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Annals of Neurology

Simon J Schreiner, Lukas L Imbach, Esther Werth, Rositsa Poryazova, Heide Baumann-Vogel, Philipp O Valko, Tobias Murer, Daniela Noain, Christian R Baumann
Growing evidence from Alzheimer disease supports a potentially beneficial role of slow-wave sleep in neurodegeneration. However, the importance of slow-wave sleep in Parkinson disease is unknown. In 129 patients with Parkinson disease, we retrospectively tested whether sleep slow waves, objectively quantified with polysomnography, relate to longitudinal changes in Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power of sleep slow waves was associated with slower motor progression, particularly of axial motor symptoms, over a mean time of 4...
March 18, 2019: Annals of Neurology
Carmel Armon
No abstract text is available yet for this article.
March 18, 2019: Annals of Neurology
Carmel Armon
No abstract text is available yet for this article.
March 15, 2019: Annals of Neurology
Antonio F Martínez-Monseny, Mercè Bolasell, Laura Callejón-Póo, Daniel Cuadras, Verónica Freniche, Débora C Itzep, Susanna Gassiot, Pedro Arango, Didac Casas-Alba, Eugenia de la Morena, Javier Corral, Raquel Montero, Celia Pérez-Cerdá, Belén Pérez, Rafael Artuch, Jaak Jaeken, Mercedes Serrano
OBJECTIVE: Phosphomannomutase deficiency (PMM2-CDG) causes cerebellar syndrome and stroke-like episodes (SLEs). SLEs are also described in patients with gain-of-function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested. Impairment in N-glycosylation of CaV2.1 promotes gain-of-function effects and may participate in cerebellar syndrome in PMM2-CDG. AZATAX was designed to establish whether acetazolamide is safe and improves cerebellar syndrome in PMM2-CDG. METHODS: A clinical trial included PMM2-CDG patients with a 6-month first-phase single acetazolamide therapy group, followed by a randomized 5-week withdrawal phase...
March 14, 2019: Annals of Neurology
Andrea Morotti, Giorgio Busto, Andrea Bernardoni, Carmine Tamborino, Enrico Fainardi
We investigated whether CT perfusion can identify intracerebral hemorrhage patients at high risk of hematoma growth (HG). A total of 155 subjects underwent CT perfusion on admission. Variables associated with log-transformed absolute HG were explored with multivariable linear regression. Perihematomal cerebral blood volume (CBV) was inversely associated with HG (B=-0.20,p<0.001), independently from blood pressure, ICH volume and other confounders. This association was not dose-dependent and only very low CBV (<1...
March 12, 2019: Annals of Neurology
Chih-Hsien Tseng, Yin-Hsiu Chien, Ni-Chung Lee, Yung-Chin Hsu, Shinn-Forng Peng, Wen-Yih I Tseng, Wuh-Liang Hwu
OBJECTIVE: Children with aromatic l-amino acid decarboxylase (AADC) deficiency suffer from severe motor dysfunction. Restoration of dopamine levels in the putamen by gene therapy has led to significant improvement in motor function. This study explored brain structure changes in patients. METHODS: Brain diffusion tensor imaging (DTI) were performed before and 12 months after gene therapy. Whole-brain tract-specific analysis was performed to assess white matter microstructural integrity...
March 12, 2019: Annals of Neurology
Collin J Anderson, Karla P Figueroa, Alan D Dorval, Stefan M Pulst
OBJECTIVE: Degenerative cerebellar ataxias (DCAs) affect up to 1 in 5,000 people worldwide, leading to incoordination, tremor, and falls. Loss of Purkinje cells, nearly universal across DCAs, dysregulates the dentatothalamocortical network. To address the paucity of treatment strategies, we developed an electrical stimulation-based therapy for DCAs targeting the dorsal dentate nucleus. METHODS: We tested this therapeutic strategy in the Wistar Furth shaker rat model of Purkinje cell loss resulting in tremor and ataxia...
March 10, 2019: Annals of Neurology
Lucia Aa Giannini, Sharon X Xie, Corey T McMillan, Mendy Liang, Andrew Williams, Charles Jester, Katya Rascovsky, David A Wolk, Sharon Ash, Edward B Lee, John Q Trojanowski, Murray Grossman, David J Irwin
OBJECTIVE: To measure postmortem burden of frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) or tau (FTLD-Tau) proteinopathy across hemispheres in primary progressive aphasia (PPA) using digital histopathology, and identify clinicopathological correlates of these distinct proteinopathies. METHODS: In an autopsy cohort of PPA (FTLD-TDP=13, FTLD-Tau=14), we analyzed laterality and regional distribution of postmortem pathology, quantified using a validated digital histopathological approach, in available brain tissue from up to eight cortical regions bilaterally...
March 9, 2019: Annals of Neurology
Bruce A C Cree, Jill A Hollenbach, Riley Bove, Gina Kirkish, Simone Sacco, Eduardo Caverzasi, Antje Bischof, Tristan Gundel, Alyssa H Zhu, Nico Papinutto, William A Stern, Carolyn Bevan, Andrew Romeo, Douglas S Goodin, Jeffrey M Gelfand, Jennifer Graves, Ari J Green, Michael R Wilson, Scott S Zamvil, Chao Zhao, Refujia Gomez, Nicholas R Ragan, Gillian Q Rush, Patrick Barba, Adam Santaniello, Sergio E Baranzini, Jorge R Oksenberg, Roland G Henry, Stephen L Hauser
OBJECTIVE: Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pre-treatment era. Nonetheless, in our recently reported prospective cohort more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2-years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation...
March 9, 2019: Annals of Neurology
Rachel C Nolan, Mengling Liu, Omar Akhand, Peter A Calabresi, Friedemann Paul, Axel Petzold, Lisanne Balk, Alexander U Brandt, Elena H Martínez-Lapiscina, Shiv Saidha, Pablo Villoslada, Abdullah Abu Al-Hassan, Raed Behbehani, Elliot M Frohman, Teresa Frohman, Joachim Havla, Bernhard Hemmer, Hong Jiang, Benjamin Knier, Thomas Korn, Letizia Leocani, Athina Papadopoulou, Marco Pisa, Hanna Zimmermann, Steven L Galetta, Laura J Balcer
OBJECTIVE: To determine the optimal thresholds for inter-eye differences in retinal nerve fiber and ganglion cell+inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. BACKGROUND: Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS: In this multi-center international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium...
March 9, 2019: Annals of Neurology
Martina Absinta, Govind Nair, Maria Chiara G Monaco, Dragan Maric, Nathanael J Lee, Seung-Kwon Ha, Nicholas J Luciano, Pascal Sati, Steven Jacobson, Daniel S Reich
Accumulating evidence corroborates the role of the "central vein sign" in the radiological diagnosis of multiple sclerosis (MS). Here, we report human MRI-pathological data that inflammation-dependent intracerebral remodeling of the vessel wall is directly associated with the prominence of intralesional veins on susceptibility-based MRI. In adult marmosets with experimental autoimmune encephalomyelitis (EAE), vessel-wall fibrosis was detected early in the demyelinating process, even in lesions less than two weeks old, though fibrosis was more evident after 6 weeks...
March 7, 2019: Annals of Neurology
Eva-Verena Griemert, Susanne M Schwarzmaier, Regina Hummel, Christina Gölz, Dong Yang, Winfried Neuhaus, Malgorzata Burek, Carola Y Förster, Ivan Petkovic, Raimund Trabold, Nikolaus Plesnila, Kristin Engelhard, Michael K Schäfer, Serge C Thal
OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates posttraumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. METHODS: We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury (TBI)...
March 6, 2019: Annals of Neurology
Nina Kerstin Wenke, Jakob Kreye, Ewa Andrzejak, Adriana van Casteren, Jonas Leubner, Manuela S Murgueitio, S Momsen Reincke, Christopher Secker, Lars Schmidl, Christian Geis, Frauke Ackermann, Marc Nikolaus, Craig C Garner, Hedda Wardemann, Gerhard Wolber, Harald Prüss
Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is the most common autoimmune encephalitis related to autoantibody-mediated synaptic dysfunction. Cerebrospinal fluid-derived human monoclonal NR1 autoantibodies showed low numbers of somatic hypermutations or were unmutated. These unexpected germline-configured antibodies showed weaker binding to the NMDAR than matured antibodies from the same patient. In primary hippocampal neurons, germline NR1 autoantibodies strongly and specifically reduced total and synaptic NMDAR currents in a dose- and time-dependent manner...
March 6, 2019: Annals of Neurology
Anil R Wadhwani, Amira Affaneh, Stephanie Van Gulden, John A Kessler
OBJECTIVE: The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). While APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age-related cognitive impairment, neurological injury, and neurodegeneration. Here we show that endogenous expression of E4 in stem-cell derived neurons predisposes them to injury and promotes the release of phosphorylated tau...
March 6, 2019: Annals of Neurology
Xinyi Leng, Linfang Lan, Hing Lung Ip, Jill Abrigo, Fabien Scalzo, Haipeng Liu, Xueyan Feng, Ka Lung Chan, Florence Sy Fan, Sze Ho Ma, Hui Fang, Yuming Xu, Jingwei Li, Bing Zhang, Yun Xu, Yannie Oy Soo, Vincent Ct Mok, Simon Ch Yu, David S Liebeskind, Ka Sing Wong, Thomas W Leung
OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50-99% ICAS confirmed in CT angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR =Pressurepost - stenotic /Pressurepre - stenotic ) and translesional wall shear stress ratio (WSSR =WSSstenotic - throat /WSSpre - stenotic ) were obtained in each sICAS lesion...
March 6, 2019: Annals of Neurology
Niccolo Candelise, Matthias Schmitz, Franc Llorens, Anna Villar-Piqué, Maria Cramm, Tobias Thom, Susana Margarida da Silva Correia, José Eriton Gomes da Cunha, Wiebke Möbius, Tiago F Outeiro, Valentina González Álvarez, Martina Banchelli, Cristiano D'Andrea, Marella de Angelis, Saima Zafar, Alberto Rabano, Paolo Matteini, Inga Zerr
OBJECTIVES: Currently, the exact reasons why different α-synucleinopathies exhibit variable pathologies and phenotypes are still unknown. A potential explanation may be the existence of distinctive α-synuclein conformers or strains. Here, we intend to analyse the seeding activity of Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) brain derived α-synuclein seeds via real-time quaking-induced conversion (RT-QuIC) and to investigate the structure and morphology of the α-synuclein aggregates generated via RT-QuIC...
February 25, 2019: Annals of Neurology
Jing Xu, Meret Branscheidt, Heidi Schambra, Levke Steiner, Mario Widmer, Jörn Diedrichsen, Jeff Goldsmith, Martin Lindquist, Tomoko Kitago, Andreas R Luft, John W Krakauer, Pablo A Celnik
OBJECTIVE: Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition from the intact to the damaged hemisphere prior to movement execution (pre-movement-IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke, and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal pre-movement-IHI is causal to poor behavioral outcome, and should therefore be present early after stroke when motor impairment is at its worst...
February 25, 2019: Annals of Neurology
Silvia Morbelli, Andrea Chincarini, Matthias Brendel, Axel Rominger, Rose Bruffaerts, Rik Vandenberghe, Milica G Kramberger, Maja Trost, Valentina Garibotto, Nicolas Nicastro, Giovanni B Frisoni, Afina W Lemstra, Jessica van der Zande, Andrea Pilotto, Alessandro Padovani, Sara Garcia-Ptacek, Irina Savitcheva, Miguel A Ochoa-Figueroa, Annette Davidsson, Valle Camacho, Enrico Peira, Dario Arnaldi, Matteo Bauckneht, Matteo Pardini, Gianmario Sambuceti, Dag Aarsland, Flavio Nobili
OBJECTIVE: To identify brain regions whose metabolic impairment contributes to DLB clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB-hypometabolic-pattern. METHODS: Brain FDG-PET and information on core features were available in 171 patients belonging to the imaging repository of the European DLB-consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance...
February 25, 2019: Annals of Neurology
Pietro Guaraldi, Giovanna Calandra-Buonaura, Federica Provini, Pietro Cortelli
No abstract text is available yet for this article.
February 25, 2019: Annals of Neurology
Joel C Geerling, Aaron D Boes
No abstract text is available yet for this article.
February 25, 2019: Annals of Neurology
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