Clinical impact of early brain atrophy in clinically isolated syndromes

2013 ◽  
Vol 19 (14) ◽  
pp. 1878-1886 ◽  
Author(s):  
F Pérez-Miralles ◽  
J Sastre-Garriga ◽  
M Tintoré ◽  
G Arrambide ◽  
C Nos ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Grey Matter ◽  
Brain Volume ◽  
First Year ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
Mcdonald Criteria ◽  
Brain Volume Loss ◽  
Clinical Onset ◽  
The Impact

Background: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. Objectives: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. Methods: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. Results: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (− 0.65% versus + 0.059%; p < 0.001). PBVC decreases below − 0.817% independently predicted shorter times to a second attack. Conclusions: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.

Brain Volume Loss During the First Year of Interferon-Beta Treatment in Multiple Sclerosis: Baseline Inflammation and Regional Brain Volume Dynamics

2016 ◽  
Vol 26 (5) ◽  
pp. 532-538 ◽  
Author(s):  
Angela Vidal-Jordana ◽  
Jaume Sastre-Garriga ◽  
Francisco Pérez-Miralles ◽  
Deborah Pareto ◽  
Jordi Rio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Brain Volume ◽  
First Year ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Regional Brain ◽  
Regional Brain Volume

Reversible brain atrophy following liver transplantation for biliary atresia in childhood

2020 ◽  
pp. 10.1212/CPJ.0000000000000991
Author(s):  
Aikaterini Fitsiori ◽  
Valérie McLin ◽  
Seema Toso ◽  
Maria-Isabel Vargas
Keyword(s):  
Liver Transplantation ◽  
Anorexia Nervosa ◽  
Biliary Atresia ◽  
Brain Atrophy ◽  
Early Life ◽  
Rare Case ◽  
Brain Volume ◽  
The Other ◽  
Volume Loss ◽  
Brain Volume Loss

A great deal of the brain's ultimate structure and capacity is shaped early in life, before the age of 3 years.1The influence of optimal nutrition during early life on brain development has been demonstrated by numerous studies.1–3 On the other hand, brain volume loss is accepted to be progressive with age and may be permanent. However, reversible brain atrophy has been demonstrated in adults with anorexia nervosa4 and reported in children suffering from kwashiorkor.5,6 We would like to report on a rare case of reversible brain atrophy in a child following correction of malabsorption.

scholarly journals Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

2020 ◽  
Author(s):  
Sehoon Park ◽  
Soojin Lee ◽  
Yaerim Kim ◽  
Semin Cho ◽  
Kwangsoo Kim ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
White Matter ◽  
Grey Matter ◽  
Mendelian Randomization ◽  
Brain Volume ◽  
Causal Effect ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
White Matter Volume ◽  
Matter Volume

AbstractBackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.MethodsThis study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.ResultsA higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.ConclusionsAF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.

scholarly journals The reduction of astrocytes and brain volume loss in anorexia nervosa—the impact of starvation and refeeding in a rodent model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Linda Frintrop ◽  
Stefanie Trinh ◽  
Johanna Liesbrock ◽  
Christina Leunissen ◽  
Julia Kempermann ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Brain Volume ◽  
Rodent Model ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
The Impact

scholarly journals Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis

2016 ◽  
Vol 22 (10) ◽  
pp. 1297-1305 ◽  
Author(s):  
Ludwig Kappos ◽  
Nicola De Stefano ◽  
Mark S Freedman ◽  
Bruce AC Cree ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Volume ◽  
Objective Measure ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: ‘No evidence of disease activity’ (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression (‘NEDA-3’), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. Objective: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 (‘NEDA-4’) Methods: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%–1.2%). Results: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01–4.41; p < 0.0001). Conclusion: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.

Brain volume loss precedes cognitive decline in the first year after ischaemic stroke

2017 ◽  
Vol 88 (5) ◽  
pp. e1.59-e1
Author(s):  
Emilio Werden ◽  
Toby Cumming ◽  
Laura Bird ◽  
Mohamed Khlif ◽  
Amy Brodtmann
Keyword(s):  
Cognitive Decline ◽  
Ischaemic Stroke ◽  
Brain Volume ◽  
First Year ◽  
Volume Loss ◽  
Brain Volume Loss

scholarly journals Grey matter atrophy is associated with disability increase in natalizumab-treated patients

2016 ◽  
Vol 23 (4) ◽  
pp. 556-566 ◽  
Author(s):  
Ethel Ciampi ◽  
Deborah Pareto ◽  
Jaume Sastre-Garriga ◽  
Angela Vidal-Jordana ◽  
Carmen Tur ◽  
...  
Keyword(s):  
Grey Matter ◽  
First Year ◽  
Volume Loss ◽  
Significant Volume ◽  
Brain Volume Loss ◽  
Lower Baseline ◽  
Brain Parenchymal Fraction ◽  
Left Caudate ◽  
Brain Parenchymal ◽  
Post Hoc

Background: Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. Objective: To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). Methods: We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. Results: Significant BVL was observed during first year: brain parenchymal fraction (BPF): −1.12% ( p < 0.001); white matter fraction (WMF): −0.9% ( p = 0.001); grey matter fraction (GMF): −1.28% ( p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (−0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. Conclusion: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.

Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes

2013 ◽  
Vol 19 (9) ◽  
pp. 1175-1181 ◽  
Author(s):  
Angela Vidal-Jordana ◽  
Jaume Sastre-Garriga ◽  
Francisco Pérez-Miralles ◽  
Carmen Tur ◽  
Mar Tintoré ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Volume ◽  
Corticosteroid Treatment ◽  
First Year ◽  
Volume Loss ◽  
White Matter Volume ◽  
Volume Changes ◽  
Brain Volumes ◽  
Matter Volume ◽  
Brain Volume Loss

Background: Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect. Objective: To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy. Methods: We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes. Results: The PBVC decrease was faster during the first year (−1.10% ± 1.43%), as compared to the second (−0.51% ± 0.96%) ( p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions ( p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and −1.72% ( p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC ( p = 0.022) and WMF change ( p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes. Conclusion: Early brain volume loss during natalizumab therapy is mainly due to WMF volume loss and it is related to the inflammatory activity present at the onset of therapy. We found that the pseudoatrophy effect is mostly due to white matter volume changes.

scholarly journals The aging human brain: A causal analysis of the effect of sex and age on brain volume

2020 ◽  
Author(s):  
Jaime Gómez-Ramírez ◽  
Miguel A. Fernández-Blázquez ◽  
Javier González-Rosa
Keyword(s):  
Old Age ◽  
Brain Atrophy ◽  
Healthy Subjects ◽  
Brain Volume ◽  
Causal Analysis ◽  
Intracranial Volume ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Mri Scans ◽  
The Brain

AbstractThe goal of this work is to study how brain volume loss at old age is affected by factors such as age, APOE gene, sex, and school level. The study of brain volume loss at old age relative to young age requires at least in principle two MRI scans performed at both young and old age. There is, however, a way to address the problem by having only one MRI scan at old age. We compute the total brain loss of elderly subjects as the ratio between the estimated brain volume and the estimated total intracranial volume. Magnetic resonance imaging (MRI) scans of 890 healthy subjects aged 69 to 85 were assessed. The causal analysis of factors affecting brain atrophy was performed using Probabilistic Bayesian Modeling and the mathematics of Causal Inference. We find that healthy subjects get into their seventies with an average brain volume loss of 30% from their maximum brain volume at a young age. Both age and sex are causally related to brain atrophy, with women getting to elderly age with 1% larger brain volume relative to intracranial volume than men. How the brain ages and what are the reasons for sex differences in adult lifespan are causal questions that need to be addressed with causal inference and empirical data. The graphical causal modeling presented here can be instrumental in understanding a puzzling scientific inquiry-the biological age of the brain.

Pathological cut-offs of global and regional brain volume loss in multiple sclerosis

2017 ◽  
Vol 25 (4) ◽  
pp. 541-553 ◽  
Author(s):  
Tomas Uher ◽  
Manuela Vaneckova ◽  
Jan Krasensky ◽  
Lukas Sobisek ◽  
Michaela Tyblova ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Grey Matter ◽  
Brain Volume ◽  
Healthy Controls ◽  
Volume Loss ◽  
Whole Brain ◽  
Brain Volume Loss ◽  
Regional Brain ◽  
Mri Scans ◽  
Regional Brain Volume

Background: Volumetric MRI surrogate markers of disease progression are lacking. Objective: To establish cut-off values of brain volume loss able to discriminate between healthy controls and MS patients. Methods: In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS (SPMS) patients and 58 healthy controls were included in this longitudinal study. A total of 11,438 MRI scans performed on the same MRI scanner with the same protocol were analysed. Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated. We investigated cut-offs able to discriminate between healthy controls and MS patients. Results: At a predefined specificity of 90%, the annualised percentage change cut-off of corpus callosum volume (−0.57%) was able to distinguish between healthy controls and patients with the highest sensitivity (51% in CIS, 48% in RRMS and 42% in SPMS patients). Lower sensitivities (22%−49%) were found for cut-offs of whole brain, grey matter and thalamic volume loss. Among CIS and RRMS patients, cut-offs were associated with greater accumulation of disability. Conclusion: We identified cut-offs of annualised global and regional brain volume loss rates able to discriminate between healthy controls and MS patients.

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