Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: A voxel-based analysis study.

In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

OBJECTIVE: To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). METHODS: 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm(3)) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. RESULTS: Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. CONCLUSIONS: In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, there is increasing evidence that demyelination, and neuronal damage occurs preferentially in cortical grey matter next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid mediated factors. White matter lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing white matter abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative magnetic resonance imaging and compares the abnormalities between secondary progressive and relapsing remitting multiple sclerosis. Forty-three patients with relapsing remitting and 28 with secondary progressive multiple sclerosis, and 38 healthy control subjects were included in this study. T1-weighted volumetric, magnetization transfer and proton density/T2-weighted scans were acquired for all subjects. From the magnetization transfer data, magnetization transfer ratio maps were prepared. White matter tissue masks were derived from SPM8 segmentations of the T1-weighted images. Normal-appearing white matter masks were generated by subtracting white matter lesions identified on the proton density/T2 scan, and a two-voxel perilesional ring, from the SPM8 derived white matter masks. White matter was divided in concentric bands, each ∼1-mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and normal-appearing white matter and lesion magnetization transfer ratio values were then computed for the 10 bands nearest to the ventricles. Compared with controls, magnetization transfer ratio in the normal-appearing white matter bands was significantly lower in patients with multiple sclerosis. In controls, magnetization transfer ratio was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the multiple sclerosis groups, relative to controls, reductions in magnetization transfer ratio were greater in the secondary progressive multiple sclerosis compared with relapsing remitting multiple sclerosis group, and these reductions were greatest next to the ventricles and became smaller with distance from them. White matter lesion magnetization transfer ratio reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the relapsing remitting and secondary progressive multiple sclerosis groups. These findings suggest that in people with multiple sclerosis, and more so in secondary progressive than relapsing remitting multiple sclerosis, tissue structural abnormalities in normal-appearing white matter and white matter lesions are greatest near the ventricles. This would be consistent with a cerebrospinal fluid or ependymal mediated pathogenesis

Magnetisation transfer ratio measures in normal appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis (MS), there is increasing evidence that demyelination, and neuronal damage within and beyond lesions, occurs preferentially in cortical grey matter (GM) next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid (CSF) mediated factors. White matter (WM) lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing (NA) WM abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative MR imaging and compares the abnormalities between SPMS and relapsing remitting (RR) MS. Forty-three people with RRMS and 28 with SPMS, and 38 healthy controls, were included in this study. T1-weighted volumetric, magnetisation transfer (MT) and PD/T2-weighted scans were acquired for all subjects. From the MT data, MT ratio (MTR) maps were prepared. WM tissue masks were derived from SPM8 segmentations of the T1-weighted images. NAWM masks were generated by subtracting WM lesions identified on the PD/T2 scan, and a 2 voxel perilesional ring, from the SPM8 derived WM masks. WM was divided in concentric bands, each about 1 mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and NAWM and lesion MTR values were then computed for the ten bands nearest to the ventricles. Compared with controls, MTR in the NAWM bands was significantly lower in MS. In controls, MTR was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the MS groups, relative to controls, reductions in MTR were greater in the SPMS compared with RRMS group, and these reductions were greatest next to the ventricles and became smaller with distance from them. WM lesion MTR reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the RR and SPMS groups. These findings suggest that in people with MS, and more so in SPMS than RRMS, tissue structural abnormalities in NAWM and WM lesions are greatest near the ventricles. This would be consistent with a CSF or ependymal mediated pathogenesis

Instabilities and robust control in natural resource management

Most renewable natural resources exhibit marked demographic and environmental stochasticities, which are exarcebated in management decisions by the uncertainty regarding the choice of an appropriate model to describe system dynamics. Moreover, demand and supply analysis often indicates the presence of instabilities and multiple equilibria, which may lead to management problems that are intensified by uncertainty on the evolution of the resource stock. In this paper the fishery management problem is used as an example to explore the potential of robust optimal control, where the objective is to choose a harvesting rule that will work under a range of admissible specifications for the stock-recruitment equation. The paper derives robust harvesting rules leading to a unique equilibrium, which could be helpful in the design of policy instruments such as robust quota systems.info:eu-repo/semantics/publishedVersio

Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study

BACKGROUND: In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. OBJECTIVE: To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. METHODS: Seventy-two people with MS (46 relapsing–remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. RESULTS: Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. CONCLUSION: Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability

An intranasal selective antisense oligonucleotide impairs lung cyclooxygenase-2 production and improves inflammation, but worsens airway function, in house dust mite sensitive mice

<p>Abstract</p> <p>Background</p> <p>Despite its reported pro-inflammatory activity, cyclooxygenase (COX)-2 has been proposed to play a protective role in asthma. Accordingly, COX-2 might be down-regulated in the airway cells of asthmatics. This, together with results of experiments to assess the impact of COX-2 blockade in ovalbumin (OVA)-sensitized mice in vivo, led us to propose a novel experimental approach using house dust mite (HDM)-sensitized mice in which we mimicked altered regulation of COX-2.</p> <p>Methods</p> <p>Allergic inflammation was induced in BALBc mice by intranasal exposure to HDM for 10 consecutive days. This model reproduces spontaneous exposure to aeroallergens by asthmatic patients. In order to impair, but not fully block, COX-2 production in the airways, some of the animals received an intranasal antisense oligonucleotide. Lung COX-2 expression and activity were measured along with bronchovascular inflammation, airway reactivity, and prostaglandin production.</p> <p>Results</p> <p>We observed impaired COX-2 mRNA and protein expression in the lung tissue of selective oligonucleotide-treated sensitized mice. This was accompanied by diminished production of mPGE synthase and PGE₂in the airways. In sensitized mice, the oligonucleotide induced increased airway hyperreactivity (AHR) to methacholine, but a substantially reduced bronchovascular inflammation. Finally, mRNA levels of hPGD synthase remained unchanged.</p> <p>Conclusion</p> <p>Intranasal antisense therapy against COX-2 in vivo mimicked the reported impairment of COX-2 regulation in the airway cells of asthmatic patients. This strategy revealed an unexpected novel dual effect: inflammation was improved but AHR worsened. This approach will provide insights into the differential regulation of inflammation and lung function in asthma, and will help identify pharmacological targets within the COX-2/PG system.</p