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Tej D. Azad, Rogelio Esparza, Navjot Chaudhary, and Steven D. Chang

OBJECT

Metastatic disease to the craniovertebral junction (CVJ) is rare but presents unique management challenges. To date, studies on using stereotactic radiosurgery (SRS) for CVJ metastases have been limited to case reports and small case series. The aim of this analysis was to evaluate the utility of SRS in the management of these secondary lesions.

METHODS

Clinical and radiological information from the charts of 25 patients with metastatic disease of the CVJ who were treated with SRS between 2005 and 2013 at the Stanford CyberKnife Center were retrospectively reviewed.

RESULTS

Seven male and 18 female patients with a median age of 58 years (range 34–94 years) were identified. The most common primary tumors were breast cancer (n = 5) and non-small cell lung cancer (n = 5), and the most frequent symptom was neck pain (n = 17). The average tumor volume treated was 15.9 cm3 (range 0.16–54.1 cm3), with a mean marginal radiation dose of 20.3 Gy (range 15–25.5 Gy). The median follow-up was 18 months (range 1–81 months), though 1 patient was lost to follow-up.

SRS provided radiographic tumor stability in over 80% of patients, offered pain alleviation in nearly two-thirds of patients, and produced no serious complications. Moreover, SRS preserved spinal stability in all but 1 patient, in whom pre-SRS stability was established. There was no evidence of radiation toxicity in the patient population. Median survival was 28 months (range 2–81 months), with survival of 13.3% at 5 years.

CONCLUSIONS

In the absence of unstable pathological fracture and spinal cord compression, metastatic tumors of the CVJ can be safely and effectively treated with SRS. This treatment option offers palliative pain relief and can halt tumor progression with only a low risk of complications or spinal instability.

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Tej D. Azad, Anand Veeravagu, and Gary K. Steinberg

Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.

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Tej D. Azad and Hugues Duffau

The optimal surgical management of gliomas requires a balance between surgical cytoreduction and preservation of neurological function. Preoperative functional neuroimaging, such as functional MRI (fMRI) and diffusion tensor imaging (DTI), has emerged as a possible tool to inform patient selection and surgical planning. However, evidence that preoperative fMRI or DTI improves extent of resection, limits neurological morbidity, and broadens surgical indications in classically eloquent areas is lacking. In this review, the authors describe facets of functional neuroimaging techniques that may limit their impact on neurosurgical oncology and critically evaluate the evidence supporting fMRI and DTI for patient selection and operative planning in glioma surgery. The authors also propose alternative applications for functional neuroimaging in the care of glioma patients.

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Anand Veeravagu, Tyler S. Cole, Tej D. Azad, and John K. Ratliff

OBJECT

The significant medical and economic tolls of spinal disorders, increasing volume of spine surgeries, and focus on quality metrics have made it imperative to understand postoperative complications. This study demonstrates the utility of a longitudinal administrative database for capturing overall and procedure-specific complication rates after various spine surgery procedures.

METHODS

The Thomson Reuters MarketScan Commercial Claims and Encounters and the Medicare Supplemental and Coordination of Benefits database was used to conduct a retrospective analysis of longitudinal administrative data from a sample of approximately 189,000 patients. Overall and procedure-specific complication rates at 5 time points ranging from immediately postoperatively (index) to 30 days postoperatively were computed.

RESULTS

The results indicated that the frequency of individual complication types increased at different rates. The overall complication rate including all spine surgeries was 13.6% at the index time point and increased to 22.8% at 30 days postoperatively. The frequencies of wound dehiscence, infection, and other wound complications exhibited large increases between 10 and 20 days postoperatively, while complication rates for new chronic pain, delirium, and dysrhythmia increased more gradually over the 30-day period studied. When specific surgical procedures were considered, 30-day complication rates ranged from 8.6% in single-level anterior cervical fusions to 27.3% in multilevel combined anterior and posterior lumbar spine fusions.

CONCLUSIONS

This study demonstrates the usefulness of a longitudinal administrative database in assessing postoperative complication rates after spine surgery. Use of this database gave results that were comparable to those in prospective studies and superior to those obtained with nonlongitudinal administrative databases. Longitudinal administrative data may improve the understanding of overall and procedure-specific complication rates after spine surgery.

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Othman Bin Alamer, Adrian E. Jimenez, and Tej D. Azad

Craniosynostosis (CS) is a congenital disease that arises due to premature ossification of single or multiple sutures, which results in skull deformities. The surgical management of single-suture CS continues to evolve and is driven by a robust body of clinical research; however, the molecular underpinnings of CS remain poorly understood. Despite long-standing hypotheses regarding the interaction of genetic predisposition and environmental factors, formal investigation of the epigenetic underpinnings of CS has been limited. In an effort to catalyze further investigation into the epigenetic basis of CS, the authors review the fundamentals of epigenetics, discuss recent studies that shed light on this emerging field, and offer hypotheses regarding the role of epigenetic mechanisms in the development of single-suture CS.

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Michael C. Jin, Zachary A. Medress, Tej D. Azad, Vanessa M. Doulames, and Anand Veeravagu

Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell–based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.

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Tej D. Azad, James Pan, Ian D. Connolly, Austin Remington, Christy M. Wilson, and Gerald A. Grant

Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

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Anand Veeravagu, Ian D. Connolly, Layton Lamsam, Amy Li, Christian Swinney, Tej D. Azad, Atman Desai, and John K. Ratliff

OBJECTIVE

The authors performed a population-based analysis of national trends, costs, and outcomes associated with cervical spondylotic myelopathy (CSM) in the United States. They assessed postoperative complications, resource utilization, and predictors of costs, in this surgically treated CSM population.

METHODS

MarketScan data (2006–2010) were used to retrospectively analyze the complications and costs of different spine surgeries for CSM. The authors determined outcomes following anterior cervical discectomy and fusion (ACDF), posterior fusion, combined anterior/posterior fusion, and laminoplasty procedures.

RESULTS

The authors identified 35,962 CSM patients, comprising 5154 elderly (age ≥ 65 years) patients (mean 72.2 years, 54.9% male) and 30,808 nonelderly patients (mean 51.1 years, 49.3% male). They found an overall complication rate of 15.6% after ACDF, 29.2% after posterior fusion, 41.1% after combined anterior and posterior fusion, and 22.4% after laminoplasty. Following ACDF and posterior fusion, a significantly higher risk of complication was seen in the elderly compared with the nonelderly (reference group). The fusion level and comorbidity-adjusted ORs with 95% CIs for these groups were 1.54 (1.40–1.68) and 1.25 (1.06–1.46), respectively. In contrast, the elderly population had lower 30-day readmission rates in all 4 surgical cohorts (ACDF, 2.6%; posterior fusion, 5.3%; anterior/posterior fusion, 3.4%; and laminoplasty, 3.6%). The fusion level and comorbidity-adjusted odds ratios for 30-day readmissions for ACDF, posterior fusion, combined anterior and posterior fusion, and laminoplasty were 0.54 (0.44–0.68), 0.32 (0.24–0.44), 0.17 (0.08–0.38), and 0.39 (0.18–0.85), respectively.

CONCLUSIONS

The authors' analysis of the MarketScan database suggests a higher complication rate in the surgical treatment of CSM than previous national estimates. They found that elderly age (≥ 65 years) significantly increased complication risk following ACDF and posterior fusion. Elderly patients were less likely to experience a readmission within 30 days of surgery. Postoperative complication occurrence, and 30-day readmission were significant drivers of total cost within 90 days of the index surgical procedure.

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Tej D. Azad, Michael C. Jin, Lydia J. Bernhardt, and Chetan Bettegowda

Diffuse midline glioma (DMG) is a highly malignant childhood tumor with an exceedingly poor prognosis and limited treatment options. The majority of these tumors harbor somatic mutations in genes encoding histone variants. These recurrent mutations correlate with treatment response and are forming the basis for molecularly guided clinical trials. The ability to detect these mutations, either in circulating tumor DNA (ctDNA) or cerebrospinal fluid tumor DNA (CSF-tDNA), may enable noninvasive molecular profiling and earlier prediction of treatment response. Here, the authors review ctDNA and CSF-tDNA detection methods, detail recent studies that have explored detection of ctDNA and CSF-tDNA in patients with DMG, and discuss the implications of liquid biopsies for patients with DMG.

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Tej D. Azad, Maziyar Kalani, Terrill Wolf, Alisa Kearney, Yohan Lee, Lisa Flannery, David Chen, Ryan Berroya, Matthew Eisenberg, Jon Park, Lawrence Shuer, Alison Kerr, and John K. Ratliff

OBJECT

Demonstrating the value of spine care requires adequate outcomes assessment. Long-term outcomes are best measured as overall improvement in quality of life (QOL) after surgical intervention. Present registries often require parallel data entry, introducing inefficiencies and limiting compliance. The authors detail the methodology of constructing an integrated electronic health record (EHR) system to collect QOL metrics and demonstrate the effect of data collection on routine clinical workflow. A streamlined approach to collecting QOL data can capture patient data without requiring dual data entry and without increasing clinic visit times.

METHODS

Through extensive literature review, a combination of QOL assessments was selected, consisting of the Patient Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index, and visual analog scale for pain. These metrics were used to provide assessment of QOL following spine surgery and were incorporated into standard clinic workflow by a multidisciplinary team of surgeons, advanced practice providers, and health care information technology specialists. A clinical dashboard tracking more than 25 patient variables was developed. Clinic flow was assessed and opportunities for improvement reviewed. Duration of clinic visits before and after initiation of QOL measure capture was recorded, with assessment of mean clinic visit times for the 12 months before and the 12 months after implementation.

RESULTS

The integrated QOL capture was instituted for 3 spine surgeons in a tertiary care academic center. In the 12-month period prior to initiating collection of QOL data, 806 new patient visits were completed with an average visit time of 127.9 ± 51.5 minutes. In the 12 months after implementation, 1013 new patient visits were recorded, with 791 providing QOL measures with an average visit time of 117.0 ± 45.7 minutes. Initially the primary means of collecting patient outcome data was via paper form, with gradual transition to collection via entry into the electronic medical records system. To improve electronic data capture, paper forms were eliminated and an online portal used as part of the patient rooming process. This improved electronic capture to nearly 98% without decreasing the number of patients enrolled in the process.

CONCLUSIONS

A systematic approach to collecting spine-related QOL data within an EHR system is feasible and offers distinct advantages over registries that require dual data entry. The process of data collection does not impact patients’ clinical visit or providers’ clinical workflow. This approach is scalable, and may form the foundation for a decentralized outcomes registry network.