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.

Volume changes of thalamus, hippocampus and cerebellum are associated with specific CSF profile in MS

2021 ◽  
pp. 135245852110317
Author(s):  
Albulena Bajrami ◽  
Roberta Magliozzi ◽  
Anna I Pisani ◽  
Francesca B Pizzini ◽  
Francesco Crescenzo ◽  
...  
Keyword(s):  
Cerebellar Cortex ◽  
Grey Matter ◽  
Multivariable Analysis ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
Volume Changes ◽  
Inflammatory Profile ◽  
And Control ◽  
Control Regions

Background: The underlying pathogenesis of surface-in grey matter abnormalities in MS, demonstrated by both neuropathology and advanced MRI analyses, is under investigation and it might be related to CSF-mediated mechanism of inflammation and/or damage. Objective: To examine the link of CSF inflammatory profile with the damage of three regions early-involved in MS and bordering with CSF: thalamus, hippocampus and cerebellum. Methods: In this longitudinal, prospective study, we evaluated, in 109 relapsing–remitting MS patients, at diagnosis and after 2-year follow-up, the association between the baseline CSF level of 19 inflammatory mediators and the volume changes of thalamus, hippocampus, cerebellar cortex and control regions (globus pallidus, putamen). Results: The multivariable analysis showed that the CXCL13 and sCD163 CSF levels at baseline were independent predictors of thalamus ([Formula: see text]; p < 0.001) and hippocampus ([Formula: see text]; p < 0.001) volume change after 2-year follow-up. These molecules, plus CCL25, IFN-γ and fibrinogen, were independent predictors of the cerebellar cortex volume loss ([Formula: see text]; p < 0.001). No independent predictors of volume changes of the control regions were found. Conclusion: Our results indicate an association between the CSF inflammatory profile and grey matter volume loss of regions anatomically close to CSF boundaries, thus supporting the hypothesis of a surface-in GM damage in MS.

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.

scholarly journals Negative symptoms and longitudinal grey matter tissue loss in adolescents at risk of psychosis: Preliminary findings from a 6-year follow-up study

2016 ◽  
Vol 208 (6) ◽  
pp. 565-570 ◽  
Author(s):  
Andrew G. McKechanie ◽  
Thomas W. J. Moorhead ◽  
Andrew C. Stanfield ◽  
Heather C. Whalley ◽  
Eve C. Johnstone ◽  
...  
Keyword(s):  
At Risk ◽  
Negative Symptoms ◽  
Grey Matter ◽  
Imaging Techniques ◽  
Tissue Loss ◽  
Psychotic Symptoms ◽  
Grey Matter Volume ◽  
Left Temporal Lobe ◽  
Left Posterior

BackgroundNegative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques.AimsTo examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms.MethodA total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart.ResultsWhen comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus.ConclusionsNegative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

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.

scholarly journals Increased serum malondialdehyde levels are associated with grey matter volume loss in patients with non-alcoholic cirrhosis

2019 ◽  
Vol 9 (2) ◽  
pp. 230-237 ◽  
Author(s):  
Wei Zheng ◽  
Wen-Wei Zhu ◽  
Zhi-Chao Feng ◽  
Qi Liang ◽  
Peng-Fei Rong ◽  
...  
Keyword(s):  
Grey Matter ◽  
Alcoholic Cirrhosis ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
Matter Volume

scholarly journals Brain atrophy and employment in multiple sclerosis patients: a 10-year follow-up study

2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090248
Author(s):  
Cecilie Jacobsen ◽  
Robert Zivadinov ◽  
Kjell-Morten Myhr ◽  
Turi O Dalaker ◽  
Ingvild Dalen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Grey Matter ◽  
Resonance Imaging ◽  
Cortical Volume ◽  
Deep Grey Matter ◽  
Multiple Sclerosis Patients ◽  
The Unemployed

Background Multiple sclerosis is often associated with unemployment. The contribution of grey matter atrophy to unemployment is unclear. Objectives To identify magnetic resonance imaging biomarkers of grey matter and clinical symptoms associated with unemployment in multiple sclerosis patients. Methods Demographic, clinical data and 1.5 T magnetic resonance imaging scans were collected in 81 patients at the time of inclusion and after 5 and 10 years. Global and tissue-specific volumes were calculated at each time point. Statistical analysis was performed using a mixed linear model. Results At baseline 31 (38%) of the patients were unemployed, at 5-year follow-up 44 (59%) and at 10-year follow-up 34 (81%) were unemployed. The unemployed patients had significantly lower subcortical deep grey matter volume ( P < 0.001), specifically thalamus, pallidus, putamen and hippocampal volumes, and cortical volume ( P = 0.011); and significantly greater T1 ( P < 0.001)/T2 ( P < 0.001) lesion volume than the employed patient group at baseline. Subcortical deep grey matter volumes, and to a lesser degree cortical volume, were significantly associated with unemployment throughout the follow-up. Conclusion We found significantly greater atrophy of subcortical deep grey matter and cortical volume at baseline and during follow-up in the unemployed patient group. Atrophy of subcortical deep grey matter showed a stronger association to unemployment than atrophy of cortical volume during the follow-up.

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