Bio

Bio


Dr. Tene Cage is a Clinical Assistant Professor of Neurological Surgery at Stanford University. She received a B.A. degree from Harvard University and graduated with cum laude honors. She then went on to complete her medical school education and Neurological Surgery residency training at the University of California San Francisco (UCSF) School of Medicine. She also has completed a Neurotrauma fellowship at UCSF and San Francisco General Hospital with Geoff Manley, MD, PhD where she received specialized training in caring for patients after traumatic brain and spinal cord injuries.

She has been a member of the Alpha Omega Alpha Medical Society since 2010. During residency, she was awarded the Exceptional Physician Award from UCSF Medical Center and the Howard Nafzigger Award from the UCSF Department of Neurological Surgery for outstanding patient care.

Dr. Cage has comprehensive neurosurgical training in treating traumatic brain injury, traumatic spine injury, degenerative and oncologic spine disorders, as well as extra-axial and intra-axial brain tumors.

Her research interest focuses on working towards eliminating health disparities in neurosurgical outcomes. She specifically focuses on understanding the association between socioeconomic and demographic characteristics and patient outcomes following traumatic brain injury. Dr. Cage has authored over 30 research articles and has received grants to support her research including the UCSF Genentech Foundation Research Fellow Award and the Howard Hughes Medical Institute Research Fellow Award. Her research has been recognized with the Lucien J. Rubenstein Memorial Award from the American Brain Tumor Association, the Young Investigator Award from the Pediatric Brain Tumor Foundation, and the Best Basic Science Research Paper Award from UCSF Neurological Surgery residency program.

She is also dedicated to and passionate about student and resident mentorship and training.

Academic Appointments


Honors & Awards


  • Auxillary to the Sinkler-Miller Medical Association Scholarship, Sinkler-Miller Medical Association (2003)
  • Sinkler-Miller Medical Association Scholarship, Sinkler-Miller Medical Association (2004)
  • Lucien J. Rubenstein Memorial Award, American Brain Tumor Association (2005)
  • Research Fellow, UCSF Genentech Foundation (2005-5006)
  • Research Fellow, Howard Hughes Medical Institute (2006-2007)
  • Young Investigator Award, The Pediatric Brain Tumor Foundation (2007)
  • Howard Nafzigger Award for outstanding patient care, UCSF Neurological Surgery (2013)
  • Delmar C. Sanders, MD Scholarship, Sinkler-Miller Medical Association (2015, 2016)
  • Exceptional Physician Award, UCSF Medical Center (2015)
  • Best Basic Science Research Paper Award, UCSF Neurological Surgery Residency Program (2018)

Boards, Advisory Committees, Professional Organizations


  • Member, Congress of Neurological Surgeons (2010 - Present)
  • Member, Alpha Omega Alpha Medical Society (2010 - Present)

Professional Education


  • Fellowship, University of California San Francisco, Neurotrauma Fellowship (2018)
  • Residency, University of California San Francisco, Neurological Surgery (2016)
  • Internship, University of California San Francisco, Neurological Surgery (2011)
  • M.D., University of California San Francisco School of Medicine, Medicine (2010)
  • B.A., Harvard University, Biology with certificate in Neurobiology, cum laude (2001)

Research & Scholarship

Current Research and Scholarly Interests


Dr. Cage's research interest is in working towards eliminating health disparities in neurosurgical outcomes. She specifically focuses on understanding the association between socioeconomic and demographic characteristics and patient outcomes following traumatic brain injury.

Publications

All Publications


  • Preinjury employment status as a risk factor for symptomatology and disability in mild traumatic brain injury: A TRACK-TBI analysis NEUROREHABILITATION Yue, J. K., Rick, J. W., Morrissey, M., Taylor, S. R., Deng, H., Suen, C. G., Vassar, M. J., Cnossen, M. C., Lingsma, H. F., Yuh, E. L., Mukherjee, P., Gardner, R. C., Valadka, A. B., Okonkwo, D. O., Cage, T. A., Manley, G. T., TRACK-TBI Investigators 2018; 43 (2): 169?82

    Abstract

    Preinjury employment status may contribute to disparity, injury risk, and recovery patterns following mild traumatic brain injury (MTBI).To characterize associations between preinjury unemployment, prior comorbidities, and outcomes following MTBI.MTBI patients from TRACK-TBI Pilot with complete six-month outcomes were extracted. Preinjury unemployment, comorbidities, injury factors, and intracranial pathology were considered. Multivariable regression was performed for employment and outcomes, correcting for demographic and injury factors. Mean-differences (B) and 95% CIs are reported. Statistical significance was assessed at p < 0.05.162 MTBI patients were aged 39.8±15.4-years and 24.6% -unemployed. Unemployed patients demonstrated increased psychiatric comorbidities (45.0% -vs.- 23.8%; p = 0.010), drug use (52.5% -vs.- 21.3%; p < 0.001), smoking (62.5% -vs.- 27.0%; p < 0.001), prior TBI (78.4% -vs.- 55.0%; p = 0.012), and lower education (15.0% -vs.- 45.1% college degree; p = 0.003). On multivariable analysis, unemployment associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended: B = - 0.50, 95% CI [- 0.88, - 0.11]), increased psychiatric disturbance (Brief Symptom Inventory-18: B = 6.22 [2.33, 10.10]), postconcussional symptoms (Rivermead Questionnaire: B = 4.91 [0.38, 9.44]), and post-traumatic stress disorder (PTSD Checklist-Civilian: B = 5.99 [0.76, 11.22]). No differences were observed for cognitive measures or satisfaction with life.Unemployed patients are at risk for preinjury psychosocial comorbidities, poorer six-month functional recovery and increased psychiatric/postconcussional/PTSD symptoms. Resource allocation and return precautions should be implemented to mitigate and/or prevent the decline of at-risk patients.

    View details for DOI 10.3233/NRE-172375

    View details for Web of Science ID 000443290000007

    View details for PubMedID 30040754

  • Ethnicity, Race, and Postoperative Stroke Risk Among 53,593 Patients with Asymptomatic Carotid Stenosis Undergoing Revascularization WORLD NEUROSURGERY Garcia, R. M., Yoon, S., Cage, T., Potts, M. B., Lawton, M. T. 2017; 108: 246?53

    Abstract

    The incidence of postoperative stroke after carotid endarterectomy is an uncommon event, and differences by racial and ethnic subgroups are not described fully in the literature.To investigate the impact of race and ethnicity on postoperative stroke risk among patients with asymptomatic carotid stenosis undergoing carotid endarterectomy.The American College of Surgeons National Surgical Quality Improvement Program database was searched for patients between the dates 2008 and 2015 to identify patients undergoing carotid endarterectomy with no history of stroke. Four racial and ethnic subgroups were included: non-Hispanic white, Hispanic white, non-Hispanic back, and non-Hispanic Asian. In addition to a descriptive statistical analysis, univariate and multivariate regression models were created to adjust for cardiovascular and perioperative risk factors and corrected for multiple comparisons.Among the 53,593 patients identified meeting the inclusion criteria, 788 (1.45%) patients experienced a stroke within 30 days. The non-Hispanic white group compared with the minority subgroups had a lower risk of postoperative stroke (1.43% vs. 1.67%, P = 0.18). The greatest difference was between the non-Hispanic white and Hispanic white groups, but this was not significant on multivariable analysis (odds ratio 1.40, 95% confidence interval 0.97-2.02, P = 0.08) after adjustment for risk stroke factors. The strongest predictors of postoperative stroke were perioperative blood transfusion, dependent functional status, and longer operative time.There was no difference between the racial and ethnic groups and the proportion of postoperative stroke among patients undergoing revascularization for asymptomatic carotid stenosis.

    View details for DOI 10.1016/j.wneu.2017.08.184

    View details for Web of Science ID 000415874900035

    View details for PubMedID 28890012

  • Big dreams, little sleep: dreams during pregnancy after prior pregnancy loss. Holistic nursing practice Van, P., Cage, T., Shannon, M. ; 18 (6): 284?92

    Abstract

    Sleep patterns and dream content may be affected by stressful life events such as pregnancy loss. Women who are pregnant subsequent to a prior pregnancy loss tend to have anxious and emotionally charged experiences during their pregnancies. Dreams can affect pregnancy outcomes, specifically premature birth. This qualitative study is the first investigation to explore sleep disturbances caused by dreams as experienced by a diverse group of women pregnant subsequent to a pregnancy loss. Our analysis resulted in the identification of 4 categories of dreams. We offer clinical assessment and intervention strategies to support these women prenatally and present suggestions for research to facilitate our understanding of their experiences.

    View details for PubMedID 15624275

  • Prospective comparison of long-term pain relief rates after first-time microvascular decompression and stereotactic radiosurgery for trigeminal neuralgia. Journal of neurosurgery Wang, D. D., Raygor, K. P., Cage, T. A., Ward, M. M., Westcott, S., Barbaro, N. M., Chang, E. F. 2018; 128 (1): 68?77

    Abstract

    OBJECTIVE Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD), stereotactic radiosurgery (SRS), and radiofrequency ablation (RFA). Although the efficacy of each procedure has been described, few studies have directly compared these treatment modalities on pain control for TN. Using a large prospective longitudinal database, the authors aimed to 1) directly compare long-term pain control rates for first-time surgical treatments for idiopathic TN, and 2) identify predictors of pain control. METHODS The authors reviewed a prospectively collected database for all patients who underwent treatment for TN between 1997 and 2014 at the University of California, San Francisco. Standardized collection of data on preoperative clinical characteristics, surgical procedure, and postoperative outcomes was performed. Data analyses were limited to those patients who received a first-time procedure for treatment of idiopathic TN with > 1 year of follow-up. RESULTS Of 764 surgical procedures performed at the University of California, San Francisco, for TN (364 SRS, 316 MVD, and 84 RFA), 340 patients underwent first-time treatment for idiopathic TN (164 MVD, 168 SRS, and 8 RFA) and had > 1 year of follow-up. The analysis was restricted to patients who underwent MVD or SRS. Patients who received MVD were younger than those who underwent SRS (median age 63 vs 72 years, respectively; p < 0.001). The mean follow-up was 59 ± 35 months for MVD and 59 ± 45 months for SRS. Approximately 38% of patients who underwent MVD or SRS had > 5 years of follow-up (60 of 164 and 64 of 168 patients, respectively). Immediate or short-term (< 3 months) postoperative pain-free rates (Barrow Neurological Institute Pain Intensity score of I) were 96% for MVD and 75% for SRS. Percentages of patients with Barrow Neurological Institute Pain Intensity score of I at 1, 5, and 10 years after MVD were 83%, 61%, and 44%, and the corresponding percentages after SRS were 71%, 47%, and 27%, respectively. The median time to pain recurrence was 94 months (25th-75th quartiles: 57-131 months) for MVD and 53 months (25th-75th quartiles: 37-69 months) for SRS (p = 0.006). A subset of patients who had MVD also underwent partial sensory rhizotomy, usually in the setting of insignificant vascular compression. Compared with MVD alone, those who underwent MVD plus partial sensory rhizotomy had shorter pain-free intervals (median 45 months vs no median reached; p = 0.022). Multivariable regression demonstrated that shorter preoperative symptom duration (HR 1.005, 95% CI 1.001-1.008; p = 0.006) was associated with favorable outcome for MVD and that post-SRS sensory changes (HR 0.392, 95% CI 0.213-0.723; p = 0.003) were associated with favorable outcome for SRS. CONCLUSIONS In this longitudinal study, patients who received MVD had longer pain-free intervals compared with those who underwent SRS. For patients who received SRS, postoperative sensory change was predictive of favorable outcome. However, surgical decision making depends upon many factors. This information can help physicians counsel patients with idiopathic TN on treatment selection.

    View details for DOI 10.3171/2016.9.JNS16149

    View details for PubMedID 28298026

  • Penetrating knife injury to the skull: A case report in pediatric neurosurgical care TRAUMA-ENGLAND Cage, T. A., Sanai, N., Lawton, M. T., Auguste, K. I. 2017; 19 (4): 302?7
  • Use of Subdural Evacuating Port System Following Open Craniotomy with Excision of Native Dura and Membranes for Management of Chronic Subdural Hematoma CUREUS Cage, T., Bach, A., McDermott, M. W. 2017; 9 (4): e1197

    Abstract

    An 86-year-old woman was admitted to the intensive care unit with a chronic subdural hematoma (CSDH) and rapid onset of worsening neurological symptoms. She was taken to the operating room for a mini-craniotomy for evacuation of the CSDH including excision of the dura and CSDH membrane. Postoperatively, a subdural evacuation port system (SEPS) was integrated into the craniotomy site and left in place rather than a traditional subdural catheter drain to evacuate the subdural space postoperatively. The patient had a good recovery and improvement of symptoms after evacuation and remained clinically well after the SEPS was removed. We offer the technique of dura and CSDH membrane excision plus SEPS drain as an effective postoperative alternative to the standard craniotomy leaving the native dura intact with traditional subdural drain that overlies the cortical surface of the brain in treating patients with CSDH.

    View details for DOI 10.7759/cureus.1197

    View details for Web of Science ID 000453620700068

    View details for PubMedID 28560123

    View details for PubMedCentralID PMC5446221

  • A Superior Cerebellar Convexity Two-Part Craniotomy to Access the Paramedian Supra and Infratentorial Space: Technical Note CUREUS Cage, T., Benet, A., Golfinos, J., McDermott, M. W. 2016; 8 (6): e664

    Abstract

    A craniotomy over the superior cerebellar convexity for approaches to this region typically involves a small infratentorial craniotomy and then drilling down of the bone to expose some portion of the transverse/sigmoid sinuses. The authors describe the anatomy of the region and the method for a two-part paramedian occipital and suboccipital craniotomy (supra and infratentorial) that may have time-saving, safety, and cosmetic advantages. For this technique, a supratentorial craniotomy is used to expose the transverse sinus from above, and subsequently, dissection across the sinus over the cerebellar convexity can be done under direct vision. The two bone pieces are joined on the inner table side while plates for fixation above the superior nuchal line can be counter-sunk to avoid post-operative pain from the prominence of screws. There is no need for cranioplasty materials since there is no burring down of bone for adequate exposure of the transverse sinus. The technique has been used by two senior surgeons over the years convincing them of the speed, safety, and utility of the technique. Here, the authors present a single example of the technique.

    View details for DOI 10.7759/cureus.664

    View details for Web of Science ID 000453612400039

    View details for PubMedID 27493846

    View details for PubMedCentralID PMC4968780

  • Surgical Approach to the Spinal Accessory Nerve Atlas of Neurosurgical Techniques: Spine and Peripheral Nerves Cage, T. A., Benet, A., Titus, E. W., Kliot, M. edited by Fessler, R. G., Sekhar, L. N. Thieme. 2016; Second Edition: 836?842
  • Surgical Approach to the Axillary Nerve Atlas of Neurosurgical Techniques: Spine and Peripheral Nerves Benet, A., Cage, T. A., Kliot, M. edited by Fessler, R. G., Sekhar, L. N. Thieme. 2016; Second Edition: 843?848
  • Visualization of nerve fibers and their relationship to peripheral nerve tumors by diffusion tensor imaging NEUROSURGICAL FOCUS Cage, T. A., Yuh, E. L., Hou, S. W., Birk, H., Simon, N. G., Noss, R., Rao, A., Chin, C. T., Kliot, M. 2015; 39 (3): E16

    Abstract

    OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber's intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach.

    View details for DOI 10.3171/2015.6.FOCUS15235

    View details for Web of Science ID 000360980100014

    View details for PubMedID 26323818

  • Downregulation of MYCN through PI3K inhibition in mouse models of pediatric neural cancer FRONTIERS IN ONCOLOGY Cage, T., Chanthery, Y., Chesler, L., Grimmer, M., Knight, Z., Shokat, K., Weiss, W. A., Gustafson, W. 2015; 5: 111

    Abstract

    The MYCN proto-oncogene is associated with poor outcome across a broad range of pediatric tumors. While amplification of MYCN drives subsets of high-risk neuroblastoma and medulloblastoma, dysregulation of MYCN in medulloblastoma (in the absence of amplification) also contributes to pathogenesis. Since PI3K stabilizes MYCN, we have used inhibitors of PI3K to drive degradation. In this study, we show PI3K inhibitors by themselves induce cell cycle arrest, with modest induction of apoptosis. In screening inhibitors of PI3K against MYCN, we identified PIK-75 and its derivative, PW-12, inhibitors of both PI3K and of protein kinases, to be highly effective in destabilizing MYCN. To determine the effects of PW-12 treatment in vivo, we analyzed a genetically engineered mouse model for MYCN-driven neuroblastoma and a model of MYCN-driven medulloblastoma. PW-12 showed significant activity in both models, inducing vascular collapse and regression of medulloblastoma with prominent apoptosis in both models. These results demonstrate that inhibitors of lipid and protein kinases can drive apoptosis in MYCN-driven cancers and support the importance of MYCN as a therapeutic target.

    View details for DOI 10.3389/fonc.2015.00111

    View details for Web of Science ID 000359136300001

    View details for PubMedID 26029667

    View details for PubMedCentralID PMC4429235

  • VISUALIZING AXON REGENERATION AFTER PERIPHERAL NERVE INJURY WITH MAGNETIC RESONANCE TRACTOGRAPHY NEUROLOGY Simon, N. G., Narvid, J., Cage, T., Banerjee, S., Ralph, J. W., Engstrom, J. W., Kliot, M., Chin, C. 2014; 83 (15): 1382?84

    View details for DOI 10.1212/WNL.0000000000000861

    View details for Web of Science ID 000345337300020

    View details for PubMedID 25186862

    View details for PubMedCentralID PMC4189102

  • High-resolution ultrasonography and diffusion tensor tractography map normal nerve fascicles in relation to schwannoma tissue prior to resection Report of 2 cases JOURNAL OF NEUROSURGERY Simon, N. G., Cage, T., Narvid, J., Noss, R., Chin, C., Kliot, M. 2014; 120 (5): 1113?17

    Abstract

    The goals of the present study were to demonstrate the ability of high-resolution ultrasonography to delineate normal nerve fascicles within or around peripheral nerve sheath tumors (NSTs). A blinded examiner evaluated 2 patients with symptomatic upper limb NSTs with high-resolution ultrasonography performed in the perioperative suite using a portable ultrasonography system. Ultrasonographic examinations located the tumor mass and identified the normal nerve fascicles associated with the mass. The locations of normal nerve tissue were mapped and correlated with results of MR tractography, operative inspection, and intraoperative electrophysiological monitoring. The study demonstrated a close correlation between normal nerve fascicles identified by ultrasonography, MR tractography, and intraoperative electrophysiological mapping. In particular, ultrasonographic examinations accurately identified the surface regions of the tumor without overlying normal nerve tissue. These preliminary data suggest that preoperative ultrasonographic examinations may provide valuable information, supplementary to the information obtained from intraoperative electrophysiological monitoring. Identification of normal nerve tissue prior to surgery may provide additional information regarding the risk of iatrogenic nerve injury during percutaneous tumor biopsy or open resection of the tumor and may also aid in selecting the optimum surgical approach.

    View details for DOI 10.3171/2014.2.JNS131975

    View details for Web of Science ID 000334903500013

    View details for PubMedID 24628610

  • Peripheral Nerve Problems: An Overview for Patients and Their Family Members Comprehensive Guide to Neurosurgical Conditions Birk, H. S., Cage, T. A., Kliot, M. edited by Agrawal, A., Britz, G. Springer. 2014: 129?144
  • Histologic grade and extent of resection are associated with survival in pediatric spinal cord ependymomas CHILDS NERVOUS SYSTEM Safaee, M., Oh, M. C., Kim, J. M., Aranda, D., Tarapore, P. E., Cage, T. A., Gupta, N., Parsa, A. T. 2013; 29 (11): 2057?64

    Abstract

    Prognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS).A comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included.A total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR)?=?0.248, p?=?0.022). Moreover, older age (HR?=?0.818, p?=?0.026), GTR (HR?=?0.042, p?=?0.013), and anaplastic grade (HR?=?19.847, p?=?0.008) demonstrated a significant association with OS in a multivariate model.Among pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.

    View details for DOI 10.1007/s00381-013-2149-x

    View details for Web of Science ID 000326283900017

    View details for PubMedID 23677177

  • Dual reinnervation of biceps muscle after side-to-side anastomosis of an intact median nerve and a damaged musculocutaneous nerve Case report JOURNAL OF NEUROSURGERY Cage, T. A., Simon, N. G., Bourque, S., Noss, R., Engstrom, J. W., Ralph, J. W., Kliot, M. 2013; 119 (4): 929?33

    Abstract

    Traumatic peripheral nerve injury can lead to significant long-term disability for previously healthy persons. Damaged nerve trunks have been traditionally repaired using cable grafts, but nerve transfer or neurotization procedures have become increasingly popular because the axonal regrowth distances are much shorter. These techniques sacrifice the existing nerve pathway, so muscle reinnervation depends entirely on the success of the repair. Providing a supplemental source of axons from an adjacent intact nerve by using side-to-side anastomosis might reinnervate the target muscle without compromising the function of the donor nerve. The authors report a case of biceps muscle reinnervation after side-to-side anastomosis of an intact median nerve to a damaged musculocutaneous nerve. The patient was a 34-year-old man who had sustained traumatic injury primarily to the right upper and middle trunks of the brachial plexus. At 9 months after the injury, because of persistent weakness, the severely damaged upper trunk of the brachial plexus was repaired with an end-to-end graft. When 8 months later biceps function had not recovered, the patient underwent side-to-side anastomosis of the intact median nerve to the adjacent distal musculocutaneous nerve via epineural windows. By 9 months after the second surgery, biceps muscle function had returned clinically and electrodiagnostically. Postoperative electromyographic and nerve conduction studies confirmed that the biceps muscle was being reinnervated partly by donor axons from the healthy median nerve and partly by the recovering musculocutaneous nerve. This case demonstrates that side-to-side anastomosis of an intact median to an injured musculocutaneous nerve can provide dual reinnervation of the biceps muscle while minimizing injury to both donor and recipient nerves.

    View details for DOI 10.3171/2013.5.JNS122359

    View details for Web of Science ID 000324964400015

    View details for PubMedID 23767892

  • Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children CHILDS NERVOUS SYSTEM Cage, T. A., Samagh, S. P., Mueller, S., Nicolaides, T., Haas-Kogan, D., Prados, M., Banerjee, A., Auguste, K. I., Gupta, N. 2013; 29 (8): 1313?19

    Abstract

    Diffuse intrinsic pontine gliomas (DIPGs) are rapidly progressive and aggressive tumors that usually arise in children. Their anatomic location makes gross total surgical resection impossible, and fewer than 10% of patients survive more than 2 years after diagnosis. Often, these lesions are treated based on imaging characteristics alone. However, despite aggressive chemotherapy and radiation treatments available, prognosis remains poor. There is therefore a need for new therapies directed by biologic profiling. This necessitates a tissue diagnosis and, therefore, surgical biopsy. We have reviewed the results of biopsy for DIPGs in children at a single institution and compared our results to those available in the literature to elucidate the utility of biopsy for DIPGs.A historical cohort study was performed using medical records of patients under the age of 18 who underwent surgical biopsy of a DIPG at a single institution.Nine patients were included, four males and five females. Age at presentation ranged from 8 months to 10 years (average 5.7 years). Pathologic diagnoses included five high grade (WHO grade III or IV) gliomas and four low grade (WHO grade II) astrocytomas. There were no intraoperative complications, and only one patient developed a new postoperative neurologic deficit.Stereotactic biopsy of DIPGs is essential to obtain a pathologic diagnosis and is associated with low morbidity. This technique is important to elucidate biological characteristics of these tumors in order to direct multidisciplinary treatment plans possibly involving chemotherapy, radiation therapy, or other future clinical trial interventions for children with DIPGs.

    View details for DOI 10.1007/s00381-013-2101-0

    View details for Web of Science ID 000321952500016

    View details for PubMedID 23666401

  • Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid Case report JOURNAL OF NEUROSURGERY Cage, T. A., Pekmezci, M., Prados, M., Berger, M. S. 2013; 118 (6): 1220?23

    Abstract

    Recurrent glioblastoma (GBM) can occur locally or at distant sites within the brain. Though MRI is the standard imaging modality for primary and recurrent GBM, the full extent of diffuse lesions may not be appreciated on MRI alone. Glioblastomas with ependymal and/or subependymal spread are examples of diffuse infiltrative tumors that are incompletely seen on MRI. Some other adjuvant visualization technique such as intraoperative fluorescence-assisted 5-aminolevulinic acid (5-ALA) could be used to assist the surgeon in localizing the infiltrating tumor. The authors report on a 56-year-old man who presented 7 years after initial resection of an occipital lobe GBM with imaging consistent with distant discrete foci of tumor recurrence. Because these foci were distant from the original resection cavity, there was concern for diffuse, infiltrative tumor elsewhere throughout the brain versus a distant multicentric recurrence. Therefore, the patient was given 5-ALA prior to surgery to aid in tumor detection intraoperatively. Using fluorescent visualization of the resection cavity, it was confirmed that there was subependymal and ependymal spread of the recurrent tumor along the lateral ventricle connecting the recurrence to the previous tumor site. Magnetic resonance imaging may not completely detect the presence of diffuse tumor infiltrating the ependymal or subependymal spaces. Therefore, adjunct intraoperative use of fluorescence-assisted visualization with 5-ALA may be helpful in highlighting and detecting infiltrative tumor to accurately detect tumor burden and distinguish it from a separate multicentric recurrence.

    View details for DOI 10.3171/2013.1.JNS121537

    View details for Web of Science ID 000319366400015

    View details for PubMedID 23421452

  • A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas JOURNAL OF NEUROSURGERY-PEDIATRICS Cage, T. A., Clark, A. J., Aranda, D., Gupta, N., Sun, P. P., Parsa, A. T., Auguste, K. I. 2013; 11 (6): 673?81

    Abstract

    Ependymoma is the third most common primary brain tumor in children. Tumors are classified according to the WHO pathological grading system. Prior studies have shown high levels of variability in patient outcomes within and across pathological grades. The authors reviewed the results from the published literature on intracranial ependymomas in children to describe clinical outcomes as they relate to treatment modality, associated mortality, and associated progression-free survival (PFS).A search of English language peer-reviewed articles describing patients 18 years of age or younger with intracranial ependymomas yielded data on 182 patients. These patients had undergone treatment for ependymoma with 1 of 5 modalities: 1) gross-total resection (GTR), 2) GTR as well as external beam radiation therapy (EBRT), 3) subtotal resection (STR), 4) STR as well as EBRT, or 5) radiosurgery. Mortality and outcome data were analyzed for time to tumor progression in patients treated with 1 of these 5 treatment modalities.Of these 182 patients, 69% had supratentorial ependymomas and 31% presented with infratentorial lesions. Regardless of tumor location or pathological grade, STR was associated with the highest rates of mortality. In contrast, GTR was associated with the lowest rates of mortality, the best overall survival, and the longest PFS. Children with WHO Grade II ependymomas had lower mortality rates when treated more aggressively with GTR. However, patients with WHO Grade III tumors had slightly better survival outcomes after a less aggressive surgical debulking (STR+EBRT) when compared with GTR.Mortality, PFS, and overall survival vary in pediatric patients with intracranial ependymomas. Pathological classification, tumor location, and method of treatment play a role in outcomes. In this study, GTR was associated with the best overall and PFS rates. Patients with WHO Grade II tumors had better overall survival after GTR+EBRT and better PFS after GTR alone. Patients with WHO Grade III tumors had better overall survival after STR+EBRT. Patients with infratentorial tumors had improved overall survival compared with those with supratentorial tumors. Progression-free survival was best in those patients with infratentorial tumors following STR+EBRT. Consideration of all of these factors is important when counseling families on treatment options.

    View details for DOI 10.3171/2013.2.PEDS12345

    View details for Web of Science ID 000319366900010

    View details for PubMedID 23540528

  • A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma CHILDS NERVOUS SYSTEM Clark, A. J., Cage, T. A., Aranda, D., Parsa, A. T., Sun, P. P., Auguste, K. I., Gupta, N. 2013; 29 (2): 231?38

    Abstract

    Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma.We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan-Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared.A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p = 0.76; 1-year PFS 89 vs 84%; 5-year PFS 77 vs 73%, respectively). One-year PFS was 84% for STR+XRT compared to 76% for STR alone while 5-year PFS was 73% for STR+XRT compared to 43% for STR alone (log-rank; p = 0.003).Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR.

    View details for DOI 10.1007/s00381-012-1926-2

    View details for Web of Science ID 000314028100010

    View details for PubMedID 23089933

  • DNET: Dysembryoplastic Neuroepithelial Tumors Tumors of the Pediatric Central Nervous System Cage, T. A., Tihan, T., Gupta, N. edited by Keating, R. F., Goodrich, J. T., Packer, R. J. Thieme. 2013; Second Edition: 313?318
  • Treatment-related morbidity and the management of pediatric craniopharyngioma A systematic review JOURNAL OF NEUROSURGERY-PEDIATRICS Clark, A. J., Cage, T. A., Aranda, D., Parsa, A. T., Auguste, K. I., Gupta, N. 2012; 10 (4): 293?301

    Abstract

    Craniopharyngiomas are benign tumors but their close anatomical relationship with critical neurological, endocrine, and vascular structures makes gross-total resection (GTR) with minimal morbidity difficult to achieve. Currently, there is controversy regarding the extent, timing, and modality of treatment for pediatric craniopharyngioma.The authors performed a systematic review of the published literature on pediatric craniopharyngioma to determine patterns of clinical practice and the reported outcomes of standard treatment strategies. This yielded 109 studies, which contained data describing extent of resection for a total of 531 patients. Differences in outcome were examined based upon extent of resection and choice of radiation treatment.Gross-total resection was associated with increased rates of new endocrine dysfunction (OR 5.4, p < 0.001), panhypopituitarism (OR 7.8, p = 0.006), and new neurological deficits (OR 9.9, p = 0.03) compared with biopsy procedures. Subtotal resection (STR) was not associated with an increased rate of new neurological deficits. Gross-total was associated with increased rates of diabetes insipidus (OR 7.7, p = 0.05) compared with the combination of STR and radiotherapy (RT). The addition of RT to STR was associated with increased rates of panhypopituitarism (OR 9.9, p = 0.01) but otherwise similar rates of morbidities.Although subject to the limitations of a literature review, this report suggests that GTR is associated with increased rates of endocrinopathies compared with STR + RT, and this should be considered when planning goals of surgery.

    View details for DOI 10.3171/2012.7.PEDS11436

    View details for Web of Science ID 000309485300009

    View details for PubMedID 22920295

  • High-Grade Gliomas in Children NEUROSURGERY CLINICS OF NORTH AMERICA Cage, T. A., Mueller, S., Haas-Kogan, D., Gupta, N. 2012; 23 (3): 515-+

    Abstract

    High-grade gliomas (HGGs) are malignant tumors and typically include glioblastoma multiforme and anaplastic astrocytoma subtypes. Brainstem gliomas and ependymomas are separate entities with respect to clinical presentation, treatment, prognosis, and outcome in comparison with supratentorial HGGs. In children, these tumors account for 3% to 7% of newly diagnosed brain tumors and 20% of all diagnoses of pediatric supratentorial brain tumors. These neoplasms are highly proliferative and mitotically active and of glial origin. This article reviews clinical, diagnostic, and pathologic features of HGG and current treatments and potential future therapies specific to pediatric patients with HGGs.

    View details for DOI 10.1016/j.nec.2012.04.007

    View details for Web of Science ID 000307024800016

    View details for PubMedID 22748663

  • A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia Clinical article JOURNAL OF NEUROSURGERY Rowland, N. C., Englot, D. J., Cage, T. A., Sughrue, M. E., Barbaro, N. M., Chang, E. F. 2012; 116 (5): 1035?41

    Abstract

    Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature.A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol.Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery.Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.

    View details for DOI 10.3171/2012.1.JNS111105

    View details for Web of Science ID 000303088800016

    View details for PubMedID 22324422

  • Distinct patterns of human medulloblastoma dissemination in the developing chick embryo nervous system CLINICAL & EXPERIMENTAL METASTASIS Cage, T. A., Louie, J. D., Liu, S. R., Alvarez-Buylla, A., Gupta, N., Hyer, J. 2012; 29 (4): 371?80

    Abstract

    Medulloblastoma (MB) is the most common malignant primary brain tumor in children. Aggressive tumors that disseminate along the leptomeninges carry extremely poor prognoses. Mechanisms that predict dissemination are poorly understood. Our objective was to develop a reliable and reproducible model to study MB dissemination. We have created a chicken-human xenograft to study features of MB with leptomeningeal dissemination. Human MB cell lines (D283, Daoy), primary human MB cells (SF8113), and primary genetic mouse model (Math1cre:SmoM2 flox/flox) MB cells were either transfected to express green fluorescent protein (GFP) or were labeled with a membrane permeable green fluorescent probe. Cells were then injected as aggregates or implanted as pellets into the developing chicken brain immediately after neural tube closure at embryonic day 2 (E2). Most embryos were harvested three days after implantation (E5) though some were harvested up to E15. The developing brain was analyzed via whole mount fluorescent imaging and tissue section immunohistochemistry. Human and mouse MBs survived in the developing chicken central nervous system (CNS). They exhibited distinct patterns of incorporation and dissemination into the CNS that were consistent with observed phenotypes of the corresponding human patient or mouse host. Specifically, metastatic D283 cells disseminated along the leptomeninges whereas Daoy, primary mouse MB, and primary human MB cells did not. This work supports an avian-human xenograft as a successful model to study patterns of MB dissemination. Our model provides a basis for manipulating cell signaling mechanisms to understand critical targets involved in MB dissemination.

    View details for DOI 10.1007/s10585-012-9456-6

    View details for Web of Science ID 000300893200007

    View details for PubMedID 22322278

  • Self-reported functional outcome after surgical intervention in patients with idiopathic normal pressure hydrocephalus JOURNAL OF CLINICAL NEUROSCIENCE Cage, T. A., Auguste, K. I., Wrensch, M., Wu, Y. W., Gupta, N. 2011; 18 (5): 649?54

    Abstract

    The goal of this study was to characterize long-term social and functional outcomes in adults treated for idiopathic normal pressure hydrocephalus (NPH). Data for 252 patients treated medically or surgically for idiopathic NPH were obtained through the Hydrocephalus Association Database Project. Data on post-surgical outcomes including improvement in symptoms, the need for in-home care, ability to drive, and employment status were analyzed. Most patients (73.7%) surveyed were treated with a shunt, an endoscopic third ventriculostomy (ETV), or both. More patients who underwent surgery reported driving and being employed compared to those who did not have surgery. Most shunt patients had improvements in gait (81.1%), urinary incontinence (55.9%), and dementia (64.4%). Overall, shunt patients reported more dramatic improvements in quality of life as compared to ETV patients (72.2% versus 55.6%). Treating idiopathic NPH with cerebrospinal fluid diversion facilitates a return to independence through improved functional and social outcomes.

    View details for DOI 10.1016/j.jocn.2010.08.028

    View details for Web of Science ID 000289813900011

    View details for PubMedID 21371890

  • Clinical Characteristics and Surgical Outcomes of Patients Presenting With Meningiomas Arising Predominantly From the Floor of the Middle Fossa NEUROSURGERY Sughrue, M. E., Cage, T., Shangari, G., Parsa, A. T., McDermott, M. W. 2010; 67 (1): 80?86

    Abstract

    Little is known regarding meningiomas that primarily arise from the floor of the middle fossa as opposed to the sphenoid wing, the cavernous sinus, the anterior petrous ridge, or the lateral convexity dura.Given the relative paucity of literature addressing this disease entity, we review the University of California at San Francisco (UCSF) experience with these tumors.Between 1991 and 2006, 1228 patients were seen by neurosurgeons at UCSF for meningiomas of which 17 (1.1%) patients met our criteria for a "middle fossa floor" meningioma, of which 15 underwent first-time surgery and were included in this series. The most common presenting symptoms were headache (9 patients), seizures (6 patients), trigeminal nerve dysfunction (5 patients), hearing loss (5 patients), gait disturbance (5 patients), and cognitive decline (3 patients). All patients underwent surgical resection via frontotemporal craniotomy, with or without orbitozygomatic osteotomy.We were able to achieve a Simpson grade 1 or 2 resection in 10 of 15 patients (67%). The operative morbidity was clustered in 5 patients, as 10 of 15 patients (67%) experienced no operative morbidity. There were 4 known clinical recurrences in this group at 5 years median follow-up. All patients had either higher grade tumors, or received a Simpson grade 3 or higher resection.We present the clinical characteristics and surgical outcome of a series of patients presenting with meningiomas primarily arising from the concave floor of the middle cranial fossa. Given the relatively uncommon nature of these lesions, more investigation into the clinical behavior of this entity is warranted.

    View details for DOI 10.1227/01.NEU.0000370938.46353.77

    View details for Web of Science ID 000278875400022

    View details for PubMedID 20559094

  • Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas JOURNAL OF NEURO-ONCOLOGY Cage, T. A., Lamborn, K. R., Ware, M. L., Frankfurt, A., Chakalian, L., Berger, M. S., McDermott, M. W. 2009; 93 (1): 151?56

    Abstract

    Patients with brain tumors including intracranial meningiomas are at increased risk for developing deep vein thrombosis (DVTs) and suffering thromboembolic events (VTEs). Many surgeons are concerned that early use of low dose enoxaparin may increase the risk of intracranial hemorrhage which outweighs the benefit of DVT/VTE reduction. We aimed to address concerns around the use of enoxaparin after meningioma resection in the development of postoperative intracranial hemorrhages and DVT/VTEs. This is a retrospective review of 86 patients with intracranial meningiomas who underwent craniectomy and surgical resection of the mass, treated by one attending surgeon at UCSF Medical Center between 2000 and 2005. Within 48 h after surgery patients treated 2003-2005 routinely received enoxaparin therapy unless there was documented intracranial hemorrhage, lumbar subarachnoid drain, enoxaparin hypersensitivity, or thrombocytopenia (n = 24). These were compared to a cohort treated 2000-2002 who did not receive the drug (n = 62). Exclusion criteria were prior VTEs or coagulopathies. The groups were similar in tumor and surgical characteristics. Enoxaparin therapy did not increase the incidence of intracranial hemorrhage following surgical meningioma resection and the incidence of DVTs/VTEs was 0% (n = 0) versus 4.8% (n = 3) in the non-enoxaparin group. Results did not reach statistical significance. In this retrospective study, postoperative administration of enoxaparin following meningioma resection does not increase the risk of intracranial hematoma though enoxaparin administration may slightly decrease the incidence of post-surgical thromboembolic events. Due to study design and power, we were not able to demonstrate DVT/VTE reduction with statistical significance.

    View details for DOI 10.1007/s11060-009-9886-4

    View details for Web of Science ID 000265941600014

    View details for PubMedID 19430892

  • Stage-specific and opposing roles of BDNF, NT-3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry EUROPEAN JOURNAL OF NEUROSCIENCE Catapano, L. A., Arlotta, P., Cage, T. A., Macklis, J. D. 2004; 19 (9): 2421?34

    Abstract

    Cellular repair of neuronal circuitry affected by neurodegenerative disease or injury may be approached in the adult neocortex via transplantation of neural precursors ("neural stem cells") or via molecular manipulation and recruitment of new neurons from endogenous precursors in situ. A major challenge for potential future approaches to neuronal replacement will be to specifically direct and control progressive differentiation, axonal projection and connectivity of neural precursors along a specific neuronal lineage. This goal will require a progressively more detailed understanding of the molecular controls over morphologic differentiation of specific neuronal lineages, including neurite outgrowth and elongation, in order to accurately permit and direct proper neuronal integration and connectivity. Here, we investigate controls over the morphologic differentiation of a specific prototypical lineage of cortical neurons: callosal projection neurons (CPN). We highly enriched CPN to an essentially pure population, and cultured them at three distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labelling, followed by fluorescence-activated cell sorting. We find that specific peptide growth factors exert direct stage-specific positive and negative effects over the morphologic differentiation and process outgrowth of CPN. These effects are distinct from the effects of these growth factors on CPN survival [Catapano et al. (2001)J. Neurosci., 21, 8863-8872]. These data may be critical for the future goal of directing lineage-specific neuronal differentiation of transplanted or endogenous precursors/"stem cells" toward cellular repair of complex cortical circuitry.

    View details for DOI 10.1111/j.1460-9568.2004.03303.x

    View details for Web of Science ID 000221126700008

    View details for PubMedID 15128396

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