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Articles 1 - 30 of 94
Full-Text Articles in Neurology
Unveiling The Potential Application Of Intraoperative Brain Smear For Brain Tumor Diagnosis In Low-Middle-Income Countries: A Comprehensive Systematic Review, Muhammad Shakir, Ahmed Altaf, Hawra Hussain, Syed Muhammad Aqeel Abidi, Zoey Petitt, Mahnoor Tariq, Ahmed Gilani, Syed Ather Enam
Unveiling The Potential Application Of Intraoperative Brain Smear For Brain Tumor Diagnosis In Low-Middle-Income Countries: A Comprehensive Systematic Review, Muhammad Shakir, Ahmed Altaf, Hawra Hussain, Syed Muhammad Aqeel Abidi, Zoey Petitt, Mahnoor Tariq, Ahmed Gilani, Syed Ather Enam
Section of Neurosurgery
Background: Immediate intraoperative histopathological examination of tumor tissue is indispensable for a neurosurgeon to track surgical resection. A brain smear is a simple, rapid, and cost-effective technique, particularly important in the diagnosis of brain tumors. The study aims to determine the effectiveness of intraoperative brain smear in the diagnosis of brain tumors in low- and middle-income countries (LMICs), while also evaluating its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy.
Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Google Scholar. The retrieved articles were independently screened by two reviewers. The …
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Department of Pathology and Laboratory Medicine
Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …
Intracranial Mesenchymal Tumors With Fet-Creb Fusion Are Composed Of At Least Two Epigenetic Subgroups Distinct From Meningioma And Extracranial Sarcomas, Emily A. Sloan, Rohit Gupta, Christian Koelsche, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer E. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din
Intracranial Mesenchymal Tumors With Fet-Creb Fusion Are Composed Of At Least Two Epigenetic Subgroups Distinct From Meningioma And Extracranial Sarcomas, Emily A. Sloan, Rohit Gupta, Christian Koelsche, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer E. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din
Department of Pathology and Laboratory Medicine
Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of …
Atypical Involvement Of Central Nervous System In Classic Hodgkin Lymphoma: A Case Report, Shanila Ahmed, Babar Irfan, Muhammad Raza, Ghulam Haider
Atypical Involvement Of Central Nervous System In Classic Hodgkin Lymphoma: A Case Report, Shanila Ahmed, Babar Irfan, Muhammad Raza, Ghulam Haider
Section of Haematology/Oncology
Background: Hodgkin lymphoma is a systemic disease that commonly involves the cervical, supraclavicular, and mediastinal lymph nodes. The involvement of central nervous system in Hodgkin lymphoma is extremely rare, and diagnosis is usually established using distinct morphological and immunohistochemical staining on the tissue biopsied. Extranodal presentation of HL is a rare occurrence. It has been evident that prognosis is encouraging in patients with disease that is limited to just central nervous system initially or as relapse, compared with involvement of multiple sites of relapse.
Case presentation: We herein report a case of a 35-year-old South-East Asian male with relapsed Hodgkin …
Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo
Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo
Biostatistics Faculty Publications
Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …
Case Report: Post-Partum Headache, Alaleh Ebrahimi
Case Report: Post-Partum Headache, Alaleh Ebrahimi
Rowan-Virtua Research Day
Cerebral venous sinus thromboses are rare and occur in 5 people/1,000,000, more commonly in women that are pregnant at about 202/100,000 deliveries with an 11.63% mortality rate. It is believed that pregnancy being a hypercoagulable state is one of the main reasons that it is more common in pregnant and post-partum women. Common symptoms include sudden onset headache, blurry vision, focal neuro deficits, seizures and altered mental status.
Space-Occupying Brain Lesions, Trauma-Related Tau Astrogliopathy, And Artag: A Report Of Two Cases And A Literature Review, Adam D. Bachstetter, Filip G. Garrett, Gregory A. Jicha, Peter T. Nelson
Space-Occupying Brain Lesions, Trauma-Related Tau Astrogliopathy, And Artag: A Report Of Two Cases And A Literature Review, Adam D. Bachstetter, Filip G. Garrett, Gregory A. Jicha, Peter T. Nelson
Spinal Cord and Brain Injury Research Center Faculty Publications
Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age-affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the …
Gliosarcoma In Patients Under 20 Years Of Age. A Clinicopathologic Study Of 11 Cases And Detailed Review Of The Literature, Nasir Ud Din, Hira Ishtiaq, Shabina Rahim, Jamshid Abdul Ghafar, Zubair Ahmad
Gliosarcoma In Patients Under 20 Years Of Age. A Clinicopathologic Study Of 11 Cases And Detailed Review Of The Literature, Nasir Ud Din, Hira Ishtiaq, Shabina Rahim, Jamshid Abdul Ghafar, Zubair Ahmad
Department of Pathology and Laboratory Medicine
Background: Gliosarcoma is a rare variant of IDH- wild type glioblastoma with both glial and mesenchymal differentiation. It accounts for approximately 2% of glioblastomas and has a poor prognosis similar to that of classic glioblastoma. It is seen mostly between 40 and 60 years of age with a mean age over 50 years. Pediatric gliosarcoma is even rarer than gliosarcoma in adults. We describe the clinicopathological features of gliosarcoma in patients under 20 years of age and determine whether there are significant differences from gliosarcoma in adults. We also present detailed review of published literature on pediatric gliosarcoma.
Methods: Slides …
Gastroenteropancreatic Neuroendocrine Tumours: Clinicopathological Evaluation At Shifa International Hospital, Islamabad, Nadira Mamoon, Hania Naveed, Mariam Abid, Humaira Nasir, Imran Nazir Ahmad, Zujajah Hameed, Asna Haroon Khan
Gastroenteropancreatic Neuroendocrine Tumours: Clinicopathological Evaluation At Shifa International Hospital, Islamabad, Nadira Mamoon, Hania Naveed, Mariam Abid, Humaira Nasir, Imran Nazir Ahmad, Zujajah Hameed, Asna Haroon Khan
Department of Pathology and Laboratory Medicine
Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification.
Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018.
Results: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine …
Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter
Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter
Spinal Cord and Brain Injury Research Center Faculty Publications
Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …
Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo
Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo
Pharmacology and Nutritional Sciences Faculty Publications
Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …
Pharmacological Intervention In Children With Autism Spectrum Disorder With Standard Supportive Therapies Significantly Improves Core Signs And Symptoms: A Single-Center, Retrospective Case Series, Hamza A. Alsayouf, Haitham Talo, Marisa L. Biddappa, Mohammad Qasaymeh, Shadi Qasem, Emily De Los Reyes
Pharmacological Intervention In Children With Autism Spectrum Disorder With Standard Supportive Therapies Significantly Improves Core Signs And Symptoms: A Single-Center, Retrospective Case Series, Hamza A. Alsayouf, Haitham Talo, Marisa L. Biddappa, Mohammad Qasaymeh, Shadi Qasem, Emily De Los Reyes
Pathology and Laboratory Medicine Faculty Publications
Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively. Here, we investigated the use of these medications in younger patients aged 4 years and older.
Patients and Methods: This retrospective case series included 18 children (mean age, 5.7 years) with ASD treated at the Kids …
Longitudinal Assessment Of Dementia Measures In Down Syndrome, Lisa Mason Koehl, Jordan P. Harp, Kathryn L. Van Pelt, Elizabeth Head, Frederick A. Schmitt
Longitudinal Assessment Of Dementia Measures In Down Syndrome, Lisa Mason Koehl, Jordan P. Harp, Kathryn L. Van Pelt, Elizabeth Head, Frederick A. Schmitt
Neurology Faculty Publications
Introduction: Early detection of dementia symptoms is critical in Down syndrome (DS) but complicated by clinical assessment barriers. The current study aimed to characterize cognitive and behavioral impairment using longitudinal trajectories comparing several measures of cognitive and behavioral functioning.
Methods: Measures included global cognitive status (Severe Impairment Battery [SIB]), motor praxis (Brief Praxis Test [BPT]), and clinical dementia informant ratings (Dementia Questionnaire for People with Learning Disabilities [DLD]). One-year reliability was assessed using a two-way mixed effect, consistency, single measurement intraclass correlation among non-demented participants. Longitudinal assessment of SIB, BPT, and DLD was completed using linear mixed effect models.
Results: …
Intracranial Mesenchymal Tumor With Fet-Creb Fusion - A Unifying Diagnosis For The Spectrum Of Intracranial Myxoid Mesenchymal Tumors And Angiomatoid Fibrous Histiocytoma-Like Neoplasms, Emily A. Sloan, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer M. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din, Emily Carr-Boy, Michael Watson
Intracranial Mesenchymal Tumor With Fet-Creb Fusion - A Unifying Diagnosis For The Spectrum Of Intracranial Myxoid Mesenchymal Tumors And Angiomatoid Fibrous Histiocytoma-Like Neoplasms, Emily A. Sloan, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer M. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din, Emily Carr-Boy, Michael Watson
Department of Pathology and Laboratory Medicine
Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here we studied twenty patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and 4 male patients had a median age of 14 years (range …
Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson
Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson
Biostatistics Faculty Publications
To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …
Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head
Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head
Sanders-Brown Center on Aging Faculty Publications
Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.
Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.
Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …
Investigation Of Japanese Encephalitis Virus As A Cause Of Acute Encephalitis In Southern Pakistan, April 2015-January 2018, Tazeen Fatima, Abida Rais, Erum Khan, Susan L. Hills, Trudy V. Chambers, Aneeta Hotwani, Shahida Qureshi, Saad Shafqat, Saima Malik, Farah Qamar, Fatima Mir, Anthony A. Marfin, Anita K. M. Zaidi, Asif Raza Khowaja, Sadia Shakoor
Investigation Of Japanese Encephalitis Virus As A Cause Of Acute Encephalitis In Southern Pakistan, April 2015-January 2018, Tazeen Fatima, Abida Rais, Erum Khan, Susan L. Hills, Trudy V. Chambers, Aneeta Hotwani, Shahida Qureshi, Saad Shafqat, Saima Malik, Farah Qamar, Fatima Mir, Anthony A. Marfin, Anita K. M. Zaidi, Asif Raza Khowaja, Sadia Shakoor
Department of Pathology and Laboratory Medicine
Background: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan.
Methods: Persons aged ≥1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples …
Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen
Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen
Neurology Faculty Publications
Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …
B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe
B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe
Neurology Faculty Publications
Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including …
Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock
Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock
Sanders-Brown Center on Aging Faculty Publications
Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to …
Intravascular Lymphoma With Progressive Cns Hemorrhage And Multiple Dissections., Ricky Chen, Gurjeet Singh, J Scott Mcnally, Cheryl A Palmer, Adam De Havenon
Intravascular Lymphoma With Progressive Cns Hemorrhage And Multiple Dissections., Ricky Chen, Gurjeet Singh, J Scott Mcnally, Cheryl A Palmer, Adam De Havenon
Articles, Abstracts, and Reports
Introduction: Intravascular lymphoma (IVL) is an uncommon and often fatal disease characterized by intraluminal proliferation of lymphomatous cells within blood vessels. Because of a heterogeneous clinical presentation and lack of sensitive diagnostic protocols, diagnosis of IVL is most often made at autopsy. However, with early diagnosis and appropriate chemotherapy, the prognosis is greatly improved and complete remission is possible. In order to broaden the possible presentations of IVL, we present a patient with an atypical manifestation of biopsy-proven intravascular large B-cell lymphoma who suffered dissections of both intracranial and extracranial arteries in addition to progressive intracranial hemorrhages.
Conclusion: IVL is …
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons.This article has an associated First Person interview with the first author of the paper.
Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang
Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang
Department of Neurology Faculty Papers
BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.
METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.
RESULTS: Mdivi-1 effectively …
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …
Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano
Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano
Neurology Faculty Publications
BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.
METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.
RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …
Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo
Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo
Pathology and Laboratory Medicine Faculty Publications
TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …
Diagnostic Accuracy Of Diffusion Weighted Mri In Differentiating Benign And Malignant Meningiomas, Din Muhammad Sohu, Saba Sohail, Rehana Shaikh
Diagnostic Accuracy Of Diffusion Weighted Mri In Differentiating Benign And Malignant Meningiomas, Din Muhammad Sohu, Saba Sohail, Rehana Shaikh
Department of Radiology
Objective: To determine the diagnostic accuracy of DWI in differentiating benign and malignant meningiomas keeping histopathology as gold standard.
Methods: This was a descriptive analytical study conducted at Radiology Department, DUHS/Dr. Ruth K. M. Pfau Civil Hospital Karachi, from August 2016 to March 2018.It included152 patients clinically suspected of meningioma on conventional neuroimaging. Imaging features of DWI were compared with histopathology findings. The diagnostic accuracy of DWI was calculated in terms of sensitivity, specificity, accuracy, PPV and NPV using histopathology as gold standard.
Results: There were 59 male and 93 female patients with mean age of 55.38±9.8 years. Mean duration …
Tobacco Smoking And Dementia In A Kentucky Cohort: A Competing Risk Analysis, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Gregory E. Cooper, David W. Fardo, Frederick A. Schmitt, Richard J. Kryscio
Tobacco Smoking And Dementia In A Kentucky Cohort: A Competing Risk Analysis, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Gregory E. Cooper, David W. Fardo, Frederick A. Schmitt, Richard J. Kryscio
Epidemiology and Environmental Health Faculty Publications
Tobacco smoking was examined as a risk for dementia and neuropathological burden in 531 initially cognitively normal older adults followed longitudinally at the University of Kentucky’s Alzheimer’s Disease Center. The cohort was followed for an average of 11.5 years; 111 (20.9%) participants were diagnosed with dementia, while 242 (45.6%) died without dementia. At baseline, 49 (9.2%) participants reported current smoking (median pack-years = 47.3) and 231 (43.5%) former smoking (median pack-years = 24.5). The hazard ratio (HR) for dementia for former smokers versus never smokers based on the Cox model was 1.64 (95% CI: 1.09, 2.46), while the HR for …
Report Of An Inferior Rectal Nerve Variant Arising From The S3 Ventral Ramus., Graham Dupont, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs
Report Of An Inferior Rectal Nerve Variant Arising From The S3 Ventral Ramus., Graham Dupont, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs
Articles, Abstracts, and Reports
In surgical approaches to the perineum in general and anal region specifically, considering the possible variations of the inferior rectal nerve is important for the surgeon. Normally, the inferior rectal nerve originates as a branch of the pudendal nerve. However, during routine dissection, a variant of the inferior rectal nerve was found where it arose directly from the third sacral nerve ventral ramus (S3). Many cases have described the inferior rectal nerve arising independently from the sacral plexus, most commonly from the fourth sacral nerve root (S4); however, few cases have reported the inferior rectal nerve arising from S3. Herein, …
Neck Movement During Cervical Transforaminal Epidural Injections And The Position Of The Vertebral Artery: An Anatomical Study., Juan J Altafulla, Emre Yilmaz, Stefan Lachkar, Joe Iwanaga, Jacob Peacock, Zachary Litvack, R Shane Tubbs
Neck Movement During Cervical Transforaminal Epidural Injections And The Position Of The Vertebral Artery: An Anatomical Study., Juan J Altafulla, Emre Yilmaz, Stefan Lachkar, Joe Iwanaga, Jacob Peacock, Zachary Litvack, R Shane Tubbs
Articles, Abstracts, and Reports
Background: Cervical transforaminal epidural steroid injections (CTFESIs) are sometimes performed in patients with cervical radiculopathy secondary to nerve-root compression. Neck movements for patient positioning may include rotation, flexion, and extension. As physicians performing such procedures do not move the neck for fear of injuring the vertebral artery, we performed fluoroscopy and cadaveric dissection to analyze any movement of the vertebral artery during head movement and its relation to the foramina in the setting of CTFESI.
Purpose: To determine cervical rotational positioning for optimized vertebral artery location in the setting of cervical transforaminal epidural steroid injections.
Material and Methods: Four sides …