Investigation of oxidative stress in patients with multifocal motor neuropathy.

Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

[Dissections of the supraaortic arteries]. / A szupraaortikus erek disszekciói.

Dissection of the cervical and intracranial vasculature is a rare but important cause of ischaemic stroke especially in young adults. In the majority of cases it affects the extracranial vessels, mostly the internal carotid artery. It might be categorized as spontaneous or traumatic, causing diverse clinical symptoms. Dissection might lead to ipsilateral stroke mainly by artery-to-artery embolisation. Due to its relative rarity compared to the classic ischaemic stroke of the elderly, there are much less clinically relevant information for the clinician to rely on. Several large, randomised, multicentered, prospective studies and some smaller, retrospective analyses have been published recently concerning the genetic background, epidemiology, acute care and secondary prevention of supraaortic arterial dissection which helps the neurologist to provide evidence-based care for his patient. Our aim is to give a short, up-to-date overview of arterial dissections with two case reports.

Circulating microRNAs correlate with structural and functional MRI parameters in patients with multiple sclerosis.

Introduction: Circulating microRNAs are promising biomarkers for multiple sclerosis (MS). Our aim was to correlate serum microRNA levels with various magnetic resonance imaging (MRI) parameters. Methods: We recruited 50 MS patients and measured cervical spine and cerebral white matter lesions together with regional brain volumes. Microstructural changes in the white matter were investigated with diffusion tensor imaging. Magnetic resonance spectroscopy was performed to measure cerebral metabolites. Functional connectivity within the default mode network was examined with resting-state functional MRI. On the day of the MRI measurements, we collected serum samples and carried out quantitative analysis of ten pre-selected microRNAs using droplet digital PCR. Results: Serum level of miR-143.3p could differentiate between MS subtypes and had lower levels in progressive MS types. We found significant associations between microRNA levels and MRI measures: (1) higher miR-92a.3p and miR-486.5p levels were associated with greater total white matter lesion volumes within the cervical spine, (2) decreased miR-142.5p levels was associated with reduced total creatinine concentration and (3) miR-92a.3p, miR-142.5p and miR-486.5p levels were associated with functional connectivity strengths between specific nodes of the default mode network. Specifically, we found a negative association between miR-92a.3p and miR-486.5p levels and connectivity strength between the lateral temporal cortex and posterior inferior parietal lobule, and a positive association between miR-142.5p level and connectivity strength between the retrosplenial cortex and temporal pole. However, miRNA levels were not associated with regional brain volumes. Conclusion: We provide here further evidence that circulating microRNAs may show correlation with both structural and functional neuroimaging outcomes in patients with MS.

Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis.

Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain volumes and white matter (WM) lesion load in MS. Concentrations of OPN in blood and CSF were related to MRI findings 10.1 ± 2.0 years later in 46 patients with MS. OPN concentration was measured by ELISA, while regional brain volumes and lesion load was assessed by magnetic resonance imaging (MRI) using 3D MPRAGE sequence and automated MR volumetry. OPN measured in the CSF was associated with several regional brain volumes and WM lesion load measured 10.1 ± 2.0 years later. CSF OPN concentration correlated with long-term enlargement of lateral- and inferior lateral ventricles and the elevation of gross CSF volume, in conjunction with the reduction of several cortical/subcortical gray matter and WM volumes. Serum OPN showed no long-term association with regional brain volumes. OPN measured from the CSF but not from the serum was associated with lower regional brain volumes measured a decade later, indicating the primary role of inflammation within the CNS in developing long-term brain related alterations.

Microstructural and functional brain abnormalities in multiple sclerosis predicted by osteopontin and neurofilament light.

BACKGROUND: Osteopontin (OPN) is a proinflammatory biomarker, and neurofilament light chain (NFL) levels reflect axonal damage. Resting-state functional MRI (rs-fMRI) defines brain networks during wakeful rest. OBJECTIVE: To examine, if levels of OPN and NFL are associated on the long term with (i) lesion evolution, (ii) changes in normal-appearing white matter (NAWM) microstructure and (iii) functional connectivity in multiple sclerosis (MS). METHODS: Concentration of NFL and OPN in the blood and CSF were related to MRI findings 10.3 ± 2.8 years later in 53 patients with MS. NFL was examined by Simoa method, OPN by ELISA. Lesion volume in the brain and cervical spinal cord was examined by 3D FLAIR images. Voxel-wise images of fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were examined by tract-based spatial statistics corrected for gender, age and lesion volume. Metabolites were examined by single-voxel MR-spectroscopy in the NAWM. Fifty-five default mode network connections were examined by rs-fMRI corrected for gender, age, MS subtype and current therapy as covariates. RESULTS: While NFL in paired serum and CSF positively correlated (p = 0.019), there was no correlation between serum and CSF OPN. Higher OPN levels in the CSF but not in the serum showed association with increased brain WM lesion volume (p = 0.009) in 10.3 ± 2.8 years. Higher OPN in the CSF was associated with reduced FA, increased MD, and reduced RD in different NAWM areas 10.3 ± 2.8 years later. Higher OPN in the serum and CSF were associated with increased connectivity strength between the medial prefrontal cortex (MPFC) and other regions except with inferior parietal lobule. NFL in the CSF and in the serum was associated with decreased connectivity strength except for ventral MPFC-hippocampal formation. Neither serum OPN nor NFL at the time of the MRI were associated with functional connectivity changes. CONCLUSION: While serum NFL levels reflects CNS production, OPN in serum and CSF may have different cellular sources. OPN within the CSF but not in the serum may forecast development of lesions and microstructural abnormalities in 10 years, indicating the detrimental role of CNS inflammation on the long-term. Although both OPN and NFL in the CSF were associated with functional connectivity changes in 10 years, NFL was associated with decreased strength possibly indicating general axonal loss. In contrast, the positive association of OPN levels in the CSF with increased connectivity strength in 10 years may point to adaptive re-organization due to inflammatory WM lesions and microstructural changes.

The effect of mechanochemical activation upon the intercalation of a high-defect kaolinite with formamide.

The effect of mechanochemical activation upon the intercalation of formamide into a high-defect kaolinite has been studied using a combination of X-ray diffraction, thermal analysis, and DRIFT spectroscopy. X-ray diffraction shows that the intensity of the d(001) spacing decreases with grinding time and that the intercalated high-defect kaolinite expands to 10.2 A. The intensity of the peak of the expanded phase of the formamide-intercalated kaolinite decreases with grinding time. Thermal analysis reveals that the evolution temperature of the adsorbed formamide and loss of the inserting molecule increases with increased grinding time. The temperature of the dehydroxylation of the formamide-intercalated high-defect kaolinite decreases from 495 to 470 degrees C with mechanochemical activation. Changes in the surface structure of the mechanochemically activated formamide-intercalated high-defect kaolinite were followed by DRIFT spectroscopy. Fundamentally the intensity of the high-defect kaolinite hydroxyl stretching bands decreases exponentially with grinding time and simultaneously the intensity of the bands attributed to the OH stretching vibrations of water increased. It is proposed that the mechanochemical activation of the high-defect kaolinite caused the conversion of the hydroxyls to water which coordinates the kaolinite surface. Significant changes in the infrared bands assigned to the hydroxyl deformation and amide stretching and bending modes were observed. The intensity decrease of these bands was exponentially related to the grinding time. The position of the amide C=O vibrational mode was found to be sensitive to grinding time. The effect of mechanochemical activation of the high-defect kaolinite reduces the capacity of the kaolinite to be intercalated with formamide.