Symptomatic Degenerative Disc Research Articles

Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration

BACKGROUND CONTEXTIntervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration. PURPOSETo investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS). STUDY DESIGNThis study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors’ institution. METHODSHematoxylin and eosin (H&E), Alcian blue–PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed. RESULTSPatients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc. CONCLUSIONSMMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration. CLINICAL SIGNIFICANCEMMP-1 IHC score may be used as an indicator of IVD degeneration.

Study to Evaluate the Safety and Preliminary Efficacy of IDCT, a Treatment for Symptomatic Lumbar Disc Degeneration

Study to Evaluate the Safety and Preliminary Efficacy of IDCT, a Treatment for Symptomatic Lumbar Disc Degeneration

The NECK trial: Effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blinded randomized controlled trial

BACKGROUNDMotion preserving anterior cervical disc arthroplasty (ACDA) in patients with cervical radiculopathy was introduced to prevent symptomatic adjacent disc degeneration as compared with anterior cervical discectomy and fusion (ACDF). Prior reports suggest that ACDF is not more effective than anterior cervical discectomy (ACD) alone for the treatment of cervical radiculopathy. PURPOSETo evaluate whether patients with cervical radiculopathy due to a herniated disc benefit more from undergoing ACDA, ACDF, or ACD in terms of clinical outcome measured by the neck disability index (NDI). STUDY DESIGNDouble-blinded randomized controlled trial. METHODSOne hundred-nine patients with one level herniated disc were randomized to one of the following treatments: ACDA, ACDF with intervertebral cage, ACD without fusion. Clinical and radiological outcome was measured by NDI, Visual Analogue Scale (VAS) neck pain, VAS arm pain, SF36, EQ-5D, patients’ self-reported perceived recovery, radiographic cervical curvature, and adjacent segment degeneration parameters at baseline and until two years after surgery. BBraun Medical paid €298.837 to cover the costs for research nurses. RESULTSThe NDI declined from 41 to 47 points at baseline to 19 ± 15 in the ACD group, 19 ± 18 in the ACDF group, and 20 ± 22 in the ACDA group after surgery (p=.929). VAS arm and neck pain declined to half its baseline value and decreased below the critical value of 40 mm. Quality of life, measured by the EQ-5D, increased in all three groups. Adjacent segment degeneration parameters were comparable in all three groups as well. No statistical differences were demonstrated between the treatment groups. CONCLUSIONSThe hypothesis that ACDA would lead to superior clinical outcome in comparison to ACDF or ACD could not be confirmed during a 2-year follow-up time period. Single level ACD without implanting an intervertebral device may be a reasonable alternative to ACDF or ACDA.

319. Is Chronic Vertebral Disk Infection With Low Virulence Bacteria a Common Cause of Back Pain?

BackgroundIn 1998 Modic described changes in vertebral body marrow with magnetic resonance imaging, and related those changes to pathological findings in the adjacent disc that were similar to those seen in bacterial discitis. As early as 2001 Stirling noted a relationship between sciatica and Propionibacterium acnes cultured from disc space material obtained at discectomy. In 2013 Albert demonstrated that Modic type I changes, strongly associated with low back pain, responded to 100 days of antibiotic treatment in a large randomized controlled trial. The findings were controversial, and we proposed that modern microdiscectomy techniques would minimize the potential for contamination with the common skin bacteria reported most often in previous studies.MethodsWe performed a prospective uncontrolled case series of patients undergoing microdiscectomy for symptomatic disc degeneration or herniation. Subjects were greater than 18 years old, nonpregnant, with chronic low back pain, and meeting standard criteria for microdiscectomy. After giving informed consent, data were extracted from existing medical records and cultures of disc material were obtained at discectomy prior to perioperative prophylactic antibiotics, and were processed by standard methodology for aerobic, anaerobic and acid-fast bacterial growth.ResultsThirty-three patients were included in the study, mean age 52.6 (SE 3.1), 19 females and 14 males. The study was terminated after these 33 cases when only one aerobic culture was positive from one male subject, and this for a minimal growth of Staphylococcus epidermidis.ConclusionIf a significant fraction of chronic low back pain is indeed caused by chronic infection with low-virulence bacteria, this would be a paradigm shift in the evaluation and management of a common and often debilitating condition. In our study of patients with chronic low back pain undergoing microdiscectomy, we did not find evidence of chronic low-virulence bacterial infection.Disclosures All authors: No reported disclosures.

Thursday, September 27, 2018 3:35 PM–5:05 PM Section on Motion Technology Abstract Presentations: 140. Impact of range of motion on progression of adjacent segment disease: disc versus disc

BACKGROUND CONTEXT Previously, long term outcomes investigating range of motion (ROM) preservation over time between an investigational arm mobile core device (MCD) and control arm controlled core device (CCD) have been reported. No studies have looked at the relationship of ROM to the progression of adjacent segment disease (ASD) between disc prostheses. PURPOSE The primary purpose of this study was to compare changes in ROM between two lumbar TDRs. Secondarily the relationship between incremental degrees of motion maintained to progression of ASD was investigated. STUDY DESIGN/SETTING This is a post hoc analysis of data collected from a large, prospective, multicenter clinical trial. PATIENT SAMPLE As part of the clinical trial, 175 patients received either the investigational MCD or the CCD control device. All patients were treated for symptomatic disc degeneration unresponsive to minimum 6 months nonoperative care. OUTCOME MEASURES The primary outcome measure was ROM and the progression of ASD. METHODS ROM was evaluated through radiographs at the index level at baseline (preoperative) and at 5-years postoperative. At 5-years, a change in adjacent ASD was defined as >1 grade increase. RESULTS Results: At baseline both MCD and CCD patients had similar index level ROM of 6.6° and 6.2°, respectively (p=.6). At 5-years postoperative patients with a CCD had an average ROM of 4.2° which represented a statistically significant reduction from baseline (p=.02). Patients with a MCD had an average ROM of 6.1° at 5-years which was similar to the baseline ROM (p=.4). In a comparison between groups, patients with a CCD had 31% less ROM at 5-years postoperative than patients with a MCD (p=.02). In this same patient group the protective effect of ROM on progression of ASD was measured. For every degree of ROM preserved, the likelihood of the progression of ASD at the superior level declined consistently. Patients receiving an MCD were less likely to have progression of ASD at 5-years than patients who received a CCD (8.8% vs. 19%, p=.05). CONCLUSIONS These data show that there may be a relationship between the maintenance of motion over time and the progression of ASD. While additional analysis is warranted, a novel new MCD may be better at maintaining ROM and thus better at delaying ASD than the earlier generation CCD. FDA DEVICE/DRUG STATUS aclivL, ProDisc-L and Charite are approved for this indication.

Wednesday, September 26, 2018 3:35 PM – 5:05 PM Preserving Spinal Motion: 90. Seven-year outcomes of lumbar total disc replacement systems on patient lifestyle and quality of life

BACKGROUND CONTEXT Degenerative disc disease (DDD) is a potentially debilitating condition resulting in pain and decreased functional ability in patients. Lumbar total disc replacement (TDR) helps to alleviate this pain and dysfunction and potentially allows for a return to preinjury activities. PURPOSE The purpose of this study was to evaluate quality of life (QoL) at 7 years post-TDR compared to preoperative status. STUDY DESIGN/SETTING Data for the analysis were collected from a Food and Drug Administration regulated prospective, randomized study conducted at multiple sites. PATIENT SAMPLE Patients were randomly allocated (2:1) to treatment with an investigational TDR device (activL, n=218) or FDA-approved control TDR devices (ProDisc-L, n=65 or Charite, n=41). All were treated for single-level symptomatic disc degeneration unresponsive to at least 6 months of nonoperative care. OUTCOME MEASURES The primary outcome measure was the SF-36. Secondary evaluations included work status, patient satisfaction, and use of pain medication. METHODS Follow-up occurred at 6 weeks and 3, 6, 12 and 24 months and every year thereafter up to 7-years postsurgery. Data from the preoperative baseline and the 7 year follow-up are reported. RESULTS At 7 years, 77% and 73% of activL and control patients (respectively) showed improvements in mental component scores (MCS) for the SF-36 compared to baseline. Similarly, physical component scores (PCS) improved for 92% and 86% of activL and control patients at 7 years postsurgery. Clinically significant improvements in MCS and PCS scores (≥15% improvement from baseline) occurred in approximately 44% (MCS) and 62% (PCS) of all TDR patients combined at 6 weeks, increased to 61% (MCS) and 80% (PCS) at 12 months and remained constant through to 7 years. Approximately 53% of all TDR patients returned to work without restriction by 12 months, which increased to 64% and 54% for activL and control patients at 7 years. Most ActivL patients were able to return to the same workload as before their back injury at 7 years, whereas more control patients worked in sedentary jobs at 7 years than before their back injury. Patient satisfaction at 7 years postsurgery showed 97% of all TDR patients were “very satisfied” or “somewhat satisfied” with the procedure, and 93% indicated that they would “definitely” or “probably” undergo the procedure again for the same condition. 97% of ActivL and 89% of control patients indicated that the treatment was “very” or “moderately” effective in eliminating their symptoms. Decreases in the proportion of patients utilizing pain medication were noted in both groups. At baseline, 90% and 92% of ActivL and control patients were using medications for pain control, which decreased by half by 7 years. CONCLUSIONS The results of this analysis indicate that lumbar TDR is effective at helping to improve patient's quality of life, potentially facilitating return to work and reducing pain medication usage. FDA DEVICE/DRUG STATUS activL, ProDisc-L, Charite artificial discs (Approved for this indication)

Degenerative Lumbar Spine Disease: Estimating Global Incidence and Worldwide Volume.

Study Design:Meta-analysis-based calculation.Objectives:Lumbar degenerative spine disease (DSD) is a common cause of disability, yet a reliable measure of its global burden does not exist. We sought to quantify the incidence of lumbar DSD to determine the overall worldwide burden of symptomatic lumbar DSD across World Health Organization regions and World Bank income groups.Methods:We used a meta-analysis to create a single proportion of cases of DSD in patients with low back pain (LBP). Using this information in conjunction with LBP incidence rates, we calculated the global incidence of individuals who have DSD and LBP (ie, their DSD has neurosurgical relevance) based on the Global Burden of Disease 2015 database.Results:We found that 266 million individuals (3.63%) worldwide have DSD and LBP each year; the highest and lowest estimated incidences were found in Europe (5.7%) and Africa (2.4%), respectively. Based on population sizes, low- and middle-income countries have 4 times as many cases as high-income countries. Thirty-nine million individuals (0.53%) worldwide were found to have spondylolisthesis, 403 million (5.5%) individuals worldwide with symptomatic disc degeneration, and 103 million (1.41%) individuals worldwide with spinal stenosis annually.Conclusions:A total of 266 million individuals (3.63%) worldwide were found to have DSD and LBP annually. Significantly, data quality is higher in high-income countries, making overall quantification in low- and middle-income countries less complete. A global effort to address degenerative conditions of the lumbar spine in regions with high demand is important to reduce disability.

A comparison of zero-profile anchored spacer (ROI-C) and plate fixation in 2-level noncontiguous anterior cervical discectomy and fusion- a retrospective study

BackgroundAnterior cervical discectomy and fusion (ACDF) is the classic surgical treatment for symptomatic cervical degenerative disc disease (CDDD). However, there is controversy over the best surgical management in patients with two noncontiguous symptomatic levels of CDDD.MethodsFrom April 2011 to May 2014, 44 patients with two noncontiguous symptomatic levels of CDDD underwent skip-level ACDFs. In Group NoPlate, 23 cases underwent 2 noncontiguous levels of ACDF using zero-profile anchored spacer; and in Group Plate, 21 cases underwent 2 noncontiguous levels of ACDF using cages and plates. Operation-related paraeters for each group were recorded and compared. Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) scores at preoperation and postoperation were compared with at least a 2-year follow-up. Cervical lordosis was analyzed before surgery, 1 month after surgery, 3 months after surgery, and at final follow-up.ResultsMean follow-up was 35.4 ± 6.5 (range 24–48) months. Significant improvement on the JOA, NDI scores and cervical lordosis was noted in each group (p < 0.05), and there were no significant difference in terms of JOA, NDI scores, cervical lordosis and fusion rate between the two groups (P > 0.05). The operation time in Group NoPlate was significantly shorter than in Group Plate (p < 0.05), and the incidence of dysphagia and adjacent segment degeneration in Group NoPlate was significantly lower than in Group Plate (p < 0.05).ConclusionsROI-C and cages with plate fixation were both effective in two-level noncontiguous ACDF, and there were no significant difference in clinical outcomes, fusion rate, and cervical lordosis. However, ROI-C was associated with shorter operative time, lower incidence of dysphagia and adjacent segment degeneration.

Progression of Adjacent-level Degeneration After Lumbar Total Disc Replacement: Results of a Post-hoc Analysis of Patients With Available Radiographs From a Prospective Study With 5-year Follow-up.

Post-hoc analysis of 5-year follow-up data from a randomized, multicenter trial. The aim of this study was to investigate the incidence of progression in radiographic adjacent-level degeneration (ΔALD) from preoperative assessment to 5 years after total disc replacement (TDR) and the relationship of these changes with range of motion and clinical adjacent-level disease. A secondary objective was to compare adjacent-level degeneration (ALD) outcomes between TDR and fusion. Fusion is associated with high rates of ALD in symptomatic lumbar disc degeneration. TDR may reduce this risk. In total, 175 patients with single-level, symptomatic, lumbar disc degeneration who had received activL or ProDisc-L and had a preoperative and 5-year postoperative radiograph available were included. Over 5-year follow-up, ΔALD was defined as an increase in ALD of ≥1 grade and clinical ALD was defined as surgical treatment at the level adjacent to an index TDR. Matching-adjusted indirect comparisons were conducted to compare ALD outcomes after TDR (current trial) with those after fusion (published trial). At 5-year follow-up, 9.7% (17/175) of TDR patients had ΔALD at the superior level. In patients with preoperative ALD at the superior level, most (88% [23/26]) showed no radiographic progression over 5 years. The rate of clinical ALD was 2.3% (4/175) and none of these patients had ALD at baseline. For each degree of range of motion gained at the TDR level, there was a consistent decrease in the percentage of patients with ΔALD. After matching and adjustment of baseline characteristics, TDR had a significantly lower likelihood of ΔALD than fusion (odds ratio 0.32; 95% confidence interval 0.13, 0.76). The rates of ΔALD and clinical ALD in this TDR population were similar to those previously reported in the literature for TDR at 5-year follow-up. TDR had a significantly lower rate of ΔALD than fusion. 3.

The Incidence and Association of Mental Depression with Symptomatic Lumbar Degenerative Disc Disease and Treatment Outcome

Study Design: Prospective analytical study. Objectives: The aim was to determine the association between mental depression and symptomatic Lumbar Degenerative Disc Disease (LDDD) in patients with no previous background of mental disorder. We also aimed at determining the incidence of mental depressions in patients with LDDD and the effects of the treatment on the mental depression. Methodology: One hundred and sixty patients with no prior history of mental or behavioral disorders who presented with low back pains arising from LDDD and met inclusion criteria were studied. The clinical findings and Depression Screening Test pro-forma were completed for each. The extracted information was analyzed using Statistical Package for Social Science (SPSS) version 24.0. The statistical significance was set at P < 0.05. Results: One hundred and fifty-three patients completed the study, with a male to female ratio of 1:1.5 and the mean age of the patients was 48.5 years. The marital status was 4.4% single, 86.9% married, 3.8% divorce/separate and 5% widow/widower. Their levels of education were: no formal education (10.00%), primary school level (8.10%), secondary level (27.50%) and Tertiary level (54.40%). Conclusions: This study showed the incidence of mental depression in 32% of the patients with LDDD. We also noted a statistically significant relationship between symptomatic LDDD and level of mental depression with significant improvement in the level of depression at 6th month after treatment. Hence, assessment of the patients’ mental health is important in the management of LDDD.

Instrumented Posterolateral Spinal Arthrodesis as an Effective Treatment for Single Level Symptomatic Vacuum Lumbar Disc Degeneration in Elderly Patients

Background Data: Lumbar intervertebral disc vacuum phenomenon is an advanced form of spinal destabilizing degenerative changes. It is common in the elderly population and can cause refractory low back pain.Purpose: To evaluate the efficacy and safety of instrumented posterolateral fusion in treating symptomatic lumbar single level vacuum phenomenon in elderly population.Study Design: Retrospective descriptive clinical case series.Patients and Methods: Twenty-one patients (16 males & 5 females), aging more than 65 years, had all their files reviewed. They were operated by instrumented posterolateral fusion to treat chronic refractory low back pain due to single level intervertebral lumbar disc vacuum phenomenon. They underwent operation after failure of adequate 6 months conservative management. Age, gender, symptoms duration, spinal level affected, surgery duration, length of hospital stay, intra or post-operative complications, visual analogue scale VAS for pain, and Lenke’s graft fusion classification at 1, 3 & 6 months postoperatively were all recorded.Results: The results of this study showed the most affected level was L4/L5, mean age was 73±7 years, mean symptoms duration was 11 years, mean surgery duration was 137±29 minutes, and mean VAS for preoperative-postoperative pain improvement was 5.9±1.2. Good fusion (Lenke’s grades A & B) was reported in 81% of patients. No major intra or postoperative complications.Conclusion: Instrumented posterolateral fusion in elderly population patients with mono-segmental advanced disc degeneration may yield clinical outcome with low operative risk. (2017ESJ150)

P157 - Asia-Pacific Multicenter, Prospective, Randomized, Trial Comparing Arthroplasty vs Anterior Cervical Discectomy and Fusion in the Treatment of Symptomatic Cervical Disc Degeneration

P157 - Asia-Pacific Multicenter, Prospective, Randomized, Trial Comparing Arthroplasty vs Anterior Cervical Discectomy and Fusion in the Treatment of Symptomatic Cervical Disc Degeneration

Long-term clinical results following Charite III lumbar total disc replacement

Background ContextLumbar total disc replacement (TDR) operation represents an alternative to lumbar fusion for the treatment of symptomatic lumbar intervertebral disc degeneration and has gained increasing attention in recent years. PurposeThis study aimed to assess clinical outcomes in a cohort of patients with TDR and the long-term survival rate of the prostheses. Study DesignThis is a retrospective, single-center clinical study. Patient SampleThe sample comprised 30 patients, giving a total of 35 prostheses after an average follow-up (FU) of 15.2 years following TDR, which was performed for the treatment of lumbar degenerative disc disease. Outcome MeasuresClinical evaluation included visual analog scale (VAS) and the Oswestry Disability Index (ODI). Radiological parameters of intervertebral disc height (IDH), range of motion (ROM), lumbar lordosis, lumbar scoliosis, and prosthesis position were evaluated in surgical and adjacent levels. Complications and re-operation rates were also assessed. MethodsClinical evaluation and radiological parameters were evaluated preoperatively and at final FU. All data were collected by members of our department, including research assistants and nurses who were not involved in the decision making of this study. ResultsThirty of the 35 patients participated in the final FU. The cumulative survival rate of the prosthesis at a mean FU of 15.4 years was 100%. The clinical success rate was 93.3%. The VAS and ODI scores at final FU were significantly lower than preoperatively (p<.001). The average ROM of the operated and superior adjacent segment decreased significantly at the final FU, whereas the inferior adjacent segment was not affected. The IDH of all surgical and adjacent levels were well maintained at the final FU. Ten patients had a lumbar scoliosis >3° and the mean angle was 8.5°, of which 7 had left convex curvature. Three prostheses were offset more than 5 mm from the midline on the coronal plane. Four prostheses showed subsidence. Twenty-six operative segments and five adjacent segments showed heterotopic ossification. Two patients of the total 35-patient cohort underwent a secondary operation. ConclusionsSatisfactory clinical results and good prosthesis survival can be achieved in the long term. Lumbar TDR surgeries also have the potential to reduce the incidence of adjacent segment disease.

An international consensus on the appropriate evaluation and treatment for adults with spinal deformity.

Evaluation and surgical management for adult spinal deformity (ASD) patients varies between health care providers. The purpose of this study is to identify appropriateness of specific approaches and management strategies for the treatment of ASD. From January to July 2015, the AOSpine Knowledge Deformity Forum performed a modified Delphi survey where 53 experienced deformity surgeons from 24 countries, rated the appropriateness of management strategies for multiple ASD clinical scenarios. Four rounds were performed: three surveys and a face-to-face meeting. Consensus was achieved with ≥70% agreement. Appropriate surgical goals are improvement of function, pain, and neural symptoms. Appropriate preoperative patient evaluation includes recording information on history and comorbidities, and radiographic workup, including long standing films and MRI for all patients. Preoperative pulmonary and cardiac testing and DEXA scan is appropriate for at-risk patients. Intraoperatively, appropriate surgical strategies include long fusions with deformity correction for patients with large deformity and sagittal imbalance, and pelvic fixation for multilevel fusions with large curves, sagittal imbalance, and osteoporosis. Decompression alone is inappropriate in patients with large curves, sagittal imbalance, and progressive deformity. It is inappropriate to fuse to L5 in patients with symptomatic disk degeneration at L5-S1. These results provide guidance for informed decision-making in the evaluation and management of ASD. Appropriate care for ASD, a very diverse spectrum of disease, must be responsive to patient preference and values, and considerations of the care provider, and the healthcare system. A monolithic approach to care should be avoided.

Selective Anterior Thoracolumbar Fusion in Adolescent Idiopathic Scoliosis: Long-Term Results After 17-Year Follow-Up.

Prospectively updated long-term data and retrospective case series analysis. To report the long-term results of selective anterior instrumented thoracolumbar (ThL) fusion in adolescent idiopathic scoliosis (AIS). The results of anterior selective fusion in AIS have been reported up to 2 and 5 years follow-up. However, there is a lack of evidence of long-term results of this surgical approach. Forty-two consecutive patients with main thoracolumbar/lumbar AIS who had undergone surgery for a selective anterior ThL instrumented fusion with more than 12 years of follow-up met inclusion criteria. Preoperative, postoperative (1-yr), and final updated radiographic parameters were recorded. Final ODI and SRS-22 questionnaires were evaluated. Thirty-five patients were finally recruited (5 were lost and 2 refused). The mean age at surgery was 16.6 years. The mean final follow-up was 17.3 years (12-24 yr).The ThL preoperative Cobb was 49.5° ± 9, obtaining a postoperative correction of 79%±13 and final correction of 72% ± 18. The preoperative thoracic curve (31.4° ± 14.2) obtained a spontaneous postoperative correction to 18.4° ± 11.9, maintained at final follow-up (17.8° ± 10.8). Apical vertebral rotation improved from 25.8° ± 7.8 to 9.2° ± 5.5 and finally to 8° ± 5.2 (P = 0.001). Sagittal parameters (T5-T12 = 27.2° and L1-S1=56.9°) did not change significantly postoperatively nor by final follow-up. Coronal balance improved from 2.4 cm to 1.6 cm postoperatively and 0.8 cm at final follow-up (P = 0.006). The disc angulation below the last instrumented vertebra improved with follow-up from 7.6° to 5.7° (P = 0.012).There were no revision surgeries or infections. One patient showed a symptomatic lower disc degeneration requiring lumbar pain surgery. Final SRS-22 global score was 4.3/5. The final ODI scored 6/100. In the long term, selective anterior thoracolumbar instrumentation with a single solid rod in AIS maintained good corrections on the three planes with no major complications or infections, no revision surgeries, and with satisfactory final functional and clinical outcomes. 4.

Influence of rabbit notochordal cells on symptomatic intervertebral disc degeneration: anti-angiogenic capacity on human endothelial cell proliferation under hypoxia.

Symptomatic degenerative disc disease (DDD) is associated with neovascularization and nerve ingrowth into intervertebral discs (IVDs). Notochordal cells (NCs) are key cells that may lead to regeneration of IVDs. However, their activities under conditions of hypoxia, the real environment of IVD, are not well known. We hypothesized that NCs may inhibit neovascularization by interacting with endothelial cells (ECs) under hypoxia. Human IVDs were isolated and cultured to produce nucleus pulposus (NP) cell conditioned medium (NPCM). Immortalized human microvascular ECs were cultured in NPCM with notochordal cell-rich rabbit nucleus pulposus cells (rNC) under hypoxia. Vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), and interleukin-8 (IL-8) were analyzed by ELISA. Focal adhesion kinase (FAK), filamentous actin (F-actin), and platelet-derived growth factor (PDGF) were evaluated to investigate EC activity. Wound-healing migration assays were performed to examine EC migration. The VEGF level of EC cells cultured in NPCM was significantly higher under hypoxia compared to normoxia. VEGF expression was significantly decreased, and FAK, F-actin, PDGF expression were inhibited when ECs were cocultured with rNCs under hypoxia. ECs cocultured with rNC in NPCM showed significantly decreased migratory activity compared to those without rNC under hypoxia. The angiogenic capacity of ECs was significantly inhibited by NCs under hypoxia via a VEGF-related pathway. Our results suggest that NCs may play a key role in the development of IVDs by inhibiting vascular growth within the disc, and this may be a promising novel therapeutic strategy for targeting vascular ingrowth in symptomatic DDD.

Treatment of Symptomatic Lumbar Disc Degeneration with the VariLift-L Interbody Fusion System: Retrospective Review of 470 Cases.

Many first generation stand-alone fusion cages required endplate decortication and surgical impaction during the procedure resulting in segmental subsidence, implant migration and loss of lordosis postoperatively. The primary objective of this study was to evaluate radiographically, in a large series of patients, whether engineering and design modifications incorporated in a specific stand-alone, expandable interbody fusion device (VariLift(®)-L) adequately addressed previously recognized deficiencies of stand-alone interbody cages. In this retrospective chart review of 470 patients (642 treated levels), we evaluated radiographic evidence of fusion, subsidence and migration following a one- or two-level PLIF procedure utilizing this stand-alone expandable interbody fusion device. A secondary objective was to corroborate the low morbidity and symptomatic improvements achieved with previous interbody cage devices used to treat symptomatic disc degeneration. The average postoperative followup was 3.9 ± 1.8 years and a solid fusion rate of 94% was achieved among patients with ≥ 9 months of radiographic followup. Subsidence > 3 mm was noted at 10 levels with no cases of device migration. Composite back pain severity scores improved from 8.5 ± 1.5 preoperatively to 0.8 ± 1.5 at final followup (p<0.001) and 94% of patients met or exceeded the minimal clinical important difference of 3.8 points. Eighteen patients required reoperation following the index procedure; 16 of these patients were treated for adjacent segment disease. The VariLift-L device has excellent clinical and technical performance characteristics, providing adequate stabilization of the anterior column without the need for supplemental posterior instrumentation. Level of Evidence IV. IRB Approval: Expedited Federal Register Categories 5& 7: Methodist IRB 3/30/2011; Informed Consent statement: retrospective data collection, patients signed consent forms allowing for data to be used for research. This stand-alone expandable fusion device produced high fusion rates, a low incidence of reoperation and effective symptom relief in a "real world" setting among a large group of patients with refractory symptomatic disc degeneration.

Hyaluronic Acid Based Hydrogels Attenuate Inflammatory Receptors and Neurotrophins in Interleukin-1β Induced Inflammation Model of Nucleus Pulposus Cells.

Inflammation plays an important role in symptomatic intervertebral disc degeneration and is associated with the production of neurotrophins in sensitizing innervation into the disc. The use of high molecular weight (HMw) hyaluronic acid (HA) hydrogels offers a potential therapeutic biomaterial for nucleus pulposus (NP) regeneration as it exerts an anti-inflammatory effect and provides a microenvironment that is more suitable for NP. Therefore, it was hypothesized that cross-linked HMw HA hydrogels modulate the inflammatory receptor of IL-1R1, MyD88 and neurotrophin expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in an in vitro inflammation model of NP. HA cross-linking was optimized using various concentrations of 4-arm PEG-amine by determination of free carboxyl groups of HA and unreacted free amine groups of PEG-amine. The optimally cross-linked HA hydrogels were characterized for hydrolytic stability, enzymatic degradation and cytotoxicity on NP cells. The therapeutic effect of HA hydrogels was further investigated in IL-1β induced inflammation on NP cell cultures and the mechanism of HA by examining the expression of cell surface receptor of CD44. Hydrogel was optimally cross-linked at 75 mM PEG, stable in phosphate buffered saline, and showed greater than 40% resistance to enzymatic degradation. No cytotoxic effect of NP cells was observed in the presence of hydrogels for 1, 3, and 7 days. IL-1R1 and MyD88 were significantly suppressed. Additionally, NGF and BDNF mRNA were down-regulated after treatment with cross-linked HA hydrogel. Possible protective mechanism of HA is shown by high expression of CD44 receptor of NP cells after HA treatment in which suggest the binding of HA to CD44 receptor and prevent NP cells from further undergoing inflammation. These results indicate that optimally stabilized cross-linked HMw HA hydrogel has a therapeutic effect in response to inflammation-associated pain and becomes an ideal matrices hydrogel for NP regeneration.

Comparison of One-Level versus Two-Level Anterior Cervical Discectomy and Fusion: Clinical and Radiograph Follow-Up at 60 Months in Patients Serving as Control Groups in Randomized Trials

Introduction Anterior cervical discectomy and fusion (ACDF) has become a standard surgical option for patients with neck pain or radicular symptoms who failed nonoperative care. Although outcomes are generally good in patients undergoing single-level procedures, results for two-level cases have been less consistent. The purpose of this study was to compare results of single level. ACDF with those of two-level ACDF in patients serving as control groups in a total disc replacement trial. Materials and Methods This was a post hoc analysis of data from two control arms of the Food and Drug Administration regulated trial for the Mobi-C artificial disc. As the control treatment, ACDF with allograft and anterior plate was performed at one level in 81 patients and at two levels in 105 patients for the treatment of symptomatic disc degeneration. The study selection criteria, surgical technique, and outcome measures were identical with the only exception being pathology and surgery at one or two levels. Radiographic assessments were performed by an independent laboratory. In the two-level group, both the levels had to be radiographically fused for the patient to be considered fused. Results Gender, age, body mass index, and 5-year follow-up rates (∼ 75%) were similar in the two groups. Operative time and blood loss were significantly less in the single-level cases ( p &lt; 0.05). Preoperative Neck Disability Index (NDI) scores were similar in the two groups and both improved significantly by 6 weeks and remained significantly improved through follow-up ( p &lt; 0.05). The scores improved by approximately 50% in both the groups. Scores in the single-level group were significantly less at several time points. Visual analog scale scores assessing neck and arm pain followed a pattern similar to NDI, with significant improvement in both groups at 6 weeks' postoperative being maintained through 5 years, with few significant differences between groups. Both groups had significant improvements in SF-12 PCS and MCS scores by 6 months which were maintained throughout follow-up. The single-level group had significantly greater PCS scores at 12-month follow-up and thereafter ( p &lt; 0.05). There were no significant differences in MCS scores between the groups. At 5 years, there was no significant difference in index level secondary surgery rates (11.1 vs. 16.2%). At 60 months, the one-level group fusion rate was 93.3versus 86.1% in the two-level group (not statistically significant). Fusion rates were significantly greater in the one-level group at 6 and 12 months. There was a trend (not statistically significant) for greater adjacent segment degeneration at the inferior segment in the two-level group. Conclusion The design of the disc replacement study created a unique opportunity to compare one- versus two-level ACDF control groups, which used the same inclusion/exclusion criteria and evaluations. Single-level ACDF outcomes were better on a few measures. However, patients in both groups had significantly improved scores on various outcome measures early after surgery and these improvements were maintained throughout 5-year follow-up.

Comparison of Clinical Outcomes for Anterior versus 360 Fusion at the Fusion Level of Lumbar Hybrid Surgery

Introduction Options for treating two-level symptomatic disc degeneration after failure of nonoperative care includes fusion, total disc replacement (TDR), or a hybrid with fusion at one level and TDR at the other. Often the hybrid procedure involved an instrumented 360 fusion. However, the option for a standalone ALIF in a hybrid has rarely been addressed. The purpose of this study was to compare the outcomes of hybrid TDR/fusion surgery for ALIF versus 360 at the fusion level. Methods The study group included 135 patients undergoing hybrid surgery using TDR at one level and either ALIF ( n = 83) or instrumented 360 fusion ( n = 52) at the adjacent segment. The majority of cases were performed with TDR at L4–L5 and fusion at L5–S1. Only patients who had surgery at least 12 months before this study were included. The mean length of follow-up was similar in the two groups (∼24 months in both groups). Outcome measures included Oswestry Disability Index (ODI), visual analog scales (VAS) assessing back and leg pain, and reoperations. Results The mean operative blood loss was significantly less in the hybrid/ALIF group compared with the hybrid/360 group (71.7 vs. 142.1 mL; p &lt; 0.01). The mean ODI scores before surgery were approximately 46 in both the groups. The scores improved significantly in both groups to the means of about 30 ( p &lt; 0.01) with no significant difference between the two groups ( p &gt; 0.40). Mean VAS back and leg pain scores also improved significantly in both groups with no significant differences between groups ( Fig. 1 ). [Figure: see text] The reoperation rate was significantly greater in the hybrid/360 group than in the hybrid/ALIF group (23.1 vs. 3.6%; p &lt; 0.01). Reoperations in the hybrid/360 group included six reoperations for removal of painful posterior instrumentation, one to treat a wound infection, one decompression of the fusion level of the hybrid, three were for treatment of a symptomatic adjacent segment, and two were due to TDR malpositioning or displacement. Hybrid/ALIF reoperations included two patients undergoing decompression for stenosis and one underwent fusion two levels above the index surgery. Discussion This study found that the outcomes are similar between hybrids performed with ALIF versus 360 fusion adjacent to the TDR level with the exceptions of a significantly greater reoperation rate and mean blood loss in the hybrid/360 group. These results support that unless there is a defined indication for the posterior procedure, standalone ALIF is a viable option for lumbar hybrid surgery.