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https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#1
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28342444/acid-ceramidase-deficiency-in-mice-results-in-a-broad-range-of-central-nervous-system-abnormalities
#2
Jakub Sikora, Shaalee Dworski, E Ellen Jones, Mustafa A Kamani, Matthew C Micsenyi, Tomo Sawada, Pauline Le Faouder, Justine Bertrand-Michel, Aude Dupuy, Christopher K Dunn, Ingrid Cong Yang Xuan, Josefina Casas, Gemma Fabrias, David R Hampson, Thierry Levade, Richard R Drake, Jeffrey A Medin, Steven U Walkley
Farber disease is a rare autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-onset progressive visceral and neurologic disease. To understand the neurologic abnormality, we investigated behavioral, biochemical, and cellular abnormalities in the central nervous system of Asah1(P361R/P361R) mice, which serve as a model of Farber disease. Behaviorally, the mutant mice had reduced voluntary locomotion and exploration, increased thigmotaxis, abnormal spectra of basic behavioral activities, impaired muscle grip strength, and defects in motor coordination...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28340257/cd8-positive-t-cell-leukoencephalitis-with-astrocytopathy-clinically-presenting-as-neuromyelitis-optica
#3
Diana L Thomas, Jody Manners, Daniel Marker, Joseph Mettenburg, Geoffrey Murdoch, Bryan Stevens, Guoji Wang, Clayton Wiley
We describe a novel disease entity with the clinical and radiologic presentation of neuromyelitis optica (NMO) and widespread CD8-positive T-cell leukoencephalitis and astrocytopathy. The 59-year-old female patient had a complex 2-year neurological history that included early changes in cognition and memory, progressive lower extremity motor dysfunction, and multimodal sensory involvement. MRI of the spinal cord showed increased T2 signal in the central cord extending from C2 through T4. MRI of the brain showed symmetric radial enhancement in periventricular deep white matter without evidence of demyelinating lesions...
March 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28340083/evaluating-the-patterns-of-aging-related-tau-astrogliopathy-unravels-novel-insights-into-brain-aging-and-neurodegenerative-diseases
#4
Gabor G Kovacs, John L Robinson, Sharon X Xie, Edward B Lee, Murray Grossman, David A Wolk, David J Irwin, Dan Weintraub, Christopher F Kim, Theresa Schuck, Ahmed Yousef, Stephanie T Wagner, Eunran Suh, Vivianna M Van Deerlin, Virginia M-Y Lee, John Q Trojanowski
The term "aging-related tau astrogliopathy" (ARTAG) describes pathological accumulation of abnormally phosphorylated tau protein in astrocytes. We evaluated the correlates of ARTAG types (i.e., subpial, subependymal, white and gray matter, and perivascular) in different neuroanatomical regions. Clinical, neuropathological, and genetic (eg, APOE ε4 allele, MAPT H1/H2 haplotype) data from 628 postmortem brains from subjects were investigated; most of the patients had been longitudinally followed at the University of Pennsylvania...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28338052/dissociable-diffusion-mri-patterns-of-white-matter-microstructure-and-connectivity-in-alzheimer-s-disease-spectrum
#5
Nhat Trung Doan, Andreas Engvig, Karin Persson, Dag Alnæs, Tobias Kaufmann, Jaroslav Rokicki, Aldo Córdova-Palomera, Torgeir Moberget, Anne Brækhus, Maria Lage Barca, Knut Engedal, Ole A Andreassen, Geir Selbæk, Lars T Westlye
Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer's disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336929/developmental-whole-brain-white-matter-alterations-in-transgenic-huntington-s-disease-monkey
#6
Yuguang Meng, Jie Jiang, Jocelyne Bachevalier, Xiaodong Zhang, Anthony W S Chan
Transgenic Huntington's disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Progressive developmental white matter alterations in HD monkeys were widespread and were observed not only in fiber bundles connecting cortical areas to the striatum (e...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336784/evaluation-of-the-effect-of-fingolimod-treatment-on-microglial-activation-using-serial-pet-imaging-in-multiple-sclerosis
#7
Marcus Sucksdorff, Eero Rissanen, Jouni Tuisku, Salla Nuutinen, Teemu Paavilainen, Johanna Rokka, Juha Rinne, Laura Airas
Traditionally, multiple sclerosis (MS) has been considered a white matter (WM) disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, i.e. in areas of normal appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using an 18 kDa translocator protein (TSPO) binding radioligands and positron emission tomography (PET). It is unknown whether fingolimod affects microglial activation in MS...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28336779/validation-of-the-semi-quantitative-static-suvr-method-for-18-f-av45-pet-by-pharmacokinetic-modeling-with-an-arterial-input-function
#8
Julie Ottoy, Jeroen Verhaeghe, Ellis Niemantsverdriet, Leonie Wyffels, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Steven Deleye, Tobi Van den Bossche, Sara Van Mossevelde, Sarah Ceyssens, Jan Versijpt, Sigrid Stroobants, Sebastiaan Engelborghs, Steven Staelens
Increased brain uptake of [(18)F]-AV45 visualized by PET is a key biomarker for Alzheimer's disease (AD). The standardized uptake value ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min [(18)F]-AV45 (291 ± 67 MBq) and 1-min [(15)O]-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD dementia, 15 amnestic mild cognitive impairment (aMCI) and 10 cognitively healthy controls (HC)...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28335684/bone-marrow-derived-endothelial-progenitor-cell-treatment-in-a-model-of-lateral-fluid-percussion-injury-in-rats-evaluation-of-acute-and-subacute-outcome-measures
#9
Eugene Park, Katya J Park, Elaine Liu, Rongcai Jiang, Jian-Ning Zhang, Andrew J Baker
Traumatic brain injury (TBI) continues to be a serious healthcare issue while therapies to treat TBI remain elusive. Promising results from the use of endothelial progenitor cells (EPCs) in numerous disease states highlight the pleiotropic capacity of this cell type. We have previously demonstrated that EPC conditioned media reduces axonal degeneration following in vitro OGD insult and concurrently improves white matter and microvascular outcome in vivo following midline fluid percussion injury. In the current study we evaluated the effectiveness of allogeneic endothelial cells derived from rat bone marrow on microvascular recovery and neuronal sparing following lateral fluid percussion injury...
March 23, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28335021/mri-visible-perivascular-space-location-is-associated-with-alzheimer-s-disease-independently-of-amyloid-burden
#10
Gargi Banerjee, Hee Jin Kim, Zoe Fox, H Rolf Jäger, Duncan Wilson, Andreas Charidimou, Han Kyu Na, Duk L Na, Sang Won Seo, David J Werring
Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment...
February 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334938/clinical-and-genetic-characterization-of-leukoencephalopathies-in-adults
#11
David S Lynch, Anderson Rodrigues Brandão de Paiva, Wei Jia Zhang, Enrico Bugiardini, Fernando Freua, Leandro Tavares Lucato, Lucia Inês Macedo-Souza, Rahul Lakshmanan, Justin A Kinsella, Aine Merwick, Alexander M Rossor, Nin Bajaj, Brian Herron, Paul McMonagle, Patrick J Morrison, Deborah Hughes, Alan Pittman, Matilde Laurà, Mary M Reilly, Jason D Warren, Catherine J Mummery, Jonathan M Schott, Matthew Adams, Nick C Fox, Elaine Murphy, Indran Davagnanam, Fernando Kok, Jeremy Chataway, Henry Houlden
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all...
March 2, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334875/white-matter-changes-in-paediatric-multiple-sclerosis-and-monophasic-demyelinating-disorders
#12
Giulia Longoni, Robert A Brown, Parya MomayyezSiahkal, Colm Elliott, Sridar Narayanan, Amit Bar-Or, Ruth Ann Marrie, E Ann Yeh, Massimo Filippi, Brenda Banwell, Douglas L Arnold
Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334869/emerging-concepts-in-sporadic-cerebral-amyloid-angiopathy
#13
Andreas Charidimou, Gregoire Boulouis, M Edip Gurol, Cenk Ayata, Brian J Bacskai, Matthew P Frosch, Anand Viswanathan, Steven M Greenberg
Sporadic cerebral amyloid angiopathy is a common, well-defined small vessel disease and a largely untreatable cause of intracerebral haemorrhage and contributor to age-related cognitive decline. The term 'cerebral amyloid angiopathy' now encompasses not only a specific cerebrovascular pathological finding, but also different clinical syndromes (both acute and progressive), brain parenchymal lesions seen on neuroimaging and a set of diagnostic criteria-the Boston criteria, which have resulted in increasingly detected disease during life...
March 13, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#14
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28329254/periodic-limb-movements-and-white-matter-hyperintensities-in-first-ever-minor-stroke-or-high-risk-tia
#15
Mark I Boulos, Brian J Murray, Ryan T Muir, Fuqiang Gao, Gregory M Szilagyi, Menal Huroy, Alexander Kiss, Arthur S Walters, Sandra E Black, Andrew S Lim, Richard H Swartz
Study Objectives: Emerging evidence suggests that periodic limb movements (PLMs) may contribute to the development of cerebrovascular disease. White matter hyperintensities (WMHs), a widely accepted biomarker for cerebral small vessel disease, are associated with incident stroke and death. We evaluated the association between increased PLM indices and WMH burden in patients presenting with stroke or transient ischemic attack (TIA), while controlling for vascular risk factors and stroke severity...
December 29, 2016: Sleep
https://www.readbyqxmd.com/read/28328855/head-to-head-comparison-of-11c-pib-and-18f-fc119s-for-a%C3%AE-imaging-in-healthy-subjects-mild-cognitive-impairment-patients-and-alzheimer-s-disease-patients
#16
Byung Hyun Byun, Byung Il Kim, Su Yeon Park, In Ok Ko, Kyo Chul Lee, Kyeong Min Kim, Yu Kyeong Kim, Jun-Young Lee, Seon Hee Bu, Jung Hwa Kim, Dae Yoon Chi, Jeong Ho Ha, Sang Moo Lim
As a new beta amyloid (Aβ) positron emission tomography (PET) tracer, F-FC119S has shown higher cortical uptake in patients with Alzheimer's disease (AD) than that in healthy control subjects without adverse effects in a previous preliminary study. The aim of this study was to compare F-FC119S PET and C-PiB PET in healthy control (HC) subjects, mild cognitive impairment (MCI) patients, and AD patients.A total of 48 subjects, including 28 HC subjects, 10 MCI patients, and 10 AD patients, underwent static F-FC119S PET (30 minutes after intravenous [i...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327087/nt5c2-novel-splicing-variant-expands-the-phenotypic-spectrum-of-spastic-paraplegia-spg45-case-report-of-a-new-member-of-thin-corpus-callosum-spg-subgroup
#17
Mahmoud F Elsaid, Khalid Ibrahim, Nader Chalhoub, Ahmed Elsotouhy, Noora El Mudehki, Alice Abdel Aleem
BACKGROUND: Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative diseases. Thin Corpus Callosum (TCC) associated HSP is a distinguished subgroup of complex forms. Purines and pyrimidine, the basic DNA and RNA components, are regulating the cell metabolism, having roles in signal transduction, energy preservation and cellular repair. Genetic defects in nucleotide metabolism related genes have been only recently implicated in brain and neurodegenerative diseases' pathogenesis...
March 21, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28326436/reference-region-selection-and-the-association-between-the-rate-of-amyloid-accumulation-over-time-and-the-baseline-amyloid-burden
#18
Janusch Blautzik, Matthias Brendel, Julia Sauerbeck, Sebastian Kotz, Franziska Scheiwein, Peter Bartenstein, John Seibyl, Axel Rominger
Relative quantitative analysis of amyloid plaque burden in Alzheimer's disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs...
March 22, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28324319/white-matter-measures-are-near-normal-in-controlled-hiv-infection-except-in-those-with-cognitive-impairment-and-longer-hiv-duration
#19
Lucette A Cysique, James R Soares, Guangqiang Geng, Maia Scarpetta, Kirsten Moffat, Michael Green, Bruce J Brew, Roland G Henry, Caroline Rae
The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV- and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm(2); fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL...
March 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28324197/the-spectrum-of-magnetic-resonance-findings-in-cerebrotendinous-xanthomatosis-redefinition-and-evidence-of-new-markers-of-disease-progression
#20
Andrea Mignarri, Maria Teresa Dotti, Antonio Federico, Nicola De Stefano, Marco Battaglini, Irene Grazzini, Paolo Galluzzi, Lucia Monti
Cerebrotendinous xanthomatosis (CTX) is a metabolic disease characterized by systemic signs and neurological impairment, which can be prevented if chenodeoxycholic acid (CDCA) treatment is started early. Despite brain MRI represents an essential diagnostic tool, the spectrum of findings is worth to be reappraised, and follow-up data are needed. We performed clinical evaluation and brain MRI in 38 CTX patients. Sixteen of them who were untreated at baseline examination underwent clinical and MRI follow-up after long-term treatment with CDCA...
March 21, 2017: Journal of Neurology
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