Neurology Commons^™

Neuroinflammation And Its Role In Depression– A Review Of Emerging Biomarkers And Therapeutic Targets, Sophia M. Valerino

Advances in Clinical Medical Research and Healthcare Delivery

Major depressive disorder (MDD) is a prevalent and debilitating mental illness that affects millions globally. Traditionally, the pathophysiology of MDD was thought to be due primarily neurotransmitter imbalances. However, emerging research highlights the role of neuroinflammation in MDD pathogenesis. Elevated levels of pro-inflammatory cytokines, microglial activation, and blood-brain barrier dysfunction have been implicated in the etiology of MDD. Additionally, biomarkers such as C-reactive protein and neuroimaging findings further support the neuroinflammatory hypothesis. This growing body of evidence has led to increased interest in novel treatment approaches, including anti-inflammatory medications and lifestyle interventions, as potential therapeutic strategies. While selective serotonin reuptake …

Gabapentin Induced Seizures: A Rare Presentation Of Toxicity, Muhammad Umer Mukhtar, Akaansha Varma, Abdullah M. Firoze Ahmed

Advances in Clinical Medical Research and Healthcare Delivery

Gabapentin is a medication used for the management of neuropathic pain, focal seizures, and several other medical conditions. We report a case of a young male who experienced generalized tonic clonic seizures following the intentional ingestion of 31 grams of gabapentin. This case describes an unusual manifestation of gabapentin toxicity, namely seizures, and highlights the overdose of gabapentin for recreational purposes. Furthermore, this report emphasizes the rising misuse of gabapentin and underscores the importance of providers remaining vigilant in recognizing potential substance use disorders.

Improvements In Eeg Tracing Following Initiation Of Cannabidiol: A Case Report, Katherine Horman, Ara Hall, Kailash Pawar

Posters

No abstract provided.

“Now That The Baby Is Out, I Can Be Vaccinated”: A Qualitative Study On Covid-19 Vaccine Hesitancy In Pregnant Women In Kilifi, Kenya, Angela Koech, Onesmus Wanje, Grace Mwashigadi, Geoffrey Katana, Richmond Mdindi, Peter Mwangome, Rachel Craik, Marianne Vidler, Mai-Lei Kinshella, Marleen Temmerman

Centre of Excellence in Women and Child Health

COVID-19 vaccines are safe and effective in pregnancy, but vaccine hesitancy limits uptake and effectiveness. This study explored COVID-19 vaccine hesitancy in pregnancy in Kilifi, coastal Kenya, to elicit reasons for vaccine hesitancy and acceptance, and to compile misconceptions around vaccination in pregnancy. Twenty-three in-depth interviews were conducted with pregnant women, mothers who had given birth in the previous 2 years and health workers (community health promoters, nurses, and supervisors). Data were analyzed using thematic template analysis based on the Vaccine Hesitancy Determinants Matrix. Concern about vaccine safety for the unborn baby was a major driver of hesitancy. Many pregnant …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Normative Growth Trajectories Of Fetal Brain Regions Validated By Satisfactory Maturation Of Neurodevelopmental Domains At 2 Years Of Age, Madeleine Wyburd, Stephen Kennedy, Michelle Fernandes, Nicola Dinsdale, Linde Hesse, Robert Gunier, Leila Ismail, Eric Ohuma, Michael Gravett, Maria Carvalho

Obstetrics and Gynaecology, East Africa

We previously constructed a qualitative, 3D ultrasound derived atlas of the normative spatiotemporal dynamics of fetal brain maturation. Here, using the same healthy multi-national cohort, we applied deep learning methods to 4205 fetal brain scans from 18–27 weeks’ gestation, to produce an extensive, quantitative description of the growth of 16 fetal brain structures associated with satisfactory domain-specific neurodevelopmental scores at 2 years of age. The methodology, which is publicly available, takes less than 10 seconds per scan. We define 28 region-specific, functionally relevant, normative growth trajectories, a ratio between the relative volumes of the insular (rILV) and parietal (rPLV) lobes …

Mapping Social Determinants Of Health Data In Sub-Saharan Africa: A Scoping Review Protocol, Felix Anyiam, Jessica Gjonaj, Ngeresa Osango, Richard Mugo, Peace Aber, Jasmit Shah, Judith Mangeni, Rajesh Vedanthan, Joseph Hogan, Ann Mwangi

Internal Medicine, East Africa

Introduction Research has increasingly underscored the impact of factors such as socioeconomic status, education, healthcare access, housing and environmental conditions in shaping population health outcomes. These factors, collectively called social determinants of health (SDOH), provide crucial context for understanding drivers of health outcomes. In sub-Saharan Africa (SSA), the study of SDOH is critical due to the region’s unique sociocultural and economic conditions. Understanding how SDOH interacts with health systems and capturing SDOH in data is crucial for informing modelling efforts and policies improving population health more effectively. This scoping review aims to map the types of data used to capture …

Two Lysosomal Genes Atp13a2 And Gba1 Interact To Drive Neurodegeneration, Mingxue Gu, Jinghan Zhao, Mingxi Deng, Guang Lin, Xueyang Pan, Wenwen Lin, Mengqi Ma, Jinyong Kim, Seul Kee Byeon, Akhilesh Pandey, Lara M Lange, Chad A Shaw, Jonggeol Kim, Joanne Trinh, Christine Klein, Oguz Kanca, Joshua M Shulman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Background: Parkinson’s disease (PD) is a genetically complex disorder in which combinations of heterozygous risk variants may contribute to pathogenesis. Many PD risk loci encode lysosomal genes, such as GBA1, a common and potent risk factor, conferring at least a 5-fold increase. However, the mechanisms of GBA1 penetrance remain poorly understood.

Methods: Using Drosophila melanogaster, we performed a genetic interaction screen of lysosomal storage disorder (LSD) genes to identify dominant modifiers of Gba1b (fly homolog of GBA1). Age-dependent locomotor assessments, electroretinograms (ERG), transmission electron microscopy (TEM) analyses and quantification of dopaminergic (DA) neurons were used to assess …

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

2025 Highlights In Non-Invasive Neurostimulation And Neuromodulation For Headache Management, Chai Ching Ng, Hsiangkuo Yuan

Department of Jefferson Headache Center Papers and Presentations

No abstract available

Tead-Independent Mechanisms Of Yap Function In Cardiomyocyte Cell Cycle Reentry, Bing Xie, Jeffrey Steimle, Vaibhav Deshmukh, Lin Liu, Chang-Ru Tsai, Todd R Heallen, Wyatt Paltzer, Yuka Morikawa, Fansen Meng, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA …

Using The Linear References From The Pangenome To Discover Missing Autism Variants, Yang Sui, Jiadong Lin, Michelle D Noyes, Youngjun Kwon, Isaac Wong, Nidhi Koundinya, William T Harvey, Mei Wu, Kendra Hoekzema, Katherine M Munson, Gage H Garcia, Jordan Knuth, Julie Wertz, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Rafael A Polo Prieto, Rebecca Meyer-Schuman, Fisher Cherry, Davut Pehlivan, Bernhard Suter, Jonas A Gustafson, Danny E Miller, Human Pangenome Reference Consortium (Hprc), Hanna Berk-Rauch, Tomasz J Nowakowski, Aravinda Chakravarti, Huda Y Zoghbi, Evan E Eichler

Duncan NRI Faculty and Staff Publications

To better understand large-effect pathogenic variation associated with autism, we generated long-read sequencing (LRS) data to construct phased and near-complete genome assemblies (average contig N50 = 43 Mbp, QV = 56) for 189 individuals from 51 families with unsolved cases. We applied read- and assembly-based strategies to facilitate comprehensive characterization of de novo mutations, structural variants (SVs), and DNA methylation. Using LRS pangenome controls, we efficiently filtered >97% of common SVs exclusive to 87 offspring. We find no evidence of increased autosomal SV burden for probands when compared to unaffected siblings yet observe a suggestive trend toward an increased SV …

Single-Cell Rna Sequencing Suggests Different Progenitor Lineages Between Idh Mutant And Idhwt Glioma, Iyad Alnahhas, Allison Kayne, Mehak Khan, Wenyin Shi

Department of Neurology Faculty Papers

Introduction Single-cell RNA sequencing has elucidated the heterogeneity in cancer. Single-cell glioblastoma (GBM) analyses have also proposed the resemblance of GBM cells to radial glia and outer radial glia (oRG) supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17-19) and classified NPCs based on their expression of THY1 (CD90), CD24 and EGFR. Ventricular radial glia are THY1⁻CD24⁻EGFR⁺ whereas oRG are THY1⁻CD24⁻EGFR⁻. Early neuron precursors are CD24⁺THY1⁻EGFR …

Rare Heterozygous De Novo Variants In Rapgef2 Are Associated With A Neurodevelopmental Disorder, Ali H Bereshneh, Kirkland A Wilson, Xueyang Pan, Shabab B Hannan, Megan A Cooper, Jullianne Diaz, Eyby Leon, Tiana M Moses, Mahshid S Azamian, Daryl A Scott, Ping Yee Billie Au, Juan Pablo Appendino, Ingrid E Scheffer, Antony Kaspi, Melanie Bahlo, Michael S Hildebrand, Angela T Morgan, Ekanem Ekure, Joshua M Shulman, Friedhelm Hildebrandt, Jennifer E Posey, Paul Kruszka, Eric Vilain, Shinya Yamamoto, Oguz Kanca, Seth Berger, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

Methods: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We …

Teriparatide Use In Osteopenic Patients Undergoing Single-Level Lumbar Fusion Associated With Decreased 2-Year Revision Rates, Mitchell K. Ng, Ariel N. Rodriguez, Abigail Razi, Ahmed K. Emara, Brian T. Ford, Ameer Tabbaa, Divya Gouni, Jacquelyn J. Xu, Paul G. Mastrokostas, Jad Bou Monsef, Afshin E. Razi

Rothman Institute Papers

Context:  Low bone density is common among lumbar fusion patients and increases the risks of pseudarthrosis, hardware failure, and revision. Teriparatide improves bone mass and fusion in osteoporosis, but its benefit in osteopenia or normal bone remains uncertain.

Aims:  To evaluate the association between teriparatide exposure and (1) postoperative complications, (2) 90-day readmission, and (3) 2-year reoperation, stratified by bone health status (osteoporotic, osteopenic, and normal) in patients undergoing single-level lumbar fusion.

Setting and Design:  A retrospective cohort study using the PearlDiver database from 2010 to 2021 identified patients undergoing single-level lumbar fusion.

Subjects and Methods:  Patients on teriparatide were …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Real-World Multicenter Assessment Of Sustained Clinical Outcomes After Digital Deep Brain Stimulation, Alireza Gharabaghi, Sergiu Groppa, Elena Casas, Alfons Schnitzler, Laura Muñoz-Delgado, Vicky L. Marshall, Jessica Karl, Lin Zhang, Ramiro Alvarez, Mary S. Feldman, Michael J. Soileau, Lan Luo, Benjamin L. Walter, Chengyuan Wu, Hong Lei, Damian M. Herz, Devyani Nanduri, Claudia A. Salazar, Corneliu Luca, Daniel Weiss

Department of Neurosurgery Faculty Papers

Remote, internet-based deep brain stimulation programming for Parkinson's disease accelerates clinical benefits postoperatively by improving access to therapy adjustments compared to in-clinic optimization. After completion of the initial digital programming phase, we show that clinical outcomes, quality of life, and safety remain sustained over at least twelve months under routine care conditions. Embedding a randomized trial within a larger cohort study enables long-term, real-world evaluation, offering a scalable and pragmatic model for assessing complex digital interventions in routine clinical care. (NCT05269862 registered on 2022-03-08 and NCT04071847 registered on 2019-08-28).

Optimal Timing Of Cranioplasty Post-Decompressive Craniectomy In Traumatic Brain Injury: A Systematic Review, Meta-Analysis, And Overview Of Ongoing Trials, Ashviniy Thamilmaran, Shaan Patel, Shiva A. Nischal, Honey Panchal, Kush Kale, Pious D. Patel, Jack Jallo, James S. Harrop

Department of Neurosurgery Faculty Papers

BACKGROUND: The optimal timing of cranioplasty (CP) following decompressive craniectomy (DC) for the management of traumatic brain injury (TBI) remains debated. Prior studies comparing early CP (EC) and late CP (LC) report conflicting outcomes, compounded by inconsistent timing thresholds and limited attention to effect modifiers such as implant material.

OBJECTIVE: To perform a systematic review and meta-analysis comparing outcomes of EC (≤ 90 days) versus LC (> 90 days) after DC for TBI, with particular evaluation of ultra-EC (<  35 days) and implant material.

METHODS: MEDLINE, Embase, and CENTRAL were electronically searched from inception to April 2025, supplemented by manual screening of references and grey …