Primary anterior lumbar interbody fusion, with and without posterior instrumentation: a 1,377-patient cohort from a multicenter spine registry.

BACKGROUND CONTEXT: Lumbar interbody instrumentation techniques are common and effective surgical options for a variety of lumbar degenerative pathologies. Anterior lumbar interbody fusion (ALIF) has become a versatile and powerful means of decompression, stabilization, and reconstruction. As an anterior only technique, the integrity of the posterior muscle and ligaments remain intact. Adding posterior instrumentation to ALIF is common and may confer benefits in terms of higher fusion rate but could contribute to adjacent segment degeneration due to additional rigidity. Large clinical studies comparing stand-alone ALIF with and without posterior supplementary fixation (ALIF+PSF) are lacking. PURPOSE: To compare rates of operative nonunion and adjacent segment disease (ASD) in ALIF with or without posterior instrumentation. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients (≥18 years old) who underwent primary ALIF for lumbar degenerative pathology between levels L4 to S1 over a 12-year period. Exclusion criteria included trauma, cancer, infection, supplemental decompression, noncontiguous fusions, prior lumbar fusions, and other interbody devices. OUTCOME MEASURES: Reoperation for nonunion and ASD compared between ALIF only and ALIF+PSF. METHODS: Reoperations were modeled as time-to-events where the follow-up time was defined as the difference between the primary ALIF procedure and the date of the outcome of interest. Crude cumulative reoperation probabilities were reported at 5-years follow-up. Multivariable Cox proportional hazard regression was used to evaluate risk of operative nonunion and for ASD adjusting for patient characteristics. RESULTS: The study consisted of 1,377 cases; 307 ALIF only and 1070 ALIF+PSF. Mean follow-up time was 5.6 years. The 5-year crude nonunion incidence was 2.4% for ALIF only and 0.5% for ALIF+PSF; after adjustment for covariates, a lower operative nonunion risk was observed for ALIF+PSF (HR=0.22, 95% CI=0.06-0.76). Of the patients who are deemed potentially suitable for ALIF alone, one would need to add posterior instrumentation in 53 patients to prevent one case of operative nonunion at a 5-year follow-up (number needed to treat). Five-year operative ASD incidence was 4.3% for ALIF only and 6.2% for ALIF+PSF; with adjustments, no difference was observed between the cohorts (HR=0.96, 95% CI=0.54-1.71). CONCLUSIONS: While the addition of posterior instrumentation in ALIFs is associated with lower risk of operative nonunion compared with ALIF alone, operative nonunion is rare in both techniques (<5%). Accordingly, surgeons should evaluate the added risks associated with the addition of posterior instrumentation and reserve the supplemental posterior fixation for patients that might be at higher risk for operative nonunion. Rates of operative ASD were not statistically higher with the addition of posterior instrumentation suggesting concern regarding future risk of ASD perhaps should not play a role in considering supplemental posterior instrumentation in ALIF.

Brain and lung metastasis of uterine leiomyosarcoma: illustrative case.

BACKGROUND: Uterine leiomyosarcoma is a rare, extremely aggressive tumor with a high rate of metastasis. Five-year survival for individuals with metastatic disease is only 10%-15%. Metastases to the brain are exceptionally rare and are associated with poor survival. OBSERVATIONS: The authors report a case of uterine leiomyosarcoma that metastasized to the brain in a 51-year-old woman. A single lesion on magnetic resonance imaging was discovered in the right posterior temporo-occipital region 44 months after resection of the primary uterine tumor. The patient underwent a right occipital craniotomy with gross-total resection of the tumor and is receiving adjuvant stereotactic radiosurgery and chemotherapy with gemcitabine and docetaxel. At 8 months postresection, the patient remains alive and asymptomatic with no sign of recurrence. A literature review of prior reported cases was conducted to analyze patterns of approach to patient treatment and survival. LESSONS: The authors found an apparent survival benefit in patients receiving adjuvant radiation therapy.

PLF+PS or ALIF+PS: which has a lower operative nonunion rate? Analysis of a cohort of 2,061 patients from a National Spine Registry.

BACKGROUND CONTEXT: Although fusion rates in posterolateral lumbar fusions with pedicle screws (PLF+PS) and anterior lumbar interbody fusions with pedicle screws (ALIF+PS) have been reported, there has been no consensus on superiority with respect to clinical outcome and nonunion rates. Most studies determine nonunion rates based on radiographic studies; however, many of these nonunions are asymptomatic and may not require reoperations. Hence, a potentially more clinically useful measure is the reoperation rate for symptomatic nonunions, which we term the operative nonunion rate. PURPOSE: To determine if there is a difference in operative nonunion rates between PLF+PS versus ALIF+PS. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients (≥18 years old) with the diagnosis of lumbar spondylolisthesis or lumbar spinal stenosis who underwent primary elective PLF+PS and ALIF+PS for 1-level and 2-level fusions (L4-S1) between 2009 and 2018. OUTCOME MEASURES: Reoperation rates for symptomatic nonunions (ie, operative nonunion rates). METHODS: Patients were followed until validated operative nonunions, membership termination, death, or 03/31/2019. Descriptive statistics and 2-year incidence rates for operative nonunions were calculated by fusion-level, fusion type, and levels fused. Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate operative nonunion rates with adjustment for covariates or risk change estimates more than 10%. RESULTS: We identified 2,061 patients (PLF+PS:1,491, ALIF+PS:570) with average follow-up time of 4.8 (±3.1) years and average time to operative nonunion of 1.3 (±1.2) yrs. Comparatively, unadjusted 1-level and 2-level incidence rates for operative nonunions were higher in PLF+PS versus ALIF+PS. For 1-level procedures these were 0.9% (95% CI=0.4-1.6) versus 0.6% (95% CI=0.1-2.1); 2-level, 2.0% (95% CI=0.8-4.0) versus 0.9% (95% CI=0.1-3.3). However, there were no observed significant differences in risks for operative nonunions in multivariable models comparing PLF+PS versus ALIF+PS (HR=0.3, 95% CI=0.1-1.1), 1-level versus 2-level fusions (HR=1.8, 95% CI=0.8-4.3), or by fusion level (L4-L5: HR=1.0, 95% CI=0.4-2.7; L5-S1: HR=2.0, 95% CI=0.7-5.4). CONCLUSIONS: A large cohort of patients with lumbar fusions between L4 to S1 and an average follow-up of >4 years found that although there was a trend for higher operative nonunions in PLF+PS compared with ALIF+PS, this was not statistically significant. The role of spinal alignment was not investigated.

Operative Nonunion Rates in Posterolateral Lumbar Fusions: Analysis of a Cohort of 2591 Patients from a National Spine Registry.

OBJECTIVE: Radiographic nonunion rates in the literature for posterolateral lumbar fusions with pedicle screws (PLFs) range from 8.1% to 43.3% but may not represent nonunion rates. A few small studies have reported reoperations for symptomatic nonunions (operative nonunions) to range from 3.2% to 13.9%. The objective of this study is to determine operative nonunion rates for 1-level, 2-level, 3-level, and ≥4-level PLFs and to determine the risks for these nonunions. METHODS: A retrospective cohort study, using data from the Kaiser Permanente Spine Registry, identified adult patients (≥18 years old) who underwent PLFs for degenerative disc disease. Multivariable Cox proportional hazards regression and Kaplan-Meier survival estimates using the log-rank statistic were used to evaluate operative nonunion rates. RESULTS: The cohort consisted of 2591 patients with single-level and multilevel PLFs with mean follow-up of 4.6 years, time to operative nonunion of 1.52 years, and 2-year operative nonunion rate of 1.08%. Compared with single-level fusions, patients with 3-level and ≥4-level fusion had 2.8 and 3.7 times higher risk of operative nonunions. Patients with PLFs involving L5-S1 had 2.5 times the risk of an operative nonunion compared with those without. CONCLUSIONS: Our study reports results from one of the largest cohort of patients for the first time with single-level and multilevel instrumented PLFs and found a 2-year operative nonunion rate of 1.08% with increased risk of nonunion for constructs that included L5-S1 and ≥3-level fusions. Operative nonunion combines clinical and radiographic data and provides an alternative measure of fusion rates.

Motion preserving management of unstable traumatic clivus fracture extending through bilateral occipital condyles.

We describe non-operative management a rare traumatic clival fracture extending through the bilateral occipital condyles. Clinical History: A 26-year-old female who was involved in a high-speed motor vehicle crash presented to an outside facility with difficulty speaking. Subsequent CT of the cervical spine demonstrated a fracture of the clivus with extension through the bilateral occipital condyles. She was then transferred to our hospital for further management where complete trauma survey noted multiple other injuries including traumatic subarachnoid hemorrhage, spinal epidural hematoma, bilateral pneumothoraces, liver laceration, bilateral upper extremity injuries, and lumbosacral fractures. Additional spinal imaging was negative for any associated vascular or spinal cord injury. Given her young age, there was a strong interest to preserve craniocervical motion and the decision was made to treat her with non-operatively with halo placement. After 18 weeks of rigid fixation, follow up imaging demonstrated completely healed fractures and at twenty-one weeks post fixation she demonstrated preserved motion of the craniocervical junction. This is a review of the literature and case report regarding this rare entity and its management.

Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.

BACKGROUND CONTEXT: A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein 2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to upregulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE: The purpose of the present study was to develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING: The setting of this study is the laboratory investigation. METHODS: Disc injury was induced in 272 rats via 21-ga needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the magnetic resonance imaging (MRI) index (number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers using a previously described histologic grading scale. Genetically, nuclei pulposi were harvested, and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. RESULTS: Radiologically, discs treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks after treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated improved grades compared with discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. CONCLUSIONS: Degenerate discs treated with 5 mg/mL of simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal noninjured IVDs. In addition, the gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was upregulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD.

Symptomatic calcified perineural cyst after use of bone morphogenetic protein in transforaminal lumbar interbody fusion: a case report.

BACKGROUND CONTEXT: Human recombinant bone morphogenetic protein-2 (BMP-2) is commonly used in spinal surgery to augment arthrodesis, and a number of potential complications have been documented. PURPOSE: To present the case of a delayed radiculopathy that occurred because of a calcified perineural cyst that formed after an L4-L5 transforaminal lumbar interbody fusion (TLIF) in which BMP-2 was used. STUDY DESIGN/SETTING: Case report of a 70-year-old man presented with back and right lower extremity pain. METHODS: A 70-year-old man who had previously undergone a right L4-L5 TLIF presented 20 months after surgery with progressively radiating right leg pain. Imaging revealed a right-sided L4-L5 cystic lesion posterior to the interbody cage. The patient underwent reexploration, and a calcified mass was discovered. RESULTS: Histopathology revealed fragments of organized collagenous connective tissue, new collagen, and partially calcified fragments of fibrocartilage, bone, and ligament. CONCLUSIONS: This is the first reported case of a symptomatic calcified perineural cyst developing after a fusion procedure in which BMP-2 was used. The presence of connective tissue with metaplastic bone formation and maturation within the lesion suggests that formation of the cyst was secondary to application of BMP-2, as it possesses both osteogenic and chondrogenic capabilities.

Schmorl's nodes.

INTRODUCTION: First described in 1927, a Schmorl's node (SN) is the herniation of nucleus pulposus (NP) through the cartilaginous and bony end plate into the body of the adjacent vertebra. SNs are common findings on imaging, and although most SNs are asymptomatic, some have been shown to become painful lesions. In this manuscript, we review the literature regarding the epidemiology, clinical presentation, pathogenesis, imaging, and management of SNs. MATERIALS AND METHODS: Using databases from the US National Library of Medicine and the National Institutes of Health, relevant articles were identified. RESULTS: While several theories regarding the pathogenesis of SNs have been proposed, an axial load model appears to have the greatest supporting evidence. Symptomatic SNs are thought to be due to the inflammatory response solicited by the herniation of NP into the well-vascularized vertebral body. Management options for symptomatic SNs vary, ranging from medical management to surgical fusion. CONCLUSION: SNs are common lesions that are often asymptomatic. In certain cases, SNs can cause back pain. No consensus on pathogenesis exists. There is no established treatment modality for symptomatic SNs.

Bone morphogenetic proteins and degenerative disk disease.

Bone morphogenetic proteins (BMPs) are involved not only in osteogenesis but also in chondrogenesis. They play an important role in the development and maintenance of the intervertebral disk (IVD). For this reason, an increasing amount of research has been performed to examine the relationship between BMPs and degenerative disk disease (DDD). Moreover, researchers are examining the safe use of BMPs as a potential treatment for diskogenic back pain. We performed a literature search using databases from the US National Library of Medicine and the National Institutes of Health to identify studies relating BMPs to DDD. According to in vitro and in vivo studies in different animal and human IVDs, BMP-2 and BMP-7 are upregulated with aging and with induced disk injury; this represents an anabolic response. Direct administration of BMP-2 to IVD cells results in increased production of components of the extracellular matrix. Upregulation of the BMP pathway via other agents, namely simvastatin and LIM mineralization protein-1, has resulted in similar outcomes. Adenoviruses loaded with BMPs, transfected either directly to IVD cells or via articular chondrocytic vectors, also resulted in reversal of the typical findings in DDD. We conclude that the use of BMPs to treat DDD has a promising future. Further studies are indicated to determine optimal delivery and efficacy in humans.

Complication avoidance and management in anterior lumbar interbody fusion.

The goal of this study was to review the literature to compare strategies for avoiding and treating complications from anterior lumbar interbody fusion (ALIF), and thus provide a comprehensive aid for spine surgeons. A thorough review of databases from the US National Library of Medicine and the National Institutes of Health was conducted. The complications of ALIF addressed in this paper include pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus, and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion rates included the use of frozen rather than freeze-dried allograft, cage instrumentation, and bone morphogenetic protein. Lower cage heights appear to reduce the risk of subsidence. The most common vascular injury is venous laceration, which occurs less frequently when using nonthreaded interbody grafts such as iliac crest autograft or femoral ring allograft. Left iliac artery thrombosis is the most common arterial injury, and its occurrence can be minimized by intermittent release of retraction intraoperatively. The risk of retrograde ejaculation is significantly higher with laparoscopic approaches, and thus should be avoided in male patients. Despite precautionary measures, complications from ALIF may occur, but treatment options do exist. Bowel obstruction can be treated conservatively with neostigmine or with decompression. In cases of postoperative lymphocele, resolution can be attained by creating a peritoneal window. By recognizing ways to minimize complications, the spine surgeon can safely use ALIF procedures.

Injury severity differentially alters sensitivity to dexamethasone after traumatic brain injury.

We have reported differential short- and long-term dysregulation of the neuroendocrine stress response after traumatic brain injury (TBI) produced by controlled cortical impact (CCI). We have now investigated three possible mechanisms for this TBI-induced dysregulation: (1) effects on the sensitivity of negative-feedback systems to glucocorticoids; (2) effects on the sensitivity of pituitary corticotrophs to corticotropin-releasing hormone (CRH); and (3) effects on neuronal loss in the hilar region of the dentate gyrus and in the CA3b layer of the dorsal hippocampus. TBI was induced to the left parietal cortex in adult male rats with a pneumatic piston, at two different impact velocities and compression depths, to produce either moderate or mild CCI. At 7 and 35 days after surgery, the rats were injected SC with the synthetic glucocorticoid analog dexamethasone (DEX; 0.01, 0.10, or 1.00 mg/kg) or saline, and 2 h later were subjected to 30 min of restraint stress and tail vein blood collection. Whereas all doses of DEX suppressed corticosterone (CORT) and adrenocorticotropic hormone (ACTH) responses to stress on both days, CORT and ACTH were significantly more suppressed after 0.01 mg/kg DEX in the moderate TBI group than in the mild TBI or sham groups. At both 7 and 35 days post-TBI, CRH (1.0 and 10.0 microg/kg IP) stimulated CORT and ACTH in all rats, regardless of injury condition. Hippocampal cell loss was greatest at 48 days after moderate TBI. Enhanced sensitivity to glucocorticoid negative feedback and greater hippocampal cell loss, but not altered pituitary responses to CRH, contribute to the short- and long-term attenuation of the neuroendocrine stress response following moderate TBI. The role of TBI-induced alterations in glucocorticoid receptors in limbic system sites in enhanced glucocorticoid feedback sensitivity requires further investigation.

Injury severity differentially affects short- and long-term neuroendocrine outcomes of traumatic brain injury.

Having reported that traumatic brain injury (TBI), produced by moderate lateral controlled cortical impact (CCI), causes long-term dysregulation of the neuroendocrine stress response, the aim of this study was to assess short- and long-term effects of both moderate and mild CCI on stress-induced hypothalamic-pituitary-adrenal (HPA) function. TBI was induced to the left parietal cortex in adult male rats with a pneumatic piston, at two different impact velocities and compression depths to produce either a moderate or mild CCI. Controls underwent sham surgery without injury. Commencing at one week after recovery from surgery, rats were exposed to stressors: 30-min restraint (days 7, 34, and 70) or 15-min forced swim (days 21 and 54). Tail vein blood was analyzed for corticosterone (CORT) content by radioimmunoassay. On days 7 and 21, the stress-induced HPA responses were significantly attenuated by both mild and moderate CCI. Significant attenuation of the CORT response to stress persisted through day 70 after moderate CCI. In contrast, stress-induced CORT levels on days 34, 54, and 70 were significantly enhanced after mild CCI. Differential effects of injury severity were also observed on motor function in a forelimb test on post-injury day 12 and on cortical lesion volume and hippocampal cell loss at day 70, but not on working memory in a radial maze on day 15. The differing short- and long-term stress-induced HPA responses may be mediated by differential effects of moderate and mild CCI on the efficiency of glucocorticoid negative feedback or signaling among hypothalamic and extrahypothalamic components of the neuroendocrine stress-response system.

Lasting neuroendocrine-immune effects of traumatic brain injury in rats.

Traumatic brain injury (TBI) is a principal cause of long-term physical, cognitive, behavioral, and social deficits in young adults, which frequently coexist with a high incidence of substance abuse disorders. However, few studies have examined the long-term effects of TBI on the neuroendocrine-immune system. TBI was induced in adult male rats under isoflurane anesthesia by cortical contusion injury with a pneumatic piston positioned stereotaxically over the left parietal cortex. Controls underwent sham surgery without injury. At 4 weeks post-injury, the plasma corticosterone response to 30-min restraint stress was significantly blunted in TBI rats compared to the sham controls. One week later, transmitters were implanted for continuous biotelemetric recording of body temperature and spontaneous locomotor activity. At 6 weeks post-injury, the febrile response to i.p. injection of the bacterial endotoxin, lipopolysaccharide (LPS; 50 microg/kg), was significantly lower in TBI than in sham rats. At 8 weeks, swimming in the forced swim test was significantly less in TBI than sham rats. At 9 weeks, rats were rendered ethanol (EtOH) dependent by feeding an EtOH-containing liquid diet for 14 days. Cosine rhythmometry analysis of circadian body temperature Midline Estimating Statistic of Rhythm (MESOR), amplitudes, and acrophases indicated differential effects of EtOH and withdrawal in the two groups. Light- and dark-phase activity analysis indicated that TBI rats were significantly more active than the sham group, and that EtOH and withdrawal differentially affected their activity. Given the extensive interactions of the neuroendocrine-immune systems, these results demonstrate that TBI produces lasting dysregulation amidst the central substrates for allostasis and circadian rhythmicity.

Alcohol consumption in traumatic brain injury: attenuation of TBI-induced hyperthermia and neurocognitive deficits.

Clinical and animal studies indicate that hyperthermia during or after traumatic brain injury (TBI) is associated with poor outcome. Alcohol intoxication, a complicating risk factor in many cases of head injury, has been found to both worsen or attenuate posttraumatic neural damage and outcome. The purpose of the present study was to determine whether chronic ethanol consumption would affect TBI-induced hyperthermia and deficits in spatial learning. TBI was produced by cortical contusion injury in adult male rats. We first characterized the TBI-induced febrile response using probes implanted intraperitoneally (ip) or intracerebroventricularly for continuous biotelemetric recording of core body and brain temperatures and locomotor activity. In another experiment, rats, implanted with ip probes, were fed a liquid diet containing ethanol (5% w/v, 35% ethanol-derived calories); control rats were pair-fed the isocaloric liquid diet (P-P). At 14 days after commencement of diet feeding, TBI or sham surgery was performed, and the ethanol-fed rats were divided into two groups: half were transferred to the isocaloric diet (E-P) and the other half remained on the ethanol-containing diet (E-E). TBI produced a significant febrile response in all rats, that persisted for at least 6 days in the E-P and P-P groups but lasted for only 2 days in the E-E group. When tested at 3-4 weeks after TBI, E-E rats required significantly fewer trials than E-P rats to reach criterion in the Morris water maze. In sum, continuous consumption of ethanol before and after TBI attenuated TBI-induced hyperthermia and deficits in spatial learning. Whereas the results suggest that this ethanol regimen may be neuroprotective, a causal relationship between the two outcomes remains to be determined.