Showing papers by "James T. Rutka published in 2010"

Current concepts: Nanomedicine

Abstract: From the Institute of Biomaterials and Biomedical Engineering (B.Y.S.K., W.C.W.C.), Terrence Donnelly Centre for Cellular and Biomolecular Research (B.Y.S.K., W.C.W.C.), the Department of Materials Science and Engineering (W.C.W.C.), and the Department of Chemical Engineering (W.C.W.C.), University of Toronto (B.Y.S.K., J.T.R., W.C.W.C.); and the Division of Neurosurgery (B.Y.S.K., J.T.R.) and the Arthur and Sonia Labatt Brain Tumour Research Centre ( J.T.R.), Hospital for Sick Children (B.Y.S.K., J.T.R.) — both in Toronto. Address reprint requests to Dr. Chan at the Institute of Biomaterials and Biomedical Engineering, Donnelly Centre for Cellular and Biomolecular Research, 164 College St., 407, University of Toronto, Toronto, ON M5S 3G9, Canada, or at warren.chan@ utoronto.ca.

The SFRP family of WNT inhibitors function as novel tumor suppressor genes epigenetically silenced in medulloblastoma.

Abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Dysregulation of WNT signaling occurs in up to 20% of cases. Using a genome-wide approach, we identified the secreted frizzled-related protein 1, 2 and 3 (SFRP1, SFRP2 and SFRP3) family of WNT inhibitors as putative tumor suppressor genes silenced by promoter region methylation in MB. SFRP1, SFRP2 and SFRP3 expression increased after 5-aza-2′-deoxycytidine treatment. SFRP1, SFRP2 and SFRP3 methylation was identified in 23.5, 3.9 and 15.7% of primary MB specimens, respectively, by methylation-specific PCR. Stable SFRP1, SFRP2 and SFRP3 expression reduced phospho-DVL2 levels and hindered MB cell proliferation and colony formation in soft agar in vitro. In 60% of primary tumors, SFRP1 was expressed at levels twofold lower than that in normal cerebellum. SFRP1 expression impaired tumor formation in vivo in flank and orthotopic intracerebellar xenograft models and conferred a significant survival advantage (P<0.0001). We identify for the first time tumor suppressor gene function of SFRP genes in MB, and suggest that loss of WNT pathway inhibition due to SFRP gene silencing is an additional mechanism that may contribute to excessive WNT signaling in this disease.

Genomics of medulloblastoma: from Giemsa-banding to next-generation sequencing in 20 years

Abstract: Advances in the field of genomics have recently enabled the unprecedented characterization of the cancer genome, providing novel insight into the molecular mechanisms underlying malignancies in humans. The application of high-resolution microarray platforms to the study of medulloblastoma has revealed new oncogenes and tumor suppressors and has implicated changes in DNA copy number, gene expression, and methylation state in its etiology. Additionally, the integration of medulloblastoma genomics with patient clinical data has confirmed molecular markers of prognostic significance and highlighted the potential utility of molecular disease stratification. The advent of next-generation sequencing technologies promises to greatly transform our understanding of medulloblastoma pathogenesis in the next few years, permitting comprehensive analyses of all aspects of the genome and increasing the likelihood that genomic medicine will become part of the routine diagnosis and treatment of medulloblastoma.

Silencing of Thrombospondin-1 Is Critical for Myc-Induced Metastatic Phenotypes in Medulloblastoma

Abstract: Mechanisms by which c-Myc (Myc) amplification confers aggressive medulloblastoma phenotypes are poorly defined. Here, we show using orthotopic models that high Myc expression promotes cell migration/invasion and induces metastatic tumors, which recapitulate aggressive histologic features of Myc-amplified primary human medulloblastoma. Using ChIP-chip analysis, we identified cell migration and adhesion genes, including Tsp-1/THBS1, ING4, PVRL3, and PPAP2B, as Myc-bound loci in medulloblastoma cells. Expression of Tsp-1 was most consistently and robustly diminished in medulloblastoma cell lines and primary human tumors with high Myc expression (n = 101, P = 0.032). Strikingly, stable Tsp-1 expression significantly attenuated in vitro transformation and invasive/migratory properties of high Myc-expressing medulloblastoma cells without altering cell proliferation, whereas RNA interference-mediated Myc knockdown was consistently accompanied by increased Tsp-1 levels and reduced cell migration and invasion in medulloblastoma cells. Chromatin immunoprecipitation (ChIP) assays revealed colocalization of Myc and obligate partner Max and correlated diminished RNA polymerase II occupancy (∼3-fold decrease, P < 0.01) with increased Myc binding at a core Tsp-1 promoter. Reporter gene and/or gel shift assays confirmed direct repression of Tsp-1 transcription by Myc and also identified JPO2, a Myc interactor associated with metastatic medulloblastoma, as a cofactor in Myc-mediated Tsp-1 repression. These findings indicate the Myc-regulatory network targets Tsp-1 via multiple mechanisms in medulloblastoma transformation, and highlight a novel critical role for Tsp-1 in Myc-mediated aggressive medulloblastoma phenotypes.

Hemispherectomy for the Control of Intractable Epilepsy in Childhood: Comparison of 2 Surgical Techniques in a Single Institution

Abstract: BACKGROUND: Hemispherectomy is an established neurosurgical procedure for catastrophic epilepsy in childhood. However, the technique used to achieve an optimum outcome remains to be determined. OBJECTIVE: We examined the influence of hemidecortication (HD) vs per-insular hemispherotomy (PIH) on patient outcome. METHODS: The medical records of 4 1 children undergoing hemispherectomy were reviewed for patient demographics, clinical criteria, and surgical outcomes. RESULTS: HD and PIH were performed in 21 and 20 children, respectively. The mean age at surgery for HD was 54 months and 61 months for PIH. The median durations of surgery for HD and PIH were 5 hours and 7 hours, respectively (P < .001). For HD, 6 patients required a second surgery and 3 required a third. One PIH patient required a second procedure. Postoperative shunting was required in 5 HD patients, but only 1 PIH patient. All patients had increased hemiparesis after surgery. The overall mean follow-up time was 72 months. Engel class I or II outcomes after initial surgery were better after PIH (85%) compared with HD (48%) (P < .02). After subsequent surgeries for seizure control, 4 HD patients and 1 PIH patient improved to Engel class I or II. CONCLUSION: Hemispherectomy is an effective surgical procedure for childhood intractable catastrophic epilepsy. In patients with diffuse hemispheric disorder, PIH tends to have fewer major complications, more favorable seizure outcomes, and a decreased need for subsequent surgical procedures, including shunting for hydrocephalus, compared with HD.

Revision of vagal nerve stimulation (VNS) electrodes: review and report on use of ultra-sharp monopolar tip

Abstract: As a result of the increasingly popularity of vagal nerve stimulation (VNS) for intractable seizures, neurosurgeons not uncommonly encounter cases which require electrode revision. We examine our experience of VNS revision and reports the use of the ultra-sharp monopolar tip for safe dissection and removal of the electrode from the vagus nerve. A retrospective review was performed from January 2000 to Dec 2009 reviewed eight cases of VNS revision. The indications for VNS revision were device malfunction manifesting with increased seizures or increased impedance of the device and infection. The time from initial VNS implantation to revision ranged from 6 to 108 months (mean: 38 months). The entire VNS electrode system, was removed in seven cases and the helical coils were left in-situ in one case who did not derive any benefit from VNS and it was deemed unnecessary to subject the patient to the additional risk of vagal nerve injury. One case had dislodgement of the lower two coils and three cases had dense scarring to the vagus nerve causing high impedance and malfunction. The other three cases demonstrated no fibrotic scar tissue between the helical coils and the vagus nerve. Four cases had replacement of new VNS system but the case of infected VNS stimulator was not replaced as there was no benefit from the device. VNS revision is normally performed in cases of device malfunction or infection and can be safely performed using a combination of ultra-sharp monopolar coagulation and sharp dissection.

Diffusion tensor tractography detection of functional pathway for the spread of epileptiform activity between temporal lobe and Rolandic region.

Abstract: The aim of the study was to assess the connectivity between magnetoencephalographic (MEG) dipoles in the temporal lobe and Rolandic region in children with temporal lobe epilepsy using diffusion tensor imaging (DTI) tractography. Six pediatric patients with intractable focal epilepsy had MEG performed, which showed MEG dipoles over both temporal and Rolandic regions in a unilateral hemisphere. DTI tractography was performed on each patient. Six control subjects were studied for comparison. Two volumes of interest (VOIs) that encompassed the MEG dipoles were drawn, one placed in temporal lobe and the other in Rolandic region. Similar VOIs were placed in the contralateral side in the patients and on both sides in controls. Fractional anisotropy (FA) and trace of the external capsules were compared between patients and controls. In all patients, a tractography pathway traversing through the external capsule, connecting the temporal and Rolandic MEG dipoles, was visualized. However, on the contralateral hemisphere in each patient, there was no evidence of a similar fiber tract. There was no corresponding tractography pathway identified in either hemisphere within the controls. There were no significant differences in FA and trace between the seizure focus side and contralateral side in the patients. There was no significant difference in FA, but a difference in trace between patients and controls. We have found aberrant tractography pathway traversing through the external capsule, connecting two distant foci of epileptiform activity. Chronic interictal epileptogenic discharge could play a causal role in the de novo organization of these tracts.

Image guidance and neuromonitoring in neurosurgery

Abstract: The localization of tumors and epileptogenic foci within the somatosensory or language cortex of the brain of a child poses unique neurosurgical challenges. In the past, lesions in these regions were not treated aggressively for fear of inducing neurological deficits. As a result, while function may have been preserved, the underlying disease may not have been optimally treated, and repeat neurosurgical procedures were frequently required. Today, with the advent of preoperative brain mapping, image guidance or neuronavigation, and intraoperative monitoring, peri-Rolandic and language cortex lesions can be approached directly and definitively with a high degree of confidence that neurosurgical function will be maintained. The preoperative brain maps can now be achieved with magnetic resonance imaging (MRI), functional MRI, magnetoencephalography, and diffusion tensor imaging. Image guidance systems have improved significantly and include the use of the intraoperative MRI. Somatosensory, motor, and brainstem auditory-evoked potentials are used as standard neuromonitoring techniques in many centers around the world. Added to this now is the use of continuous train-of-five monitoring of the integrity of the corticospinal tract while operating in the peri-Rolandic region. We are in an era where continued advancements can be expected in mapping additional pathways such as visual, memory, and hearing pathways. With these new advances, neurosurgeons can expect to significantly improve their surgical outcomes further.

Mapping of the cortical spinal tracts using magnetoencephalography and diffusion tensor tractography in pediatric brain tumor patients.

Abstract: Prior to resection of a cerebral brain tumor, mapping of the functional and structural anatomy of the adjacent tissue is essential to reduce the risk of damage to descending and ascending pathways. We investigated the effectiveness of concurrent magnetoencephalography (MEG) and diffusion tensor imaging (DTI) tractography to delineate the motor cortex and associated corticospinal tract (CST) in a case series of children with brain tumors seen for pre-surgical evaluation. Using activation points generated from MEG to launch tractography, we delineated the CST of four patients and eight control subjects. Displacement of the CST was considerably larger in children with tumors located in the center of the hemisphere than in children whose tumors were more posteriorly located. Our findings suggest that the use of concurrent MEG and DTI may be an effective tool in the pre-surgical evaluation of eloquent cortex and associated white matter tracts in pediatric brain tumor patients.

Stimulation threshold potentials of intraoperative cortical motor mapping using monopolar trains of five in pediatric epilepsy surgery

Abstract: Objective Direct cortical stimulation in commonly used for the accurate localization of the motor cortex but the electrical threshold stimulation parameters with this technique had not been fully established.

Intraoperative angiography during microsurgical removal of arteriovenous malformations in children.

Abstract: Object Confirming the successful management of pediatric arteriovenous malformations (AVMs) requires high-quality postoperative digital subtraction angiography. Although the role of intraoperative angiography during the microsurgical removal of AVMs is well established in adults, the technique has several limitations including poor image quality, uniplanar image acquisition, and absent full heparin protection. Here, the authors report on their experience with high-quality intraoperative angiography during the surgical management of pediatric AVMs in their image-guided therapy (IGT) facility. Methods The authors retrospectively reviewed the demographic, clinical, and radiological characteristics of 22 patients who underwent the surgical management of AVMs at the Hospital for Sick Children in Toronto, with the aid of high-quality intraoperative or immediate postresection cerebral angiography via a transfemoral approach. Results Between January 2000 and August 2009, 18 children (mean age 13.05 ± 4.04 years, ...

Genetics of medulloblastoma: clues for novel therapies.

Abstract: Medulloblastoma is the most common malignant brain tumor in children. Current medulloblastoma therapy entails surgery, radiation and chemotherapy. The 5-year survival rate for patients ranges from 40 to 70%, with most survivors suffering from serious long-term treatment-related sequelae. Additional research on the molecular biology and genetics of medulloblastoma is needed to identify robust prognostic markers for disease-risk stratification, to improve current treatment regimes and to discover novel and more effective molecular-targeted therapies. Recent advances in molecular biology have led to the development of powerful tools for the study of medulloblastoma tumorigenesis, which have revealed new insights into the molecular underpinnings of this disease. Here we discuss the signaling pathway alterations implicated in medulloblastoma pathogenesis, the techniques used in molecular profiling of these tumors and recent molecular subclassification schemes. Particular emphasis is given to the identification of novel molecular targets for less toxic, patient-tailored therapeutic approaches.

Immunolocalization of Fascin, an Actin-Bundling Protein and Glial Fibrillary Acidic Protein in Human Astrocytoma Cells

Abstract: Fascin is a 55-kDa globular protein that functions to organize filamentous-actin into parallel bundles. A role for fascin in cell migration has led to its study in many tumor types. In this report, we investigate fascin in astrocytomas. We show that fascin is expressed in astrocytes and in a panel of human astrocytoma cell lines. Immunofluorescence analysis demonstrates that fascin and the intermediate filament protein, glial fibrillary acidic protein (GFAP), are both expressed in the perinuclear region and within cytoplasmic processes of astrocytes and astrocytoma cells. Amino acid residues within the NH2 terminus of GFAP can undergo phosphorylation; these modifications regulate intermediate filament disassembly and occur during cytokinesis. We show that fascin and specific phosphorylated species of GFAP colocalize within dividing cells. Finally, we demonstrate that fascin co-immunoprecipitates with GFAP and that immunocomplex formation is preferential for GFAP phosphorylated at serine residues 8 and 13. These data show that fascin and GFAP are immunolocalized regionally within cells and tumors of astrocytic origin and suggest that their binding may occur during dynamic reorganization of intermediate filaments.

Excellence in neurosurgery program building: enhancing the academic mission.

Abstract: Having talked about excellence in research in neurosurgical oncology and clinical neurosurgery, I will use this opportunity to speak about excellence in neurosurgery program building and enhancing the academic neurosurgery mission. It has been my great honor to serve as chairman of the Division of Neurosurgery at the University of Toronto these past 10 years. I have had the distinct pleasure of serving with many talented faculty and neurosurgery residents. As a result, it has been relatively straightforward to build programs around these individuals who have been instrumental in the initiatives that have come forward in our division.

Surgical approaches to epilepsy

Abstract: Surgical treatment for epilepsy is the only currently available treatment that provides the patient with the possibility of becoming seizure free and off anticonvulsants. This article describes many of the recent advances in the field of epilepsy surgery that are used by the epilepsy team to render patients seizure free without neurological or cognitive deficit. In particular, this article discusses the role of magnetoencephalography, recent advances in MRI techniques for preoperative brain mapping, invasive electrode recording and neuronavigation for the work-up of patients prior to definitive surgical treatment. We then discuss the outcome following different epilepsy surgical procedures, including vagal-nerve stimulation, multiple subpial resections and corpus callosotomy. Finally, we describe techniques that do not currently have an established role but hold promise in the treatment of epilepsy. These techniques include deep-brain stimulation and additional forms of neural stimulation for the patient ...

Abstract 4347: Medulloblastoma comprises four distinct diseases

Abstract: Prior attempts to subgroup medulloblastoma (MB) using genomics have identified 4-6 distinct molecular subtypes, including two subgroups driven by activated Wnt and Shh signaling. We performed an integrative analysis on a cohort of 103 primary MBs using a combination of Affymetrix expression and SNP genotyping arrays to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups. Both unsupervised hierarchical clustering and principal component analysis of expression data reveals very high confidence for the existence of four medulloblastoma subgroups: WNT, SHH, Group C, and Group D. Additional bioinformatic analyses using non-negative matrix factorization (NMF) and subclass mapping (SubMap) further strengthens the support for the four subgroups. These subgroups exhibit distinct demographics: SHH tumors occur in infants and adults, Group C tumors are restricted to children, and WNT and Group D tumors are found across all age groups. While the sex ratio for the entire cohort is ∼1.5:1 (M:F), the sex ratio for WNT group tumors was ∼1:3. We identified a number of previously uncharacterized, subgroup-specific regions of chromosomal abnormality including 9p, 3q, 20q, and 21q gain in SHH tumors, 1q gain and 5q, 16q, and 10q loss in Group C tumors, and near universal isochromosome 17q and frequent loss of the X chromosome in Group D tumors. These regions likely harbor subgroup-specific oncogenes and tumor suppressor genes that could be targets for rationale therapy. Our demographic, transcriptional, and genetic data support the non-overlapping character of these four subgroups of MB. We identified ‘signature’ genes over-expressed in each subgroup for which there are high quality commercial antibodies available. Staining two separate MB tissue microarrays containing 294 non-overlapping tumors for DKK1 (WNT), SFRP1 (SHH), NPR3 (Group C), and KCNA1 (Group D) demonstrated that 288/294 (98%) tumors stained positive for only a single marker. Analysis of the demographics in these patients validated the results observed in our discovery series studied at the RNA level. Leptomeningeal dissemination was highly over-represented in Group C (47%) followed by Group D (30%) patients. A multivariate analysis that included age, extent of resection, histology, M stage, and subgroup revealed that only LCA histology and Group C affiliation were prognostic. As M0 Group C tumors have a very poor prognosis, we suggest that Group C patients include many of the children with ‘average-risk’ MB who relapse after current therapies. Our data highly support the existence of four independent subtypes of MB that differ in their demographics, transcription, genetic events, rate of metastases, and clinical outcome. Our novel ‘4 antibody’ technique is capable of determining MB subgroup through immunohistochemistry on formalin-fixed, paraffin-embedded material suggesting that it will be broadly generalizable across the globe. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4347.

Pediatric sinonasal undifferentiated carcinoma: case report and literature review.

Abstract: aggressive malignancy arising from the nasal cavity and paranasal sinuses. Sinonasal undifferentiated carcinoma was first reported in 1986 by Frierson et al, and since then less than 100 cases have been reported in the literature.1 One previous pediatric case has been described in a 12-year-old boy in India.2 Sinonasal undifferentiated carcinoma is histologically classified as part of a spectrum of neuroendocrine carcinomas originating from the Schneiderian epithelium or the nasal ectoderm in the paranasal sinuses.1 Here, we report only the second case of SNUC to arise in childhood involving a teenager with disease arising from the nasal cavity and extending through the paranasal air sinuses into the anterior cranial fossa and brain.

Medulloblastoma-PNET, Craniopharyngioma Adult Tumors of Pediatric Origin

Abstract: According to the new WHO classification, embryonal tumors comprise medulloblastomas, primitive neuroectodermal tumors (PNET), medulloepitheliomas, ependymoblastomas, and neuroblastomas. We include here also craniopharyngiomas.

Introduction: neurogenomics and neuroproteomics

Abstract: 1 For this issue of Neurosurgical Focus, we are pleased to present a spectrum of interesting articles covering a wide range of contemporary genomic and proteomic topics specifically related to neurosurgical diseases. The authors review a broad range of contemporary population genetic and molecular techniques available for the study of neurological disease. The issue begins with articles on broadly applied population genetic tools used to identify the relative risk of neurosurgical diseases among the kindred of affected individuals. One such example is the Utah population data bank described by Niazi et al. Subsequent articles describe game-changing contemporary molecular techniques used to provide screening for genetic alterations associated with a specific disease or phenotype. Examples are the genome-wide association studies described by Cowperthwaite et al. and the next-generation screening techniques for genetic alteration applied to medulloblastomas by Taylor et al. A review of the role of miRNAs in brain tumor biology is provided by Kalani et al. Chen and colleagues describe the identification of distinct functional genomic alterations among vast genetic changes as a strategy to target tumor cell vulnerabilities with novel therapies. The application of siRNA technology to induce therapeutic functional changes in gene expression in glioblastoma multiforme cells is described in the article by Thaker et al. In the remaining articles the authors discuss genetic and proteomic changes associated with specific diseases, including head trauma (Dardiotis et al.), Parkinson disease (Hadjigeorgiou et al.), and neurofibromatosis Type 1 (Gottfried et al.). Dhandapani et al. discuss their novel proteomic studies in patients with subarachnoid hemorrhage, which provide proof of principle and promise for future development of diagnostic and therapeutic innovations in this emerging and fascinating area of research. Finally, Vannemreddy and colleagues provide data supporting a role for eNOS in the clinical presentation of intraventricular hemorrhage. Collectively, these papers serve as a solid primer in genomics and proteomics for the practicing neurosurgeon and convey some of the most exciting recent molecular science developments relevant to neurosurgical disease. Introduction: neurogenomics and neuroproteomics

Choroid Plexus Tumors

Abstract: Choroid plexus tumors (CPTs) are rare, primary brain tumors arising from the neuroepithelium of the choroid plexus. Although they may be found in patients of any age, the vast majority occur in the pediatric population. Up to 70% of these neoplasms occur in children, with over half arising in children under 2 years of age [39]. The annual incidence for CPTs is low, with 0.3 cases/ million reported [23]. Despite this, the annual incidence in the pediatric age group is as high as 3–5%, and up to 12% in those children under 2 years of age [22, 25]. CPTs account for 0.4–0.8% of all brain tumors, between 0.9% and 3% of all primary pediatric brain tumors, and up to 10–20% of pediatric brain tumors during the first year of life [1, 10, 11, 46]. Case reports exist describing in utero findings of CPTs by ultrasound, or of the diagnosis of CPTs in the neonate, suggesting that some of these lesions may occur congenitally [3, 36, 55].

Dysembryoplastic Neuroectodermal Tumors

Abstract: Dysembryoplastic neuroectodermal or neuroepithelial tumor (DNET) was initially described by Daumas-Duport et al. [5] in 1988 as a mixed tumor with glial and neuronal elements, and has been included in the World Health Organization classification of brain tumors as a separate entity [11]. It is considered as hamartomatous, low-grade lesion (WHO grade I) due to the dysplastic appearance of the lesion and the surrounding cortex. It constitutes about 1.5% of all pediat-ric intracranial tumors. They mainly occur in the temporal lobe followed by the frontal and occipital lobe or the cerebellum and brain stem [16]. Macroscopically, DNETs are most of the time confined to the cerebral cortex, but may extend into the adjacent white matter. DNETs typically manifest during childhood or early adulthood with often medically refractory epileptic seizures. The seizure focus is frequently in the temporal location, and the lesion most often found in the temporal lobe, followed by the frontal lobes, and is only rarely located in other lobes. Associated cranial bone deformities with thinning of the overlying calvarium may be present. Histologically, DNETs are characterized by the presence of a specific element and by a nodular component. The specific elements consist of oligoden-droglia-like cells that are distributed within a mucinous matrix, in which normal and dysplastic ganglion-like neurons appear to be floating (“floating neurons”). Although increased cellularity and some pleomorphism may be present, these lesions are devoid of anaplastic features. Based on the results of immunohistochemical studies, DNETs are considered to originate from progenitor cells with potential for glial and neuronal differentiation. The surgical outcome is excellent. Even after subtotal resection recurrences are rare.

Excellence in clinical neurosurgery: practice and judgment make perfect.

Abstract: Having discussed the importance of excellence in research in neurosurgery in my previous lecture, I will now make a strong case for the pursuit of excellence in clinical neurosurgery. Here, the adage ‘‘practice makes perfect’’ will be used time and again to underscore the important roles of repetition of manual and intellectual tasks to achieve excellence in our subspecialty. To this adage, however, I have also added the concept of ‘‘judgment,’’ which comes into play whenever we look after our patients with neurosurgical disease. It takes judgment to know when to operate, but perhaps more important, when not to operate. Even the most skillful technical neurosurgeons run the risk of unexpected patient outcomes if good judgment is not applied to the patients on whom they operate. It is the combination of practice and judgment that perhaps sets us apart as neurosurgeons from other professionals in which a lapse in judgment in their disciplines would not have the far-reaching ramifications that it does for us and our patients. Some of the other disciplines I will be reviewing here in terms of practice making perfect include performance piano and professional tennis and golf as examples.

Tumors of the Skull Base in Children

Abstract: Tumors of the skull base present a difficult therapeutic challenge to the neurosurgeon because of the complexity involved in approaching these lesions. However, with recent technical advances and the development of specialized centers with teams of physicians interested in managing these patients, the removal and cure of skull base tumors is now possible. While many of the surgical approaches developed to approach skull base tumors have been reported for adults, there have been few such reports for children. In general, children pose unique anatomical challenges for the skull base surgeon because of the constraints of the developing skull and the small size of the patients.