Database : MEDLINE
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[PMID]: 25590041
[Au] Autor:Ringelstein M; Albrecht P; Südmeyer M; Harmel J; Müller AK; Keser N; Finis D; Ferrea S; Guthoff R; Schnitzler A; Hartung HP; Methner A; Aktas O
[Ad] Address:Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany....
[Ti] Title:Subtle retinal pathology in amyotrophic lateral sclerosis.
[So] Source:Ann Clin Transl Neurol;1(4):290-7, 2014 Apr.
[Is] ISSN:2328-9503
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Amyotrophic lateral sclerosis (ALS) is characterized by neuro-ophthalmological abnormalities beyond disturbed oculomotor control such as decreased visual acuity and disturbed visual evoked potentials. Here we report retinal alterations in a cohort of 24 patients with clinically definite (n = 20) or probable (n = 4) ALS as compared to matched controls. High-resolution spectral domain optical coherence tomography with retinal segmentation revealed a subtle reduction in the macular thickness and the retinal nerve fiber layer (RNFL) as well as a marked thinning of the inner nuclear layer (INL). Our data indicate an unprecedented retinal damage pattern and suggest neurodegeneration beyond the motor system in this disease.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Da] Date of entry for processing:150115
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1002/acn3.46

  2 / 181480 MEDLINE  
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[PMID]: 25590039
[Au] Autor:Leong SY; Rao VT; Bin JM; Gris P; Sangaralingam M; Kennedy TE; Antel JP
[Ad] Address:Neuroimmunology Unit, Montreal Neurological Institute, McGill University Montreal, Quebec, Canada, H3A 2B4....
[Ti] Title:Heterogeneity of oligodendrocyte progenitor cells in adult human brain.
[So] Source:Ann Clin Transl Neurol;1(4):272-83, 2014 Apr.
[Is] ISSN:2328-9503
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Remyelination in multiple sclerosis has been attributed to the presence of oligodendrocyte progenitor cells (OPCs) in brain parenchyma. However, the precise identity of these progenitors is poorly defined. Here, we characterized populations of OPCs in the adult human brain and examined their myelination capacity and profile of miRNAs. Comparisons were made with fetal OPCs and mature oligodendrocytes. METHODS: We isolated human adult and fetal (early-to-mid second trimester) OPCs from surgically resected brain tissues using O4-, A2B5-, and MOG-directed fluorescence activated cell sorting and transplanted them into dysmyelinated shiverer slices to examine their myelination capacity. We used qRT-PCR to analyze expression of selective miRNAs implicated in OPC biology. RESULTS: Three subsets of putative OPCs were identified in adult brains: (1) A2B5(+), (2) O4(low), and (3) A2B5(+)O4(high)MOG(+) progenitors. In comparison, fetal brains contained (1) A2B5(+), (2) O4(+), and (3) A2B5(+)O4(+) progenitors, but no MOG(+) cells. We demonstrate that like fetal OPCs, adult OPCs have the capacity to ensheathe cerebellar axons. However, adult OPCs exhibit low to undetectable expression of miRNAs that were highly expressed in O4-expressing fetal OPCs. Adult OPCs also express different miRNAs compared to mature oligodendrocytes. INTERPRETATION: We conclude that phenotypically distinct subsets of OPCs are present in adult human brain and these OPCs show differential miRNA expression compared to fetal OPCs and mature oligodendrocytes. These suggest that remyelination in adult brain may involve multiple populations of progenitors within the brain and that OPC differentiation in adulthood may be differentially regulated compared to development.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Da] Date of entry for processing:150115
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1002/acn3.55

  3 / 181480 MEDLINE  
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[PMID]: 24881003
[Au] Autor:Doucet GE; Sharan A; Pustina D; Skidmore C; Sperling MR; Tracy JI
[Ad] Address:Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
[Ti] Title:Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy.
[So] Source:Brain Topogr;28(1):113-26, 2015 Jan.
[Is] ISSN:1573-6792
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s10548-014-0366-6

  4 / 181480 MEDLINE  
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[PMID]: 25573524
[Au] Autor:Rinker JR; Salter AR; Walker H; Amara A; Meador W; Cutter GR
[Ad] Address:Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA Birmingham VA Medical Center, Birmingham, Alabama, USA....
[Ti] Title:Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey.
[So] Source:BMJ Open;5(1):e006714, 2015.
[Is] ISSN:2044-6055
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVES: (1)To describe the prevalence and severity of tremor in patients with multiple sclerosis (MS) registered within a large North American MS registry; (2) to provide detailed descriptions on the characteristics and severity of tremor in a subset of registrants and (3) to compare several measures of tremor severity for strength of agreement. SETTING: The North American Research Committee on MS (NARCOMS) registry. PARTICIPANTS: Registrants of NARCOMS reporting mild or greater tremor severity. OUTCOME MEASURES: We determined the cross-sectional prevalence of tremor in the NARCOMS registry over three semiannual updates between fall 2010 and fall 2011. A subset of registrants (n=552) completed a supplemental survey providing detailed descriptions of their tremor. Outcomes included descriptive characteristics of their tremors and correlations between outcome measures to determine the strength of agreement in assessing tremor severity. RESULTS: The estimated prevalence of tremor in NARCOMS ranged from 45% to 46.8%, with severe tremor affecting 5.5-5.9% of respondents. In the subset completing the supplemental survey, mild tremor severity was associated with younger age of MS diagnosis and tremor onset than those with moderate or severe tremor. However, tremor severity did not differ by duration of disease or tremor. Respondents provided descriptions of tremor symptoms on the Clinical Ataxia Rating Scale, which had a moderate to good (ρ=0.595) correlation with the Tremor Related Activities of Daily Living (TRADL) scale. Objectively scored Archimedes' spirals had a weaker (ρ=0.358) correlation with the TRADL. Rates of unemployment, disability and symptomatic medication use increased with tremor severity, but were high even among those with mild tremor. CONCLUSIONS: Tremor is common among NARCOMS registrants and severely disabling for some. Both ADL-based and symptom-descriptive measures of tremor severity can be used to stratify patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/bmjopen-2014-006714

  5 / 181480 MEDLINE  
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[PMID]: 25444364
[Au] Autor:Gündüz K; Kurt RA; Erden E
[Ad] Address:Department of Opthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. Electronic address: eyemd@ada.net.tr.
[Ti] Title:Ectopic orbital meningioma: report of two cases and literature review.
[So] Source:Surv Ophthalmol;59(6):643-8, 2014 Nov-Dec.
[Is] ISSN:1879-3304
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Ectopic orbital meningioma is a rare tumor usually affecting the medial orbit. We present two cases that occurred in a 56-year-old woman and a 28-year-old man. The tumors in both patients were subtotally excised via orbitotomy surgery and were located in the superior quadrant in one of our patients and in the temporal quadrant in the other. Following histopathologic diagnosis, external beam radiotherapy (EBRT) was administered to one patient and intensity modulated radiotherapy to the other. We identified 12 other well-documented cases of ectopic orbital meningioma previously reported. Ectopic meningioma should be considered in the differential diagnosis of medial as well as lateral and superior orbital tumors. The tumor is usually well circumscribed but can be ill defined in imaging studies. There are intralesional calcifications and sclerosis of adjacent bone in some cases. Ectopic orbital meningioma can recur after incomplete excision. Based on the efficacy of EBRT in optic nerve sheath meningioma, we used this treatment to decrease the risk of recurrence in our two patients and found no tumor recurrence at follow-ups of 24 and 74 months, but one patient had severe vision loss from radiation retinopathy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Js] Journal subset:IM
[St] Status:In-Process

  6 / 181480 MEDLINE  
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[PMID]: 25281497
[Au] Autor:Ansari MK; Yong HY; Metz L; Yong VW; Zhang Y
[Ad] Address:Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 1N4, Canada....
[Ti] Title:Changes in tissue directionality reflect differences in myelin content after demyelination in mice spinal cords.
[So] Source:J Struct Biol;188(2):116-22, 2014 Nov.
[Is] ISSN:1095-8657
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Changes in myelin integrity are key manifestations of many neurological diseases including multiple sclerosis but precise measurement of myelin in vivo is challenging. The goal of this study was to evaluate myelin content in histological images obtained from a lysolecithin mouse model of demyelination, using a new quantitative method named structure tensor analysis. Injury was targeted at the dorsal column of mice spinal cords. We obtained 16 histological images stained with luxol fast blue for myelin from 9 mice: 9 images from lesion epicenter and 7 from a distant area 500-µm away from the epicenter. In each image, we categorized 3 tissue types: healthy, completely demyelinated, and partially demyelinated. Structure tensor analysis was applied to quantify the coherency (anisotropy), energy (trace of dominant directions), and angular entropy (degree of disorder) of each tissue. We found that completely demyelinated lesions had significantly lower coherency and energy but higher angular entropy than partially demyelinated and healthy tissues at both the epicenter and distant areas of the injury. In addition, the coherency of healthy tissue was greater than partially demyelinated tissue at each site. Within tissue category, we did not find differences in any measure between spinal cord locations. Our findings suggest that greater myelin integrity is associated with better tissue anisotropy, independent of injury location. Structure tensor analysis may serve as a new tool for quantitative measurement of myelin content in white matter, and this may help understand disease mechanisms and development in MS and other demyelinating disorders.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1412
[Js] Journal subset:IM
[St] Status:In-Process

  7 / 181480 MEDLINE  
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[PMID]: 25227585
[Au] Autor:Castro-Rojas C; Deason K; Hussain RZ; Hayardeny L; Cravens PC; Yarovinsky F; Eagar TN; Arellano B; Stüve O
[Ad] Address:Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, TX, USA....
[Ti] Title:Testing effects of glatiramer acetate and fingolimod in an infectious model of CNS immune surveillance.
[So] Source:J Neuroimmunol;276(1-2):232-5, 2014 Nov 15.
[Is] ISSN:1872-8421
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Immune surveillance of the CNS is critical for preventing infections; however, there is no accepted experimental model to assess the risk of infection when utilizing disease-modifying agents. We tested two approved agents for patients with multiple sclerosis (MS), glatiramer acetate and fingolimod, in an experimental model of CNS immune surveillance. C57BL/6 mice were infected with the ME49 strain of the neuroinvasive parasite Toxoplasma gondii (T. gondii) and then treated with GA and fingolimod. Neither treatment affected host survival; however, differences were observed in parasite load and in leukocyte numbers in the brains of infected animals. Here we demonstrate that this model could be a useful tool for analyzing immune surveillance.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1412
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Process

  8 / 181480 MEDLINE  
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[PMID]: 25307057
[Au] Autor:Choi SH; Kim YH; Hebisch M; Sliwinski C; Lee S; D'Avanzo C; Chen H; Hooli B; Asselin C; Muffat J; Klee JB; Zhang C; Wainger BJ; Peitz M; Kovacs DM; Woolf CJ; Wagner SL; Tanzi RE; Kim DY
[Ad] Address:1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2]....
[Ti] Title:A three-dimensional human neural cell culture model of Alzheimer's disease.
[So] Source:Nature;515(7526):274-8, 2014 Nov 13.
[Is] ISSN:1476-4687
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-ß plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-ß peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-ß-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-ß species and phosphorylated tau but did not demonstrate amyloid-ß plaques or neurofibrillary tangles. Here we report that FAD mutations in ß-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-ß, including amyloid-ß plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-ß generation with ß- or γ-secretase inhibitors not only decreased amyloid-ß pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-ß-mediated tau phosphorylation. We have successfully recapitulated amyloid-ß and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.
[Mh] MeSH terms primary: Alzheimer Disease/metabolism
Alzheimer Disease/pathology
Cell Culture Techniques/methods
Models, Biological
Neural Stem Cells/metabolism
[Mh] MeSH terms secundary: Alzheimer Disease/genetics
Amyloid beta-Peptides/chemistry
Amyloid beta-Peptides/genetics
Amyloid beta-Peptides/metabolism
Cell Differentiation
Drug Evaluation, Preclinical/methods
Extracellular Space/metabolism
Glycogen Synthase Kinase 3/metabolism
Humans
Microtubule-Associated Proteins/metabolism
Neural Stem Cells/pathology
Neurites/metabolism
Phosphorylation
Presenilin-1/metabolism
Protein Aggregation, Pathological
Reproducibility of Results
tau Proteins/chemistry
tau Proteins/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Amyloid beta-Peptides); 0 (MAP2 protein, human); 0 (Microtubule-Associated Proteins); 0 (Presenilin-1); 0 (presenilin 1, mouse); 0 (tau Proteins); EC 2.7.11.26 (Glycogen Synthase Kinase 3)
[Em] Entry month:1412
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[Da] Date of entry for processing:141113
[St] Status:MEDLINE
[do] DOI:10.1038/nature13800

  9 / 181480 MEDLINE  
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[PMID]: 24993505
[Au] Autor:Stüve O; Warnke C; Deason K; Stangel M; Kieseier BC; Hartung HP; von Büdingen HC; Centonze D; Forsthuber TG; Knappertz V
[Ad] Address:Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA, olafstuve@yahoo.com.
[Ti] Title:CD19 as a molecular target in CNS autoimmunity.
[So] Source:Acta Neuropathol;128(2):177-90, 2014 Aug.
[Is] ISSN:1432-0533
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the most prevalent neuroinflammatory diseases of the central nervous system (CNS). The immunological cascade of these disorders is complex, and the exact spatial and temporal role of different immune cells is not fully understood. Although MS has been considered for many years to be primarily T cell driven, it is well established that B cells and the humoral immune response play an important role in its pathogenesis. This has long been evident from laboratory findings that include the presence of oligoclonal bands in the CSF. In NMO, the importance of the humoral immune system appears even more obvious as evidenced by pathogenic antibodies against aquaporin 4 (AQP4). Besides their capacity to mature into antibody-producing plasma cells, B cells are potent antigen-presenting cells to T lymphocytes and they can provide soluble factors for cell activation and differentiation to other immune-competent cells. In MS and NMO, there are substantial data from clinical trials that B cell depletion with CD20-directed agents is effective and relatively safe. Plasma cells, which produce antibodies against molecular targets expressed by the host, but which also provide humoral immune responses against pathogens, are not targeted by anti-CD20 therapies. Therefore, the depletion of CD19-expressing cells would offer potential advantages with regard to efficacy, but potentially higher risks with regard to infectious complications. This review will outline the rationale for CD19 as a molecular target in CNS autoimmunity. The current stage of drug development is illustrated. Potential safety concerns will be discussed.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1407
[Cu] Class update date: 150117
[Lr] Last revision date:150117
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1007/s00401-014-1313-z

  10 / 181480 MEDLINE  
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[PMID]: 25338872
[Au] Autor:Honda H; Hamasaki H; Wakamiya T; Koyama S; Suzuki SO; Fujii N; Iwaki T
[Ad] Address:Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
[Ti] Title:Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions.
[So] Source:Neuropathology;35(1):37-43, 2015 Feb.
[Is] ISSN:1440-1789
[Cp] Country of publication:Australia
[La] Language:eng
[Ab] Abstract:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons and appearance of skein-like inclusions. The inclusions are composed of trans-activation response (TAR) DNA-binding protein 43 (TDP-43), a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPA1 and hnRNPA2/B1 are hnRNPs that interact with the C-terminus of TDP-43. Using immunohistochemistry, we investigated the association between TDP-43 and hnRNPA1 in ALS spinal motor neurons. We examined spinal cords of seven ALS cases and six muscular dystrophy cases (used as controls) for the presence of TDP-43 and hnRNPA1 protein. In the control cases, hnRNPA1 immunoreactivity in motor neurons was intense in the nucleus and weak in the cytoplasm where it showed a fine granular appearance. In the ALS cases, hnRNPA1 immunoreactivity in motor neurons was reduced in the nuclei of neurons with skein-like inclusions but was not detected in the skein-like inclusions. The marked loss of hnRNPA1 in motor neurons with concomitant cytoplasmic aggregation of TDP-43 may represent a severe disturbance of mRNA processing, suggesting a key role in progressive neuronal death in ALS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1501
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/neup.12153


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