Showing papers by "James T. Rutka published in 2006"

Vagal nerve stimulation for refractory epilepsy in children: indications and experience at The Hospital for Sick Children.

Abstract: The management of intractable epilepsy in children is a challenging problem. For those patients who do not respond to antiepileptic drugs and are not candidates for epilepsy surgery, vagal nerve stimulation (VNS), can be a viable alternative for reducing seizure frequency. We have reviewed the historical and clinical background of VNS treatment. We also include our experience at The Hospital for Sick Children in children who underwent VNS implantation. Forty-one children underwent VNS implantation for epilepsy over 6 years. After a mean follow-up of 31 months, 15 (38%) patients had a seizure frequency reduction of more than 90%. Fifteen (38%) children failed to respond to the VNS treatment. The device was removed in five children: in one, due to late infection; the other four could not tolerate the side effects of chronic VNS therapy. Two patients required reimplantation due to electrode failure. The most common side effects in our series were cough and vocal disturbances. Our results show that VNS implantation can be a safe and effective alternative therapy for children with drug-resistant epilepsy who are not candidates for epilepsy surgery.

Human Telomere Reverse Transcriptase Expression Predicts Progression and Survival in Pediatric Intracranial Ependymoma

Abstract: Purpose Pediatric intracranial ependymomas are a heterogeneous group of neoplasms with unpredictable clinical and biologic behavior. As part of ongoing studies to identify potential biologic and therapeutic markers, we analyzed the role of human telomere reverse transcriptase (hTERT; the catalytic subunit of telomerase) expression as a prognostic marker for this disease. Patients and Methods Primary intracranial ependymomas that were resected at our institution between 1986 and 2004 were identified through the pathology and oncology databases. A tissue array was constructed from the patient samples and hTERT expression was evaluated by immunohistochemistry. Twenty-one samples were also analyzed for telomerase activity (telomerase repeat amplification protocol assay). Results Eighty-seven tumors from 65 patients were analyzed. Five-year progression-free survival was 57% (SEM, 12%) and 21% (SEM, 8%) for hTERT-negative and hTERT-positive tumors, respectively (P = .002). Five-year overall survival was 84% (SE...

Temporal lobe surgery for intractable epilepsy in children: an analysis of outcomes in 126 children.

Abstract: OBJECTIVE: Temporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. METHODS: We reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. RESULTS: The mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous malformations in four children. Ganglioglioma and astrocytoma were the most common tumors encountered. Mesial temporal sclerosis was found in 16 patients (13%), astrogliosis in 15 patients (12%), and cortical dysplasia in eight patients (7%). Postoperative follow-up of at least 2 years was available for 106 patients and ranged up to 13.0 years. Seventy-four percent of patients had an Engel Class I or II outcome. Patients with temporal lobe lesions had better outcomes compared with those without lesions (P < 0.05). Patients without a history of secondary generalization of seizures also had a better outcome when compared with those with secondary generalization. Complications in the form of contralateral homonymous hemianopsia, dysphasia, and infection were found in 5% of patients. Twelve patients had a second temporal lobe procedure for intractable recurrent seizures. After a second procedure, seven patients returned to a seizure-free state. CONCLUSION: Temporal lobe resections for epilepsy in children are effective and safe procedures, with a favorable impact on seizure control. Repeat temporal resections for recurrent seizures may also be effective in restoring a seizure-free outcome to children.

Weight gain in craniopharyngioma--a model for hypothalamic obesity.

Abstract: Objectives: To evaluate (1) the pattern of post-operative weight gain and (2) the risk factors associated with the development of post-operative weight gain and obesity in children treated for craniopharyngioma. Study design: The records of 43 children who had primary craniopharyngioma resection were reviewed. Neurological, endocrine, anthropometric and radiological risk factors for the development of obesity nd for post-operative increase in BMI SDS were analyzed. Results: Twenty-five patients (58%) became obese post-operatively. Obesity was significantly associated with higher BMI SDS at presentation and pre-operative hydrocephalus (p <0.05). Increased BMI SDS from 0-12 months was significantly associated with post-operative MRI evidenced hypothalamic damage and higher BMI at presentation (p <0.05). Conclusions: Children who developed hypothalamic obesity had a significant, rapid BMI increase over the first 6 months, followed by stabilization, with no regression of BMI SDS.

The neurosurgical workforce in North America: a critical review of gender issues.

Abstract: Objective The role of women in Western society has changed dramatically in the past several decades. Despite this, many gender disparities still exist for professionals in the health care sector. In neurosurgery, a disproportionately small percentage of the workforce in the United States and Canada is female. These figures are lower than most reported in other medical specialties. This review critically examines factors that may be influencing women's ability to advance in demanding subspecialties such as neurosurgery. Methods The literature on women in medicine, and surgery in particular, were reviewed to identify different issues facing women currently in practice in neurosurgery. In addition, the concerns of prospective trainees were examined. Results There remain many challenges for women entering neurosurgery, including unique lifestyle concerns, limited mentorship, out-dated career programs, and deep-seeded societal beliefs. Discrimination and harassment are also contributing factors. Conclusion If neurosurgery is to continue to progress as a subspecialty, the issue of gender inequality needs to be scrutinized more closely. Innovative programs must be developed to meet the needs of current female faculty members and to ensure attracting the brightest individuals of both genders into a career in neurosurgery.

Array CGH analysis of pediatric medulloblastomas

Abstract: Brain tumors are the second most common childhood cancer. We used high-resolution array comparative genomic hybridization (aCGH) to analyze losses and gains of genetic material from 24 medulloblastomas. The bacterial artificial chromosome clones were ordered on the array, allowing for an average resolution of approximately 420 kilobases. The advantage of this high resolution is that the breakpoints associated with subregional chromosome copy number aberrations can be accurately defined, which in turn allows candidate genes within these regions to be readily defined. In this analysis, we confirmed the frequent involvement of loss of 17p and gain of 17q, although we have now established the position of the breakpoint that consistently lies in the chr17:18318880–19046234 region of the chromosome. Other frequent losses were seen on 8p, 10q, 16q, and 20p, and frequent gains were seen on 2p, 4p, 7, and 19. In addition, the fine-resolution mapping provided by aCGH made it possible to define small chromosome deletions in 1q23.3–q24.2, 2q13.12–q13.2, 6q25–qter, 8p23.1, 10q25.1, and 12q13.12–q13.2. Overall, amplification events were rare, the most common involving MYC (16%), on 8q, although isolated events were seen in 10p11 and 3q. © 2005 Wiley-Liss, Inc.

Molecular pathways triggering glioma cell invasion.

Abstract: The efficacy of treating malignant gliomas with adjuvant therapies remains largely unsuccessful due to the inability to effectively target invading cells. Although our understanding of glioma oncogenesis has steadily improved, the molecular mechanisms that mediate glioma invasion are still poorly understood. It is clear that genetic alterations in malignant gliomas affect cell proliferation and cell cycle control, which are the targets of most chemotherapeutic agents. However, effective therapy against cell invasion has been less successful. Future treatment protocols must incorporate pharmacotherapeutic strategies that target resistant infiltrative glioma cells as well as proliferating ones. Thus, delineating the point of convergence of signaling pathways, which mediate glioma invasion, proliferation and apoptosis, may identify novel targets that can serve as possible points of therapeutic intervention. The optimization of novel strategies will require reliable preclinical testing using an in vivo animal model of brain invasion. Current applications of existing animal models are not currently optimized or characterized for use in glioma invasion research. As such, the development of a bona fide brain invasion model in vivo must be established. Progress in understanding molecular mechanisms driving glioma invasion will be critical to the success of managing and improving the outcome of patients with this grave disease.

Imaging findings in primary intracranial atypical teratoid/rhabdoid tumors.

Abstract: Background: Intracranial atypical teratoid/rhabdoid tumors (AT/RT) are rare and extremely aggressive neoplasms seen primarily in childhood. Imaging features are often considered non-specific. However, correct diagnosis of AT/RT is important because these tumors have a markedly different clinical prognosis and require more aggressive therapy.Objective: To determine the imaging features of AT/RT.Materials and methods: We retrospectively analyzed imaging findings in 11 patients with primary intracranial AT/RT presenting over a period of 5 years. CT (n=11), MR (n=7), clinical (n=11) and pathological (n=11) features were evaluated. FISH analysis showing monosomy of chromosome 22 (absence of bcr 22q11 locus) was available for three patients. Immunohistochemical staining for INI-1 (BAF47) was performed on all tumors. Results: There were 11 patients, 6 boys and 5 girls. The age of presentation varied from 1 month to 15 years (average age 3 years 8 months). Six tumors were located in the posterior fossa and five in the supratentorial compartment. The tumors showed a hyperdense solid component (64%) that showed moderate to marked enhancement with contrast medium. On MR imaging, the predominant signal pattern was isointensity on T1-weighted images (57%) and T2 shortening with heterogeneity on T2-weighted images (86%). All tumors were large in size (average 4.2×3.7 cm), and there was a tendency for calcification (36%), hemorrhage (46%), necrosis (46%) and perifocal edema (100%). There was also a high tendency for subarachnoid dissemination, with five patients (46%) demonstrating brain and/or spinal metastasis. At follow-up (n=7), six patients showed local recurrence. At the time of recurrence, all these patients showed extensive leptomeningeal spread of the disease in both intracranial and intraspinal compartments. Conclusion: There are no specific imaging features for intracranial AT/RT. But a high tendency toward large size, a hyperdense solid component on CT scan with calcification, hemorrhage, necrosis and subarachnoid spread suggest that this tumor should be considered in the differential diagnosis of large pediatric intracranial tumors.

Imaging surgical epilepsy in children

Abstract: Epilepsy surgery rests heavily upon magnetic resonance imaging (MRI). Technical developments have brought significantly improved efficacy of MR imaging in detecting and assessing surgical epileptogenic lesions, while more clinical experience has brought better definition of the pathological groups. MRI is fairly efficient in identifying developmental, epilepsy-associated tumors such as ganglioglioma (with its variants gangliocytoma and desmoplastic infantile ganglioglioma), the complex, simple and nonspecific forms of dysembryoplastic neuroepithelial tumor, and the rare pleomorphic xanthoastrocytoma. The efficacy of MR imaging is not as good for the diagnosis of focal cortical dysplasia (FCD), as it does not necessarily correlate with histopathological FCD subtypes and does not show the real extent of the dysplasia which may even be missed in a high percentage of cases. Further developments with better, multichannel coils, higher magnetic fields, specific sequences, and different approaches (such as diffusion tensor imaging) for depicting the structural abnormalities may hopefully improve this efficacy. A general review of the MR features of the diverse pathologies concerned with epilepsy surgery in the pediatric context is provided with illustrative images.

Vascularity and angiogenesis as predictors of growth in optic pathway/hypothalamic gliomas

Abstract: Object The authors’ aim in conducting this study was to investigate retrospectively the prognostic significance of angiogenic features in optic pathway/hypothalamic gliomas (OPHGs) in children. Methods Patients were identified in whom a diagnosis of OPHG was made using pathological analysis at the Toronto Hospital for Sick Children between 1985 and 2002. Tumor specimens were reviewed for diagnostic accuracy and adequacy of the specimen. Sections were immunostained with factor VIII to assess microvessel density (MVD). A ratio of α–smooth muscle actin to factor VIII immunostaining was calculated to arrive at a vascular maturity index (VMI). Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) immunostaining were performed to evaluate angiogenic factors. In addition, the MIB-1 labeling index (LI) was used to assess proliferation. These factors were evaluated with respect to progression-free survival (PFS). Forty-one of 60 patients originally identified had adequate samples and follow up for in...

Efficacy of Dexamathasone on Cerebral Swelling and Seizures during Subdural Grid EEG Recording in Children

Abstract: Summary: Purpose: To evaluate the impact of steroid treatment on cerebral swelling and seizures during subdural grid EEG (SGEEG) monitoring. Methods: We reviewed data from 37 pediatric patients with intractable epilepsy who underwent SGEEG monitoring and divided the patients into those who received dexamethasone and those who did not. We then correlated administration of steroids to incidence of cerebral swelling on computed tomography (CT) scans and to frequency of seizures during SGEEG. Results: Twenty-three patients received dexamethasone prophylactically every 6 hours (dosage range, 1–7.5 mg; mean, 3.2 mg) from the first day of SGEEG placement (group A); 14 patients received no dexamethasone (group B). Eight (21.6%) of 37 patients experienced cerebral swelling on CT: two (9%) were in group A, and six (42.9%) were in group B (p < 0.05). SGEEG monitoring time for recording habitual seizures that localized cortical areas for surgical excision was longer in group A (1–6 days; mean, 3.0) than it was in group B (1–3 days; mean, 2.2), (p < 0.05). Habitual seizures were recorded in 36 patients. One group A patient experienced obtundation due to cerebral swelling, and monitoring in this patient was discontinued. Conclusions: The prophylactic administration of steroids to pediatric patients during SGEEG monitoring is efficacious for reducing cerebral swelling. Although it decreases the frequency of habitual seizures and increases seizure-monitoring time, dexamethasone reduces the risk of complications from cerebral swelling during the SGEEG procedure.

Multiple subpial transections in pediatric epilepsy: indications and outcomes

Abstract: Multiple subpial transection (MST) is a surgical technique mainly used when epileptiform activity arises from eloquent or functional brain cortex. In the medical literature, there are relatively few studies reporting the efficacy and safety of this procedure in adults and in children. We review the scientific rationale, the indications, and the results of this procedure. Neuroanatomic studies show that the basic functional cortical unit is arranged vertically, and epileptic activity spreads horizontally. Minimal cortical unit is essential for maintenance of cortical activity. Vertical incisions in the cortex interrupt transverse synaptic connections, preventing seizure propagation while preserving the vertical column subserving neuronal function. In the past, it has been difficult to assess the efficacy of MSTs per se, as they have usually been performed together with cortical resection or lesionectomy. After MSTs, studies show that 33–46% of treated children are in Engel class I or II. The permanent complication rate is low with no permanent language or motor disabilities. MST is a safe procedure with unclear specific efficacy. It has been used mainly in conjunction with cortical resection or lesionectomy, when the eloquent cortex is involved in the seizure activity. Further prospective studies are needed to define the role of MST in epilepsy surgery.

Topographic movie of ictal high-frequency oscillations on the brain surface using subdural EEG in neocortical epilepsy.

Abstract: Summary: Purpose: To understand the rapid dynamic changes of ictal intracranial high-frequency oscillations (HFOs) in neocortical epilepsy. Methods: We integrated multiple band frequency analysis and brain-surface topographic maps of HFOs from ictal subdural EEG (SDEEG) recordings. We used SDEEG to record partial seizures consisting of right-arm jerks with secondary generalization in a 17-year-old right-handed girl. We selected 20-s EEG sections that included preclinical seizure recordings. We averaged the HFO power between 60 and 120 Hz for 25 selected electrodes, made topographic maps from these averaged powers, and superimposed the maps on the brain-surface image. We filmed consecutive HFO maps at a 10-ms frame rate. Results: Before clinical seizure onset, high-power HFOs emerged at the superior portion of the left precentral gyrus, then appeared in the middle of the left postcentral gyrus, and subsequently reverberated between both regions as well as the posterior portion of the left postcentral gyrus. Right-arm extension and facial grimacing started as the HFO power decreased. As generalized tonic–clonic seizures evolved, HFO power increased but remained within the central region. Conclusions: Topographic movies of intracranial HFOs on the brain surface allow visualization of the dynamic ictal changes in neocortical epilepsy.

Preoperative simulation of intracerebral epileptiform discharges: synthetic aperture magnetometry virtual sensor analysis of interictal magnetoencephalography data.

Abstract: Object Magnetoencephalography (MEG) has been used for the preoperative localization of epileptic equivalent current dipoles (ECDs) in neocortical epilepsy. Spatial filtering can be applied to MEG data by means of synthetic aperture magnetometry (SAM), and SAM virtual sensor analysis can be used to estimate the strength and temporal course of the epileptic source in the region of interest. To evaluate the clinical usefulness of this approach, the authors compare the results of SAM virtual sensor analysis to the results of ECD analysis, subdural electroencephalography (EEG) findings, and surgical outcomes in pediatric patients with neocortical epilepsy. Methods Ten pediatric patients underwent MEG, invasive subdural EEG, and cortical resection for neocortical epilepsy. The authors compared the morphological characteristics, quantity, location, and distribution of the epileptiform discharges assessed using SAM and ECD analysis, and subdural EEG findings (interictal discharges and ictal onset zones). In nine ...

Molecular biology of human gliomas

Abstract: Human gliomas are the most common primary central nervous system neoplasm, and they are a complex, heterogeneous, and difficult disease to treat. In the past two decades, advances in molecular biology have revolutionized our understanding of the mechanism by which these neoplasms are initiated and progress. While surgery, radiation therapy, and chemotherapy have roles to play in the treatment of patients with gliomas; these therapies are self-limited because of the intrinsic resistance of glioma cells to therapy, and the diffusely infiltrating nature of the lesions. It is now known that malignant gliomas arise from a number of well-characterized genetic alterations and activations of oncogenes and inactivation of tumor suppressor genes. These genetic alterations disrupt critical cell cycle, growth factor activation, apoptotic, cell motility, and invasion pathways that lead to phenotypic changes and neoplastic transformation. Research in each of these fields has uncovered potential therapeutic targets that look promising for disease control. Gliomas can now be modeled with fidelity and reproducibility using several transgenic and knockout strategies. Transgenic mouse models are facilitating the testing of various therapeutic strategies in vivo. Finally, the recognition of the putative brain tumor stem cell, the tumor initiating cell in brain cancer, provides an enticing target through which we could eliminate the source of the brain tumor with increased efficacy and less toxicity to normal tissues. In this review, we provide an up-to-date discussion of the many of key technologies and tools that are being used in molecular biology to advance our understanding of the biological behavior of human malignant gliomas.

Role of spinal MRI in the follow‐up of children treated for medulloblastoma

Abstract: BACKGROUND. The purpose of the current study was to describe the usefulness of spinal magnetic resonance imaging (MRI) in children with medulloblastoma or primitive neuroectodermal tumor (PNET) of the posterior fossa. METHODS. Children consecutively diagnosed with medulloblastoma/PNET and followed in the Hospital for Sick Children/Toronto were identified. A homogenous cohort of children treated with craniospinal irradiation as part of their initial treatment was considered. Contrast-enhanced spinal MRIs done concomitantly with cranial MRIs (doublets) were reviewed. Recurrence was defined as any new abnormal lesion (in the brain or in the spine) in symptomatic or asymptomatic patients. Doublets after the first recurrence were excluded in the final analysis. The utility of a spinal MRI in the presence of a negative cranial MRI was assessed. RESULTS. In all, 73 patients (21 females and 52 males; median age, 6.6 years, median follow-up time, 4.3 years) had at least 1 evaluable doublet during the follow-up period. Since concomitant cranial and spinal MRI was introduced as the standard evaluation for medulloblastoma/PNET in 1991, 286 doublets were evaluable. Fourteen spinal MRIs and 25 cranial MRIs showed new nodular or leptomeningeal lesions. In 2 patients, repeat MRIs ruled out recurrence (false-positive). All confirmed spinal recurrences were associated with intracranial recurrence. Of 261 doublets with negative cranial MRI, no new lesion was identified on spinal MRI. CONCLUSIONS. An absence of progression on cranial MRI is highly predictive of absence of progression on spinal MRI. There is little evidence that surveillance spinal MRI (in children who underwent craniospinal radiation as part of their initial treatment) improves the detection of recurrences in children with medulloblastoma. Cancer 2006. © 2006 American Cancer Society.

The role of magnetoencephalography in pediatric epilepsy surgery.

Abstract: Magnetoencephalography (MEG) is a new diagnostic imaging and brain mapping device that has been recently used in the context of pediatric epilepsy, epilepsy surgery, and neuronavigation. MEG allows for the placement of magnetic spike sources on a conventional magnetic resonance imaging scan, the so-called magnetic source imaging, so that the localization of epileptiform activity in a child can be determined. Considerable effort is placed on analyzing the configuration and number of spike waves by MEG that relate to a primary epileptiform discharge. Such MEG spike clusters are corroborated now by intraoperative invasive subdural grid monitoring that show good correlation in the majority of cases. Another important role of MEG relates to the mapping of critical regions of brain function using known paradigms for speech, motor, sensory, visual, and auditory brain cortex. When linked to standard neuronavigation devices, MEG brain mapping can be extremely helpful to the neurosurgeon approaching nonlesional epilepsy cases or lesional cases where the safest and most direct route to the surgical disease can be selected. As paradigms for brain mapping improve and as MEG software upgrades become more sensitive to analyzing all types of spike sources, MEG will play an increasingly important role in pediatric neurosurgery, especially for the child with intractable epilepsy.

Neurosurgical implications of neurofibromatosis Type I in children.

Abstract: Neurofibromatosis Type 1 (NF1) is one of the most common inherited diseases in humans It is caused by a mutation in the NF1 gene on chromosome 17, and is associated with numerous central and peripheral nervous system manifestations Children with NF1 are at high risk of harboring numerous lesions that may require the attention of a neurosurgeon Some of these include optic nerve gliomas, hydrocephalus, intraspinal tumors, and peripheral nerve tumors Although most of the neoplasms that affect the brain, spine, and peripheral nerves of children are low-grade lesions, there is a small but real risk that some of these lesions may become high grade over time, requiring other forms of therapy than surgery alone Other associated disorders that may result from NF1 in childhood include Chiari malformation Type I, scoliosis, and pulsating exophthalmos from the absence of the sphenoid wing In this review, the major lesions that are found in children with NF1 are reviewed as well as the types of treatment that are offered by neurosurgeons and other members of the treating team Today, optimum care of the child with NF1 is provided by a multidisciplinary team comprising neurosurgeons, neurologists, ophthalmologists, radiologists, orthopedic surgeons, and plastic surgeons

Endoscopic fenestration of a symptomatic cavum septum pellucidum: technical case report.

Abstract: Objective Cysts of the septum pellucidum (CSPs) may become symptomatic because of obstruction of cerebrospinal fluid flow, resulting in increased intracranial pressure and hydrocephalus requiring surgical intervention. Endoscopic fenestration may be the most effective and least invasive technique to treat this pathological condition. Clinical presentation An 11-year-old boy sought treatment for frequent episodes of severe headache. On examination, he had papilledema. There was evidence on magnetic resonance imaging scans of a space-occupying CSP with obstructive hydrocephalus. Intervention The endoscopic technique of fenestration of both lateral walls of an enlarged CSP via a left frontal approach under ultrasound guidance using a rigid endoscope was successful. After surgery, the patient became asymptomatic, his papilledema resolved, and magnetic resonance imaging scans demonstrated collapse of the walls of the CSP toward the midline. Conclusion Neuroendoscopic fenestration should be strongly considered as the treatment of choice for symptomatic CSPs. This procedure alone can lead to complete resolution of clinical symptoms and hydrocephalus, can reduce the size of the CSP, and can obviate the need for an implantable cerebrospinal fluid shunt.

Current concepts in the molecular genetics of pediatric brain tumors: implications for emerging therapies

Abstract: Background The revolution in molecular biology that has taken place over the past 2 decades has provided researchers with new and powerful tools for detailed study of the molecular mechanisms giving rise to the spectrum of pediatric brain tumors. Application of these tools has greatly advanced our understanding of the molecular pathogenesis of these lesions.

Magnetoencephalographic spike sources associated with auditory auras in paediatric localisation-related epilepsy.

Abstract: Objective: To characterise magnetoencephalographic spike sources in paediatric patients with auditory auras and recurrent localisation-related epilepsy. Methods: Six patients (four boys and two girls (ages 7–14 years) were retrospectively studied. All patients had auditory auras as part of their initial seizure manifestation, including four patients who underwent previous brain surgery. Scalp video electroencephalography and magnetoencephalography (MEG) were carried out in six patients, intraoperative electrocorticography in three patients and extraoperative intracranial video electroencephalography in one patient. MEG auditory-evoked fields (AEFs) were studied in four patients. Results: Three patients had elementary auditory auras, one had complex auditory aura and two had both complex and elementary auras. All six patients had clustered MEG spike sources with coexisting scattered spike sources. MEG clusters were localised in the superior temporal gyrus with surrounding scatters in four patients (two left and two right); two patients had scattered spikes in the superior temporal gyrus in addition to clustered MEG spike sources in the left inferior and middle frontal gyri or parieto-occipital region. AEFs were located within an MEG cluster in one patient and within 3 cm of a cluster in two patients. Surgical resection, including the regions of MEG clusters, was carried out in four patients. Three of four patients who had previous surgeries were seizure free at 2 years after excision of the MEG cluster region. Conclusions: MEG spike sources clustered in the superior temporal gyrus in six patients with auditory auras. These spike sources were in close proximity or seemed to engulf the magnetic AEF. Areas with MEG spike sources contained the residual or recurrent epileptogenic zone after incomplete cortical excision for lesional epilepsy.

Gliomas: quo vadis.

Abstract: INTRODUCTION The pessimist would say that there has been little advancement in the management of malignant gliomas in the past 30 years. However, recent basic science research discoveries and published studies in high-impact scientific journals these past few years provide more than enough optimism for patients and treating-physicians alike. We are on the threshold of considerable, significant change in the way in which we care for patients with gliomas, both from a neurosurgical and an oncological standpoint. However, before we illustrate how the field of glioma management has changed, it is prudent to take stock of our past and where we were less than 100 years ago.

Regulation of the Cell Cycle and Interventional Developmental Therapeutics

Abstract: A complex series of molecular signaling events are responsible for cell division. Early in the cell cycle, cues determine whether a cell will initiate a round of replication or withdraw from cell division and enter a state of quiescence. Passage through the restriction point (RP), designated the “point of no return”, marks cellular commitment to a new round of division. Genetic mutations affecting molecules that control proliferation predispose to tumorigenesis. Many of the identified mutations associated with cancer cells give rise to molecules that are no longer able to appropriately regulate the mammalian cell cycle and the end result is neoplasia. Here, we review the critical elements that enable cell cycle progression as well as the positive and negative regulators that facilitate the process. In addition, the development and implementation of therapeutic modalities that exploit cell cycle inhibition are examined.

Treatment Modalities for Ependymomas in Children

Abstract: Incidence and Natural History Ependymomas are among the most common primary brain tumors of children younger than 5 years of age, accounting for 10% to 12% of all brain tumors in the pediatric population and 2.5% of all intracranial gliomas. Ependymomas are believed to develop from oncogenetic events, in which ependymal lineage cells arising from the ventricular lining of the brain and the central canal of the spinal cord are transformed. These tumors classically show an age-based site preference, with supratentorial and spinal compartments more often involved in adults and the infratentorial compartment more often involved in children. Ninety percent of ependymomas occur intracranially, and approximately two thirds of these arise in the posterior fossa. The mean age at the time of diagnosis is between 3 and 6 years, with more then 25% of ependymomas found in children under the age of 3 years. Sixty percent of supratentorial ependymomas are found within the lateral or third ventricles; the remaining 40% may lie in an extraventricular cerebral parenchymal location. Ependymomas occur with equal frequency in both sexes. Most ependymomas are sporadic tumors, but some may be associated with neurofibromatosis type 2 (NF2). There are no known causative agents for ependymomas, although various viruses, such as SV-40, have been implicated in some studies. Treatment Modalities for Ependymomas in Children