Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure

2019 ◽  
Vol 25 (7) ◽  
pp. 927-936 ◽  
Author(s):  
Frederik Bartels ◽  
Katharina Nobis ◽  
Graham Cooper ◽  
Eva Wendel ◽  
Robert Cleaveland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Clinical Presentation ◽  
Brain Volume ◽  
Volume Loss ◽  
Brain Growth ◽  
Whole Brain ◽  
Brain Volumes ◽  
Brain Volume Loss

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

scholarly journals NIMG-55. A QUANTITATIVE ANALYSIS OF BRAIN VOLUME DYNAMICS IN PCNSL PATIENTS TREATED WITH HIGH-DOSE METHOTREXATE-BASED THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii160-ii160
Author(s):  
Ananyaa Sivakumar ◽  
David Kamson ◽  
Fayez Estephan ◽  
Sebastian Lambrecht ◽  
Omar Dzaye ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Volume ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Volume Loss ◽  
Brain Volumes ◽  
Brain Volume Loss ◽  
Dose Methotrexate

Abstract BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX. SUBJECTS/METHODS We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to cerebral volume (nWML). RESULTS The average rate of cerebral volume change was -2.1±1.9%/year. Half of patients showed marked cerebral volume loss in the first year (-5.6±1.4% vs. -2.0±1.4%; n=10; p=0.003) with the most prominent change occurring within 6-months of treatment initiation (-4.2±1.7% vs. -0.5±1.6; n=12; p=0.004). Cerebral volume loss reached a plateau after the 1-year mark in both groups (0.3±0.8%/year vs. 1.4±3.3%/year; n=8; p=0.4). Patients younger than 61 years exhibited markedly higher rates of cerebral volume loss (-6.2±1.1%/year vs. 2.4±1.5%/year p=0.003), which was corroborated by strong inverse correlation between age and cerebral volume loss (Pearson’s r=-0.82, p=0.004). Neither the cerebellar volume, nor the nWML load correlated with age. CONCLUSION In the present cohort, brain volume loss was approximately four-fold higher than what is described in the healthy aging. Younger patients treated with HD-MTX exhibited more severe cerebral volume loss, which may be due to higher initial brain volume reserve. Detailed analyses of a larger sample are underway.

scholarly journals The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis

2017 ◽  
Vol 25 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Alexander Pichler ◽  
Michael Khalil ◽  
Christian Langkammer ◽  
Daniela Pinter ◽  
Stefan Ropele ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Brain Volume ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Lesion Load ◽  
Brain Volumes ◽  
Brain Volume Loss ◽  
The Impact

Background: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. Methods: We identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. Results: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29–54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6 cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. Conclusion: VRF are associated with lower brain volume already in early MS but do not lead to increased brain volume loss during 3.5 years of follow-up.

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 Natalizumab Induces Changes of Cerebrospinal Fluid Measures in Multiple Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2230
Author(s):  
Ranjani Ganapathy Subramanian ◽  
Dana Horakova ◽  
Manuela Vaneckova ◽  
Balazs Lorincz ◽  
Jan Krasensky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Mixed Models ◽  
Brain Volume ◽  
Oligoclonal Bands ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Igg Index ◽  
Natalizumab Treatment

Background: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. Aim: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. Methods: Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models. Results: Natalizumab induced a decrease in CSF leukocytes (p < 1 × 10−15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10−15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was −0.50% (IQR = −0.96, −0.16) and was predicted by the baseline IgM index (B = −0.37; p = 0.003). Conclusions: Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment.

scholarly journals Trajectories of brain volume change over 13 years in chronic schizophrenia

2019 ◽  
Author(s):  
Claudia Barth ◽  
Kjetil N. Jørgensen ◽  
Laura A. Wortinger ◽  
Stener Nerland ◽  
Erik G. Jönsson ◽  
...  
Keyword(s):  
Volume Change ◽  
Brain Volume ◽  
Chronic Schizophrenia ◽  
Volume Loss ◽  
Total Brain Volume ◽  
Brain Volumes ◽  
Matter Volume ◽  
Brain Volume Loss ◽  
Total Brain

AbstractImportanceSchizophrenia is a leading cause of disability worldwide, with an illness course that putatively deteriorates over time. Whether the notion of a progressive brain disease holds in its chronic stage is debated.ObjectiveTo investigate brain volume change and the impact of iatrogenic factors in chronic schizophrenia patients (duration of illness at baseline 16.17 ± 8.14 years) and controls over 13 years.DesignParticipants were recruited as part of the Human Brain Informatics study. Data acquisition took place between 1999 and 2018, including baseline, 5- and 13-years follow-up.SettingNaturalistic longitudinal case-control study.ParticipantsThe sample consisted of 143 participants, of whom 64 were patients with chronic schizophrenia (20% female, mean age at baseline 40.5 ± 7.7 years) and 79 healthy controls (37% female, mean age at baseline 42.8 ± 8.4 years). T1-weighted structural imaging and information about medication use were obtained at each time point.ExposureAntipsychotic medication and other prescribed drugs.Main Outcome(s) and Measure(s)Individual total and tissue-specific brain volumes, as well as two-time point percentage brain and ventricle volume change.ResultsPatients had lower total brain volume at baseline. Yet, trajectories in total brain volume and gray matter volume loss as well as ventricular enlargement did not differ relative to controls. White matter volume was similar between groups at baseline and 5-year but diverged between 5-year and 13-year follow-up, with accelerated loss in patients. While antipsychotic exposure did not show an association with brain volume loss over time, higher medication load was associated with lower brain volume across time points. Patients on second-generation antipsychotics alone showed lowest total brain volume, only after accounting for add-on drug use.Conclusion and RelevanceWe found limited evidence for progressive brain volume loss in chronic schizophrenia, beyond normal aging. Stable differences in patient brain volumes relative to controls may primarily occur during the first years of illness. All prescribed drugs need to be considered when examining the impact of antipsychotic medication on brain structure.Key PointsQuestionIs chronic schizophrenia associated with progressive brain volume loss beyond normal aging?FindingsWhile brain volume was lower at baseline, patient trajectories of brain volume change over a 13-year follow-up period differed little from healthy individuals. Small effects indicated greater white matter volume loss in patients during the late phase of follow-up. Stable differences in patient brain volumes seem explicable by antipsychotic medication class and respective add-on drugs.MeaningWe found limited evidence of progressive brain volume loss, beyond normal aging, in chronic schizophrenia over 13 years.

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

scholarly journals Learning ability correlates with brain atrophy and disability progression in RRMS

2018 ◽  
Vol 90 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria Pia Sormani ◽  
Nicola De Stefano ◽  
Gavin Giovannoni ◽  
Dawn Langdon ◽  
Daniela Piani-Meier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Practice Effect ◽  
Wilcoxon Test ◽  
Learning Ability ◽  
Lesion Volume ◽  
Volume Loss ◽  
Disability Progression ◽  
Brain Volume Loss ◽  
Quartile Group

ObjectiveTo assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis.MethodsWe compared screening (day −14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years.ResultsThe mean PASAT score at screening was 45.38, increasing on average by 3.18 from day −14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates.ConclusionsShort-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

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