Neurology Commons^™

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 …

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 …

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 …

Pathogenesis Of Polyglutamine Diseases: Piecing Together A Complex Molecular Puzzle, Esmeralda Villavicencio Gonzalez, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

Dandelion Tumor With Polycranial Neuropathies, Elena Salikhova-Neace, Petros Keoseyan, Anna Belits, Ethan Mccarty, Judd Jensen, Emily Lampe

Continental and Mountain Divisions GME Resarch Day 2026

No abstract provided.

Refractory Status Epilepticus After Hair Transplant: A Case Of Lidocaine Toxicity In A Post-Craniotomy Patient, Sarai Arbus, Cheyenne Lockwood, Max Wei, Andrew Labelle

Continental and Mountain Divisions GME Resarch Day 2026

No abstract provided.

Nitrous Oxide And Hirayama: A Special Case, Sierra Sandler, Natasha Hamilton, Elena Salikhova-Neace, Jeannette Betz, Alexis Taylor

Continental and Mountain Divisions GME Resarch Day 2026

No abstract provided.

Diplopia In Metastatic Hepatocellular Carcinoma With Spread To The Sphenoid Sinus, Elena Salikhova-Neace, Anna Belits, Petros Keoseyan, Ethan Mccarty, Judd Jensen, Katrina Lancaster-Shorts, Emily Lampe

Continental and Mountain Divisions GME Resarch Day 2026

No abstract provided.

Implementation And Clinical Utility Of Ultra-Low-Field Portable Magnetic Resonance Imaging For Postprocedural Neurological Evaluation In Ambulatory Neurosurgery: Illustrative Cases, Devan Patel, Vinay Jaikumar, Taysia P. T. Morioka, Laz Rifkin, Kenneth S. Jacoby, Jaims Lim, Anais Andrade, Aimee C. Degaetano, Pui Man Rosalind Lai, Elad I. Levy

EVMS School of Health Professions Faculty Publications

BACKGROUND

Elective endovascular neurosurgical procedures are increasingly performed in ambulatory neurosurgery centers, enabled by advances in catheter technology, safety of conscious sedation, and refined patient selection. Although complication rates are low, rapid evaluation of postprocedural neurological deficits remains critical. Conventional MRI is often impractical in outpatient or procedural settings, whereas ultra-low-field portable MRI (ULF-pMRI) systems (such as Swoop) allow bedside imaging with favorable diagnostic performance.

OBSERVATIONS

Two women in their 60s developed acute neurological deficits at an ambulatory neurosurgery center (ANSC) after diagnostic cerebral angiography in one case and elective internal carotid artery flow diversion in the other. In both …

Refining Aicardi Syndrome Diagnostic Criteria: An Expert-Based Consensus Using A Modified Delphi Approach, Silvia Masnada, Valentina De Giorgis, Umberto Carugo, Nadia Bahi-Buisson, Mara Cavallin, Mark Corbett, Manuela Formica, Jozef Gecz, Natalia Petros, Emilio Perucca, Anna Pichiecchio, Paolo Fusar Poli, Elliott H Sherr, Ignatia B Van Den Veyver, Federico Zara, Martin Geroldinger, Pierangelo Veggiotti, Alexis Arzimanoglou

Duncan NRI Faculty and Staff Publications

Background and objectives: Aicardi syndrome (AIC) is a rare neurodevelopmental disorder historically characterised by the presence of chorioretinal lacunae, corpus callosum agenesis, infantile spasms and several supporting features that aid in diagnosis. However, the unclear aetiology and evolving diagnostic tools have led to ongoing reconsideration of the criteria, based on individual approaches. Our study aimed to establish, for the first time, an expert-based consensus on diagnostic criteria for AIC by integrating both existing and novel ones.

Methods: A geographically diverse and multidisciplinary group of expert physicians was invited to participate in a modified Delphi study, to achieve consensus on major, …

Telethon Undiagnosed Disease Program: Structured Approach To Solving Rare Childhood-Onset Genetic Diseases, Annalaura Torella, Manuela Morleo, Carmine Spampanato, Raffaele Castello, Mariateresa Zanobio, Giulio Piluso, Pasquale Di Letto, Maria Elena Onore, Sarah Iffat Rahman, Francesco Musacchia, Michele Pinelli, Giuseppina Vitiello, Giulia De Riso, Angelo Selicorni, Milena Mariani, Cecilia Daolio, Valeria Capra, Marcello Scala, Francesca Nardecchia, Serena Galosi, Mario Mastrangelo, Filippo Manti, Donatella Milani, Corrado Romano, Donatella Greco, Claudia Ciaccio, Stefano D'Arrigo, Arianna De Laurentiis, Antonietta Coppola, Marcella Zollino, Domizia Pasquetti, Federica Francesca L'Erario, Albina Tummolo, Claudia Santoro, Livia Garavelli, Carla Marini, Stefania Bigoni, Alfonsina Tirozzi, Viviana Cetrangolo, Giancarlo Parenti, Diego Di Bernardo, Angela Peron, Silvia Maitz, Andrea Accogli, Gerarda Cappuccio, Sandro Banfi, Giorgio Casari, Andrea Ballabio, Nicola Brunetti-Pierri, Vincenzo Nigro, Telethon Undiagnosed Disease Study Group

Duncan NRI Faculty and Staff Publications

Purpose: Many children with severe genetic disorders remain undiagnosed despite advanced genomic technologies. Early diagnosis is vital for prognosis, genetic counseling, and targeted treatment development. This study aims to increase diagnostic rates in complex pediatric cases and foster research into disease mechanisms.

Methods: Launched in 2016, the Telethon Undiagnosed Diseases Program provides a structured, multicenter approach to rare disease diagnosis. Standardized case submission criteria ensured consistent clinical data collection. Children with severe, multisystemic disorders and prior negative genetic tests were eligible. After case approval, trio-based exome sequencing was performed, with regular reanalysis for unsolved cases until December 2024.

Results: Between …

Transverse Myelitis, Children's Health School Services

School Guides

Educator guide about how to support students with transverse myelitis.

Traumatic Brain Injury, Children's Health School Services

School Guides

Educator guide about how to support students with traumatic brain injury.

Neuromyelitis Optica, Children's Health School Services

School Guides

Educator guide about how to support students with neuromyelitis optica.

Limbic Encephalitis, Children's Health School Services

School Guides

Educator guide about how to support students with limbic encephalitis.

Functional Neurological Disorder, Children's Health School Services

School Guides

Educator guide about how to support students with functional neurological disorder.

Real-World Anti-Amyloid Therapy Beyond Traditional Symptomatic Populations: A Longitudinal Case Series, Jayoung Han, Yuan Fang, Darlingtina Esiaka, Olufunmilola Abraham

Mathematics & Statistics Faculty Publications

Introduction: Anti-amyloid monoclonal antibodies are approved as disease-modifying therapies for early Alzheimer’s disease (AD), but real-world evidence remains limited, particularly among individuals treated during preclinical or minimally symptomatic stages. This study characterized clinical and biomarker trajectories among anti-amyloid therapy recipients across disease stages.

Method: We conducted a longitudinal retrospective case series of three biomarker-positive individuals from the Alzheimer’s Disease Neuroimaging Initiative who received lecanemab or donanemab. Clinical, cognitive, cerebrospinal fluid, plasma biomarker, and amyloid PET data were examined.

Results: In all three cases, most of the observation period preceded anti-amyloid therapy initiation. Clinical trajectories varied by biomarker profile and treatment …