Contrast enhanced ultrasound for traumatic spinal cord injury: an overview of current and future applications.

STUDY DESIGN: Systematic review. OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is an imaging modality that has only recently seen neurosurgical application. CEUS uses inert microbubbles to intraoperatively visualize vasculature and perfusion of the brain and spinal cord in real time. Observation and augmentation of spinal cord perfusion is vital component of the management of traumatic spinal cord injury, yet there are limited imaging modalities to evaluate spinal cord perfusion. CEUS provides an intraoperative imaging tool to evaluate spinal cord perfusion in real time. The objective of this review is to evaluate the current literature on the various applications and benefits of CEUS in traumatic spinal cord injury. SETTING: South Carolina, USA. METHODS: This review was written according to the PRISMA 2020 guidelines. RESULTS: 143 articles were found in our literature search, with 46 of them being unique. After excluding articles for relevance to CEUS and spinal cord injury, we were left with 10 papers. Studies in animal models have shown CEUS to be an effective non-invasive imaging modality that can detect perfusion changes of injured spinal cords in real time. CONCLUSION: This imaging modality can provide object perfusion data of the nidus of injury, surrounding penumbra and healthy neural tissue in a traumatized spinal cord. Investigation in its use in humans is ongoing and remains promising to be an effective diagnostic and prognostic tool for those suffering from spinal cord injury.

Establishing a Standardized Method for the Effective Intraoperative Collection and Biological Preservation of Brain Tumor Tissue Samples Using a Novel Tissue Preservation System: A Pilot Study.

BACKGROUND: Glioblastoma (GB) is an aggressive tumor showing extensive intertumoral and intratumoral heterogeneity. Several possible reasons contribute to the historical inability to develop effective therapeutic strategies for treatment of GB. One such challenge is the inability to consistently procure high-quality biologically preserved specimens for use in molecular research and patient-derived xenograft model development. No scientifically derived standardized method exists for intraoperative tissue collection specifically designed with the fragility of RNA in mind. METHODS: In this investigation, we set out to characterize matched specimens from 6 GB patients comparing the traditional handling and collection processes of intraoperative tissue used in most neurosurgical operating rooms versus an automated resection, collection, and biological preservation system (APS) which captures, preserves, and biologically maintains tissue in a prescribed and controlled microenvironment. Matched specimens were processed in parallel at various time points and temperatures, evaluating viability, RNA and protein concentrations, and isolation of GB cell lines. RESULTS: We found that APS-derived GB slices stored in an APS modified medium remained viable and maintained high-quality RNA and protein concentration for up to 24 hours. CONCLUSIONS: Our results showed that primary GB cell cultures derived in this manner had improved growth over widely used collection and preservation methods. By implementing an automated intraoperative system, we also eliminated inconsistencies in methodology of tissue collection, handling and biological preservation, establishing a repeatable and standardized practice that does not require additional staff or a laboratory technician to manage it.

Thoracic Endovascular Aortic Repair for Iatrogenic Injury of the Thoracic Aorta.

PURPOSE: Address iatrogenic injury to the descending thoracic aorta by breached spinal screws through a novel approach of concomitant spinal screw removal and thoracic endovascular repair (TEVAR) placement. CASE REPORT: A 36-year-old female with idiopathic scoliosis underwent T4 to L3 bilateral pedicle instrumentation with spinal fusion and correction of scoliosis deformity. Ten months post-operative, she continued to complain of mid-thoracic pain; computed tomography (CT) angiography revealed protrusion of the left T5 and T6 transpedicular screws into her descending thoracic aorta by 3 and 5 mm, respectively. She was taken to the odds ratio (OR) in a combination case with vascular and neurosurgery. Positioned in the right lateral decubitus position, TEVAR was successfully deployed while neurosurgery concurrently removed the invading spinal screws via posterior spinal exposure. Neurosurgery then completely revised the spinal hardware during the same operation. The patient progressed well throughout the remainder of her hospital stay and was discharged on postoperative day 4. Two-year angiography demonstrated a well-placed TEVAR with no extravasation or aortic abnormality. CONCLUSIONS: In the setting of iatrogenic aortic injury due to pedicle screws, concomitant TEVAR and spinal screw removal is a safe and feasible treatment option that allows for spinal reconstruction to occur without multiple trips to the operating room.

Clinical outcomes for patients with lateral lumbar radiculopathy treated by percutaneous endoscopic transforaminal discectomy versus tubular microdiscectomy: A retrospective review.

BACKGROUND: Surgical management of lateral lumbar radiculopathy is evolving. TMD (Tubular microdiscectomy) and TELD (Transforaminal endoscopic lumbar discectomy) have emerged as viable MIS treatments. We aim to compare clinical outcomes of both techniques for the treatment of lateral lumbar radiculopathy in relation to pre-operative lumbar foraminal stenosis grade (LFS). METHODS: Retrospective observational cohort study of patients with back and leg pain from single level foraminal nerve root compression that underwent TMD or TELD. Data analyzed included pre- and post-operative VAS leg and back pain, MacNab clinical outcome scores, hospital length of stay, complication rates, and operative time. Outcomes were correlated with a pre-operative MRI grading system for LFS. RESULTS: 109 patients were enrolled (71 TELD and 38 TMD). Back and leg VAS pain scores improved in TELD and TMD (p < 0.0001). Patients with grade III stenosis showed significantly higher VAS scores (p < 0.01), and worse functional outcomes at latest follow-up compared with grade I/II LFS. Overall, there was no difference in outcome between procedure groups except that TMD VAS back pain scores were lower than TELD at last follow up (p < 0.05). Clinical outcome comparisons between procedures relating to LFS grade showed higher correlation of LFS to TELD (Spearman's rho (ρ)= 0.342 for TMD and 0.606 TELD). Regression analyses demonstrated correlation between higher-grade foraminal stenosis and poorer outcomes in TELD and TMD. CONCLUSIONS: Both TELD and TMD are viable for treating lateral lumbar radiculopathy. Higher-grade foraminal stenosis can be indicative of poorer outcomes regardless of procedure type, however, the severity of pre-operative LFS correlates with clinical outcomes in TELD more significantly than TMD.

Evaluation of open and minimally invasive spinal surgery for the treatment of thoracolumbar metastatic epidural spinal cord compression: a systematic review.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) is a debilitating sequela of cancer that results in pain, disability, and neurologic deficits. Surgical techniques have included open surgical (OS) techniques with anterior and/or posterior decompression and fusion procedures. Further technical evolution has led to minimally invasive spinal (MIS) decompression and fusion. The objective of this study is to compare MIS to OS techniques in the treatment of thoracolumbar MESCC. METHODS: A review of the literature was performed using PubMed database. Inclusion criteria included patients 18 years or older, thoracolumbar MESCC, and surgeries with instrumented fusion. A total of 451 articles met the inclusion criteria and further analysis narrowed them down to 81 articles. Variables collected included blood loss, length of stay, operative time, pre- and postoperative Frankel grade, and complications. RESULTS: A total of 5726 papers were collected, with a total of 81 papers meeting final inclusion criteria: 26 papers with MIS technique and 55 with OS. A total of 2267 patients were evaluated. They were split into three surgical subtypes of MIS and OS: posterior decompression and fusion, partial corpectomy, and complete corpectomy. Overall, MIS had lower operative time, blood loss, and complications compared to OS. A timeline analysis showed reduction of complication rates in MIS surgery between papers published over a 28-year period. CONCLUSION: MESCC carries significant morbidity and mortality. Surgical approaches for palliative treatment should account for this fact. We conclude that MIS techniques offer a viable alternative to traditional OS approaches with lower overall morbidity and complications.

Analysis of the P53N a Novel Protein Encoded on Chromosome 22q12.1-12.3 in Glioblastomas and Ependymomas Specimens.

The P53N gene maps precisely to human chromosome sub-band 22q12.1-12.3, a region where loss of heterozygosity has been reported in 30% of astrocytic tumors and associated with progression to anaplasia. Moreover, a putative tumor suppressor gene has been indicated on 22q11 region involved in pathogenesis of ependymal tumors. Our objectives to examine the expression level of novel membrane-associated protein (termed P53N) encoded by a novel human gene on chromosome 22q12.1-12.3 in glioblastomas and ependymomas. Serial analysis of gene expression (SAGE) and immunofluorescence analysis of the P53N in the brain tumor tissues were performed. Our analysis revealed that there was high expression of the P53N mRNA in brain ependymoma and brain well-differentiated astrocytoma libraries. The P53N protein. P53N protein contains a high mobility group (HMG) domain at amino acid positions 301 to 360 expressed highly in glioblastoma and ependymoma specimens. Anti-P53N carboxyl-terminal peptide antibody localized the P53N protein to the cytoplasmic membranes of protoplasmic astrocytes in the glioblastoma and ependymoma specimens. These results are in good agreement with the SAGE analysis and the predicted transmembrane topology for the P53N protein and support a possible transmembrane model in which the P53N contains a predicted transmembrane region with its amino terminus localized to the inside of the cytoplasmic membrane.

Utility of intraoperative ultrasonography for resection of pituitary adenomas: a comparative retrospective study.

BACKGROUND: The evolution of pituitary surgery has made it a safe and effective form of treatment; however, risks of inadequate tumor resection, cerebrospinal fluid (CSF) leak, pituitary dysfunction, and vascular injury still exist. The use of intraoperative ultrasonography (IOUS) in pituitary surgery has been well described. Recent advancements in ultrasound technology have allowed for expanded utility as described here. METHODS: A retrospective review was performed between January 2016 and December 2019. One hundred thirty-eight patients (mean age 53.7 years, 47% females) were identified undergoing transsphenoidal surgery for pituitary tumors. Thirty-four patients had IOUS performed using a side-firing ultrasound probe, while 104 did not. Data was analyzed for preoperative (demographics, clinical, and radiographic features), perioperative (blood loss, operative time), and postoperative (complications, length of stay, hormone remission, and extent of resection) outcomes. RESULTS: There were no significant differences in patient age, gender, tumor volume, Knosp grade, and hormone-secreting status between the two groups. Patients treated using IOUS had significantly higher rates of gross total resection (79% vs. 44%, p = 0.0008), shorter operative times (74 vs. 146 min, p < 0.0001), lower blood loss (119 vs. 284 cc, p < 0.0001), and hospital stays (2.9 vs. 4.2 days, p = 0.001). Overall complication rates were lower in the IOUS group compared to standard pituitary surgery but did not reach significance. CONCLUSIONS: Recent improvements in ultrasound technology have allowed for miniaturization of probes capable of delivering high-resolution images. The use of IOUS in transsphenoidal pituitary surgery may significantly increase rates of gross total resection, while decreasing blood loss, hospital LOS, and operative time.

Targeting Subventricular Zone Progenitor Cells with Intraventricular Liposomal Encapsulated Cytarabine in Patients with Secondary Glioblastoma : A Report of Two Cases.

BACKGROUND: Current treatments for glioblastoma (GB), the most common and malignant primary brain tumor are inadequate and as such, the median survival for most patients with GB is on the order of months, even after cytoreductive surgery, radiation and chemotherapy. CASE DESCRIPTION: Current study reports two cases of glioblastoma (GB) with subventricular zone (SVZ) involvement. SVZ biopsies demonstrated the presence of hypercellularity, nestin immunoreactivity, and a Ki-67 labeling index (LI) of 1-2%. Interestingly, tumor morphology and proliferative indices are different in the SVZ specimens than the hemispheric recurrences, which displayed similar nestin immunoreactivity, but a greater LI of 10%. Biopsy specimens demonstrated both intense nestin immunoreactivity and GFAP immunoreactivity in and around the GB recurrence. Nestin positive cells were more abundant closer to the SVZ nearest to the dorsolateral horn of the left lateral ventricle, while GFAP immunoreactivity was more intense closer to the center of the tumor recurrence. Additionally, co-labeling of cells with Ki67 and several different progenitor markers (CD133, CD140, TUJ-1, and nestin) demonstrated that these cells found in and around the GB recurrence were actively dividing. Having failed standard therapy with evidence of bi-hemispheric spread and progression to GB, we report a novel approach of using intraventricular liposomal encapsulated cytarabine (DepoCyt) for the treatment for GB by suppressing glial progenitor cells that surround the ventricular system in patients with GB. CONCLUSIONS: MRI and immunohistochemistry demonstrated that the SVZ is the incubator for future recurrences of GB and propose targeting SVZ progenitor cells with intraventricular liposomal encapsulated Ara-C. Two patients treated using this novel regimen have demonstrated partial radiographic responses warranting further studies looking at targeting the subventricular zone.

Analysis of P78: A Novel Cytoplasmic Membrane-Associated Protein Encoded on Chromosome 19q13.3 in Glioma Specimens.

Allelic losses of the q13.3 region of chromosome 19 have been documented in all major types of diffuse gliomas, strongly suggesting the presence of a 19q13.3 tumor suppressor gene responsible for these malignancies. The P78 gene precisely maps to 19q13.3, the glioma candidate region, and encodes a recently identified novel protein (P78). The purpose of this study was to determine P78 protein expression in gliomas. Serial analysis of gene expression (SAGE) reveals P78 mRNA expression to be significantly reduced in high-grade gliomas such as glioblastoma (GB), as compared with the low-grade tumors including astrocytomas, oligodendrogliomas, and ependymomas. We observed the distribution of staining of P78 protein was concentrated on the cell membranes of the luminal epithelial cells, not cytoplasm. In contrast, the pre-immune serum controls demonstrated no staining. These results demonstrate that P78 protein is highly expressed in the cytoplasmic membranes of low but not high-grade astrocytomas, and correlates with grade of malignancy. In these double immunostaining experiments, the anti-Map-2 and anti-NeuN antibodies did not stain round cells that were stained with the anti-P78 carboxyl-terminal peptide antibodies, demonstrating that these round cells were not neurons, and likely protoplasmic astrocytes. Current results also suggest that the astrocytes stained with the anti-P78 carboxyl-terminal peptide antibody are likely protoplasmic astrocytes. We also observed preincubation of anti-P78 carboxyl-terminal antibodies with immunizing peptides abolished immunostaining in gliomas. These results suggest a role for the P78 protein in the process of abnormal growth in glial tumors.

Endoscopic decompression of epidural spinal metastasis causing lumbar radiculopathy through a transforaminal approach: report of two cases.

Radiculopathy in patients with metastatic spine disease (MSD) may be palliated with open or microsurgical techniques. However, delay of chemoradiation, infection risk, extended hospitalization periods, and surgical site pain may complicate surgical efforts to improve these patients' lives. Endoscopic approaches, heretofore used almost exclusively in degenerative spine disease, may also palliate debilitating pain while mitigating the drawbacks of surgical intervention in providing focal tumor debulking. Specimen for histopathologic diagnosis, which is of increasing importance in oncology treatments, may also be obtained by the endoscopic approach. The first case is of a 61-year-old woman with right thigh pain and weakness referable to a foraminal component of metastatic disease who underwent transforaminal endoscopic decompression through a single port with resolution of her primary pain complaint. The second case is of a 50-year-old man with history of urothelial cancer who presented with L5 radicular pain referable to foraminal tumor compression who underwent similar procedure with stabilization of his primary pain complaints. Adequate tissue biopsy was obtained in both cases. Endoscopic technique may allow direct visualization with minimal morbidity for effective decompression of symptomatic metastatic disease resulting from compression of the exiting and traversing nerve roots. Patients compromised from systemic disease may benefit from this less invasive approach that requires neither endotracheal intubation nor extended hospital stay.

Strategies for posterior-only minimally invasive surgery in thoracolumbar metastatic epidural spinal cord compression.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) is a debilitating sequela of cancer. Here, we evaluated various subtypes of posterior-only minimally invasive spinal (MIS) procedures utilized to address different cancers. METHODS: Within this retrospective review, we analyzed the treatment of thoracolumbar MESCC treated with three MIS techniques: decompression and fusion (Subgroup A), partial corpectomy (Subgroup B), and full corpectomy (Subgroup C). RESULTS: There were 51 patients included in the study; they averaged 58.7 years of age, and 51% were females. Most tumors were in the thoracic spine (51%). The average preoperative Frankel grade was D (62.7%); 69% (35) improved postoperatively. The patients were divided as follows: subgroup A (15 patients = 29.4%), B (19 patients = 37.3%), and C (17 patients = 33.3%). The length of hospitalization was similar (~5.4 days) for all groups. The overall complication rate was 31%, while blood loss was lower in Subgroups A and B versus C. CONCLUSION: Different MIS surgical techniques were utilized in patients with thoracic and/or lumbar MESCC. Interestingly, clinical outcomes were similar between MIS subgroups, in this study, with a trend toward higher complications and greater blood loss associated with those undergoing more aggressive MIS procedures (e.g., full corpectomy and fusion).

Case-based review: ependymomas in adults.

Ependymomas are rare primary central nervous system (CNS) tumors in adults. They occur most commonly in the spinal cord, and have classically been graded histologically into World Health Organization (WHO) grades I, II, or III based on the level of anaplasia. Recent data are showing that genetic heterogeneity occurs within the same histological subgroup and that ependymomas arising from different CNS locations have different molecular signatures. This has renewed interest in developing targeting therapies based on molecular profiles especially given the variable outcomes with radiation and the poor results with cytotoxic agents. In this paper, we present the case of a 46-year-old woman with a classic presentation of spinal cord ependymoma and discuss the current histopathological and molecular classification for ependymomas as well as current guidelines for patient management.

Minimally invasive percutaneous screw fixation of traumatic spondylolisthesis of the axis.

OBJECT Most cases of traumatic spondylolisthesis of the axis (hangman's fracture) can be treated nonoperatively with reduction and subsequent immobilization in a rigid cervical collar or halo. However, in some instances, operative management is necessary and can be accomplished by using either anterior or posterior fusion techniques. Because open posterior procedures can result in significant blood loss, pain, and limited cervical range of motion, other less invasive options for posterior fixation are needed. The authors describe a minimally invasive, navigation-guided technique for surgical treatment of Levine-Edwards (L-E) Type II hangman's fractures. METHODS For 5 patients with L-E Type II hangman's fracture requiring operative reduction and internal fixation, percutaneous screw fixation directed through the fracture site was performed. This technique was facilitated by use of intraoperative 3D fluoroscopy and neuronavigation. RESULTS Of the 5 patients, 2 were women, 3 were men, and age range was 46-67 years. No intraoperative or postoperative complications occurred. All patients wore a rigid cervical collar, and flexion-extension radiographs were obtained at 6 months. For all patients, dynamic imaging demonstrated a stable construct. CONCLUSIONS L-E type II hangman's fractures can be safely repaired by using percutaneous minimally invasive surgical techniques. This technique may be appropriate, depending on circumstances, for all L-E Type I and II hangman's fractures; however, the degree of associated ligament injury and disc disruption must be accounted for. Percutaneous fixation is not appropriate for L-E Type III fractures because of significant displacement and ligament and disc disruption. This report is meant to serve as a feasibility study and is not meant to show superiority of this procedure over other surgical options.

Occipital condyle to cervical spine fixation in the pediatric population.

Fixation at the craniovertebral junction (CVJ) is necessary in a variety of pediatric clinical scenarios. Traditionally an occipital bone to cervical fusion is preformed, which requires a large amount of hardware to be placed on the occiput of a child. If a patient has previously undergone a posterior fossa decompression or requires a decompression at the time of the fusion procedure, it can be difficult to anchor a plate to the occipital bone. The authors propose a technique that can be used when faced with this difficult challenge by using the occipital condyle as a point of fixation for the construct. Adult cadaveric and a limited number of case studies have been published using occipital condyle (C-0) fixation. This work was adapted for the pediatric population. Between 2009 and 2012, 4 children underwent occipital condyle to axial or subaxial spine fixation. One patient had previously undergone posterior fossa surgery for tumor resection, and 1 required decompression at the time of operation. Two patients underwent preoperative deformity reduction using traction. One child had a Chiari malformation Type I. Each procedure was performed using polyaxial screw-rod constructs with intraoperative neuronavigation supplemented by a custom navigational drill guide. Smooth-shanked 3.5-mm polyaxial screws, ranging in length from 26 to 32 mm, were placed into the occipital condyles. All patients successfully underwent occipital condyle to cervical spine fixation. In 3 patients the construct extended from C-0 to C-2, and in 1 from C-0 to T-2. Patients with preoperative halo stabilization were placed in a cervical collar postoperatively. There were no new postoperative neurological deficits or vascular injuries. Each patient underwent postoperative CT, demonstrating excellent screw placement and evidence of solid fusion. Occipital condyle fixation is an effective option in pediatric patients requiring occipitocervical fusion for treatment of deformity and/or instability at the CVJ. The use of intraoperative neuronavigation allows for safe placement of screws into C-0, especially when faced with a challenging patient in whom fixation to the occipital bone is not possible or is less than ideal.

Natural history and risk factors for adjacent vertebral fractures in the fracture intervention trial.

STUDY DESIGN: Retrospective analysis of prospectively collected follow-up data for 2.9 years. OBJECTIVE: To determine the natural history of subsequent morphometric fracture rates at adjacent levels (one level above or below a previous known baseline fracture) in a large patient database. SUMMARY OF BACKGROUND DATA: The long-term risk and risk factors for adjacent-level vertebral fractures in patients with osteoporosis are unknown. METHODS: The fracture intervention trial is a large randomized, placebo-controlled trial of alendronate treatment for osteoporosis. Data from both bisphosphonate-treated and bisphosphonate-naive patients (N = 1950, vertebral fracture arm) was analyzed to detect incident morphometric fracture rates. RESULTS: During a mean follow-up of 2.9 years, 3.4% of patients in the alendronate group and 7.4% in the placebo group experienced adjacent-level vertebral fractures. The annual rate of adjacent-level vertebral fractures was 1.2% in the alendronate group, and 2.5% in the placebo group (overall, 1.8% per year in both groups combined). As expected, the thoracolumbar region (defined as T11, T12, and L1) seemed to be the most prone to new adjacent-level fractures. Among females with baseline prevalent fractures at the thoracolumbar junction, who subsequently experienced at least one new fracture anywhere along the spine (N = 124), 40.3% had a new adjacent-level fracture in this region. Older age at randomization, lower bone mineral density, inactivity, and placebo therapy were significantly associated with the development of adjacent-level fractures in univariate analysis (P ≤ 0.05). Multivariate analysis indicated decreased odds of adjacent-level fractures with bisphosphonate therapy and higher bone mineral density, and increased odds with older age at randomization (P ≤ 0.05). CONCLUSION: New vertebral fractures adjacent to prevalent fractures occurred relatively infrequently in this treatment trial of alendronate in females with osteoporosis, and were more common with older age at randomization, lower bone mineral density and placebo treatment.

Percutaneous vertebroplasty for osteoporotic vertebral compression fractures in the nonagenarians: a prospective study evaluating pain reduction and new symptomatic fracture rate.

STUDY DESIGN: A prospective observational cohort study of consecutive osteoporotic vertebral compression fractures (VCFs) in ≥ 90-year-old patients evaluated at a multidisciplinary, university spine center. OBJECTIVE: Assess efficacy, safety, and new fracture occurrence after percutaneous vertebroplasty (PV) in a large uncontrolled cohort of ultra elderly VCF patients. SUMMARY OF BACKGROUND DATA: VCFs are associated with increased morbidity and mortality. Percutaneous injection of polymethylmethacryl-ate into the fractured vertebral body, vertebroplasty, has been extensively performed as an effective minimally-invasive treatment option for VCF patients. The patient sample included consecutive, osteoporotic patients with symptomatic VCFs electing to enter the study. METHODS: Baseline visual analogue scale rating, analgesic usage, duration of symptoms. Subsequent VAS ratings, analgesic utilization, and new fractures were assessed within 30 minutes after the procedure, at 2 weeks, 1 month, 3 months, 6 months, 1 year, and 2 years postprocedure. OUTCOME MEASURES: Visual Analogue Scale score, analgesic utilization, patient satisfaction, cement extravasation, and new fractures. RESULTS.: A total of 123 (74% female) underwent PV for 163 VCFs. Eleven patients did not complete final follow-up at 2 years due to death unrelated to the PV procedure. The mean VAS score was 7.6 at baseline and 3.1 at 30 minutes after the procedure, and 2.3, 1.2, 1.1, 0.9, 0.8, and 0.5 at 2 weeks, 1 month, 3 months, 6 months, 1 year, and 2 years, respectively. Improvement over time was statistically significant using repeated measures analysis of variance (P < 0.05). No complications were encountered during the follow-up intervals. Thirteen new fractures were observed (10.6%) at a mean 20.8 weeks (1-52 weeks) after PV with 6 new fractures (4.9%) involving an adjacent level in 5 patients (4.1%). CONCLUSION: Vertebroplasty for VCFs in the very elderly appears effective and safe without increased risk of adjacent level fracture.