scholarly journals Patterns of brain neurodegeneration in early-stage relapsing-remitting multiple sclerosis

2021 ◽  
Author(s):  
Rozanna Meijboom ◽  
Elizabeth N. York ◽  
Agniete Kampaite ◽  
Mathew A. Harris ◽  
Nicole White ◽  
...  
Keyword(s):  
Early Stage ◽  
Occipital Lobe ◽  
Structural Mri ◽  
Longitudinal Change ◽  
Subcortical Structures ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Cortical Regions ◽  
The Brain ◽  
Over Time

Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in early-stage RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N=354) underwent 3T structural MRI at diagnosis and 1-year follow-up, as part of the Scottish multicentre 'FutureMS' study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter [GM] only), to establish patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the cerebrum, cerebellum and brainstem. Volumetric analyses showed a decrease over time (q<0.05) in bilateral cortical GM and NAWM, multiple subcortical structures, cerebellar GM and the brainstem. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 28 regions and 17/28; temporal: 18/18 and 15/18; parietal: 14/14 and 11/14; occipital: 7/8 and 8/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal lobe and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread neurodegeneration was observed in early-stage RRMS; particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions. Volumetric and VBM results emphasise different as well as overlapping patterns of longitudinal change, and provide potential response markers for existing therapies and trials of neuroprotective agents.

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

Oxidative damage to DNA in plaques of MS brains

1998 ◽  
Vol 4 (5) ◽  
pp. 413-418 ◽  
Author(s):  
Olga Vladimirova ◽  
John O'Connor ◽  
Alan Cahill ◽  
Hansjuerg Alder ◽  
Catalin Butunoi ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Degenerative Process ◽  
Oxidative Markers ◽  
Normal Appearing White Matter ◽  
The Central Nervous System ◽  
Cortical Regions ◽  
Tissue Alterations ◽  
Oxidative Damage To Dna ◽  
The Brain ◽  
Cerebellar Symptoms

A major cause of clinical disability in multiple sclerosis (MS) is related to a degenerative process in the central nervous system (CNS) which ultimately develops from a potentially reversible inflammation and demyelination. The mechanism of this degenerative process within MS lesions is not completely understood. We hypothesize that oxidative damage to DNA secondary to inflammation may contribute to irreversible tissue alterations in a plaque. To test this assumption, we determined the level of a DNA oxidative marker, 8-hydroxy-deoxy-guanosine (8-OH-dG) in the normal appearing white matter (NAWM), plaque and cortical regions of cerebella from MS patients who suffered from severe cerebellar symptoms during the course of the disease, and in NAWM and cortical regions of cerebella from non-neurological controls. We found a significant increase in DNA oxidation within plaques compared to NAWM specimens in MS cerebella. A tendency for increase of oxidative markers in normal appearing cortical tissues located in the proximity of MS plaques was also observed when compared to those in control cortical specimens. Oxidative damage to DNA in MS lesions, and in neuron rich areas located in the proximity of these lesions is likely related to the release of reactive oxygen species (ROS) and nitric oxide (NO) during inflammation in the brain. This biochemical impairment of DNA and of other macromolecules may contribute to the development of severe clinical disability through the induction of degenerative changes within and outside of plaques in MS brains.

scholarly journals Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

2013 ◽  
Vol 20 (8) ◽  
pp. 1066-1073 ◽  
Author(s):  
Silvia Mangia ◽  
Adam F Carpenter ◽  
Andy E Tyan ◽  
Lynn E Eberly ◽  
Michael Garwood ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Magnetic Resonance Images ◽  
Relaxation Methods ◽  
Normal Appearing White Matter ◽  
Relaxation Parameters ◽  
Relapsing Remitting ◽  
Cortical Gray Matter ◽  
The Brain

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls ( p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups ( p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

scholarly journals Analyzing Microarray Data of Alzheimer's Using Cluster Analysis to Identify the Biomarker Genes

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Satya vani Guttula ◽  
Apparao Allam ◽  
R. Sridhar Gumpeny
Keyword(s):  
Cluster Analysis ◽  
Microarray Data ◽  
Senile Plaques ◽  
Dynamic Change ◽  
Hierarchical Cluster ◽  
Gene Expression Omnibus ◽  
The Other ◽  
Cortical Regions ◽  
The Brain ◽  
Over Time

Alzheimer is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. The experimental data is taken from Gene Expression Omnibus. A hierarchical Cluster analysis and TreeView were performed to group genes on the basis of the expression pattern. The dynamic change of expression over time and diverse patterns of expression support the concept of a complex local milieu. TreeView allows the organized data to be visualized. List of 24 genes were obtained which showed high expression levels. Three genes, SORL1, APP, and APOE, are suspected to cause Alzheimer’s whereas the other 21 genes are related to other diseases but may also be found to be associated with Alzheimer’s, and these are TMEM59, CCT4, IGF2R, SFPQ, PRDX3, RNF14, IDS, SSBP1, SYNE2, TXNL4A, STXBP3, SMARCB1, ULK2, AGTPBP1, FABP7, CALB1, H2AFY, COPA, SAP18, ATIC and SYNCRIP.

scholarly journals T155. PROGRESSION OF NEUROANATOMICAL ABNORMALITIES AFTER FIRST-EPISODE OF PSYCHOSIS: A 3-YEAR LONGITUDINAL STRUCTURAL MRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S289-S290
Author(s):  
Theophilus Akudjedu ◽  
Giulia Tronchin ◽  
Shane McInerney ◽  
Cathy Scanlon ◽  
Joanne Kenney ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Negative Symptoms ◽  
Psychotic Disorders ◽  
Structural Mri ◽  
Ventricular Volume ◽  
Imaging Biomarkers ◽  
First Episode ◽  
Subcortical Structures ◽  
The Right ◽  
Over Time

Abstract Background The extent and location of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated the progressive profile of ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls (HC), and whether any progressive neuroanatomical changes were related to clinical factors. Methods High resolution 1.5T T1-weighted MR images were obtained from 28 FEP patients and 28 HCs shortly after presentation to services and again after 3-year follow-up. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses were used to compare progressive changes in relation to subcortical structures/ventricles and thickness across the cortical mantle, respectively, between groups. Partial correlations were used to determine associations of progressive neuroanatomical change with clinical and functional characteristics. Results Compared with controls, patients displayed progressively reduced volume of the caudate [F(1,51)=5.86, p=0.02, Hedges’ g=0.66], putamen [F(1,51)=6.06, p=0.02, g=0.67] and thalamus [F(1,51)=6.99, p=0.01, g=0.72], with a trend for increased lateral ventricular volume [F(1,51)=3.37, p=0.07, g=0.50] more prominent on the right [F(1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F(1,52)=5.11, p=0.028)] at a mean difference of 0.844% [95% CI (0.095, 1.593)] in the left lateral orbitofrontal region (LLOFR) over the 3-year period. In FEP individuals, greater reduction in putamen volume over time was associated with low cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global assessment of functioning (r=-0.41, p=0.04). Discussion Our results demonstrate existence of localised progressive structural disturbance in the subnetwork of the cortico-striato-thalamo-cortical circuitry after the onset of psychosis. Furthermore, increasing ventricular volume is a neuroanatomical marker of poorer clinical and functional outcome. These findings lend weight to the evidence of early progressive brain changes in psychotic disorders and thus, this knowledge could potentially contribute to the identification of imaging biomarkers for timely intervention.

scholarly journals A tractometry investigation of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis

2021 ◽  
Author(s):  
Danka Jandric ◽  
Geoff JM Parker ◽  
Hamied Haroon ◽  
Valentina Tomassini ◽  
Nils Muhlert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Function ◽  
White Matter ◽  
Cognitive Dysfunction ◽  
Network Structure ◽  
Test Performance ◽  
Cognitive Domains ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
The Brain

Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts share a similar network structure it would be expected that tracts within a network are similarly affected by MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in diffusion metrics across white matter (WM) tracts. We investigated whether separate networks, based on normal variation or pathology, appear, and how this relates to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract components to predict test performance across cognitive domains. We found that a single component which captured pathology across all tracts explained the most variance and that there was little evidence for separate, smaller network patterns of pathology. WM tract components were weak, but significant, predictors of cognitive function in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS.

Abnormal cervical cord function contributes to fatigue in multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1552-1559 ◽  
Author(s):  
MA Rocca ◽  
M Absinta ◽  
P Valsasina ◽  
M Copetti ◽  
D Caputo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Structural Mri ◽  
Group Differences ◽  
Cervical Cord ◽  
Focal Lesions ◽  
Cross Sectional ◽  
Normal Appearing White Matter ◽  
The Right ◽  
The Brain

Background/Objective We aimed to investigate whether cervical cord damage and dysfunction is associated with the presence and severity of fatigue in multiple sclerosis (MS) using a multiparametric magnetic resonance (MR) approach. Methods: Cervical cord functional magnetic resonance imaging (fMRI) during a tactile stimulation of the right hand, and structural brain and cord MRI were acquired from 20 controls, 15 MS patients without fatigue (NF) and 20 MS patients with fatigue (F). Between-group differences in the extent of focal lesions and diffusivity abnormalities in the brain and cord, cord-normalized cross-sectional area (CSAn) and fMRI activity were assessed. Results: All structural MRI measures differed significantly among groups, except for cord lesion number and CSAn. Compared with controls, NF-MS patients experienced higher cord recruitment ( p=0.04). Compared with F-MS, NF-MS patients had a lower brain normal-appearing white matter average fractional anisotropy ( p=0.001) and increased cord recruitment ( p=0.02). In patients with MS, the extent of cord recruitment was correlated with the severity of fatigue ( r=-0.34, p=0.04). Compared with the other two groups, F-MS patients had a more diffuse recruitment of cord quadrants on the axial and longitudinal planes. Conclusions: Abnormalities of function, but not of structure, of the cervical cord are likely to contribute to the pathogenesis of fatigue in MS.

scholarly journals A whole-brain connectivity map of mouse insular cortex

2020 ◽  
Author(s):  
Daniel A. Gehrlach ◽  
Thomas N. Gaitanos ◽  
Alexandra S. Klein ◽  
Caroline Weiand ◽  
Alexandru A. Hennrich ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Insular Cortex ◽  
Structural Basis ◽  
Subcortical Structures ◽  
Whole Brain ◽  
Brain Functions ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
The Brain

AbstractThe insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly reciprocal, the IC connectivity with subcortical structures was often unidirectional, revealing prominent top-down and bottom-up pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.

scholarly journals Five years functional connectivity reorganization without clinical or cognitive decline in MS

2020 ◽  
Author(s):  
Einar August Høgestøl ◽  
Samuele Ghezzo ◽  
Gro Owren Nygaard ◽  
Thomas Espeseth ◽  
Piotr Sowa ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Atrophy ◽  
Structural Mri ◽  
Resting State Fmri ◽  
Network Modelling ◽  
Brain Connectome ◽  
Relapsing Remitting ◽  
Structural Brain Damage ◽  
Time Changes ◽  
Over Time

ABSTRACTObjective1) To assess fMRI-based functional connectivity (FC) anomalies in early multiple sclerosis (MS), 2) To determine the relation between FC changes and structural brain damage due to disease progression 3) To study the association between FC changes and cognitive and physical disability.MethodsStructural MRI and resting-state fMRI were acquired from 76 early relapsing-remitting MS patients at baseline (average disease duration 71.7 months ± 63) and after five years. Ninety-four healthy controls (HCs) matched for age and sex were included at baseline. Independent component analysis (ICA) and network modelling were used to measure FC. FC variation was related to expanded disability status scale and neuropsychological outcomes. Brain and lesion volumes were quantified using standard methods. We used the 25 independent components obtained from ICA to estimate the longitudinal stability of the brain connectome as a proxy for functional reorganization over time.ResultsThe MS subjects were clinically and cognitively stable. Compared to HCs, FC abnormalities were detected within networks and in single connections in patients with early MS at baseline. Over time, FC was relatively invariable, but changes in FC were associated with progression of brain atrophy (ρ = 0.39, p = .06). No significant relationship with clinical and cognitive measures or lesion load was detected.ConclusionPatients with MS showed evidence of altered FC in the early stages of the disease. Over time, changes in FC seem to be related to a progression of brain atrophy, which are known to precede changes in clinical and cognitive functioning.

scholarly journals A whole-brain connectivity map of mouse insular cortex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Daniel A Gehrlach ◽  
Caroline Weiand ◽  
Thomas N Gaitanos ◽  
Eunjae Cho ◽  
Alexandra S Klein ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Insular Cortex ◽  
Structural Basis ◽  
Subcortical Structures ◽  
Whole Brain ◽  
Brain Functions ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
The Brain

The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type-specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly bidirectional, the IC connectivity with subcortical structures was often unidirectional, revealing prominent cortical-to-subcortical or subcortical-to-cortical pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.

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