Browsing by Subject "Neurology"

Now showing 1 - 10 of 19
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    ADAS-viewer: web-based application for integrative analysis of multi-omics data in Alzheimer’s disease
    (Springer Nature, 2021-03-19) Han, Seonggyun; Shin, Jaehang; Jung, Hyeim; Ryu, Jane; Minassie, Habtamu; Nho, Kwangsik; Koh, Insong; Lee, Younghee; Radiology and Imaging Sciences, School of Medicine
    Alzheimer’s disease (AD) is a neurodegenerative disorder and is represented by complicated biological mechanisms and complexity of brain tissue. Our understanding of the complicated molecular architecture that contributes to AD progression benefits from performing comprehensive and systemic investigations with multi-layered molecular and biological data from different brain regions. Since recently different independent studies generated various omics data in different brain regions of AD patients, multi-omics data integration can be a useful resource for better comprehensive understanding of AD. Here we present a web platform, ADAS-viewer, that provides researchers with the ability to comprehensively investigate and visualize multi-omics data from multiple brain regions of AD patients. ADAS-viewer offers means to identify functional changes in transcript and exon expression (i.e., alternative splicing) along with associated genetic or epigenetic regulatory effects. Specifically, it integrates genomic, transcriptomic, methylation, and miRNA data collected from seven different brain regions (cerebellum, temporal cortex, dorsolateral prefrontal cortex, frontal pole, inferior frontal gyrus, parahippocampal gyrus, and superior temporal gyrus) across three independent cohort datasets. ADAS-viewer is particularly useful as a web-based application for analyzing and visualizing multi-omics data across multiple brain regions at both transcript and exon level, allowing the identification of candidate biomarkers of Alzheimer’s disease.
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    Contemporary Neuroscience Core Curriculum for Medical Schools
    (Wolters Kluwer, 2021-10-04) Gelb, Douglas J.; Kraakevik, Jeff; Safdieh, Joseph E.; Agarwal, Sachin; Odia, Yazmin; Govindarajan, Raghav; Quick, Adam; Soni, Madhu; AAN Undergraduate Education Subcommittee (UES); Bickel, Jennifer; Gamaldo, Charlene; Hannon, Peter; Hatch, Hayden A. M.; Hernandez, Christian; Merlin, Lisa R.; Noble, James M.; Reyes-Iglesias, Yolanda; Salas, Rachel Marie E.; Sandness, David James; Treat, Lauren; AAN Education Committee; Benameur, Karima; Brown, Robert D., Jr.; DeLuca, Gabriele C.; Garg, Neeta; Goldstein, Larry B.; Gutmann, Laurie; Henchcliffe, Claire; Hessler, Amy; Jordan, Justin T.; Kilgore, Shannon M.; Khan, Jaffar; Levin, Kerry H.; Mohile, Nimish A.; Nevel, Kathryn S.; Roberts, Kirk; Said, Rana R.; Simpson, Ericka P.; Sirven, Joseph I.; Smith, A. Gordon; Southerland, Andrew Mebane; Wilson, Rujuta B.; Neurology, School of Medicine
    Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also because the nervous system plays such a critical role in the function of every organ system. Because of the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the preclerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are reassessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the preclerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.
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    Core outcomes in neonatal encephalopathy: a qualitative study with parents
    (BMJ, 2022) Quirke, Fiona; Ariff, Shabina; Battin, Malcolm; Bernard, Caitlin; Bloomfield, Frank H.; Daly, Mandy; Devane, Declan; Haas, David M.; Healy, Patricia; Hurley, Tim; Kibet, Vincent; Kirkham, Jamie J.; Koskei, Sarah; Meher, Shireen; Molloy, Eleanor; Niaz, Maira; Ní Bhraonáin, Elaine; Omukagah Okaronon, Christabell; Tabassum, Farhana; Walker, Karen; Biesty, Linda; Obstetrics and Gynecology, School of Medicine
    Objective: To identify the outcomes considered important to parents or caregivers of infants diagnosed with neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia in high-income and low- to middle-income countries (LMiCs), as part of the outcome-identification process in developing a core outcome set (COS) for the treatment of neonatal encephalopathy. Design: A qualitative study involving 25 semistructured interviews with parents or other family members (caregivers) of infants who were diagnosed with, and treated for, neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia. Setting: Interviews were conducted in high-income countries (HiCs) (n=11) by Zoom video conferencing software and in LMiCs (n=14) by phone or face to face. Findings: Parents identified 54 outcomes overall, which mapped to 16 outcome domains. The domains identified were neurological outcomes, respiratory outcomes, gastrointestinal outcomes, cardiovascular outcomes, motor development, cognitive development, development (psychosocial), development (special senses), cognitive development, development (speech and social), other organ outcomes, survival/living outcomes, long-term disability, hospitalisation, parent-reported outcomes and adverse events. Conclusions: This study provides insight into the outcomes that parents of infants diagnosed with neonatal encephalopathy have identified as the most important, to be considered in the process of developing a COS for the treatment of neonatal encephalopathy. We also provide description of the processes employed to ensure the inclusion of participants from LMiCs as well as HiCs.
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    Digital Scientific Platform for Independent Content in Neurology: Rigorous Quality Guideline Development and Implementation
    (JMIR, 2022-06-09) Kantor, Daniel; Farlow, Martin; Ludolph, Albert; Montaner, Joan; Sankar, Raman; Sawyer, Robert N., Jr.; Stocchi, Fabrizio; Lara, Agnès; Clark, Sarah; Deschet, Karine; Ouyahia, Loucif; Hadjiat, Yacine; Neurology, School of Medicine
    Background: Digital communication has emerged as a major source of scientific and medical information for health care professionals. There is a need to set up an effective and reliable methodology to assess and monitor the quality of content that is published on the internet. Objective: The aim of this project was to develop content quality guidelines for Neurodiem, an independent scientific information platform dedicated to neurology for health care professionals and neuroscientists. These content quality guidelines are intended to be used by (1) content providers as a framework to meet content quality standards and (2) reviewers as a tool for analyzing and scoring quality of content. Methods: Specific scientific criteria were designed using a 5-point scale to measure the quality of curated and original content published on the website: for Summaries, (1) source reliability and topic relevance for neurologists, (2) structure, and (3) scientific and didactic value; for Congress highlights, (1) relevance of congress selection, (2) congress coverage based on the original program, and (3) scientific and didactic value of individual abstracts; for Expert points of view and talks, (1) credibility (authorship) and topic relevance for neurologists, (2) scientific and didactic value, and (3) reliability (references) and format. The criteria were utilized on a monthly basis and endorsed by an independent scientific committee of widely recognized medical experts in neurology. Results: Summary content quality for the 3 domains (reliability and relevance, structure, and scientific and didactic value) increased in the second month after the implementation of the guidelines. The domain scientific and didactic value had a mean score of 8.20/10. Scores for the domains reliability and relevance (8-9/10) and structure (45-55/60) showed that the maintenance of these 2 quality items over time was more challenging. Talks (either in the format of interviews or slide deck-supported scientific presentations) and expert point of view demonstrated high quality after the implementation of the content quality guidelines that was maintained over time (15-25/25). Conclusions: Our findings support that content quality guidelines provide both (1) a reliable framework for generating independent high-quality content that addresses the educational needs of neurologists and (2) are an objective evaluation tool for improving and maintaining scientific quality level. The use of these criteria and this scoring system could serve as a standard and reference to build an editorial strategy and review process for any medical news or platforms.
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    Discovering Value and Impact: Evaluating a New Art Therapy in Neuroscience and Medicine Program
    (2017) Riddle, Maria; King, Juliet
    This study is a mixed-method approach for evaluating a new Art Therapy in Neuroscience and Medicine (ATNM) program within an outpatient academic medical center that provides a range of medical and psychiatric services to individuals with neurologic and psychiatric conditions. The aims were to assess the value of the ATNM program and the impact it has on affecting depressive mood among individuals who were receiving art therapy services (N=15). The Patient Health Questionnaire-9 (PHQ-9) and Client Satisfaction Questionnaire-8 (CSQ-8) were used to obtain baseline data regarding depressive mood and client satisfaction. Patient demographics were gathered using the ATNM tracking system and the medical center’s electronic medical record system to further understand the value and impact of the program. The preliminary data indicated an overall significant level of depression and anxiety among the referrals of patients having chronic neurological conditions. A high level of patient satisfaction and substantial benefit from art therapy intervention was noted in the results from the CSQ-8. Further evaluation of the program is recommended as an ongoing part of assessing the impact and value of the ATNM program.
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    Enhancing excitatory activity of somatosensory cortex alleviates neuropathic pain through regulating homeostatic plasticity
    (Nature Publishing group, 2017-10-06) Xiong, Wenhui; Ping, Xingjie; Ripsch, Matthew S.; Chavez, Grace Santa Cruz; Hannon, Heidi Elise; Jiang, Kewen; Bao, Chunhui; Jadhav, Vaishnavi; Chen, Lifang; Chai, Zhi; Ma, Cungen; Wu, Huangan; Feng, Jianqiao; Blesch, Armin; White, Fletcher A.; Jin, Xiaoming; Anatomy and Cell Biology, School of Medicine
    Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic pain. We hypothesize that development of cortical hyperexcitability underlying neuropathic pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation and activity loss, and can be controlled by enhancing cortical activity. In a mouse model of neuropathic pain, in vivo two-photon imaging and patch clamp recording showed initial loss and subsequent recovery and enhancement of spontaneous firings of somatosensory cortical pyramidal neurons. Unilateral optogenetic stimulation of cortical pyramidal neurons both prevented and reduced pain-like behavior as detected by bilateral mechanical hypersensitivity of hindlimbs, but corpus callosotomy eliminated the analgesic effect that was ipsilateral, but not contralateral, to optogenetic stimulation, suggesting involvement of inter-hemispheric excitatory drive in this effect. Enhancing activity by focally blocking cortical GABAergic inhibition had a similar relieving effect on the pain-like behavior. Patch clamp recordings from layer V pyramidal neurons showed that optogenetic stimulation normalized cortical hyperexcitability through changing neuronal membrane properties and reducing frequency of excitatory postsynaptic events. We conclude that development of neuropathic pain involves abnormal homeostatic activity regulation of somatosensory cortex, and that enhancing cortical excitatory activity may be a novel strategy for preventing and controlling neuropathic pain.
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    Establishment and characterization of patient-derived xenograft of a rare pediatric anaplastic pleomorphic xanthoastrocytoma (PXA) bearing a CDC42SE2-BRAF fusion
    (Springer Nature, 2023-06-06) Damayanti, Nur P.; Saadatzadeh, M. Reza; Dobrota, Erika; Ordaz, Josue D.; Bailey, Barbara J.; Pandya, Pankita H.; Bijangi-Vishehsaraei, Khadijeh; Shannon, Harlan E.; Alfonso, Anthony; Coy, Kathy; Trowbridge, Melissa; Sinn, Anthony L.; Zhang, Zhong-Yin; Gallagher, Rosa I.; Wulfkuhle, Julia; Petricoin, Emanuel; Richardson, Angela M.; Marshall, Mark S.; Lion, Alex; Ferguson, Michael J.; Balsara, Karl E.; Pollok, Karen E.; Neurological Surgery, School of Medicine
    Pleomorphic xanthoastrocytoma (PXA) is a rare subset of primary pediatric glioma with 70% 5-year disease free survival. However, up to 20% of cases present with local recurrence and malignant transformation into more aggressive type anaplastic PXA (AXPA) or glioblastoma. The understanding of disease etiology and mechanisms driving PXA and APXA are limited, and there is no standard of care. Therefore, development of relevant preclinical models to investigate molecular underpinnings of disease and to guide novel therapeutic approaches are of interest. Here, for the first time we established, and characterized a patient-derived xenograft (PDX) from a leptomeningeal spread of a patient with recurrent APXA bearing a novel CDC42SE2-BRAF fusion. An integrated -omics analysis was conducted to assess model fidelity of the genomic, transcriptomic, and proteomic/phosphoproteomic landscapes. A stable xenoline was derived directly from the patient recurrent tumor and maintained in 2D and 3D culture systems. Conserved histology features between the PDX and matched APXA specimen were maintained through serial passages. Whole exome sequencing (WES) demonstrated a high degree of conservation in the genomic landscape between PDX and matched human tumor, including small variants (Pearson's r = 0.794-0.839) and tumor mutational burden (~ 3 mutations/MB). Large chromosomal variations including chromosomal gains and losses were preserved in PDX. Notably, chromosomal gain in chromosomes 4-9, 17 and 18 and loss in the short arm of chromosome 9 associated with homozygous 9p21.3 deletion involving CDKN2A/B locus were identified in both patient tumor and PDX sample. Moreover, chromosomal rearrangement involving 7q34 fusion; CDC42SE-BRAF t (5;7) (q31.1, q34) (5:130,721,239, 7:140,482,820) was identified in the PDX tumor, xenoline and matched human tumor. Transcriptomic profile of the patient's tumor was retained in PDX (Pearson r = 0.88) and in xenoline (Pearson r = 0.63) as well as preservation of enriched signaling pathways (FDR Adjusted P < 0.05) including MAPK, EGFR and PI3K/AKT pathways. The multi-omics data of (WES, transcriptome, and reverse phase protein array (RPPA) was integrated to deduce potential actionable pathways for treatment (FDR < 0.05) including KEGG01521, KEGG05202, and KEGG05200. Both xenoline and PDX were resistant to the MEK inhibitors trametinib or mirdametinib at clinically relevant doses, recapitulating the patient's resistance to such treatment in the clinic. This set of APXA models will serve as a preclinical resource for developing novel therapeutic regimens for rare anaplastic PXAs and pediatric high-grade gliomas bearing BRAF fusions.
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    Hemichorea-hemiballismus due to diabetic striatopathy a serious complication of uncontrolled diabetes
    (BMJ, 2024-05-22) Middleton, Brian; Albany, Zhanna; Kamer, Aaron; Kara, Areeba; Radiology and Imaging Sciences, School of Medicine
    We report the case of a man in his mid-80s with diabetes mellitus who presented to the emergency department with a 1-day history of right-sided choreiform movements and falls. Laboratory tests revealed blood glucose of 597 mg/dL. Non-contrast CT imaging of his head demonstrated a faint hyperdensity involving the left lentiform nucleus and brain MRI showed a hyperintensity in the left basal ganglia on T1-weighted images. These lesions are typical of diabetic striatopathy. Symptoms of hemichorea/hemiballismus did not resolve with glycaemic control and several pharmacological agents were tried with eventual improvement with risperidone. He was discharged to a rehabilitation facility and had mild persistent arm chorea at 6-month follow-up.
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    High-throughput segmentation of unmyelinated axons by deep learning
    (Springer Nature, 2022-01-24) Plebani, Emanuele; Biscola, Natalia P.; Havton, Leif A.; Rajwa, Bartek; Shemonti, Abida Sanjana; Jaffey, Deborah; Powley, Terry; Keast, Janet R.; Lu, Kun‑Han; Dundar, M. Murat; Computer and Information Science, School of Science
    Axonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats. All unmyelinated axons in these images are individually annotated and used as labeled data to train and validate a deep instance segmentation network. We investigate the effect of different training strategies on the overall segmentation accuracy of the network. We extensively validate the segmentation algorithm as a stand-alone segmentation tool as well as in an expert-in-the-loop hybrid segmentation setting with preliminary, albeit remarkably encouraging results. Our algorithm achieves an instance-level F1 score of between 0.7 and 0.9 on various test images in the stand-alone mode and reduces expert annotation labor by 80% in the hybrid setting. We hope that this new high-throughput segmentation pipeline will enable quick and accurate characterization of unmyelinated fibers at scale and become instrumental in significantly advancing our understanding of connectomes in both the peripheral and the central nervous systems.
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    Lawful physician-hastened death: AAN position statement
    (Wolters Kluwer, 2018-02-27) Russell, James A.; Epstein, Leon G.; Bonnie, Richard J.; Conwit, Robin; Graf, William D.; Kirschen, Matthew; Kurek, Julie A.; Larriviere, Daniel G.; Pascuzzi, Robert M.; Rizzo, Matthew; Sattin, Justin A.; Simmons, Zachary; Taylor, Lynne; Tsou, Amy; Williams, Michael A.; Neurology, School of Medicine