MRI phenotypes with high neurodegeneration are associated with peripheral blood B-cell changes.

Little is known about the mechanisms leading to neurodegeneration in multiple sclerosis (MS) and the role of peripheral blood cells in this neurodegenerative component. We aimed to correlate brain radiological phenotypes defined by high and low neurodegeneration with gene expression profiling of peripheral blood mononuclear cells (PBMC) from MS patients. Magnetic resonance imaging (MRI) scans from 64 patients with relapsing-remitting MS (RRMS) were classified into radiological phenotypes characterized by low (N = 27) and high (N = 37) neurodegeneration according to the number of contrast-enhancing lesions, the relative volume of non-enhancing black holes on T1-weighted images, and the brain parenchymal fraction. Gene expression profiling was determined in PBMC using microarrays, and validation of selected genes was performed by polymerase chain reaction (PCR). B-cell immunophenotyping was conducted by flow cytometry. Microarray analysis revealed the B-cell specific genes FCRL1, FCRL2, FCRL5 (Fc receptor-like 1, 2 and 5 respectively), and CD22 as the top differentially expressed genes between patients with high and low neurodegeneration. Levels for these genes were significantly down-regulated in PBMC from patients with MRI phenotypes characterized by high neurodegeneration and microarray findings were validated by PCR. In patients with high neurodegeneration, immunophenotyping showed a significant increase in the expression of the B-cell activation markers CD80 in naïve B cells (CD45+/CD19+/CD27-/IgD+), unswitched memory B cells (CD45+/CD19+/CD27+/IgD+), and switched memory B cells (CD45+/CD19+/CD27+/IgD-), and CD86 in naïve and switched memory B cells. These results suggest that RRMS patients with radiological phenotypes showing high neurodegeneration have changes in B cells characterized by down-regulation of B-cell-specific genes and increased activation status.

[Spanish multi-centre observational study of the first attacks suggestive of multiple sclerosis: the PREM cohort]. / Estudio observacional multicentrico espanol de primeros episodios sugestivos de esclerosis multiple: cohorte PREM.

INTRODUCTION: Recent studies have shown the need to optimise the management of patients after a first attack suggestive of multiple sclerosis (MS). Our aim is to determine whether the results from follow-ups in these studies are reproducible within a Spanish multi-centre context. PATIENTS AND METHODS: The PREM study (observational prospective Spanish multi-centre study at 24 months) included patients in the first three months following a first event suggestive of MS with at least two typical lesions in a magnetic resonance scan. The Expanded Disability Status Scale (EDSS) was obtained and the presence of attacks was evaluated basally and at 3, 6, 9, 12, 18 and 24 months; a magnetic resonance scan was performed basally and at 6 and 24 months so as to be able to calculate the brain volume and the volumes of the lesions (T1, T2 and T1 after administering gadolinium). McDonald and Poser criteria were evaluated during the follow-up. A subgroup of patients was followed up for a total period of four years. RESULTS: Altogether 110 patients (67% females) with a mean age of 30.2 years were included in the study; 22 patients dropped out of the study before it finished. Poser criteria were met by 19% and 45% of patients at 6 months and 24 months, respectively; 63% and 71% satisfied McDonald criteria. The EDSS decreased significantly (-0.94; p < 0.001) and development of atrophy was observed (-1.2%; p < 0.001) at 24 months. CONCLUSIONS: Results of the follow-up of patients with first attacks suggestive of MS within a Spanish multi-centre context are wholly comparable with those from international clinical trials performed in these patients.

Polycrystallization effects on the nanoscale electrical properties of high-k dielectrics.

In this study, atomic force microscopy-related techniques have been used to investigate, at the nanoscale, how the polycrystallization of an Al2O3-based gate stack, after a thermal annealing process, affects the variability of its electrical properties. The impact of an electrical stress on the electrical conduction and the charge trapping of amorphous and polycrystalline Al2O3 layers have been also analyzed.

Hyperacute ischemic stroke: middle cerebral artery susceptibility sign at echo-planar gradient-echo MR imaging.

PURPOSE: To evaluate the accuracy of echo-planar T2*-weighted magnetic resonance (MR) sequences in detection of acute middle cerebral artery (MCA) or internal carotid artery (ICA) thrombotic occlusion. MATERIALS AND METHODS: Forty-two consecutive patients with stroke involving the MCA territory underwent MR imaging within 6 hours after clinical onset. MR examination included echo-planar T2*-weighted, diffusion-weighted (DW), and perfusion-weighted (PW) imaging and MR angiography. Presence or absence of the susceptibility sign on echo-planar T2*-weighted images, which is indicative of acute thrombotic occlusion involving MCA or ICA, was assessed in consensus by two observers blinded to clinical information and other MR imaging data. Differences in lesion volume on DW and PW images between patients with and those without the susceptibility sign were evaluated with the Mann-Whitney test. P <.05 was considered to indicate a significant difference. RESULTS: Thirty patients (71%) had a positive susceptibility sign that correlated with MCA or ICA occlusion at MR angiography in all cases (sensitivity, 83%; specificity, 100%). Mean lesion volume on PW images was higher in patients with a positive susceptibility sign (P =.01), but no significant differences were found in mean lesion volume on DW images. Cases in which the susceptibility sign was identified proximal to MCA divisional bifurcation (27 patients) showed a mean perfusion deficit of 83.9% of the total MCA territory (range, 50%-100%). CONCLUSION: Presence of the susceptibility sign proximal to MCA bifurcation provides fast and accurate detection of acute proximal MCA or ICA thrombotic occlusion.