Venous drainage of the spine and spinal cord is accomplished through a complex network of venous structures compartmentalized to intrinsic, extrinsic, and extradural systems. As the literature on this topic is scarce, the following review was performed to summarize the available literature into a single coherent format. The medical literature on the spinal venous system was reviewed using online sources as well as historical documents that were not available online in regard to history, embryology, anatomy, and physiology with a particular emphasis on the pathology affecting this system. The spinal venous system is complex and variable. Proper understanding of all aspects is critical for the management of the pathology that results from its failure.

The ability of αIIbβ3 to bind ligands and undergo outside-in signaling is regulated by three divalent cation binding sites in the β I domain. Specifically, the metal ion-dependent adhesion site (MIDAS) and the synergistic metal binding site (SyMBS) are thought to be required for ligand binding due to their synergy between Ca(2+) and Mg(2+). The adjacent to MIDAS (ADMIDAS) is an important ligand binding regulatory site that also acts as a critical link between the β I and hybrid domains for signaling. Mutations in this site have provided conflicting results for ligand binding and adhesion in different integrins. We have mutated the β3 SyMBS and ADMIDAS. The SyMBS mutant abolished ligand binding and outside-in signaling, but when an activating glycosylation mutation in the αIIb Calf 2 domain was introduced, the ligand binding affinity and signaling were restored. Thus, the SyMBS is important but not absolutely required for integrin bidirectional signaling. The ADMIDAS mutants showed reduced ligand binding affinity and abolished outside-in signaling, and the activating glycosylation mutation could fully restore integrin signaling of the ADMIDAS mutant. We propose that the ADMIDAS ion stabilizes the low-affinity state when the integrin headpiece is in the closed conformation, whereas it stabilizes the high-affinity state when the headpiece is in the open conformation with the swung-out hybrid domain.

While glioblastoma multiforme (GBM) is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs) remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed “glioma stem cells” (GSCs), “glioma progenitor cells,” or “glioma-initiating cells,” which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGG must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses (oHSV), genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oHSV.

Three divalent cation binding sites in the integrin β I domain have been shown to regulate ligand binding and adhesion. However, the degree of ligand binding and adhesion varies among integrins. The αLβ2 and α4β7 integrins show an increase in ligand binding affinity and adhesion when one of their ADMIDAS (adjacent to MIDAS, or the metal ion-dependent adhesion site) residues is mutated. By contrast, the α2β1, α5β1, and αIIbβ3 integrins show a decrease in binding affinity and adhesion when their ADMIDAS is mutated. Our study here indicated that integrin αVβ3 had lower affinity when the ADMIDAS was mutated. By comparing the primary sequences of these integrin subunits, we propose that one residue associated with the MIDAS (β3 Ala(252)) may account for these differences. In the β1 integrin subunit, the corresponding residue is also Ala, whereas in both β2 and β7 integrin subunits, it is Asp. We mutated the β3 residue Ala(252) to Asp and combined this mutant with mutations of one or two ADMIDAS residues. The mutant A252D showed reduced ligand binding affinity and adhesion. The ligand binding affinity and adhesion were increased when this A252D mutant was paired with mutations of one ADMIDAS residue. But when paired with mutations of two ADMIDAS residues the mutant nearly abolished ligand-binding ability, which was restored by the activating glycosylation mutation. Our study suggests that the variation of this residue contributes to the different ligand binding affinities and adhesion abilities among different integrin families.

Purpose: Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder found in approximately 1 of every 3000 individuals. Neurofibromatosis type 1 can have vascular manifestations including aneurysms, stenoses, and arteriovenous malformations. The purpose of this article is to describe the clinical manifestations of NF1 vasculopathy, discuss therapeutic options, and highlight endovascular therapies from our institutional experience. Materials and Methods: The radiology information system was searched for cases of NF1. Cases with vasculopathy managed with endovascular therapies were included. Demographics, clinical histories, procedural details, and outcomes were recorded. A review of the literature for the management strategies of NF1 vasculopathy was performed. Results: Two pediatric patients with NF1 were identified, both of whom presented with hypertension found to be secondary to renal artery stenosis. One of the patients also had infrarenal aortic narrowing. Both patients were successfully treated with balloon angioplasty, resulting in improved blood pressures. The review of the literature identified case series of pharmacologic, surgical, and endovascular therapies, although, endovascular therapies appear to be preferred due to lower morbidity and mortality. Conclusions: NF1 vasculopathy is a rare condition that most often presents with hypertension due to renal artery stenosis. In these situations, endovascular management is the preferred approach.