scholarly journals The neural basis of fatigue in multiple sclerosis

2018 ◽  
Vol 8 (6) ◽  
pp. 492-500 ◽  
Author(s):  
Ana Margarida Novo ◽  
Sonia Batista ◽  
Carolina Alves ◽  
Otília C. d’Almeida ◽  
Inês Brás Marques ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Internal Capsule ◽  
Cerebral Peduncle ◽  
Neural Basis ◽  
Focal Lesions ◽  
External Capsule ◽  
Impact Scale

BackgroundFatigue is a frequent disabling symptom in multiple sclerosis (MS), but its pathophysiology remains incompletely understood. This study aimed to explore the underlying neural basis of fatigue in patients with MS.MethodsWe enrolled 60 consecutive patients with MS and 60 healthy controls (HC) matched on age, sex, and education. Fatigue was assessed using the Portuguese version of the Modified Fatigue Impact Scale (MFIS). All participants underwent 3T brain MRI (conventional and diffusion tensor imaging [DTI] sequences). White matter (WM) focal lesions were identified and T1/T2 lesion volumes were computed. Tract-based spatial statistics were applied for voxel-wise analysis of DTI metrics fractional anisotropy and mean diffusivity (MD) on normal-appearing WM (NAWM). Using Freesurfer software, total and regional volumes of cortical and subcortical gray matter (GM) were calculated.ResultsCompared to HC, patients with MS scored significantly higher on MFIS (33.8 ± 19.7 vs 16.5 ± 15.1, p < 0.001). MFIS scores were not significantly correlated with T1/T2 lesion volumes, total GM volume, or any regional volume of cortical and subcortical GM. Significant correlations were found between global scores of MFIS and MD increase of the NAWM skeleton, including corona radiata, internal capsule, external capsule, corticospinal tract, cingulum, corpus callosum, fornix, superior longitudinal fasciculus, superior fronto-occipital fasciculus, sagittal stratum, posterior thalamic radiation, cerebral peduncle, and uncinate fasciculus.ConclusionsIn this study, fatigue was associated with widespread NAWM damage but not with lesion load or GM atrophy. Functional disconnection, caused by diffuse microstructural WM damage, might be the main neural basis of fatigue in MS.

Disconnection as a mechanism for social cognition impairment in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Sonia Batista ◽  
Carolina Alves ◽  
Otília C. d’Almeida ◽  
Ana Afonso ◽  
Ricardo Félix-Morais ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Social Cognition ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Uncinate Fasciculus ◽  
Neural Basis ◽  
Cognition Impairment

Objective:To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS).Methods:We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM.Results:Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus.Conclusions:These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

Signs of MRI affection of brain in сlassical Amyotrophic Lateral Sclerosis patients

2016 ◽  
Vol 7 (2) ◽  
pp. 69-78 ◽  
Author(s):  
Tima R Stuchevskaya ◽  
Dmitriy I Rudenko ◽  
Valery M Kazakov ◽  
Olga F Pozdnyakova ◽  
Alexandr V Pozdnyakov ◽  
...  
Keyword(s):  
Brain Mri ◽  
Disease Onset ◽  
Internal Capsule ◽  
Diagnostic Value ◽  
Cerebral Peduncle ◽  
Focal Lesions ◽  
Duration Of Symptoms ◽  
Posterior Limb ◽  
Cerebral Mri ◽  
Mri Changes

T2 hyperintensive focal lesions were found on brain MRI only in 41 patients (9.7 %) from the ALS group (n = 423). Female were 20 (48,8 %) and male - 21 (51,2 %), aged 31 to 78 years (middle age is 56 ± 4). Focal MRI lesions were found exclusively in projection of the intracranial section of the corticospinal tract. They were always bilateral and symmetrical and were located at one or two levels, most often in the posterior limb of internal capsule and in cerebral peduncle (85 % and 60 % correspondingly). They were less frequent in the radiate crown, semioval center or medulla. There was no reliable correlation between MRI changes and clinical type of ALS, age of disease onset, duration of symptoms and region of onset of muscle weakness and atrophy. Foci of hyperintensive MRI signal in the ALS did not change in terms of time and space, and did not accumulate contrast media with disease progression. This prevents from using routine T1 and T2 mode MRI for monitoring the course of the disease, its prognosis and treatment efficiency. We can recommend cerebral MRI for early diagnostics of ALS and also to rule out other diseases which may resemble ALS. However diagnostic value of 1.5 Tesla MRI is quite limited for diagnostics of classic ALS and its subtypes (PLS and PBP).

Fatigue in multiple sclerosis: The contribution of occult white matter damage

2016 ◽  
Vol 22 (13) ◽  
pp. 1676-1684 ◽  
Author(s):  
Alvino Bisecco ◽  
Giuseppina Caiazzo ◽  
Alessandro d’Ambrosio ◽  
Rosaria Sacco ◽  
Simona Bonavita ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Tensor ◽  
Cerebral Peduncle ◽  
Superior Longitudinal Fasciculus ◽  
Normal Appearing White Matter ◽  
External Capsule ◽  
Mri Protocol ◽  
Fatigue Severity ◽  
Magnetic Resonance Imaging Mri

Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.

scholarly journals Advanced Analysis of Diffusion Tensor Imaging Along With Machine Learning Provides New Sensitive Measures of Tissue Pathology and Intra-Lesion Activity in Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Olayinka Oladosu ◽  
Wei-Qiao Liu ◽  
Bruce G. Pike ◽  
Marcus Koch ◽  
Luanne M. Metz ◽  
...  
Keyword(s):  
Machine Learning ◽  
Multiple Sclerosis ◽  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Characteristic Curve ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
High Angular Resolution ◽  
Advanced Analysis ◽  
Single Shell

Tissue pathology in multiple sclerosis (MS) is highly complex, requiring multi-dimensional analysis. In this study, our goal was to test the feasibility of obtaining high angular resolution diffusion imaging (HARDI) metrics through single-shell modeling of diffusion tensor imaging (DTI) data, and investigate how advanced measures from single-shell HARDI and DTI tractography perform relative to classical DTI metrics in assessing MS pathology. We examined 52 relapsing-remitting MS patients who had 3T anatomical brain MRI and DTI. Single-shell HARDI modeling yielded 5 sub-voxel-based metrics, totalling 11 diffusion measures including 4 DTI and 2 tractography metrics. Based on machine learning of 3-dimensional regions of interest, we evaluated the importance of the measures through several tissue classification tasks. These included two within-subject comparisons: lesion versus normal appearing white matter (NAWM); and lesion core versus shell. Further, by stratifying patients as having high (above 75%ile) and low (below 25%ile) number of MS lesions, we also performed 2 classifications between subjects for lesions and NAWM respectively. Results showed that in lesion-NAWM analysis, HARDI orientation distribution function (ODF) energy, DTI fractional anisotropy (FA), and HARDI orientation dispersion index were the top three metrics, which together achieved 65.2% accuracy and 0.71 area under the receiver operating characteristic curve (AUROC). In core-shell analysis, DTI mean diffusivity (MD), radial diffusivity, and FA were the top three metrics, and MD dominated the classification, which achieved 59.3% accuracy and 0.59 AUROC alone. Between patients, FA was the leading feature in lesion comparisons, while ODF energy was the best in NAWM separation. Collectively, single-shell modeling of common diffusion data can provide robust orientation measures of lesion and NAWM pathology, and DTI metrics are most sensitive to intra-lesion abnormality. Combined analysis of both advanced and classical diffusion measures may be critical for improved understanding of MS pathology.

scholarly journals Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuang Ding ◽  
Yu Guo ◽  
Xiaoya Chen ◽  
Silin Du ◽  
Yongliang Han ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Blue Staining ◽  
Resonance Imaging ◽  
The Mean ◽  
Underlying Mechanisms

AbstractThe aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Abstract WP366: Quantitative Diffusion Tensor Tractography of the Corticospinal Tract as a Predictive Outcome Parameter in Patients With Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Bastian Volbers ◽  
Angelika Mennecke ◽  
Nicola Kästle ◽  
Hagen B Huttner ◽  
Stefan Schwab ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Corticospinal Tract ◽  
Diffusion Tensor ◽  
Clinical Status ◽  
Internal Capsule ◽  
Favorable Outcome ◽  
Outcome Variable ◽  
Cerebral Peduncle ◽  
Prognostic Impact ◽  
Posterior Limb

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease with poor outcome. Established predictive markers include initial hematoma size, clinical status, intraventricular bleeding and age. However, prognostic assessment is often difficult which additionally burdens patients and caregivers and complicates rehabilitation. Functional outcome especially relies on motor function which is correlated with the integrity of the Corticospinal Tract (CST). Diffusion Tensor (DT) Tractography allows visualization of the CST. However, sufficient data about the prognostic impact of quantitative CST assessment is lacking. Methods: We prospectively enrolled patients with spontaneous supratentorial ICH admitted between 08/2012 und 08/2015. Informed consent and ethical approval was obtained. MRI scan was performed on day 5±1. DT data was normalized to MNI Space and Q-Space diffeomorphic reconstruction was performed using DSI-studio. CST was reconstructed based on quantitative anisotropy (QA) using the CST region (JHU white matter atlas) as seeding region and cerebral peduncle as region of interest (ROI). Fractional Anisotropy (FA) and QA were analyzed in the seeding and ROI region and in the posterior limb of the internal capsule (PLIC). Dichotomized modified Rankin Scale on day 90 (favorable outcome = mRS 0-2) was assessed as primary outcome variable. Results: 33 patients, mean age 70.7 y (standard deviation (SD) 12.9), 12 male, 21 with lobar hemorrhage, mean ICH volume on admission 16.5 (SD 11.3) cm 3 were included. 16 patients had a favorable outcome on day 90 (median mRS 3 (IQR 1-3.5). Mean number of reconstructed CST fiber pathways ipsilateral to ICH was higher in patients with favorable outcome (11343 (SD 8201)) than in patients with unfavorable outcome (4868 (SD 3221), p=0.008). Median QA and FA values in the PLIC ipsilateral to ICH were also higher in patients with favorable outcome (QA: 18.9 (IQR 16.2-23.3) vs. 14.6 (IQR 11.7 - 17.7), p=0.016, FA: 0.49 (IQR 0.45-0.53) vs. 0.41 (IQR 0.38-0.49), p=0.026). Conclusion: Higher FA- and QA-values in the PLIC and higher numbers of CST fiber pathways ipsilateral to ICH seem to be associated with a favorable outcome. DT Imaging may turn out as a useful quantitative predictive marker in the acute phase of ICH.

Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football

2019 ◽  
Vol 25 (09) ◽  
pp. 950-960 ◽  
Author(s):  
Douglas P. Terry ◽  
Catherine M. Mewborn ◽  
L. Stephen Miller
Keyword(s):  
High School ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Region Of Interest ◽  
Internal Capsule ◽  
Later Life ◽  
Cognitive Outcomes ◽  
High School Football ◽  
Former Athletes

AbstractObjective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p &lt; .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p &lt; .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

scholarly journals Diffusion Tensor Imaging Evaluation of Corticospinal Tract Hyperintensity in Upper Motor Neuron-Predominant ALS Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Venkateswaran Rajagopalan ◽  
Didier Allexandre ◽  
Guang H. Yue ◽  
Erik P. Pioro
Keyword(s):  
Diffusion Tensor Imaging ◽  
Motor Neuron ◽  
Corticospinal Tract ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Internal Capsule ◽  
Proton Density ◽  
Imaging Evaluation ◽  
Axonal Pathology ◽  
Als Patients

Amyotrophic lateral sclerosis (ALS) patients with predominant upper motor neuron (UMN) signs occasionally have hyperintensity of corticospinal tract (CST) on T2- and proton-density-(PD-) weighted brain images. Diffusion tensor imaging (DTI) was used to assess whether diffusion parameters along intracranial CST differ in presence or absence of hyperintensity and correspond to UMN dysfunction. DTI brain scans were acquired in 47 UMN-predominant ALS patients with (n=21) or without (n=26) CST hyperintensity and in 10 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in four regions of interests (ROIs) along CST. Abnormalities (P<0.05) were observed in FA, AD, or RD in CST primarily at internal capsule (IC) level in ALS patients, especially those with CST hyperintensity. Clinical measures corresponded well with DTI changes at IC level. The IC abnormalities suggest a prominent axonopathy in UMN-predominant ALS and that tissue changes underlying CST hyperintensity have specific DTI changes, suggestive of unique axonal pathology.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

2015 ◽  
Vol 22 (5) ◽  
pp. 620-627 ◽  
Author(s):  
MA Rocca ◽  
M Sonkin ◽  
M Copetti ◽  
E Pagani ◽  
DL Arnold ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Structural Integrity ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

scholarly journals 18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

2019 ◽  
Author(s):  
Nicolas Nicastro ◽  
Patricia Vazquez Rodriguez ◽  
Maura Malpetti ◽  
William Richard Bevan-Jones ◽  
P. Simon Jones ◽  
...  
Keyword(s):  
White Matter ◽  
Progressive Supranuclear Palsy ◽  
Pet Imaging ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
White Matter Integrity ◽  
Tau Pathology ◽  
Cross Sectional ◽  
White Matter Changes

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.

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