Dataset Information

Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.

ABSTRACT:

Purpose

Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.

Materials and methods

Thirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing white matter. Patients were stratified in a high- and low-inflammatory group according to the number of new contrast enhancing lesions.

Results

Thirteen patients were classified as high-inflammatory. Compared to low-inflammatory patients, the high-inflammatory group demonstrated significantly higher CBV (p = 0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent variables associated with CBV and CBF revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV.

Conclusion

This work provides evidence that high inflammatory lesion load is associated with increased CBV and CBF, underlining the role of global modified microcirculation prior to leakage of the blood-brain barrier in the pathophysiology of MS. Perfusion changes might therefore be sensitive to active inflammation apart from lesion development without local blood-brain barrier breakdown, and could be utilized to further assess the metabolic aspect of current inflammation.

SUBMITTER: Bester M

PROVIDER: S-EPMC4361628 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.

Bester Maxim M Forkert Nils Daniel ND Stellmann Jan Patrick JP Stürner Klarissa K Aly Lilian L Drabik Anna A Young Kim Lea KL Heesen Christoph C Fiehler Jens J Siemonsen Susanne S

PloS one 20150316 3

<h4>Purpose</h4>Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.<h4>Materials and methods</h4>Thirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic s ...[more]

PMID: 25774497

Similar Datasets

Project description:Normal-appearing white matter is far from normal in multiple sclerosis; little is known about the precise pathology or spatial pattern of this alteration and its relation to subsequent lesion formation. This study was undertaken to evaluate normal-appearing white matter abnormalities in brain areas where multiple sclerosis lesions subsequently form, and to investigate the spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis. Brain MRIs of pre-lesion normal-appearing white matter were analysed in participants with new T2 lesions, pooled from three clinical trials: SYNERGY (NCT01864148; n = 85 with relapsing multiple sclerosis) was the test data set; ASCEND (NCT01416181; n = 154 with secondary progressive multiple sclerosis) and ADVANCE (NCT00906399; n = 261 with relapsing-remitting multiple sclerosis) were used as validation data sets. Focal normal-appearing white matter tissue state was analysed prior to lesion formation in areas where new T2 lesions later formed (pre-lesion normal-appearing white matter) using normalized magnetization transfer ratio and T2-weighted (nT2) intensities, and compared with overall normal-appearing white matter and spatially matched contralateral normal-appearing white matter. Each outcome was analysed using linear mixed-effects models. Follow-up time (as a categorical variable), patient-level characteristics (including treatment group) and other baseline variables were treated as fixed effects. In SYNERGY, nT2 intensity was significantly higher, and normalized magnetization transfer ratio was lower in pre-lesion normal-appearing white matter versus overall and contralateral normal-appearing white matter at all time points up to 24 weeks before new T2 lesion onset. In ASCEND and ADVANCE (for which normalized magnetization transfer ratio was not available), nT2 intensity in pre-lesion normal-appearing white matter was significantly higher compared to both overall and contralateral normal-appearing white matter at all pre-lesion time points extending up to 2 years prior to lesion formation. In all trials, nT2 intensity in the contralateral normal-appearing white matter was also significantly higher at all pre-lesion time points compared to overall normal-appearing white matter. Brain atlases of normal-appearing white matter abnormalities were generated using measures of voxel-wise differences in normalized magnetization transfer ratio of normal-appearing white matter in persons with multiple sclerosis compared to scanner-matched healthy controls. We observed that overall spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis largely recapitulated the anatomical distribution of probabilities of T2 hyperintense lesions. Overall, these findings suggest that intrinsic spatial properties and/or longstanding precursory abnormalities of normal-appearing white matter tissue may contribute to the risk of autoimmune acute demyelination in multiple sclerosis.

Project description:Multiple sclerosis (MS) is a neurodegenerative inflammatory disease where an autoimmune response to components of the central nervous system leads to a loss of myelin and subsequent neurological deterioration. People with MS can develop primary or secondary progressive disease (PPMS, SPMS) and differentiation of the specific differences in the pathogenesis of these two courses, at the molecular level, is currently unclear. Recently, lipidomics studies using human biofluids, mainly plasma and cerebrospinal fluid, have highlighted a possible role for lipids in the initiation and progression of MS. However, there is a lack of lipidomics studies in MS on CNS tissues, such as normal-appearing white matter (NAWM), where local inflammation initially occurs. Herein, we developed an untargeted reverse phase ultra-performance liquid chromatography time of flight tandem mass spectrometry (RP-UPLC-TOF MSE)-based workflow, in combination with multivariate and univariate statistical analysis, to assess significant differences in lipid profiles in brain NAWM from post-mortem cases of PPMS, SPMS and controls. Groups of eight control, nine PPMS and seven SPMS NAWM samples were used. Correlation analysis of the identified lipids by RP-UPLC-TOF MSE was undertaken to remove those lipids that correlated with age, gender and post-mortem interval as confounding factors. We demonstrate that there is a significantly altered lipid profile of control cases compared with MS cases and that progressive disease, PPMS and SPMS, can be differentiated on the basis of the lipidome of NAWM with good sensitivity, specificity and prediction accuracy based on receiver operating characteristic (ROC) curve analysis. Metabolic pathway analysis revealed that the most altered lipid pathways between PPMS and SPMS were glycerophospholipid metabolism, glycerophosphatidyl inositol (GPI) anchor synthesis and linoleic acid metabolism. Further understanding of the impact of these lipid alterations described herein associated with progression will provide an increased understanding of the mechanisms underpinning progression and highlight possible new therapeutic targets.

Dataset Information

Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.

Purpose

Materials and methods

Results

Conclusion

Publications

Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets