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Kari Hanson, Carly Isder, Kristen Shogren, Anthony L. Mikula, Lichun Lu, Michael J. Yaszemski, and Benjamin D. Elder

OBJECTIVE

The use of intrawound vancomycin powder in spine surgery has been shown to decrease the rate of surgical site infections; however, the optimal dose is unknown. High-dose vancomycin inhibits osteoblast proliferation in vitro and may decrease the rate of solid arthrodesis. Bone marrow–derived mesenchymal stem cells (BMSCs) are multipotent cells that are a source of osteogenesis in spine fusions. The purpose of this study was to determine the effects of vancomycin on rat BMSC viability and differentiation in vitro.

METHODS

BMSCs were isolated from the femurs of immature female rats, cultured, and then split into two equal groups; half were treated to stimulate osteoblastic differentiation and half were not. Osteogenesis was stimulated by the addition of 50 µg/mL l-ascorbic acid, 10 mM β-glycerol phosphate, and 0.1 µM dexamethasone. Vancomycin was added to cell culture medium at concentrations of 0, 0.04, 0.4, or 4 mg/mL. Early differentiation was determined by alkaline phosphatase activity (4 days posttreatment) and late differentiation by alizarin red staining for mineralization (9 days posttreatment). Cell viability was determined at both the early and late time points by measurement of formazan colorimetric product.

RESULTS

Viability within the first 4 days decreased with high-dose vancomycin treatment, with cells receiving 4 mg/mL vancomycin having 40%–60% viability compared to the control. A gradual decrease in alizarin red staining and nodule formation was observed with increasing vancomycin doses. In the presence of the osteogenic factors, vancomycin did not have deleterious effects on alkaline phosphatase activity, whereas a trend toward reduced activity was seen in the absence of osteogenic factors when compared to osteogenically treated cells.

CONCLUSIONS

Vancomycin reduced BMSC viability and impaired late osteogenic differentiation with high-dose treatment. Therefore, the inhibitory effects of high-dose vancomycin on spinal fusion may result from both reduced BMSC viability and some impairment of osteogenic differentiation.

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Anthony L. Mikula, Jeremy L. Fogelson, Soliman Oushy, Zachariah W. Pinter, Pierce A. Peters, Kingsley Abode-Iyamah, Arjun S. Sebastian, Brett Freedman, Bradford L. Currier, David W. Polly, and Benjamin D. Elder

OBJECTIVE

Pelvic incidence (PI) is a commonly utilized spinopelvic parameter in the evaluation and treatment of patients with spinal deformity and is believed to be a fixed parameter. However, a fixed PI assumes that there is no motion across the sacroiliac (SI) joint, which has been disputed in recent literature. The objective of this study was to determine if patients with SI joint vacuum sign have a change in PI between the supine and standing positions.

METHODS

A retrospective chart review identified patients with a standing radiograph, supine radiograph, and CT scan encompassing the SI joints within a 6-month period. Patients were grouped according to their SI joints having either no vacuum sign, unilateral vacuum sign, or bilateral vacuum sign. PI was measured by two independent reviewers.

RESULTS

Seventy-three patients were identified with an average age of 66 years and a BMI of 30 kg/m2. Patients with bilateral SI joint vacuum sign (n = 27) had an average absolute change in PI of 7.2° (p < 0.0001) between the standing and supine positions compared to patients with unilateral SI joint vacuum sign (n = 20) who had a change of 5.2° (p = 0.0008), and patients without an SI joint vacuum sign (n = 26) who experienced a change of 4.1° (p = 0.74). ANOVA with post hoc Tukey test showed a statistically significant difference in the change in PI between patients with the bilateral SI joint vacuum sign and those without an SI joint vacuum sign (p = 0.023). The intraclass correlation coefficient between the two reviewers was 0.97 for standing PI and 0.96 for supine PI (p < 0.0001).

CONCLUSIONS

Patients with bilateral SI joint vacuum signs had a change in PI between the standing and supine positions, suggesting there may be increasing motion across the SI joint with significant joint degeneration.

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Anthony L. Mikula, Jeremy L. Fogelson, Soliman Oushy, Zachariah W. Pinter, Pierce A. Peters, Kingsley Abode-Iyamah, Arjun S. Sebastian, Brett Freedman, Bradford L. Currier, David W. Polly, and Benjamin D. Elder

OBJECTIVE

Pelvic incidence (PI) is a commonly utilized spinopelvic parameter in the evaluation and treatment of patients with spinal deformity and is believed to be a fixed parameter. However, a fixed PI assumes that there is no motion across the sacroiliac (SI) joint, which has been disputed in recent literature. The objective of this study was to determine if patients with SI joint vacuum sign have a change in PI between the supine and standing positions.

METHODS

A retrospective chart review identified patients with a standing radiograph, supine radiograph, and CT scan encompassing the SI joints within a 6-month period. Patients were grouped according to their SI joints having either no vacuum sign, unilateral vacuum sign, or bilateral vacuum sign. PI was measured by two independent reviewers.

RESULTS

Seventy-three patients were identified with an average age of 66 years and a BMI of 30 kg/m2. Patients with bilateral SI joint vacuum sign (n = 27) had an average absolute change in PI of 7.2° (p < 0.0001) between the standing and supine positions compared to patients with unilateral SI joint vacuum sign (n = 20) who had a change of 5.2° (p = 0.0008), and patients without an SI joint vacuum sign (n = 26) who experienced a change of 4.1° (p = 0.74). ANOVA with post hoc Tukey test showed a statistically significant difference in the change in PI between patients with the bilateral SI joint vacuum sign and those without an SI joint vacuum sign (p = 0.023). The intraclass correlation coefficient between the two reviewers was 0.97 for standing PI and 0.96 for supine PI (p < 0.0001).

CONCLUSIONS

Patients with bilateral SI joint vacuum signs had a change in PI between the standing and supine positions, suggesting there may be increasing motion across the SI joint with significant joint degeneration.

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Jeffery D. St. Jeor, Taylor J. Jackson, Ashley E. Xiong, Aamir Kadri, Brett A. Freedman, Arjun S. Sebastian, Bradford L. Currier, Ahmad Nassr, Jeremy L. Fogelson, Kurt A. Kennel, Paul A. Anderson, and Benjamin D. Elder

OBJECTIVE

The goal of this study was to compare different recognized definitions of osteoporosis in patients with degenerative lumbar spine pathology undergoing elective spinal fusion surgery to determine which patient population should be considered for preoperative optimization.

METHODS

A retrospective review of patients in whom lumbar spine surgery was planned at 2 academic medical centers was performed, and the rate of osteoporosis was compared based on different recognized definitions. Assessments were made based on dual-energy x-ray absorptiometry (DXA), CT Hounsfield units (HU), trabecular bone score (TBS), and fracture risk assessment tool (FRAX). The rate of osteoporosis was compared based on different definitions: 1) the WHO definition (T-score ≤ −2.5) at total hip or spine; 2) CT HU of < 110; 3) National Bone Health Alliance (NBHA) guidelines; and 4) “expanded spine” criteria, which includes patients meeting NBHA criteria and/or HU < 110, and/or “degraded” TBS in the setting of an osteopenic T-score. Inclusion criteria were adult patients with a DXA scan of the total hip and/or spine performed within 1 year and a lumbar spine CT scan within 6 months of the physician visit.

RESULTS

Two hundred forty-four patients were included. The mean age was 68.3 years, with 70.5% female, 96.7% Caucasian, and the mean BMI was 28.8. Fracture history was reported in 53.8% of patients. The proportion of patients identified with osteoporosis on DXA, HUs, NBHA guidelines, and the authors’ proposed “expanded spine” criteria was 25.4%, 36.5%, 75%, and 81.9%, respectively. Of the patients not identified with osteoporosis on DXA, 31.3% had osteoporosis based on HU, 55.1% had osteoporosis with NBHA, and 70.4% had osteoporosis with expanded spine criteria (p < 0.05), with poor correlations among the different assessment tools.

CONCLUSIONS

Limitations in the use of DXA T-scores alone to diagnose osteoporosis in patients with lumbar spondylosis has prompted interest in additional methods of evaluating bone health in the spine, such as CT HU, TBS, and FRAX, to inform guidelines that aim to reduce fracture risk. However, no current osteoporosis assessment was developed with a focus on improving outcomes in spinal surgery. Therefore, the authors propose an expanded spine definition for osteoporosis to identify a more comprehensive cohort of patients with potential poor bone health who could be considered for preoperative optimization, although further study is needed to validate these results in terms of clinical outcomes.

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Patrick M. Flanigan, Anthony L. Mikula, Pierce A. Peters, Soliman Oushy, Jeremy L. Fogelson, Mohamad Bydon, Brett A. Freedman, Arjun S. Sebastian, Bradford L. Currier, Ahmad Nassr, Kurt A. Kennel, Paul A. Anderson, David W. Polly, and Benjamin D. Elder

OBJECTIVE

Opportunistic Hounsfield unit (HU) determination from CT imaging has been increasingly used to estimate bone mineral density (BMD) in conjunction with assessments from dual energy x-ray absorptiometry (DXA). The authors sought to compare the effect of teriparatide on HUs across different regions in the pelvis, sacrum, and lumbar spine, as a surrogate measure for the effects of teriparatide on lumbosacropelvic instrumentation.

METHODS

A single-institution retrospective review of patients who had been treated with at least 6 months of teriparatide was performed. All patients had at least baseline DXA as well as pre- and post-teriparatide CT imaging. HUs were measured in the pedicle, lamina, and vertebral body of the lumbar spine, in the sciatic notch, and at the S1 and S2 levels at three different points (ilium, sacral body, and sacral ala).

RESULTS

Forty patients with an average age of 67 years underwent a mean of 20 months of teriparatide therapy. Mean HUs of the lumbar lamina, pedicles, and vertebral body were significantly different from each other before teriparatide treatment: 343 ± 114, 219 ± 89.2, and 111 ± 48.1, respectively (p < 0.001). Mean HUs at the S1 level for the ilium, sacral ala, and sacral body were also significantly different from each other: 124 ± 90.1, −10.7 ± 61.9, and 99.1 ± 72.1, respectively (p < 0.001). The mean HUs at the S2 level for the ilium and sacral body were not significantly different from each other, although the mean HU at the sacral ala (−11.9 ± 52.6) was significantly lower than those at the ilium and sacral body (p = 0.003 and 0.006, respectively). HU improvement occurred in most regions following teriparatide treatment. In the lumbar spine, the mean lamina HU increased from 343 to 400 (p < 0.001), the mean pedicle HU increased from 219 to 242 (p = 0.04), and the mean vertebral body HU increased from 111 to 134 (p < 0.001). There were also significant increases in the S1 sacral body (99.1 to 130, p < 0.05), S1 ilium (124 vs 165, p = 0.01), S1 sacral ala (−10.7 vs 3.68, p = 0.04), and S2 sacral body (168 vs 189, p < 0.05).

CONCLUSIONS

There was significant regional variation in lumbar and sacropelvic HUs, with most regions significantly increasing following teriparatide treatment. The sacropelvic area had lower HU values than the lumbar spine, more regional variation, and a higher degree of correlation with BMD as measured on DXA. While teriparatide treatment resulted in HUs > 110 in the majority of the lumbosacral spine, the HUs in the sacral ala remained suggestive of severe osteoporosis, which may limit the effectiveness of fixation in this region.

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Yagiz Ugur Yolcu, Waseem Wahood, Abdullah T. Eissa, Mohammed Ali Alvi, Brett A. Freedman, Benjamin D. Elder, and Mohamad Bydon

OBJECTIVE

Platelet-rich plasma (PRP) is a biological agent obtained by centrifuging a sample of blood and retrieving a high concentration of platelets and plasma components. The concentrate is then stimulated for platelet secretion of various growth factors and cytokines. Although it is not widely used in clinical practice, its role in augmenting bony union among patients undergoing spinal fusion has been assessed in several clinical studies. The objective of this study was to perform a systematic review and meta-analysis of the existing literature to determine the efficacy of PRP use in spinal fusion procedures.

METHODS

A comprehensive literature search was conducted using PubMed, Scopus, and EMBASE for studies from all available dates. From eligible studies, data regarding the fusion rate and method of assessing fusion, estimated blood loss (EBL), and baseline and final visual analog scale (VAS) scores were collected as the primary outcomes of interest. Patients were grouped by those undergoing spinal fusion with PRP and bone graft (PRP group) and those only with bone graft (graft-only group).

RESULTS

The literature search resulted in 207 articles. Forty-five full-text articles were screened, of which 11 studies were included, resulting in a meta-analysis including 741 patients. Patients without PRP were more likely to have a successful fusion at the last follow-up compared with those with PRP in their bone grafts (OR 0.53, 95% CI 0.34–0.84; p = 0.006). There was no statistically significant difference with regard to change in VAS scores (OR 0.00, 95% CI −2.84 to 2.84; p > 0.99) or change in EBL (OR 3.67, 95% CI −67.13–74.48; p = 0.92) between the groups.

CONCLUSIONS

This study found that the additional use of PRP was not associated with any significant improvement in patient-reported outcomes and was actually found to be associated with lower fusion rates compared with standard grafting techniques. Thus, PRP may have a limited role in augmenting spinal fusion.

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Teriparatide treatment increases Hounsfield units in the lumbar spine out of proportion to DEXA changes

Presented at the 2019 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Anthony L. Mikula, Ross C. Puffer, Jeffery D. St. Jeor, James T. Bernatz, Jeremy L. Fogelson, A. Noelle Larson, Ahmad Nassr, Arjun S. Sebastian, Brett A. Freedman, Bradford L. Currier, Mohamad Bydon, Michael J. Yaszemski, Paul A. Anderson, and Benjamin D. Elder

OBJECTIVE

The authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA).

METHODS

A retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment.

RESULTS

Fifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1–4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2–46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from −2.4 ± 1.5 to −1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from −2.5 ± 1.1 to −2.3 ± 1.0 (p value = 0.31).

CONCLUSIONS

Teriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons’ subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors’ knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

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Lorenzo Rinaldo, Adip G. Bhargav, Cody L. Nesvick, Giuseppe Lanzino, and Benjamin D. Elder

OBJECTIVE

Although ventricular shunting is an effective therapy for idiopathic normal pressure hydrocephalus (iNPH), the effect of shunt valve type on the incidence of revision surgery is not well defined. To address this issue, shunt revision rates between patients with iNPH receiving a fixed-setting valve (FSV) versus a programmable valve (PV) were compared.

METHODS

Patients with iNPH treated with ventricular shunting between 2001 and 2017 were included for analysis. The incidence of shunt revision was noted and risk factors for revision were identified using a Cox proportional hazards model. Costs associated with admission for ventricular shunt procedures were obtained from the Vizient national database.

RESULTS

There were 348 patients included for analysis, with 98 patients (28.1%) receiving a PV. Shunt revision occurred in 73 patients (21.0%), with 12 patients (3.4%) undergoing multiple revisions. Overall revision rates were lower in patients receiving a PV (13.3% vs 24.0%; p = 0.027), as was the incidence of multiple revisions (0.0% vs 4.8%; p = 0.023). Patients with initial placement of an FSV were also more likely to undergo valve exchange during follow-up (12.4% vs 2.0%; p = 0.003). Patients with a PV were less likely to undergo revision due to persistent symptoms without obstruction (2.0% vs 8.8%; p = 0.031) and distal obstruction (1.0% vs 6.8%; p = 0.030). In a multivariate Cox proportional hazards model, initial placement of a PV was associated with reduced risk of revision due to persistent symptoms without obstruction (OR 0.27, 95% CI 0.04–0.93; p = 0.036). PVs were associated with more frequent shunt series (1.3 vs 0.6; p < 0.001) and head CT scans (3.6 vs 2.7; p = 0.038) during follow-up. There was no significant difference in mean total costs between patients receiving an FSV and a PV ($24,282.50 vs $24,396.90; p = 0.937).

CONCLUSIONS

The authors’ results suggest that PVs lead to reduced rates of shunt revision in patients with iNPH, and decreased risk of revision due to persistent symptoms of iNPH, thereby justifying the higher upfront cost of PVs despite similar overall treatment costs between these devices.

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Enrico Giordan, Giorgio Palandri, Giuseppe Lanzino, Mohammad Hassan Murad, and Benjamin D. Elder

OBJECTIVE

Different CSF diversion procedures (ventriculoperitoneal, ventriculoatrial, and lumboperitoneal shunting) have been utilized for the treatment of idiopathic normal pressure hydrocephalus. More recently, endoscopic third ventriculostomy has been suggested as a reasonable alternative in some studies. The purpose of this study was to perform a systematic review and meta-analysis to assess overall rates of favorable outcomes and adverse events for each of these treatments. An additional objective was to determine the outcomes and complication rates in relation to the type of valve utilized (fixed vs programmable).

METHODS

Multiple databases (PubMed, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) were searched for studies involving patients with idiopathic ventriculomegaly, no secondary cause of hydrocephalus, opening pressure < 25 mm Hg on high-volume tap or drainage trial, and age > 60 years. Outcomes included the proportion of patients who showed improvement in gait, cognition, and bladder function. Adverse events considered in the analysis included postoperative ischemic/hemorrhagic complications, subdural fluid collections, seizures, need for revision surgery, and infection.

RESULTS

A total of 33 studies, encompassing 2461 patients, were identified. More than 75% of patients experienced improvement after shunting, without significant differences among the different techniques utilized. Overall, gait improvement was observed in 75% of patients, cognitive function improvement in more than 60%, and improvement of incontinence in 55%. Adjustable valves were associated with a reduction in revisions (12% vs 32%) and subdural collections (9% vs 22%) as compared to fixed valves.

CONCLUSIONS

Outcomes did not differ significantly among different CSF diversion techniques, and overall improvement was reported in more than 75% of patients. The use of programmable valves decreased the incidence of revision surgery and of subdural collections after surgery, potentially justifying the higher initial cost associated with these valves.

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Eric W. Sankey, Benjamin D. Elder, Ann Liu, Kathryn A. Carson, C. Rory Goodwin, Ignacio Jusué-Torres, and Daniele Rigamonti

OBJECTIVE

Factors associated with emergency department admission and/or shunt revision for idiopathic intracranial hypertension (IIH) are unclear. In this study, the associations of several factors with emergency department admission and shunt revision for IIH were explored.

METHODS

The authors performed a retrospective review of 31 patients (169 total emergency department visits) who presented to the emergency department for IIH-related symptoms between 2003 and 2015. Demographics, comorbidities, symptoms, IIH diagnosis and treatment history, ophthalmological examination, diagnostic lumbar puncture (LP), imaging findings, and data regarding admission and management decisions were collected. Multivariable general linear models regression analysis was performed to assess the predictive factors associated with admission and shunt revision.

RESULTS

Thirty-one adult patients with a history of shunt placement for IIH visited the emergency department a total of 169 times for IIH-related symptoms, with a median of 3 visits (interquartile range 2–7 visits) per patient. Five patients had more than 10 emergency department visits. Baseline factors associated with admission included male sex (OR 10.47, 95% CI 2.13–51.56; p = 0.004) and performance of an LP (OR 3.10, 95% CI 1.31–7.31; p = 0.01). Contrastingly, older age at presentation (OR 0.94, 95% CI 0.90–0.99; p = 0.01), and a greater number of prior emergency department visits (OR 0.94, 95% CI 0.89–0.99; p = 0.02) were slightly protective against admission. The presence of papilledema (OR 11.62, 95% CI 3.20–42.16; p < 0.001), Caucasian race (OR 40.53, 95% CI 2.49–660.09 p = 0.009), and systemic hypertension (OR 7.73, 95% CI 1.11–53.62; p = 0.03) were independent risk factors for shunt revision. In addition, a greater number of prior emergency department visits (OR 0.86, 95% CI 0.77–0.96; p = 0.009) and older age at presentation (OR 0.93, 95% CI 0.87–0.99; p = 0.02) were slightly protective against shunt revision, while there was suggestive evidence that presence of a programmable shunt (OR 0.23, 95% CI 0.05–1.14; p = 0.07) was a protective factor against shunt revision. Of note, location of the proximal catheter in the ventricle or lumbar subarachnoid space was not significantly associated with admission or shunt revision in the multivariable analyses.

CONCLUSIONS

The decision to admit a shunt-treated patient from the emergency department for symptoms related to IIH is challenging. Knowledge of factors associated with the need for admission and/or shunt revision is required. In this study, factors such as male sex, younger age at presentation, lower number of prior emergency department visits, and performance of a diagnostic LP were independent predictors of admission. In addition, papilledema was strongly predictive of the need for shunt revision, highlighting the importance of an ophthalmological examination for shunt-treated adults with IIH who present to the emergency department.