SP can be considered the cutaneous sign of an underlying venous anomaly. If treatment is contemplated, analysis of the drainage pattern of the SP has to be performed. Treatment should be avoided in dominant SP or if its accessory role constitutes the only collateral pathway of an underlying venous anomaly.

Background and Purpose-The purpose of this article is to describe "cerebral proliferative angiopathy" (CPA) as a clinical entity, which may be regarded as separate from "classical" brain AVMs in angioarchitecture, natural history, clinical presentation, and, therefore, treatment and which can be discerned from other cerebral AVMs by characteristic imaging features. Methods-In a prospectively entered databank encompassing 1434 patients with brain AVMs, a subgroup of 49 patients harboring specific angiographic characteristics were identified. Their charts and imaging films were retrospectively reviewed. Results-We found a preponderance of CPA in young (mean age: 22) females (67%). Clinical symptoms were seizures, disabling headaches, and stroke-like symptoms; hemorrhagic presentations were exceptional. On cross-sectional imaging, CPA demonstrated as a diffuse network of densely enhancing vascular spaces with intermingled normal brain parenchyma. The discrepancy between the large size of the nidus and the small shunting volume, the absence of flow-related aneurysms, the presence of diffuse angiogenesis (eg, transdural supply, progressive arterial occlusion), and the small calibre of a multitude of feeding arteries and draining veins were the angiographic hallmarks of this disease. Conclusion-The diffuse angiogenetic activity is presumably related to reduced perinidal perfusion and subsequent chronic cortical ischemia. Natural history demonstrates a low risk of hemorrhage. CPA may be regarded as a separate clinical entity different to "classical" cerebral AVMs, because normal brain is interspersed with the abnormal vascular channels increasing the risk of neurological deficit in aggressive treatments, which in the light of the natural history does not seem to be indicated. (Stroke. 2008;39:878-885.)

Phage display technology has been widely used for antibody affinity maturation for decades. The limited library sequence diversity together with excessive redundancy and labour-consuming procedure for candidate identification are two major obstacles to widespread adoption of this technology. We hereby describe a novel library generation and screening approach to address the problems. The approach started with the targeted diversification of multiple complementarity determining regions (CDRs) of a humanized anti-ErbB2 antibody, HuA21, with a small perturbation mutagenesis strategy. A combination of three degenerate codons, NWG, NWC, and NSG, were chosen for amino acid saturation mutagenesis without introducing cysteine and stop residues. In total, 7,749 degenerate oligonucleotides were synthesized on two microchips and released to construct five single-chain antibody fragment (scFv) gene libraries with 4 x 106 DNA sequences. Deep sequencing of the unselected and selected phage libraries using the Illumina platform allowed for an in-depth evaluation of the enrichment landscapes in CDR sequences and amino acid substitutions. Potent candidates were identified according to their high frequencies using NGS analysis, by-passing the need for the primary screening of target-binding clones. Furthermore, a subsequent library by recombination of the 10 most abundant variants from four CDRs was constructed and screened, and a mutant with 158-fold increased affinity (Kd = 25.5 pM) was obtained. These results suggest the potential application of the developed methodology for optimizing the binding properties of other antibodies and biomolecules.

Within the group of giant and large aneurysms the subgroup of the so-called “partially thrombosed” aneurysms can be differentiated according to clinical and neuroimaging findings. The present study was carried out to determine the site of bleeding of these aneurysms and what implications concerning their pathomechanism can be drawn from these findings. Twenty patients aged two to 77 (mean 44) years who exhibited a partially thrombosed aneurysm that had recently bled were included. Images (MRI including T1 pre- and postcontrast and T2 weighted images in multiple planes, CT and digital subtraction angiography) and patients' charts were reviewed. MRI showed an onion-skin appearance of the thrombus in 19 patients, rim enhancement of the aneurysm wall (either partial or complete) in 17, and a perifocal edema in 16 patients. The acute hemorrhage was typically crescent-shaped and located at the periphery of the aneurysm, distant from the perfused lumen of the aneurysm within the thrombosed part of the aneurysm. The current denomination “partially thrombosed” intracranial arterial aneurysms leads to the presumption that thrombus is present endoluminal whereas in fact the site of hemorrhage is within the vessel wall. A more accurate nomination would, therefore, be “aneurysms with intra mural hemorrhage”. The enhancing wall and the edematous reaction of the adjacent brain parenchyma might be a sign for an inflammatory pathomechanism which is reinforced by histological and pathophysiological studies. This disease should be regarded as a clinical entity separate from saccular or non-thrombosed giant or large aneurysms.

The high rate of rebleeding and consequent mortality among the patients treated conservatively argues for treatment in the acute phase. Treatment should be guided by each patient's angiomorphology, clinical condition and the experience of the neurosurgical/neuroradiological team. Options include endovascular or surgical trapping of the dissection and proximal occlusion and embolisation of the parent artery at the site of the dissection.