Intracranial Dural Arteriovenous Fistulas: The Sinus and Non-Sinus Concept

AbstractIntroduction: Dural arteriovenous fistulas (dAVFs) account for 10–15% of all intracranial arteriovenous lesions. Different classification strategies have been proposed in the course of the years. None of them seems to guide the treatment strategy. Objective: We expose the experience of the vascular group at Niguarda Hospital and we propose a very practical classification method based on the location of the shunt. We divide dAVF in sinus and non-sinus in order to simplify our daily practice, as this classification method is simply based on the involvement of the sinuses. Material and Methods: 477 intracranial dural arteriovenous fistulas have been treated. 376 underwent endovascular treatment and 101 underwent surgical treatment. Cavernous sinus DAVFs and Galen ampulla malformations have been excluded from this series as they represent a different pathology per se. 376 dAVFs treated by endovascular approach: 180 were sinus and 179 were non-sinus. 101 dAVFs treated with surgical approach: 15 were sinus and 86 were non-sinus. Discussion: Of the 477 intracranial dAVF the recorded mortality and severe disability was 3% and morbidity less than 4%. All patients underwent a postoperative DSA with nearly 100% of complete occlusion of the fistula. At a mean follow-up of 5 years in one case there was a non-sinus fistula recurrence, due to the presence of a partial clipping of "piè" of the vein. Conclusions: The sinus and non-sinus concept has guided our institution for years and has led to good clinical results. This paper intends to share this practical classification with the neurosurgical community

Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries

There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology

Occurrence of cumulative amino acid positions in NadA fragments obtained after two rounds of selection, as determined by traditional random picking of 50 plaques followed by Sanger sequencing of individual clones.

<p>Occurrence of cumulative amino acid positions in NadA fragments obtained after two rounds of selection, as determined by traditional random picking of 50 plaques followed by Sanger sequencing of individual clones.</p

Enrichment of phage clones predicted to display authentic NadA fragments on their surface after selection with a serum pool from volunteers immunized with the Bexero vaccine.

<p>Frequency values reported in the vertical axis in panels A–C refer to the occurrence, per single amino acid position, of sequences predicted to express authentic NadA fragments, relative to those predicted to express irrelevant or no polypeptides. The inset in figure A reports the same data with a higher y-axis magnification. The horizontal axis reports the amino acid positions of the translated NadA sequence. A, unselected library; B and C, library outputs after one and two rounds of selection, respectively. D, Cumulative enrichment factors for each amino acid position derived from NadA fragments obtained after one (blue line) and two (red line) rounds of selection; colored bars in the horizontal axis refer to NadA domains; the area between the dashed vertical lines correspond to the cell binding region of NadA <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114159#pone.0114159-Tavano1" target="_blank">[18]</a>. E and F, enrichment factors of NadA fragments after one and two rounds of selection, respectively. Only the fragments laying in the upper quartile of enrichment factors values are shown.</p

Immunoreactivity of selected phage clones corresponding to different fragments of the <i>N. meningitidis</i> NadA antigen.

<p>Immunoreactivity of selected phage clones corresponding to different fragments of the <i>N. meningitidis</i> NadA antigen.</p

Properties of the antigen-specific phage library before and after selection with a pool of serum samples from volunteers immunized with the Bexero anti-MenB vaccine.

<p>A–C, abundance of “natural frame” <i>nadA</i> fragments in the library before (A) and after the first and second rounds of selection (B and C, respectively). Each point represents the number of unique fragments (vertical axis) displaying the number of copies indicated in the horizontal axis; D–F, <i>nadA</i> fragment length distribution before (D) and after the first and second rounds of selection (E and F, respectively).</p

Schematic outline of the epitope mapping approach.

<p>The gene encoding the antigen is fragmented by DNAse digestion and the gene fragments are inserted into lambda phage vectors. The phage library is mixed with immune serum and phage particles binding to immunoglobulins are separated using Protein-G coated magnetic beads. The inserts of the phage population obtained after selection are massively sequenced and compared with those of the original unselected library using an <i>ad hoc</i> developed software which identifies the region(s) of the antigen targeted by serum antibodies.</p

Unruptured Aneurysms Italian Study (UAIS) background and method

Treatment of unruptured cerebral aneurysms still represents an unsettled question in neurosurgical and neuroradiological communities. Although nowadays the indication for treatment have become relatively clear, indeed uncertainity remains for what concerns the proper treatment modality (surgical or endovascular) in terms of both the risk and the mid and long-term efficacy of the two procedures. The "Unruptured Aneurysms Italian Study" is a cooperative prospective study which aims to delineate the "State of the Art" in a nation based population. It has been designed: 1) to depict the nationwide modality of treatment of Unruptured Aneurysms, 2) to assess in the most objective way the overall treatment-related mortality and morbidity as well as the surgical and endovascular risk in the respective patient populations (it is not a surgical versus endovascular study) and 3) to asses the efficacy of the different procedures in the mid and long term periods. The study started on June 2003 and to June 2006, 637 patients have been enrolled. The study will end when the 1000th patient is enrolled