Neurobiology of Central Nervous System Tumors in Children

Abstract

C entral nervous system tumors represent a leading cause of death and disability in children. Over the course of several decades, better treatments for leukemia, including the use of combination chemotherapy, decreased the rates of cancer recurrence, significantly improving life expectancy. Similar combination treatments for central nervous system tumors have improved survival for children with specific tumor types, but late effects of therapy can be disabling. Scientific advances have clarified the pathogenesis of many disorders characterized by neurological dysfunction. As a result, new diagnostic tools and therapies have been developed and refined. The rapid pace of discovery in basic and clinical neurosciences continues unabated. What are the challenges for today’s child neurology practitioners? First, there is ongoing concern that children with central nervous system tumors should be diagnosed sooner after onset of symptoms, especially since magnetic resonance imaging (MRI) is readily available in many communities. Although there is no real evidence that early diagnosis changes life expectancy, smaller tumors can be surgically resected with fewer complications, and gross total resection of several pediatric tumors has been linked to improved outcomes. There are probably several reasons why diagnosis of a brain tumor can take several months from onset of symptoms. Headache from migraines in children is at least 1000 times more prevalent than headache caused by brain tumors. Headaches from increased intracranial pressure or migraine are associated with nausea and vomiting, and both can produce nocturnal distress. Moreover, the ophthalmoscope can be underutilized in high-volume primary care practices so that papilledema, for example, may not be detected in early stages. The child neurology community should reflect on how best to increase awareness and advocate for primary care practitioners’ recognition of symptoms and signs of increased intracranial pressure in children. An important second challenge that relates to the management of children with central nervous system tumors by child neurologists is how to determine which molecular diagnostic strategies, sophisticated neuroimaging tools, or innovative therapies should be adopted. Since 2001, the National Institutes of Health (NIH), the Child Neurology Society, and various foundations and associations have funded the annual Neurobiology of Disease in Children Conference. Central nervous system tumors were the focus of the October 10, 2007 symposium, which brought together clinicians, scientists, caregivers, and NIH program officers to determine how best to translate research findings to enhance clinical understanding and practice. The conference format included formal presentations, question-and-answer sessions, panel discussions, and open discussions to directly address conference objectives, which were as follows: (1) to review scientific advances and determine their relevance to current and future clinical practice in child neurology; (2) to coordinate efforts across clinical and basic science disciplines, lay organizations, and the NIH to review current research initiatives and define future directions; and (3) to disseminate the proceedings of the symposia to ensure that clinicians and basic scientists are informed about scientific advances, current research initiatives, and future directions. The symposium directors, Drs Roger Packer and Ian Pollack, both highly respected leaders in the field of pediatric central nervous system tumors, selected speakers and panelists to ensure authoritative presentations on key topics and productive discussions on research directions. The question-and-answer sessions after each set of talks encouraged brainstorming between panelists and the audience of child neurologists about the best directions of future research and how clinicians can contribute. In the conference’s first session, ‘‘Clinical Aspects of Central Nervous System Tumors,’’ we reviewed progress in improving survival rates associated with some of the most common pediatric tumor types, such as medulloblastoma. Advances in neuroimaging techniques, including From the Charles P. Darby Children’s Research Institute, Medical University of South Carolina, Charleston, South Carolina.