Increased total sodium concentration in gray matter better explains cognition than atrophy in MS
Adil MaaroufBertrand AudoinFanelly PariollaudSoraya GheribAudrey RicoElisabeth SoulierSylviane Confort‐GounyMaxime GuyeLothar R. SchadJean PelletierJean‐Philippe RanjevaWafaa Zaaraoui
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Abstract:
Objective:
To investigate whether brain total sodium accumulation assessed by 23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS).Methods:
Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction).Results:
The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0–4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively.Conclusions:
This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.To monitor the interaction between the clinical manifestation of the secondary progressive form of multiple sclerosis (SPMS) expressed in the Expanded Disability Status Scale (EDSS) and abnormal findings in magnetic resonance imaging (MRI) of the brain. To compare a time line of brain atrophy in patients with SPMS, patients with relapsing-remitting multiple sclerosis (RRMS) and the healthy population.Brain atrophy, volume of increased signal lesions on Fluid Attenuated Inversion Recovery Sequence (FLAIR) sequence (s.c.lesion load) and decreased signal lesions on T1 weighted sequence (s.c. black holes) were measured semi-automatically and correlated with EDSS in 12 patients. Further, we compared a time line of brain parenchyma fraction (BPF) loss in patients with SPMS, patients with RRMS and the healthy population.In patients with SPMS, no statistical correlation was found between lesion load in FLAIR and EDSS and there was also no significant statistical correlation (p=0.1134) between the volume of "black holes" and EDSS. However, we did confirm a significant correlation between increase in brain atrophy and clinical status (p=0.0093). Comparison of patients with SPMS or RRMS and the healthy population revealed that brain atrophy progressed most rapidly in patients with SPMS.The presence of a statistically significant difference in BPF loss between patients with SPMS or RRMS and the healthy population merits further study despite the small size of our sample. We postulate that the measurement of brain atrophy could be helpful in determining the transition of RRMS to SPMS and thereby predict the progression of the disease in the future.
Fluid-attenuated inversion recovery
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In relapsing-remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real-world setting.A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability-worsening events and of confirmed disability-worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months.Using a fixed baseline EDSS reference, the cumulative probability of 6-year overall confirmed disability-worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability-worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability-worsening events).In a real-world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse in RRMS patients.
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Abstract White matter is often severely affected after human ischaemic stroke. While animal studies have suggested that various factors may contribute to white matter structural damage after ischaemic stroke, the characterization of damaging processes to the affected hemisphere after human stroke remains poorly understood. Thus, the present study aims to thoroughly describe the longitudinal pattern of evolution of diffusion magnetic resonance imaging metrics in different parts of the ipsilesional white matter after stroke. We acquired diffusion and anatomical images in 17 patients who had suffered from a single left hemisphere ischaemic stroke, at 24–72 h, 8–14 days and 6 months post-stroke. For each patient, we created three regions of interest: (i) the white matter lesion; (ii) the perilesional white matter; and (iii) the remaining white matter of the left hemisphere. We extracted diffusion metrics (fractional anisotropy, mean, axial and radial diffusivities) for each region and conducted two-way repeated measures ANOVAs with stage post-stroke (acute, subacute and chronic) × regions of interest (white matter lesion, perilesional white matter and remaining white matter). Fractional anisotropy values stayed consistent across time-points, with significantly lower values in the white matter lesion compared to the perilesional white matter and remaining white matter tissue. Fractional anisotropy values of the perilesional white matter were also significantly lower than that of the remaining white matter. Mean, axial and radial diffusivities in the white matter lesion were all decreased in the acute stage compared to perilesional white matter and remaining white matter, but significantly increased in both the subacute and chronic stages. Significant increases in mean and radial diffusivities in the perilesional white matter were seen in the later stages of stroke. Our findings suggest that various physiological processes are at play in the acute, subacute and chronic stages following ischaemic stroke, with the infarct territory and perilesional white matter affected by ischaemia at different rates and to different extents throughout the stroke recovery stages. The examination of multiple diffusivity metrics may inform us about the mechanisms occurring at different time-points, i.e. focal swelling, axonal damage or myelin loss.
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Objective To investigate the effects of short-term enriched environment on the white matter and the myelinated fibers in the white matter of aged male rats. Methods Twenty 24-month old male SD rats were reared in enriched environment(EE) or standard environment(SE) for 4 months,respectively.Four rats were randomly selected from each group.The white matter and the myelinated fibers in the rat white matter were quantitatively investigated with transmission electronic microscopy and stereological techniques. Results The white matter volume,the total length and total volume of the myelinated fibers in the white matter and the total volume of axons in the white matter of EE rats were all significantly larger than those of SE rats.The mean inner diameter and outer diameter of myelinated fibers,the total volume of myelin sheaths,the mean thickness of myelin sheaths,the mean inner perimeter and outer perimeter of myelin sheaths and the cross-sectional areas of the myelinated fibers,myelin sheaths and axons were not significantly different between EE and SE rats.Conclusion Short-term enriched environment has positive effects on the white matter and myelinated fibers in the white matter in 24-month male rats.These results suggest that short-term enriched environment might induce the remyelination of the demyelinated fibers in the white matter of aged male rats.
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The importance of macrostructural white matter changes, including white matter lesions and atrophy, in intact brain functioning is increasingly being recognized. Diffusion tensor imaging (DTI) enables measurement of the microstructural integrity of white matter. Loss of white matter integrity in aging has been reported, but whether this is inherent to the aging process itself or results from specific white matter pathology is unknown. In 832 persons aged 60 years and older from the population-based Rotterdam Study, we measured fractional anisotropy (FA) and directional diffusivities in normal-appearing white matter using DTI. All subjects' DTI measures were projected onto a common white matter skeleton to enable robust voxelwise comparison. With increasing age, multiple regions showed significant decreases in FA or increases in axial or radial diffusivity in normal-appearing white matter. However, nearly all of these regional changes were explained by either white matter atrophy or by white matter lesions; each of which related to changes in distinct brain regions. These results indicate that loss of white matter integrity in aging is primarily explained by atrophy and lesion formation and not by the aging process itself. Furthermore, white matter atrophy and white matter lesion formation relate to loss of integrity in distinct brain regions, indicating the two processes are pathophysiologically different. PMID: 18755279
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