 should be followed for any necessary expedited search. Fol- 4. Based on content expert’s review, NASS lowing #3, depending on the time frame allowed, research staff will then coordinate with the deeper searching may be conducted as described by Galter medical librarian the second level the full protocol or request of full-text articles may searching to identify relevant “related ar- occur. If full-text articles are requested, #8 should ticles.” also be included. Use of the expedited protocol or any deviation from the full protocol should be 5. Galter will forward results to Research Staff documented with explanation. to share with appropriate NASS staff. Following these protocols will help ensure that 6. NASS staff share related articles search NASS recommendations are (1) based on a thor- results with an appropriate content expert ough review of relevant literature; (2) are truly (NASS Committee member or other) to based on a uniform, comprehensive search strategy; assess relevance of this second set of articles, and (3) represent the current best research evidence and identify appropriate articles to review available. Research staff will maintain a search his- and on which to run a second “related ar- tory in EndNote for future use or reference. ticles” search.

Appendix E: Literature Search Parameters

Natural History of Degenerative Lumbar Spondylolisthesis (Work Group 1) Search Strategies

Search Strategies by Clinical Question:

1. What is the best working definition of degenerative lumbar spondylolisthesis?

Reviewed book chapters (see reference section).

2. What is the natural history of degenerative lumbar spondylolisthesis?

Degenerative Lumbar Spondylolisthesis – natural hx – broad (((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH])) NOT ((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH]) AND (English[lang]) AND ((infant[MeSH] OR child[MeSH] OR adolescent[MeSH])) AND (Humans[Mesh]) AND (“1966”[EDat] : “3000”[EDat]))) OR ((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH]) AND (English[lang]) AND (adult[MeSH]) AND (Humans[Mesh]) AND (“1966”[PDat] : “3000”[PDat]))

Degenerative Lumbar Spondylolisthesis – natural hx – narrow ((((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH])) NOT ((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text

Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH]) AND (English[lang]) AND ((infant[MeSH] OR child[MeSH] OR adolescent[MeSH])) AND (Humans[Mesh]) AND (“1966”[EDat] : “3000”[EDat]))) OR ((natural history[Text Word] OR natural course[All Fields] OR nonsurgical[All Fields] OR nonoperative[All Fields] OR (conservative[All Fields] AND (“therapy”[Subheading] OR (“therapeutics”[TIAB] NOT Medline[SB]) OR “therapeutics”[MeSH Terms] OR treatment[Text Word] OR therapy[Text Word])) OR untreated[All Fields]) AND (“Spondylolisthesis”[MeSH]) AND (English[lang]) AND (adult[MeSH]) AND (Humans[Mesh]) AND (“1966”[PDat] : “3000”[PDat]))) AND degenerative[All Fields]

Databases Searched:  MEDLINE (PubMed)  ACP Journal Club  Cochrane Database of Systematic reviews  Database of Abstracts of Reviews of Effectiveness (DARE)  Cochrane Central Register of Controlled Trials

Diagnosis/Imaging of Degenerative Lumbar Spondylolisthesis (Work Group 2) Search Strategies

Search Strategies by Clinical Question:

1. What are the most appropriate historical and physical exam findings consistent with the diagnosis of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (signs OR symptoms OR diagnosis OR diagnosis, differential OR physical findings OR exam OR historical findings)

Search name: DLS + diagnosis (48 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Diagnosis”[MAJR] OR “Signs and Symptoms”[MAJR] OR “Spondylolisthesis/diagnosis”[MAJR:noexp] OR “Physical Examination”[MAJR] OR diagnosis[title])

2. What are the most appropriate diagnostic tests for degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (diagnostic tests OR physical finding OR signs) AND (accuracy OR validity OR reliability)

Search name #1: DLS + diagnostic tests (124 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum- bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Diagnostic Techniques and Procedures”[Mesh] OR “Diagnostic Imaging”[Mesh])

Search name #2: DLS + diagnostic tests + validity – narrow (10 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum-

bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND ((“Reproducibility of Results”[Mesh] OR “Sensitivity and Specificity”[Mesh]) AND “Diagnostic Techniques and Procedures”[Mesh])

Outcome Measures for Degenerative Lumbar Spondylolisthesis (Work Group 3) Search Strategies

Search Strategies by Clinical Question: What are the appropriate outcome measures for the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND functional outcome measures

Search name: DLS + functional outcome measures (104 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND ((“Outcome Assessment (Health Care)”[Mesh] OR “Treatment Outcome”[Mesh] OR “Outcome and Process Assessment (Health Care)”[Mesh]) OR “functional outcome”[text word])

Medical/Interventional Treatment of Degenerative Lumbar Spondylolisthesis (Work Group 4) Search Strategies

Search Strategies by Clinical Question: 1. Do medical/interventional treatments improve outcomes in the treatment of degenerative lumbar spondylolisthesis compared to the natural history of the disease? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND natural history AND (medical management OR nonoperative management OR conservative management OR medical treatment OR nonoperative treatment OR conservative treatment OR nonsurgical OR rehabilitation)

Search name #1: DLS + nonsurgical (41 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (nonoperative[All Fields] OR conservative[All Fields] OR nonsurgical[All Fields] OR (“rehabilitation”[Subheading] OR “rehabilitation”[MeSH Terms] OR rehabilitation[Text Word]) OR “clinical management”[All Fields] OR “spondylolisthesis/therapy”[MeSH:noexp])

Search name #2: DLS + nonsurgical + natural history (6 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (nonoperative[All Fields] OR conservative[All Fields] OR nonsurgical[All Fields] OR (“rehabilitation”[Subheading] OR “rehabilitation”[MeSH Terms] OR rehabilitation[Text Word]) OR “clinical management”[All Fields] OR “spondylolisthesis/therapy”[MeSH:noexp]) AND (“natural history”[All Fields] OR “natural course”[All Fields] OR untreated[All Fields])

2. What is the role of pharmacological treatment in the management of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (pharmacological treatment

OR pharmacological management OR drug OR medication)

Search name: DLS + pharmacological management (17 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Drug Therapy”[Mesh] OR “drug therapy “[Subheading] OR (“Analgesics”[Mesh] OR “Analgesics “[Pharmacological Action]) OR (“Anti-Inflammatory Agents”[Mesh] OR “Anti-Inflammatory Agents”[Pharmacological Action]) OR drug[text word] OR medication[text word] OR medications[text word])

3. What is the role of physical therapy/exercise in the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (physical therapy OR exercise OR exercise therapy OR rehabilitation)

Search name: DLS + (physical therapy or exercise OR rehab) (13 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Physical Therapy Modalities”[Mesh] OR “Exercise”[Mesh] OR “Exertion”[Mesh] OR “Physical Fitness”[Mesh] OR “Exercise Movement Techniques”[Mesh] OR (“Rehabilitation”[Mesh] OR “rehabilitation “[Sub- heading]) OR “physical therapy”[title] OR “rehabilitation”[title] OR exercise[title] OR physiotherapy[title])

4. What is the role of manipulation in the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (manipulation OR chiropractic care)

Search name: DLS + manipulation (3 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum-

bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Musculoskeletal Manipulations”[Mesh] OR (“chiropractic”[MeSH Terms] OR chiropractic[Text Word]) OR manipulat*[All Fields])

5. What is the role of epidural steroid injections in the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND injections

Search name: DLS + injections (4 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Injections”[Mesh] OR injection*)

6. What is the role of ancillary treatments such as bracing, traction, electrical stimulation and transcutaneous electrical stimulation (TENS) in the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (bracing OR traction OR electrical stimulation OR transcutaneous electrical stimulation OR TENS)

Search name: DLS + electrical stimulation, etc. (7 articles) Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (“Braces”[Mesh] OR bracing[All Fields] OR “Traction”[Mesh] OR “Electric Stimulation”[Mesh] OR “Transcutaneous Electric Nerve Stimulation”[Mesh] OR ((“transcutaneous electric nerve stimulation”[TIAB] NOT Medline[SB]) OR “transcutaneous electric nerve stimulation”[MeSH Terms] OR TENS[Text Word]) OR “Electric Stimulation Therapy”[Mesh])

7. What is the long-term result of medical/interventional management of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (medical management OR nonoperative management OR conservative management OR medical treatment OR nonoperative treatment OR conservative treatment OR nonsurgical OR rehabilitation) AND long term outcomes

Search name: DLS + nonsurgical + long-term outcomes (17 articles) This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 75

Search strategy: “degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (nonoperative[All Fields] OR conservative[All Fields] OR nonsurgical[All Fields] OR (“rehabilitation”[Subheading] OR “rehabilitation”[MeSH Terms] OR rehabilitation[Text Word]) OR “clinical management”[All Fields] OR “spondylolisthesis/therapy”[MeSH:noexp]) AND (“Time”[Mesh] OR “Longitudi- nal Studies”[Mesh] OR “long-term”[All Fields])

Surgical Treatment of Degenerative Lumbar Spondylolisthesis (Work Group 5) Search Strategies

Search Strategies by Clinical Question: 1. Do surgical treatments improve outcomes in the treatment of degenerative lumbar spondylolisthesis compared to the natural history of the disease? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (surgery OR operation) AND natural history

Search name #1: DLS + surgical procedures (222 articles) Search strategy: (“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum- bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Surgical Procedures, Operative”[Mesh] OR “Lumbar Vertebrae/surgery”[Mesh] OR “Lumbosacral Region/ surgery”[Mesh] OR “Spondylolisthesis/surgery”[Mesh:noexp])

Search name #2: DLS + surgical procedures + natural history (8 articles) Search strategy: (“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum- bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Surgical Procedures, Operative”[Mesh] OR “Lumbar Vertebrae/surgery”[Mesh] OR “Lumbosacral Re- gion/surgery”[Mesh] OR “Spondylolisthesis/surgery”[Mesh:noexp]) AND ((“natural history”[MeSH Terms] OR natural history[Text Word]) OR (natural[All Fields] AND course[All Fields]) OR untreated[All Fields])

Note: There is little or none on comparisons between surgical intervention and natural history of DLS. I’ve included one search on surgical interventions and a second on the same with natural history.

2. Does surgical decompression alone improve surgical outcomes in the treatment of degenerative lumbar spondylolisthesis compared to medical/interventional treatment alone or the natural history of the disease? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (surgical decompression OR laminectomy OR laminotomy OR foraminotomy) AND [(medical management OR nonoperative management OR conservative management OR medical treatment OR nonoperative treatment OR conservative treatment OR nonsurgical OR rehabilitation) OR natural history]

Search name: DLS + decompression + (nonsurgical or natural history) (21 articles) Search strategy: (“Decompression, Surgical”[Mesh] OR “Laminectomy”[Mesh] OR laminotomy[text word] OR foraminotomy[text word] OR surgical decompression[text word]) AND ((“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“lumbar spondylolisthesis”[All Fields] AND degenerative[All Fields]) OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang]) AND (nonoperative[All Fields] OR conservative[All Fields] OR non-surgical[All Fields] OR (“rehabilitation”[Subheading] OR “rehabilitation”[MeSH Terms] OR rehabilitation[Text Word]) OR “clinical management”[All Fields] OR “spondylolisthesis/therapy”[MeSH:noexp])) OR ((“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR ( “Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND ((“natural history”[MeSH Terms] OR natural history[Text Word]) OR (natural[All Fields] AND course[All Fields]) OR untreated[All Fields])))

3. Does the addition of lumbar fusion, with or without instrumentation, to surgical decompression improve surgical outcomes in the treatment of degenerative lumbar spondylolisthesis compared to treatment by decompression alone? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (surgical decompression OR laminectomy OR laminotomy OR foraminotomy) AND (fusion OR arthrodesis) AND (instrumentation OR pedicle screw OR hardware)

Search name: DLS + decompression + lumbar fusion (61 articles) Search strategy: ((“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Decompression, Surgical”[Mesh] OR “Laminectomy”[Mesh] OR laminotomy[text word] OR foraminotomy[text word] OR surgical decompression[text word])) AND (“Arthrodesis”[Mesh] OR “Spinal Fusion”[Mesh] OR lumbar fusion[text word])

Note: The above search does not limit to instrumentation because the question specifies “with or without instrumentation”. Therefore I deviated from the search string you provided. Of course, instrumentation may still be included, but it will be broader than that, looking at fusion. The next search looks at the same string with instrumentation.

4. Does the addition of instrumentation to decompression and fusion for degenerative spondylolisthesis improve surgical outcomes compared with decompression and fusion alone? Same search string as #4

Search name: DLS + decompression + lumbar fusion (29 articles) Search strategy: (((“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Decompression, Surgical”[Mesh] OR “Laminectomy”[Mesh] OR laminotomy[text word] OR foraminotomy[text word] OR surgical decompression[text word])) AND (“Arthrodesis”[Mesh] OR “Spinal Fusion”[Mesh] OR lumbar fusion[text word])) AND (“instrumentation “[Subheading] OR instrumentation[title] OR “Bone Screws”[Mesh] OR pedicle screw[text word] OR pedicle screws[text word])

5. How do outcomes of decompression with posterolateral fusion compare with those for 360° fusion (anterior-posterior OR transforaminal lumbar interbody fusion OR posterior lumbar interbody fusion) for treatment of degenerative spondylolisthesis? Same search string as #4

Search name: DLS + (posterolateral or 360 degree fusion) (20 articles) Search strategy: ((“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lumbosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Decompression, Surgical”[Mesh] OR “Laminectomy”[Mesh] OR laminotomy[text word] OR foraminotomy[text word] OR surgical decompression[text word])) AND (anterior-posterior[All Fields] OR (transforaminal[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word]) AND interbody[All Fields] AND fusion[All Fields]) OR (posterior[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word]) AND interbody[All Fields] AND fusion[All Fields]) OR “posterolateral fusion”[text word] OR “360 degree fusion”[text word])

Note: I didn’t use the same search string as Q 4 because the terms “posterolateral”, “ anterior- posterior”, etc. were a lot more specific than just fusion. I used these and other terms from the question itself.

6. What is the role of reduction with fusion in the treatment of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND reduction AND (slip OR listhesis OR spine) AND (fusion OR arthrodesis) This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 79

Search name: DLS + reduction + fusion (17 articles) Search strategy: (“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum- bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND reduction[text word] AND (slip[All Fields] OR listhesis[All Fields] OR (“spine”[MeSH Terms] OR spine[Text Word]) OR spinal[All Fields]) AND (“Arthrodesis”[Mesh] OR “Spinal Fusion”[Mesh] OR lumbar fusion[text word])

7. What is the long-term result (4+ years) of surgical management of degenerative lumbar spondylolisthesis? degenerative lumbar spondylolisthesis [NOT spondylolysis] AND (surgery OR operation) AND long term outcomes

Search name: DLS + surgical management + long-term result (114 articles) Search strategy: (“degenerative lumbar spondylolisthesis”[All Fields] OR “lumbar degenerative spondylolisthesis”[All Fields] OR (“degenerative spondylolisthesis”[All Fields] AND ((“lumbosacral region”[TIAB] NOT Medline[SB]) OR “lumbosacral region”[MeSH Terms] OR lumbar[Text Word])) OR (“Spondylolisthesis”[MAJR:noexp] AND (“Lum- bosacral Region”[Mesh] OR “Lumbar Vertebrae”[Mesh]) AND degenerative[All Fields]) AND (“humans”[MeSH Terms] AND English[lang])) AND (“Surgical Procedures, Operative”[Mesh] OR “Lumbar Vertebrae/surgery”[Mesh] OR “Lumbosacral Region/ surgery”[Mesh] OR “Spondylolisthesis/surgery”[Mesh:noexp]) AND (“Time”[Mesh] OR “Longitudinal Studies”[Mesh] OR “long-term”[All Fields])

Databases Searched:  MEDLINE (PubMed)  ACP Journal Club  Cochrane Database of Systematic Reviews  Database of Abstracts of Reviews of Effectiveness (DARE)  Cochrane Central Register of Controlled Trials

Appendix F: Evidentiary Tables

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Natural History What is the natural history of degenerative lumbar spondylolisthesis?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Diagnosis/Imaging Question 1: What are the most appropriate historical and physical exam findings consistent with the diagnosis of degenerative lumbar spondylolisthesis?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Diagnosis/Imaging Question 2: What are the most appropriate diagnostic tests for degenerative lumbar spondylolisthesis?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Outcome Measures What are the appropriate outcome measures for the treatment of degenerative lumbar spondylolisthesis?

Note: The Zurich Claudication Questionnaire (ZCQ) represents an evolution of Swiss Spinal Stenosis Questionnaire (SSS). Conclusions made about either questionnaire can be extrapolated to the other.

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 1: Do surgical treatments improve outcomes in the treatment of degenerative lumbar spondylolisthesis compared to the natural history of the disease?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 2: Does surgical decompression alone improve outcomes in the treatment of degenerative lumbar spondylolisthesis compared to medical/interventional treatment alone or the natural history of the disease?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 3: Does the addition of lumbar fusion, with or without instrumentation, to surgical decompression improve surgical outcomes in the treatment of degenerative lumbar spondylolisthesis compared to treatment by decompression alone?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 4: Does the addition of instrumentation to decompression and fusion for degenerative spondylolisthesis improve surgical outcomes compared with decompression and fusion alone?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 5: How do outcomes of decompression with posterolateral fusion compare with those for 360° fusion (anterior- posterior OR transforaminal lumbar interbody fusion OR posterior lumbar interbody fusion) for treatment of degenerative spondylolisthesis?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 6: What is the role of reduction (deliberate attempt to reduce via surgical technique) with fusion in the treatment of degenerative lumbar spondylolisthesis?

Evidentiary Table. Degenerative Lumbar Spondylolisthesis, Surgical Treatment Question 7: What is the long-term result (4+ years) of surgical management of degenerative lumbar spondylolisthesis?

This clinical guideline should not be construed as including all proper methods of care or excluding other acceptable methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. NASS Clinical Guidelines – Degenerative Lumbar Spondylolisthesis 127 VI. Degenerative Lumbar Spondylolisthesis Guideline References 1. Adachi K, Futami T, Ebihara A, et al. Spinal canal gapophyseal (facet) joints: a role in the pathogenesis of enlargement procedure by restorative laminoplasty spinal pain syndromes and degenerative spondylolisthe- for the treatment of lumbar canal stenosis. Spine J. sis. Semin Neurol. Jun 2002;22(2):187-196. 2003;3(6):471-478. 16. Beutler WJ, Fredrickson BE, Murtland A, Sweeney CA, 2. Anderson PA, Tribus CB, Kitchel SH. Treatment of Grant WD, Baker D. The natural history of spondyloly- neurogenic claudication by interspinous decompression: sis and spondylolisthesis: 45-year follow-up evaluation. application of the X STOP device in patients with lum- Spine. 2003;28(10):1027-1035; discussion 1035. bar degenerative spondylolisthesis. J Neurosurg Spine. 17. Boden SD, Riew KD, Yamaguchi K, Branch TP, Schell- 2006;4(6):463-471. inger D, Wiesel SW. Orientation of the lumbar facet 3. Apel DM, Lorenz MA, Zindrick MR. Symptomatic joints: association with degenerative disc disease. J Bone spondylolisthesis in adults: four decades later. Spine. Joint Surg Am. 1996;78(3):403-411. 1989;14(3):345-348. 18. Bolesta MJ, Bohlman HH. Degenerative spondylolisthe- 4. Atlas SJ, Delitto A. Spinal stenosis: surgical ver- sis. Instr Course Lect. 1989;38:157-165. sus nonsurgical treatment. Clin Orthop Relat Res. 19. Bono CM, Lee CK. The influence of subdiagnosis on ra- 2006;443:198-207. diographic and clinical outcomes after lumbar fusion for 5. Austin RC, Branch CL, Jr., Alexander JT. Novel bio- degenerative disc disorders: an analysis of the literature absorbable interbody fusion spacer-assisted fusion from two decades. Spine. 2005;30(2):227-234. for correction of spinal deformity. Neurosurg Focus. 20. Booth KC, Bridwell KH, Eisenberg BA, Baldus CR, 2003;14(1):e11. Lenke LG. Minimum 5-year results of degenerative 6. Bassewitz H, Herkowitz H. Lumbar stenosis with spon- spondylolisthesis treated with decompression and instru- dylolisthesis: current concepts of surgical treatment. Clin mented posterior fusion. Spine. 1999;24(16):1721-1727. Orthop Relat Res. 2001(384):54-60. 21. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, 7. Bednar DA. Surgical management of lumbar degenera- Baldus C. The role of fusion and instrumentation in the tive spinal stenosis with spondylolisthesis via posterior treatment of degenerative spondylolisthesis with spinal reduction with minimal laminectomy. J Spinal Disord stenosis. J Spinal Disord. 1993;6(6):461-472. Tech. 2002;15(2):105-109. 22. Brown MD, Lockwood JM. Degenerative spondylolis- 8. Belfi LM, Ortiz AO, Katz DS. Computed tomography thesis. Instr Course Lect. 1983;32:162-169. evaluation of spondylolysis and spondylolisthesis in 23. Buttermann GR, Garvey TA, Hunt AF, et al. asymptomatic patients. Spine. 2006;31(24):E907-910. Lumbar fusion results related to diagnosis. Spine. 9. Ben-Galim P, Reitman CA. The distended facet sign: an 1998;23(1):116-127. indicator of position-dependent spinal stenosis and de- 24. Cauchoix J, Benoist M, Chassaing V. Degenerative spon- generative spondylolisthesis. Spine J. 2007;7(2):245-248. dylolisthesis. Clin Orthop Relat Res. 1976(115):122-129. 10. Bendo JA, Ong B. Importance of correlating static and 25. Chang P, Seow KH, Tan SK. Comparison of the results dynamic imaging studies in diagnosing degenerative lum- of spinal fusion for spondylolisthesis in patients who are bar spondylolisthesis. Am J Orthop. 2001;30(3):247-250. instrumented with patients who are not. Singapore Med 11. Benini A, Plotz G. Reduction and stabilization without J. 1993;34(6):511-514. laminectomy for unstable degenerative spondylolisthesis: 26. Cinotti G, Postacchini F, Fassari F, Urso S. Predisposing a preliminary report. Neurosurgery. 1995;37(4):843-844. factors in degenerative spondylolisthesis. A radiographic 12. Benoist M. The natural history of lumbar degenerative and CT study. Int Orthop. 1997;21(5):337-342. spinal stenosis. Joint Bone Spine. Oct 2002;69(5):450-457. 27. Crawford NR, Cagli S, Sonntag VK, Dickman CA. Bio- 13. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. mechanics of grade I degenerative lumbar spondylolis- Facet joint remodeling in degenerative spondylolisthesis: thesis. Part 1: in vitro model. J Neurosurg. 2001;94(1 an investigation of joint orientation and tropism. Eur Suppl):45-50. Spine J. 1998;7(5):376-380. 28. Cummins J, Lurie JD, Tosteson TD, et al. Descriptive 14. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. The epidemiology and prior healthcare utilization of pa- role of lumbar lordosis, vertebral end-plate inclination, tients in the Spine Patient Outcomes Research Trial’s disc height, and facet orientation in degenerative spon- (SPORT) three observational cohorts: disc herniation, dylolisthesis. J Spinal Disord. 1999;12(1):68-73. spinal stenosis, and degenerative spondylolisthesis. Spine. 15. Berven S, Tay BB, Colman W, Hu SS. The lumbar zy- 2006;31(7):806-814.

29. Dai LY. Orientation and tropism of lumbar facet pressive posterolateral fusion for patients with degen- joints in degenerative spondylolisthesis. Int Orthop. erative spondylolisthesis and spinal stenosis. Spine. 2001;25(1):40-42. 2004;29(2):173-174. 30. Dai LY, Jia LS, Yuan W, Ni B, Zhu HB. Direct repair of 44. Fitzgerald JA, Newman PH. Degenerative spondylolis- defect in lumbar spondylolysis and mild isthmic spon- thesis. J Bone Joint Surg Br. 1976;58(2):184-192. dylolisthesis by bone grafting, with or without facet joint 45. France JC, Yaszemski MJ, Lauerman WC, et al. A fusion. Eur Spine J. 2001;10(1):78-83. randomized prospective study of posterolateral lumbar 31. Dall BE, Rowe DE. Degenerative spondylolisthesis. Its fusion. Outcomes with and without pedicle screw instru- surgical management. Spine. 1985;10(7):668-672. mentation. Spine. 15 1999;24(6):553-560. 32. Detwiler PW, Porter RW, Han PP, Karahalios DG, 46. Frazier DD, Lipson SJ, Fossel AH, Katz JN. As- Masferrer R, Sonntag VK. Surgical treatment of lum- sociations between spinal deformity and outcomes bar spondylolisthesis. Adv Tech Stand Neurosurg. after decompression for spinal stenosis. Spine. 2000;26:331-346. 1997;22(17):2025-2029. 33. DeWald CJ, Vartabedian JE, Rodts MF, Hammerberg 47. Frymoyer JW, Selby DK. Segmental instability. Rationale KW. Evaluation and management of high-grade spon- for treatment. Spine. 1985;10(3):280-286. dylolisthesis in adults. Spine. 2005;30(6 Suppl):S49-59. 48. Fujiya M, Saita M, Kaneda K, Abumi K. Clinical study 34. Dupuis PR, Yong-Hing K, Cassidy JD, Kirkaldy-Willis on stability of combined distraction and compres- WH. Radiologic diagnosis of degenerative lumbar spinal sion rod instrumentation with posterolateral fusion instability. Spine. 1985;10(3):262-276. for unstable degenerative spondylolisthesis. Spine. 35. Elster AD, Jensen KM. Computed tomography of spon- 1990;15(11):1216-1222. dylolisthesis: patterns of associated pathology. J Comput 49. Gaetani P, Aimar E, Panella L, et al. Functional disability Assist Tomogr. 1985;9(5):867-874. after instrumented stabilization in lumbar degenera- 36. Epstein JA, Epstein BS, Lavine LS, Carras R, Rosenthal tive spondylolisthesis: a follow-up study. Funct Neurol. AD. Degenerative lumbar spondylolisthesis with an in- 2006;21(1):31-37. tact neural arch (pseudospondylolisthesis). J Neurosurg. 50. Gehrchen PM, Dahl B, Katonis P, Blyme P, Tondevold E, 1976;44(2):139-147. Kiaer T. No difference in clinical outcome after poste- 37. Epstein BS, Epstein JA, Jones MD. Degenerative spon- rolateral lumbar fusion between patients with isthmic dylolisthesis with an intact neural arch. Radiol Clin spondylolisthesis and those with degenerative disc North Am. 1977;15(2):275-287. disease using pedicle screw instrumentation: a compara- 38. Epstein NE, Epstein JA, Carras R, Lavine LS. Degenera- tive study of 112 patients with 4 years of follow-up. Eur tive spondylolisthesis with an intact neural arch: a review Spine J. 2002;11(5):423-427. of 60 cases with an analysis of clinical findings and the 51. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Pro- development of surgical management. Neurosurgery. spective outcomes evaluation after decompression with 1983;13(5):555-561. or without instrumented fusion for lumbar stenosis and 39. Epstein NE. Lumbar laminectomy for the resection of degenerative Grade I spondylolisthesis. J Neurosurg synovial cysts and coexisting lumbar spinal stenosis or Spine. 2004;1(3):267-272. degenerative spondylolisthesis: an outcome study. Spine. 52. Gibson JN, Grant IC, Waddell G. The Cochrane review 2004;29(9):1049-1055; discussion 1056. of surgery for lumbar disc prolapse and degenerative 40. Feffer HL, Wiesel SW, Cuckler JM, Rothman RH. lumbar spondylosis. Spine. 1 1999;24(17):1820-1832. Degenerative spondylolisthesis. To fuse or not to fuse. 53. Gibson JN, Waddell G, Grant IC. Surgery for degenera- Spine. 1985;10(3):287-289. tive lumbar spondylosis. Cochrane Database Syst Rev. 41. Fernandez-Fairen M, Sala P, Ramirez H, Gil J. A pro- 2000(3):CD001352. spective randomized study of unilateral versus bilateral 54. Gibson JN, Waddell G. Surgery for degenerative instrumented posterolateral lumbar fusion in degenera- lumbar spondylosis. Cochrane Database Syst Rev. tive spondylolisthesis. Spine. 2007;32(4):395-401. 2005(4):CD001352. 42. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, 55. Glaser JA, Bernhardt M, Found EM, McDowell GS, Montgomery DM, Kurz LT. 1997 Volvo Award winner Wetzel FT. Lumbar arthrodesis for degenerative condi- in clinical studies. Degenerative lumbar spondylolisthesis tions. Instr Course Lect. 2004;53:325-340. with spinal stenosis: a prospective, randomized study 56. Grob D, Humke T, Dvorak J. Direct pediculo-body fixa- comparing decompressive laminectomy and arthrod- tion in cases of spondylolisthesis with advanced interver- esis with and without spinal instrumentation. Spine. tebral disc degeneration. Eur Spine J. 1996;5(4):281-285. 1997;22(24):2807-2812. 57. Grobler LJ, Robertson PA, Novotny JE, Ahern JW. 43. Fischgrund JS. The argument for instrumented decom- Decompression for degenerative spondylolisthesis and

spinal stenosis at L4-5. The effects on facet joint mor- 2001;24(4):195-199. phology. Spine. 1993;18(11):1475-1482. 72. Inoue S, Watanabe T, Goto S, Takahashi K, Takata K, 58. Grobler LJ, Robertson PA, Novotny JE, Pope MH. Sho E. Degenerative spondylolisthesis. Pathophysiology Etiology of spondylolisthesis. Assessment of the and results of anterior interbody fusion. Clin Orthop role played by lumbar facet joint morphology. Spine. Relat Res. 1988;227:90-98. 1993;18(1):80-91. 73. Ito S, Yamada Y, Tuboi S, Muro T. Specific pattern of 59. Hackenberg L, Halm H, Bullmann V, Vieth V, Schneider ruptured annulus fibrosus in lumbar degenerative spon- M, Liljenqvist U. Transforaminal lumbar interbody fu- dylolisthesis. Neuroradiology. 1990;32(6):460-463. sion: a safe technique with satisfactory three to five year 74. Ito Y, Oda H, Taguchi T, Inoue H, Kawai S. Results of results. Eur Spine J. 2005;14(6):551-558. surgical treatment for lumbar canal stenosis due to de- 60. Hansraj KK, O’Leary PF, Cammisa FP, Jr., et al. De- generative spondylolisthesis: enlargement of the lumbar compression, fusion, and instrumentation surgery for spinal canal. J Orthop Sci. 2003;8(5):648-656. complex lumbar spinal stenosis. Clin Orthop Relat Res. 75. Iwamoto J, Takeda T. Effect of surgical treatment on 2001(384):18-25. physical activity and bone resorption in patients with 61. Hashimoto T, Oha F, Shigenobu K, et al. Mid-term neurogenic intermittent claudication. J Orthop Sci. clinical results of Graf stabilization for lumbar degenera- 2002;7(1):84-90. tive pathologies. a minimum 2-year follow-up. Spine J. 76. Jackson A, Isherwood I. Does degenerative disease 2001;1(4):283-289. of the lumbar spine cause arachnoiditis? A magnetic 62. Hee HT, Wong HK. The long-term results of surgical resonance study and review of the literature. Br J Radiol. treatment for spinal stenosis in the elderly. Singapore 1994;67(801):840-847. Med J. 2003;44(4):175-180. 77. Jacobsen S, Sonne-Holm S, Rovsing H, Monrad H, 63. Herkowitz HN, Kurz LT. Degenerative lumbar spon- Gebuhr P. Degenerative lumbar spondylolisthesis: an dylolisthesis with spinal stenosis. A prospective study epidemiological perspective: the Copenhagen Osteoar- comparing decompression with decompression and in- thritis Study. Spine. 2007;32(1):120-125. tertransverse process arthrodesis. J Bone Joint Surg Am. 78. Jaovisidha S, Techatipakorn S, Apiyasawat P, Laohacha- 1991;73(6):802-808. roensombat W, Poramathikul M, Siriwongpairat P. 64. Herkowitz HN. Spine update. Degenerative lumbar Degenerative disk disease at lumbosacral junction: plain spondylolisthesis. Spine. 1995;20(9):1084-1090. film findings and related MRI abnormalities. J Med Assoc 65. Herno A, Partanen K, Talaslahti T, et al. Long-term Thai. 2000;83(8):865-871. clinical and magnetic resonance imaging follow-up as- 79. Jayakumar P, Nnadi C, Saifuddin A, Macsweeney E, sessment of patients with lumbar spinal stenosis after Casey A. Dynamic degenerative lumbar spondylolis- laminectomy. Spine. 1999;24(15):1533-1537. thesis: diagnosis with axial loaded magnetic resonance 66. Herron LD, Trippi AC. L4-5 degenerative spondylolis- imaging. Spine. 2006;31(10):E298-301. thesis. The results of treatment by decompressive lamine- 80. Jin J, Jianxiong S, Guixing Q, Hong Z, Xisheng W, ctomy without fusion. Spine. 1989;14(5):534-538. Yipeng W. Surgical treatment of spondylolisthe- 67. Hilibrand AS, Rand N. Degenerative lumbar stenosis: sis with SOCON instrumentation. Chin Med Sci J. diagnosis and management. J Am Acad Orthop Surg. 2000;15(2):111-114. 1999;7(4):239-249. 81. Johnson JR, Kirwan EO. The long-term results of fusion 68. Hirabayashi S, Kumano K, Kuroki T. Cotrel-Dubousset in situ for severe spondylolisthesis. J Bone Joint Surg Br. pedicle screw system for various spinal disorders. Merits 1983;65(1):43-46. and problems. Spine. 1991;16(11):1298-1304. 82. Johnsson KE, Willner S, Johnsson K. Postoperative in- 69. Houten JK, Post NH, Dryer JW, Errico TJ. Clinical and stability after decompression for lumbar spinal stenosis. radiographically/neuroimaging documented outcome Spine. 1986;11(2):107-110. in transforaminal lumbar interbody fusion. Neurosurg 83. Kanayama M, Hashimoto T, Shigenobu K, et al. Adja- Focus. 2006;20(3):E8. cent-segment morbidity after Graf ligamentoplasty com- 70. Huang KF, Chen TY. Clinical results of a single central pared with posterolateral lumbar fusion. J Neurosurg. interbody fusion cage and transpedicle screws fixation 2001;95(1 Suppl):5-10. for recurrent herniated lumbar disc and low-grade spon- 84. Kanayama M, Hashimoto T, Shigenobu K, Oha F, Ishida dylolisthesis. Chang Gung Med J. 2003;26(3):170-177. T, Yamane S. Intraoperative biomechanical assessment 71. Ido K, Urushidani H. Radiographic evaluation of of lumbar spinal instability: validation of radiographic posterolateral lumbar fusion for degenerative spon- parameters indicating anterior column support in lumbar dylolisthesis: long-term follow-up of more than 10 years spinal fusion. Spine. 2003;28(20):2368-2372. vs. midterm follow-up of 2-5 years. Neurosurg Rev. 85. Kanayama M, Hashimoto T, Shigenobu K, Yamane S,

Bauer TW, Togawa D. A prospective randomized study bach H, Schramm J. Degenerative lumbar spondylolis- of posterolateral lumbar fusion using osteogenic pro- thesis-induced radicular compression: nonfusion-related tein-1 (OP-1) versus local autograft with ceramic bone decompression in selected patients without hypermo- substitute: emphasis of surgical exploration and histo- bility on flexion-extension radiographs. J Neurosurg. logic assessment. Spine. 2006;31(10):1067-1074. 2002;97(3 Suppl):281-286. 86. Kauppila LI, Eustace S, Kiel DP, Felson DT, Wright 99. Kuntz KM, Snider RK, Weinstein JN, Pope MH, Katz AM. Degenerative displacement of lumbar vertebrae. JN. Cost-effectiveness of fusion with and without instru- A 25-year follow-up study in Framingham. Spine. mentation for patients with degenerative spondylolisthe- 1998;23(17):1868-1873; discussion 1873-1864. sis and spinal stenosis. Spine. 2000;25(9):1132-1139. 87. Kawakami M, Tamaki T, Ando M, Yamada H, Hashi- 100. Kurz LT, Garfin SR, Unger AS, Thorne RP, Rothman zume H, Yoshida M. Lumbar sagittal balance influences RH. Intraspinal synovial cyst causing sciatica. J Bone the clinical outcome after decompression and posterolat- Joint Surg Am. 1985;67(6):865-871. eral spinal fusion for degenerative lumbar spondylolis- 101. Kwon BK, Albert TJ. Adult low-grade acquired spon- thesis. Spine. 2002;27(1):59-64. dylolytic spondylolisthesis: evaluation and management. 88. Kim NH, Lee JW. The relationship between isth- Spine. 2005;30(6 Suppl):S35-41. mic and degenerative spondylolisthesis and the con- 102. Lamberg T, Remes V, Helenius I, Schlenzka D, Seit- figuration of the lamina and facet joints. Eur Spine J. salo S, Poussa M. Uninstrumented in situ fusion for 1995;4(3):139-144. high-grade childhood and adolescent isthmic spon- 89. Kimura I, Shingu H, Murata M, Hashiguchi H. Lum- dylolisthesis: long-term outcome. J Bone Joint Surg Am. bar posterolateral fusion alone or with transpedicular 2007;89(3):512-518. instrumentation in L4-L5 degenerative spondylolisthesis. 103. Lauber S, Schulte TL, Liljenqvist U, Halm H, Hack- J Spinal Disord. 2001;14(4):301-310. enberg L. Clinical and radiologic 2-4-year results of 90. Kinoshita T, Ohki I, Roth KR, Amano K, Moriya H. transforaminal lumbar interbody fusion in degenera- Results of degenerative spondylolisthesis treated with tive and isthmic spondylolisthesis grades 1 and 2. Spine. posterior decompression alone via a new surgical ap- 2006;31(15):1693-1698. proach. J Neurosurg. 2001;95(1 Suppl):11-16. 104. Laus M, Tigani D, Alfonso C, Giunti A. Degenerative 91. Kirkaldy-Willis WH, Wedge JH, Yong-Hing K, Reilly J. spondylolisthesis: lumbar stenosis and instability. Chir Pathology and pathogenesis of lumbar spondylosis and Organi Mov. 1992;77(1):39-49. stenosis. Spine. 1978;3(4):319-328. 105. Laus M, Tigani D, Pignatti G, et al. Posterolateral spinal 92. Kleeman TJ, Hiscoe AC, Berg EE. Patient out- fusion: a study of 123 cases with a long-term follow-up. comes after minimally destabilizing lumbar stenosis Chir Organi Mov. 1994;79(1):69-79. decompression: the “Port-Hole” technique. Spine. 106. Lee TC. Reduction and stabilization without lamine- 2000;25(7):865-870. ctomy for unstable degenerative spondylolisthesis: a 93. Klopfenstein JD, Kim LJ, Feiz-Erfan I, Dickman CA. preliminary report. Neurosurgery. 1994;35(6):1072-1076. Retroperitoneal approach for lumbar interbody fusion 107. Lefkowitz DM, Quencer RM. Vacuum facet phenom- with anterolateral instrumentation for treatment of spon- enon: a computed tomographic sign of degenerative dylolisthesis and degenerative foraminal stenosis. Surg spondylolisthesis. Radiology. 1982;144(3):562. Neurol. 2006;65(2):111-116; discussion 116. 108. Lombardi JS, Wiltse LL, Reynolds J, Widell EH, Spen- 94. Knox BD, Harvell JC, Jr., Nelson PB, Hanley EN, Jr. cer C, 3rd. Treatment of degenerative spondylolisthesis. Decompression and luque rectangle fusion for degenera- Spine. 1985;10(9):821-827. tive spondylolisthesis. J Spinal Disord. 1989;2(4):223-228. 109. Lorenz R. Lumbar spondylolisthesis. Clinical syndrome 95. Knuttson F. The instability associated with disc degener- and operative experience with Cloward’s technique. Acta ation in the lumbar spine. Acta Radiol. 1944;25:593-609. Neurochir (Wien). 1982;60(3-4):223-244. 96. Konno S, Kikuchi S. Prospective study of surgical treat- 110. Lowe RW, Hayes TD, Kaye J, Bagg RJ, Luekens CA. ment of degenerative spondylolisthesis: comparison Standing roentgenograms in spondylolisthesis. Clin Or- between decompression alone and decompression with thop Relat Res. 1976(117):80-84. graf system stabilization. Spine. 2000;25(12):1533-1537. 111. Maheshwaran S, Davies AM, Evans N, Broadley P, 97. Kornblum MB, Fischgrund JS, Herkowitz HN, Abra- Cassar-Pullicino VN. Sciatica in degenerative spon- ham DA, Berkower DL, Ditkoff JS. Degenerative lumbar dylolisthesis of the lumbar spine. Ann Rheum Dis. spondylolisthesis with spinal stenosis: a prospective 1995;54(7):539-543. long-term study comparing fusion and pseudarthrosis. 112. Mardjetko SM, Connolly PJ, Shott S. Degenerative Spine. 2004;29(7):726-733; discussion 733-724. lumbar spondylolisthesis. A meta-analysis of literature 98. Kristof RA, Aliashkevich AF, Schuster M, Meyer B, Ur- 1970-1993. Spine. 1994;19(20 Suppl):2256S-2265S.

113. Mariconda M, Fava R, Gatto A, Longo C, Milano C. 2001;39(1):55-71, v-vi. Unilateral laminectomy for bilateral decompression of 127. Nojiri K, Matsumoto M, Chiba K, Toyama Y, Momo- lumbar spinal stenosis: a prospective comparative study shima S. Comparative assessment of pedicle morphology with conservatively treated patients. J Spinal Disord Tech. of the lumbar spine in various degenerative diseases. Surg 2002;15(1):39-46. Radiol Anat. 2005;27(4):317-321. 114. Markwalder TM. Surgical management of neurogenic 128. Okawa A, Shinomiya K, Komori H, Muneta T, Arai Y, claudication in 100 patients with lumbar spinal stenosis Nakai O. Dynamic motion study of the whole lumbar due to degenerative spondylolisthesis. Acta Neurochir spine by videofluoroscopy. Spine. 1998;23(16):1743-1749. (Wien). 1993;120(3-4):136-142. 129. Okuda T, Baba I, Fujimoto Y, et al. The pathology of 115. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah ligamentum flavum in degenerative lumbar disease.Spine. SM, O’Neil J, Wai EK. The surgical management of de- 2004;29(15):1689-1697. generative lumbar spondylolisthesis: a systematic review. 130. Okuda S, Oda T, Miyauchi A, Haku T, Yamamoto T, Spine. 2007;32(16):1791-1798. Iwasaki M. Surgical outcomes of posterior lumbar inter- 116. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis body fusion in elderly patients. J Bone Joint Surg Am. in grade I degenerative lumbar spondylolisthesis: a com- 2006;88(12):2714-2720. parative study of outcomes following laminoplasty and 131. Okuyama K, Kido T, Unoki E, Chiba M. PLIF with a ti- laminectomy with instrumented spinal fusion. J Orthop tanium cage and excised facet joint bone for degenerative Sci. 2005;10(3):270-276. spondylolisthesis-in augmentation with a pedicle screw. J 117. Matsunaga S, Sakou T, Morizono Y, Masuda A, Demirtas Spinal Disord Tech. 2007;20(1):53-59. AM. Natural history of degenerative spondylolisthesis. 132. Onda A, Otani K, Konno S, Kikuchi S. Mid-term and Pathogenesis and natural course of the slippage. Spine. long-term follow-up data after placement of the Graf 1990;15(11):1204-1210. stabilization system for lumbar degenerative disorders. J 118. Matsunaga S, Ijiri K, Hayashi K. Nonsurgically man- Neurosurg Spine. 2006;5(1):26-32. aged patients with degenerative spondylolisthesis: a 133. Palmer S, Turner R, Palmer R. Bilateral decompression 10- to 18-year follow-up study. J Neurosurg. 2000;93(2 of lumbar spinal stenosis involving a unilateral approach Suppl):194-198. with microscope and tubular retractor system. J Neuro- 119. McAfee PC, Ullrich CG, Yuan HA, Sherry RG, Lock- surg. 2002;97(2 Suppl):213-217. wood RC. Computed tomography in degenerative spinal 134. Panagiotis ZE, Athanasios K, Panagiotis D, Minos T, stenosis. Clin Orthop Relat Res. 1981(161):221-234. Charis M, Elias L. Functional outcome of surgical treat- 120. McAfee PC, DeVine JG, Chaput CD, et al. The indi- ment for multilevel lumbar spinal stenosis. Acta Orthop. cations for interbody fusion cages in the treatment of 2006;77(4):670-676. spondylolisthesis: analysis of 120 cases. Spine. 2005;30(6 135. Park YK, Chung HS. Instrumented facet fusion for the Suppl):S60-65. degenerative lumbar disorders. Acta Neurochir (Wien). 121. McCulloch JA. Microdecompression and uninstru- 1999;141(9):915-920. mented single-level fusion for spinal canal steno- 136. Penning L, Blickman JR. Instability in lumbar spon- sis with degenerative spondylolisthesis. Spine. dylolisthesis: a radiologic study of several concepts. AJR 1998;23(20):2243-2252. Am J Roentgenol. 1980;134(2):293-301. 122. McGregor AH, Cattermole HR, Hughes SP. Global 137. Plotz GM, Benini A. Surgical treatment of degenera- spinal motion in subjects with lumbar spondylolysis and tive spondylolisthesis in the lumbar spine: no reposition spondylolisthesis: does the grade or type of slip affect without prior decompression. Acta Neurochir (Wien). global spinal motion? Spine. 2001;26(3):282-286. 1995;137(3-4):188-191. 123. McGregor AH, Anderton L, Gedroyc WM, Johnson J, 138. Ploumis A, Transfeldt EE, Gilbert TJ, Jr., Mehbod AA, Hughes SP. The use of interventional open MRI to assess Dykes DC, Perra JE. Degenerative lumbar scoliosis: ra- the kinematics of the lumbar spine in patients with spon- diographic correlation of lateral rotatory olisthesis with dylolisthesis. Spine. 2002;27(14):1582-1586. neural canal dimensions. Spine. 2006;31(20):2353-2358. 124. Mochida J, Suzuki K, Chiba M. How to stabilize a single 139. Podichetty VK, Spears J, Isaacs RE, Booher J, Biscup level lesion of degenerative lumbar spondylolisthesis. RS. Complications associated with minimally invasive Clin Orthop Relat Res. 1999(368):126-134. decompression for lumbar spinal stenosis. J Spinal Disord 125. Nasca RJ. Rationale for spinal fusion in lumbar spinal Tech. 2006;19(3):161-166. stenosis. Spine. 1989;14(4):451-454. 140. Posner I, White AA, 3rd, Edwards WT, Hayes WC. A 126. Nizard RS, Wybier M, Laredo JD. Radiologic as- biomechanical analysis of the clinical stability of the sessment of lumbar intervertebral instability and de- lumbar and lumbosacral spine. Spine. 1982;7(4):374-389. generative spondylolisthesis. Radiol Clin North Am. 141. Postacchini F, Perugia D. Degenerative lumbar spon-

dylolisthesis. Part I: Etiology, pathogenesis, pathomor- fusion in degenerative spondylolisthesis. Eur Spine J. phology, and clinical features. Ital J Orthop Traumatol. 2005;14(1):55-60. 1991;17(2):165-173. 156. Sanderson PL, Wood PL. Surgery for lumbar spi- 142. Postacchini F, Cinotti G, Perugia D. Degenerative nal stenosis in old people. J Bone Joint Surg Br. lumbar spondylolisthesis. II. Surgical treatment. Ital J 1993;75(3):393-397. Orthop Traumatol. 1991;17(4):467-477. 157. Sato K, Wakamatsu E, Yoshizumi A, Watanabe N, Irei 143. Postacchini F, Cinotti G. Bone regrowth after surgical O. The configuration of the laminas and facet joints in decompression for lumbar spinal stenosis. J Bone Joint degenerative spondylolisthesis. A clinicoradiologic study. Surg Br. 1992;74(6):862-869. Spine. 1989;14(11):1265-1271. 144. Postacchini F, Cinotti G, Perugia D, Gumina S. The 158. Sato K, Kikuchi S. Clinical analysis of two-level com- surgical treatment of central lumbar stenosis. Multiple pression of the cauda equina and the nerve roots in lum- laminotomy compared with total laminectomy. J Bone bar spinal canal stenosis. Spine. 1997;22(16):1898-1903; Joint Surg Br. 1993;75(3):386-392. discussion 1904. 145. Potter BK, Freedman BA, Verwiebe EG, Hall JM, Polly 159. Satomi K, Hirabayashi K, Toyama Y, Fujimura Y. A DW, Jr., Kuklo TR. Transforaminal lumbar interbody clinical study of degenerative spondylolisthesis. Ra- fusion: clinical and radiographic results and complica- diographic analysis and choice of treatment. Spine. tions in 100 consecutive patients. J Spinal Disord Tech. 1992;17(11):1329-1336. 2005;18(4):337-346. 160. Schnake KJ, Schaeren S, Jeanneret B. Dynamic stabili- 146. Pratt RK, Fairbank JC, Virr A. The reliability of the zation in addition to decompression for lumbar spinal Shuttle Walking Test, the Swiss Spinal Stenosis Ques- stenosis with degenerative spondylolisthesis. Spine. tionnaire, the Oxford Spinal Stenosis Score, and the 2006;31(4):442-449. Oswestry Disability Index in the assessment of patients 161. Schnee CL, Freese A, Ansell LV. Outcome analysis for with lumbar spinal stenosis. Spine. 2002;27(1):84-91. adults with spondylolisthesis treated with posterolateral 147. Prolo DJ, Oklund SA, Butcher M. Toward uniformity in fusion and transpedicular screw fixation. J Neurosurg. evaluating results of lumbar spine operations. A para- 1997;86(1):56-63. digm applied to posterior lumbar interbody fusions. 162. Sears W. Posterior lumbar interbody fusion for degen- Spine. 1986;11(6):601-606. erative spondylolisthesis: restoration of sagittal bal- 148. Radu AS, Menkes CJ. Update on lumbar spinal steno- ance using insert-and-rotate interbody spacers. Spine J. sis. Retrospective study of 62 patients and review of the 2005;5(2):170-179. literature. Rev Rhum Engl Ed. 1998;65(5):337-345. 163. Sengupta DK, Herkowitz HN. Lumbar spinal stenosis. 149. Rechtine GR, Sutterlin CE, Wood GW, Boyd RJ, Mans- Treatment strategies and indications for surgery. Orthop field FL. The efficacy of pedicle screw/plate fixation Clin North Am. 2003;34(2):281-295. on lumbar/lumbosacral autogenous bone graft fusion 164. Sengupta DK. Point of view: Dynamic stabiliza- in adult patients with degenerative spondylolisthesis. J tion in addition to decompression for lumbar spinal Spinal Disord. 1996;9(5):382-391. stenosis with degenerative spondylolisthesis. Spine. 150. Remes V, Lamberg T, Tervahartiala P, et al. Long-term 2006;31(4):450. outcome after posterolateral, anterior, and circumfer- 165. Silvers HR, Lewis PJ, Asch HL. Decompressive lum- ential fusion for high-grade isthmic spondylolisthesis bar laminectomy for spinal stenosis. J Neurosurg. in children and adolescents: magnetic resonance imag- 1993;78(5):695-701. ing findings after average of 17-year follow-up. Spine. 166. Sinaki M, Lutness MP, Ilstrup DM, Chu CP, Gramse 2006;31(21):2491-2499. RR. Lumbar spondylolisthesis: retrospective comparison 151. Robertson PA, Grobler LJ, Novotny JE, Katz JN. and three-year follow-up of two conservative treatment Postoperative spondylolisthesis at L4-5. The role of facet programs. Arch Phys Med Rehabil. 1989;70(8):594-598. joint morphology. Spine. 1993;18(11):1483-1490. 167. Soren A, Waugh TR. Spondylolisthesis and related dis- 152. Rosenberg NJ. Degenerative spondylolisthesis. Predis- orders. A correlative study of 105 patients. Clin Orthop posing factors. J Bone Joint Surg Am. 1975;57(4):467-474. Relat Res. 1985(193):171-177. 153. Rosenberg NJ. Degenerative spondylolisthesis: surgical 168. Stoll TM, Dubois G, Schwarzenbach O. The dynamic treatment. Clin Orthop Relat Res. 1976(117):112-120. neutralization system for the spine: a multi-center study 154. Rothman SL, Glenn WV, Jr., Kerber CW. Multiplanar of a novel non-fusion system. Eur Spine J. 2002;11 Suppl CT in the evaluation of degenerative spondylolisthesis. A 2:S170-178. review of 150 cases. Comput Radiol. 1985;9(4):223-232. 169. Stone AT, Tribus CB. Acute progression of spon- 155. Rousseau MA, Lazennec JY, Bass EC, Saillant G. Predic- dylolysis to isthmic spondylolisthesis in an adult. Spine. tors of outcomes after posterior decompression and 2002;27(16):E370-372.

170. Stucki G, Daltroy L, Liang MH, Lipson SJ, Fossel AH, follow-up pilot study evaluating the safety and efficacy Katz JN. Measurement properties of a self-administered of op-1 putty (rhbmp-7) as an adjunct to iliac crest outcome measure in lumbar spinal stenosis. Spine. autograft in posterolateral lumbar fusions. Eur Spine J. 1996;21(7):796-803. 2005;14(7):623-629. 171. Takahashi K, Kitahara H, Yamagata M, et al. Long- 181. Vamvanij V, Ferrara LA, Hai Y, Zhao J, Kolata R, Yuan term results of anterior interbody fusion for treat- HA. Quantitative changes in spinal canal dimensions ment of degenerative spondylolisthesis. Spine. using interbody distraction for spondylolisthesis. Spine. 1990;15(11):1211-1215. 2001;26(3):E13-18. 172. Takayanagi K, Takahashi K, Yamagata M, Moriya H, Ki- 182. Vibert BT, Sliva CD, Herkowitz HN. Treatment of insta- tahara H, Tamaki T. Using cineradiography for continu- bility and spondylolisthesis: surgical versus nonsurgical ous dynamic-motion analysis of the lumbar spine. Spine. treatment. Clin Orthop Relat Res. 2006;443:222-227. 2001;26(17):1858-1865. 183. Vitzthum HE, Konig A, Seifert V. Dynamic examina- 173. Teplick JG, Laffey PA, Berman A, Haskin ME. Di- tion of the lumbar spine by using vertical, open magnetic agnosis and evaluation of spondylolisthesis and/or resonance imaging. J Neurosurg. 2000;93(1 Suppl):58-64. spondylolysis on axial CT. AJNR Am J Neuroradiol. 184. Vogt MT, Rubin D, Valentin RS, et al. Lumbar olis- 1986;7(3):479-491. thesis and lower back symptoms in elderly white 174. Tokuhashi Y, Matsuzaki H, Sano S. Evaluation of women. The Study of Osteoporotic Fractures. Spine. clinical lumbar instability using the treadmill. Spine. 1998;23(23):2640-2647. 1993;18(15):2321-2324. 185. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical ver- 175. Tsai KH, Chang GL, Lin HT, Kuo DC, Chang LT, Lin sus nonsurgical treatment for lumbar degenerative spon- RM. Differences of lumbosacral kinematics between dylolisthesis. N Engl J Med. 2007;356(22):2257-2270. degenerative and induced spondylolisthetic spine. Clin 186. Wood KB, Popp CA, Transfeldt EE, Geissele AE. Ra- Biomech (Bristol, Avon). 2003;18(6):S10-16. diographic evaluation of instability in spondylolisthesis. 176. Unnanantana A. Posterolateral lumbar fusion for de- Spine. 1994;19(15):1697-1703. generative spondylolisthesis: experiences of a modified 187. Yone K, Sakou T, Kawauchi Y, Yamaguchi M, Yanase M. technique without instrumentation. J Med Assoc Thai. Indication of fusion for lumbar spinal stenosis in elderly 1997;80(9):570-574. patients and its significance. Spine. 1996;21(2):242-248. 177. Vaccaro AR, Garfin SR. Degenerative lumbar spon- 188. Yue WM, Tan SB. Distant skip level discitis and vertebral dylolisthesis with spinal stenosis, a prospective study osteomyelitis after caudal epidural injection: a case report comparing decompression with decompression and of a rare complication of epidural injections. Spine. intertransverse process arthrodesis: a critical analysis. 2003;28(11):E209-211. Spine. 1997;22(4):368-369. 189. Zdeblick TA. A prospective, randomized study of lum- 178. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot safety bar fusion. Preliminary results. Spine. 1993;18(8):983-991. and efficacy study of OP-1 putty (rhBMP-7) as an 190. Zhao J, Wang X, Hou T, He S. One versus two BAK fu- adjunct to iliac crest autograft in posterolateral lumbar sion cages in posterior lumbar interbody fusion to L4-L5 fusions. Eur Spine J. 2003;12(5):495-500. degenerative spondylolisthesis: a randomized, controlled 179. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study prospective study in 25 patients with minimum two-year evaluating the safety and efficacy of OP-1 Putty (rh- follow-up. Spine. 2002;27(24):2753-2757. BMP-7) as a replacement for iliac crest autograft in 191. Zhao J, Hou T, Wang X, Ma S. Posterior lumbar posterolateral lumbar arthrodesis for degenerative spon- interbody fusion using one diagonal fusion cage dylolisthesis. Spine. 2004;29(17):1885-1892. with transpedicular screw/rod fixation. Eur Spine J. 180. Vaccaro AR, Patel T, Fischgrund J, et al. A 2-year 2003;12(2):173-177.