Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

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

Multiple Sclerosis Journal ◽

10.1177/1352458512473190 ◽

2013 ◽

Vol 19 (9) ◽

pp. 1175-1181 ◽

Cited By ~ 55

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.

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

10.21203/rs.3.rs-898452/v1 ◽

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.

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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 ◽

10.1371/journal.pone.0259717 ◽

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.

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Cerebral MR Morphometry and Neurodevelopmental Outcome in Children before Fontan Procedure at 2 Years of Age: White Matter Volume Is Smaller after Norwood Procedure

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0036-1571859 ◽

2016 ◽

Vol 64 (S 02) ◽

Author(s):

B. Reich ◽

W. Knirsch ◽

K. Mayer ◽

R. Tuura ◽

I. Scheer ◽

...

Keyword(s):

White Matter ◽

Fontan Procedure ◽

Neurodevelopmental Outcome ◽

Norwood Procedure ◽

White Matter Volume ◽

Matter Volume

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Reduced Relationship to Cortical White Matter Volume Revealed by Tractography-Based Segmentation of the Corpus Callosum in Young Children With Developmental Delay

American Journal of Psychiatry ◽

10.1176/ajp.2006.163.12.2157 ◽

2006 ◽

Vol 163 (12) ◽

pp. 2157-2163 ◽

Cited By ~ 13

Author(s):

Carissa Cascio ◽

Martin Styner ◽

Rachel G. Smith ◽

Michele D. Poe ◽

Guido Gerig ◽

...

Keyword(s):

White Matter ◽

Young Children ◽

Corpus Callosum ◽

Developmental Delay ◽

White Matter Volume ◽

Matter Volume

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Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2440 ◽

2011 ◽

Vol 96 (4) ◽

pp. 1129-1135 ◽

Cited By ~ 39

Author(s):

Ingrid Hansen-Pupp ◽

Holger Hövel ◽

Ann Hellström ◽

Lena Hellström-Westas ◽

Chatarina Löfqvist ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Preterm Infants ◽

Brain Volumes ◽

Very Preterm Infants ◽

Very Preterm ◽

Matter Volume ◽

Total Brain ◽

Igf I ◽

Igfbp 3

Abstract Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001–0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.

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