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[PMID]: 26077779
[Au] Autor:Perriard G; Mathias A; Enz L; Canales M; Schluep M; Gentner M; Schaeren-Wiemers N; Du Pasquier RA
[Ad] Address:Laboratory of Neuroimmunology, Center of Research in Neurosciences, Department of Clinical Neurosciences and Service of Immunology and Allergy, Department of Medicine, CHUV, 1011, Lausanne, Switzerland....
[Ti] Title:Interleukin-22 is increased in multiple sclerosis patients and targets astrocytes.
[So] Source:J Neuroinflammation;12:119, 2015.
[Is] ISSN:1742-2094
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Increasing evidences link T helper 17 (Th17) cells with multiple sclerosis (MS). In this context, interleukin-22 (IL-22), a Th17-linked cytokine, has been implicated in blood brain barrier breakdown and lymphocyte infiltration. Furthermore, polymorphism between MS patients and controls has been recently described in the gene coding for IL-22 binding protein (IL-22BP). Here, we aimed to better characterize IL-22 in the context of MS. METHODS: IL-22 and IL-22BP expressions were assessed by ELISA and qPCR in the following compartments of MS patients and control subjects: (1) the serum, (2) the cerebrospinal fluid, and (3) immune cells of peripheral blood. Identification of the IL-22 receptor subunit, IL-22R1, was performed by immunohistochemistry and immunofluorescence in human brain tissues and human primary astrocytes. The role of IL-22 on human primary astrocytes was evaluated using 7-AAD and annexin V, markers of cell viability and apoptosis, respectively. RESULTS: In a cohort of 141 MS patients and healthy control (HC) subjects, we found that serum levels of IL-22 were significantly higher in relapsing MS patients than in HC but also remitting and progressive MS patients. Monocytes and monocyte-derived dendritic cells contained an enhanced expression of mRNA coding for IL-22BP as compared to HC. Using immunohistochemistry and confocal microscopy, we found that IL-22 and its receptor were detected on astrocytes of brain tissues from both control subjects and MS patients, although in the latter, the expression was higher around blood vessels and in MS plaques. Cytometry-based functional assays revealed that addition of IL-22 improved the survival of human primary astrocytes. Furthermore, tumor necrosis factor α-treated astrocytes had a better long-term survival capacity upon IL-22 co-treatment. This protective effect of IL-22 seemed to be conferred, at least partially, by a decreased apoptosis. CONCLUSIONS: We show that (1) there is a dysregulation in the expression of IL-22 and its antagonist, IL-22BP, in MS patients, (2) IL-22 targets specifically astrocytes in the human brain, and (3) this cytokine confers an increased survival of the latter cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s12974-015-0335-3

  2 / 186671 MEDLINE  
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[PMID]: 26106458
[Au] Autor:Haider L
[Ad] Address:Department of Neuroimmunology, Center for Brain Research and Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
[Ti] Title:Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis.
[So] Source:Oxid Med Cell Longev;2015:725370, 2015.
[Is] ISSN:1942-0994
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative "inside-out" and primary inflammation-driven "outside-in" hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration. The brain weighs only a few percent of the body mass but accounts for approximately 20% of the total basal oxygen consumption of mitochondria. Oxidative stress induces mitochondrial injury in patients with multiple sclerosis and energy failure in the central nervous system of susceptible individuals. The interconnected mechanisms responsible for free radical production in patients with multiple sclerosis are as follows: (i) inflammation-induced production of free radicals by activated immune cells, (ii) liberation of iron from the myelin sheets during demyelination, and (iii) mitochondrial injury and thus energy failure-related free radical production. In the present review, the different sources of oxidative stress and their relationships to patients with multiple sclerosis considering tissue injury mechanisms and clinical aspects have been discussed.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1155/2015/725370

  3 / 186671 MEDLINE  
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[PMID]: 26106552
[Au] Autor:Fling BW; Gera Dutta G; Horak FB
[Ad] Address:Department of Neurology, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA ; Portland VA Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239-9264, USA.
[Ti] Title:Functional connectivity underlying postural motor adaptation in people with multiple sclerosis.
[So] Source:Neuroimage Clin;8:281-9, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:A well-characterized neural network is associated with motor learning, involving several brain regions known to have functional and structural deficits in persons with multiple sclerosis (PwMS). However, it is not known how MS affects postural motor learning or the neural networks involved. The aim of this study was to gain a better understanding of the neural networks underlying adaptation of postural responses within PwMS. Participants stood on a hydraulically driven, servo-controlled platform that translated horizontally forward and backward in a continuous sinusoidal pattern across multiple trials over two consecutive days. Our results show similar postural adaptation between PwMS and age-matched control participants despite overall deficits in postural motor control in PwMS. Moreover, PwMS demonstrated better retention the following day. PwMS had significantly reduced functional connectivity within both the cortico-cerebellar and cortico-striatal motor loops; neural networks that subserve implicit motor learning. In PwMS, greater connectivity strength within the cortico-cerebellar circuit was strongly related to better baseline postural control, but not to postural adaptation as it was in control participants. Further, anti-correlated cortico-striatal connectivity within the right hemisphere was related to improved postural adaptation in both groups. Taken together with previous studies showing a reduced reliance on cerebellar- and proprioceptive-related feedback control in PwMS, we suggest that PwMS may rely on cortico-striatal circuitry to a greater extent than cortico-cerebellar circuitry for the acquisition and retention of motor skills.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.04.023

  4 / 186671 MEDLINE  
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[PMID]: 26106562
[Au] Autor:Jain S; Sima DM; Ribbens A; Cambron M; Maertens A; Van Hecke W; De Mey J; Barkhof F; Steenwijk MD; Daams M; Maes F; Van Huffel S; Vrenken H; Smeets D
[Ad] Address:icometrix, R&D, Leuven, Belgium....
[Ti] Title:Automatic segmentation and volumetry of multiple sclerosis brain lesions from MR images.
[So] Source:Neuroimage Clin;8:367-75, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The location and extent of white matter lesions on magnetic resonance imaging (MRI) are important criteria for diagnosis, follow-up and prognosis of multiple sclerosis (MS). Clinical trials have shown that quantitative values, such as lesion volumes, are meaningful in MS prognosis. Manual lesion delineation for the segmentation of lesions is, however, time-consuming and suffers from observer variability. In this paper, we propose MSmetrix, an accurate and reliable automatic method for lesion segmentation based on MRI, independent of scanner or acquisition protocol and without requiring any training data. In MSmetrix, 3D T1-weighted and FLAIR MR images are used in a probabilistic model to detect white matter (WM) lesions as an outlier to normal brain while segmenting the brain tissue into grey matter, WM and cerebrospinal fluid. The actual lesion segmentation is performed based on prior knowledge about the location (within WM) and the appearance (hyperintense on FLAIR) of lesions. The accuracy of MSmetrix is evaluated by comparing its output with expert reference segmentations of 20 MRI datasets of MS patients. Spatial overlap (Dice) between the MSmetrix and the expert lesion segmentation is 0.67 ± 0.11. The intraclass correlation coefficient (ICC) equals 0.8 indicating a good volumetric agreement between the MSmetrix and expert labelling. The reproducibility of MSmetrix' lesion volumes is evaluated based on 10 MS patients, scanned twice with a short interval on three different scanners. The agreement between the first and the second scan on each scanner is evaluated through the spatial overlap and absolute lesion volume difference between them. The spatial overlap was 0.69 ± 0.14 and absolute total lesion volume difference between the two scans was 0.54 ± 0.58 ml. Finally, the accuracy and reproducibility of MSmetrix compare favourably with other publicly available MS lesion segmentation algorithms, applied on the same data using default parameter settings.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.05.003

  5 / 186671 MEDLINE  
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[PMID]: 26106563
[Au] Autor:Guizard N; Coupé P; Fonov VS; Manjón JV; Arnold DL; Collins DL
[Ad] Address:Montreal Neurological Institute, McGill University, Canada....
[Ti] Title:Rotation-invariant multi-contrast non-local means for MS lesion segmentation.
[So] Source:Neuroimage Clin;8:376-89, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Multiple sclerosis (MS) lesion segmentation is crucial for evaluating disease burden, determining disease progression and measuring the impact of new clinical treatments. MS lesions can vary in size, location and intensity, making automatic segmentation challenging. In this paper, we propose a new supervised method to segment MS lesions from 3D magnetic resonance (MR) images using non-local means (NLM). The method uses a multi-channel and rotation-invariant distance measure to account for the diversity of MS lesions. The proposed segmentation method, rotation-invariant multi-contrast non-local means segmentation (RMNMS), captures the MS lesion spatial distribution and can accurately and robustly identify lesions regardless of their orientation, shape or size. An internal validation on a large clinical magnetic resonance imaging (MRI) dataset of MS patients demonstrated a good similarity measure result (Dice similarity = 60.1% and sensitivity = 75.4%), a strong correlation between expert and automatic lesion load volumes (R(2) = 0.91), and a strong ability to detect lesions of different sizes and in varying spatial locations (lesion detection rate = 79.8%). On the independent MS Grand Challenge (MSGC) dataset validation, our method provided competitive results with state-of-the-art supervised and unsupervised methods. Qualitative visual and quantitative voxel- and lesion-wise evaluations demonstrated the accuracy of RMNMS method.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.05.001

  6 / 186671 MEDLINE  
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[PMID]: 26106538
[Au] Autor:Romero K; Pavisian B; Staines WR; Feinstein A
[Ad] Address:Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada....
[Ti] Title:Multiple sclerosis, cannabis, and cognition: A structural MRI study.
[So] Source:Neuroimage Clin;8:140-7, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:OBJECTIVE: A subset of patients with multiple sclerosis (MS) smoke cannabis to relieve symptoms including spasticity and pain. Recent evidence suggests that smoking cannabis further impairs cognition in people with MS and is linked to impaired functional brain changes. No such association, however, has been reported between cannabis use and structural brain changes, hence the focus of the present study. METHODS: Twenty patients with MS who smoke cannabis for symptom relief, and 19 matched non-cannabis-smoking MS patients were given the Brief Repeatable Neuropsychological Battery and structural MRI scans. Images were segmented into gray matter and white matter, and subsequently analysed with Partial Least Squares, a data-driven multivariate technique that explores brain-behaviour associations. RESULTS: In both groups, the Partial Least Squares analysis yielded significant correlations between cognitive scores and both gray matter (33% variance, p < .0001) and white matter (17% variance, p < .05) volume. Gray matter volume in the thalamus, basal ganglia, medial temporal, and medial prefrontal regions, and white matter volume in the fornix correlated with cognitive deficits. Crucially, the analysis indicated that brain volume reductions were associated with more extensive cognitive impairment in the cannabis versus the non-cannabis MS group. INTERPRETATION: These results suggest that cannabis use in MS results in more widespread cognitive deficits, which correlate with tissue volume in subcortical, medial temporal, and prefrontal regions. These are the first findings demonstrating an association between cannabis use, cognitive impairment and structural brain changes in MS patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.04.006

  7 / 186671 MEDLINE  
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[PMID]: 26106550
[Au] Autor:Asaf A; Evan S; Anat A
[Ad] Address:Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
[Ti] Title:Injury to white matter tracts in relapsing-remitting multiple sclerosis: A possible therapeutic window within the first 5 years from onset using diffusion-tensor imaging tract-based spatial statistics.
[So] Source:Neuroimage Clin;8:261-6, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:DTI studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression. In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration. DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (<1 year), moderate (1 up to 6 years) and long (6-10 years) disease duration periods. Statistical analyses of the fractional anisotropy (FA) data were performed using tract-based spatial statistics (TBSS). Whole-brain skeletal FA measurements showed a significant decrease between healthy controls and the short MS disease duration group, as well as between moderate disease duration and long disease duration groups, but failed to show a significant difference between short and moderate disease duration groups. Voxelwise analysis revealed clusters of diffuse FA reductions in 40 WM tracts when comparing healthy controls and MS short disease duration group, with the point of maximal significant difference located in the left inferior longitudinal fasciculus. Comparing short with long disease duration groups, progressive FA reduction was demonstrated across 30 WM tracts, with the point of maximal significant difference migrating to the body of the corpus callosum. A non-linear pattern of WM microstructure disruption occurs in RRMS. Alterations are seen early in the disease course within 1 year from onset, reach a plateau within the next 5 years, and only later additional WM changes are detected. An important period of a possible therapeutic window therefore exists within the early disease stage.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.04.020

  8 / 186671 MEDLINE  
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[PMID]: 26106534
[Au] Autor:Droby A; Fleischer V; Carnini M; Zimmermann H; Siffrin V; Gawehn J; Erb M; Hildebrandt A; Baier B; Zipp F
[Ad] Address:Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ; Neuroimage Center (NIC) of the Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University, Mainz, Germany....
[Ti] Title:The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients.
[So] Source:Neuroimage Clin;8:110-6, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Infratentorial lesions have been assigned an equivalent weighting to supratentorial plaques in the new McDonald criteria for diagnosing multiple sclerosis. Moreover, their presence has been shown to have prognostic value for disability. However, their spatial distribution and impact on network damage is not well understood. As a preliminary step in this study, we mapped the overall infratentorial lesion pattern in relapsing-remitting multiple sclerosis patients (N = 317) using MRI, finding the pons (lesion density, 14.25/cm(3)) and peduncles (13.38/cm(3)) to be predilection sites for infratentorial lesions. Based on these results, 118 fiber bundles from 15 healthy controls and a subgroup of 23 patients showing lesions unilaterally at the predilection sites were compared using diffusion tensor imaging to analyze the impact of an isolated infratentorial lesion on the affected fiber tracts. Fractional anisotropy, mean diffusion as well as axial and radial diffusivity were investigated at the lesion site and along the entire fiber tract. Infratentorial lesions were found to have an impact on the fractional anisotropy and radial diffusivity not only at the lesion site itself but also along the entire affected fiber tract. As previously found in animal experiments, inflammatory attack in the posterior fossa in multiple sclerosis impacts the whole affected fiber tract. Here, this damaging effect, reflected by changes in diffusivity measures, was detected in vivo in multiple sclerosis patients in early stages of the disease, thus demonstrating the influence of a focal immune attack on more distant networks, and emphasizing the pathophysiological role of Wallerian degeneration in multiple sclerosis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2015.03.003

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[PMID]: 26106524
[Au] Autor:Kern KC; Gold SM; Lee B; Montag M; Horsfall J; O'Connor MF; Sicotte NL
[Ad] Address:Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA....
[Ti] Title:Thalamic-hippocampal-prefrontal disruption in relapsing-remitting multiple sclerosis.
[So] Source:Neuroimage Clin;8:440-7, 2015.
[Is] ISSN:2213-1582
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Cortical, thalamic and hippocampal gray matter atrophy in relapsing-remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. OBJECTIVE: To assess MS damage to a hippocampal-thalamic-prefrontal network and the relative contributions of its components to specific cognitive domains. METHODS: We calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity. RESULTS: RRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory. CONCLUSIONS: Hippocampal-thalamic-prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1016/j.nicl.2014.12.015

  10 / 186671 MEDLINE  
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[PMID]: 26106267
[Au] Autor:Kitano S; Kino Y; Yamamoto Y; Takitani M; Miyoshi J; Ishida T; Saito Y; Arima K; Satoh J
[Ad] Address:Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan....
[Ti] Title:Bioinformatics Data Mining Approach Suggests Coexpression of AGTPBP1 with an ALS-linked Gene C9orf72.
[So] Source:J Cent Nerv Syst Dis;7:15-26, 2015.
[Is] ISSN:1179-5735
[Cp] Country of publication:New Zealand
[La] Language:eng
[Ab] Abstract:BACKGROUND: Expanded GGGGCC hexanucleotide repeats located in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene represent the most common genetic abnormality for familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Formation of nuclear RNA foci, accumulation of repeat-associated non-ATG-translated dipeptide-repeat proteins, and haploinsufficiency of C9orf72 are proposed for pathological mechanisms of C9ALS/FTD. However, at present, the physiological function of C9orf72 remains largely unknown. METHODS: By searching on a bioinformatics database named COXPRESdb composed of the comprehensive gene coexpression data, we studied potential C9orf72 interactors. RESULTS: We identified the ATP/GTP binding protein 1 (AGTPBP1) gene alternatively named NNA1 encoding a cytosolic carboxypeptidase whose mutation is causative of the degeneration of Purkinje cells and motor neurons as the most significant gene coexpressed with C9orf72. We verified coexpression and interaction of AGTPBP1 and C9orf72 in transfected cells by immunoprecipitation and in neurons of the human brain by double-labeling immunohistochemistry. Furthermore, we found a positive correlation between AGTPBP1 and C9orf72 mRNA expression levels in the set of 21 human brains examined. CONCLUSIONS: These results suggest that AGTPBP1 serves as a C9orf72 interacting partner that plays a role in the regulation of neuronal function in a coordinated manner within the central nervous system.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1506
[Cu] Class update date: 150627
[Lr] Last revision date:150627
[Da] Date of entry for processing:150624
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4137/JCNSD.S24317


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