High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in pediatric epilepsy surgery.

Objective: We determined whether kurtosis analysis of intracranial electroencephalogram (EEG) can estimate the localization of the epileptogenic zone.

Methods: We analyzed 29 pediatric epilepsy patients who underwent intracranial EEG before focal resective surgery. We localized the brain regions with high kurtosis, the seizure onset zone (SOZ) and the regions with high-rate, high-amplitude and long-duration interictal paroxysms ≥20 Hz.

Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct.

Recent integrative genomic approaches have defined molecular subgroups of medulloblastoma that are genetically and clinically distinct. Sonic hedgehog (Shh) medulloblastomas account for one-third of all cases and comprise the majority of infant and adult medulloblastomas. To discern molecular heterogeneity among Shh-medulloblastomas, we analyzed transcriptional profiles from four independent Shh-medulloblastoma expression datasets (n = 66).

Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature.

Unlabelled: Gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provides a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood-brain barrier disruption.

PCDH10 is a candidate tumour suppressor gene in medulloblastoma.

Purpose: The aim of this study was to investigate the genetic and epigenetic mechanisms contributing to PCDH10 down-regulation in medulloblastoma. We examined the role of PCDH10 as a mediator of medulloblastoma cell proliferation, cell cycle progression, and cell migration.

Methods: We identified a focal homozygous deletion of PCDH10 in medulloblastoma by surveying a cohort of 212 tumours by Affymetrix SNP array analysis.

Neurosurgical management of extraaxial central nervous system infections in children.

Object: Extraaxial infections of the CNS, including subdural empyema and epidural abscess, are rare but potentially life-threatening conditions. Symptoms are usually progressive, and early diagnosis is therefore important. Early intervention with appropriate treatment offers the best opportunity for eradicating the infection and promoting maximal neurological recovery.

Focal-onset myoclonic seizures and secondary bilateral synchrony.

We present a child with myoclonic seizures, epileptic spasms and generalized epileptiform discharges on scalp EEG. Magnetoencephalography and coherence-phase analysis for scalp EEG suggested focal onset in the left hemisphere. Intracranial video EEG confirmed seizure onset in the left frontal lobe with ictal high-frequency oscillations.

Cost-effectiveness of pediatric epilepsy surgery compared to medical treatment in children with intractable epilepsy.

Purpose: Due to differences in epilepsy types and surgery, economic evaluations of epilepsy treatment in adults cannot be extrapolated to children. We evaluated the cost-effectiveness of epilepsy surgery compared to medical treatment in children with intractable epilepsy.

Method: Decision tree analysis was used to evaluate the cost-effectiveness of surgery relative to medical management.

Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma.

Medulloblastoma is the most common pediatric posterior fossa malignancy, with a 5-year overall survival of only 60% and many survivors experiencing treatment-related morbidity secondary to current therapeutic regimens. With an improved understanding of the molecular basis for this disease, the opportunity to develop novel treatments with more tolerable toxicity profiles that target key molecular pathways, now exists. Recently, the hepatocyte growth factor (HGF)/MET signaling pathway has been implicated in medulloblastoma pathogenesis.

Hemispherectomy for the control of intractable epilepsy in childhood: comparison of 2 surgical techniques in a single institution.

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 peri-insular hemispherotomy (PIH) on patient outcome.

Epigenetic regulation of glial fibrillary acidic protein by DNA methylation in human malignant gliomas.

Glial fibrillary acidic protein (GFAP) is an intermediate filament expressed in glial cells that stabilizes and maintains the cytoskeleton of normal astrocytes. In glial tumors, GFAP expression is frequently lost with increasing grade of malignancy, suggesting that GFAP is important for maintaining glial cell morphology or regulating astrocytoma cell growth. Most permanent human glioma cell lines are GFAP negative by immunocytochemistry.

Topographic movie of intracranial ictal high-frequency oscillations with seizure semiology: epileptic network in Jacksonian seizures.

Purpose: We developed a technique to produce images of dynamic changes in ictal high-frequency oscillations (HFOs) >40 Hz recorded on subdural electroencephalography (EEG) that are time-locked to the ictal EEG and ictal semiology video. We applied this technique to Jacksonian seizures to demonstrate ictal HFO propagation along the homunculus in the primary sensory-motor cortex to visualize the underlying epileptic network.

Methods: We analyzed intracranial ictal EEGs from two patients with intractable Jacksonian seizures who underwent epilepsy surgery.

Intraoperative angiography during microsurgical removal of arteriovenous malformations in children.

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.

Medulloblastoma comprises four distinct molecular variants.

Purpose: Recent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups.

Methods: We determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas.

Genetics of medulloblastoma: clues for novel therapies.

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.

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

Purpose: 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.

Methods: A retrospective review was performed from January 2000 to Dec 2009 reviewed eight cases of VNS revision.

Image guidance and neuromonitoring in neurosurgery.

Introduction: 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.

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

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.