Neurology Commons^™

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

The Cgas/Sting Pathway: Friend Or Foe In Regulating Cardiomyopathy, Weiyue Wang, Yuanxu Gao, Hyun Kyoung Lee, Albert Cheung-Hoi Yu, Markus Kipp, Hannes Kaddatz, Jiangshan Zhan

Duncan NRI Faculty and Staff Publications

Inflammation is a central hallmark of cardiomyopathy, where misdirected immune responses contribute to chronic myocardial dysfunction. Among the emerging molecular mechanisms implicated in this process, the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has garnered increasing attention. Acting as a key cytosolic DNA sensor, the cGAS/STING pathway orchestrates inflammatory responses triggered by microbial infections or endogenous cellular stressors such as autophagy and apoptosis. Despite its pivotal role, the precise molecular mechanisms regulating this pathway and its role in cardiomyopathy-associated inflammation remain poorly understood and subject to ongoing debate. To address this scientific gap, we first reviewed key …

A Hierarchy Of Pdz Domain Scaffolding Proteins Clusters The Kv1 K+ Channel Protein Complex At The Axon Initial Segment, Wei Zhang, Victoria L Palfini, Yu Wu, Xiaoyun Ding, Allison J Melton, Yudong Gao, Yuki Ogawa, Matthew N Rasband

Faculty, Staff and Students Publications

Action potentials are initiated and modulated at the axon initial segment (AIS) by highly clustered ion channels. Voltage-gated Kv1 potassium channels underlie most outward AIS K+ current. AIS Kv1 channels exist in a large protein complex including ADAM22, Caspr2, and LGI1. However, their clustering mechanisms remain unknown. Because Kv1 channels have a highly conserved PDZ-binding motif, we used CRISPR-based genome editing to screen 18 PDZ domain-containing proteins identified in our previous AIS proximity proteome for their AIS localization. Among these, we found that the scaffolding proteins SCRIB and PSD93 are highly enriched at the AIS. Using CRISPR-mediated knockout, cell surface …

A Multicenter, Propensity Score-Matched Analysis Of Functional Outcomes And Recanalization Success With Or Without Trevo For Medium And Distal Vessel Occlusion, James E Siegler, Manisha Koneru, Hamza Shaikh, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Vivek Yedavalli, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Jeremy J Heit, Robert W Regenhardt, Rami Z Morsi, Tareq Kass-Hout, Nicholas Vigilante, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil A Sheth, Muhammed Amir Essibayi, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, Piers Klein, Mohamad Abdalkader, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Jane Khalife, Ankit Rana, Adrien Guenego, Adam A Dmytriw, Mad Mt Investigators

Faculty, Staff and Student Publications

BackgroundEndovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes.MethodsA retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried. The primary outcome of favorable shift in 90-day modified Rankin Scale (mRS) was compared between patients treated with Trevo versus other devices on first pass using 1:1 propensity score matching (PSM) with multivariable adjustment. Secondary outcomes included the number of pass attempts, final thrombolysis in cerebral infarction (TICI) score …

International Multi-Center Study Of Middle Meningeal Artery Embolization For Chronic Subdural Hematoma In Cancer Patients: Efficacy, Safety, And Outcomes In A High-Risk Population, Avi A Gajjar, Mohamed M Salem, Georgios S Sioutas, Rashad Jabarkheel, Okkes Kuybu, Jane Khalife, Daniel A Tonetti, Gustavo Cortez, Adam A Dmytriw, Diego Alejandro Ortega Moreno, William Smith, Robert W Regenhardt, Kate T Carroll, Zachary A Abecassis, Juan Francisco Ruiz Rodriguez, Oleg Shekhtman, Alex Nguyen Hoang, Alexander A Khalessi, Cordell Baker, Matthias Matejka, Nicole M Cancelliere, Christoph J Griessenauer, Ramesh Grandhi, Peter Kan, Omar Tanweer, Michael R Levitt, Christopher J Stapleton, Vitor Mendes Pereira, Brian Jankowitz, Howard A Riina, Aman B Patel, Ricardo Hanel, Ajith J Thomas, Michael J Lang, Bradley A Gross, Jan-Karl Burkhardt, Visish M Srinivasan

Faculty, Staff and Students Publications

Background

Middle meningeal artery embolization (MMAE) is a promising treatment for chronic subdural hematoma (cSDH). Cancer patients are at risk for cSDH due to thrombocytopenia. The efficacy of MMAE in this population has not been studied.

Methods

We conducted a retrospective analysis of 76 patients who underwent 94 MMAEs for cSDH at 12 tertiary centers across North America and Europe between February 2018 and January 2023. We analyzed patient demographics, clinical profiles, procedural details, and outcomes. The primary outcome was cSDH progression, while secondary outcomes included radiographic resolution, mortality, 90-day functional outcomes, functional improvement, and procedural complications.

Results

Radiographic improvement …

Effect Of Race On Procedural And Clinical Outcomes In Middle Meningeal Artery Embolization For Primary And Adjunctive Treatment Of Chronic Subdural Hematoma, Santiago Gomez-Paz, Mohamed M Salem, Cordell Baker, Okkes Kuybu, Georgios S Sioutas, Kate T Carroll, Mira Salih, Adam A Dmytriw, Jane Khalife, William Smith, Diego Alejandro Ortega Moreno, Robert W Regenhardt, Nicole M Cancelliere, Alejandro M Spiotta, Omar Tanweer, Christopher J Stapleton, Michael Lang, Vitor M Pereira, Aman B Patel, Adnan H Siddiqui, Elad I Levy, Christopher S Ogilvy, Daniel Tonetti, Ajith J Thomas, Visish M Srinivasan, Brian T Jankowitz, Michael R Levitt, Bradley A Gross, Jan-Karl Burkhardt, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

We investigated racial disparities in radiologic and clinical outcomes of patients after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) with or without evacuation surgery.

Methods

This multicenter retrospective study includes consecutive patients who underwent MMAE across 11 institutions in North America (10 in the United States and 1 in Canada). Patients were stratified using self-reported racial data. Outcomes of interest were complications, treatment failure/reoperations, resolution of hematoma, and functional independence at last follow-up. Multivariable regression models were used to assess and adjust for relevant confounders.

Results

A total of 557 patients underwent 663 MMAEs, including 323 …

Long-Term Outcomes Of Resolute Onyx Zotarolimus-Eluting Stents For Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Omid Shoraka, Ramesh Grandhi, Samantha Miller, Joanna Roy, Vinay Jaikumar, Basel Musmar, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Adnan H Siddiqui, Farhan Siddiq, Ameer E Hassan

Faculty, Staff and Students Publications

Background

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke. The Medtronic Resolute Onyx Zotarolimus-eluting stents (RO-ZES) are promising in preventing stroke recurrence compared with medical management (MM) and percutaneous angioplasty and stenting (PTAS) at both 30-day and one-year follow-ups. We evaluated long-term outcomes for patients treated with RO-ZES, PTAS, or MM.

Methods

A retrospective multicenter study was conducted including patients who underwent RO-ZES stenting for symptomatic ICAD between March 2018 and May 2023, with follow-up through October 2024. Propensity score-matched control groups, representing MM and PTAS, were derived from the SAMMPRIS trial. Primary outcomes included recurrence rates …

Intracellular Inclusions Induced By Patient-Derived And Amplified Α-Synuclein Aggregates Are Morphologically Indistinguishable, Rabab Al-Lahham, Mark E Corkins, Mohd Ishtikhar, Prakruti Rabadia, Santiago Ramirez, Victor Banerjee, Mohammad Shahnawaz

Faculty, Staff and Student Publications

Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients' brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and …

Brain And Cerebrospinal Fluid 3d Center Of Mass Shift After Spaceflight, Katherine G Warthen, Stuart H Sater, Larry A Kramer, Khader M Hasan, Michael A Williams, Millennia Young, Brandon R Macias, Steven S Laurie, Bryn A Martin

Faculty, Staff and Student Publications

A subset of long-duration spaceflight astronauts at the International Space Station has been documented to develop spaceflight associated neuro-ocular syndrome (SANS). Researchers have sought to understand SANS by quantification of ocular and brain structural changes thought to be associated with weightlessness induced headward fluid shift. Brain tissue shift and cerebrospinal fluid (CSF) redistribution has been observed as measured by MRI on return to Earth, and not fully quantified. To improve the understanding of this phenomenon, we developed and applied automated methods to quantify 3D center of mass shift within the skull of the extra-axial cerebrospinal fluid (eaCSF) and brain after …

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Alzheimer’S Disease Protective Allele Of Clusterin Modulates Neuronal Excitability Through Lipid-Droplet-Mediated Neuron-Glia Communication, Xiaojie Zhao, Yan Li, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Alena Kozlova, Matthew J Moulton, Lindsey D Goodman, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Duncan NRI Faculty and Staff Publications

Background: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms have not been extensively studied.

Methods: Bulk ATAC-seq was performed in induced pluripotent stem cells (iPSCs) differentiated various brain cell types to identify allele-specific open chromatin (ASoC) SNPs. CRISPR-Cas9 editing generated isogenic pairs, which were then differentiated into glutamatergic neurons (iGlut). Transcriptomic analysis and functional studies of iGlut co-cultured with mouse astrocytes assessed neuronal excitability and lipid droplet formation.

Results: We identified a putative causal SNP of CLU that impacted neuronal chromatin accessibility to transcription-factor(s), with …

Genome-Wide Association Meta-Analyses Of Drug-Resistant Epilepsy, Costin Leu, Andreja Avbersek, Remi Stevelink, Helena Martins Custodio, Siwei Chen, Doug Speed, Caitlin A Bennett, Lina Jonsson, Unnur Unnsteinsdóttir, Andrea L Jorgensen, Gianpiero L Cavalleri, Norman Delanty, John J Craig, Chantal Depondt, Michael R Johnson, Bobby P C Koeleman, Emadeldin Hassanin, Maryam Erfanian Omidvar, Roland Krause, Holger Lerche, Anthony G Marson, Terence J O'Brien, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Hreinn Stefansson, Kari Stefansson, Patrick May, Benjamin M Neale, Dennis Lal, Samuel F Berkovic, Epi25 Collaborative, Epipgx Consortium, Sanjay M Sisodiya

Faculty, Staff and Student Publications

Background: Epilepsy is one of the most common neurological disorders, affecting over 50 million people worldwide. One-third of people with epilepsy do not respond to currently available anti-seizure medications, constituting one of the most important problems in epilepsy. Little is known about the molecular pathology of drug resistance in epilepsy, in particular, possible underlying genetic factors are largely unknown.

Methods: We performed a genome-wide association study (GWAS) in two epilepsy cohorts of European ancestry, comparing drug-resistant (N = 4208) to drug-responsive individuals (N = 2618) followed by meta-analyses across the studies. Next, we performed subanalyses split into two broad subtypes: …

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …

Otolaryngology-Assisted Approach For Anterior Cervical Discectomy And Fusion, M Benjamin Larkin, Anthony K Allam, Cyrus B King, N Eddie Liou, Alexander E Ropper

Faculty, Staff and Students Publications

First introduced in 1955, anterior cervical discectomy and fusion (ACDF) surgery has seen minimal changes over the years. Its reproducibility, impressive long-term results, and minimal complication rates have established it as one of the most frequently performed cervical spinal fusion surgeries. Yet, postoperative dysphagia remains a concern with a 60% incidence rate. An otolaryngologist's expertise regarding cervical fascial anatomy can inform the spine surgeon's approach to an ACDF to potentially reduce postoperative dysphagia rates. We describe an illustrative case of a 35-year-old woman who presented with 8/10 neck and arm pain along with numbness in her fourth and fifth digits …

Challenges And Opportunities Of Acquiring Cortical Recordings For Chronic Adaptive Deep Brain Stimulation, Jeffrey Herron, Aura Kullmann, Timothy Denison, Wayne K Goodman, Aysegul Gunduz, Wolf-Julian Neumann, Nicole R Provenza, Maryam M Shanechi, Sameer A Sheth, Philip A Starr, Alik S Widge

Faculty, Staff and Students Publications

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex. Yet capturing those markers requires the placement of cortex-optimized electrodes in addition …

Metastatic Medulloblastoma Remodels The Local Leptomeningeal Microenvironment To Promote Further Metastatic Colonization And Growth, Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino De Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G Lucas, Charles G Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N Rich, Xiaochong Wu, Xi Huang, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges …

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Methods

Results

Author Correction: Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

Mapping The Developmental Profile Of Ventricular Zone-Derived Neurons In The Human Cerebellum, Anders W Erickson, Henry Tan, Liam D Hendrikse, Jake Millman, Zachary Thomson, Joseph Golser, Omar Khan, Guanyi He, Kathleen Bach, Arpit Suresh Mishra, Janja Kopic, Zeljka Krsnik, Ferechte Encha-Razavi, Giulia Petrilli, Fabien Guimiot, Evelina Silvestri, Kimberly A Aldinger, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

The cerebellar ventricular zone (VZ) is the primary source of progenitors that generate cerebellar GABAergic neurons, including Purkinje cells (PCs) and interneurons (INs). This study provides detailed characterization of human cerebellar GABAergic neurogenesis using transcriptomic and histopathological analyses and reveals conserved and unique features compared to rodents. We show that the sequential progression of neurogenesis is conserved and occurs before 8 postconception weeks. Notably, PC differentiation occurs in the outer subventricular zone (SVZ), a region absent in the mouse cerebellum. Human PCs are generated during a compact two-week period before the onset of cerebral cortex histogenesis. A subset of human …

The Potential Of Brain Organoids In Addressing The Heterogeneity Of Synucleinopathies, Xiao-Jun Diao, Claudio Soto, Fei Wang, Yu Wang, Yun-Cheng Wu, Abhisek Mukherjee

Faculty, Staff and Student Publications

Synucleinopathies are a group of diseases characterized by neuronal and glial accumulation of α-synuclein (aSyn) linked with different clinical presentations, including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Dementia with Lewy Bodies (DLB) and Multiple system atrophy (MSA). Interestingly, the structure of the aSyn aggregates can vary across different synucleinopathies. Currently, it is unclear how the aSyn protein can aggregate into diverse structures and affect distinct cell types and various brain regions, leading to different clinical symptoms. Recent advances in induced pluripotent stem cells (iPSCs)-based brain organoids (BOs) technology provide an unprecedented opportunity to define the etiology of synucleinopathies …

Inhibition Of Soluble Epoxide Hydrolase Confers Neuroprotection And Restores Microglial Homeostasis In A Tauopathy Mouse Model, Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li, Li Gan, Hui Zheng

Center on Aging Staff Publications

Background: The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

Methods: Here we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the …

New Insights Into Epileptic Spasm Generation And Treatment From The Ttx Animal Model, John W Swann, Carlos J Ballester-Rosado, Chih-Hong Lee

Duncan NRI Faculty and Staff Publications

Currently, we have an incomplete understanding of the mechanisms underlying infantile epileptic spasms syndrome (IESS). However, over the past decade, significant efforts have been made to develop IESS animal models to provide much-needed mechanistic information for therapy development. Our laboratory has focused on the TTX model and in this paper, we review some of our findings. To induce spasms, tetrodotoxin (TTX) is infused into the neocortex of infant rats. TTX produces a lesion at its infusion site and thus mimics IESS resulting from acquired structural brain abnormalities. Subsequent electrophysiological studies showed that the epileptic spasms originate from neocortical layer V …

Epidemiology Of Tourette Syndrome, Abdullah Yasir Yilmaz, Joseph Jankovic

Faculty, Staff and Students Publications

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies.

Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms "Tourette syndrome", "tics", "tic disorders", "epidemiology", "prevalence", …

Changes Of Eeg Beta Band Power And Functional Connectivity During Spaceflight: A Retrospective Study, Adrián Quivira-Lopesino, María Sevilla-García, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Ana Maria Cebolla, Guy Cheron, Michael Funke, Fernando Maestu

Faculty, Staff and Student Publications

Spaceflight exposes astronauts to unique conditions like microgravity, which may affect brain function, though it remains underexplored compared to other physiological systems. Astronauts often report temporary neurological symptoms, such as disorientation, visual disturbances, and motor issues, potentially linked to structural and electrophysiological brain changes. To investigate this, electroencephalography (EEG) is a reliable tool to study brain activity in space, measuring oscillatory activity and functional connectivity (FC). This study analyzed EEG data from five male astronauts during three stages: pre-flight, during low Earth orbit (LEO), and post-flight in a 2-min task-free eyes-closed (EC) condition followed by another 2-min of eyes-open (EO) …

Incident Hearing Loss And Subsequent Risk Of Dementia: The Health And Retirement Study 2010-2018, Jingkai Wei, Youngran Kim, Yike Li, Donglan Zhang, Casey Crump

Faculty, Staff and Student Publications

Background and Objectives

Research Design and Methods

Short- And Long-Term Effects Of Early Versus Delayed Treatment With Ocrelizumab On Cerebellar Volume Loss In Patients With Rms And Ppms, Douglas L Arnold, Shannon Kolind, Haz-Edine Assemlal, Amit Bar-Or, Matilde Inglese, Ludwig Kappos, Katrin Parmar, Till Sprenger, Anthony Traboulsee, Irene M Vavasour, Jerry S Wolinsky, Corrado Bernasconi, Ulrike Bonati, Stefano Magon, Björn Tackenberg, Laura Gaetano

Faculty, Staff and Student Publications

Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model. …

Nitrate Ameliorates Alcohol-Induced Cognitive Impairment Via Oral Microbiota, Xiangxue Li, Zhaojun Ni, Weixiong Shi, Kangqing Zhao, Yanjie Zhang, Lina Liu, Zhong Wang, Jie Chen, Zhoulong Yu, Xuejiao Gao, Ying Qin, Jingwen Zhao, Wenjuan Peng, Jie Shi, Thomas R Kosten, Lin Lu, Lei Su, Yanxue Xue, Hongqiang Sun

Faculty, Staff and Students Publications

Alcohol use is associated with cognitive impairment and dysregulated inflammation. Oral nitrate may benefit cognitive impairment in aging through altering the oral microbiota. Similarly, the beneficial effects of nitrate on alcohol-induced cognitive decline and the roles of the oral microbiota merit investigation. Here we found that nitrate supplementation effectively mitigated cognitive impairment induced by chronic alcohol exposure in mice, reducing both systemic and neuroinflammation. Furthermore, nitrate restored the dysbiosis of the oral microbiota caused by alcohol consumption. Notably, removing the oral microbiota led to a subsequent loss of the beneficial effects of nitrate. Oral microbiota from donor alcohol use disordered …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

Leveraging Pretrained Language Models For Seizure Frequency Extraction From Epilepsy Evaluation Reports, Rashmie Abeysinghe, Shiqiang Tao, Samden D Lhatoo, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Seizure frequency is essential for evaluating epilepsy treatment, ensuring patient safety, and reducing risk for Sudden Unexpected Death in Epilepsy. As this information is often described in clinical narratives, this study presents an approach to extracting structured seizure frequency details from such unstructured text. We investigated two tasks: (1) extracting phrases describing seizure frequency, and (2) extracting seizure frequency attributes. For both tasks, we fine-tuned three BERT-based models (bert-large-cased, biobert-large-cased, and Bio_ClinicalBERT), as well as three generative large language models (GPT-4, GPT-3.5 Turbo, and Llama-2-70b-hf). The final structured output integrated the results from both tasks. GPT-4 attained the best performance …

Somatodendritic Orientation Determines Tdcs-Induced Neuromodulation Of Purkinje Cell Activity In Awake Mice, Carlos A Sánchez-León, Guillermo Sánchez-Garrido Campos, Marta Fernández, Álvaro Sánchez-López, Javier F Medina, Javier Márquez-Ruiz

Faculty, Staff and Students Publications

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by …