Alan S. Hilibrand

Radiculopathy and Myelopathy at Segments Adjacent to the Site of a Previous Anterior Cervical Arthrodesis

BACKGROUND We studied the incidence, prevalence, and radiographic progression of symptomatic adjacent-segment disease, which we defined as the development of new radiculopathy or myelopathy referable to a motion segment adjacent to the site of a previous anterior arthrodesis of the cervical spine. METHODS A consecutive series of 374 patients who had a total of 409 anterior cervical arthrodeses for the treatment of cervical spondylosis with radiculopathy or myelopathy, or both, were followed for a maximum of twenty-one years after the operation. The annual incidence of symptomatic adjacent-segment disease was defined as the percentage of patients who had been disease-free at the start of a given year of follow-up in whom new disease developed during that year. The prevalence was defined as the percentage of all patients in whom symptomatic adjacent-segment disease developed within a given period of follow-up. The natural history of the disease was predicted with use of a Kaplan-Meier survivorship analysis. The hypothesis that new disease at an adjacent level is more likely to develop following a multilevel arthrodesis than it is following a single-level arthrodesis was tested with logistic regression. RESULTS Symptomatic adjacent-segment disease occurred at a relatively constant incidence of 2.9 percent per year (range, 0.0 to 4.8 percent per year) during the ten years after the operation. Survivorship analysis predicted that 25.6 percent of the patients (95 percent confidence interval, 20 to 32 percent) who had an anterior cervical arthrodesis would have new disease at an adjacent level within ten years after the operation. There were highly significant differences among the motion segments with regard to the likelihood of symptomatic adjacent-segment disease (p<0.0001); the greatest risk was at the interspaces between the fifth and sixth and between the sixth and seventh cervical vertebrae. Contrary to our hypothesis, we found that the risk of new disease at an adjacent level was significantly lower following a multilevel arthrodesis than it was following a single-level arthrodesis (p<0.001). More than two-thirds of all patients in whom the new disease developed had failure of nonoperative management and needed additional operative procedures. CONCLUSIONS Symptomatic adjacent-segment disease may affect more than one-fourth of all patients within ten years after an anterior cervical arthrodesis. A single-level arthrodesis involving the fifth or sixth cervical vertebra and preexisting radiographic evidence of degeneration at adjacent levels appear to be the greatest risk factors for new disease. Therefore, we believe that all degenerated segments causing radiculopathy or myelopathy should be included in an anterior cervical arthrodesis. Although our findings suggest that symptomatic adjacent-segment disease is the result of progressive spondylosis, patients should be informed of the substantial possibility that new disease will develop at an adjacent level over the long term.

Surgical versus nonsurgical therapy for lumbar spinal stenosis.

BACKGROUND Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. METHODS Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. RESULTS A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. CONCLUSIONS In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].).

Surgical Versus Nonoperative Treatment for Lumbar Disc Herniation Four-Year Results for the Spine Patient Outcomes Research Trial (SPORT)

Study Design. Concurrent, prospective, randomized, and observational cohort study. Objective. To assess the 4-year outcomes of surgery versus nonoperative care. Summary of Background Data. Although randomized trials have demonstrated small short-term differences in favor of surgery, long-term outcomes comparing surgical to nonoperative treatment remain controversial. Methods. Surgical candidates with imaging-confirmed lumbar intervertebral disc herniation meeting SPORT eligibility criteria enrolled into prospective, randomized (501 participants), and observational cohorts (743 participants) at 13 spine clinics in 11 US states. Interventions were standard open discectomy versus usual nonoperative care. Main outcome measures were changes from baseline in the SF-36 Bodily Pain (BP) and Physical Function (PF) scales and the modified Oswestry Disability Index (ODI - AAOS/Modems version) assessed at 6 weeks, 3 months, 6 months, and annually thereafter. Results. Nonadherence to treatment assignment caused the intent-to-treat analyses to underestimate the treatment effects. In the 4-year combined as-treated analysis, those receiving surgery demonstrated significantly greater improvement in all the primary outcome measures (mean change surgery vs. nonoperative; treatment effect; 95% CI): BP (45.6 vs. 30.7; 15.0; 11.8 to 18.1), PF (44.6 vs. 29.7; 14.9;12.0 to 17.8) and ODI (−38.1 vs. −24.9; −13.2; −15.6 to −10.9). The percent working was similar between the surgery and nonoperative groups, 84.4% versus 78.4% respectively. Conclusion. In a combined as-treated analysis at 4 years, patients who underwent surgery for a lumbar disc herniation achieved greater improvement than nonoperatively treated patients in all primary and secondary outcomes except work status.

Surgical versus nonoperative treatment for lumbar spinal stenosis four-year results of the Spine Patient Outcomes Research Trial.

Study Design. Randomized trial and concurrent observational cohort study. Objective. To compare 4 year outcomes of surgery to nonoperative care for spinal stenosis. Summary of Background Data. Surgery for spinal stenosis has been shown to be more effective compared to nonoperative treatment over 2 years, but longer-term data have not been analyzed. Methods. Surgical candidates from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a randomized cohort (RC) or observational cohort (OC). Treatment was standard decompressive laminectomy or standard nonoperative care. Primary outcomes were SF-36 bodily pain (BP) and physical function scales and the modified Oswestry Disability index assessed at 6 weeks, 3 months, 6 months, and yearly up to 4 years. Results. A total of 289 patients enrolled in the RC and 365 patients enrolled in the OC. An as-treated analysis combining the RC and OC and adjusting for potential confounders found that the clinically significant advantages for surgery previously reported were maintained through 4 years, with treatment effects (defined as mean change in surgery group minus mean change in nonoperative group) for bodily pain 12.6 (95% confidence interval [CI], 8.5–16.7); physical function 8.6 (95% CI, 4.6–12.6); and Oswestry Disability index −9.4 (95% CI, −12.6 to −6.2). Early advantages for surgical treatment for secondary measures such as bothersomeness, satisfaction with symptoms, and self-rated progress were also maintained. Conclusion. Patients with symptomatic spinal stenosis treated surgically compared to those treated nonoperatively maintain substantially greater improvement in pain and function through 4 years.

Lumbar Adjacent Segment Degeneration and Disease After Arthrodesis and Total Disc Arthroplasty

Study Design. Systematic review of published incidence of radiographic adjacent segment degeneration (ASDeg) and symptomatic adjacent segment disease (ASDis) after arthrodesis or total disc replacement. Objective. Assess impact of surgery method and other factors on the incidence of ASDeg and ASDis. Summary of Background Data. Twenty-seven articles, none of which were class I or II, met the inclusion criteria. Twenty involved arthrodesis (1732 patients) and 7 involved arthroplasty (758 patients). Nineteen detailed ASDeg and 16 detailed ASDis. Methods. Data were established for number of patients, gender, average patient age, incidence of ASDeg and ASDis, average time to follow-up, and level and type of surgery. Multivariate logistic regression was used to identify which parameters had a significant effect on the incidence of ASDeg and ASDis. Results. Three hundred fourteen of 926 patients in the arthrodesis group (34%) and 31 out of 313 patients in the total disc replacement group (9%) developed ASDeg. (P < 0.0001) Multivariate logistic regression indicated that higher odds of ASDeg were associated with: older patients (P < 0.001); arthodesis (P = 0.0008); and longer follow-up (P = 0.0025). For ASDis, 173/1216 (14%) arthrodesis patients developed ASDis compared to 7/595 (1%) of arthroplasty patients (P < 0.0001). Using multivariate logistic regression, higher odds of ASDis were seen in studies with fusion (P < 0.0001), higher percentages of male patients (P = 0.0019), and shorter follow-up (P < 0.05). Conclusion. Analysis of the literature suggests a correlation between fusion and the development of ASDeg compared to arthroplasty, but this association is dampened by the influence of patient age. There is a stronger correlation between fusion and ASDis compared to arthroplasty. The data supports only a class C recommendation (lowest tier) for the use of arthroplasty to reduce ASDis and disc degeneration compared to arthrodesis.

Complications associated with single-level transforaminal lumbar interbody fusion.

BACKGROUND CONTEXT The transforaminal lumbar interbody fusion (TLIF) procedure has become an increasingly popular means of obtaining a circumferential fusion while avoiding the morbidity of the anterior approach. Concerns remain, however, regarding the clinical efficacy and safety of its use. PURPOSE The purpose of this study was to evaluate the complications of the single-level TLIF procedure. The difference in complications observed with the use of iliac crest autograft compared with rhBMP-2 will be assessed. STUDY DESIGN Retrospective cohort study; a review of complications. METHODS Patients who underwent a single-level TLIF between January 2004 to May 2007 with either autograft iliac crest or rhBMP-2 were identified. A retrospective review of these patients included operative reports, pre- and postoperative medical records, most recent postoperative dynamic and static lumbar radiographs, and computed tomography scans (when available). RESULTS A total of 130 patients met the study criteria; 119 patients were available for follow-up, with an average radiographic follow-up of 19.1 months and an average clinical follow-up of 27.6 months. Thirty-three patients received iliac crest autograft and 86 patients received rhBMP-2. Complications occurred in 40 of the 119 study patients (33.6%). The autograft group had a higher complication rate (45.5% vs. 29.1%), but the difference was not statistically significant (p=.09). Complications in the autograft group included persistent donor-site pain (30.3%), donor-site infection (3.1%), lumbar wound infection (6.1%), and postoperative radiculitis (3.0%). Complications in the rhBMP-2 group included postoperative radiculitis (14.0%), vertebral osteolysis (5.8%), ectopic bone formation (2.3%), and lumbar wound infection (3.5%). A hydrogel sealant (Duraseal; Confluent Surgical Inc., Waltham, MA, USA) was used in 37 out of 86 patients in the rhBMP-2 group. The use of this sealant decreased the rate of postoperative radiculitis in the rhBMP-2 group from 20.4% to 5.4% (p=.047). The radiographic nonunion rate at most recent follow-up was 3.0% in the autograft group and 3.5% (p=.90) in the rhBMP-2 group. CONCLUSIONS The most common complications in the autograft group were related to the donor site. The most common complication in the rhBMP-2 group was postoperative radiculitis, the incidence of which is reduced by the use of a hydrogel sealant.

The Influence of Obesity on the Outcome of Treatment of Lumbar Disc Herniation: Analysis of the Spine Patient Outcomes Research Trial (SPORT)

BACKGROUND Questions remain as to the effect that obesity has on patients managed for symptomatic lumbar disc herniation. The purpose of this study was to determine if obesity affects outcomes following the treatment of symptomatic lumbar disc herniation. METHODS An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial for the treatment of lumbar disc herniation. A comparison was made between patients with a body mass index of <30 kg/m² (nonobese) (n = 854) and those with a body mass index of ≥30 kg/m² (obese) (n = 336). Baseline patient demographic and clinical characteristics were documented. Primary and secondary outcomes were measured at baseline and at regular follow-up time intervals up to four years. The difference in improvement from baseline between operative and nonoperative treatment was determined at each follow-up period for both groups. RESULTS At the time of the four-year follow-up evaluation, improvements over baseline in primary outcome measures were significantly less for obese patients as compared with nonobese patients in both the operative treatment group (Short Form-36 physical function, 37.3 compared with 47.7 points [p < 0.001], Short Form-36 bodily pain, 44.2 compared with 50.0 points [p = 0.005], and Oswestry Disability Index, -33.7 compared with -40.1 points [p < 0.001]) and the nonoperative treatment group (Short Form-36 physical function, 23.1 compared with 32.0 points [p < 0.001] and Oswestry Disability Index, -21.4 compared with -26.1 points [p < 0.001]). The one exception was that the change from baseline in terms of the Short Form-36 bodily pain score was statistically similar for obese and nonobese patients in the nonoperative treatment group (30.9 compared with 33.4 points [p = 0.39]). At the time of the four-year follow-up evaluation, when compared with nonobese patients who had been managed operatively, obese patients who had been managed operatively had significantly less improvement in the Sciatica Bothersomeness Index and the Low Back Pain Bothersomeness Index, but had no significant difference in patient satisfaction or self-rated improvement. In the present study, 77.5% of obese patients and 86.9% of nonobese patients who had been managed operatively were working a full or part-time job. No significant differences were observed in the secondary outcome measures between obese and nonobese patients who had been managed nonoperatively. The benefit of surgery over nonoperative treatment was not affected by body mass index. CONCLUSIONS Obese patients realized less clinical benefit from both operative and nonoperative treatment of lumbar disc herniation. Surgery provided similar benefit over nonoperative treatment in obese and nonobese patients.

A Pilot Study Evaluating the Safety and Efficacy of OP-1 Putty (rhBMP-7) as a Replacement for Iliac Crest Autograft in Posterolateral Lumbar Arthrodesis for Degenerative Spondylolisthesis

Study Design. A prospective, randomized, controlled, multicenter clinical study was conducted. Objective. To compare the clinical and radiographic outcomes of patients treated with OP-1 (BMP-7) Putty to autogenous iliac crest bone graft for one-level uninstrumented posterolateral fusion of the lumbar spine following decompressive laminectomy for the treatment of symptomatic degenerative spondylolisthesis with spinal stenosis. Background. Preclinical studies have demonstrated that osteoinductive recombinant human osteogenic protein1 in the form of OP-1 Putty is successful at achieving a posterolateral fusion in rabbits and dogs without any significant safety concerns. Methods. Thirty-six patients with degenerative lumbar spondylolisthesis and symptoms of neurogenic claudication were randomized (2:1) to either OP-1 Putty (3.5 mg of OP-1 per side) or autogenous iliac crest bone graft for one-level uninstrumented posterolateral fusion following a decompressive laminectomy. Enrollment in the study was complete when 24 OP-1 Putty patients and 12 autograft patients had been randomized and treated. A patient administered Oswestry scale and SF-36 scale were used to determine clinical outcomes. Independent, blinded neuroradiologists reviewed both static and dynamic radiographs to determine fusion status. Results. At the 1-year follow-up, 32 patients were available for clinical analysis and 29 patients were available for radiographic review. Clinical success as measured on the Oswestry scale was achieved by 18 of 21 (86%) OP-1 Putty patients and 8 of 11 (73%) autograftpatients. SF-36 pain index scores showed similar results. Fourteen of 19 (74%) OP-1 Putty patients and 6 of 10 (60%) autograft patients achieved a successful posterolateral fusion fulfilling all fusion criteria. Of the 29 evaluable patients, 15 were both clinical and radiographic successes, 5 were radiographic successes but were clinicalfailures, 1 patient was both a radiographic and clinical failure, and 8 patients were radiographic failures but were clinical successes. No systemic toxicity, ectopic bone formation, recurrent stenosis, or other adverse events related to the OP-1 Putty implant were observed. Conclusion. Although the posterolateral spine is a challenging fusion environment in patients with degenerative spondylolisthesis, successful radiographic fusion was obtained using OP-1 Putty at a rate that was similar to autograft given the number of patients in this study. Importantly, there were no apparent adverse consequences related to the use of the OP-1 Putty implant in this patient population.

Impact of neck and arm pain on overall health status.

Study Design. A prospective, multicenter, cross-sectional analysis of data from the National Spine Network database. Objectives. To compare the relative impact of radicular and axial symptoms associated with disease of the cervical spine on general health as measured by the SF-36 Health Survey, and to compare the impact of these symptoms among patients of varying age and symptom duration. Background. Degenerative disorders of the cervical spine can cause debilitating symptoms of neck and arm pain. Physicians generally treat radiculopathy more aggressively than axial neck pain alone, although it has never been shown that the presence of radiculopathy leads to a greater impairment of physical and mental function. Materials and Methods. SF-36 Health Survey data were collected from all consenting patients seen within the National Spine Network. Patients with symptoms referable to the cervical spine (as per their physician) were included (n = 1,809). SF-36 scores for all eight scales (bodily pain (BP), vitality (VT), general health (GH), mental health (MH), physical function (PF), role physical (RP), role emotional (RE), and social function (SF), and two summary scales (Physical Component Summary [PCS] and Mental Component Summary [MCS]) were calculated. Age/gender normative scores were subtracted from the scale scores to produce a negative “impact” score, which reflected how far below normal health status these patients were. Patients were grouped according to location of symptoms (axial only, radicular only, or axial and radicular), age (younger than 40, 40 to 60, and older than 60 years), and symptom duration (acute: <6 wk; subacute: 6 wk–6 mo; and chronic: >6 mo). SF-36 scores were compared between all groups using analysis of variance and multiple comparisons with Bonferroni adjustment. Results. Patients who presented with both axial and radicular symptoms had the lowest SF-36 scores relative to age and gender norms. These scores were significantly lower than those for patients with only axial or only radicular symptoms across all eight subscales (P < 0.05–P < 0.0001). Scores for patients with only axial pain were significantly lower than for patients with only radicular pain for VT (P < 0.04) and GH (P < 0.004). Patients younger than 40 and those between ages 40 to 60 years were significantly more impacted by their symptoms than patients older than 60 years for all eight scales (P < 0.01). PCS scores were similar for acute, subacute, and chronic groups, whereas MCS scores were significantly worse for patients with chronic pain. Conclusions. Combined neck and arm pain were much more disabling than either symptom alone. Younger patients (younger than 40 or 40–60) were more affected by these symptoms than patients older than 60 years. In addition, as symptom duration increased, a negative impact on mental health was observed, although chronic symptoms did not affect physical health. This study suggests that patients with a significant component of axial pain in conjunction with cervical radiculopathy should be considered the most affected of all patients with cervical spondylosis. Given the evidence that the treatment methods at the disposal of physicians are effective, this study suggests that prompt treatment of these patients may help avoid the harmful effects of chronic symptoms on mental functioning, especially among younger patients who were found to be more impacted by the symptoms.

Industry Support and Correlation to Study Outcome for Papers Published in Spine

Study Design. Retrospective review of articles published in the journal Spine. Objectives. To evaluate potential correlations between research sponsorship and study outcome. Summary of Background Data. Industry sponsorship has traditionally been associated with more positive results than non-funded or peer-reviewed funded projects in other areas of medicine. The association of such sponsorship and study outcome has not been addressed previously in spine research. Methods. Articles from the journal Spine from January 2002 to July 2003 were reviewed. These were examined for the subject evaluated, type of study design, funding source, and conclusion reached. Results. Of 1143 articles, 527 met inclusion criteria of having abstract, materials/methods, and conclusion sections. Industry support was reported for 84 (15.9%), foundation support for 67 (12.7%), government support for 54 (10.2%), institution support for 17 (3.2%), and no funding was reported for 304 (57.9%). The odds ratio of industry funded reporting positive results was 3.3 times that of studies with any other funding sources (P < 0.001). Conclusions. Industry funded studies demonstrated a statistically greater likelihood to report positive results than studies with other funding sources. Potential explanations for this are biased study design, biased experimental technique, biased result interpretation, or publication bias. Although the expense of research and limited funding sources have forced an increased reliance on industry support for funding basic science and clinical spine research, this does introduce the potential for bias and must be recognized by the reader.