Rapid Implementation of a 3-Dimensional-Printed Patient-Specific Titanium Sacrum Implant for Severe Neuropathic Spinal Arthropathy and Guide to Compassionate US Regulatory Approval.

BACKGROUND AND OBJECTIVE: Rapid design and production of patient-specific 3-dimensional-printed implants (3DPIs) present a novel opportunity to restore the biomechanically demanding integrity of the lumbopelvic junction. We present a unique case of a 61-year-old patient with severe neuropathic spinal arthropathy (Charcot spine) who initially underwent a T4-to-sacrum spinal fusion. Massive bone destruction led to dissociation of his upper body from his pelvis and legs. Reconstruction of the spinopelvic continuity was planned with the aid of a personalized lumbosacral 3DPI. METHOD: Using high-resolution computed tomography scans, the custom 3DPI was made using additive titanium manufacturing. The unique 3DPI consisted of (1) a sacral platform with iliac screws, (2) modular corpectomy device with rigid connection to the sacral platform, and (3) anterior plate connection with screws for proximal fixation. The procedures to obtain compassionate use Food and Drug Administration approval were followed. The patient underwent debridement of a chronically open wound before undertaking the 3-stage reconstructive procedure. The custom 3DPI and additional instrumentation were inserted as part of a salvage rebuilding procedure. RESULTS: The chronology of the rapid implementation of the personalized sacral 3DPI from decision, design, manufacturing, Food and Drug Administration approval, and surgical execution lasted 28 days. The prosthesis was positioned in the defect according to the expected anatomic planes and secured using a screw-rod system and a vascularized fibular bone strut graft. The prosthesis provided an ideal repair of the lumbosacral junction and pelvic ring by merging spinal pelvic fixation, posterior pelvic ring fixation, and anterior spinal column fixation. CONCLUSION: To the best of our knowledge, this is the first case of a multilevel lumbar, sacral, and sacropelvic neuropathic (Charcot) spine reconstruction using a 3DPI sacral prosthesis. As the prevalence of severe spine deformities continues to increase, adoption of 3DPIs is becoming more relevant to offer personalized treatment for complex deformities.

Predictors of Postoperative Segmental and Overall Lumbar Lordosis in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Consecutive Case Series.

STUDY DESIGN: Retrospective Case-Series. OBJECTIVES: Due to heterogeneity in previous studies, the effect of MI-TLIF on postoperative segmental lordosis (SL) and lumbar lordosis (LL) remains unclear. Therefore, we aim to identify radiographic factors associated with lordosis after surgery in a homogenous series of MI-TLIF patients. METHODS: A single-center retrospective review identified consecutive patients who underwent single-level MI-TLIF for grade 1 degenerative spondylolisthesis from 2015-2020. All surgeries underwent unilateral facetectomies and a contralateral facet release with expandable interbody cages. PROs included the ODI and NRS-BP for low-back pain. Radiographic measures included SL, disc height, percent spondylolisthesis, cage positioning, LL, PI-LL mismatch, sacral-slope, and pelvic-tilt. Surgeries were considered "lordosing" if the change in postoperative SL was ≥ +4° and "kyphosing" if ≤ -4°. Predictors of change in SL/LL were evaluated using Pearson's correlation and multivariable regression. RESULTS: A total of 73 patients with an average follow-up of 22.5 (range 12-61) months were included. Patients experienced significant improvements in ODI (29% ± 22% improvement, P < .001) and NRS-BP (3.3 ± 3 point improvement, P < .001). There was a significant increase in mean SL (Δ3.43° ± 4.37°, P < .001) while LL (Δ0.17° ± 6.98°, P > .05) remained stable. Thirty-eight (52%) patients experienced lordosing MI-TLIFs, compared to 4 (5%) kyphosing and 31 (43%) neutral MI-TLIFs. A lower preoperative SL and more anterior cage placement were associated with the greatest improvement in SL (ß = -.45° P = .001, ß = 15.06° P < .001, respectively). CONCLUSIONS: In our series, the majority of patients experienced lordosing or neutral MI-TLIFs (n = 69, 95%). Preoperative radiographic alignment and anterior cage placement were significantly associated with target SL following MI-TLIF.

Treatment of sacroiliac joint laxity-induced coronal imbalance with the kickstand rod technique.

BACKGROUND: Considerations of the sacroiliac joint (SIJ) and its role in causing lower back and limb pain have taken a secondary role ever since Mixter and Barr's hallmark article in 1934 on the herniated nucleus pulposus. However, recent literature has highlighted the contribution of sacroiliac joint degeneration in the development of failed back surgery syndrome (FBSS), especially in patients undergoing lumbar or lumbosacral spinal fusion surgeries. Many reports have studied the anatomy, physiology, and clinical significance of the sacroiliac joint, but none have linked its dysfunction with other spinal deformities. CASE DESCRIPTION: A 63-year-old female with a history of multiple complex instrumented spinal fusions presented to our institution with progressive leftward coronal imbalance despite successful arthrodesis from T3 through S1. She was initially treated with decompression and reimplantation, but adjacent segment disease at the SIJ led to laxity, distal failure, and a worsening coronal deformity. A mechanical fall after her decompression surgery led to a dramatically increased coronal imbalance, which was ultimately treated using Lenke's kickstand rod technique. At 3.5 years follow up, the patient's coronal balance remains stable. CONCLUSION: Few studies have related SIJ degeneration and laxity with spinal deformity. Our case describes SIJ degeneration that evolved to joint laxity, which ultimately produced a leftward coronal imbalance according to the adjacent segment disease mechanism. Additionally, we describe the use of a kickstand rod to effectively correct the coronal imbalance, reduce pain levels, promote SIJ arthrodesis, and prevent further SIJ-related issues without significant complications over 3 years post-operation.

Association Between Neighborhood-Level Socioeconomic Disadvantage and Patient-Reported Outcomes in Lumbar Spine Surgery.

BACKGROUND: Despite an increased understanding of the impact of socioeconomic status on neurosurgical outcomes, the impact of neighborhood-level social determinants on lumbar spine surgery patient-reported outcomes remains unknown. OBJECTIVE: To evaluate the impact of geographic social deprivation on physical and mental health of lumbar surgery patients. METHODS: A single-center retrospective cohort study analyzing patients undergoing lumbar surgery for degenerative disease from 2015 to 2018 was performed. Surgeries were categorized as decompression only or decompression with fusion. The area deprivation index was used to define social deprivation. Study outcomes included preoperative and change in Patient-Reported Outcomes Measurement (PROMIS) physical function (PF), pain interference (PI), depression, and anxiety (mean follow-up: 43.3 weeks). Multivariable imputation was performed for missing data. One-way analysis of variance and multivariable linear regression were used to evaluate the association between area deprivation index and PROMIS scores. RESULTS: In our cohort of 2010 patients, those with the greatest social deprivation had significantly worse mean preoperative PROMIS scores compared with the least-deprived cohort (mean difference [95% CI]-PF: -2.5 [-3.7 to -1.4]; PI: 3.0 [2.0-4.1]; depression: 5.5 [3.4-7.5]; anxiety: 6.0 [3.8-8.2], all P < .001), without significant differences in change in these domains at latest follow-up (PF: +0.5 [-1.2 to 2.2]; PI: -0.2 [-1.7 to 2.1]; depression: -2 [-4.0 to 0.1]; anxiety: -2.6 [-4.9 to 0.4], all P > .05). CONCLUSION: Lumbar spine surgery patients with greater social deprivation present with worse preoperative physical and mental health but experience comparable benefit from surgery than patients with less deprivation, emphasizing the need to further understand social and health factors that may affect both disease severity and access to care.

Geometric analysis of pedicle subtraction osteotomy (PSO) for Kyphosis correction: anterior lengthening may occur at the osteotomized body as well as at the discs above and below.

OBJECTIVE: To validate the authors kyphosis correction formula for pedicle subtraction osteotomy (PSO) cases. Additionally, to use the formula to evaluate the safety of PSO by determining if there is anterior lengthening. METHODS: Twenty-two patients with primarily kyphosis corrected by PSO and with clear landmarks on preoperative and postoperative x-rays were selected. Several anatomical lines and angle measurements were utilized as depicted previously in the Vertebral Column Resection formula (see below). Two approximations were calculated: the geometric approximation (G) = (tanG°*2 + 1)*15° and the rough approximation (R) which is about the same amount of actual shortening (x), if parallel length (y) ≥ 40; twice of x, if y < 40. For each patient, the change of segmental kyphosis angle (K°) was measured and compared with G° and R°, and the correlation between each value was analyzed. RESULTS: The absolute Mean ± SE for K - G and K - R was 2.33° ± 0.34 and 6.09° ± 0.58, respectively. K - G is < 3° (p = 0.03). K - R is < 8° (p = 0.001). In other words, K was close to G and R and thus can be predicted by these approximations. Average posterior shortening, anterior shortening, and kyphosis correction at each level were 20.8 ± 2.0 mm, - 3.64 ± 1.5 mm (which equates to anterior lengthening), and 31.05° ± 2.0, respectively. Anterior lengthening occurred in 13 cases (in 4 cases, both at the body as well as at the disc above and below.) The correlation between posterior and anterior shortening was 0.03 (p = 0.88). There were 3 cage insertion cases: 1 had anterior lengthening, while 2 had anterior shortening even with the cage. CONCLUSION: This study validated the geometric and rough approximations originally used in PVCR patients, for PSO patients. Additionally, this study found that anterior lengthening may occur in PSOs usually at the discs, but occasionally at the osteotomized body.

Comparison of local and regional radiographic outcomes in minimally invasive and open TLIF: a propensity score-matched cohort.

OBJECTIVE: Local and regional radiographic outcomes following minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) versus open TLIF remain unclear. The purpose of this study was to provide a comprehensive assessment of local and regional radiographic parameters following MI-TLIF and open TLIF. The authors hypothesized that open TLIF provides greater segmental and global lordosis correction than MI-TLIF. METHODS: A single-center retrospective cohort study of consecutive patients undergoing MI- or open TLIF for grade I degenerative spondylolisthesis was performed. One-to-one nearest-neighbor propensity score matching (PSM) was used to match patients who underwent open TLIF to those who underwent MI-TLIF. Sagittal segmental radiographic measures included segmental lordosis (SL), anterior disc height (ADH), posterior disc height (PDH), foraminal height (FH), percent spondylolisthesis, and cage position. Lumbopelvic radiographic parameters included overall lumbar lordosis (LL), pelvic incidence (PI)-lumbar lordosis (PI-LL) mismatch, sacral slope (SS), and pelvic tilt (PT). Change in segmental or overall lordosis after surgery was considered "lordosing" if the change was > 0° and "kyphosing" if it was ≤ 0°. Student t-tests or Wilcoxon rank-sum tests were used to compare outcomes between MI-TLIF and open-TLIF groups. RESULTS: A total of 267 patients were included in the study, 114 (43%) who underwent MI-TLIF and 153 (57%) who underwent open TLIF, with an average follow-up of 56.6 weeks (SD 23.5 weeks). After PSM, there were 75 patients in each group. At the latest follow-up both MI- and open-TLIF patients experienced significant improvements in assessment scores obtained with the Oswestry Disability Index (ODI) and the numeric rating scale for low-back pain (NRS-BP), without significant differences between groups (p > 0.05). Both MI- and open-TLIF patients experienced significant improvements in SL, ADH, and percent corrected spondylolisthesis compared to baseline (p < 0.001). However, the MI-TLIF group experienced significantly larger magnitudes of correction with respect to these metrics (ΔSL 4.14° ± 4.35° vs 1.15° ± 3.88°, p < 0.001; ΔADH 4.25 ± 3.68 vs 1.41 ± 3.77 mm, p < 0.001; percent corrected spondylolisthesis: -10.82% ± 6.47% vs -5.87% ± 8.32%, p < 0.001). In the MI-TLIF group, LL improved in 44% (0.3° ± 8.5°) of the cases, compared to 48% (0.9° ± 6.4°) of the cases in the open-TLIF group (p > 0.05). Stratification by operative technique (unilateral vs bilateral facetectomy) and by interbody device (static vs expandable) did not yield statistically significant differences (p > 0.05). CONCLUSIONS: Both MI- and open-TLIF patients experienced significant improvements in patient-reported outcome (PRO) measures and local radiographic parameters, with neutral effects on regional alignment. Surprisingly, in our cohort, change in SL was significantly greater in MI-TLIF patients, perhaps reflecting the effect of operative techniques, technological innovations, and the preservation of the posterior tension band. Taking these results together, no significant overall differences in LL between groups were demonstrated, which suggests that MI-TLIF is comparable to open approaches in providing radiographic correction after surgery. These findings suggest that alignment targets can be achieved by either MI- or open-TLIF approaches, highlighting the importance of surgeon attention to these variables.

Pharyngoesophageal Damage from Hardware Extrusion at an Average of 7.5 Years After Anterior Cervical Diskectomy and Fusion: A Case Series, Discussion of Risk Factors, and Guide for Management.

OBJECTIVE: We present a single-institution case series of patients who experienced pharyngoesophageal damage, specifically from extruded hardware occurring at an average of 7.5 years after anterior cervical diskectomy and fusion (ACDF). METHODS: A retrospective chart review was conducted of patients who had undergone ACDF with subsequent delayed pharyngoesophageal perforation or erosion from extruded hardware ≥1 year after surgery. A discussion of the literature surrounding this complication, including risk factors and management, is also presented. RESULTS: Nine patients were identified (average age 58 years, 66.7% male) among a total of 4122 ACDF patients (incidence: 0.22%). Average time to injury was 7.5 years. Indications for initial ACDF were degenerative cervical disease (n = 7), ankylosing spondylitis (n = 1), and cervical fracture (n = 1). Eight patients had prior multilevel ACDF spanning 2 (n = 4), 3 (n = 1), or 4 levels (n = 2). Fusion levels for prior ACDF included C5-C7 (n = 3), C3-C7 (n = 2), C4-C7 (n = 1), C4-C6 (n = 1), C2-C5 (n = 1), and C6-C7 (n = 1). Pharyngoesophageal injuries included esophageal perforation (n = 3), pharyngeal perforation (n = 2), esophageal erosion (n = 3), and pharyngoesophageal erosion (n = 1). In most (n = 6) cases, the cause of pharyngoesophageal damage was due to ≥1 extruded screws. Dysphagia (n = 8) was the most common presenting symptom. For perforations (n = 5), 2 repairs used a rotational flap to reinforce a primary closure; the other 3 cases were repaired via primary closure. CONCLUSIONS: Pharyngoesophageal damage caused by extruded hardware may occur several years after ACDF. These delayed complications are difficult to predict. Proper screw placement may be the most important factor for minimizing the chances of this potentially devastating complication, particularly with multilevel constructs.

Decompression of Lumbar Central Spinal Canal Stenosis Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: This was a retrospective clinical series. OBJECTIVE: The objective of this study was to evaluate radiologic changes in central spinal canal dimensions following minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) with placement of a static or an expandable interbody device. SUMMARY OF BACKGROUND DATA: MIS-TLIF is used to treat lumbar degenerative diseases and low-grade spondylolisthesis. MIS-TLIF enables direct and indirect decompression of lumbar spinal stenosis, with patients experiencing relief from radiculopathy and neurogenic claudication. However, the effects of MIS-TLIF on the central spinal canal are not well-characterized. MATERIALS AND METHODS: We identified patients who underwent MIS-TLIF for degenerative lumbar spondylolisthesis and concurrent moderate to severe spinal stenosis. We selected patients who had both preoperative and postoperative magnetic resonance imaging (MRI) and upright lateral radiographs of the lumbar spine. Measurements on axial T2-weighted MRI scans include anteroposterior and transverse dimensions of the dural sac and osseous spinal canal. Measurements on radiographs include disk height, neural foraminal height, segmental lordosis, and spondylolisthesis. We made pairwise comparisons between each of the central canal dimensions and lumbar sagittal segmental radiologic outcome measures relative to their corresponding preoperative values. Correlation coefficients were used to quantify the association between changes in lumbar sagittal segmental parameters relative to changes in radiologic outcomes of central canal dimensions. Statistical analysis was performed for "all patients" and further stratified by interbody device subgroups (static and expandable). RESULTS: Fifty-one patients (age 60.4 y, 68.6% female) who underwent MIS-TLIF at 55 levels (65.5% at L4-L5) were included in the analysis. Expandable interbody devices were used in 45/55 (81.8%) levels. Mean duration from surgery to postoperative MRI scan was 16.5 months (SD 11.9). MIS-TLIF was associated with significant improvements in dural sac dimensions (anteroposterior +0.31 cm, transverse +0.38 cm) and osseous spinal canal dimensions (anteroposterior +0.16 cm, transverse +0.32 cm). Sagittal lumbar segmental parameters of disk height (+0.56 cm), neural foraminal height (+0.35 cm), segmental lordosis (+4.26 degrees), and spondylolisthesis (-7.5%) were also improved following MIS-TLIF. We did not find meaningful associations between the changes in central canal dimensions relative to the corresponding changes in any of the sagittal lumbar segmental parameters. Stratified analysis by interbody device type (static and expandable) revealed similar within-group changes as in the overall cohort and minimal between-group differences. CONCLUSIONS: MIS-TLIF is associated with radiologic decompression of neural foraminal and central spinal canal stenosis. The mechanism for neural foraminal and central canal decompression is likely driven by a combination of direct and indirect corrective techniques.

Transfacet Minimally Invasive Transforaminal Lumbar Interbody Fusion With an Expandable Interbody Device-Part I: 2-Dimensional Operative Video and Technical Report.

BACKGROUND: Advances in operative techniques and minimally invasive technologies have evolved to maximize patient outcomes and radiographic results, while reducing morbidity and recovery time. OBJECTIVE: To describe the operative technique for a transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) as a proposed modification to the standard approach MIS-TLIF. METHODS: We present the case of a 72-yr-old man with left-sided lumbar radiculopathy. Preoperative imaging demonstrated degenerative lumbar anterolisthesis at L4-5, with associated canal and neuroforaminal stenosis. The patient underwent transfacet MIS-TLIF at L4-L5. We describe the preoperative planning, patient positioning, incision and dissection, pedicle screw insertion, transfacet approach to the working access corridor, discectomy, interbody device placement, fixation, and closure. RESULTS: The transfacet MIS-TLIF utilizes 3 key techniques to safely maximize surgical correction: (1) a limited bony resection based on the superior articular process, leaving the medial inferior articular process, lateral superior articular process, and rostral pars intact, providing a working bony corridor that protects the traversing and exiting nerve roots; (2) decortication and release of the contralateral facet joint to provide additional capacity for indirect decompression and provide the first point of osseous fusion; and (3) placement of an expandable interbody device that provides additional indirect decompression to the working side and contralateral foramen. CONCLUSION: The transfacet MIS-TLIF uniquely leverages a bony working corridor to access the disc space for discectomy and interbody placement. Transfacet MIS-TLIF is a feasible solution for lumbar spinal reconstruction to maximize direct and indirect decompression of the neuroforamina and central spinal canal in patients with lumbar degenerative diseases and low-grade spondylolisthesis.

Transfacet Minimally Invasive Transforaminal Lumbar Interbody Fusion With an Expandable Interbody Device-Part II: Consecutive Case Series.

BACKGROUND: Advances in operative techniques and instrumentation technology have evolved to maximize patient outcomes following minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). The transfacet MIS-TLIF is a modified approach to the standard MIS-TLIF that leverages a bony working corridor to access the disc space for discectomy and interbody device placement. OBJECTIVE: To evaluate clinical and radiographic results following transfacet MIS-TLIF using an expandable interbody device. METHODS: We performed a retrospective review of consecutive patients who underwent transfacet MIS-TLIF for degenerative lumbar spondylolisthesis. Patient-reported outcome measures for pain and disability were assessed. Sagittal lumbar segmental parameters and regional lumbopelvic parameters were assessed on upright lateral radiographs obtained preoperatively and during follow-up. RESULTS: A total of 68 patients (61.8% male) underwent transfacet MIS-TLIF at 74 levels. The mean age was 63.4 yr and the mean follow-up 15.2 mo. Patients experienced significant short- and long-term postoperative improvements on the numeric rating scale for low back pain (-2.3/10) and Oswestry Disability Index (-12.0/50). Transfacet MIS-TLIF was associated with an immediate and sustained reduction of spondylolisthesis, and an increase in index-level disc height (+0.71 cm), foraminal height (+0.28 cm), and segmental lordosis (+6.83°). Patients with preoperative hypolordosis (<40°) experienced significant increases in segmental (+9.10°) and overall lumbar lordosis (+8.65°). Pelvic parameters were not significantly changed, regardless of preoperative alignment. Device subsidence was observed in 6/74 (8.1%) levels, and fusion in 50/53 (94.3%) levels after 12 mo. CONCLUSION: Transfacet MIS-TLIF was associated with clinical improvements and restoration of radiographic sagittal segmental parameters. Regional alignment correction was observed among patients with hypolordosis at baseline.

Validation of the Disabilities of the Arm, Shoulder, and Hand in Patients Undergoing Cervical Spine Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the performance and convergent validity of the disabilities of the arm, shoulder, and hand (DASH) in comparison with the visual analog scale (VAS) for pain, and neck disability index (NDI) in patients undergoing cervical spine surgery. SUMMARY OF BACKGROUND DATA: Neck-specific disability scales do not adequately assess concurrent upper extremity involvement in patients with cervical spine disorders. The DASH is a patient-reported outcomes (PRO) instrument designed to measure functional disability due to upper extremity conditions but has additionally been shown to perform well in patients with neck disorders. METHODS: We identified patients who underwent cervical spine surgery at our institution between 2013 and 2016. We collected demographic information, clinical characteristics, and PRO measures-DASH, VAS, NDI-preoperatively, as well as early and late postoperatively. We calculated descriptive statistics and changes from baseline in PROs. Correlation coefficients were used to quantify the association between PRO measures. The analysis was stratified by radiculopathy and myelopathy diagnoses. RESULTS: A total of 1046 patients (52.8% male) with PROs data at baseline were included in the analysis. The mean age at surgery ±â€ŠSD was 57.2 ±â€Š11.3 years, and postoperative follow-up duration 12.7 ±â€Š10.7 months. The most common surgical procedure was anterior cervical discectomy and fusion (71.1%). Patients experienced clinically meaningful postoperative improvements in all PRO measures. The DASH showed moderate positive correlations with VAS preoperatively (Spearman rho = 0.43), as well as early (rho = 0.48) and late postoperatively (rho = 0.60). DASH and NDI scores were strongly positively correlated across operative states (Preoperative rho = 0.74, Early Postoperative rho = 0.78, Late Postoperative rho = 0.82). Stratified analysis by preoperative diagnosis showed similar within-groups trends and pairwise correlations. However, radiculopathy patients experienced larger magnitude early and late change scores. CONCLUSION: The DASH is a valid and responsive PRO measure to evaluate disabling upper extremity involvement in patients undergoing cervical spine surgery. LEVEL OF EVIDENCE: 3.

Population-based approaches to treatment and readmission after spinal cord injury.

BACKGROUND: Recent studies in surgical and non-surgical specialties have suggested that patients admitted on the weekend may have worse outcomes. In particular, patients with stroke and acute cardiovascular events have shown worse outcomes with weekend treatment. It is unclear whether this extends to patients with spinal cord injury (SCI). This study was designed to evaluate factors for readmission after index hospitalization for spinal cord injury. METHODS: This cohort was constructed from the State Inpatient Databases of California, New York, and Florida. For this study 14,396 patients with SCI were identified. The primary outcome measure evaluated was 30-day readmission. Secondary measures include in-hospital complications. Univariate and multivariate analysis were utilized to evaluate covariates. c2, Fisher's exact, and linear, logistic, and modified Poisson regression methods were utilized for statistical analysis. Propensity score methods were used with matched pairs analysis performed by the McNemar's Test. RESULTS: Weekend admission was not associated with increased 30- day readmission rates in multivariate analysis. Race and discharge to a facility (RR 1.60 [1.43-1.79]) or home with home care (RR 1.23 [1.07-1.42]), were statistically significant risk factors for readmission. Payor status did not affect rates of readmission. In propensity score matched pairs analysis, weekend admission was not associated with increased odds of 30-day readmission (OR 1.04 [0.89-1.21]). Patients admitted to high volume centers had significantly lower risk of readmission when compared with patients admitted to low volume centers. CONCLUSIONS: Our results suggest that the weekend effect, described previously in other patient populations, may not play as important a role in patients with SCI.

Fractional anisotropy to quantify cervical spondylotic myelopathy severity.

BACKGROUND: A number of clinical tools exist for measuring the severity of cervical spondylotic myelopathy (CSM). Several studies have recently described the use of non-invasive imaging biomarkers to assess severity of disease. These imaging markers may provide an additional tool to measure disease progression and represent a surrogate marker of response to therapy. Correlating these imaging biomarkers with clinical quantitative measures is critical for accurate therapeutic stratification and quantification of axonal injury. METHODS: Fourteen patients and seven healthy control subjects were enrolled. Patients were classified as mildly (7) or moderately (7) impaired based on Modified Japanese Orthopedic Association Scale. All patients underwent diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) analyses. In addition to standard neurological examination, all participants underwent 30-m Walking Test, 9-hole Peg Test (9HPT), grip strength, key pinch, and vibration sensation thresholds in the index finger and great toe. Differences in assessment scores between controls, mild and moderate CSM patients were correlated with DTI and DBSI derived fractional anisotropy (FA). RESULTS: Clinically, 30-meter walking times were significantly longer in the moderately impaired group than in the control group. Maximum 9HPT times were significantly longer in both the mildly and moderately impaired groups as compared to normal controls. Scores on great toe vibration sensation thresholds were lower in the mildly impaired and moderately impaired groups as compared to controls. We found no clear evidence for any differences in minimum grip strength, minimum key pinch, or index finger vibration sensation thresholds. There were moderately strong associations between DTI and DBSI FA values and 30-meter walking times and 9HPT. CONCLUSIONS: The 30-m Walking Test and 9HPT were both moderately to strongly associated with DTI/DBSI FA values. FA may represent an additional measure to help differentiate and stratify patients with mild or moderate CSM.

Spinal Fusion for Pediatric Spondylolisthesis: National Trends, Complications, and Short-Term Outcomes.

BACKGROUND: Current surgical management guidelines for pediatric spondylolisthesis (PS) are reliant on data from single-center cohorts. OBJECTIVE: To analyze national trends and predictors of short-term outcomes in spinal fusion surgery for PS by performing a retrospective cross-sectional analysis of the Kids' Inpatient Database (KID). METHODS: The KID (sampled every 3 yr) was queried from 2003 to 2012 to identify all cases (age 5-17) of spinal fusion for PS (n = 2646). We analyzed trends in patient characteristics, surgical management, and short-term outcomes. Both univariate and multivariable analyses were utilized. RESULTS: The 2646 spinal fusions for PS included posterior-only fusions (86.8%, PSF), anterior lumbar interbody fusions (4.8%, ALIF), and combined anterior and posterior fusions (8.4%, APLF) procedures. The utilization of APLF decreased over time (9.9%-6.4%, P = .023), whereas the number of total spinal fusions and the proportion of PSF and ALIF procedures have not changed significantly. Uptrends in Medicaid insured individuals (1.2%-18.9%), recombinant human bone morphogenetic protein-2 insertion (8.8%-16.6%), decompression (34.7%-42.8%), and mean inflation-adjusted hospital costs ($21 855-$32 085) were identified (all P < .001). In multivariable analysis, Medicaid status (odds ratio [OR] = 1.93, P = .004), teaching hospitals (OR = 1.94, P = .01), decompression (OR = 1.78, P = .004), and the APLF procedure (OR = 2.47, P = .001) increased the likelihood of complication occurrence (all P < .001). CONCLUSION: The addition of decompression during fusion and the APLF procedure were associated with more in-hospital complications, though this may have been indicative of greater surgical complexity. The utilization of the APLF procedure has decreased significantly, while costs associated with the treatment of PS have increased over time.

Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy.

We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy. SIGNIFICANCE: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. Cancer Discov; 6(11); 1230-6. ©2016 AACR.See related commentary by Snyder and Wolchok, p. 1210This article is highlighted in the In This Issue feature, p. 1197.

Posterior Cervical Fusion With Recombinant Human Bone Morphogenetic Protein-2: Complications and Fusion Rate at Minimum 2-Year Follow-Up.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The purpose of this study was to determine the fusion rate and evaluate the complications associated with the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) in posterior cervical fusion. SUMMARY OF BACKGROUND DATA: The rates of fusion and complications associated with the use of rhBMP-2 in posterior cervical fusion is unclear, though recent work has shown up to a 100% fusion rate. METHODS: We independently reviewed consecutive series of patients who underwent posterior cervical, occipitocervical, or cervicothoracic instrumented fusion augmented with rhBMP-2. Two surgeons at a tertiary-referral, academic medical center performed all operations, and each patient had a minimum of 2-year follow-up. Fusion status was determined by bony bridging on computed tomography scans, absence of radiolucency around instrumentation, and absence of motion on lateral flexion/extension radiographs. RESULTS: Fifty-seven patients with a mean age of 56.7±13.2 years and mean follow-up of 37.7±20.6 months were analyzed. Forty-eight patients (84.2%) had undergone previous cervical surgery, and 42.1% had a preexisting nonunion. Constructs spanned 5.6±2.6 levels; 19.3% involved the occiput, whereas 61.4% crossed the cervicothoracic junction. The mean rhBMP-2 dose was 21.1±8.7 mg per operation. Iliac crest autograft was used for 29.8% of patients. Six patients (10.5%) experienced nonunion; only 2 required revision. In each case of nonunion, instrumentation crossed the occipitocervical or cervicothoracic junction. However, none of the analyzed variables was statistically associated with nonunion. Fourteen patients (24.6%) suffered complications, with 7 requiring additional surgery. CONCLUSIONS: The observed fusion rate of rhBMP-2-augmented posterior cervical, occipitocervical, and cervicothoracic fusions was 89.5%. This reflects the complicated nature of the patients included in the current study and demonstrates that rhBMP-2 cannot always overcome the biomechanical challenges entailed in spanning the occipitocervical or cervicothoracic junction.

Spinal fusion for pediatric neuromuscular scoliosis: national trends, complications, and in-hospital outcomes.

OBJECTIVE The objective of this study was to determine if the recent changes in technology, surgical techniques, and surgical literature have influenced practice trends in spinal fusion surgery for pediatric neuromuscular scoliosis (NMS). In this study the authors analyzed recent trends in the surgical management of NMS and investigated the effect of various patient and surgical factors on in-hospital complications, outcomes, and costs, using the Nationwide Inpatient Sample (NIS) database. METHODS The NIS was queried from 2002 to 2011 using International Classification of Diseases, Ninth Edition, Clinical Modification codes to identify pediatric cases (age < 18 years) of spinal fusion for NMS. Several patient, surgical, and short-term outcome factors were included in the analyses. Trend analyses of these factors were conducted. Both univariate and multivariable analyses were used to determine the effect of the various patient and surgical factors on short-term outcomes. RESULTS Between 2002 and 2011, a total of 2154 NMS fusion cases were identified, and the volume of spinal fusion procedures increased 93% from 148 in 2002 to 286 in 2011 (p < 0.0001). The mean patient age was 12.8 ± 3.10 years, and 45.6% of the study population was female. The overall complication rate was 40.1% and the respiratory complication rate was 28.2%. From 2002 to 2011, upward trends (p < 0.0001) were demonstrated in Medicaid insurance status (36.5% to 52.8%), presence of ≥ 1 comorbidity (40.2% to 52.1%), and blood transfusions (25.2% to 57.3%). Utilization of posterior-only fusions (PSFs) increased from 66.2% to 90.2% (p < 0.0001) while combined anterior release/fusions and PSF (AR/PSF) decreased from 33.8% to 9.8% (< 0.0001). Intraoperative neurophysiological monitoring (IONM) underwent increasing utilization from 2009 to 2011 (15.5% to 20.3%, p < 0.0001). The use/harvest of autograft underwent a significant upward trend between 2002 and 2011 (31.3% to 59.8%, p < 0.0001). In univariate analysis, IONM use was associated with decreased complications (40.7% to 33.1%, p = 0.049) and length of stay (LOS; 9.21 to 6.70 days, p <0.0001). Inflation-adjusted mean hospital costs increased nearly 75% from 2002 to 2011 ($36,805 to $65,244, p < 0.0001). In the multivariable analysis, nonwhite race, highest quartile of median household income, greater preexisting comorbidity, long-segment fusions, and use of blood transfusions were found to increase the likelihood of complication occurrence (all p < 0.05). In further multivariable analysis, independent predictors of prolonged LOS included older age, increased preexisting comorbidity, the AR/PSF approach, and long-segment fusions (all p < 0.05). Lastly, the likelihood of increased hospital costs (at or above the 90th percentile for LOS, 14 days) was increased by older age, female sex, Medicaid insurance status, highest quartile of median household income, AR/PSF approach, long-segment fusion, and blood transfusion (all p < 0.05). In multivariable analysis, the use of autograft was associated with a lower likelihood of complication occurrence and prolonged LOS (both p < 0.05). CONCLUSIONS Increasing use of IONM and posterior-only approaches may combat the high complication rates in NMS. The trends of increasing comorbidities, blood transfusions, and total costs in spinal fusion surgery for pediatric NMS may indicate an increasingly aggressive approach to these cases.

Interpedicular height as a predictor of radicular pain in adult degenerative scoliosis.

BACKGROUND CONTEXT: Spine surgeons must correlate clinical presentation with radiographic findings in a patient-tailored approach. Despite the prevalence of adult degenerative scoliosis (ADS), there are few radiographic markers to predict the presence of radiculopathy. Emerging data suggest that spondylolisthesis, obliquity, foraminal stenosis, and curve concavity may be associated with radiculopathy in ADS. PURPOSE: The purpose of this study was to determine if radicular pain in ADS is associated with reduced interpedicular heights (IPHs) as measured on routine radiographs. STUDY DESIGN/SETTING: This is a retrospective case-controlled study. PATIENT SAMPLE: The authors carried out a retrospective chart review at a tertiary care referral center that included ADS patients referred to scoliosis surgeons between 2012 and 2014. Inclusion criteria included patients with ADS and no prior thoracolumbar surgery. Data were collected from initial spine surgeon clinic notes and radiographs. OUTCOME MEASURES: Clinical outcome data included presence, side(s), and level(s) of radicular pain; presence of motor deficits; and presence of sensory deficits. METHODS: Variables included age, gender, Scoliosis Research Society-30 (SRS-30) and Oswestry Disability Index (ODI) questionnaire data, and radiographic measurements. Radiographic measurements included Cobb angles and L1 to S1 IPHs on upright and supine radiographs. Associations between variables and outcome measures were assessed with univariate and multivariate statistical analyses. Authors have no conflicts of interests relevant to this study. RESULTS: A total of 200 patients with an average age of 51 years met the inclusion criteria. Sixty of the 200 patients presented with radicular pain. Older age was associated with radicular pain, weakness, and sensory deficits. Patients who were 55 years or older were approximately eight times more likely to have radicular pain (odds ratio [OR]=7.96, 95% confidence interval [CI]: 3.73, 17.0; p<.001), five times more likely to have motor deficit (OR=5, 95% CI: 2.55, 9.79; p<.001), and five times more likely to have sensory deficit (OR=5.2, 95% CI: 2.65, 10.2; p<.001) than those younger than 55. More caudally located nerve roots are more likely to develop radicular pain (p<.001). Motor deficits were associated with worse SRS-30 functional (p=.02) and ODI scores (p=.005), but radicular pain and sensory deficits were not associated with lower SRS-30 or ODI scores. Ipsilateral and same-level radicular pain were associated with reduced IPH on supine radiographs (p=.002 and p=.0002, respectively). Finally, reduced IPH on upright radiographs was associated with side- and level-specific radicular pain (p=.04). CONCLUSIONS: Radicular pain in ADS patients is associated with reduced IPHs and older age. Measuring IPHs on routine radiographs may be helpful in associating clinical radiculopathy with radiographic measures to guide patient management and surgical planning.

Magnetic Resonance Imaging Biomarker of Axon Loss Reflects Cervical Spondylotic Myelopathy Severity.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords. SUMMARY OF BACKGROUND DATA: A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies. METHODS: Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss. RESULTS: Median DBSI-inflammation volume is similar in control (266 µL) and mild CSM (171 µL) subjects, with a significant overlap of the middle 50% of observations (quartile 3 - quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 µL; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10-5 and 2 x 10-4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases. CONCLUSION: DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 µL in axon volume. LEVEL OF EVIDENCE: 3.