scholarly journals Cortical involvement determines impairment 30 years after a clinically isolated syndrome

Brain ◽  
2021 ◽  
Author(s):  
Lukas Haider ◽  
Ferran Prados ◽  
Karen Chung ◽  
Olivia Goodkin ◽  
Baris Kanber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Disease Duration ◽  
Magnetization Transfer ◽  
Clinically Isolated Syndrome ◽  
Cervical Cord ◽  
Grey Matter Volume ◽  
Cortical Lesions ◽  
Matter Volume

Abstract Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.

Two-year study of cervical cord volume and myelin water in primary progressive multiple sclerosis

2010 ◽  
Vol 16 (6) ◽  
pp. 670-677 ◽  
Author(s):  
C. Laule ◽  
IM Vavasour ◽  
Y. Zhao ◽  
AL Traboulsee ◽  
J. Oger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Grey Matter ◽  
Interquartile Range ◽  
Cervical Cord ◽  
Controlled Clinical Trial ◽  
Grey Matter Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Matter Volume

Background: Spinal cord involvement in multiple sclerosis (MS) is common and an important element in disability. Previous studies demonstrated smaller cervical cord area at the C2 level in MS compared to controls, and a decrease in cord area over 12 months, most marked in primary progressive MS (PPMS). A subset of subjects participating in a multicentre, double-blind, placebo-controlled clinical trial evaluating the efficacy of glatiramer acetate in PPMS (PROMiSe trial) were followed for 2 years. Methods: 24 PPMS subjects, randomized to placebo ( n = 9) and glatiramer acetate ( n = 15), and 24 matched controls were studied. Cervical cord volume (CCV) at C2—3 was determined using a 3D inversion recovery (IR)-prepared spoiled-gradient echo sequence. Myelin water fraction (MWF) at C2—3 was obtained using a 32-echo IR-prepared relaxation sequence. Scans were repeated at baseline, years 1 and 2. Results: Baseline CCV was significantly smaller for PPMS than controls [median (interquartile range) 951 (829—1043) vs. 1072 (1040—1129) mm3, p = 0.0004] and MWF trended to be lower in PPMS cord [median (interquartile range) 0.225 (0.187—0.267) vs. 0.253 (0.235—0.266), p = 0.12]. Baseline CCV correlated with baseline Expanded Disability Status Scale, disease duration, brain white and grey matter volume. In PPMS, CCV was significantly decreased at year 1 (—0.83%, p = 0.04) and year 2 (—1.65%, p = 0.02). Baseline MWF correlated with baseline CCV and brain white and grey matter volume. MWF was significantly decreased from baseline for PPMS at year 2 (—10.5%, p = 0.01). Treatment effect was not detected on change in CCV nor MWF. Conclusions: Metrics at the level of the cord, including volume and MWF at C2—3, were lower in PPMS than controls and changed over 2 years only in PPMS.

Cerebrospinal fluid neurofilament light levels mark grey matter volume in clinically isolated syndrome suggestive of multiple sclerosis

2017 ◽  
Vol 24 (8) ◽  
pp. 1039-1045 ◽  
Author(s):  
Carla Tortorella ◽  
Vita Direnzo ◽  
Maddalena Ruggieri ◽  
Stefano Zoccolella ◽  
Mariangela Mastrapasqua ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
White Matter ◽  
Grey Matter ◽  
Brain Volume ◽  
Clinically Isolated Syndrome ◽  
Grey Matter Volume ◽  
Neurofilament Light ◽  
Brain Volumes ◽  
Matter Volume

Background: Brain atrophy is a known marker of irreversible tissue damage in multiple sclerosis (MS). Cerebrospinal fluid (CSF) osteopontin (OPN) and neurofilament light chain (NF-L) have been proposed as candidate surrogate markers of inflammatory and neurodegenerative processes in MS. Objective: To evaluate the relationship between CSF NF-L and OPN levels and brain grey and white matter volumes in patients with clinically isolated syndrome (CIS) suggestive of MS. Methods: A total of 41 CIS patients and 30 neurological controls (NCs) were included. CSF NF-L and OPN were measured by commercial ELISA. Measures of brain volume (normalized brain volume (NBV), normalized grey matter volume (NGV), peripheral grey matter volume (PGV), normalized white matter volume (WMV), and ventricular volume) were obtained by SIENAX. Corpus callosum index (CCI) was calculated. Brain volumes were categorized into ‘high’ and ‘low’ according to the median value. Results: CSF NF-L and OPN levels were higher in CIS patients in comparison with NCs. CIS patients with ‘low’ TGV, PGV, and TBV showed higher CSF NF-L levels than CIS patients with ‘high’ brain volumes. TGV and PGV correlated inversely with NF-L levels, whereas CCI was inversely related to OPN levels. CSF NF-L was the only independent predictor of TGV and PGV. Conclusion: CSF NF-L tracks mainly grey matter damage in patients with CIS suggestive of MS.

scholarly journals Education modulates brain maintenance in presymptomatic frontotemporal dementia

2019 ◽  
Vol 90 (10) ◽  
pp. 1124-1130 ◽  
Author(s):  
Stefano Gazzina ◽  
Mario Grassi ◽  
Enrico Premi ◽  
Maura Cosseddu ◽  
Antonella Alberici ◽  
...  
Keyword(s):  
At Risk ◽  
Frontotemporal Dementia ◽  
Grey Matter ◽  
Principal Component ◽  
Grey Matter Volume ◽  
Brain Reserve ◽  
Matter Volume ◽  
Brain Maintenance ◽  
Over Time

ObjectiveCognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

Whole brain and grey matter volume of Japanese patients with multiple sclerosis

2017 ◽  
Vol 306 ◽  
pp. 68-75 ◽  
Author(s):  
Tetsuya Akaishi ◽  
Ichiro Nakashima ◽  
Shunji Mugikura ◽  
Masashi Aoki ◽  
Kazuo Fujihara
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Japanese Patients ◽  
Grey Matter Volume ◽  
Whole Brain ◽  
Matter Volume

scholarly journals INFLUENCE OF PSYCHOTIC EPISODES ON GREY MATTER VOLUME CHANGES IN PATIENTS WITH SCHIZOPHRENIA

2020 ◽  
Author(s):  
Antonija Ružić Baršić ◽  
Gordana Rubeša ◽  
Diana Mance ◽  
Damir Miletić ◽  
Lea Gudelj ◽  
...  
Keyword(s):  
Grey Matter ◽  
Disease Duration ◽  
Severe Illness ◽  
Grey Matter Volume ◽  
Healthy Controls ◽  
Voxel Based Morphometry ◽  
Matter Volume ◽  
Multiple Regions ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Background: Schizophrenia is a severe illness whose clinical course is characterized by various numbers of psychotic episodes (PE). The neurotoxic hypothesis (NH) of schizophrenia assumes that psychosis is biologically toxic. The aim of the study was to investigate whether schizophrenia patients (SP) with multiple PE have greater grey matter volume (GMV) reduction compared to SP with fewer PE.Subjects and methods: We enrolled 106 adult SP and 63 healthy controls. Demographic and clinical data were collected and statistically analysed for all included subjects. Magnetic resonance imaging (MRI) of the brain was acquired on a 1.5 T scanner. SP were grouped according to the number of PE into a group with up to 3 PE (SCHG-1) and with 4 or more PE (SCHG-2). SCHG-1 was further subdivided into two groups regarding to disease duration (DD). Voxel based morphometry (VBM) analyses were performed between SP groups as well as between SP groups and the healthy controls group (HCG).Results: No relevant GMV differences were detected between SP groups. Comparison between HCG and SCHG-1 showed only 3 regions with reduced GMV, while multiple regions with reduced GMV were detected when comparing HCG and SCHG-2. Conclusions: GMV reduction in schizophrenia varies depending on the number of PE when compared to HCG, regardless of disease duration (DD), but PE is not the only contributing factor that leads to neurotoxicity.

scholarly journals Usefulness of two-dimensional measurements for the evaluation of brain volume and disability in multiple sclerosis

2022 ◽  
Vol 8 (1) ◽  
pp. 205521732110707
Author(s):  
Satori Ajitomi ◽  
Juichi Fujimori ◽  
Ichiro Nakashima
Keyword(s):  
Multiple Sclerosis ◽  
Processing Speed ◽  
Lateral Ventricle ◽  
Grey Matter ◽  
Brain Volume ◽  
Grey Matter Volume ◽  
Two Dimensional ◽  
Whole Brain ◽  
Brain Volumes ◽  
Matter Volume

Background Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS). Objective To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS. Methods In this cross-sectional analysis, eighty-five consecutive Japanese MS patients—relapsing-remitting MS (81%) and progressive MS (19%)—underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure whole-brain and grey matter volume. 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), brain width, bicaudate ratio, and corpus callosum index (CCI), were obtained from each scan. Correlations between 2D measurements and 3D measurements, the Expanded Disability Status Scale (EDSS), or processing speed were analysed. Results The third and lateral ventricle widths were well-correlated with the whole-brain volume ( p < 0.0001), grey matter volume ( p < 0.0001), and EDSS scores ( p = 0.0001, p = .0004, respectively).The least squares regression model revealed that 78% of the variation in whole-brain volume could be explained using five explanatory variables, namely, LVW, CCI, age, sex, and disease duration. By contrast, the partial correlation coefficient excluding the effect of age showed that the CCI was significantly correlated with the EDSS and processing speed ( p < 0.0001). Conclusion Ventricle width correlated well with brain volumes, while the CCI correlated well with age-independent (i.e. disease-induced) disability.

scholarly journals Deep grey matter volume loss drives disability worsening in multiple sclerosis

2017 ◽  
Author(s):  
Arman Eshaghi ◽  
Ferran Prados ◽  
Wallace Brownlee ◽  
Daniel R. Altmann ◽  
Carmen Tur ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Standard Deviation ◽  
Grey Matter ◽  
Therapeutic Interventions ◽  
Tissue Loss ◽  
Cerebral White Matter ◽  
Spatiotemporal Pattern ◽  
Grey Matter Volume ◽  
Volume Loss

AbstractObjectiveGrey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.MethodsWe analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsingremitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.ResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).InterpretationThis large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions.

Sign in / Sign up

Export Citation Format

Share Document