Targeted inactivation of the Septin2 and Septin9 genes in myelinating Schwann cells of mice

The formation of axon-enwrapping myelin sheaths by oligodendrocytes in the central nervous system (CNS) involves the assembly of a scaffolding septin filament comprised of the subunits SEPTIN2, SEPTIN4, SEPTIN7 and SEPTIN8. Conversely, in the peripheral nervous system (PNS) myelin is synthesized by a different cell type termed Schwann cells, and it remained unknown if septins also assemble as a multimer in PNS myelin. According to prior proteome analysis, PNS myelin comprises the subunits SEPTIN2, SEPTIN7, SEPTIN8, SEPTIN9 and SEPTIN11, which localize to the paranodal and abaxonal myelin sub-compartments. Here we use the Cre/loxP-system to delete the Septin9-gene specifically in Schwann cells, causing a markedly reduced abundance of SEPTIN9 in sciatic nerves, implying that Schwann cells are the main cell type expressing SEPTIN9 in the nerve. However, Septin9-deficiency in Schwann cells did not affect the abundance or localization of other septin subunits. In contrast, when deleting the Septin2-gene in Schwann cells the abundance of all relevant septin subunits was markedly reduced, including SEPTIN9. Notably, we did not find evidence that deleting Septin2 or Septin9 in Schwann cells impairs myelin biogenesis, nerve conduction velocity or motor/sensory capabilities, at least at the assessed timepoints. Our data thus show that SEPTIN2 but not SEPTIN9 is required for the formation or stabilization of a septin multimer in PNS myelin in vivo; however, its functional relevance remains to be established

Diagnosis and follow-up evaluation of central nervous system vasculitis: an evaluation of vessel-wall MRI findings

OBJECTIVE To approach the clinical value of MRI with vessel wall imaging (VWI) in patients with central nervous system vasculitis (CNSV), we analyzed patterns of VWI findings both at the time of initial presentation and during follow-up. METHODS Stenoocclusive lesions, vessel-wall contrast enhancement (VW-CE) and diffusion-restricted lesions were analyzed in patients with a diagnosis of CNSV. On available VWI follow-up, progression, regression or stability of VW-CE were evaluated and correlated with the clinical status. RESULTS Of the 45 patients included, 28 exhibited stenoses visible on MR angiography (MRA-positive) while 17 had no stenosis (MRA-negative). VW-CE was found in 2/17 MRA-negative and all MRA-positive patients (p < 0.05). 79.1% (53/67) of stenoses showed VW-CE. VW-CE was concentric in 88.3% and eccentric in 11.7% of cases. Diffusion-restricted lesions were found more frequently in relation to stenoses with VW-CE than without VW-CE (p < 0.05). 48 VW-CE lesions in 23 patients were followed over a median time of 239.5~days. 13 VW-CE lesions (27.1%) resolved completely, 14 (29.2%) showed partial regression, 17 (35.4%) remained stable and 4 (8.3%) progressed. 22/23 patients received immunosuppressive therapy for the duration of follow-up. Patients with stable or progressive VW-CE were more likely (p < 0.05) to have a relapse (14/30 cases) than patients with partial or complete regression of VW-CE (5/25 cases). CONCLUSION Concentric VW-CE is a common finding in medium/large-sized vessel CNSV. VW-CE might represent active inflammation in certain situations. However, follow-up VWI findings proved ambiguous as persisting VW-CE despite immunosuppressive therapy and clinical remission was a frequent finding

Multiple Sclerosis: Improved Detection of Active Cerebral Lesions With 3-Dimensional T1 Black-Blood Magnetic Resonance Imaging Compared With Conventional 3-Dimensional T1 GRE Imaging

Objectives: The aim of this study was to assess the diagnostic accuracy of a modified high-resolution whole-brain three-dimensional T1-weighted black-blood sequence (T1-weighted modified volumetric isotropic turbo spin echo acquisition [T1-mVISTA]) in comparison to a standard three-dimensional T1-weighted magnetization-prepared rapid gradient echo (MP-RAGE) sequence for detection of contrast-enhancing cerebral lesions in patients with relapsing-remitting multiple sclerosis (MS).& para;& para;Materials and Methods: After institutional review board approval and informed consent, 22 patients (8 men;aged 31.0 +/- 9.2 years) with relapsing-remitting MS were included in this monocentric prospective cohort study.& para;& para;Contrast-enhanced T1-mVISTA and MP-RAGE, both with 0.8 mm(3) resolution, were performed in all patients. In a substudy of 12 patients, T1-mVISTA was compared with a T1-mVISTA with 1.0 mm(3) resolution (T1-mVISTA_1.0). Reference lesions were 2-defined by an experienced neuroradiologist using all available sequences and served as the criterion standard. T1-mVISTA, T1-mVISTA_1.0, and MP-RAGE sequences were read in random order 4 weeks apart. Image quality, visual contrast enhancement, contrast-to-noise-ratio (CNR), diagnostic confidence, and lesion size were assessed and compared by Wilcoxon and Mann-Whitney U tests.& para;& para;Results: Eleven of 22 patients displayed contrast-enhancing lesions. Visual contrast enhancement, CNR, and diagnostic confidence of contrast-enhancing MS lesions were significantly increased in T1-mVISTA compared with MP-RAGE (P < 0.001). Significantly more contrast-enhancing lesions were detected with T1-mVISTA than with MP-RAGE (71 vs 39, respectively;P < 0.001). With MP-RAGE, 25.6% of lesions were missed in the initial reading, whereas only 4.2% of lesions were missed with T1-mVISTA. Increase of the voxel volume from 0.8 mm to 1.0 mm isotropic in T1-mVISTA_1.0 did not affect the detect-ability of lesions, whereas scan time was decreased from 4:43 to 1:55 minutes.& para;& para;Conclusions: Three-dimensional T1-mVISTA improves the detection rates of contrast-enhancing cerebral MS lesions compared with conventional 3D MP-RAGE sequences by increasing CNR of lesions and might, therefore, be useful in patient management

Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice

Objectives: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minori

Effect of the concentrations of nucleating agents ZrO2 and TiO2 on the crystallization of Li2O–Al2O3–SiO2 glass: an X-ray diffraction and TEM investigation

In order to study the effect of ZrO2 and TiO2 on the nucleation mechanism in a lithium aluminosilicate glass, a composition similar to that of the commercially available ROBAX™ glass (Schott AG) was modified. Glasses with different concentrations of ZrO2 and TiO2 were melted and studied using differential scanning calorimetry measurement. The glasses are thermally treated for different periods of time and at various temperatures and then investigated by X-ray diffraction and electron microscopy. Both scanning electron microscopy and transmission electron microscopy were applied to study size and shape of the formed crystal phases and possibly to obtain lattice plane distances. Increasing the concentration of the nucleation agents led to the spontaneous formation of Zr1−xTi1+xO4 nano crystals during cooling. In any case, the nuclei contain much more titania than zirconia, possess an elongated shape, and are embedded in a shell enriched in alumina

The evidence of phase separation droplets in the crystallization process of a Li2O-Al2O3-SiO2 glass with TiO2 as nucleating agent: An X-ray diffraction and (S)TEM-study supported by EDX-analysis

Lithiumalumosilicate glasses are of great importance for industrial applications, because they enable the preparation of glass ceramics with coefficients of thermal expansion close to zero. While detailed studies of the effect of ZrO2 on nucleation and crystal growth have already been performed in recent years, the effect of TiO2 was up to now not reported in detail. It is shown for the first time, that liquid/liquid phase separation is the initial step of nucleation in lithiumalumosilicate glasses containing TiO2. During temperature treatment above the glass transition temperature, at 740 °C for 0.25–24 h, in the formed droplets, TiO2 nanocrystals precipitate. The formed phases were investigated by XRD- and TEM and STEM-EDX to illustrate the phase developments as well as the resulting microstructures and the local enrichments of the respective components as a function of time. Longer crystallization times resulted in the formation of crystalline lithiumalumosilicate (LAS) with a high-quartz structure. These crystals are notably larger than the TiO2 crystals and are growing with increasing treatment time and temperature. The evidence of anatase formation was obtained from high resolution TEM from the lattice spacings because it cannot be distinguished from the high quartz structure using XRD