Draf III extension in the endoscopic endonasal transethmoidal, transcribriform approach through the back wall of the frontal sinus: a cadaveric study

OBJECTIVE: The Draf III (modified endoscopic Lothrop) has been proposed to extend the endonasal transethmoidal, transfovea ethmoidalis and transcribriform approach through the back wall of the frontal sinus. The exposure is time-consuming, increases the risk of cerebrospinal fluid (CSF) leak and the indications for use are not well-described. There is little data quantifying the advantage it conveys over the approach without the Draf III. METHODS: An endoscopic, endonasal transfovea, transcribriform approach was performed in 5 fresh, injected cadaver heads. Anatomic boundaries and measurements of the exposure were compared before and after addition of a Draf III. Pre- and post- dissection CT scans were obtained and additional radiographic measurements were made to quantify the additional exposure provided by the Draf III. Two clinical cases are presented where a Draf III was utilized. RESULTS: Radiographic measurements: The mean anterior to posterior boundary from frontal sinus to planum sphenoidale pre-Draf III was 3.0 cm and post-Draf III was 3.8 cm with an average change of 0.8 cm. Cadaveric measurements: Following the Draf III, the mean anterior to posterior boundary from the posterior wall of frontal sinus to the planum sphenoidale increased from 3.0 cm to 4.3 cm. Average increase of 1.3 cm with an average increased area of view of 1.79 cm2. CONCLUSIONS: This study quantifies the increase field of view provided by the Draf III during anterior skull base dissection. Recommendations for pre-operative examination of radiographic evidence are provided to help identify which individuals would benefit from the additional exposure

Cerebral White Matter Oxidation and Nitrosylation in Young Rodents With Kaolin-Induced Hydrocephalus

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1 alpha was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.Canadian Institutes of Health ResearchCanadian Institutes of Health ResearchManitoba Health Research CouncilManitoba Health Research CouncilCanada Research Chair in Developmental NeuropathologyCanada Research Chair in Developmental NeuropathologyCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-Brazil)CNPq (Conselho Nacional de Desenvolvimento Cientifico e TecnologicoBrazil)Manitoba Institute of Child HealthManitoba Institute of Child Healt

Building Team Medicine in the Management of CNS Metastases

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000–400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiation techniques, as well as targeted and immune therapies, have enanled patient to live longer, thus increasing the risk for the development of CNS, brain, and leptomeningeal metastases (BM and LM). Patients who develop CNS metastases have often been heavily treated, and options for future treatment could best be addressed by multidisciplinary teams. Studies have indicated that patients with brain metastases have improved survival outcomes when cared for in high-volume academic institutions using multidisciplinary teams. This manuscript discusses a multidisciplinary approach for both parenchymal brain metastases as well as leptomeningeal metastases implemented in three academic institutions. Additionally, with the increasing development of healthcare systems, we discuss optimizing the management of CNS metastases across healthcare systems and integrating basic and translational science into our clinical care to further improve outcomes. This paper summarizes the existing therapeutic approaches to the treatment of BM and LM and discusses novel and emerging approaches to optimizing access to neuro-oncologic care while simultaneously integrating multidisciplinary teams in the care of patients with BM and LM

Surgical approaches to posterior fossa tumours

Lesions of the fourth ventricle and foramen magnum can be difficult to manage surgically due to their proximity to critical brainstem structures. Understanding the anatomy of the fourth ventricle, lower cranial nerves, and basilar cisterns remains paramount for deciding surgical approaches to this location. Detailed preoperative workup and planning are necessary to minimize surgical morbidity and maximize tumour resection. This chapter provides an overview of the relevant anatomy and surgical techniques for lesions in the posterior fossa, specifically the fourth ventricle the foramen magnum. We will split this chapter into two main sections: microsurgical approaches to the fourth ventricle and skull base approaches to the foramen magnum

The genomic landscape of schwannoma

Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19-Mb chromosomal inversion on chromosome 10q. The fusion was associated with male gender predominance, occurring in one out of every six men with schwannoma. Methylation profiling identified distinct molecular subgroups of schwannomas that were associated with anatomical location. Expression of the SH3PXD2A-HTRA1 fusion resulted in elevated phosphorylated ERK, increased proliferation, increased invasion and in vivo tumorigenesis. Targeting of the MEK-ERK pathway was effective in fusion-positive Schwann cells, suggesting a possible therapeutic approach for this subset of tumors