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Annals of Neurology

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https://www.readbyqxmd.com/read/28318059/low-normal-csf-a%C3%AE-42-levels-predict-clinical-progression-in-non-demented-subjects
#1
Betty M Tijms, Daniela Bertens, Rosalinde E Slot, Alida A Gouw, Charlotte E Teunissen, Philip Scheltens, Wiesje M van der Flier, Pieter Jelle Visser
We studied whether continuous lower normal cerebrospinal fluid (CSF) amyloid β 1-42 (≥640 pg/ml) levels related with rate of clinical progression in a sample of 393 non-demented memory clinic patients. Lower normal levels were associated with faster clinical progression and this depended on baseline cognitive status (subjective cognitive decline: HR = 0.59, p <.05; mild cognitive impairment: HR=0.12, p <.001), indicating that normal CSF amyloid levels do not exclude incident Alzheimer's disease. These findings suggest that research on preclinical markers for Alzheimer's disease should take the continuum of CSF amyloid β 1-42 levels within the normal range into account...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28318044/pathomechanisms-of-anti-cn1a-autoantibodies-in-sporadic-inclusion-body-myositis
#2
Nozomu Tawara, Satoshi Yamashita, Xiao Zhang, Mai Korogi, Ziwei Zhang, Tsukasa Doki, Yoshimasa Matsuo, Shunya Nakane, Yasushi Maeda, Kazuma Sugie, Naoki Suzuki, Masashi Aoki, Yukio Ando
OBJECTIVE: Sporadic inclusion body myositis (sIBM), an intractable progressive muscle disease, frequently occurs in older persons. sIBM pathogenesis may involve protein degradation dysfunction and immune abnormalities. Autoantibodies recognizing cytosolic 5'-nucleotidase 1A (cN1A) were found in plasma and serum from sIBM patients. Whether anti-cN1A autoantibodies play a pathogenic role in sIBM is controversial, however. This study investigated the pathogenic properties of anti-cN1A autoantibodies in sIBM pathogenesis...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28318037/deoxycytidine-and-deoxythymidine-treatment-for-thymidine-kinase-2-deficiency
#3
Carlos Lopez-Gomez, Rebecca J Levy, Maria J Sanchez-Quintero, Marti Juanola-Falgarona, Emanuele Barca, Beatriz Garcia-Diaz, Saba Tadesse, Caterina Garone, Michio Hirano
OBJECTIVE: Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2(-/-) ) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28318035/inclusion-body-myositis-pathogenesis-steady-progress
#4
EDITORIAL
Steven A Greenberg
No abstract text is available yet for this article.
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28271559/novel-screening-for-transthyretin-amyloidosis-by-using-fat-ultrasonography
#5
Yohei Misumi, Mitsuharu Ueda, Taro Yamashita, Teruaki Masuda, Yumiko Kinoshita, Masayoshi Tasaki, Terumasa Nagase, Yukio Ando
We aimed to assess the possibility of using a noninvasive screening method for hereditary transthyretin amyloidosis by means of abdominal fat ultrasonography. Quantitative analysis of ultrasound B-mode images demonstrated a significant increase in mean echogenicity and a loss of the normal structure of the layers of fat tissue in patients with hereditary transthyretin amyloidosis (n = 19). The ultrasound features of the fat tissue and the degree of amyloid deposition seen histopathologically showed a significant correlation...
March 8, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253561/the-neurology-of-acutely-failing-respiratory-mechanics
#6
Eelco F M Wijdicks
Forces involved in breathing-which effectively pull in air-are the diaphragmatic, intercostal, spine, and neck muscles. Equally important are the bulbar musculature maintaining the architecture of a patent airway conduit and abdominal wall and internal intercostal muscles providing cough. Acute injury along a neural trajectory from brainstem to muscle will impair the coordinated interaction between these muscle groups. Acutely failing respiratory mechanics can be caused by central and peripheral lesions. In central lesions, the key lesion is in the nucleus ambiguus innervating the dilator muscles of the soft palate, pharynx, and larynx, but abnormal respiratory mechanics rarely coincide with abnormalities of the respiratory pattern generator...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253550/olig1-is-required-for-noggin-induced-neonatal-myelin-repair
#7
Jennifer K Sabo, Vivi Heine, John C Silbereis, Lucas Schirmer, Steven W Levison, David H Rowitch
Objective - Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic injury, the downstream functional targets are poorly understood. The bHLH protein Olig1 promotes oligodendrocyte (OL) development and is essential during remyelination in adult mice. Here, we investigated whether Olig1 function is required downstream of BMP antagonism for the response to injury in the neonatal brain...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253549/the-immune-response-of-the-human-brain-to-abdominal-surgery
#8
Anton Forsberg, Simon Cervenka, Malin Jonsson Fagerlund, Lars S Rasmussen, Henrik Zetterberg, Helena Erlandsson Harris, Pernilla Stridh, Eva Christensson, Anna Granström, Anna Schening, Karin Dymmel, Nina Knave, Niccolò Terrando, Mervyn Maze, Jacqueline Borg, Andrea Varrone, Christer Halldin, Kaj Blennow, Lars Farde, Lars I Eriksson
OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. While preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by Positron Emission Tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers and cognitive function...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253547/wounded-brain-ailing-heart-central-autonomic-network-disruption-in-acute-stroke
#9
Peter Sörös, Vladimir Hachinski
No abstract text is available yet for this article.
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253546/fdg-metabolism-associated-with-tau-amyloid-interaction-predicts-memory-decline
#10
Bernard J Hanseeuw, Rebecca A Betensky, Aaron P Schultz, Kate V Papp, Elizabeth C Mormino, Jorge Sepulcre, John S Bark, Danielle M Cosio, Molly LaPoint, Jasmeer P Chhatwal, Dorene M Rentz, Reisa A Sperling, Keith Johnson
OBJECTIVE: To evaluate in normal older adults and preclinical Alzheimer's disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. METHODS: We acquired positron emission tomography using F18 Flortaucipir (tau), C11 Pittsburgh Compound B (amyloid) and F18 Fluorodeoxyglucose in 90 clinically normal elderly of the Harvard Aging Brain Study. RESULTS: Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253544/stroke-in-right-dorsal-anterior-insular-cortex-is-related-to-myocardial-injury
#11
Thomas Krause, Kathrin Werner, Jochen B Fiebach, Kersten Villringer, Sophie K Piper, Karl Georg Haeusler, Matthias Endres, Jan F Scheitz, Christian H Nolte
OBJECTIVE: Elevated levels of cardiac troponin and especially their relative changes over time indicate acute myocardial injury. They are also frequently observed after acute ischemic stroke (AIS), indicating poor functional outcome and increased mortality. However, recent evidence showed that in most AIS patients myocardial injury is not caused by coronary ischemia. Instead, stroke lesion location has been suggested to precipitate myocardial injury. METHODS: Voxel-based lesion-symptom mapping (VLSM) was employed in 299 patients who had an MRI-confirmed acute ischemic stroke within the anterior circulation and a high-sensitivity cardiac Troponin T (hs-cTnT) acquired on the day of admission...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253543/computed-tomography-based-acute-stroke-lesion-timing-and-patient-stratification
#12
LETTER
Risto A Kauppinen, Michael J Knight
No abstract text is available yet for this article.
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28253542/reply-to-a-letter-to-the-editor-related-article-computed-tomography-based-quantification-of-lesion-water-uptake-identifies-patients-within-4-5-hours-of-stroke-onset-a-multicenter-observational-study-observational-study-ann
#13
LETTER
https://www.readbyqxmd.com/read/28253535/homozygous-mutations-in-vamp1-cause-a-presynaptic-congenital-myasthenic-syndrome
#14
Vincenzo Salpietro, Weichun Lin, Andrea Delle Vedove, Markus Storbeck, Yun Liu, Stephanie Efthymiou, Andreea Manole, Sarah Wiethoff, Qiaohong Ye, Anand Saggar, Kenneth McElreavey, Shyam Krishnakumar, Matthew Pitt, Oscar Bello, James E Rothman, Lina Basel-Vanagaite, Monika Weisz Hubshman, Sharon Aharoni, Adnan Y Manzur, Brunhilde Wirth, Henry Houlden
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is required for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1(lew/lew) mice, observing neurophysiological features of presynaptic impairment, similar to the patients...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28241384/quantitative-muscle-ultrasound-detects-disease-progression-in-duchenne-muscular-dystrophy
#15
Craig M Zaidman, Jim S Wu, Kush Kapur, Amy Pasternak, Lavanya Madabusi, Sung Yim, Adam Pacheck, Heather Szelag, Tim Harrington, Basil T Darras, Seward B Rutkove
OBJECTIVE: We assessed changes in quantitative muscle ultrasound data in boys with Duchenne muscular dystrophy (DMD) and healthy controls to determine if ultrasound can serve as a biomarker of disease progression. Two approaches were used: grey scale level (GSL), measured from the ultrasound image, and quantitative backscatter analysis (QBA) measured directly from the received echoes. METHODS: GSL and QBA were obtained from six unilateral arm/leg muscles in 36 boys with DMD and 28 healthy boys (age 2-14 years) for up to 2 years...
February 27, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28224701/pathogenic-role-of-anti-srp-and-anti-hmgcr-antibodies-in-necrotizing-myopathies-myofiber-atrophy-and-impairment-of-muscle-regeneration-in-necrotizing-autoimmune-myopathies
#16
Louiza Arouche-Delaperche, Yves Allenbach, Damien Amelin, Corinna Preusse, Vincent Mouly, Wladimir Mauhin, Gaelle Dzangue Tchoupou, Laurent Drouot, Olivier Boyer, Werner Stenzel, Gillian Butler-Browne, Olivier Benveniste
OBJECTIVE: Immune mediated necrotizing myopathies (IMNM) may be associated with either anti-SRP or anti-HMGCR antibodies (Abs) and the titer of these Abs is correlated with the disease activity. We investigated if anti-SRP and anti-HMGCR Abs could be involved in muscle damages. METHODS: Muscle biopsies of patients were analyzed for atrophy and regeneration, by measuring the fibers size and by performing immunostaining of neonatal myosin heavy chain. To further understand the role of the Abs in the pathology, we performed muscle cell co-culture with the Abs...
February 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28224671/outcomes-after-diagnosis-of-mild-cognitive-impairment-in-a-large-autopsy-series
#17
Erin L Abner, Richard J Kryscio, Frederick A Schmitt, David W Fardo, Daniela C Moga, Eseosa T Ighodaro, Gregory A Jicha, Lei Yu, Hiroko H Dodge, Chengjie Xiong, Randall L Woltjer, Julie A Schneider, Nigel J Cairns, David A Bennett, Peter T Nelson
OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI). METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States. RESULTS: Mean follow-up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39...
February 22, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28220542/the-gut-microbiome-in-human-neurological-disease-a-review
#18
REVIEW
Helen Tremlett, Kylynda C Bauer, Silke Appel-Cresswell, Brett B Finlay, Emmanuelle Waubant
Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high-throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression...
February 21, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28220527/recessive-mypn-mutations-cause-cap-myopathy-with-occasional-nemaline-rods
#19
Xavière Lornage, Edoardo Malfatti, Chrystel Chéraud, Raphaël Schneider, Valérie Biancalana, Jean-Marie Cuisset, Matteo Garibaldi, Bruno Eymard, Michel Fardeau, Anne Boland, Jean-François Deleuze, Julie Thompson, Robert-Yves Carlier, Johann Böhm, Norma B Romero, Jocelyn Laporte
Congenital myopathies are phenotypically and genetically heterogeneous. We describe homozygous truncating mutations in MYPN in 2 unrelated families with a slowly progressive congenital cap myopathy. MYPN encodes the Z-line protein myopalladin implicated in sarcomere integrity. Functional experiments demonstrate that the mutations lead to mRNA defects and to a strong reduction in full-length protein expression. Myopalladin signals accumulate in the caps together with alpha-actinin. Dominant MYPN mutations were previously reported in cardiomyopathies...
February 21, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28220524/language-functional-mri-and-direct-cortical-stimulation-in-epilepsy-preoperative-planning
#20
Alison Austermuehle, John Cocjin, Richard Reynolds, Shubhi Agrawal, Leigh Sepeta, William D Gaillard, Kareem A Zaghloul, Sara Inati, William H Theodore
OBJECTIVE: Presurgical language assessment can help minimize damage to eloquent cortex during resective epilepsy surgery. Two methods for presurgical language mapping are functional MRI (fMRI) and direct cortical stimulation (DCS) of implanted subdural electrodes. We compared fMRI results to DCS to help optimize noninvasive language localization and assess its validity. METHODS: We studied 19 patients referred for presurgical evaluation of drug-resistant epilepsy...
February 21, 2017: Annals of Neurology
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