Neurological Surgery
Research
Neurosurgeons at Morgan Stanley Children's Hospital of NewYork-Presbyterian are committed to furthering the understanding and advancing the treatment of brain tumors, neural tube defects, and other serious – and sometimes terminal – disorders of the nervous system of children and adolescents.
Through a combination of basic laboratory studies and clinical data from the operating room, neurosurgeons at Morgan Stanley Children's Hospital are providing answers to the difficult problems faced by children and their families. In addition to world-class surgical care, physicians are pushing the frontiers of neurosurgery to provide safer treatments and better solutions to problems once deemed hopeless.
The neurosurgery program at Morgan Stanley Children's Hospital is actively involved in basic and translational research of brain tumors in children and adolescents. Through collaborations with world-renowned researchers at Columbia University and Harvard Medical School, the Gabriele Bartoli Brain Tumor Research Laboratory is investigating how the immune system interacts with childhood brain tumors. Primary brain tumors are the most common solid cancer among children, and medulloblastomas (MEDs) are the most frequent malignant brain tumor in pediatric patients. In the last decade there have been significant advances in the use of chemotherapy to treat childhood brain tumors, with 5-year survival rates for pediatric MEDs of greater than 70%. Nonetheless, early recurrence of disease and adverse effects of prior treatment are commonplace.
One approach aims at understanding the fundamental developmental processes that go wrong and lead to childhood brain tumors in the first place. Tumors in children frequently occur in the cerebellum, and by studying its development, researchers hope to shed light on the mechanisms of tumor formation and strategies to stop their progression. CXCR4 is a molecule that plays an integral role in the developing cerebellum and it is also associated with glioblastoma multiforme (the most common malignant brain tumor in adults), breast cancer metastasis, and von Hippel-Lindau syndrome. Without CXCR4, immature cells in the cerebellum continue to migrate and divide – mimicking a precancerous state. Therefore, derangements in molecular pathways involving CXCR4 could turn normal cells into cancerous cells, leading to tumors like medulloblastoma. By studying basic developmental genes such as CXCR4, the research aims to provide new and more specific therapeutic targets in fighting children's brain tumors.
Accordingly, neurosurgeons at Morgan Stanley Children's Hospital believe that the discovery and use of an appropriate immunotherapeutic strategy for MEDs, in conjunction with current chemotherapies, could significantly improve the current treatment of this disease. Recent data have demonstrated that cells of the immune system (including T cells, B cells, and monocytes/macrophages) frequently infiltrate pediatric MEDs, suggesting that immunity could impact tumor survival/proliferation in vivo. The hospital's neurosurgeons hypothesize that pediatric MEDs avoid immune attack by up-regulation of non-functional "decoy" receptors against death receptor ligands and cytokines that would lead to growth arrest or killing. Therefore they are seeking a better understanding of the role of these receptors in the malignancy and survival of pediatric MEDs, which could lead to novel immunotherapeutic strategies.
The neurosurgeons have also been collecting clinical information since 1998, using intraoperative electrophysiological monitoring to help determine whether opening of the dura (a thick membrane that surrounds the brain and spinal cord) is a necessary component of surgery for children with Chiari I malformation. They have discovered that most of the improvement in nerve impulses through the brain and spinal cord occurs after removal of the bone. However, these neurosurgeons have not detected any further improvement after opening the dura, suggesting that children may not require this additional step of surgery.
For the past two years, the Hospital's neurosurgeons have performed a less invasive operation where the dura is not opened during surgery. So far, the clinical and radiographic results have been excellent – without any significant operative complications after bony decompression without dural opening. This is important because the complication rate after surgery has been reported to be nearly four times higher if the dura is opened during surgery.
In addition, through collaboration with Great Ormond Street Hospital in London and the Department of Genetics and Development at Columbia, basic science research is at work to gain a better understanding of neural tube defects. Those are the most common birth effects that affect the brain and spinal cord. Studies in the Division of Pediatric Neurosurgery focus upon programmed cell death (apoptosis), a fundamental process in development, cancer, stroke and epilepsy, and the role it plays in anencephaly and spina bifida.
