Neurology Commons^™

Recreational Outdoor Injury And Mortality In Texas State Parks Between 2012 And 2021, Mohammad I Hirzallah, Ebubechi K Adindu, Julliet C Ogu, Tania Allison, May Kamleh

Faculty, Staff and Students Publications

Introduction

Methods

The Metastatic Role Of The Cxcl10-Cxcr3 Axis And Its Therapeutic Potential In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Xiang Chen, Margaret A Clement, Zoe D Man, Angela M Major, Mathew C Weiser, Jun Xu, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

The CXCL10-CXCR3 axis regulates immunity, tumorigenesis, and metastasis in multiple cancers. Yet, its roles in osteosarcoma (OS), the predominant pediatric malignant bone tumor, are not fully defined. Our prior work has shown that elevated serum CXCL10 levels correlate with poor OS prognosis. The current study delves deeper by investigating how CXCL10-mediated CXCR3 signaling influences OS growth and metastatic spread. In vitro, CXCL10 and related CXCR3 ligands (CXCL4, CXCL9, and CXCL11) enhanced OS tumor cell migration. In an orthotopic xenograft mouse model with a newly created CXCR3 knockout (KO) mutant, tumor growth and lung metastasis decreased significantly when compared with …

Author Correction: Inhibitory Specificity From A Connectomic Census Of Mouse Visual Cortex, Casey M Schneider-Mizell, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Leila Elabbady, Clare Gamlin, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, Sven Dorkenwald, J Alexander Bae, Manuel A Castro, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, William Wong, Jingpeng Wu, Jacob Reimer, Andreas S Tolias, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

No abstract provided.

Nf2 Loss-Of-Function And Hypoxia Drive Radiation Resistance In Grade 2 Meningiomas, Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick Desouza, Kyle P Mcgeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Duncan NRI Faculty and Staff Publications

Background: World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. Grade 2 meningiomas with histopathological necrosis have been associated with worse local control (LC) after radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown.

Methods: We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival after ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as 8 G2Ms by single nuclei RNA sequencing.

Results: NF2 loss-of-function (LOF) …

Middle Meningeal Artery Embolization As A Perioperative Adjunct To Surgical Evacuation Of Nonacute Subdural Hematomas: An Multicenter Analysis Of Safety And Efficacy, Walid K Salah, Cordell Baker, Jonathan P Scoville, Joshua C Hunsaker, Christopher S Ogilvy, Justin M Moore, Howard A Riina, Elad I Levy, Alejandro M Spiotta, Brian T Jankowitz, C Michael Cawley, Alexander A Khalessi, Omar Tanweer, Ricardo Hanel, Bradley A Gross, Okkes Kuybu, Alex Nguyen Hoang, Ammad A Baig, Mir Hojjat Khorasanizadeh, Aldo A Mendez, Gustavo Cortez, Jason M Davies, Sandra Narayanan, Brian M Howard, Michael J Lang, Adnan H Siddiqui, Ajith Thomas, Peter Kan, Jan-Karl Burkhardt, Mohamed M Salem, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

By 2030, nonacute subdural hematomas (NASHs) will likely be the most common cranial neurosurgery pathology. Treatment with surgical evacuation may be necessary, but the recurrence rate after surgery is as high as 30%. Minimally invasive middle meningeal artery embolization (MMAE) during the perioperative period has been posited as an adjunctive treatment to decrease the potential for recurrence after surgical evacuation. We evaluated the safety and efficacy of concurrent MMAE in a multi-institutional cohort.

Methods

Data from 145 patients (median age 73 years) with NASH who underwent surgical evacuation and MMAE in the perioperative period were retrospectively collected from 15 …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

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 …

Literature Review Of Stiff Person Syndrome, Mustafa Ansari, Adam Davis, Donald Penney

The Journal of Integrated Primary Care

Background: Stiff Person Syndrome (SPS) is a rare, debilitating autoimmune neurological disorder characterized by progressive muscle rigidity, painful spasms, and gait disturbances. It is strongly associated with autoantibodies against glutamic acid decarboxylase (GAD), leading to impaired GABAergic neurotransmission. SPS exists on a spectrum, with both classical and paraneoplastic variants, the latter often linked to malignancies such as breast cancer.

Methods: This review synthesizes current literature on the pathophysiology, clinical presentation, diagnostic criteria, and treatment modalities of SPS. We examine emerging therapies, including immunomodulatory approaches and antibody-targeted interventions, to address the heterogeneity of disease progression and treatment response.

Results: SPS remains …

Movement Disorders In Relapsing And Progressive Ms: A Comprehensive Prospective Evaluation Of A Large Real-Life Cohort, Hannah Kelly, Rongyi Sun, Mohamed Elkasaby, Alexander Wang, Hesham Abboud

Faculty Scholarship

Background: Recent studies suggest that movement disorders are common in early MS. However, the frequency and clinical characteristics of movement disorders at all stages of MS remain unknown. Objectives: To evaluate the frequency, clinical characteristics, and anatomical generators of movement disorders in relapsing and progressive MS. Methods: We conducted a prospective study of adult MS patients from 2016 to 2022 at a neuroimmunology clinic. Patients were evaluated for demyelination-related movement disorders via a survey and focused examination. We classified movement disorders based on phenomenology and identified anatomic correlates according to lesion locations and relation to relapses. Findings were compared between …

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 …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …

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 …

Mitochondrial Dysfunction And Parkinson's Disease: A Critical Link, Anika J. Millar

Senior Honors Theses

Parkinson’s disease is a neurodegenerative disorder, caused by the damage to and death of dopamine-releasing neurons in the brain. The substantia nigra is a major region housing dopaminergic neurons and plays a critical role in motor and cognitive function. When these neurons are compromised, dopamine levels decline, leading to the development of motor and cognitive dysfunction. Current treatments include dopamine precursors, which help to replace dopamine and relieve motor symptoms. However, while there is symptomatic treatment for Parkinson’s disease, there are no preventative therapies or cures. A potential link between mitochondrial dysfunction and Parkinson’s disease has prompted further research. Investigating …