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 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 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 Age-specific adult rat brain MRI templates and tissue probability maps

2021 ◽  
Author(s):  
Eilidh MacNicol ◽  
Paul Wright ◽  
Eugene Kim ◽  
Irene Brusini ◽  
Oscar Esteban ◽  
...  
Keyword(s):  
White Matter ◽  
Rat Brain ◽  
Grey Matter ◽  
Brain Volume ◽  
Grey Matter Volume ◽  
Total Brain Volume ◽  
Adult Rat ◽  
Matter Volume ◽  
Probability Maps ◽  
Total Brain

Age-specific resources mitigate biases in human MRI processing arising from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue’s relative contribution to total brain volume would change with age in the adult rat. However, the currently available tissue probability maps, which provide a priori information for tissue volume estimation, provide inaccurate grey matter probabilities in subcortical structures, particularly the thalamus. Consequently, age-specific templates and tissue probability maps were generated from a longitudinal study that scanned a cohort of rats at 3, 5, 11, and 17 months old. Mixed-effects models assessed the effect of age on brain, grey matter, white matter, and CSF volumes, and the relative tissue proportions. Grey and white matter volume increased with age, and the tissue proportions relative to total brain volume varied throughout adulthood. Furthermore, we present evidence of a systematic underestimation of thalamic grey matter volume with existing resources, which is mitigated with the use of age-specific tissue probability maps since the derived estimates better matched histological evidence. To reduce age-related biases in image pre-processing, a set of rat brain resources from across the adult lifespan is consequently released to expand the preclinical MRI community’s fundamental resources.

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 White Matter is Increased in the Brains of Adults With Neurofibromatosis 1

2021 ◽  
Author(s):  
Su Wang ◽  
Jan M. Friedman ◽  
Per Suppa ◽  
Ralph Buchert ◽  
Victor-Felix Mautner
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Brain Volume ◽  
Neurofibromatosis 1 ◽  
Brain Morphology ◽  
White Matter Volume ◽  
Total Brain Volume ◽  
Brain Volumes ◽  
Matter Volume ◽  
Total Brain

Abstract Background: Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Several studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, though findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1.Methods: We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results:Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1.Conclusion:Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

scholarly journals Exploring the distribution of grey and white matter brain volumes in extremely preterm children, using magnetic resonance imaging at term age and at 10 years of age

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259717
Author(s):  
Hedvig Kvanta ◽  
Jenny Bolk ◽  
Marika Strindberg ◽  
Carmen Jiménez-Espinoza ◽  
Lina Broström ◽  
...  
Keyword(s):  
White Matter ◽  
Confidence Interval ◽  
Grey Matter ◽  
Mean Difference ◽  
Grey Matter Volume ◽  
White Matter Volume ◽  
Brain Volumes ◽  
Preterm Children ◽  
Matter Volume ◽  
Extremely Preterm

Objectives To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. Study design Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. Results At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of −8.4 to −1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of −10.9 to −1.0 (p = 0.010). Conclusion Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls.

scholarly journals White Matter is Increased in the Brains of Adults with Neurofibromatosis 1

2021 ◽  
Author(s):  
Su Wang ◽  
Jan M Friedman ◽  
Per Suppa ◽  
Ralph Buchert ◽  
Victor-Felix Mautner
Keyword(s):  
White Matter ◽  
Brain Volume ◽  
Psychometric Testing ◽  
Neurofibromatosis 1 ◽  
Clinical Severity ◽  
Grey Matter Volume ◽  
Total Brain Volume ◽  
Brain Volumes ◽  
Matter Volume ◽  
Total Brain

Objective: To characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with neurofibromatosis 1 (NF1). Methods: We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results: Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1. Interpretations: Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

scholarly journals Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

2021 ◽  
pp. jnnp-2020-323541
Author(s):  
Jessica L Panman ◽  
Vikram Venkatraghavan ◽  
Emma L van der Ende ◽  
Rebecca M E Steketee ◽  
Lize C Jiskoot ◽  
...  
Keyword(s):  
White Matter ◽  
Frontotemporal Dementia ◽  
Disease Severity ◽  
Grey Matter ◽  
Clinical Stage ◽  
Data Driven ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Mutation Carriers ◽  
Individual Disease

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

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