Dr. Anand Veeravagu is Assistant Professor of Neurosurgery and Assistant Professor of Orthopedic Surgery, by courtesy, and Director of Minimally Invasive NeuroSpine Surgery here at Stanford. Dr. Veeravagu is focused on advancing minimally invasive surgical techniques for diseases of the spine and cares for patients with a wide range of spinal disorders.

Dr. Veeravagu graduated from the Johns Hopkins University Biomedical Engineering program with a focus on spinal cord injury and regeneration. Committed to medical device development, neuroregeneration, and non-invasive imaging he accepted a position to complete his MD at the Stanford University School of Medicine. While a medical student, Dr. Veeravagu worked with neurosurgery and the molecular imaging program to develop novel, non-invasive imaging tools and treatments for malignant neoplasms of central nervous system.

Dr. Veeravagu subsequently completed his neurosurgical residency at Stanford University. As a resident, Dr. Veeravagu was appointed by the President of the United States as a White House Fellow in 2012, serving as Special Assistant to Secretary of Defense Leon Panetta and Chuck Hagel to guide Department of Defense Policy on traumatic brain injury, spinal cord injury, and mental health treatment for the United States military. One of 14 people from around the nation to be selected, Dr. Veeravagu served as a speech writer, national security advisor, and health consultant directly to the Secretary of Defense.

After completion of his neurosurgical residency, Dr. Veeravagu was awarded the prestigious Neurosurgical Research and Education Foundation Post-Residency Clinical Fellowship Grant and completed his fellowship training in minimally invasive and complex deformity spine at Stanford University with both neurosurgical and orthopeadic training. Dr. Veeravagu also completed a clinical scholar rotation at the University of Miami Miller School of Medicine focused on endoscopic and robotic spine surgery.

Dr. Veeravagu’s research efforts are focused on the utilization of large national databases to assess cost, quality, and effectiveness of various treatment alogirthms as well as predictive analytics. Dr. Veeravagu is also an author and writes about current events, health policy, and public health-related topics for the San Francisco Chronicle, The Daily Beast, The BBC, and the Huffington Post.

Clinical Focus

  • Neurosurgery
  • Spine Surgery
  • Minimally Invasive Spine Surgery
  • Complex Deformity and Scoliosis Spine Surgery
  • Robotic Spine Surgery
  • Spinal Oncology
  • spondylolisthesis
  • artificial disc replacement
  • Degenerative Disc Disease
  • Adult reconstructive spinal surgery
  • Spinal cord neoplasms
  • Spinal metastatic disease
  • spinal stenosis
  • Spine Radiation Therapy & Radiosurgery

Academic Appointments

Professional Education

  • Fellowship:Stanford University Hospital and Clinics (2016) CA
  • Fellowship, University of Miami School of Medicine, Clinical Scholar in Spinal Robotics and Minimally Invasive Spine Surgery (2016)
  • Fellowship, Stanford University, Minimally Invasive and Complex Deformity Spine Neurosurgery (2016)
  • Residency:Stanford University (2015)
  • Internship:Stanford University (2010) CA
  • Medical Education:Stanford University School of Medicine (2009) CA
  • Bachelor of Science, Johns Hopkins University, Biomedical Engineering, conc. Electrical Engineering & Minor: Multicultural and Regional Studies (2005)

Clinical Trials

  • Dexamethasone With or Without Thalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining dexamethasone and thalidomide may kill more cancer cells. It is not yet known whether dexamethasone is more effective with or without thalidomide in treating multiple myeloma. PURPOSE: Randomized phase III trial to determine the effectiveness of dexamethasone with or without thalidomide in treating patients who have multiple myeloma.

    Stanford is currently not accepting patients for this trial.

    View full details

All Publications

  • Surgeon Procedure Volume and Complication Rates in Anterior Cervical Discectomy and Fusions: Analysis of a National Longitudinal Database. Clinical spine surgery Cole, T., Veeravagu, A., Zhang, M., Ratliff, J. K. 2017; 30 (5): E633-E639


    Retrospective study using the MarketScan longitudinal database (2006-2010).Compare complication rates between groups of patients undergoing anterior cervical discectomy and fusion (ACDF) procedures performed by surgeons with high versus low mean annual ACDF volume.Over the past decade the volume of ACDFs performed has increased, concurrent with greater appreciation of potential for associated complications. The effect of surgeon procedure volume on adverse events occurrence in the postoperative period has not been described.We evaluated the relationship between surgeon procedure volume and postoperative incidence of any complication using a multivariate logistic regression model. A total of 24,461 patients undergoing single and multiple level ACDFs were identified in the MarketScan database by Current Procedural Terminology coding. Annual surgeon volume was determined by tracking of anonymized surgeon identification numbers, with high-volume surgeons defined as those performing an average of at least 30 ACDF procedures annually.Over 50% of unique surgeon identifiers reported <9 ACDF operations per year, whereas the highest decile reported a range of 44-101. High surgeon volume was protective for any complication [odds ratio (OR), 72; 95% confidence interval, 0.65-0.81; P<0.0001], with an adjusted number needed to harm of 44. Patients treated by high-volume physicians specifically had lower odds of dysphagia (2.22% vs. 3.08%; OR, 0.71; P<0.0013), neurological complications (0.33% vs. 0.64%; OR, 0.52; P<0.0107), new diagnosis of chronic pain (0.48% vs. 0.82%; OR, 0.58; P<0.0119), pulmonary complications (1.10% vs. 1.58%; OR, 0.69; P<0.0138), and other wound complications (0.06% vs. 0.22%; OR, 0.28; P<0.0242).We demonstrate a possible association between higher surgeon procedure volume and decreased postoperative complications after ACDF. There was no difference observed in need for revision surgery or readmission rates.

    View details for DOI 10.1097/BSD.0000000000000238

    View details for PubMedID 28525490

  • Outpatient vs Inpatient Anterior Cervical Discectomy and Fusion: A Population-Level Analysis of Outcomes and Cost. Neurosurgery Purger, D. A., Pendharkar, A. V., Ho, A. L., Sussman, E. S., Yang, L., Desai, M., Veeravagu, A., Ratliff, J. K., Desai, A. 2017


    Outpatient anterior cervical discectomy and fusion (ACDF) is a promising candidate for US healthcare cost reduction as several studies have demonstrated that overall complications are relatively low and early discharge can preserve high patient satisfaction, low morbidity, and minimal readmission.To compare clinical outcomes and associated costs between inpatient and ambulatory setting ACDF.Demographics, comorbidities, emergency department (ED) visits, readmissions, reoperation rates, and 90-d charges were retrospectively analyzed for patients undergoing elective ACDF in California, Florida, and New York from 2009 to 2011 in State Inpatient and Ambulatory Databases.A total of 3135 ambulatory and 46 996 inpatient ACDFs were performed. Mean Charlson comorbidity index, length of stay, and mortality were 0.2, 0.4 d, and 0% in the ambulatory cohort and 0.4, 1.8 d, and 0.04% for inpatients ( P < .0001). Ambulatory patients were younger (48.0 vs 53.1) and more likely to be Caucasian. One hundred sixty-eight ambulatory patients (5.4%) presented to the ED within 30 d (mean 11.3 d), 51 (1.6%) were readmitted, and 5 (0.2%) underwent reoperation. Among inpatient surgeries, 2607 patients (5.5%) presented to the ED within 30 d (mean 9.7 d), 1778 (3.8%) were readmitted (mean 6.3 d), and 200 (0.4%) underwent reoperation. Higher Charlson comorbidity index increased rate of ED visits (ambulatory operating room [OR] 1.285, P < .05; inpatient OR 1.289, P < .0001) and readmission (ambulatory OR 1.746, P < .0001; inpatient OR 1.685, P < .0001). Overall charges were significantly lower for ambulatory ACDFs ($33 362.51 vs $74 667.04; P < .0001).ACDF can be performed in an ambulatory setting with comparable morbidity and readmission rates, and lower costs, to those performed in an inpatient setting.

    View details for DOI 10.1093/neuros/nyx215

    View details for PubMedID 28498922

  • Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool. Journal of neurosurgery. Spine Veeravagu, A., Li, A., Swinney, C., Tian, L., Moraff, A., Azad, T. D., Cheng, I., Alamin, T., Hu, S. S., Anderson, R. L., Shuer, L., Desai, A., Park, J., Olshen, R. A., Ratliff, J. K. 2017: 1-11


    OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery. RESULTS The authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

    View details for DOI 10.3171/2016.12.SPINE16969

    View details for PubMedID 28430052

  • An assessment of data and methodology of online surgeon scorecards JOURNAL OF NEUROSURGERY-SPINE Xu, L. W., Li, A., Swinney, C., Babu, M., Veeravagu, A., Wolfe, S. Q., Nahed, B. V., Ratliff, J. K. 2017; 26 (2): 235-242
  • Biopsy versus resection for themanagement of low-grade gliomas COCHRANE DATABASE OF SYSTEMATIC REVIEWS Jiang, B., Chaichana, K., Veeravagu, A., Chang, S. D., Black, K. L., Patil, C. G. 2017


    This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG.To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG.The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and for ongoing trials.We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL).A total of 1375 updated citations were searched and critically analyzed for relevance. This was undertaken independently by two review authors. The original electronic database searches yielded a total of 2764 citations. In total, 4139 citations have been critically analyzed for this updated review.No new RCTs of biopsy or resection for LGG were identified. No additional ineligible non-randomized studies (NRS) were included in this updated review. Twenty other ineligible studies were previously retrieved for further analysis despite not meeting the pre-specified criteria. Ten studies were retrospective or were literature reviews. Three studies were prospective, however they were limited to tumor recurrence and volumetric analysis and extent of resection. One study was a population-based parallel cohort in Norway, but not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally, one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection.Since the last version of this review, no new studies have been identified for inclusion and currently there are no RCTs or CCTs available on which to base definitive clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Some retrospective studies and non-randomized prospective studies do seem to suggest improved OS and seizure control correlating to higher extent of resection. Future research could focus on RCTs to determine outcomes benefits for biopsy versus resection.

    View details for DOI 10.1002/14651858.CD009319.pub3

    View details for Web of Science ID 000400759700029

    View details for PubMedID 28447767

  • Optimization of tumor resection with intra-operative magnetic resonance imaging JOURNAL OF CLINICAL NEUROSCIENCE Swinney, C., Li, A., Bhatti, I., Veeravagu, A. 2016; 34: 11-14


    Intra-operative MRI (ioMRI) may be used to optimize tumor resection. Utilization of this technology allows for the removal of residual tumor mass following initial tumor removal, maximizing the extent of resection. This, in turn, has been shown to lead to improved outcomes. Individual studies have examined the impact of ioMRI on the rate of extended resection, but a comprehensive review of this topic is needed. A literature review of the MEDLINE, EMBASE, CENTRAL, and Google Scholar databases revealed 12 eligible studies. This included 804 primary operations and 238 extended resections based on ioMRI findings. Use of ioMRI led to extended tumor resection in 13.3-54.8% of patients (mean 37.3%). Stratification by tumor type showed additional resection occurred, on average, in 39.1% of glioma resections (range 13.3-70.0%), 23.5% of pituitary tumor resections (range 13.3-33.7%), and 35.0% of nonspecific tumor resections (range 17.5-40%). Tumor type (glioma vs. pituitary) did not significantly influence the rate of further excision following ioMRI (p=0.309). There was no difference in secondary resection rate between studies limited to pediatric patients and those including adults (p=0.646). Thus, the use of intra-operative MRI frequently results in further resection of tumors. It is primarily used for the resection of gliomas and pituitary tumors. Tumor type does not appear to be a significant contributing factor to the rate of secondary tumor removal. Limited evidence suggests that extended resection may translate into improved clinical outcomes and mortality rates. However, results have not been unanimous, while clinical effect sizes have often been modest.

    View details for DOI 10.1016/j.jocn.2016.05.030

    View details for Web of Science ID 000389093300003

    View details for PubMedID 27469412

  • Cervical Osteochondroma Causing Myelopathy in Adults: Management Considerations and Literature Review. World neurosurgery Veeravagu, A., Li, A., Shuer, L. M., Desai, A. M. 2016


    Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression.We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma.We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

    View details for DOI 10.1016/j.wneu.2016.10.061

    View details for PubMedID 27777159

  • Impact of Inpatient Venous Thromboembolism Continues After Discharge: Retrospective Propensity Scored Analysis in a Longitudinal Database. Clinical spine surgery Li, A. Y., Azad, T. D., Veeravagu, A., Bhatti, I., Li, A., Cole, T., Desai, A., Ratliff, J. K. 2016: -?


    Propensity score matched retrospective study using a nationwide longitudinal database.To quantify the longitudinal economic impact of venous thromboembolism (VTE) complications in spinal fusion patients.VTE is a rare and serious complication that may occur after spine surgery. The long-term socioeconomic impact understanding of these events has been limited by small sample sizes and a lack of longitudinal follow-up. We provide a comparative economic outcomes analysis of these complications.We identified 204,308 patients undergoing spinal fusion procedures in a national billing claims database (MarketScan) between 2006 and 2010. Cohorts were balanced using 50:1 propensity score matching and outcome measures compared at 6, 12, and 18 months postoperation.A total of 1196 (0.6%) patients developed postoperative VTE, predominantly occurring following lumbar fusion (69.7%). Postoperative VTE patients demonstrated an increase in hospital length of stay (7.8 vs. 3.3 d, P<0.001) and a decreased likelihood of being discharged home (71% vs. 85%, P<0.001). A $26,306 increase in total hospital payments (P<0.001) was observed, with a disproportionate increase seen in hospital payments ($22,103, P<0.001), relative to physician payments ($1766, P=0.001).At 6, 12, and 18 months postfusion, increased rates of readmission and follow-up clinic visits were observed. Delayed readmissions were associated with decreased length of stay (3.6 vs. 4.6 d, P<0.001), but increased total payments, averaging at $21,270 per readmission. VTE patients generated greater cumulative outpatient service payments, costing $8075, $11,134, and $13,202 more at 6, 12, and 18 months (P<0.001).VTEs are associated with longer hospitalizations, a decreased likelihood of being discharged home, and overall increases of hospital resource utilization and cost in inpatient and outpatient settings. VTE patients generate greater charges in the outpatient setting and are more likely to become readmitted at 6, 12, and 18 months after surgery, demonstrating a significant socioeconomic impact long after occurrence.Level III-therapeutic.

    View details for PubMedID 27750270

  • An assessment of data and methodology of online surgeon scorecards. Journal of neurosurgery. Spine Xu, L. W., Li, A., Swinney, C., Babu, M., Veeravagu, A., Wolfe, S. Q., Nahed, B. V., Ratliff, J. K. 2016: 1-8


    OBJECTIVE Recently, 2 surgeon rating websites (Consumers' Checkbook and ProPublica) were published to allow the public to compare surgeons through identifying surgeon volume and complication rates. Among neurosurgeons and orthopedic surgeons, only cervical and lumbar spine, hip, and knee procedures were included in this assessment. METHODS The authors examined the methodology of each website to assess potential sources of inaccuracy. Each online tool was queried for reports on neurosurgeons specializing in spine surgery and orthopedic surgeons specializing in spine, hip, or knee surgery. Surgeons were chosen from top-ranked hospitals in the US, as recorded by a national consumer publication ranking system, within the fields of neurosurgery and orthopedic surgery. The results were compared for accuracy and surgeon representation, and the results of the 2 websites were also compared. RESULTS The methodology of each site was found to have opportunities for bias and limited risk adjustment. The end points assessed by each site were actually not complications, but proxies of complication occurrence. A search of 510 surgeons (401 orthopedic surgeons [79%] and 109 neurosurgeons [21%]) showed that only 28% and 56% of surgeons had data represented on Consumers' Checkbook and ProPublica, respectively. There was a significantly higher chance of finding surgeon data on ProPublica (p < 0.001). Of the surgeons from top-ranked programs with data available, 17% were quoted to have high complication rates, 13% with lower volume than other surgeons, and 79% had a 3-star out of 5-star rating. There was no significant correlation found between the number of stars a surgeon received on Consumers' Checkbook and his or her adjusted complication rate on ProPublica. CONCLUSIONS Both the Consumers' Checkbook and ProPublica websites have significant methodological issues. Neither site assessed complication occurrence, but rather readmissions or prolonged length of stay. Risk adjustment was limited or nonexistent. A substantial number of neurosurgeons and orthopedic surgeons from top-ranked hospitals have no ratings on either site, or have data that suggests they are low-volume surgeons or have higher complication rates. Consumers' Checkbook and ProPublica produced different results with little correlation between the 2 websites in how surgeons were graded. Given the significant methodological issues, incomplete data, and lack of appropriate risk stratification of patients, the featured websites may provide erroneous information to the public.

    View details for PubMedID 27661563

  • Surgeon Procedure Volume and Complication Rates in Anterior Cervical Discectomy and Fusions: Analysis of a National Longitudinal Database. Clinical spine surgery Cole, T., Veeravagu, A., Zhang, M., Ratliff, J. K. 2016: -?


    Retrospective study using the MarketScan longitudinal database (2006-2010).Compare complication rates between groups of patients undergoing anterior cervical discectomy and fusion (ACDF) procedures performed by surgeons with high versus low mean annual ACDF volume.Over the past decade the volume of ACDFs performed has increased, concurrent with greater appreciation of potential for associated complications. The effect of surgeon procedure volume on adverse events occurrence in the post-operative period has not been described.We evaluated the relationship between surgeon procedure volume and post-operative incidence of any complication using a multivariate logistic regression model. 24,461 patients undergoing single and multiple level ACDFs were identified in the MarketScan database by Current Procedural Terminology coding. Annual surgeon volume was determined by tracking of anonymized surgeon identification numbers, with high-volume surgeons defined as those performing an average of at least 30 ACDF procedures annually.Over 50% of unique surgeon identifiers reported less than 9 ACDF operations per year, while the highest decile reported a range of 44 to 101. High surgeon volume was protective for any complication (OR.72, 95% CI 0.65-0.81 P<0.0001), with an adjusted number needed to harm of 44. Patients treated by high-volume physicians specifically had lower odds of dysphagia (2.22% vs. 3.08%, OR 0.71, P<0.0013), neurological complications (0.33% vs. 0.64%, OR 0.52, P<0.0107), new diagnosis of chronic pain (0.48% vs. 0.82%, OR 0.58, P<0.0119), pulmonary complications (1.10% vs. 1.58%, OR 0.69, P<0.0138), and other wound complications (0.06% vs. 0.22%, OR 0.28, P<0.0242).We demonstrate a possible association between higher surgeon procedure volume and decreased post-operative complications following anterior cervical discectomy and fusion. There was no difference observed in need for revision surgery or readmission rates.

    View details for PubMedID 25551324

  • Delayed Presentation of Sciatic Nerve Injury after Total Hip Arthroplasty: Neurosurgical Considerations, Diagnosis, and Management. Journal of neurological surgery reports Xu, L. W., Veeravagu, A., Azad, T. D., Harraher, C., Ratliff, J. K. 2016; 77 (3): e134-8


    Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management.We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve.The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function.Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function.

    View details for DOI 10.1055/s-0035-1568134

    View details for PubMedID 27602309

    View details for PubMedCentralID PMC5011454

  • Surgical outcomes of cervical spondylotic myelopathy: an analysis of a national, administrative, longitudinal database. Neurosurgical focus Veeravagu, A., Connolly, I. D., Lamsam, L., Li, A., Swinney, C., Azad, T. D., Desai, A., Ratliff, J. K. 2016; 40 (6): E11-?


    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.

    View details for DOI 10.3171/2016.3.FOCUS1669

    View details for PubMedID 27246481

  • Predicting Occurrence of Spine Surgery Complications Using "Big Data" Modeling of an Administrative Claims Database JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Ratliff, J. K., Balise, R., Veeravagu, A., Cole, T. S., Cheng, I., Olshen, R. A., Tian, L. 2016; 98 (10): 824-834


    Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery.We used longitudinal prospective data from a national claims database and developed a predictive model incorporating complication type and frequency of occurrence following spine surgery procedures. We structured our model to assess the impact of features such as preoperative diagnosis, patient comorbidities, location in the spine, anterior versus posterior approach, whether fusion had been performed, whether instrumentation had been used, number of levels, and use of bone morphogenetic protein (BMP). We assessed a variety of adverse events. Prediction models were built using logistic regression with additive main effects and logistic regression with main effects as well as all 2 and 3-factor interactions. Least absolute shrinkage and selection operator (LASSO) regularization was used to select features. Competing approaches included boosted additive trees and the classification and regression trees (CART) algorithm. The final prediction performance was evaluated by estimating the area under a receiver operating characteristic curve (AUC) as predictions were applied to independent validation data and compared with the Charlson comorbidity score.The model was developed from 279,135 records of patients with a minimum duration of follow-up of 30 days. Preliminary assessment showed an adverse-event rate of 13.95%, well within norms reported in the literature. We used the first 80% of the records for training (to predict adverse events) and the remaining 20% of the records for validation. There was remarkable similarity among methods, with an AUC of 0.70 for predicting the occurrence of adverse events. The AUC using the Charlson comorbidity score was 0.61. The described model was more accurate than Charlson scoring (p < 0.01).We present a modeling effort based on administrative claims data that predicts the occurrence of complications after spine surgery.We believe that the development of a predictive modeling tool illustrating the risk of complication occurrence after spine surgery will aid in patient counseling and improve the accuracy of risk modeling strategies.

    View details for DOI 10.2106/JBJS.15.00301

    View details for Web of Science ID 000378644500009

    View details for PubMedID 27194492

  • Neurorestoration after stroke NEUROSURGICAL FOCUS Azad, T. D., Veeravagu, A., Steinberg, G. K. 2016; 40 (5)


    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.

    View details for DOI 10.3171/2016.2.FOCUS15637

    View details for Web of Science ID 000375119300001

    View details for PubMedID 27132523

    View details for PubMedCentralID PMC4916840

  • Abducens Nerve Avulsion and Facial Nerve Palsy After Temporal Bone Fracture: A Rare Concomitance of Injuries. World neurosurgery Azad, T. D., Veeravagu, A., Corrales, C. E., Chow, K. K., Fischbein, N. J., Harris, O. A. 2016; 88: 689 e5-8


    Avulsion of the abducens nerve in the setting of geniculate ganglion injury after temporal bone fracture is unreported previously. We discuss clinical assessment and management of a patient with traumatic avulsion of cranial nerve (CN) VI in the setting of an ipsilateral CN VII injury after temporal bone fracture and call attention to this unusual injury.A 26-year-old man suffered a temporal bone fracture after a motor vehicle accident and developed diplopia and right-sided facial droop. Six weeks after the accident, the patient was readmitted with worsening diplopia and ipsilateral facial weakness. He demonstrated absent lateral gaze on the right suggestive of either restrictive movement or right.In addition, he had right-sided facial palsy graded as 6/6 House-Brackmann. High-resolution computed tomography demonstrated a right-sided longitudinal otic capsule-sparing temporal bone fracture that propagated into the facial nerve canal and geniculate fossa. Magnetic resonance imaging revealed discontinuity of the right CN VI between the pons and the Dorello canal, as well as injury to the ipsilateral geniculate ganglion. CN VII was intact proximally, from the pons through the internal auditory canal. Consensus was reached to proceed with conservative management. At 13 months after injury, the patient reported 1/6 House-Brackmann with no improvement in CN VI function.This case illustrates 2 subtle findings on imaging with potential therapeutic implications, notably the role of surgical intervention for facial nerve palsy.

    View details for DOI 10.1016/j.wneu.2015.11.076

    View details for PubMedID 26723286

  • Junior Seau: An Illustrative Case of Chronic Traumatic Encephalopathy and Update on Chronic Sports-Related Head Injury WORLD NEUROSURGERY Azad, T. D., Li, A., Pendharkar, A. V., Veeravagu, A., Grant, G. A. 2016; 86


    Few neurologic diseases have captured the nation's attention more completely than chronic traumatic encephalopathy (CTE), which has been discovered in the autopsies of professional athletes, most notably professional football players. The tragic case of Junior Seau, a Hall of Fame, National Football League linebacker, has been the most high-profile confirmed case of CTE. Here we describe Seau's case, which concludes an autopsy conducted at the National Institutes of Health that confirmed the diagnosis.Since 1990, Junior Seau had a highly distinguished 20-year career playing for the National Football League as a linebacker, from which he sustained multiple concussions. He committed suicide on May 2, 2012, at age 43, after which an autopsy confirmed a diagnosis of CTE. His clinical history was significant for a series of behavioral disturbances. Seau's history and neuropathologic findings were used to better understand the pathophysiology, diagnosis, and possible risk factors for CTE.This high-profile case reflects an increasing awareness of CTE as a long-term consequence of multiple traumatic brain injuries. The previously unforeseen neurologic risks of American football have begun to cast doubt on the safety of the sport.

    View details for DOI 10.1016/j.wneu.2015.10.032

    View details for Web of Science ID 000369625300104

    View details for PubMedID 26493714

  • A brief history of endoscopic spine surgery. Neurosurgical focus Telfeian, A. E., Veeravagu, A., Oyelese, A. A., Gokaslan, Z. L. 2016; 40 (2): E2-?


    Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development.

    View details for DOI 10.3171/2015.11.FOCUS15429

    View details for PubMedID 26828883

  • Postoperative Visual Loss Following Lumbar Spine Surgery: A Review of Risk Factors by Diagnosis WORLD NEUROSURGERY Li, A., Swinney, C., Veeravagu, A., Bhatti, I., Ratliff, J. 2015; 84 (6): 2010-2021

    View details for DOI 10.1016/j.wneu.2015.08.030

    View details for Web of Science ID 000366286300087

    View details for PubMedID 26341434

  • Craniotomy for Resection of Meningioma: An Age-Stratified Analysis of the MarketScan Longitudinal Database WORLD NEUROSURGERY Connolly, I. D., Cole, T., Veeravagu, A., Popat, R., Ratliff, J., Li, G. 2015; 84 (6): 1864-1870


    We sought to describe complications after resection for meningioma with the use of longitudinal administrative data, which our group has shown recently to be superior to nonlongitudinal administrative data.We identified patients who underwent resection for meningioma between 2010 and 2012 in the Thomson Reuters MarketScan database. Current Procedural Terminology coding at inpatient visit was used to select for meningioma resection procedure. Comorbidities and complications were obtained by use of the International Classification of Diseases, Ninth Revision or Current Procedural Terminology coding. Associations between complications and demographic and clinical factors were evaluated with logistic regression.We identified a total of 2216 patients. Approximately 41% developed 1 or more perioperative complications. Approximately 15% were readmitted within 30 days of their procedure. The most frequent complications that occurred in our cohort were new postoperative seizures (11.8%), postoperative dysrhythmia (7.9%), intracranial hemorrhage (5.9%), and cerebral artery occlusion (5.4%). General neurosurgical complications and general neurologic complications occurred in 4.4% and 16.1% of patients, respectively. Nearly 55% of elderly patients (≥ 70 years) developed 1 or more perioperative complication (vs. 39% of nonelderly patients). After we adjusted for comorbidities, elderly status and male sex were found to be significantly associated with increased odds for a variety of complications.In this study, we report complication rates in patients undergoing resection for meningioma. Because of the longitudinal nature of the MarketScan database, we were able to capture a wide array of specific postoperative complications associated with meningioma resection procedures. Care should be taken in the selection of candidates for meningioma resection.

    View details for DOI 10.1016/j.wneu.2015.08.018

    View details for Web of Science ID 000366286300065

    View details for PubMedID 26318633

  • Improved capture of adverse events after spinal surgery procedures with a longitudinal administrative database. Journal of neurosurgery. Spine Veeravagu, A., Cole, T. S., Azad, T. D., Ratliff, J. K. 2015; 23 (3): 374-382


    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.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.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.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.

    View details for DOI 10.3171/2014.12.SPINE14659

    View details for PubMedID 26068273

  • Improved capture of adverse events after spinal surgery procedures with a longitudinal administrative database JOURNAL OF NEUROSURGERY-SPINE Veeravagu, A., Cole, T. S., Azad, T. D., Ratliff, J. K. 2015; 23 (3): 374-382
  • Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease: A Retrospective Propensity Score-Matched Study of the MarketScan Database. Spine Cole, T., Veeravagu, A., Zhang, M., Azad, T. D., Desai, A., Ratliff, J. K. 2015; 40 (13): 1033-1038


    Retrospective 2:1 propensity score-matched analysis on a national longitudinal database between 2006 and 2010.To compare rates of adverse events, revisions procedure rates, and payment differences in anterior cervical fusion procedures compared with posterior laminectomy and fusion procedures with at least 3 levels of instrumentation.The comparative benefits of anterior versus posterior approach to multilevel degenerative cervical disease remain controversial. Recent systematic reviews have reached conflicting conclusions. We demonstrate the comparative economic and clinical outcomes of anterior and posterior approaches for multilevel cervical degenerative disk disease.We identified 13,662 patients in a national billing claims database who underwent anterior or posterior cervical fusion procedures with 3 or more levels of instrumentation. Cohorts were balanced using 2:1 propensity score matching and outcomes were compared using bivariate analysis.With the exception of dysphagia (6.4% in anterior and 1.4% in posterior), overall 30-day complication rates were lower in the anterior approach group. The rate of any complication excluding dysphagia with anterior approaches was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches, 17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical approach demonstrated significantly lower rate of 30-day readmission (5.1% vs. 9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%, P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).Anterior approaches in the surgical management of multilevel degenerative cervical disease provide clinical advantages over posterior approaches, including lower overall complication rates, revision procedure rates, and decreased length of stay. Anterior approach procedures are also associated with decreased overall payments. These findings must be interpreted in light of limitations inherent to retrospective longitudinal studies including absence of subjective and radiographical outcomes.3.

    View details for DOI 10.1097/BRS.0000000000000872

    View details for PubMedID 25768690

  • Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease A Retrospective Propensity Score-Matched Study of the MarketScan Database SPINE Cole, T., Veeravagu, A., Zhang, M., Azad, T. D., Desai, A., Ratliff, J. K. 2015; 40 (13): 1033-1038
  • Nelson Syndrome: Update on Therapeutic Approaches WORLD NEUROSURGERY Azad, T. D., Veeravagu, A., Kumar, S., Katznelson, L. 2015; 83 (6): 1135-1140
  • Nelson Syndrome: Update on Therapeutic Approaches. World neurosurgery Azad, T. D., Veeravagu, A., Kumar, S., Katznelson, L. 2015; 83 (6): 1135-1140


    To review the pathophysiology and therapeutic modalities availble for Nelson syndrome.We reviewed the current literature including managment for Nelson syndrome.For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS.An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome.

    View details for DOI 10.1016/j.wneu.2015.01.038

    View details for PubMedID 25683128

  • Perspective on "the role of adjuvant radiotherapy after gross total resection of atypical meningiomas". World neurosurgery Veeravagu, A., Azad, T. D., Chang, S. D. 2015; 83 (5): 737-738

    View details for DOI 10.1016/j.wneu.2015.01.047

    View details for PubMedID 25681598

  • National trends in burn and inhalation injury in burn patients: results of analysis of the nationwide inpatient sample database. Journal of burn care & research Veeravagu, A., Yoon, B. C., Jiang, B., Carvalho, C. M., Rincon, F., Maltenfort, M., Jallo, J., Ratliff, J. K. 2015; 36 (2): 258-265


    The aim of this study was describe national trends in prevalence, demographics, hospital length of stay (LOS), hospital charges, and mortality for burn patients with and without inhalational injury and to compare to the National Burn Repository. Burns and inhalation injury cause considerable mortality and morbidity in the United States. There remains insufficient reporting of the demographics and outcomes surrounding such injuries. The National Inpatient Sample database, the nation's largest all-payer inpatient care data repository, was utilized to select 506,628 admissions for burns from 1988 to 2008 based on ICD-9-CM recording. The data were stratified based on the extent of injury (%TBSA) and presence or absence of inhalational injury. Inhalation injury was observed in only 2.2% of burns with <20% TBSA but 14% of burns with 80 to 99% TBSA. Burn patients with inhalation injury were more likely to expire in-hospital compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P < .001). Other factors associated with higher mortality were African-American race, female sex, and urban practice setting. Patients treated at rural facilities and patients with hyperglycemia had lower mortality rates. Each increase in percent of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The median in-hospital charge for a burn patient with inhalation injury was US$32,070, compared to US$17,600 for those without. Overall, patients who expired from burn injury accrued higher in-hospital charges (median, US$50,690 vs US$17,510). Geographically, California and New Jersey were the states with the highest charges, whereas Vermont and Maryland were states with the lowest charges. The study analysis provides a broad sampling of nationwide demographics, LOS, and in-hospital charges for patients with burns and inhalation injury.

    View details for DOI 10.1097/BCR.0000000000000064

    View details for PubMedID 24918946

  • Intracranial fat migration: A newly described complication of autologous fat repair of a cerebrospinal fluid leak following supracerebellar infratentorial approach. International journal of surgery case reports Ludwig, C. A., Aujla, P., Moreno, M., Veeravagu, A., Li, G. 2015; 7C: 1-5


    Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported.The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra‑ and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48 hours and had almost fully resolved within one week.This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage.This case highlights the importance of monitoring for complications of lumbar drain placement.

    View details for DOI 10.1016/j.ijscr.2014.12.008

    View details for PubMedID 25557086

  • Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database. Cure¯us Cole, T., Veeravagu, A., Zhang, M., Azad, T., Swinney, C., Li, G. H., Ratliff, J. K., Giannotta, S. L. 2015; 7 (10)


    Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusions  Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.

    View details for DOI 10.7759/cureus.369

    View details for PubMedID 26623224

    View details for PubMedCentralID PMC4659577

  • The use of bone morphogenetic protein in thoracolumbar spine procedures: analysis of the MarketScan longitudinal database SPINE JOURNAL Veeravagu, A., Cole, T. S., Jiang, B., Ratliff, J. K., Gidwani, R. A. 2014; 14 (12): 2929-2937
  • Intraoperative Neuromonitoring in Single-Level Spinal Procedures A Retrospective Propensity Score-Matched Analysis in a National Longitudinal Database SPINE Cole, T., Veeravagu, A., Zhang, M., Li, A., Ratliff, J. K. 2014; 39 (23): 1950-1959
  • Usage of Recombinant Human Bone Morphogenetic Protein in Cervical Spine Procedures: Analysis of the MarketScan Longitudinal Database. journal of bone and joint surgery. American volume Cole, T., Veeravagu, A., Jiang, B., Ratliff, J. K. 2014; 96 (17): 1409-1416


    Usage of recombinant human bone morphogenetic protein (rhBMP) in anterior cervical discectomy and fusion (ACDF) procedures is controversial. Studies suggest increased rates of dysphagia, hematoma or seroma, and severe airway compromise in anterior cervical spine procedures using rhBMP. The purpose of the present study was to determine and describe national utilization trends and complication rates associated with rhBMP usage in anterior cervical spine procedures.The MarketScan database from 2006 to 2010 was retrospectively queried to identify 91,543 patients who underwent ACDF with or without cervical corpectomy. Patient selection and outcomes were ascertained with use of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) and CPT (Current Procedural Terminology) coding. A total of 3197 patients were treated with rhBMP intraoperatively. Mean follow-up was 588 days (interquartile range [IQR], 205 to 886 days) in the non-treated cohort and 591 days (IQR, 203 to 925 days) in the rhBMP-treated cohort. Multivariate logistic regression as well as propensity score analysis were used to evaluate the association of rhBMP usage with postoperative complications.In propensity score-adjusted models, rhBMP usage was associated with an increased risk of any complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.2 to 1.5) and specific complications such as hematoma or seroma (OR = 1.8, 95% CI = 1.4 to 2.3), dysphagia (OR = 1.3, 95% CI = 1.1 to 1.5), and any pulmonary complication (OR = 1.5, 95% CI = 1.2 to 1.8) within thirty days postoperatively. There were no significant differences in the rates of readmission, in-hospital mortality, referral to pain management, new malignancy, or reoperation between the two cohorts. Usage of rhBMP was associated with a mean increase of $5545 (19%) in total payments to the hospital and primary physician (p < 0.001).We found an increased overall rate of postoperative complications in patients receiving rhBMP for cervical spinal fusion procedures compared with patients not receiving rhBMP. Hematoma or seroma, pulmonary complications, and dysphagia were also more common in the rhBMP cohort. Usage of rhBMP in a case was associated with $311 greater payments to the surgeon and $4213 greater payments to the hospital.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

    View details for DOI 10.2106/JBJS.M.01016

    View details for PubMedID 25187578

  • Usage of Recombinant Human Bone Morphogenetic Protein in Cervical Spine Procedures JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Cole, T., Veeravagu, A., Jiang, B., Ratliff, J. K. 2014; 96A (17): 1409-1416
  • Acute Lung Injury in Patients with Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Study WORLD NEUROSURGERY Veeravagu, A., Chen, Y., Ludwig, C., Rincon, F., Maltenfort, M., Jallo, J., Choudhri, O., Steinberg, G. K., Ratliff, J. K. 2014; 82 (1-2): E235-E241
  • Revision rates and complication incidence in single- and multilevel anterior cervical discectomy and fusion procedures: an administrative database study SPINE JOURNAL Veeravagu, A., Cole, T., Jiang, B., Ratliff, J. K. 2014; 14 (7): 1125-1131
  • Neurosurgical interventions for spondyloepiphyseal dysplasia congenita: clinical presentation and assessment of the literature. World neurosurgery Veeravagu, A., Lad, S. P., Camara-Quintana, J. Q., Jiang, B., Shuer, L. 2013; 80 (3-4): 437 e1-8


    BACKGROUND: Spondyloepiphyseal dysplasia (SED) is a rare disease that causes vertebral abnormalities and short-trunk dwarfism. The two forms of SED are congenita and tarda. Each form arises in a genetically distinct fashion and manifests with a different set of complications. SED congenita is more severe, and patients usually display atlantoaxial instability and odontoid hypoplasia. Patients often have various neurologic deficits caused by compression of the spinal cord. The region most affected is the craniovertebral junction (CVJ). METHODS: A review of the PubMed Database, 1970 to the present, was performed using the search term "spondyloepiphyseal dysplasia" and limited to English-language articles. The search identified 22 articles discussing COL2A1 gene mutations and 10 clinical articles describing patients with SED and associated spinal abnormalities. RESULTS: Findings from the literature concerning diagnosis, presenting symptoms, and intervention taken are discussed. Additionally, a patient with a diagnosis of SED congenita who presented with bilateral hand numbness is described. The patient underwent a suboccipital craniotomy; posterior decompression of the foramen magnum, the arch of C1, and the lamina of C2; and instrumented fusion of C1-3 to relieve his symptoms. CONCLUSIONS: In this article, the authors survey the current literature surrounding neurosurgical interventions and present an algorithm for treatment.

    View details for DOI 10.1016/j.wneu.2012.01.030

    View details for PubMedID 22381876

  • CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas. Journal of neuro-oncology Jiang, B., Veeravagu, A., Feroze, A. H., Lee, M., Harsh, G. R., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2013; 114 (2): 209-218


    The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

    View details for DOI 10.1007/s11060-013-1172-9

    View details for PubMedID 23748573

  • Volumetric Analysis of Intracranial Arteriovenous Malformations Contoured for CyberKnife Radiosurgery With 3-Dimensional Rotational Angiography vs Computed Tomography/Magnetic Resonance Imaging. Neurosurgery Veeravagu, A., Hansasuta, A., Jiang, B., Karim, A. S., Gibbs, I. C., Chang, S. D. 2013; 73 (2): 262-270


    BACKGROUND:: Accurate target delineation has significant impact on brain arteriovenous malformations (AVMs) obliteration, treatment success, and potential complications of stereotactic radiosurgery. OBJECTIVE:: We compare the nidal contouring of AVMs using fused images of contrasted computerized tomography (CT) and magnetic resonance (MRI) with matched images of three-dimensional (3-D) cerebral angiography for Cyberknife radiosurgery (CKRS) treatment planning. METHODS:: Between May 2009 and April 2012, 3-D cerebral angiography was integrated into CKRS target planning for thirty consecutive patients. The AVM nidal target volumes were delineated using fused CT and MRI scans versus fused CT, MRI, and 3-D cerebral angiography for each patient. RESULTS:: The mean volume of the AVM nidus contoured with the addition of 3-D cerebral angiography to the CT/MRI fusion (9.09 cm, 95% CI 5.39-12.8 cm) was statistically smaller than the mean volume contoured with CT/ MRI fused scans alone (14.1 cm, 95% CI 9.16-19.1 cm), with a mean volume difference of δ=5.01 cm (p=0.001). Diffuse AVM nidus was associated with larger mean volume differences in comparison to a compact nidus (δ=6.51 vs. 2.11 cm, p=0.02). The mean volume difference was not statistically associated with the patient's gender (male δ=5.61, female δ=5.06, p=0.84), prior hemorrhage status (yes δ=5.69, no δ=5.23, p=0.86), or prior embolization status (yes δ=6.80, no δ=5.95, p=0.11). CONCLUSION:: For brain AVMs treated with CKRS, the addition of 3-D cerebral angiography to CT/MRI fusions for diagnostic accuracy results in a statistically significant reduction in contoured nidal volume as compared to standard CT/MRI fusion-based contouring.

    View details for DOI 10.1227/01.neu.0000430285.00928.30

    View details for PubMedID 23615081

  • Fungal infection of a ventriculoperitoneal shunt: histoplasmosis diagnosis and treatment. World neurosurgery Veeravagu, A., Ludwig, C., Camara-Quintana, J. Q., Jiang, B., Lad, N., Shuer, L. 2013; 80 (1-2): 222 e5-222 e13

    View details for DOI 10.1016/j.wneu.2012.12.016

    View details for PubMedID 23247021

  • Acute respiratory distress syndrome and acute lung injury in patients with vertebral column fracture(s) and spinal cord injury: a nationwide inpatient sample study SPINAL CORD Veeravagu, A., Jiang, B., Rincon, F., Maltenfort, M., Jallo, J., Ratliff, J. K. 2013; 51 (6): 461-465


    Study design:Retrospective Nationwide Inpatient Sample (NIS) study.Objectives:To determine national trends in prevalence, risk factors and mortality for vertebral column fracture (VCF) and spinal cord injury (SCI) patients with and without acute respiratory distress syndrome/acute lung injury (ARDS/ALI).Setting:United States of America, 1988 to 2008.Methods:The NIS was utilized to select 284 612 admissions for VCF with and without acute SCI from 1988 to 2008 based on ICD-9-CM. The data were stratified for in-hospital complications of ARDS/ALI.Results:Patients with SCI were more likely to develop ARDS/ALI compared with those without (odds ratio (OR): 4.9, 95% confidence interval (CI) 4.7-5.2, P<0.001). Compared with patients with lumbar fractures, those with cervical, thoracic and sacral fractures were more likely to develop ARDS/ALI (P<0.001). ARDS/ALI was statistically more prevalent (P<0.01) in VCF/SCI patients with epilepsy, sepsis, cardiac arrest, congestive heart failure (CHF), hypertension, chronic obstructive pulmonary disease and metabolic disorders. Patients with female gender, surgery at rural practice setting, and coronary artery disease and diabetes were less likely to develop ARDS/ALI (P<0.001). VCF/SCI patients who developed ARDS/ALI were more likely to die in-hospital than those without ARDS/ALI (OR 6.5, 95% CI 6.0-7.1, P<0.001). Predictors of in-hospital mortality after VCF/SCI include: older age, male sex, epilepsy, sepsis, hypertension, CHF, chronic obstructive pulmonary disease and liver disease. Patients who developed ARDS/ALI stayed a mean of 25 hospital days (30-440 days) while patients without ARDS/ALI stayed a mean of 6 days (7-868 days, P<0.001).Conclusion:Our analysis demonstrates that SCI patients are more at risk for ARDS/ALI, which carries a significantly higher risk of mortality.Spinal Cord advance online publication, 12 March 2013; doi:10.1038/sc.2013.16.

    View details for DOI 10.1038/sc.2013.16

    View details for Web of Science ID 000320224100007

    View details for PubMedID 23478670

  • Brain tuberculoma in a non-endemic area. Infectious disease reports Lober, R. M., Veeravagu, A., Singh, H. 2013; 5 (1)


    Brain tuberculoma has previously accounted for up to a third of new intracranial lesions in areas endemic with tuberculosis, but is unexpected in the United States and other Western countries with improved disease control. Here we show the importance of considering this diagnosis in at-risk patients, even with no definitive pulmonary involvement. We describe a young man who presented with partial seizures and underwent craniotomy for resection of a frontoparietal tuberculoma. He subsequently completed six months of antituberculosis therapy and was doing well without neurological sequelae or evidence of recurrence five months after completion of therapy. With resurgence of tuberculosis cases in the United States and other Western countries, intracerebral tuberculoma should remain a diagnostic consideration in at-risk patients with new space occupying lesions. Mass lesions causing neurological sequelae can be safely addressed surgically and followed with antituberculosis therapy.

    View details for DOI 10.4081/idr.2013.e1

    View details for PubMedID 24470952

  • Biopsy versus resection for the management of low-grade gliomas. Cochrane database of systematic reviews Veeravagu, A., Jiang, B., Ludwig, C., Chang, S. D., Black, K. L., Patil, C. G. 2013; 4: CD009319-?


    Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG.To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG.The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to week 3 November 2012), EMBASE (1980 to Week 46 2012). Unpublished and grey literature including Metaregister, Physicians Data Query,,, and were also queried for ongoing trials.Patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT) were included. Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL).A total of 2764 citations were searched and critically analyzed for relevance. This effort was undertaken by three independent review authors.No RCTs of biopsy or resection for LGG were identified. Twenty other studies were retrieved for analysis based on pre-specified selection criteria. Ten studies were retrospective or literature reviews. Three studies were prospective but were limited to tumor recurrence or the extent of resection. One study was a population-based parallel cohort and not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was focused on high-grade gliomas and not LGG. One last RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection.Currently there are no randomized clinical trials or controlled clinical trials available on which to base clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Future research could focus on randomized clinical trials to determine outcomes benefits for biopsy versus resection.

    View details for DOI 10.1002/14651858.CD009319.pub2

    View details for PubMedID 23633369

  • Traumatic epistaxis: Skull base defects, intracranial complications and neurosurgical considerations. International journal of surgery case reports Veeravagu, A., Joseph, R., Jiang, B., Lober, R. M., Ludwig, C., Torres, R., Singh, H. 2013; 4 (8): 656-661


    Endonasal procedures may be necessary during management of craniofacial trauma. When a skull base fracture is present, these procedures carry a high risk of violating the cranial vault and causing brain injury or central nervous system infection.A 52-year-old bicyclist was hit by an automobile at high speed. He sustained extensive maxillofacial fractures, including frontal and sphenoid sinus fractures (Fig. 1). He presented to the emergency room with brisk nasopharyngeal hemorrhage, and was intubated for airway protection. He underwent emergent stabilization of his nasal epistaxis by placement of a Foley catheter in his left nare and tamponade with the Foley balloon. A six-vessel angiogram showed no evidence of arterial dissection or laceration. Imaging revealed inadvertent insertion of the Foley catheter and deployment of the balloon in the frontal lobe (Fig. 2). The balloon was subsequently deflated and the Foley catheter removed. The patient underwent bifrontal craniotomy for dural repair of CSF leak. He also had placement of a ventriculoperitoneal shunt for development of post-traumatic hydrocephalus. Although the hospital course was a prolonged one, he did make a good neurological recovery.The authors review the literature involving violation of the intracranial compartment with medical devices in the settings of craniofacial trauma.Caution should be exercised while performing any endonasal procedure in the settings of trauma where disruption of the anterior cranial base is possible.

    View details for DOI 10.1016/j.ijscr.2013.04.033

    View details for PubMedID 23792475

  • Spontaneous intracranial hypotension secondary to anterior thoracic osteophyte: Resolution after primary dural repair via posterior approach. International journal of surgery case reports Veeravagu, A., Gupta, G., Jiang, B., Berta, S. C., Mindea, S. A., Chang, S. D. 2013; 4 (1): 26-29


    Spontaneous intracranial hypotension (SIH) is an uncommon syndrome widely attributed to CSF hypovolemia, typically secondary to spontaneous CSF leak. Although commonly associated with postural headache and variable neurological symptoms, one of the most severe consequences of SIH is bilateral subdural hematomas with resultant neurological deterioration.We present the case of a patient diagnosed with SIH secondary to an anteriorly positioned thoracic osteophyte with resultant dural disruption, who after multiple attempts at nonsurgical management developed bilateral subdural hematomas necessitating emergent surgical intervention. The patient underwent a unilateral posterior repair of his osteophyte with successful anterior decompression. At 36months follow up, the patient reported completely resolved headaches with no focal neurological deficits.We outline our posterior approach to repair of the dural defect and review the management algorithm for the treatment of patients with SIH. We also examine the current hypotheses as to the origin, pathophysiology, diagnosis and treatment of this syndrome.A posterior approach was utilized to repair the dural defect caused by an anterior thoracic osteophyte in a patient with severe SIH complicated by bilateral subdural hematomas. This approach minimizes morbidity compared to an anterior approach and allowed for removal of the osteophyte and repair of the dural defect.

    View details for DOI 10.1016/j.ijscr.2012.06.009

    View details for PubMedID 23108168

  • CyberKnife stereotactic radiosurgery for the treatment of intramedullary spinal cord metastases JOURNAL OF CLINICAL NEUROSCIENCE Veeravagu, A., Lieberson, R. E., Mener, A., Chen, Y., Soltys, S. G., Gibbs, I. C., Adler, J. R., Tian, A. G., Chang, S. D. 2012; 19 (9): 1273-1277


    Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

    View details for DOI 10.1016/j.jocn.2012.02.002

    View details for Web of Science ID 000308730900014

    View details for PubMedID 22766103

  • The effect of centralization of caseload for primary brain tumor surgeries: trends from 2001-2007 ACTA NEUROCHIRURGICA Nuno, M., Mukherjee, D., Carico, C., Elramsisy, A., Veeravagu, A., Black, K. L., Patil, C. G. 2012; 154 (8): 1343-1350


    Improved patient outcomes have been associated with high-caseload hospitals for a multitude of conditions. This study analyzed adult patients undergoing surgical resection or biopsy of primary brain tumors. The aim of this study is two-fold: (1) to evaluate whether the trend towards centralization of primary brain tumor care in the US has continued during the period of between 2001 and 2007, and (2) to analyze volume-outcome effects.Surgical volume trends of adults undergoing resection/biopsy of primary supratentorial brain tumors were analyzed using the Nationwide Inpatient Sample. High- and low-caseload hospitals were defined as those performing in the highest and lowest quintile of procedures, respectively. Length of stay (LOS), mortality and discharge disposition were the main outcomes of interest.NIS estimated 124,171 patients underwent resection/biopsy of primary supratentorial brain tumors between 2001 and 2007 in the US. The average number of annual resections in the highest 2 % and lowest 25 % caseload hospitals were 322 and 12 cases, respectively. Surgeries in high-caseload hospitals increased by 137 %, while those in low-caseload centers declined by 16.0 %. Overall, mortality decreased 35 %, with a reduction of 45 % in high- (from 2.2 % to 1.2 %) and 19 % in low- (from 3.2 % to 2.6 %) caseload hospitals. High-caseload centers had lower LOS than hospitals with lower caseload centers (6.4 vs. 8.0 days, p < 0.001). Multivariate analysis showed that patients treated in low-volume hospitals had an increased risk of death (OR 1.8, CI: 1.2-2.7, p = 0.006) and adverse discharge (OR 1.4, CI: 1.1-1.7, p = 0.01).Neurosurgical caseload at the nation's high volume craniotomy centers has continued to rise disproportionately, while low-caseload centers have seen a decrease in overall surgical volume. Over the time period between 2001 and 2007 there was a trend towards improved in-hospital mortality, LOS and discharge disposition for all hospitals; however, the trend is convincingly favorable for high-caseload hospitals.

    View details for DOI 10.1007/s00701-012-1358-5

    View details for Web of Science ID 000307242500003

    View details for PubMedID 22661296

  • Management of intracranial and extracranial chordomas with CyberKnife stereotactic radiosurgery JOURNAL OF CLINICAL NEUROSCIENCE Jiang, B., Veeravagu, A., Lee, M., Harsh, G. R., Lieberson, R. E., Bhatti, I., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2012; 19 (8): 1101-1106


    Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

    View details for DOI 10.1016/j.jocn.2012.01.005

    View details for Web of Science ID 000306500400009

    View details for PubMedID 22727205

  • Renal Osteodystrophy: Neurosurgical Considerations and Challenges WORLD NEUROSURGERY Veeravagu, A., Ponnusamy, K., Jiang, B., Bydon, M., McGirt, M., Gottfried, O. N., Witham, T., Gokaslan, Z. L., Bydon, A. 2012; 78 (1-2)


    Dialysis-associated destructive spondyloarthropathy (DSA) is the major bony complication of end-stage renal disease, most commonly found in the lower cervical region. The risk factors for developing dialysis-associated DSA include duration of hemodialysis and patient age. Patients with DSA have a higher incidence of osteoporosis and poor bone mineral density, which may place them at greater risk of atraumatic fractures, instrumentation failure, and neurologic compromise.We describe a case of cervical radiculopathy due to dialysis-associated DSA atraumatic vertebral body fractures with a postoperative course that was complicated by instrumentation failure. We reviewed the literature regarding all 138 published cases, presenting the complications, surgical treatment options, and outcomes.A 44-year-old dialysis-dependent man presented with acute neck pain, radiculopathy, and weakness due to atraumatic fracture of C5 and C6 vertebral bodies. He underwent anterior C5 and C6 corpectomies, reconstruction with mesh cage and plate, and supplemental posterior instrumentation (C4-T1). Six weeks later, a computed tomography scan revealed anterior translation across the instrumented area with failure of the posterior instrumentation. He subsequently underwent traction, revision reinstrumentation from C2 to T5, and placement of external halo ring/jacket for 6 months. At 18 months later, he remains ambulatory without evidence of construct failure.Patients with renal osteodystrophy present a challenge for the spine surgeon due to compromised bone density. Hardware failure at the bone-construct interface is common in these patients, with revision surgery needed in 22% of published cases. Longer constructs with circumferential instrumentation and halo immobilization may minimize the risk of pseudoarthrosis and construct pull-out.

    View details for DOI 10.1016/j.wneu.2011.09.027

    View details for Web of Science ID 000307933400050

    View details for PubMedID 22120255

  • Intramedullary spinal cord metastasis from prostate carcinoma: a case report. Journal of medical case reports Lieberson, R. E., Veeravagu, A., Eckermann, J. M., Doty, J. R., Jiang, B., Andrews, R., Chang, S. D. 2012; 6 (1): 139-?


    Although vertebral and epidural metastases are common, intradural metastases and intramedullary spinal cord metastases are rare. The indications for the treatment of intramedullary spinal cord metastases remain controversial. We present the first biopsy-proven case of an intramedullary spinal cord metastasis from adenocarcinoma of the prostate.Our patient was a 68-year-old right-handed Caucasian man with a Gleason grade 4 + 3 prostate adenocarcinoma who had previously undergone a prostatectomy, androgen blockade and transurethral debulking. He presented with new-onset saddle anesthesia and fecal incontinence. Magnetic resonance imaging demonstrated a spindle-shaped intramedullary lesion of the conus medullaris. Our patient underwent decompression and an excisional biopsy; the lesion's pathology was consistent with metastatic adenocarcinoma of the prostate. Postoperatively, our patient received CyberKnife® radiosurgery to the resection cavity at a marginal dose of 27Gy to the 85% isodose line. At three months follow-up, our patient remains neurologically stable with no new deficits or lesions.We review the literature and discuss the indications for surgery and radiosurgery for intramedullary spinal cord metastases. We also report the novel use of stereotactic radiosurgery to sterilize the resection cavity following an excisional biopsy of the metastasis.

    View details for DOI 10.1186/1752-1947-6-139

    View details for PubMedID 22657386

  • CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas JOURNAL OF HEMATOLOGY & ONCOLOGY Veeravagu, A., Jiang, B., Patil, C. G., Lee, M., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2011; 4


    Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

    View details for DOI 10.1186/1756-8722-4-26

    View details for Web of Science ID 000291817100001

    View details for PubMedID 21645367

    View details for PubMedCentralID PMC3118387

  • Craniotomy for resection of meningioma in the elderly: a multicentre, prospective analysis from the National Surgical Quality Improvement Program JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Patil, C. G., Veeravagu, A., Lad, S. P., Boakye, M. 2010; 81 (5): 502-505


    Whether there is an increased surgical risk in elderly patients who undergo craniotomy for meningioma resection remains a point of controversy. Utilising multicentre, prospective data from the National Surgical Quality Improvement Program, the present study sought to address this controversy.All patients who underwent a craniotomy for resection of intracranial meningioma (current procedural terminology codes 61512 and 61519) between 1997 and 2006 at 123 VA hospitals around the country were included. After controlling for preoperative factors such as ASA class, race, diabetes mellitus, disseminated cancer, tobacco use, tumour location and functional health status in a multivariate logistic regression model, the effect of elderly age (age greater than 70 years) on 30 day mortality was determined.Our study included 1281 patients who underwent surgical resection of an intracranial meningioma. Although each VA completed a different number of operations, we are able to provide case volume data for approximately 60 of the 123 hospitals. The elderly cohort represented 21.2% (n=258) of our total study population. Elderly patients had a higher 30 day mortality (12.0%) than younger subjects (4.6%) (p<0.0001). Similarly, elderly patients were more likely to have one or more complications (29.8% vs 13.1%, p<0.0001). Multivariate logistic regression identified age, functional status, preoperative disseminated cancer and tumour location as important predictors of 30 day mortality. After controlling for preoperative comorbidities and risk factors, the odds of perioperative mortality in elderly patients were three times that of younger patients (OR 3.0, 95% CI 1.7 to 5.3, p=0.0102).After carefully controlling for various patient characteristics, ASA class and functional status, elderly patients have poorer outcome after surgical resection of intracranial meningioma than younger subjects.

    View details for DOI 10.1136/jnnp.2009.185074

    View details for Web of Science ID 000277541800011

    View details for PubMedID 19828483

  • The role of radiosurgery in the treatment of craniopharyngiomas NEUROSURGICAL FOCUS Veeravagu, A., Lee, M., Jiang, B., Chang, S. D. 2010; 28 (4)


    The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.

    View details for DOI 10.3171/2010.2.FOCUS09311

    View details for Web of Science ID 000276212900014

    View details for PubMedID 20367355

  • Resolution of syringomyelia after release of tethered cord SURGICAL NEUROLOGY Hsu, A. R., Hou, L. C., Veeravagu, A., Barnes, P. D., Huhn, S. L. 2009; 72 (6): 657-661


    Syringomyelia is an abnormal cystic dilatation of the spinal cord caused by excessive accumulation of CSF. Patients can develop various neurologic deficits secondary to untreated syringomyelia, some of which can be permanent despite surgical intervention.The authors present a patient with syringomyelia, aortic coarctation, and tethered cord syndrome. Serial radiographic imaging demonstrated initial significant reduction of the thoracic syrinx after coarctation repair and release of tethered cord. However, subsequent follow-up imaging revealed partial recurrence.This case provides evidence of a possible cause-effect relationship between syringomyelia and tethered cord. It demonstrates the indication of surveillance imaging of the entire spine to ensure that all potential etiologies of syringomyelia are identified and treated. Furthermore, it illustrates the complex dynamic nature of syrinx physiology and reinforces the importance of serial follow-up studies after surgical intervention.

    View details for DOI 10.1016/j.surneu.2009.05.016

    View details for Web of Science ID 000279233900026

    View details for PubMedID 19604546

  • HMG-CoA Reductase Inhibition Causes Increased Necrosis and Apoptosis in an In Vivo Mouse Glioblastoma Multiforme Model ANTICANCER RESEARCH Bababeygy, S. R., Polevaya, N. V., Youssef, S., Sun, A., Xiong, A., Prugpichailers, T., Veeravagu, A., Hou, L. C., Steinman, L., Tse, V. 2009; 29 (12): 4901-4908


    Statins are thought to have tumorolytic properties, reducing angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural pericytes within the tumor vascular tree.An orthotopic mouse glioblastoma (GL-26) model was used to investigate the effect of simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into the striatum of C5LKa mice treated with either control, low- or high-dose simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and pericytic cells within the vascular tree.Low-dose simvastatin increased necrosis and apoptosis compared to both control and high-dose simvastatin groups. High-dose simvastatin increased vessel caliber by reducing pericytic cells along the tumor vessel wall compared to both control and low-dose simvastatin groups.Simvastatin has a dual effect on tumorigenesis. At high doses, it may worsen instead of 'normalizing' tumor angio-architecture, albeit low doses affect tumor cell survival by promoting necrosis and apoptosis.

    View details for Web of Science ID 000273365700001

    View details for PubMedID 20044596

  • Risk Factors for Postoperative Spinal Wound Infections After Spinal Decompression and Fusion Surgeries SPINE Veeravagu, A., Patil, C. G., Lad, S. P., Boakye, M. 2009; 34 (17): 1869-1872


    This is a multivariate analysis of a prospectively collected database.To determine preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery.Current literature sites a postoperative infection rate of approximately 4%; however, few have completed multivariate analysis to determine factors which contribute to risk of infection.Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs' National Surgical Quality Improvement Program database. Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection.Data on 24,774 patients were analyzed. Wound infection was present in 752 (3.04%) patients, 287 (1.16%) deep, and 468 (1.89%) superficial. Postoperative infection was associated with longer hospital stay (7.12 vs. 4.20 days), higher 30-day mortality (1.06% vs. 0.5%), higher complication rates (1.24% vs. 0.05%), and higher return to the operating room rates (37% vs. 2.45%). Multivariate logistic regression identified insulin dependent diabetes (odds ratios [OR] = 1.50), current smoking (OR = 1.19) ASA class of 3 (OR = 1.45) or 4 to 5 (OR = 1.66), weight loss (OR = 2.14), dependent functional status (1.36) preoperative HCT <36 (1.37), disseminated cancer (1.83), fusion (OR = 1.24) and an operative duration of 3 to 6 hours (OR = 1.33) or >6 hours (OR = 1.40) as statistically significant predictors of postoperative infection.Using multivariate analysis of a large prospectively collected data from the National Surgical Quality Improvement Program database, we identified the most important risk factors for increased postoperative spinal wound infection. We have demonstrated the high mortality, morbidity, and hospitalization costs associated with postoperative spinal wound infections. The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients.

    View details for DOI 10.1097/BRS.0b013e3181adc989

    View details for Web of Science ID 000268720000018

    View details for PubMedID 19644339

  • Integrin alpha(v)beta(3)-Targeted Radioimmunotherapy of Glioblastoma Multiforme CLINICAL CANCER RESEARCH Veeravagu, A., Liu, Z., Niu, G., Chen, K., Jia, B., Cai, W., Jin, C., Hsu, A. R., Connolly, A. J., Tse, V., Wang, F., Chen, X. 2008; 14 (22): 7330-7339


    Abegrin is a monoclonal antibody to human integrin alphavbeta3, a cell adhesion molecule highly expressed on actively angiogenic endothelium and glioblastoma multiforme tumor cells. The purpose of this study was to evaluate the efficacy of a novel 90Y-Abegrin radioimmunotherapeutic agent in murine xenograft glioblastoma models with noninvasive in vivo molecular imaging modalities.A s.c. U87MG human glioblastoma xenograft model was used to determine maximum tolerated dose (MTD), biodistribution, dose response, and efficacy of 90Y-Abegrin. Antitumor efficacy was also characterized in an orthotopic U87MG and in a HT-29 colorectal cancer model, a low integrin-expressing carcinoma. Small-animal positron emission tomography imaging was used to correlate histologic findings of treatment efficacy.MTD and dose response analysis revealed 200 microCi per mouse as appropriate treatment dose with hepatic clearance and no organ toxicity. 90Y-Abegrin-treated U87MG tumor mice showed partial regression of tumor volume, with increased tumor volumes in 90Y-IgG, Abegrin, and saline groups. 18F-FDG imaging revealed a reduction of cell proliferation and metabolic activity whereas 18F-FLT reflected decreased DNA synthesis in the 90Y-Abegrin group. Ki67 analysis showed reduced proliferative index and quantitative terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive analysis revealed increased DNA fragmentation and apoptosis in 90Y-Abegrin animals. CD31 and 4',6-diamidino-2-phenylindole staining showed increased vascular fragmentation and dysmorphic vessel structure in 90Y-Abegrin animals only. Orthotopic U87MG tumors treated with 90Y-Abegrin displayed reduced tumor volume. HT-29 tumors showed no significant difference among the various groups.Radioimmunotherapy with 90Y-labeled Abegrin may prove promising in the treatment of highly vascular, invasive, and heterogeneous malignant brain tumors.

    View details for DOI 10.1158/1078-0432.CCR-08-0797

    View details for Web of Science ID 000261014500021

    View details for PubMedID 19010848

  • The temporal correlation of dynamic contrast-enhanced magnetic resonance imaging with tumor angiogenesis in a murine glioblastoma model 56th Annual Meeting of the Congress-of-Neurological-Surgeons Veeravagu, A., Hou, L. C., Hsu, A. R., Cai, W., Greve, J. M., Chen, X., Tse, V. MANEY PUBLISHING. 2008: 952–59


    Glioblastoma multiforme (GBM) is a WHO grade IV malignant brain tumor with poor prognosis, despite advances in surgical and adjuvant therapy. GBM is characterized by areas of central necrosis and high levels of angiogenesis, during which increased vascular permeability allows for the extravasation of endothelial progenitor cells to support blood vessel and tumor growth. The purpose of this study was to characterize changes in tumor vascular permeability, vascular density and vessel morphology in vivo during angiogenesis.An orthotropic murine (GL26) glioblastoma model was used in this study. in vivo serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in combination with histologic and molecular genetic analyses was performed to correlate in vivo imaging of vascular development.DCE-MRI revealed a significant change in tumor vessel permeability dependent upon tumor progression and size. Time to max signal intensity displayed a stepwise increase between days 21 and 24 (p<0.05), a critical period before exponential tumor growth during which a significant increase in tumor vascular density and vessel caliber is observed on histology. Furthermore, quantitative real-time PCR revealed a corollary increase in angiogenic signaling molecules before the observed changes on DCE-MRI.In vivo changes of orthotopic glioma blood vessel permeability as shown by DCE-MRI correlates with histologic quantification of vascular density and vessel caliber as well as with the molecular expression of angiogenic factors. DCE-MRI is a useful tool for non-invasive in vivo monitoring of angiogenesis in pre-clinical tumor models.

    View details for DOI 10.1179/174313208X322761

    View details for Web of Science ID 000261323000013

    View details for PubMedID 18662497

  • The Cancer Stem Cell-Vascular Niche Complex in Brain Tumor Formation STEM CELLS AND DEVELOPMENT Veeravagu, A., Bababeygy, S. R., Kalani, M. Y., Hou, L. C., Tse, V. 2008; 17 (5): 859-867


    The cancer stem cell (CSC) theory hypothesizes that a small subpopulation of cells within a tumor mass is responsible for the initiation and maintenance of the tumor. The idea that brain tumors arise from this specific subset of self-renewing, multipotent cells that serve as the locus for tumor formation, has gained great support as evidenced by recent advancements in the biology of breast and colon cancer. It is well established that recruitment of bone marrow-derived proangiogenic progenitor cells and angiogenesis are key events in the process of brain tumor formation; however, the orchestration of these events by the CSC population has only recently been unveiled. In this review, we first introduce the CSC theory and examine the functional development of the vascular niche, its purpose, constituents, and contribution to the development of the CSC-vascular niche complex. Through this discussion, we aim to shed light on the events that may be targeted for therapeutic intervention.

    View details for DOI 10.1089/scd.2008.0047

    View details for Web of Science ID 000260190100004

    View details for PubMedID 18429673

  • Outcomes after repeat transsphenoidal surgery for recurrent Cushing's disease NEUROSURGERY Patil, C. G., Veeravagu, A., Prevedello, D. A., Katznelson, L., Vance, M. L., Laws, E. R., Kelly, D. F., Oyesiku, N. M., Post, K. D., Esposito, F., Cappabianca, P. 2008; 63 (2): 266-271


    To systematically analyze patient outcomes after repeat transsphenoidal (TS) surgery for recurrent Cushing's disease.We retrospectively reviewed records of all patients with recurrent Cushing's disease who underwent repeat TS surgery for resection of a pituitary corticotroph adenoma at the University of Virginia Medical Center from 1992 to 2006. Remission at follow-up was defined as a normal postoperative 24-hour urine free cortisol, or continued need for glucocorticoid replacement after repeat TS surgery. Recurrence of the disease was defined as an elevated 24-hour urine free cortisol with clinical symptoms consistent with Cushing's disease while not receiving glucocorticoid replacement. Multivariate logistic regression was performed to evaluate the effect of potential predictors on remission. Recurrence rates, subsequent treatments, and the final endocrine status of the patients are presented.We identified 36 patients who underwent repeat TS surgery for recurrent Cushing's disease. The mean age of the patients was 40.3 years (range, 17.1-63.0 yr), and 26 were women. The median time to recurrence after initial successful TS surgery was 36 months (range, 4 mo-16 yr). Remission after repeat TS surgery was observed in 22 (61%) of the 36 patients. During the same time period, of the 338 patients who underwent first-time TS surgery for Cushing's disease, remission was achieved in 289 (85.5%). The odds of failure (to achieve remission) for patients with repeat TS surgery for recurrent Cushing's disease were 3.7 times that of patients undergoing first-time TS surgery (odds ratio, 3.7; 95% confidence interval, 1.8-7.8). Two of the 22 patients with successful repeat TS surgery had a second recurrence at 6 and 11 months, respectively. Complete biochemical and clinical remission after stereotactic radiosurgery, adrenalectomy, and ongoing ketoconazole therapy was achieved in 30 (83.3%) of the 36 patients, and active disease continued in 6 patients (16.7%).Although the success of repeat TS surgery for recurrence of Cushing's disease is less than that of initial surgery, a second procedure offers a reasonable possibility of immediate remission. If the operation is not successful, other treatments, including pituitary radiation, medical therapy, and even bilateral adrenalectomy, are required.

    View details for DOI 10.1227/01.NEU.0000313117.35824.9F

    View details for Web of Science ID 000258944100017

    View details for PubMedID 18797356

  • Moyamoya disease in pediatric patients: outcomes of neurosurgical interventions NEUROSURGICAL FOCUS Veeravagu, A., Guzman, R., Patil, C. G., Hou, L. C., Lee, M., Steinberg, G. K. 2008; 24 (2)


    Neurosurgical interventions for moyamoya disease (MMD) in pediatric patients include direct, indirect, and combined revascularization procedures. Each technique has shown efficacy in the treatment of pediatric MMD; however, no single study has demonstrated the superiority of one technique over another. In this review, the authors explore the various studies focused on the use of these techniques for MMD in the pediatric population. They summarize the results of each study to clearly depict the clinical outcomes achieved at each institution that had utilized direct, indirect, or combined techniques. In certain studies, multiple techniques were used, and the clinical or radiological outcomes were compared accordingly. Direct techniques have been shown to aid a reduction in perioperative strokes and provide immediate revascularization to ischemic areas; however, these procedures are technically challenging, and not all pediatric patients are appropriate candidates. Indirect techniques have also shown efficacy in the pediatric population but may require a longer period for revascularization to occur and perfusion deficits to be reversed. The authors concluded that the clinical efficacy of one technique over another is still unclear, as most studies have had small populations and the same outcome measures have not been applied. Authors who compared direct and indirect techniques noted approximately equal clinical outcomes with differences in radiological findings. Additional, larger studies are needed to determine the advantages and disadvantages of the different techniques for the pediatric age group.

    View details for DOI 10.3171/FOC/2008/24/2/E16

    View details for Web of Science ID 000256268400018

    View details for PubMedID 18275292

  • Glutaric acidemia type I: a neurosurgical perspective JOURNAL OF NEUROSURGERY Hou, L. C., Veeravagu, A., Hsu, A. R., Enns, G. M., Huhn, S. L. 2007; 107 (2): 167-172


    Glutaric acidemia type I (GA-I) is a rare, autosomal recessive metabolic disorder that leads to severe dystonia, basal ganglia degeneration, and bilaterally enlarged anterior middle cranial fossae. The current management of this disease includes early diagnosis with newborn screening, prevention of catabolism, carnitine supplementation, and a strict dietary protein restriction. Neurosurgical evaluation and intervention may be necessary in patients with structural lesions associated with this disease. In this report, the authors present two pediatric patients with GA-I and discuss the neurosurgical aspects of this rare medical disorder.

    View details for DOI 10.3171/PED-07/08/167

    View details for Web of Science ID 000248626600016

    View details for PubMedID 18459892

  • Integrin alpha(v)beta(3) antagonists for anti-angiogenic cancer treatment RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY Hsu, A. R., Veeravagu, A., Cai, W., Hou, L. C., Tse, V., Chen, X. 2007; 2 (2): 143-158


    Direct contact between cellular and extracellular matrix (ECM) proteins is necessary for a diverse array of physiologic processes including cellular activation, migration, proliferation, and differentiation. These direct interactions are modulated by cell adhesion molecules (CAMs) such as integrins, selectins, cadherins, and immunoglobulins. Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. Recent advances in the discovery and characterization of CAMs and their receptors, most notably integrin alpha(v)beta(3), and the clarification of their roles in disease states have laid the groundwork for the development and clinical implementation of novel anti-cancer treatments. Integrin alpha (v)beta(3) is a glycoprotein membrane receptor which recognizes ECM proteins expressing an arginine-glycine-aspartic acid (RGD) peptide sequence. The receptor is highly expressed on activated tumor endothelial cells, but not resting endothelial cells and normal organ systems, thus making alpha(v)beta(3) an appropriate target for anti-angiogenic therapeutics. In addition, alpha(v)beta(3) is also expressed on tumor cells, allowing for both tumor cell and tumor vasculature targeting of anti-integrin therapy. Throughout the past decade, numerous patents have been published and issued using alpha(v)beta(3) antagonists for the prevention and/or treatment of cancer, with many antagonists demonstrating positive pre-clinical anti-angiogenic and anti-tumor results. This review will focus on the key points and distinguishing factors for patents which use antibodies, RGD peptides, non-RGD peptides, peptidomimetics, and amine salts as alpha(v)beta(3) antagonists.

    View details for Web of Science ID 000247259700004

    View details for PubMedID 18221059

  • Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF(121)/rGel JOURNAL OF NUCLEAR MEDICINE Hsu, A. R., Cai, W., Veeravagu, A., Mohamedali, K. A., Chen, K., Kim, S., Vogel, H., Hou, L. C., Tse, V., Rosenblum, M. G., Chen, X. 2007; 48 (3): 445-454


    Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1/FLT-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF(121)/rGel) composed of the VEGF-A isoform VEGF(121) linked with a G(4)S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET.Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with (64)Cu-1,4,7,10-tetraazacyclododedane-N,N',N'',N'''-tetraacetic acid (DOTA)-VEGF(121)/rGel was performed before VEGF(121)/rGel treatment. (18)F-Fluorothymidine ((18)F-FLT) scans were obtained before and after treatment to evaluate VEGF(121)/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses.Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with (64)Cu-DOTA-VEGF(121)/rGel before treatment revealed a tumor accumulation (mean +/- SD) of 11.8 +/- 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF(121). PET with (18)F-FLT revealed significant a decrease in tumor proliferation in VEGF(121)/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF(121)/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity.The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF(121)/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.

    View details for Web of Science ID 000244937400026

    View details for PubMedID 17332623

  • Vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors as anti-angiogenic agents in cancer therapy RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY Veeravagu, A., Hsu, A. R., Cai, W., Hou, L. C., Tse, V. C., Chen, X. 2007; 2 (1): 59-71


    New blood vessel formation (angiogenesis) is fundamental to the process of tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of ligands and receptors are well established as key regulators of these processes. VEGF is a glycoprotein with mitogenic activity on vascular endothelial cells. Specifically, VEGF-receptor pathway activation results in signaling cascades that promote endothelial cell growth, migration, differentiation, and survival from pre-existing vasculature. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Recent identification of seven VEGF ligand variants (VEGF [A-F], PIGF) and three VEGF tyrosine kinase receptors (VEGFR- [1-3]) has led to the development of several novel inhibitory compounds. Clinical trials have shown inhibitors to this pathway (anti-VEGF therapies) are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. Having been first described in the 1980s, VEGF patenting activity since then has focused on anti-cancer therapeutics designed to inhibit tumoral vascular formation. This review will focus on patents which target VEGF-[A-F] and/or VEGFR-[1-3] for use in anti-cancer treatment.

    View details for Web of Science ID 000246564300004

    View details for PubMedID 18221053

  • Spinal gout in a renal transplant patient: a case report and literature review SURGICAL NEUROLOGY Hou, L. C., Hsu, A. R., Veeravagu, A., Boakye, M. 2007; 67 (1): 65-73


    Gout in the axial spine is rare. We present a case report on a renal transplant patient who developed fever and acute back pain at the L5 through S1 level secondary to sodium urate deposits. We review the literature on this rare disease and propose a management algorithm based on a resulting analysis.A 37-year-old man with a history of gout and a renal transplant for IgA nephropathy presented with acute back pain and fever without evidence of neurological deficits. Magnetic resonance imaging revealed a uniformly contrast-enhancing infiltrative process involving the right pedicle, lamina, and inferior facet of the L5 vertebra. Computed tomography-guided needle biopsy revealed a friable white tissue consistent with sodium urate crystals. Conservative treatment with steroids and narcotics was used with good symptomatic relief.Although few cases of gout involving the spine have been reported, its prevalence is likely grossly underestimated. Most patients have a history of gout and have elevated levels of serum urate level on presentation. The disease most commonly involves the lumbar spine. Patients usually have neurological deficits on presentation, and surgical decompression produces favorable outcomes. However, conservative medical management is appropriate for those with back pain only. Aggressive control of hyperuricemia is essential regardless of the method of treatment.

    View details for DOI 10.1016/j.surneu.2006.03.038

    View details for Web of Science ID 000243798000014

    View details for PubMedID 17210304

  • CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurgical focus Patil, C. G., Veeravagu, A., Bower, R. S., Li, G., Chang, S. D., Lim, M., Adler, J. R. 2007; 23 (6): E9-?


    Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

    View details for PubMedID 18081486

  • Molecular events of brain metastasis. Neurosurgical focus Santarelli, J. G., Sarkissian, V., Hou, L. C., Veeravagu, A., Tse, V. 2007; 22 (3): E1-?


    The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naive brain and cancer cells is made in advance of any metastatic breach of the blood-brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

    View details for PubMedID 17608351

  • In vivo near-infrared fluorescence imaging of integrin alpha(v)beta(3) in an orthotopic glioblastoma model MOLECULAR IMAGING AND BIOLOGY Hsu, A. R., Hou, L. C., Veeravagu, A., Greve, J. M., Vogel, H., Tse, V., Chen, X. 2006; 8 (6): 315-323


    Expression of cell adhesion molecule integrin alpha(v)beta(3) is significantly up-regulated during tumor growth, and sprouting of tumor vessels and correlates well with tumor aggressiveness. The purpose of this study was to visualize tumor integrin alpha(v)beta(3) expression in vivo by using near-infrared fluorescence (NIRF) imaging of Cy5.5-linked cyclic arginine-glycine-aspartic acid (RGD) peptide in an orthotopic brain tumor model.U87MG glioma cells transfected with the firefly luciferase gene were stereotactically injected into nude mice in the right frontal lobe. Bioluminescence imaging (BLI) using D: -luciferin substrate and small animal magnetic resonance imaging (MRI) using gadolinium contrast enhancement were conducted weekly after tumor cell inoculation to monitor intracranial tumor growth. Integrin alpha(v)beta(3) expression was assessed by using a three-dimensional optical imaging system (IVIS 200) 0-24 hours after administration of 1.5 nmol monomeric Cy5.5-RGD via the tail vein. Animals were injected intravenously with both Texas Red-tomato lectin and Cy5.5-RGD prior to sacrifice to visualize peptide localization to tumor vasculature using histology.Fluorescence microscopy demonstrated specific Cy5.5-RGD binding to both U87MG tumor vessels and tumor cells with no normal tissue binding. NIRF imaging showed highest tumor uptake and tumor to normal brain tissue ratio two hours postinjection (2.64 +/- 0.20). Tumor uptake of Cy5.5-RGD was effectively blocked by using unlabeled c(RGDyK), and injection of Cy5.5 dye alone showed nonspecific binding.Optical imaging via BLI and NIRF offer a simple, effective, and rapid technique for noninvasive in vivo monitoring and semiquantitative analysis of intracranial tumor growth and integrin alpha(v)beta(3) expression. This study suggests that NIRF via fluorescently labeled RGD peptides may provide enhanced surveillance of tumor angiogenesis and anti-integrin treatment efficacy in orthotopic brain tumor models.

    View details for DOI 10.1007/s11307-006-0059-y

    View details for Web of Science ID 000242428500001

    View details for PubMedID 17053862

  • Recurrent glioblastoma multiforme: a review of natural history and management options. Neurosurgical focus Hou, L. C., Veeravagu, A., Hsu, A. R., Tse, V. C. 2006; 20 (4): E5-?


    Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.

    View details for PubMedID 16709036