scholarly journals Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

2020 ◽  
Vol 8 (1) ◽  
pp. e906
Author(s):  
Ruth Schneider ◽  
Barbara Bellenberg ◽  
Barbara Gisevius ◽  
Sarah Hirschberg ◽  
Roman Sankowski ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gray Matter ◽  
Disease Duration ◽  
Cell Types ◽  
Volume Loss ◽  
Neurofilament Light Chain ◽  
Spinal Cord Atrophy ◽  
Neurofilament Light ◽  
Brain And Spinal Cord ◽  
Spinal Cord Volume

ObjectiveTo investigate cross-sectional associations of CSF levels of neurofilament light chain (NfL) and of the newly emerging marker chitinase 3–like protein 1 (CHI3L1) with brain and spinal cord atrophy, which are established MRI markers of disease activity in MS, to study CHI3L1 and NfL in relapsing (RMS) and progressive MS (PMS), and to assess the expression of CHI3L1 in different cell types.MethodsIn a single-center study, 131 patients with MS (42 RMS and 89 PMS) were assessed for NfL and CHI3L1 concentrations in CSF, MRI-based spinal cord and brain volumetry, MS subtype, age, disease duration, and disability. We included 42 matched healthy controls receiving MRI. CHI3L1 expression of human brain cell types was examined in 2 published single-cell RNA sequencing data sets.ResultsCHI3L1 was associated with spinal cord volume (B = −1.07, 95% CI −2.04 to −0.11, p = 0.029) but not with brain volumes. NfL was associated with brain gray matter (B = −7.3, 95% CI −12.0 to −2.7, p = 0.003) but not with spinal cord volume. CHI3L1 was suitable to differentiate between progressive or relapsing MS (p = 0.015, OR 1.0103, CI for OR 1.002–1.0187), and its gene expression was found in MS-associated microglia and macrophages and in astrocytes of MS brains.ConclusionsNfL and CHI3L1 in CSF were differentially related to brain and spinal cord atrophy. CSF CHI3L1 was associated with spinal cord volume loss and was less affected than NfL by disease duration and age, whereas CSF NfL was associated with brain gray matter atrophy. CSF NfL and CHI3L1 measurement provides complementary information regarding brain and spinal cord volumes.Classification of evidenceThis study provides Class II evidence that CSF CHI3L1 is associated with spinal cord volume loss and that CSF NfL is associated with gray matter atrophy.

scholarly journals Cross sign T2 hyperintensities in atrophic spinal cord of hereditary spastic paraplegia type 5

2020 ◽  
Author(s):  
Ning Wang ◽  
Ying Liu ◽  
Zhixian Ye ◽  
Yi Lin ◽  
Xiang Lin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Disease Severity ◽  
Disease Duration ◽  
Quantitative Mri ◽  
Strong Positive Correlation ◽  
Diagnostic Biomarker ◽  
Spinal Cord Atrophy ◽  
Neurofilament Light ◽  
Positive Correlation ◽  
Mri Features

Abstract Background: Hereditary spastic paraplegias type 5 (SPG5) is an inherited neurodegenerative disease with 27-hydroxycholesterol abnormal accumulation. Imaging and pathologic manifestations remain poorly understood due to the rare incidence. This study reveals the MRI features of SPG5, and aims to investigate a promising imaging diagnostic biomarker for SPG5.Methods: We prospectively recruited SPG5 patients and matched healthy controls from Neurogenetic Diseases Centers of Fujian province in China, clinical and MRI data of whom were collected. Abnormalities of spinal cord and brain were characterized and quantified by conventional and quantitative MRI. Comparisons were conducted between MRI and cerebrospinal fluid (CSF) bioindicators.Results: Seventeen SPG5 patients were enrolled (11 men, 6 women; age range, 13–49 years; median disease duration, 14 years). For the first time, T2 hyperintensities with “+” form (cross sign) in atrophic spinal cord was found among all SPG5 patients. To grade severity of this sign, we set up a scoring scale (cross-sign scores) in cervical spinal cords. Unexpectedly, total cross-sign scores showed a strong positive correlation with disability scale scores (r = 0.687, P = 0.002) and disease duration (r = 0.520, P = 0.032). Although total spinal cord area was reduced (cervical levels: 12-27%; thoracic levels 41-60%), no correlation was found between spinal cord atrophy and disease severity. In CSF, a positive correlation was identified between 27-hydroxycholesterol and neurofilament light (r = 0.468, P = 0.049), although 27-hydroxycholesterol and neurofilament light were unrelated to disease severity.Conclusion: Cross sign of spinal cord was established as a potentially diagnostic biomarker linked to SPG5 that can guide genetic testing and interpret genetic results. Moreover, cross-sign scoring scale is more sensitive than spinal cord area and CSF markers for monitoring SPG5 progress in our research.

scholarly journals Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

scholarly journals Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis

1999 ◽  
Vol 66 (3) ◽  
pp. 323-330 ◽  
Author(s):  
C. Liu ◽  
S. Edwards ◽  
Q. Gong ◽  
N. Roberts ◽  
L. D Blumhardt
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Three Dimensional ◽  
Spinal Cord Atrophy ◽  
Brain And Spinal Cord

scholarly journals Magnetic resonance imaging correlates of physical disability in relapse onset multiple sclerosis of long disease duration

2013 ◽  
Vol 20 (1) ◽  
pp. 72-80 ◽  
Author(s):  
H Kearney ◽  
MA Rocca ◽  
P Valsasina ◽  
L Balk ◽  
J Sastre-Garriga ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Physical Disability ◽  
Disease Duration ◽  
Resonance Imaging ◽  
Lesion Load ◽  
Brain And Spinal Cord

Background: Understanding long-term disability in multiple sclerosis (MS) is a key goal of research; it is relevant to how we monitor and treat the disease. Objectives: The Magnetic Imaging in MS (MAGNIMS) collaborative group sought to determine the relationship of brain lesion load, and brain and spinal cord atrophy, with physical disability in patients with long-established MS. Methods: Patients had a magnetic resonance imaging (MRI) scan of their brain and spinal cord, from which we determined brain grey (GMF) and white matter (WMF) fractional volumes, upper cervical spinal cord cross-sectional area (UCCA) and brain T2-lesion volume (T2LV). We assessed patient disability using the Expanded Disability Status Scale (EDSS). We analysed associations between EDSS and MRI measures, using two regression models (dividing cohort by EDSS into two and four sub-groups). Results: In the binary model, UCCA ( p < 0.01) and T2LV ( p = 0.02) were independently associated with the requirement of a walking aid. In the four-category model UCCA ( p < 0.01), T2LV ( p = 0.02) and GMF ( p = 0.04) were independently associated with disability. Conclusions: Long-term physical disability was independently linked with atrophy of the spinal cord and brain T2 lesion load, and less consistently, with brain grey matter atrophy. Combinations of spinal cord and brain MRI measures may be required to capture clinically-relevant information in people with MS of long disease duration.

scholarly journals A Rare Case of Third Ventricular Glioblastoma

2021 ◽  
Author(s):  
Asmira Gacic ◽  
Hakija Beculic ◽  
Rasim Skomorac ◽  
Alma Efendic
Keyword(s):  
Spinal Cord ◽  
Glioblastoma Multiforme ◽  
Blood Vessels ◽  
Rare Case ◽  
Third Ventricle ◽  
Cell Types ◽  
The Third ◽  
Different Cell Types ◽  
Brain And Spinal Cord ◽  
The Brain

Glioblastoma, also known as glioblastoma multiforme, is an aggressive type of cancer that is made up of abnormal astrocytic cells, but also contain a mixture of different cell types (including blood vessels) and areas of necrosis. It is often seen in the brain and spinal cord, but glioblastomas are rarely found in the third ventricle. In this case, it was diagnosed in a 22-year-old male patient and we intended to draw

scholarly journals BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer’s disease brain

Brain ◽  
2020 ◽  
Author(s):  
Cyrille Sur ◽  
James Kost ◽  
David Scott ◽  
Katarzyna Adamczuk ◽  
Nick C Fox ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Volume ◽  
Brain Regions ◽  
Volume Loss ◽  
Volumetric Mri ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Mri Changes

Abstract In the phase 3 EPOCH trial (Clinicaltrials.gov; NCT01739348), treatment with the BACE inhibitor verubecestat failed to improve cognition in patients with mild-to-moderate Alzheimer’s disease, but was associated with reduced hippocampal volume after 78 weeks as assessed by MRI. The aims of the present exploratory analyses were to: (i) characterize the effect of verubecestat on brain volume by evaluating the time course of volumetric MRI changes for a variety of brain regions; and (ii) understand the mechanism through which verubecestat might cause hippocampal (and other brain region) volume loss by assessing its relationship to measures of amyloid, neurodegeneration, and cognition. Participants were aged 55–85 years with probable Alzheimer’s disease dementia and a Mini Mental State Examination score ≥15 and ≤26. MRIs were obtained at baseline and at Weeks 13, 26, 52 and 78 of treatment. MRIs were segmented using Freesurfer and analysed using a tensor-based morphometry method. PET amyloid data were obtained with 18F-flutemetamol (Vizamyl®) at baseline and Week 78. Standardized uptake value ratios were generated with subcortical white matter as a reference region. Neurofilament light chain in the CSF was assessed as a biomarker of neurodegeneration. Compared with placebo, verubecestat showed increased MRI brain volume loss at Week 13 with no evidence of additional loss through Week 78. The verubecestat-related volumetric MRI loss occurred predominantly in amyloid-rich brain regions. Correlations between amyloid burden at baseline and verubecestat-related volumetric MRI reductions were not significant (r = 0.05 to 0.26, P-values &gt; 0.27). There were no significant differences between verubecestat and placebo in changes from baseline in CSF levels of neurofilament light chain at Week 78 (increases of 7.2 and 14.6 pg/ml for verubecestat versus 19.7 pg/ml for placebo, P-values ≥ 0.1). There was a moderate correlation between volumetric MRI changes and cognitive decline in all groups including placebo at Week 78 (e.g. r = −0.45 to −0.55, P &lt; 0.001 for whole brain), but the correlations were smaller at Week 13 and significant only for the verubecestat groups (e.g. r = −0.15 and −0.11, P &lt; 0.04 for whole brain). Our results suggest that the verubecestat-associated MRI brain volume loss is not due to generalized, progressive neurodegeneration, but may be mediated by specific effects on BACE-related amyloid processes.

scholarly journals Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Claudia Chien ◽  
Frederike Cosima Oertel ◽  
Nadja Siebert ◽  
Hanna Zimmermann ◽  
Susanna Asseyer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Graph Theory ◽  
Disease Duration ◽  
Expanded Disability Status Scale ◽  
Spinal Cord Atrophy ◽  
Disability Status ◽  
The Central Nervous System ◽  
Multimodal Network

Abstract Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.

Pathogenesis of Brain and Spinal Cord Atrophy in Multiple Sclerosis

2004 ◽  
Vol 14 (3) ◽  
pp. 5-10 ◽  
Author(s):  
Alireza Minagar ◽  
Eduardo Gonzalez Toledo ◽  
J. Steven Alexander ◽  
Roger E. Kelley
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Spinal Cord Atrophy ◽  
Brain And Spinal Cord
Sign in / Sign up

Export Citation Format

Share Document