Neurosurgical Research Programs

Integrative Research in the Prevention and Treatment of Diseases and Injury of the Brain and Spine

Diseases of the spine

A. Outcomes science, epidemiology, and clinical trials

Comprehensive outcome analysis after cervical surgery, lumbar surgery and deformity surgery, including patient generated functional outcomes, late outcomes, and Oswestry data.
C5 nerve palsy study: A prospective study requiring multimodality evoked potential and electromyographic monitoring of all patients who undergo cervical surgery in an attempt to identify and correlate intraoperative correlates of postoperative C5 palsy.
Prospective identification of patients who suffer a spinal cord injury and the subsequent development of post-traumatic syringomyelia.
Hyperperfusion treatment in spinal cord injury, a prospective cohort controlled study.
Comparison of minimal access vs. open trans-foraminal interbody fusion outcome study.
Morbidity of Anterior Exposure for Spinal Deformity.
A prospective, randomized, controlled, multi-center pilot study (300 patients) using CORTOSS® Synthetic Cortical Bone Void Filler for vertebroplasty at up to two vertebra, fractured as a result of osteoporosis, located between and including the 6^th thoracic and 5^th lumbar vertebrae.

B. Technology development and assessment

Evaluation of new Trans S1 technique for interbody fusion. FDA approval in progress.
Two-level cervical artificial disc technology. Multi-center FDA study.
Single level artificial disc technology in lumbar spine. Multi-center FDA study.

C. Basic mechanisms of neurosurgical diseases

Computerized analysis of spinal column biomechanics during gait. Impact of degenerative diseases, deformity and surgical interventions.
Finite element model of cervical spine and craniocervical junction. Development and validation of computer based platform for studying impact of disease or injury, pre-operative planning, and the design and testing of implants, fusion strategies.
Cranial spinal sagittal balance and impact on gait and swallowing.

Neurovascular biology, stroke and brain injury

A. Outcomes science, epidemiology, and clinical trials

Genotype-phenotype correlations in cerebrovascular malformations. Study of differential clinical manifestations of vascular malformations with different genotypic substrate.
Quality of life assessment of patients with hemorrhagic stroke. Outcome prediction modeling and impact of surgical interventions.
Genetic analysis of familial intracranial aneurysms.
Role of Endothelin inhibitor for vasospasm.
Prospective analysis of cerebral aneurysm growth.
Metaanalysis of endovascular treatment of unruptured aneurysms.
Thrombolytic aspiration of clot in hemorrhagic stroke.

B. Technology development and assessment

Molecular imaging of blood vessel wall in vivo. Development of novel contrast agents with specific binding to selected molecular targets in blood vessel wall and validation of molecular imaging ex vivo and in vivo.
Assessment of magnetic resonance perfusion for intracranial arterial and venous stenosis.
Assessment of the Orbit coil for intracranial aneurysms (registry).
Assessment of novel image guidance systems for cerebrovascular surgery.
Functional magnetic resonance imaging as a preoperative tool in vascular malformation surgery.
Magnetic resonance imaging as a screening tool for coiled and stented aneurysms.
Holographic image guidance for microsurgical and endovascular surgery.

C. Basic mechanisms of neurosurgical diseases

Mechanisms of genesis and clinical progression of cerebrovascular malformations. Analysis of the genetic architecture, immune response, and proteomics of cerebral cavernous malformations.
Analysis of the molecular architecture of cerebral aneurysms and clinical correlation.

Brain tumors and neurosurgical oncology

A. Outcomes science, epidemiology, and clinical trials

Randomized evaluation of convection enhanced delivery of IL 13-PE38QQR compared to Gliadel wafer with survival endpoint in glioblastoma multiforme patients at first recurrence (Multicenter Phase III Trial).
Evaluation of TP-38 in patients with glioblastoma multiforme who have recurred or progressed after previous resection and radiation therapy and are scheduled for gross total repeat resection (Multicenter Phase II Trial).
Phase I study to determine the safety of AngioMab (90 Yttrium Radiolabeled muBC-1 antibody) administered into surgically created resection cavity in patients with recurrent glioblastoma multiforme.
PRODIGE Trial: A Trial of Dalteparin Low Molecular Weight Heparin for primary prophylaxis of venous thromboembolism in brain tumor patients.
Poor Risk Medulloblastoma, PNET, or Disseminated Ependymoma: A Phase II Trial of Preradiation Multiagent Chemotherapy for Adults with "Poor Risk" Medulloblastoma, PNET, and Disseminated Ependymoma.
Newly Diagnosed Anaplastic Oligodendroglioma or Anaplastic Oligoastrocytoma:
1. Neoadjuvant Temodar single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma and anaplastic oligoastrocytoma with or without radiation therapy.
2. A Phase II Trial of intensive chemotherapy and autotransplantation for patients with newly diagnosed anaplastic oligodendroglioma.
Brain Metastasis:
1. Phase I/II multicenter trial of intra-arterial Carboplatin and oral Temozolomide for the treatment of recurrent and symptomatic residual brain metastases.
2. A randomized, double-blind, placebo-controlled Phase III study of Temozolomide or placebo added to whole brain radiation therapy for the treatment of brain metastases from non-small cell lung cancer.
Progressed/Recurred glioblastoma multiforme (non-surgical): A Phase III, randomized, open-label study of intravenous Edotecarin vs. Temozolomide or Carmustine (BCNU) or (Lomustine (CCNU).
Astrocytoma Grade 2-4 and Oligodendroglioma: Genetic/Environmental risk and outcomes for brain tumors.
High dose chemotherapy and stem cell transplant in patients with anaplastic astrocytoma.
Rituximab, Methotrexate, Procabazine and Vincristine in Combination with whole brain radiation therapy (2400cGy/4500cGy) in patients with Primary CNS Lymphoma.
A Phase III randomized, double-blind, dexamethasone-sparing study comparing human corticotropin-releasing factor (hCRF) to placebo for control of symptoms associated with peritumoral brain edema in patients with malignant brain tumor who require chronic administration of high-dose dexamethasone.
A Phase I/II Trial of Arsenic Trioxide and Temozolomide in combination with radiation therapy for patients with malignant gliomas.
A Phase I/II Trial of Temozolomide and Vinorelbine for patients with recurrent brain metastases.
A Pilot Study of combined immunochemotherapy followed by reduced dose radiation therapy for patients with newly diagnosed Primary CNS Lymphoma.
A Phase II, randomized, open label study of IV Edotecarin vs. Temozolomide or Carmustine (BCNU) or Lomustine (CCNU) in patients with Glioblastoma Multiforme at first relapse after Alkylator-based (Neo)adjuvant chemotherapy.
Phase V GliaSite Radiation Therapy System Registry Protocol for the Treatment of Resectable Brain Tumors.

B. Technology development and assessment

Rapid Translation of New Investigational Agents into CNS Tumors.
Endoscopic and image guidance in skull base surgery.
Comparative paradigms of cranial radiosurgery using Gamma Knife and Multimicroleaf Linear Accelerator technology.
Paradigms and protocols for spinal and extracranial radiosurgery using Multimicroleaf Linear Accelerator technology.
Computer and image assisted surgical simulation for training in microsurgery and skull base techniques.
Clinical study of the Medtronic Durepair Dura Regeneration Matrix.

C. Basic mechanisms of neurosurgical diseases

Differential genomics and clinical behavior of brain tumors.
Cadherin signaling and neural development.
Mechanisms regulating cell identity in ependymoma, Role of Cadherin.
Retinoid signaling in brain tumors.
The Role of a Network of Endogenous Modulators of Nuclear Factor-kappaB in the Therapy Resistance of Human High-Grade Gliomas.
Modeling a Cooperative Network Driving the Nonrandom Selection of a Distinct Genetic Landscape During Glioma Evolution.
High-Resolution Profiling of the Human Glioma Genome.
Modeling Transcriptional Networks in Human Gliomas.
Characterization of CHD5 as a Novel Tumor Suppressor on Chromosome 1p in Human Gliomas.

Functional and restorative neurosurgery, epilepsy, movement disorders, and pain

A. Outcomes science, epidemiology, and clinical trials

Convection enhanced delivery of chemotherapeutic agents for malignant brain tumors.
Prospective assessment of Deep Brain Stimulation for movement disorders.
Epidural motor cortical stimulation in patients with stroke.
Assessment of early intrathecal baclofen pump therapy for patients with head and spinal cord injury.
Early surgery for intractable epilepsy (ERSET trial).
Vagal nerve stimulation and cognition.
Upper cervical stimulation for headaches.

B. Technology development and assessment

Noninvasive optical imaging of epileptogenic brain tissue.
Assessment of subcortical field stimulation potentials for the localization of epileptogenic areas of cortex.
Functional magnetic resonance imaging for pain assessment.
Evoked potentials as a predictor of areas of paresthesia in patients undergoing spinal cord stimulator electrode placement.
Assessment of frameless stereotaxy for functional procedures.
Coregistration of subdural grids with brain imaging for epilepsy surgery planning.
Novel implanted electrodes for headaches.
Stereotactic radiosurgery paradigms for tic douloureux.

C. Basic mechanisms of neurosurgical diseases

Assessment of catamenial temporal lobe epilepsy and its association with estrogen-related changes in hippocampal architecture.
Analysis of functional cortical organization using optical imaging.
Use of optical imaging to detect functional organization of cortical regions.

Developmental neurobiology and pediatric neurosurgery

A. Outcomes science, epidemiology, and clinical trials

Impact of antibiotic coated shunt catheters on shunt infection rates.
Outcome assessment of surgical procedures for pediatric brain tumors.

B. Technology development and assessment

Intraoperative irradiation for pediatric brain tumors using Intrabeam.

C. Basic mechanisms of neurosurgical diseases

Molecular profiling of pediatric brain tumors using genomics and proteomics, and correlation with clinical behavior.
Role of Pax3 transcription factor and its downstream target genes in neural tube closure.
Mechanisms of folate rescue of neural tube defects.
Analysis of neural tube defects using transgenic models.
Role of TGF beta signaling in pediatric oncogenesis.

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