Citations

Seizures in the newborn period are common and frequently indicate serious underlying brain injury. Although accumulating evidence suggests that they may impair brain development, there are currently no evidence-based guidelines for evaluation and management of neonatal seizures. In this review, we will address some of the current controversies facing child neurologists and neonatologists, including how to define, monitor, and treat neonatal seizures.

Object Cavernous hemangiomas associated with epilepsy present an interesting surgical dilemma in terms of whether one should perform a pure lesionectomy or tailored resection, especially in the temporal lobe given the potential for cognitive damage. This decision is often guided by electrocorticography (ECoG), despite the lack of data regarding its value in cavernoma surgery. The purpose of the present study was several-fold: first, to determine the epilepsy outcome following resection of cavernomas in all brain regions; second, to evaluate the usefulness of ECoG in guiding surgical decision making; and third, to determine the optimum surgical approach for temporal lobe cavernomas. Methods The authors identified from their surgical database 173 patients who had undergone resection of cavernomas. One hundred two of these patients presented with epilepsy, and 61 harbored temporal lobe cavernomas. Preoperatively, all patients were initially evaluated by an epileptologist. The mean follow-up was 37 months. Results Regardless of the cavernoma location, surgery resulted in an excellent seizure control rate: Engel Class I outcome in 88% of patients at 2 years postoperatively. Of 61 patients with temporal lobe cavernomas, the mesial structures were involved in 35. Among the patients with temporal lobe cavernomas, those who underwent ECoG typically had a more extensive parenchymal resection rather than a lesionectomy (p < 0.0001). The use of ECoG in cases of temporal lobe cavernomas resulted in a superior seizure-free outcome: 79% (29 patients) versus 91% (23 patients) of patients at 6 months postresection, 77% (22 patients) versus 90% (20 patients) at 1 year, and 79% (14 patients) versus 83% (18 patients) at 2 years without ECoG versus with ECoG, respectively. Conclusions The surgical removal of cavernomas most often leads to an excellent epilepsy outcome. In cases of temporal lobe cavernomas, the more extensive the ECoG-guided resection, the better the seizure outcome. In addition to upholding the concept of kindling, the data in this study support the use of ECoG in temporal lobe cavernoma surgery in patients presenting with epilepsy.

The applicability of cytoreductive treatment of malignant diseases using recombinant viruses strongly depends on specific recognition of surface receptors to target exclusively neoplastic cells. A recently generated monoclonal antibody (mAb), Wue-1, specifically detects CD138+ multiple myeloma (MM) cells. In this study, a haemagglutinin (H) protein that was receptor-blinded (i.e. did not bind to CD46 and CD150) was genetically re-engineered by fusing it to a single-chain antibody fragment (scFv) derived from the Wue-1 mAb open reading frame (scFv-Wue), resulting in the recombinant retargeted measles virus (MV)-Wue. MV-Wue efficiently targeted and fully replicated in primary MM cells, reaching titres similar to those seen with non-retargeted viruses. In agreement with its altered receptor specificity, infection of target cells was no longer dependent on CD150 or CD46, but was restricted to cells that had been labelled with Wue-1 mAb. Importantly, infection with MV-Wue rapidly induced apoptosis in CD138+ malignant plasma cell targets. MV-Wue is the first fully retargeted MV using the restricted interaction between Wue-1 mAb and primary MM cells specifically to infect, replicate in and deplete malignant plasma cells.

Abstract Rationale Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood. Objectives To identify genetic risk factors for PPHTN in patients with advanced liver disease. Methods We performed a multicenter case-control study of patients with portal hypertension. Cases had a mean pulmonary artery pressure &gt;25 mm Hg, pulmonary vascular resistance &gt;240 dynes·s−1·cm−5, and pulmonary capillary wedge pressure ≤15 mm Hg. Controls had a right ventricular systolic pressure &lt; 40 mm Hg (if estimated) and normal right-sided cardiac morphology by transthoracic echocardiography. We genotyped 1,079 common single nucleotide polymorphisms (SNPs) in 93 candidate genes in each patient. Measurements and Main Results The study sample included 31 cases and 104 controls. Twenty-nine SNPs in 15 candidate genes were associated with the risk of PPHTN (P &lt; 0.05). Multiple SNPs in the genes coding for estrogen receptor 1, aromatase, phosphodiesterase 5, angiopoietin 1, and calcium binding protein A4 were associated with the risk of PPHTN. The biological relevance of one of the aromatase SNPs was supported by an association with plasma estradiol levels. Conclusions Genetic variation in estrogen signaling and cell growth regulators is associated with the risk of PPHTN. These biologic pathways may elucidate the mechanism for the development of PPHTN in certain patients with severe liver disease.