Neurology Commons^™

Sex-Biased Autophagy As A Potential Mechanism Mediating Sex Differences In Ischemic Stroke Outcome, Brian Noh, Louise D Mccullough, Jose F Moruno-Manchon

Faculty, Staff and Student Publications

Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy …

Lifelong Cerebrovascular Disease Burden Among Cadasil Patients: Analysis From A Global Health Research Network, Alan P Pan, Thomas Potter, Abdulaziz Bako, Jonika Tannous, Sudha Seshadri, Louise D Mccullough, Farhaan S Vahidy

Faculty, Staff and Student Publications

INTRODUCTION: Data reporting on patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) within the United States population is limited. We sought to evaluate the overt cerebrovascular disease burden among patients with CADASIL.

METHODS: Harmonized electronic medical records were extracted from the TriNetX global health research network. CADASIL patients were identified using diagnostic codes and those with/without history of documented stroke sub-types (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH] and transient ischemic attack [TIA]) were compared. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of stroke incidence and mortality associated with sex were computed. …

Peripheral Eosinophil Trends And Clinical Outcomes After Non-Traumatic Subarachnoid Hemorrhage, Hugo Gonzalez Gomez, Jude P J Savarraj, Atzhiry S Paz, Xuefang Ren, Hua Chen, Louise D Mccullough, Huimahn A Choi, Aaron M Gusdon

Faculty, Staff and Student Publications

Background/objective

Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH.

Methods

This retrospective observational study included patients with SAH admitted from January 2009 to July 2016. Variables included demographics, modified Fisher scale (mFS), Hunt–Hess Scale (HHS), global cerebral edema (GCE), and the presence of any infection. Peripheral eosinophil counts were examined as part of routine clinical care on admission and …

An F-Ratio-Based Method For Estimating The Number Of Active Sources In Meg, Amita Giri, John C Mosher, Amir Adler, Dimitrios Pantazis

Faculty, Staff and Student Publications

INTRODUCTION: Magnetoencephalography (MEG) is a powerful technique for studying the human brain function. However, accurately estimating the number of sources that contribute to the MEG recordings remains a challenging problem due to the low signal-to-noise ratio (SNR), the presence of correlated sources, inaccuracies in head modeling, and variations in individual anatomy.

METHODS: To address these issues, our study introduces a robust method for accurately estimating the number of active sources in the brain based on the F-ratio statistical approach, which allows for a comparison between a full model with a higher number of sources and a reduced model with fewer …

Development Of A Methodology For Large-Scale Production Of Prions For Biological And Structural Studies, Luis Concha-Marambio, Fei Wang, Enrique Armijo, Damian Gorski, Frank Ramirez, Andrew Scowcroft, Sandra Pritzkow, Claudio Soto

Faculty, Staff and Student Publications

Prion diseases are a group of infectious neurodegenerative diseases produced by the conversion of the normal prion protein (PrP^C) into the disease-associated form (PrP^Sc). Extensive evidence indicate that the main or sole component of the infectious agent is PrP^Sc, which can replicate in affected individuals in the absence of nucleic acids. However, the mechanism of PrP^C-to-PrP^Sc conversion remains elusive, which has been attributed to the lack of sufficient structural information of infectious PrP^Sc and a reliable system to study prion replication in vitro. In this article we adapted the …

Aβ Plaques Do Not Protect Against Hsv-1 Infection In A Mouse Model Of Familial Alzheimer’S Disease, And Hsv-1 Does Not Induce Aβ Pathology In A Model Of Late Onset Alzheimer’S Disease, Olga V Bocharova, Aidan Fisher, Narayan P Pandit, Kara Molesworth, Olga Mychko, Alison J Scott, Natallia Makarava, Rodney Ritzel, Ilia V Baskakov

Faculty, Staff and Student Publications

The possibility that the etiology of late onset Alzheimer's disease is linked to viral infections of the CNS has been actively debated in recent years. According to the antiviral protection hypothesis, viral pathogens trigger aggregation of Aβ peptides that are produced as a defense mechanism in response to infection to entrap and neutralize pathogens. To test the causative relationship between viral infection and Aβ aggregation, the current study examined whether Aβ plaques protect the mouse brain against Herpes Simplex Virus 1 (HSV-1) infection introduced via a physiological route and whether HSV-1 infection triggers formation of Aβ plaques in a mouse …

The Impact Of The Progresses Of Knowledge And Technologies In Pediatrics, Kristofer Harris, Yaobin Ling, Avram S Bukhbinder, Luyao Chen, Kamal N Phelps, Gabriela Cruz, Jenna Thomas, Yejin Kim, Xiaoqian Jiang, Paul E Schulz

Faculty, Staff and Student Publications

Background:

Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer’s disease (AD) and Alzheimer’s disease related dementias.

Objective:

To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus.

Methods:

A retrospective cohort study was performed using Optum’s de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated …

Association Of Vitamin D Polygenic Risk Scores And Disease Outcome In People With Multiple Sclerosis, Eleni S Vasileiou, Chen Hu, Charles N Bernstein, Fred Lublin, Jerry S Wolinsky, Gary R Cutter, Elias S Sotirchos, Kaarina Kowalec, Amber Salter, Shiv Saidha, Ellen M Mowry, Peter A Calabresi, Ruth Ann Marrie, Kathryn C Fitzgerald

Faculty, Staff and Student Publications

Background and objectives: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS.

Methods: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center …

Mechanical Thrombectomy In The Late Presentation Of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From The Society Of Vascular And Interventional Neurology Guidelines And Practice Standards Committee, Thanh N Nguyen, Alicia C Castonguay, James E Siegler, Simon Nagel, Maarten G Lansberg, Adam De Havenon, Sunil A Sheth, Mohamad Abdalkader, Jenny Tsai, Gregory W Albers, Hesham E Masoud, Tudor G Jovin, Sheila O Martins, Raul G Nogueira, Osama O Zaidat, Svin Gaps Committee

Faculty, Staff and Student Publications

Background and purpose: Recent clinical trials investigating endovascular therapy (EVT) in the extended time window have opened new treatment paradigms for late-presenting patients with large vessel occlusion (LVO) stroke. The aim of this guideline is to provide up to date recommendations for the diagnosis, selection, and medical or endovascular treatment of patients with LVO presenting in the extended time window.

Methods: The Society of Vascular & Interventional Neurology (SVIN) Guidelines and Practice Clinical Standards (GAPS) committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the current literature. Recommendations were assigned by the writing group using the …

Seizures, Vitamin D Deficiency, And Severe Hypophosphatemia: The Unique Presentation Of A Sars-Cov-2 Case, Benson Yeh, Christopher Bell, Christopher Anderson, Mack Sheraton

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV), which is related to the SARS-CoV-1 virus that caused the 2002-2004 SARS outbreak. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). It has been associated with electrolyte abnormalities. In this report, we discuss the case of a SARS-CoV-2-infected person presenting with recurrent seizure episodes resulting from hypophosphatemia. A 52-year-old male patient with questionable prior seizure history presented to the emergency department (ED) twice within eight days with recurring seizure episodes. While the physical examination at the first presentation was significant for …

Establishing A Pediatric Acute Stroke Protocol: Experience Of A New Pediatric Stroke Program And Predictors Of Acute Stroke, Kamal Phelps, Christin Silos, Susan De La Torre, Amee Moreno, Robert Lapus, Nipa Sanghani, Mary Koenig, Sean Savitz, Charles Green, Stuart Fraser

Faculty, Staff and Student Publications

INTRODUCTION: Pediatric stroke is among the top 10 causes of death in pediatrics. Rapid recognition and treatment can improve outcomes in select patients, as evidenced by recent retrospective studies in pediatric thrombectomy. We established a collaborative protocol involving the vascular neurology and pediatric neurology division in our institution to rapidly diagnose and treat pediatric suspected stroke. We also prospectively collected data to attempt to identify predictors of acute stroke in pediatric patients.

METHODS: IRB approval was obtained to prospectively collect clinical data on pediatric code stroke activations based on timing metrics in resident-physician note templates. The protocol emphasized magnetic resonance …

Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics Of Systemic Sclerosis Patients At The Preclinical Stage, Chiara Bellocchi, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi, Lorenzo Beretta

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.

METHODS: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.

RESULTS: At 4 years, 42.4% subjects progressed (evolving …

Updated Parkinson’S Disease Motor Subtypes Classification And Correlation To Cerebrospinal Homovanillic Acid And 5-Hydroxyindoleacetic Acid Levels, Christopher Adams, Jessika Suescun, Anam Haque, Kelly Block, Shivika Chandra, Timothy M Ellmore, Mya C Schiess

Faculty, Staff and Student Publications

INTRODUCTION: Motor classifications of Parkinson's Disease (PD) have been widely used. This paper aims to update a subtype classification using the MDS-UPDRS-III and determine if cerebrospinal neurotransmitter profiles (HVA and 5-HIAA) differ between these subtypes in a cohort from the Parkinson's Progression Marker Initiative (PPMI).

METHODS: UPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a formula derived from UPDRS, and a new ratio was developed for subtyping patients with the MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping …

Clinical Manifestations And Outcome Of Patients With Primary Amoebic Meningoencephalitis In Pakistan A Single-Center Experience, Shakeel Ur Rehman, Salman Farooq, Muhammad Bilal Tariq, Nosheen Nasir, Mohammad Wasay, Sobia Masood, Musa Karim

Faculty, Staff and Student Publications

Primary amoebic meningoencephalitis (PAM) is a rapidly progressing central nervous system (CNS) infection caused by Naegleria fowleri, a free-living amoeba found in warm freshwater. The disease progression is very rapid, and the outcome is nearly always fatal. We aim to describe the disease course in patients admitted with PAM in a tertiary care center in Karachi, Pakistan between the periods of 2010 to 2021. A total of 39 patients were included in the study, 33 males (84.6%). The median age of the patients was 34 years. The most frequent presenting complaint was fever, which was found in 37 patients (94.9%) …

Case Report: Navigating The Challenges: Successful Mechanical Thrombectomy In A Case Of Persistent Primitive Hypoglossal Artery, Kamran Ahmed Khan, Irfan Amjad Lutfi, Jehangir Ali Shah, Salman Farooq, Shahnoor Ahmed, Bashir Ahmed Solangi, Ayan Ahmed Khan, Fazal Zaidi, Ali Ammar, Nadeem Qamar

Faculty, Staff and Student Publications

Persistent primitive hypoglossal artery (PPHA) is a highly uncommon abnormal connection between the internal carotid artery (ICA) and vertebral artery (VA), with reported incidences ranging from 0.027 to 0.26%. Attempting endovascular intervention in such cases presents a considerable challenge as it carries a higher risk of embolization and other procedure-related complications that may affect a wide area of the brain. We present a case study involving the utilization of mechanical thrombectomy (MT) to treat an ischemic stroke in the M1 segment of the middle cerebral artery (MCA) despite the presence of PPHA. Performing mechanical thrombectomy in an anomalous vascular connection …

Epilepsy Center Characteristics And Geographic Region Influence Presurgical Testing In The United States, Stephanie M Ahrens, Kristen H Arredondo, Anto I Bagić, Shasha Bai, Kevin E Chapman, Michael A Ciliberto, Dave F Clarke, Mariah Eisner, Nathan B Fountain, Jay R Gavvala, M Scott Perry, Kyle C Rossi, Lily C Wong-Kisiel, Susan T Herman, Adam P Ostendorf, Naec Center Director Study Group

Faculty, Staff and Student Publications

bjective

Persons with drug‐resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy.

Methods

We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census …

Attitudes, Perceptions, And Preferences Towards Sars Cov-2 Testing And Vaccination Among African American And Hispanic Public Housing Residents, New York City: 2020-2021, Chigozirim Izeogu, Emily Gill, Kaitlyn Van Allen, Natasha Williams, Lorna E Thorpe, Donna Shelley

Faculty, Staff and Student Publications

Background

African American and Hispanic populations have been affected disproportionately by COVID-19. Reasons are multifactorial and include social and structural determinants of health. During the onset and height of the pandemic, evidence suggested decreased access to SARS CoV-2 testing. In 2020, the National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx)- Underserved Populations initiative to improve SARS CoV-2 testing in underserved communities. In this study, we explored attitudes, experiences, and barriers to SARS CoV-2 testing and vaccination among New York City public housing residents.

Methods

Between December 2020 and March 2021, we conducted 9 virtual focus groups among …

Population-Based Mini-Mental State Examination Norms In Adults Of Mexican Heritage In The Cameron County Hispanic Cohort, Avram S Bukhbinder, Miriam Hinojosa, Kristofer Harris, Xiaojin Li, Christine M Farrell, Madison Shyer, Nathan Goodwin, Sahar Anjum, Omar Hasan, Susan Cooper, Lois Sciba, Amanda Falk Vargas, David H Hunter, Guadalupe J Ortiz, Karen Chung, Licong Cui, Guo-Qiang Zhang, Susan P Fisher-Hoch, Joseph B Mccormick, Paul E Schulz

Faculty, Staff and Student Publications

Background:

Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings.

Objective:

To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores.

Methods:

Visits between 2004–2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by …

Hermann ("Hugh") Blaschko (1900-1993): Father Of Catecholamine Metabolism, Heinrich Taegtmeyer, Jiries Ganim, Anne B Leuppi-Taegtmeyer

Faculty, Staff and Student Publications

No abstract provided.

Dual-Task Upper Extremity Motor Performance Measured By Video Processing As Cognitive-Motor Markers For Older Adults, Changhong Wang, Mohsen Zahiri, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Introduction: The use of dual-task model such as dual-task gait has been extensively studied to assess cognitive-motor performance among older adults. However, space restriction and safety factor limit its applications in remote assessment. To address the gap, we propose a video processing-based approach to remotely quantify cognitive-motor performance using a 20-s repetitive elbow flexion-extension test with dual-task condition, called video-based motoric-cognitive meter (MCM).

Methods: Eighteen older participants (age: 78.6 ± 6.5 years) who were clinically diagnosed as having either mild cognitive impairment or dementia were included in this study. Participants were asked to perform 20-s repetitive elbow flexion-extension exercise with …

Concurrent Idh1 And Idh2 Mutations In Glioblastoma: A Case Report, Ali S Haider, Chibawanye I Ene, Paolo Palmisciano, Maryam Haider, Ganesh Rao, Leomar Y Ballester, Gregory N Fuller

Faculty, Staff and Students Publications

Isocitrate dehydrogenase (IDH) mutations are cornerstone diagnostic features in glioma classification. IDH mutations are typically characterized by mutually exclusive amino acid substitutions in the genes encoding for the IDH1 and the IDH2 enzyme isoforms. We report our institutional case of a diffuse astrocytoma with progression to secondary glioblastoma and concurrent IDH1/IDH2 mutations. A 49-year-old male underwent a subtotal resection of a lobular lesion within the right insula in 2013, revealing a WHO grade 3 anaplastic oligoastrocytoma, IDH1 mutated, 1p19q intact. Symptomatic tumor progression was suspected in 2018, leading to a surgical tumor biopsy that demonstrated WHO grade 4 IDH1 and …

Stereo-Eeg-Guided Network Modulation For Psychiatric Disorders: Surgical Considerations, Sameer A Sheth, Ben Shofty, Anusha Allawala, Jiayang Xiao, Joshua A Adkinson, Raissa K Mathura, Victoria Pirtle, John Myers, Denise Oswalt, Nicole R Provenza, Nisha Giridharan, Angela M Noecker, Garrett P Banks, Ron Gadot, Ricardo A Najera, Adrish Anand, Ethan Devara, Huy Dang, Eleonora Bartoli, Andrew Watrous, Jeffrey Cohn, David Borton, Sanjay J Mathew, Cameron C Mcintyre, Wayne Goodman, Kelly Bijanki, Nader Pouratian

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders.

OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field.

METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy …

Primary Spinal Intramedullary Anaplastic Ganglioglioma In A Pediatric Patient, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Marc Prablek, Frank Y Lin, Melissa M Blessing, Guillermo Aldave, David Bauer

Faculty, Staff and Students Publications

BACKGROUND: Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology.

CASE DESCRIPTION: A 13-year-old female presented with signs of spinal …

Editorial: Molecular Mechanisms In Ocular Development And Disease, Rajalekshmy Shyam, Daisy Y Shu, Elizabeth Zuniga-Sanchez, Deepika Vasudevan

Faculty, Staff and Students Publications

No abstract provided.

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …

Forniceal Deep Brain Stimulation In A Mouse Model Of Rett Syndrome Increases Neurogenesis And Hippocampal Memory Beyond The Treatment Period, Qi Wang, Bin Tang, Shuang Hao, Zhenyu Wu, Tingting Yang, Jianrong Tang

Faculty, Staff and Students Publications

BACKGROUND: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT.

OBJECTIVES: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice.

METHODS: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual …

Disruption Of Specific White Matter Tracts Is Associated With Neurogenic Lower Urinary Tract Dysfunction In Women With Multiple Sclerosis, Darshil Choksi, Bradley Schott, Khue Tran, Ryan Jang, Khader M Hasan, John A Lincoln, Ali Jalali, Christof Karmonik, Betsy Salazar, Rose Khavari

Faculty, Staff and Student Publications

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD.

METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI …

Biallelic Prmt7 Pathogenic Variants Are Associated With A Recognizable Syndromic Neurodevelopmental Disorder With Short Stature, Obesity, And Craniofacial And Digital Abnormalities, Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K Bijlsma, Kristen M Wigby, Diana Baralle, Mohammad Y V Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, François Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T Vulto-Van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E Nasab, A Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C Taylor, Melody Redman, Alexander P A Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Müller, Maria C Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N Schweitzer, Alison Kraus, Irene Valenzuela, Scott D Mclean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E Schnur, Erin Torti, Tobias B Haack, Carlos E Prada, Fowzan S Alkuraya, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.

METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 …

Upregulation Of The Escrt Pathway And Multivesicular Bodies Accelerates Degradation Of Proteins Associated With Neurodegeneration, Ron Benyair, Sai Srinivas Panapakkam Giridharan, Pilar Rivero-Ríos, Junya Hasegawa, Emily Bristow, Eeva-Liisa Eskelinen, Merav D Shmueli, Vered Fishbain-Yoskovitz, Yifat Merbl, Lisa M Sharkey, Henry L Paulson, Phyllis I Hanson, Samarjit Patnaik, Ismael Al-Ramahi, Juan Botas, Juan Marugan, Lois S Weisman

Duncan NRI Faculty and Staff Publications

Many neurodegenerative diseases, including Huntington’s disease (HD) and Alzheimer’s disease (AD), occur due to an accumulation of aggregation-prone proteins, which results in neuronal death. Studies in animal and cell models show that reducing the levels of these proteins mitigates disease phenotypes. We previously reported a small molecule, NCT-504, which reduces cellular levels of mutant huntingtin (mHTT) in patient fibroblasts as well as mouse striatal and cortical neurons from an HdhQ111 mutant mouse. Here, we show that NCT-504 has a broader potential, and in addition reduces levels of Tau, a protein associated with Alzheimer’s disease, as well as other tauopathies. We …

Function And Dysfunction Of The Dystonia Network: An Exploration Of Neural Circuits That Underlie The Acquired And Isolated Dystonias, Jason S Gill, Megan X Nguyen, Mariam Hull, Meike E Van Der Heijden, Ken Nguyen, Sruthi P Thomas, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through …