Five-Year Longitudinal Follow-up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Long-term outcomes following intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 5-year treatment arm results from a prospective randomized double-blind sham-controlled multi-center study.

BACKGROUND: Damaged or degenerated vertebral endplates are a significant cause of vertebrogenic chronic low back pain (CLBP). Modic changes are one objective MRI biomarker for these patients. Prior data from the treatment arm of a sham-controlled, RCT showed maintenance of clinical improvements at 2 years following ablation of the basivertebral nerve (BVN). This study reports 5-year clinical outcomes. METHODS: In total, 117 US patients were treated successfully with BVN ablation. Patient-reported outcomes of ODI, VAS, postablation treatments, and patient satisfaction were collected at a minimum of 5-years following BVN ablation. Primary outcome was mean change in ODI. Comparisons between the postablation and baseline values were made using an analysis of covariance with alpha 0.05. RESULTS: Of the 117 US treated patients 100 (85%) were available for review with a mean follow-up of 6.4 years (5.4-7.8 years). Mean ODI score improved from 42.81 to 16.86 at 5-year follow-up, a reduction of 25.95 points (p < 0.001). Mean reduction in VAS pain score was 4.38 points (baseline of 6.74, p < 0.001). In total, 66% of patients reported a > 50% reduction in pain, 47% reported a > 75% reduction in pain, and 34% of patients reported complete pain resolution. Composite responder rate using thresholds of ≥ 15-point ODI and ≥ 2-point VAS for function and pain at 5 years was 75%. CONCLUSION: CLBP patients treated with BVN ablation exhibit sustained clinical improvements in function and pain with high responder rates at a mean of 6.4 years following treatment. BVN ablation is a durable, minimally invasive treatment for vertebrogenic CLBP.

Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study.

PURPOSE: To evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP. METHODS: A total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47 years (range 25-69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2 weeks, 6 weeks and 3, 6 and 12 months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3 months. RESULTS: At 3 months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (p = 0.019, per-protocol population). A responder analysis based on ODI decrease ≥ 10 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3 months. CONCLUSION: Patients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3 months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain. These slides can be retrieved under Electronic Supplementary Material.

Degenerative Spondylolisthesis.

Degenerative spondylolisthesis (DS) is one of the more commonly encountered spine conditions. The diagnosis of DS has changed little in the last 30 years. However, there has been an evolution in the treatment of this disease entity. There have been several landmark papers that helped govern our treatment. These helped serve as the basis for the treatment arms of the Spine Patient Outcomes Research Trial (SPORT), which offers the highest quality evidence to date. Although few would argue that the fusion of the diseased segment appears to offer the best and most durable results, treatment of this disease is best tailored to the individual. Fusion may offer the best results in the young active patient, but the same results may never become evident in the medically infirm patient. Laminectomy or unilateral laminoforaminotomy still plays a role in disease treatment. This review will focus on the diagnosis and the treatment of DS as well as discuss the author's preferred treatment of this disease.

Minimally invasive spine surgery in the treatment of thoracolumbar and lumbar spine trauma.

Thoracolumbar and lumbar trauma account for the majority of traumatic spinal injuries. The mainstay of current treatments is still nonoperative therapy with bracing. Classic treatment algorithms reserved absolute surgical intervention for spinal trauma patients with neurological compromise or instability. Relative indications included incapacitating pain and obesity/body habitus making brace therapy ineffective. In the past decade, minimally invasive surgical (MIS) techniques for spine surgery have been increasingly used for degenerative conditions. These same minimally invasive techniques have seen increased use in trauma patients. The goal of minimally invasive surgery is to decrease surgical morbidity through decreased soft-tissue dissection while providing the same structural stability afforded by classic open techniques. These minimally invasive techniques involve percutaneous posterior pedicle fixation, vertebral body augmentation, and utilization of endoscopic and thoracoscopic techniques. While MIS techniques are somewhat in their infancy, an increasing number of studies are reporting good clinical and radiographic outcomes with these MIS techniques. However, the literature is still lacking high-quality evidence comparing these newer techniques to classic open treatments. This article reviews the relevant literature regarding minimally invasive spine surgery in the treatment of thoracolumbar and lumbar trauma.

Cement augmentation in vertebral burst fractures.

As a result of axial compression, traumatic vertebral burst fractures disrupt the anterior column, leading to segmental instability and cord compression. In situations with diminished anterior column support, pedicle screw fixation alone may lead to delayed kyphosis, nonunion, and hardware failure. Vertebroplasty and kyphoplasty (balloon-assisted vertebroplasty) have been used in an effort to provide anterior column support in traumatic burst fractures. Cited advantages are providing immediate stability, improving pain, and reducing hardware malfunction. When used in isolation or in combination with posterior instrumentation, these techniques theoretically allow for improved fracture reduction and maintenance of spinal alignment while avoiding the complications and morbidity of anterior approaches. Complications associated with cement use (leakage, systemic effects) are similar to those seen in the treatment of osteoporotic compression fractures; however, extreme caution must be used in fractures with a disrupted posterior wall.

Association of Poor Bone Quality with Pseudarthrosis and Poor Clinical Outcomes in Single-Level Instrumented Lumbar Arthrodesis Using Local Autologous Bone Graft.

INTRODUCTION: Although osteoporosis and low bone mineral density is thought to lead to poor fusion outcomes, few studies have adequately addressed the correlation, and they were limited by small sample size at a single institution. METHODS: We completed a secondary analysis of 182 patients enrolled at 26 spine centers across the United States in the EXO-SPINE FDA-approved clinical trial with 12-month CT-based fusion status determined by two independent, blinded radiologists. Using previously described CT-based techniques, we measured local and global Hounsfield units (HU) and examined the relationship with radiographic and clinical outcomes. RESULTS: CT scans were available for review from 95 patients, with a mean age of 56.2 years and mean global density of 153.0 HU. No relationship was observed between HU and radiographic fusion status or clinical outcomes. Although 12% of patients had lumbar vertebral body HU measurements consistent with osteoporosis, this classification had no relation with fusion or clinical outcomes. Patients with pseudarthrosis had higher Oswestry Disability Index (22.2 vs. 16.6, P = 0.037) and back pain visual analog scale (7.0 vs. 4.9, P = 0.014) scores than patients with at least unilateral fusion at the 12-month follow-up. DISCUSSION: In this large, multicenter study, lower vertebral body HU was not associated with worse fusion status after single-level instrumented posterolateral lumbar fusion using only local autologous bone graft. However, there was an association between radiographic fusion status and clinical outcomes, validating the importance of determining predictors of successful fusion. Assessment of fusion status with CT scans yielded a much lower fusion success rate with local bone graft than previously reported and may warrant additional investigation.

Comparison of axial and anterior interbody fusions of the L5-S1 segment: a retrospective cohort analysis.

STUDY DESIGN: Retrospective, multicenter review of 96 patients who underwent L5-S1 interbody fusions through either a standard anterior retroperitoneal approach or using a novel device inserted through the presacral space (AxiaLIF) in conjunction with supplemental posterior fixation between 2002 and 2010. OBJECTIVE: To compare the radiographic fusion rates and adverse events associated with anterior lumbar interbody fusion (ALIF) and AxiaLIF techniques. SUMMARY OF BACKGROUND DATA: Interbody fusions of the lumbosacral spine are frequently performed to provide anterior column support, increase the amount of surface area for bone formation, and facilitate deformity reduction. A number of different surgical approaches have been developed for this purpose including minimally invasive techniques. MATERIALS AND METHODS: Patient information and procedural data were obtained from hospital charts. Multiplanar computed tomography images were evaluated by 2 independent observers to assess fusion success at 24 months using a 4-point grading scale. In addition to reviewing the medical records to identify any complications, all of the sites were queried regarding any device-related adverse events that may have occurred. RESULTS: According to the radiographic analysis, the arthrodesis rates recorded for the ALIF and AxiaLIF cohorts were 79% and 85%, respectively (P>0.05). The numbers and types of adverse events recorded for these procedures appeared to be similar although there was 1 serious intraoperative complication (iliac artery laceration) noted in the ALIF group. CONCLUSIONS: The radiographic success and adverse events associated with AxiaLIF appear to be similar to that observed for ALIF, suggesting that this technique represents a safe and effective method for achieving an interbody fusion across the L5-S1 disk space when utilized in conjunction with posterior fixation.

Clinical Significance of Lateral Pedicle Screw Malposition in Lumbar Spine Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Our objective was to determine whether lateral pedicle screw breach affects fusion rates and patient-reported outcomes in lumbar fusion surgery. SUMMARY OF BACKGROUND DATA: Although lateral pedicle screw malposition is considered relatively benign, few studies have focused specifically on clinical outcomes or fusion rates associated with lateral screw malposition. METHODS: Twelve-month postoperative computed tomography scans were reviewed for lateral breach, severity of breach, and fusion status. Patients with lateral breach were compared with patients with no breach. Outcome measures included Numerical Pain Rating Scale for back and leg pain, Oswestry Disability Index, and SF-36 physical function (SF-36 PF). Multivariable linear and logistic regression and were adjusted for age, procedure, level, and/or baseline pain score. RESULTS: Forty-five patients (31%) demonstrated 1 or more lateral breaches as compared with 99 patients without breach. After adjusting for baseline scores and fusion level, patients with 2 or more screw breaches experienced SF-36 PF score improvements that were 3.43 points less ( P =0.016) than patients with no lateral breach. After adjusting for baseline Numerical Pain Rating Scale, there was also a significant decrease in the odds of achieving minimally clinical important difference in back pain relief in these patients. There was no observed effect of lateral breach on the odds of successful fusion. CONCLUSIONS: The current study did not observe an association between laterally malpositioned pedicle screws and nonunion. However, results are consistent with a negative effect on SF-36 PF scores and self-reported back pain at 12 months.

Spinal cord position in adolescent idiopathic scoliosis.

BACKGROUND: The use of thoracic pedicle screws in deformity surgery provides a stable fixation system. The concept of acceptably positioned screws includes a worrisome subset of screws that perforate the medial pedicle cortex and may result in some compromise of the spinal canal. A significant higher incidence of cortical wall penetration on the concave side compared with the convex was previously found. Although several authors assumed that the spinal cord hugs the concave pedicles when the spinal deformity is scoliosis, the position of spinal cord in adolescent idiopathic scoliosis (AIS) has not been studied in depth. METHODS: We reviewed 45 patients who were candidate for operative treatment for AIS between August 2007 and October 2010 at our institution. Posteroanterior and lateral 3-ft standing preoperative radiographs of the spine were reviewed to determine: Cobb angle of the thoracic curves, apex vertebra of the curves, and end vertebras of the curves. Magnetic resonance images were retrospectively reviewed. The lateral cord space (LCS) ratio, which reflects the relative position of the spinal cord in the spinal canal, was calculated for each level with a thoracic curve. RESULTS: The average LCS for thoracic curves of >50 degrees was 2.123. The average LCS for thoracic curves of <50 degrees was 1.551 (P=0.002). The LCS for the apex vertebra was 1.699. The LCS for the upper end vertebra and lower end vertebra were 1.212, 1.225, respectively (P<0.001). There was a statistically significant difference between right thoracic curves and left thoracic curve regarding the LCS. In right thoracic curve the LCS was 1.487 (1.487+0.45) while in left thoracic curve it was 0.761 (0.761+0.17) meaning that in both curves the spinal cord moved to the concave side of the curve. CONCLUSIONS: Our study confirms that spinal cord in AIS tend to follow the appearance of the curve with its being tethered on the concave side. The spinal cord is close to the pedicle around the apex area.

Pedicle Screw-Associated Violation of the Adjacent Unfused Facet Joint: Clinical Outcomes and Fusion Rates.

STUDY DESIGN: Retrospective review of a prospective randomized trial. OBJECTIVES: To compare outcome scores and fusion rates in patients with and without pedicle screw-associated facet joint violation (FJV) after a single-level lumbar fusion. METHODS: Clinical outcomes data and computed tomography (CT) imaging were reviewed for 157 patients participating in a multicenter prospective trial. Post-operative CT scans at 12-months follow-up were examined for fusion status and FJV. Patient-reported outcomes (PROs) included Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for leg and low back pain. Chi-square test of independence was used to compare proportions between groups on categorical measures. Two-sample t-test was used to identify differences in mean patient outcome scores. Logistic regression models were performed to determine association between FJV and fusion rates. RESULTS: Of the 157 patients included, there were 18 (11.5%) with FJV (Group A) and 139 (88.5%) without FJV (Group B). Patients with FJV experienced less improvement in ODI (P = .004) and VAS back pain scores (P = .04) vs patients without FJV. There was no difference in mean VAS leg pain (P = .4997). The rate of fusion at 12-months for patients with FJV (27.8%) was lower compared to those without FJV (71.2%) (P = .0002). Patients with FJV were 76% less likely to have a successful fusion at 12-months. CONCLUSION: Pedicle screw-associated violation of the adjacent unfused facet joint during single-level lumbar fusion is associated with less improvement in back pain, back pain-associated disability, and a lower fusion rate at 1-year after surgery.

An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial.

ABSTRACT: Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.

Intradiscal Delivery of Anabolic Growth Factors and a Metalloproteinase Inhibitor in a Rabbit Acute Lumbar Disc Injury Model.

BACKGROUND: The purpose of our study was to examine the effect of controlled delivery of TGF-ß3, BMP-4, and TIMP-2 with a biocompatible biopolymer, chitosan, on an acutely injured intervertebral disc (IVD) in a rabbit model. METHODS: After conducting an in vitro analysis of the chondrogenic capacity of the biomolecule cocktail use (ie, TGF-ß3, BMP-4, and TIMP-2) and confirming stem cell viability in chitosan hydrogel, 15 New Zealand white rabbits underwent a lateral approach of the L1 to L4 IVDs. In each rabbit, the L2 to L3 IVD was left pristine, whereas the L1 to L2 and the L3 to L4 IVDs in each rabbit underwent nucleotomy via a 25-G needle, and the animal was subsequently randomized to no further treatment (defect only), chitosan alone, Chitosan + TGF-ß3 + BMP-4, or chitosan + TGF-ß3 + BMP-4 + TIMP-2. At 6 weeks after injury and intervention, the rabbits were killed and spines harvested to undergo quantitative T2 magnetic resonance imaging (MRI) and subsequent histologic analysis. RESULTS: In the in vitro analysis, cells treated with experimental media containing TGF-ß3, BMP-4, and TIMP-2 exhibited staining indicative of GAG production and began to exhibit a chondrocytic morphology. Quantitative T2 MRI mapping demonstrates that discs treated with chitosan, chitosan containing TGF-ß3 and BMP-4, or chitosan containing TGF-ß3, BMP-4, and TIMP-2 had consistently higher T2 relaxation times compared with defect-only discs. When the T2 relaxation times of each treatment group and defect-only discs were normalized to the healthy control disc, it was found that the T2 relaxation time of discs treated with chitosan containing TGF-ß3 and BMP-4 and discs treated with chitosan containing TGF-ß3, BMP-4, and TIMP-2 were significantly greater compared with defect-only discs (P = .048 and P = .013, respectively). Histologically, animals that received chitosan only, or chitosan with TGF-ß3 and BMP-4, showed a significantly higher intensity of Safranin-O staining (P = .016 and P = .02, respectively) compared with control discs, whereas the difference in staining intensity in animals that received chitosan loaded with TGF-ß3, BMP-4, and TIMP-2 failed to achieve significance (P = .161). CONCLUSIONS: A combination of chitosan, TGF-ß3, and BMP-4 was effective at promoting regeneration in an acute disc injury rabbit model, whereas TIMP-2 did not have a significant effect.

Comparing rates of early pedicle screw loosening in posterolateral lumbar fusion with and without transforaminal lumbar interbody fusion.

BACKGROUND CONTEXT: Addition of interbody fusion via a transforaminal approach (TLIF) has become a popular surgical option for treatment of degenerative lumbar conditions. Although technically more complicated than posterolateral fusion surgery (PLF), it has been suggested that TLIF provides superior immediate stability and protects against early pedicle screw loosening. This theory has never been formally examined in a clinical study. PURPOSE: To determine the impact of TLIF on early pedicle screw loosening and radiographic fusion rates compared with PLF using pedicle screws alone in the treatment of single level lumbar degenerative conditions. STUDY DESIGN: Retrospective computed tomography (CT) based review. PATIENT SAMPLE: One hundred ninety-three patients underwent TLIF+PLF with local autograft bone or PLF alone with local autograft bone. OUTCOME MEASURES: Radiographic fusion rates and screw loosening were measured at 6 and 12 months using strict CT criteria. Patient self-reported outcome measures included Visual Analog Scale for low back pain and leg pain and Oswestry Disability Index. METHODS: Postoperative thin-cut CTs were examined for pedicle screw loosening and radiographic fusion status. Early screw loosening rates were determined using 6-month postoperative CT, whereas radiographic fusion rates were determined using 12-month postoperative CT. One-way analysis of variance was used to determine significant differences in mean outcome scores and other continuous measures between groups at baseline and follow-up. Chi-square test of independence or Fisher's exact test was used to compare proportions between groups on categorical measures. RESULTS: Eighty-three patients underwent TLIF+PLF (Group A) and 115 patients underwent PLF alone (Group B). At 6-month follow-up, loosening was observed in 49 of 792 total screws (6.19%). Of Group A, 7.23% of patients demonstrated loosening of one or more screws compared with 18.3% of Group B (Chi-Square value 4.98; p=.0256). Six-month radiographic fusion rates were 36.1% in Group A versus 44.3% in Group B. Twelve-month radiographic fusion rates increased to 58.6% in Group A versus 73.1% in Group B. Among Group A patients not yet fused at 6 months, screw loosening was associated with a 0% rate of radiographic fusion at 12 months versus 41.2% without screw loosening. Rates for Group B were 6.25% and 70.3%, respectively. Patient age was a significant independent predictor of loosening (p=.0336). CONCLUSIONS: TLIF appears to have a protective effect, reducing rates of early screw loosening by approximately 60% versus PLF. However, this effect appears independent of actual overall radiographic fusion rates which may be approximately 20% lower with TLIF at 12 months. TLIF may have advantages in patients where early loosening is a particular concern, for example, in the setting of increased patient age.

Association Between Opioid Use and Patient-Reported Outcomes in a Randomized Trial Evaluating Basivertebral Nerve Ablation for the Relief of Chronic Low Back Pain.

BACKGROUND: Chronic low back pain (CLBP) is a primary indication for opioid therapy. OBJECTIVE: To evaluate the hypothesis that CLBP patients reporting reduced opioid use have superior functional outcomes following basivertebral nerve (BVN) radiofrequency ablation. METHODS: This post hoc analysis from a sham-controlled trial examined short-acting opioid use from baseline through 1 yr. Opioid use was stratified into 3 groups by two blinded external reviewers. Two-sample t-tests were used to compare Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) measurements between those patients who increased or decreased their opioid usage compared to baseline. RESULTS: Actively treated patients with decreased opioid use at 12 mo had a mean ODI improvement of 24.9 ± 16.0 (n = 27) compared to 7.3 ± 9.8 (n = 18) for patients reporting increased opioid use (P < .001). In the sham arm, the improvements in ODI were 17.4 ± 16.1 (n = 19) and 1.2 ± 14.3 (n = 5; P = .053) for the patients reporting decreased vs increased opioid usage, respectively. Actively treated patients reporting decreased opioid use had a mean improvement in VAS of 3.3 ± 2.5 (n = 27) compared to 0.6 ± 1.8 (n = 18) for patients reporting increased opioid use (P < .001). In the sham arm, the improvements in VAS were 2.5 ± 2.6 (n = 19) and 1.4 ± 1.9 (n = 5; P = .374) for patients reporting decreased vs increased opioid use, respectively. CONCLUSION: Subjects undergoing BVN ablation who decreased opioid use had greater improvement in ODI and VAS scores compared with those reporting increased opioid usage. There is an association between functional benefit from BVN ablation and reduced opioid use.

Potential significance of facet joint fusion or posteromedial fusion observed on CT imaging following attempted posterolateral or posterior interbody fusion.

BACKGROUND CONTEXT: Radiologic evidence of successful lumbar fusion has traditionally been based on bridging bone spanning the intertransverse processes (posterolateral fusion or PLF) or disc space (interbody fusion, or IBF). Often, postoperative computed tomography (CT) of unsuccessful PLF and IBF demonstrates bridging bone across the facet joints or connecting the medial transverse process to the ipsilateral superior articular facet of the caudal vertebra. The significance of this finding in terms of implant stability and clinical outcomes has not previously been reported. PURPOSE: To determine rates of facet joint fusion (FJF)/posteromedial fusion (PMF) following single-level PLF surgery, with or without interbody. A secondary goal was to determine comparative outcomes associated with isolated FJF/PMF versus PLF and IBF. STUDY DESIGN: Retrospective CT-based review. PATIENT SAMPLE: Two hundred-three patients underwent single-level PLF surgery with local autograft bone or PLF+IBF with local autograft bone. OUTCOME MEASURES: Fusion was assessed at 6-months and 12-months postoperatively using strict CT criteria. Patient reported outcome measures included visual analogue scale (VAS) scores for back pain and leg pain, Oswestry Disability Index (ODI), and SF-36. METHODS: Thin-cut CTs were examined to determine whether successful fusion had occurred in seven different anatomic locations. One-way analysis of variance was used to determine significant differences in mean outcome scores and other continuous measures between groups at baseline and follow-up. Chi-square test of independence or Fisher's exact test was used to compare proportions between groups on categorical measures. RESULTS: Two hundred-three patients and 157 patients completed 6- and 12 month follow-up, respectively. At 12 months, 35.1% of PLF patients demonstrated successful unilateral/bilateral PLF. Including unilateral or bilateral FJF/PMF, the fusion rate was 73.4%. Among PLF+IBF patients, 38.1% demonstrated successful IBF/PLF. Including unilateral or bilateral FJF/PMF, the fusion rate was 55.6%. All fusion groups demonstrated significant improvement in back pain and leg pain scores as well as ODI and SF-36 PF at 6- and 12 months compared with pre-op. No significant difference in any outcome measure, rates of implant loosening or reoperation was observed between successful PLF/IBF and FJF/PMF groups. CONCLUSIONS: FJF/PMF is often observed on postoperative CT evaluation following surgery originally performed to achieve PLF or IBF. Short-term follow-up suggests no significant difference in implant loosening rates or patient reported outcomes when FJF/PMF is observed versus PLF or IBF in such patients. Long-term clinical outcomes of FJF/PMF versus PLF or IBF remain unknown. These findings apply solely to single-level instrumented spinal fusion surgery utilizing pedicle screws with or without IBF.