Annals of Neurology

Katherine Julian, Nicholas Yuhasz, Widjan Rai, Jose A Salerno, Jaime Imitola
"Stem cell tourism," the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the US. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures...
July 7, 2020: Annals of Neurology
Samia J Khoury
No abstract text is available yet for this article.
July 6, 2020: Annals of Neurology
Harold H G Tan, Henk-Jan Westeneng, Hannelore K van der Burgh, Michael A van Es, Leonhard A Bakker, Kevin van Veenhuijzen, Kristel R van Eijk, Ruben P A van Eijk, Jan H Veldink, Leonard H van den Berg
OBJECTIVE: The rs12608932 single nucleotide polymorphism in UNC13A is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) susceptibility, and may underlie differences in treatment response. We aimed to characterize the clinical, cognitive, behavioral, and neuroimaging phenotype of UNC13A in ALS patients. METHODS: We included 2,216 ALS patients without a C9orf72 mutation to identify clinical characteristics associated with the UNC13A polymorphism...
July 6, 2020: Annals of Neurology
Lindsey Wooliscroft, Devin Brown, Jeffrey Cohen, Lesli Skolarus, Elizabeth Silbermann
No abstract text is available yet for this article.
July 3, 2020: Annals of Neurology
Valérie Biousse, Nancy J Newman, Raymond P Najjar, Caroline Vasseneix, Xinxing Xu, Daniel S Ting, Léonard B Milea, Jeong-Min Hwang, Dong Hyun Kim, Hee Kyung Yang, Steffen Hamann, John J Chen, Yong Liu, Tien Yin Wong, Dan Milea
OBJECTIVE: To compare the diagnostic performance of an artificial intelligence deep learning system with that of expert neuro-ophthalmologists in classifying optic disc appearance. METHODS: The deep learning system was previously trained and validated on 14,341 ocular fundus photographs from 19 international centers. The performance of the system was evaluated on 800 new fundus photographs (400 normal optic discs, 201 papilledema [disc edema from elevated intracranial pressure], 199 other optic disc abnormalities) and compared with that of two expert neuro-ophthalmologists who independently reviewed the same randomly-presented images without clinical information...
July 3, 2020: Annals of Neurology
David Fischer, Zachary D Threlkeld, Yelena G Bodien, John E Kirsch, Susie Y Huang, Pamela W Schaefer, Otto Rapalino, Leigh R Hochberg, Bruce R Rosen, Brian L Edlow
Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands...
July 1, 2020: Annals of Neurology
Amytice Mirchi, Christine Saint-Martin, Kenneth A Myers
No abstract text is available yet for this article.
July 1, 2020: Annals of Neurology
N Petrova, E Nutma, D Carassiti, J Newman, S Amor, D R Altmann, D Baker, K Schmierer
Disability in multiple sclerosis (MS) is considered primarily a result of axonal loss. However, correlation with spinal cord cross-sectional area - a predictor of disability - is poor, questioning the unique role of axonal loss. We investigated the degree of synaptic loss in post-mortem spinal cords (18 chronic MS, eight healthy controls) using immunohistochemistry for synaptophysin and synapsin. Substantial (58-96%) loss of synapses throughout the spinal cord was detected, along with moderate (47%) loss of anterior horn neurons, notably in demyelinating MS lesions...
June 30, 2020: Annals of Neurology
Alessandra Fanciulli, Katharina Kerer, Fabian Leys, Klaus Seppi, Horacio Kaufmann, Lucy Norcliffe-Kaufmann, Gregor K Wenning
No abstract text is available yet for this article.
June 28, 2020: Annals of Neurology
Vera Rauschenberger, Niels V Wardenburg, Natascha Schaefer, Kazutoyo Ogino, Hiromi Hirata, Christina Lillesaar, Christoph J Kluck, Hans-Michael Meinck, Marc Borrmann, Andreas Weishaupt, Kathrin Doppler, Jonathan Wickel, Christian Geis, Claudia Sommer, Carmen Villmann
OBJECTIVE: Impairment of glycinergic neurotransmission leads to complex movement and behavioral disorders. Patients harboring glycine receptor autoantibodies suffer from stiff-person syndrome or its severe variant progressive encephalomyelitis with rigidity and myoclonus. Enhanced receptor internalization was proposed as the common molecular mechanism upon autoantibody binding. Although functional impairment of glycine receptors following autoantibody binding has recently been investigated, it is still incompletely understood...
June 26, 2020: Annals of Neurology
Thibaut Burg, Charlotte Bichara, Jelena Scekic-Zahirovic, Mathieu Fischer, Geoffrey Stuart-Lopez, Aurore Brunet, François Lefebvre, Matilde Cordero-Erausquin, Caroline Rouaux
OBJECTIVE: Recent studies carried on amyotrophic lateral sclerosis patients suggest that the disease may initiate in the motor cortex and spread to its targets along the corticofugal tracts. In this study, we aimed at experimentally testing the corticofugal hypothesis of amyotrophic lateral sclerosis. METHODS: Sod1G86R and Fezf2 knockout mouse lines were crossed to generate a model that ubiquitously expresses a mutant of the murine Sod1 gene, a condition sufficient to induce progressive motor symptoms and premature death, but genetically lacks corticospinal neurons and other subcerebral projection neurons, one of the main populations of corticofugal neurons...
June 26, 2020: Annals of Neurology
I A Mulder, M Li, T de Vries, T Qin, T Yanagisawa, K Sugimoto, A van den Bogaerdt, A H J Danser, M J H Wermer, A M J M van den Maagdenberg, A MaassenVanDenBrink, M D Ferrari, C Ayata
OBJECTIVE: CGRP pathway inhibitors are emerging treatments for migraine. CGRP-mediated vasodilation is, however, a critical rescue mechanism in ischemia. We, therefore, investigated whether gepants, small molecule CGRP receptor antagonists, worsen cerebral ischemia. METHODS: Middle cerebral artery was occluded for 12-60 minutes in mice. We compared infarct risk and volumes, collateral flow and neurological deficits after pretreatment with olcegepant (single or 10 daily doses of 0...
June 25, 2020: Annals of Neurology
Marc Carceles-Cordon, Francesco Mannara, Esther Aguilar, Aida Castellanos, Jesús Planagumà, Josep Dalmau
OBJECTIVE: To demonstrate that antibodies from patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis alter the levels of dopamine 1 receptor (D1R) and dopamine 2 receptor (D2R) and cause psychotic-like features in mice. METHODS: Cultured rat hippocampal neurons were treated with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, and the effects on clusters of D1R and D2R were quantified. In vivo studies included 71 C57BL/6J mice that were chronically infused with patients' or controls' CSF through ventricular catheters connected to subcutaneous osmotic pumps...
June 25, 2020: Annals of Neurology
Genna J Waldman, Kiran T Thakur, Caroline Der Nigoghossian, Vadim Spektor, Anil Mendiratta, Michelle Bell, Alyssa E Bautista, Laura Lennihan, Joshua Z Willey, Jan Claassen
No abstract text is available yet for this article.
June 25, 2020: Annals of Neurology
Daniel Goldenholz, Shira Goldenholz, Juan Romero, Rob Moss, Haoqi Sun, Brandon Westover
OBJECTIVE: There are no validated methods for predicting the timing of seizures. Using machine learning, we sought to forecast 24-hour risk of self-reported seizure from e-diaries. METHODS: Data from 5,419 patients of (including seizure count, type and duration) was split into training (3,806 patients/1,665,215 patient-days) and testing (1,613 patients/549,588 patient-days) sets with no overlapping patients. An artificial intelligence (AI) program, consisting recurrent networks followed by a multilayer perceptron ("deep learning" model) was trained to produce risk forecasts...
June 22, 2020: Annals of Neurology
Phillip L Pearl, Jonathan W Mink, Bruce H Cohen, Nigel Bamford, Nancy Bass, Lori Jordan, Mark S Wainwright, Roger Larson
No abstract text is available yet for this article.
June 22, 2020: Annals of Neurology
Seung-Hyun Lee, Yinhua Zhang, Jina Park, Bowon Kim, Yangsik Kim, Sang Hoon Lee, Gyu Hyun Kim, Yang Hoon Huh, Bokyoung Lee, Yoonhee Kim, Yeunkum Lee, Jin Yong Kim, Hyojin Kang, Su-Yeon Choi, Seil Jang, Yan Li, Shinhyun Kim, Chunmei Jin, Kaifang Pang, Eunjeong Kim, Yoontae Lee, Hyun Kim, Eunjoon Kim, Jee Hyun Choi, Jeongjin Kim, Kea Joo Lee, Se-Young Choi, Kihoon Han
OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy...
June 20, 2020: Annals of Neurology
Zoe Arvanitakis, Hoau-Yan Wang, Ana W Capuano, Amber Khan, Bouchra Taïb, Frederick Anokye-Danso, Julie A Schneider, David A Bennett, Rexford S Ahima, Steven E Arnold
OBJECTIVE: To examine associations of molecular markers of brain insulin signaling with Alzheimer's disease (AD) and cognition, among older persons with or without diabetes. METHODS: This clinical-pathologic study was derived from a community-based cohort study, the Religious Orders Study. We studied 150 individuals (mean age-at-death =87 years, 48% women): 75 with and 75 without diabetes (matched by sex on age-at-death and education). Using ELISA, immunohistochemistry and ex vivo stimulation of brain tissue with insulin, we assessed insulin signaling in the postmortem middle frontal gyrus cortex...
June 18, 2020: Annals of Neurology
Wolfgang Singer, Ann M Schmeichel, Mohammad Shahnawaz, James D Schmelzer, Bradley F Boeve, David M Sletten, Tonette L Gehrking, Jade A Gehrking, Anita D Olson, Rodolfo Savica, Mariana D Suarez, Claudio Soto, Phillip A Low
OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings to Lewy body synucleinopathies. METHODS: In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14) we utilized ELISA to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF...
June 18, 2020: Annals of Neurology
E Salari, Z V Freudenburg, M J Vansteensel, N F Ramsey
Facial expressions are important for intentional display of emotions in social interaction. For people with severe paralysis, the ability to intentionally display emotions can be impaired. Current brain-computer interfaces (BCIs) allow for linguistic communication but are cumbersome for expressing emotions. Here, we investigated the feasibility of a BCI to display emotions by decoding facial expressions. We used electrocorticographic recordings from the sensorimotor cortex of people with refractory epilepsy and classified 5 facial expressions, based on neural activity...
June 17, 2020: Annals of Neurology
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