Neurology Commons^™

Brain Functional Topology Differs By Sex In Cognitively Normal Older Adults, Zhengshi Yang, Filippo Cieri, Jefferson W. Kinney, Jeffrey L. Cummings, Dietmar Cordes, Jessica Z K Caldwell

Brain Health Faculty Research

Introduction: Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of …

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …

Downregulation Of Neurofilament Light Chain Expression In Human Neuronal-Glial Cell Co-Cultures By A Microbiome-Derived Lipopolysaccharide-Induced Mirna-30b-5p, Aileen I. Pogue, Vivian R. Jaber, Nathan M. Sharfman, Yuhai Zhao, Walter J. Lukiw

School of Medicine Faculty Publications

Microbiome-derived Gram-negative bacterial lipopolysaccharide (LPS) has been shown by multiple laboratories to reside within Alzheimer's disease (AD)-affected neocortical and hippocampal neurons. LPS and other pro-inflammatory stressors strongly induce a defined set of NF-kB (p50/p65)-sensitive human microRNAs, including a brain-enriched Homo sapien microRNA-30b-5p (hsa-miRNA-30b-5p; miRNA-30b). Here we provide evidence that this neuropathology-associated miRNA, known to be upregulated in AD brain and LPS-stressed human neuronal-glial (HNG) cells in primary culture targets the neurofilament light (NF-L) chain mRNA 3'-untranslated region (3'-UTR), which is conducive to the post-transcriptional downregulation of NF-L expression observed within both AD and LPS-treated HNG cells. A deficiency of NF-L …

Chemotherapy Coupled To Macrophage Inhibition Induces T-Cell And B-Cell Infiltration And Durable Regression In Triple-Negative Breast Cancer, Swarnima Singh, Nigel Lee, Diego A Pedroza, Igor L Bado, Clark Hamor, Licheng Zhang, Sergio Aguirre, Jingyuan Hu, Yichao Shen, Yitian Xu, Yang Gao, Na Zhao, Shu-Hsia Chen, Ying-Wooi Wan, Zhandong Liu, Jeffrey T Chang, Daniel Hollern, Charles M Perou, Xiang H F Zhang, Jeffrey M Rosen

Duncan NRI Faculty and Staff Publications

Immunosuppressive elements within the tumor microenvironment, such as tumor-associated macrophages (TAM), can present a barrier to successful anti-tumor responses by cytolytic T cells. Here we employed preclinical syngeneic p53 null mouse models of triple-negative breast cancer (TNBC) to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose cyclophosphamide coupled with the pharmacologic inhibition of TAMs using either a small molecule CSF1R inhibitor or an anti-CSF1R antibody. This therapeutic combination was effective in treating several highly aggressive TNBC murine mammary tumor and lung metastasis models. Single cell RNA sequencing characterized tumor-infiltrating lymphocytes (TIL) including helper T cells and antigen-presenting …

B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani

Department of Neurology Faculty Papers

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with …

Gut Dysbiosis And Age-Related Neurological Diseases In Females

Faculty, Staff and Student Publications

Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand …

Descriptive Analysis Of Acute Ischemic Stroke In Covid-19 Patients Through The Course Of The Covid-19 Pandemic, Amman Bhasin, Jay Liuhong Liu, Keval Shah, Amin Marji, Ricky Sareini, Shishir Rao, Wazim Mohamed, Kumar Rajamani, Parthasarathi Chamiraju, Ayaz Khawaja

Medical Student Research Symposium

Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 thru October 2020, and November 2020 thru August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (31%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

False-Positive Serum Igm/Igg To Sars-Cov-2 In A Rare Pulmonary Neuroendocrine Carcinoma With Ocular Metastasis: A Case Report, Irandi P. Pratomo, Gatut Priyonugroho, Aris Ramdhani, Dian Zamroni, Thariqah Salamah, Yayi D.B Susanto, Ramdinal A. Zairinal, Annisa N. Witjaksono, Dita Aditianingsih, Jamal Zaini

The New Ropanasuri Journal of Surgery

The Coronavirus disease 2019 (COVID-19) pandemic impacts pulmonary cancer management since it shares similar clinical features and creates fear among patients to visit hospitals due to possible in-hospital disease transmission. We report a patient who presented with a rare case of a pulmonary neuroendocrine tumor with an ocular involvement, which, unfortunately, experienced a delay in diagnostics. The first hospitalization was due to superior vena cava syndrome, pleural and pericardial effusions, and swollen left eye. The patient was diagnosed with pulmonary cancer, released after the symptoms were relieved, and expected to visit a referral hospital for further diagnostics and treatments. The …

Development Of A Core Measurement Set For Research In Degenerative Cervical Myelopathy: A Study Protocol (Ao Spine Recode-Dcm Cms), Benjamin M Davies, Alvaro Yanez Touzet, Oliver D Mowforth, Keng Siang Lee, Danyal Khan, Julio C Furlan, Michael G Fehlings, James Harrop, Carl Moritz Zipser, Ricardo Rodrigues-Pinto, James Milligan, Ellen Sarewitz, Armin Curt, Vafa Rahimi-Movaghar, Bizhan Aarabi, Timothy F Boerger, Lindsay Tetreault, Robert Chen, James D Guest, Sukhvinder Kalsi-Ryan, Iwan Sadler, Shirley Widdop, Angus G K Mcnair, Brian K Kwon, Mark R N Kotter

Department of Neurosurgery Faculty Papers

Introduction: Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit.

Methods and analysis: The CMS will be developed in …

A Peptide Blocking The Adora1-Neurabin Interaction Is Anticonvulsant And Inhibits Epilepsy In An Alzheimer's Model, Sandipan Pati, Qin Wang

Faculty, Staff and Student Publications

Epileptic seizures are common sequelae of stroke, acute brain injury, and chronic neurodegenerative diseases, including Alzheimer's disease (AD), and cannot be effectively controlled in approximately 40% of patients, necessitating the development of novel therapeutic agents. Activation of the A1 receptor (A1R) by endogenous adenosine is an intrinsic mechanism to self-terminate seizures and protect neurons from excitotoxicity. However, targeting A1R for neurological disorders has been hindered by side effects associated with its broad expression outside the nervous system. Here we aim to target the neural-specific A1R/neurabin/regulator of G protein signaling 4 (A1R/neurabin/RGS4) complex that dictates A1R signaling strength and response outcome …

De Novo Fzr1 Loss-Of-Function Variants Cause Developmental And Epileptic Encephalopathies, Sathiya N Manivannan, Jolien Roovers, Noor Smal, Candace T Myers, Dilsad Turkdogan, Filip Roelens, Oguz Kanca, Hyung-Lok Chung, Tasja Scholz, Katharina Hermann, Tatjana Bierhals, Hande S Caglayan, Hannah Stamberger, Mae Working Group Of Euroepinomics Res Consortium, Heather Mefford, Peter De Jonghe, Shinya Yamamoto, Sarah Weckhuysen, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of …

Risk Factors Of Intracerebral Hemorrhage – A Cross Sectional Study, Mir Jalal-Ud-Din, Raheel Jehangir Jadoon, Syed Affan Ali, Samia Wazir Khawaja, Zahid Gul Jadoon, Ibtisam .

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background and Objective: Stroke is the major cause of disability and one of the top causes of death in the globe. Though the rate is decreasing in the West, it is most likely growing in Asia. In Pakistan, the burden of stroke risk factors is substantial. Although data on the incidence and prevalence of stroke in Pakistan is limited, there are several published case studies demonstrating major disparities in stroke epidemiology, risk factors, kinds, and patterns. This study aims to identify risk factors of intracerebral hemorrhage among patients presenting to a teaching hospital. Methods: From August 2019 to February …

Practical Measures For Disabled’S Empowerment-Time For Economic Growth!, Mahnoor Hafeez

Pakistan Journal of Neurological Sciences (PJNS)

The objective of this article is to advocate for persons with disabilities’ (PWD) rights, to discuss issues solutions, social awareness and to promote diversity and inclusion. The word ‘Disability’ covers a wide range of irreversible permanent impairments including physical and mobility difficulties, hearing, visual impairment, specific learning disabilities including dyslexia, medical conditions and mental health problems that may hinder their full and effective participation in society on an equal basis with others.1 Handicap is the condition of being unable to perform due to physical or mental unfitness.

Parental Mosaicism For Apparent De Novo Genetic Variants: Scope, Detection, And Counseling Challenges, Roni Zemet, Ignatia B Van Den Veyver, Paweł Stankiewicz

Duncan NRI Faculty and Staff Publications

The disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next-generation sequencing technologies enabled their reliable and affordable detection through family-based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from …

Adopting Clinical Practice Guidelines For Pharmacologic Management Of Acute Spinal Cord Injury From A Developed World Context To A Developing Global Region, Seyed Behnam Jazayeri, Seyed Farzad Maroufi, Zahra Ghodsi, Heshmatollah Ghawami, Ahmad Pourrashidi, Abbas Amirjamshidi, Mojtaba Mojtahedzadeh, Jalil Arabkheradmand, Farzin Farahbakhsh, Maryam Shabany, Morteza Faghih-Jouibari, Michael G Fehlings, Brian K Kwon, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

Background: Proper utilization of high-quality clinical practice guidelines (CPGs) eliminates the dependence of patients' outcomes on the ability and knowledge of "individual" health care providers and reduces unwarranted variation in care. The aim of this study was to adapt/adopt two CPGs for pharmacologic management of acute spinal cord injury (SCI) using guideline adaptation methods.

Methods: This study was conducted based on the ADAPTE process. Following establishment of an organizing committee and choosing the health topics, we appraised the quality of the CPGs using the Appraisal of Clinical Guidelines for Research & Evaluation II (AGREE II). Then, the authors extracted and …

Real-Time Fmri Neurofeedback And Ptsd: Efficacy In Symptom Relief And Neural Circuit Restoration, Sophia F. Ryker

University Honors Theses

Background: Posttraumatic stress disorder (PTSD) is recognized by the DSM-V as resulting from exposure to a traumatic event and the subsequent, prolonged experience of intrusive symptoms, avoidance behavior, altered cognitive functioning and hyperarousal. Current treatments often do not provide relief from symptoms and there is a need for neuro-scientifically informed interventions.

Methods: Through the review of all available studies using real-time fMRI neurofeedback (rt-fMRI-NF) as a treatment for PTSD, the efficacy of this therapeutic intervention was analyzed in order to make specific recommendations for the neurofeedback protocols of future studies.

Results: Evidence demonstrated successful reduction in symptom severity and normalizing …

Post Covid-19 Vaccine (Sinovac) Cerebral Venous Sinus Thrombosis, Soban Khan, Maryam Khalil, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

SINOVAC is an inactivated virus COVID 19 vaccine given emergency authorization for COVID-19 Pandemic. Different adverse reactions have been seen in after-marketing of COVID-19 vaccines. Here we present a case of patient who developed cerebral venous sinus thrombosis two weeks after the first dose of SINOVAC vaccine.

Post Covid-19 Vaccine Guillain Barre Syndrome, Soban Khan, Maryam Khalil, Zaid Waqar, Sajid Khan, Zakir Jan

Pakistan Journal of Neurological Sciences (PJNS)

The Guillain Barre Syndrome (GBS) is an acute immune-mediated progressive polyneuropathy having an acute monophasic illness leading to paralysis. The clinical features are progressive ascending symmetrical muscle weakness that may lead to respiratory failure. Diagnosis is based upon clinical presentation and is supported by a lumbar puncture with CSF analysis demonstrating albumin-cytological dissociation, and electrophysiological studies. Our patient presented to us with progressive ascending paralysis after receiving COVID 19 vaccine.

Churg Strauss Syndrome With Neuropathy: A Case Report, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

A 24 years old man with known history of asthma came with acute presentation of ascending weakness for four days following flu like symptoms and worsening of asthma. His complete blood counts showed elevated eosinophil count. Nerve conduction showed neuropathy. He was diagnosed as Churg Strauss syndrome due to presence of asthma, eosinophilia, neuropathy and pulmonary infiltrates. Churg Strauss is a systemic eosinophilic vasculitis involving multiple organ systems that may present with neuropathy, as in this case.