Objective-Two types of endothelial progenitor cells (EPCs), early EPCs and late EPCs (also called endothelial outgrowth cells [EOCs]), were described in vitro previously. In this report, we dissect the phenotype of the precursor(s) that generate these cell types with focus on the markers CD34, CD133, and vascular endothelial growth factor receptor-2 (VEGFR2) that have been used to identify putative circulating endothelial precursors. We also included CD45 in the analysis to assess the relation between CD34 ϩ hematopoietic progenitors (HPC), CD34 ϩ endothelial precursors, and both in vitro generated EPC types. Addressing this issue might lead to a better understanding of the lineage and phenotype of the precursor(s) that give rise to both cell types in vitro and may contribute to a consensus on their flowcytometric enumeration. Methods and Results-Using

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Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy in patients who are unsuitable candidates for epilepsy surgery (Ben-Menachem 2002). Worldwide, more than 50 000 epilepsy patients have been treated with VNS. Several studies, including two large double-blind randomized clinical trials (Ben-Menachem et al. 1994;DeGiorgio et al. 2000), have confirmed the efficacy of VNS in different types of epilepsy. Seizure reduction as a result of VNS ranges from 25% to 55%, and varies considerably from patient to patient. In responders, VNS causes either a rapid or a delayed reduction in seizure frequency. However, a significant fraction (approximately one third) of patients do not respond to VNS. Because the mechanism of action of VNS in epilepsy is currently unknown, it is not clear which factors determine the patient's response to the treatment, nor what the most optimal stimulation parameters are.The vagus nerve is a mixed nerve consisting of 20% efferent (motor) and 80% afferent (sensory) fibers. The nucleus of the solitary tract receives the largest number of vagal afferents. The nucleus of the solitary tract in turn Received July 5, 2010; revised manuscript received January 18, 2011; accepted February 8, 2011.Address correspondence and reprint requests to Robrecht Raedt, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: robrecht.raedt@ugent.be 1 These authors contributed equally to this work.

SUMMARYPurpose: Fifteen percent to 25% of patients with refractory epilepsy require invasive video-electroencephalography (EEG) monitoring (IVEM) to precisely delineate the ictal-onset zone. This delineation based on the recorded intracranial EEG (iEEG) signals occurs visually by the epileptologist and is therefore prone to human mistakes. The purpose of this study is to investigate whether effective connectivity analysis of intracranially recorded EEG during seizures provides an objective method to localize the ictal-onset zone. Methods: In this study data were analyzed from eight patients who underwent IVEM at Ghent University Hospital in Belgium. All patients had a focal ictal onset and were seizure-free following resective surgery. The effective connectivity pattern was calculated during the first 20 s of ictal rhythmic iEEG activity. The outdegree, which is reflective of the number of outgoing connections, was calculated for each electrode contact for every single seizure during these 20 s. The seizure specific out-degrees were summed per patient to obtain the total out-degree. The electrode contact with the highest total out-degree was considered indicative of localization of the ictal-onset zone. This result was compared to the conclusion of the visual analysis of the epileptologist and the resected brain region segmented from postoperative magnetic resonance imaging (MRI). Key findings: In all eight patients the electrode contact with the highest total out-degree was among the contacts identified by the epileptologist as the ictal onset. This contact, that we named "the driver," always laid within the resected brain region. Furthermore, the patient-specific connectivity patterns were consistent over the majority of seizures. Significance: In this study we demonstrated the feasibility of correctly localizing the ictal-onset zone from iEEG recordings by using effective connectivity analysis during the first 20 s of ictal rhythmic iEEG activity.

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