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Biomedical subjects

James T Rutka

Publications and source records attributed to James T Rutka.

At least 19 recordsLinked to original sources
PubMed2007

Sloppy paired 1/2 regulate glial cell fates by inhibiting Gcm function.

Organization of the central nervous system during embryonic development is an intricate process involving a host of molecular players. The Drosophila segmentation genes, sloppy paired (slp) 1/2 have been shown to be necessary for development of a neuronal precursor cell subtype, the NB4-2 cells. Here, we show that slp1/2 also have roles in regulating glial cell fates. Using slp1/2 loss-of-function mutants, we show an increase in glial cell markers, glial cells missing (gcm) and reversed polarity. In contrast, misexpression of either slp1 or slp2 causes downregulation of glial cell-specific genes and alters the fate of glial and neuronal cells. Furthermore, we demonstrate that Slp1 and its mammalian ortholog, Foxg1, inhibit Gcm transcriptional activity as well as bind Gcm. Taken together, these data show that Slp1/Foxg1 regulate glial cell fates by inhibiting Gcm function.

Animals↗
PubMed2006

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

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. REVIEW: After familiarizing readers with some promising new techniques in the field of oncogenomics, this review will present the current state of knowledge as it pertains to the molecular biology of pediatric brain neoplasms. Along the way, we hope to highlight specific instances where the detailed mechanistic knowledge acquired thus far may be exploited for therapeutic advantage.

Animals↗
PubMed2006

Imaging surgical epilepsy in children.

INTRODUCTION: 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. DISCUSSION: 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.

Brain Diseases↗
PubMed2006

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

OBJECTIVES: 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. METHODS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2006

The role of magnetoencephalography in pediatric epilepsy surgery.

INTRODUCTION: 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. PRINCIPLES OF MAGNETOENCEPHALOGRAPHY: 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. FUTURE APPLICATIONS: 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.

Brain Mapping↗
PubMed2006

Multiple subpial transections in pediatric epilepsy: indications and outcomes.

OBJECTIVE: 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. METHODS: 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. CONCLUSIONS: 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.

Cerebral Cortex↗
PubMed2006

Neurosurgical implications of neurofibromatosis Type I in children.

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.

Brain Neoplasms↗
PubMed2006

Array CGH analysis of pediatric medulloblastomas.

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.

Cerebellar Neoplasms↗
PubMed2006

Appendicitis in the child with a ventriculo-peritoneal shunt: a 30-year review.

PURPOSE: Each year, about 270 children are treated at our hospital for appendicitis, and there are 200 ventriculo-peritoneal (VP) shunt procedures. The incidence of primary peritonitis after a VP shunt is 8% to 12%. The purpose of this article is to try and differentiate these 2 entities. METHODS: From 1973 to 2003 inclusive, appendicitis was diagnosed in 8 children with a VP shunt at our hospital; there were 7 boys and 1 girl with 5 acute appendicitis and 3 ruptured appendices. The first case was diagnosed on purely clinical grounds, whereas the last 7 were confirmed by ultrasonography and/or computed tomography. RESULTS: All 8 had appendectomy and the shunt was exteriorized in the 3 children with a ruptured appendix. There were no postoperative problems, and the 8 children remained well. CONCLUSION: Acute appendicitis can and does rarely occur in children with VP shunts; however, in such situations, the correct diagnosis can be confirmed by imaging. The shunt must be temporarily exteriorized if the appendix is ruptured.

Adolescent↗
PubMed2006

Efficacy of dexamathasone on cerebral swelling and seizures during subdural grid EEG recording in children.

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.

Adolescent↗
PubMed2006

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

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.

Adolescent↗
PubMed2006

Molecular biology of human gliomas.

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.

Animals↗
PubMed2006

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

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.

Career Mobility↗
PubMed2006

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

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.

Brain Diseases↗
PubMed2006

Molecular pathways triggering glioma cell invasion.

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.

Animals↗
PubMed2006

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

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 patients, MEG revealed clustered ECDs. The region exhibiting the maximum percentage (> or = 70%) of spikes/sharp waves on SAM was colocalized to clustered ECDs in seven patients. In six patients, SAM demonstrated focal spikes; in two, diffuse spikes; and in two others, focal rhythmic sharp waves. These epileptiform discharges were similar to those recorded on subdural EEG. In nine patients, concordant regions containing the maximum percentage of spikes/sharp waves were revealed by SAM and subdural EEG data. The region of the maximum percentage of spikes/sharp waves as demonstrated by SAM was colocalized to the ictal onset zone identified by subdural EEG findings in seven patients and partially colocalized in two. CONCLUSIONS: The SAM virtual sensor analysis revealed morphological characteristics, location, and distribution of epileptiform discharges similar to those shown by subdural EEG recordings. By using SAM it is possible to predict intracerebral interictal epileptiform discharges in the region of interest from noninvasively collected preoperative MEG data. The maximum interictal discharge zone identified by SAM virtual sensors correlated to clustered ECDs and the ictal onset zone on subdural EEG findings. Complementary analyses of ECDs and SAM on three-dimensional MR images can improve delineation of epileptogenic zones and lesions in neocortical epilepsy.

Adolescent↗