Neurology Commons^™

Magnesium Sulfate In The Management Of Acute Ischemic Stroke: A Review Of The Literature And Future Directions, Maximillian S Feygin, Alex Brenner, Omar Tanweer

Faculty, Staff and Students Publications

Background: The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS. Magnesium (MgSO4) provides an attractive neuroprotectant profile, having many different effects, and is inexpensive, readily available, and has a long-established safety and tolerability profile …

Exploring Individual Differences In Amygdala-Mediated Memory Modulation, Martina K Hollearn, Joseph R Manns, Lou T Blanpain, Stephan B Hamann, Kelly Bijanki, Robert E Gross, Daniel L Drane, Justin M Campbell, Krista L Wahlstrom, Griffin F Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T Willie, Cory S Inman

Faculty, Staff and Students Publications

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without …

Robust Cluster Prediction Across Data Types Validates Association Of Sex And Therapy Response In Gbm, David L Gibbs, Gino Cioffi, Boris Aguilar, Kristin A Waite, Edward Pan, Jacob Mandel, Yoshie Umemura, Jingqin Luo, Joshua B Rubin, David Pot, Jill Barnholtz-Sloan

Faculty, Staff and Students Publications

Background: Previous studies have described sex-specific patient subtyping in glioblastoma. The cluster labels associated with these "legacy data" were used to train a predictive model capable of recapitulating this clustering in contemporary contexts.

Methods: We used robust ensemble machine learning to train a model using gene microarray data to perform multi-platform predictions including RNA-seq and potentially scRNA-seq.

Results: The engineered feature set was composed of many previously reported genes that are associated with patient prognosis. Interestingly, these well-known genes formed a predictive signature only for female patients, and the application of the predictive signature to male patients produced unexpected results. …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

The Biological Intersection Between Chemotherapy-Related Cognitive Impairment And Alzheimer Disease, Matthew Torre, Camila A Zanella, Mel B Feany

Duncan NRI Faculty and Staff Publications

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive deficits, termed chemotherapy-related cognitive impairment. This review discusses biologically plausible pathways underlying both disorders, with the goal of …

Advances In Multiple Sclerosis, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...].

High Cellular Plasticity State Of Medulloblastoma Local Recurrence And Distant Dissemination, Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang

Faculty, Staff and Students Publications

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 …

A Potential Vegf-Driven Hypothesis Of Calvarial Centripetal Proliferation In Cerebral Proliferative Angiopathy, Shigeta Miyake, Timo Krings, Tze Phei Kee, Thierry A G M Huisman

Faculty, Staff and Students Publications

Cerebral proliferative angiopathy (CPA) is a rare subtype of cerebral arteriovenous malformation, characterized by unique angiographic features and clinical presentations. Although the clinical and angiographic characteristics of CPA have been well described, their impact on the surrounding tissues remains underexplored. Herein, we investigated the presence of calvarial thickening in patients with CPA, and discuss its potential pathogenesis. This retrospective multicenter cohort study enrolled 16 CPA patients from our institutions. Patients were identified by a search of the hospital medical records for key words related to "cerebral proliferative angiopathy." Data on demographics, CPA characteristics, clinical symptoms, and calvarial thickening were collected …

Foxr2 Targets Lhx6+/Dlx+ Neural Lineages To Drive Central Nervous System Neuroblastoma, Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael Mcnicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W Tsai, Andrey Korshunov, Timothy N Phoenix, Benjamin Ellezam, David T W Jones, Michael D Taylor, Pratiti Bandopadhayay, Manav Pathania, Nada Jabado, Claudia L Kleinman

Faculty, Staff and Students Publications

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal …

Is Modulation Of Immune Checkpoints On Glioblastoma-Infiltrating Myeloid Cells A Viable Therapeutic Strategy?, Ruochen Du, Jianzhong Zhang, Rimas V Lukas, Shashwat Tripathi, Jared T Ahrendsen, Michael A Curran, Crismita Dmello, Peng Zhang, Roger Stupp, Ganesh Rao, Amy B Heimberger

Faculty, Staff and Students Publications

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, …

Alzheimer’S Disease: Relationship Of Cognition And Behavior To Neurochemistry, Peter J. Whitehouse

Faculty Scholarship

Alzheimer’s disease is characterized by loss of cells and synapses in specific neural systems. The development of more effective therapies will depend on understanding the relationships between this pathology and the cognitive and behavioral impairments. In this review, focusing primarily on work in our laboratory, we will examine both classic and neuropeptide neurotransmitter systems and will discuss conceptual and methodological problems in relating clinical and biological measures.

Building Toward Population Reserve And A Critical Positive Psychiatry, Peter J. Whitehouse

Faculty Scholarship

No abstract provided.

Molecular Logic For Cellular Specializations That Initiate The Auditory Parallel Processing Pathways, Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, M Cecilia Ljungberg, Matthew J Mcginley, Laurence O Trussell, Xiaolong Jiang

Faculty, Staff and Students Publications

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the specialized cellular phenotypes in the CN. In particular, …

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …

Minimally Invasive Non-Expansile Tubular Extradural Posterior Fossa Decompression (Minted Technique) For The Management Of Chiari I.5 Malformation: Historical Overview Of Surgical Techniques, Technical Note, Proof Of Concept, Illustrative Case And Case Series. Lesser Is Better, José Alberto Israel Romero Rangel, Manuel Eduardo Soto García, Sergio Soriano Solís, Carlos Raúl Rangel Morales, Gerson Reyes Rodríguez, José Antonio Soriano Sánchez

Archives of Neurosurgery

BACKGROUND: Chiari's Malformation surgical treatment has significantly changed since the "classical" technique description by Gardner (1950). It is probably the most commonly performed approach, even when multiple techniques are available because no substantial changes nor any clear surgical objectives have been made. OBJECTIVE: To demonstrate a new cutting-edge surgical technique mastering the advantage of each surgical procedure ever described in the history of Chiari's Malformation establishing three critical points in surgical technique: clear patient-specific surgical goals, dynamic posterior fossa reconstruction, and extradural occipitoatlantal dense-adhesions release. METHODS: A comprehensive review of historically described approaches, proof of concept of surgical technique in …

Deep Dive In Sound Filtering, Cecilia Zoutewelle

A. The Science of Sound

A 7-page report, with illustrations and bullet-point summaries, on the ways we filter sounds as part of the standard process of hearing. Includes brief considerations of evolution, selective listening in conversations, and listening bias.

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …

Endoneurial Immune Interplay In Peripheral Nerve Repair: Insights And Implications For Future Therapeutic Interventions, Alina Sprenger-Svačina, Martin K R Svačina, Husniye G Otlu, Tong Gao, Kazim A Sheikh, Gang Zhang

Faculty, Staff and Student Publications

The mechanisms underlying axonal injury and repair in peripheral nerves, whether due to traumatic damage or autoimmune neuropathies, are complex and not yet fully understood. Recent research indicates that an orchestrated interplay between damaged neurons, Schwann cells, and especially endoneurial immune cells such as macrophages or T cells is crucial to achieve satisfactory nerve recovery. Following axonal injury, degenerating axons and reactive Schwann cells release chemoattractants and cytokines that recruit immune cells into the endoneurium. Among them, macrophages play a pivotal role by clearing axonal and myelin debris and subsequently creating a pro-regenerative microenvironment that supports axonal outgrowth. There is …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Immune Dynamics And B Cell Contributions To Neuroplasticity And Recovery After Stroke, Thomas A. Ujas

Theses and Dissertations--Neuroscience

This dissertation explores the dynamic interplay between the immune system and the brain across stroke and aging using clinical, post-mortem, and pre-clinical models. The immune system plays critical roles in shaping brain function, responding to injury, and mediating recovery. These studies aim to enhance our understanding of neuroimmune dynamics across spatial and temporal dimensions.

In the first part, we conducted longitudinal sampling of aneurysmal subarachnoid hemorrhage (aSAH) patients to track immune cell and cytokine changes at days 3, 5, 7, 10, and 14 post-stroke, with a focus on delayed cerebral ischemia (DCI), a common complication. We observed distinct temporal patterns, …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

The Differential Expands: Ataxia From Paraneoplastic Cerebellar Degeneration, Dominic Thomas, Md, Amy Dechet

Books, Presentations, Posters, Etc.

Introduction: Paraneoplastic cerebellar degeneration is a rare cause of cerebellar ataxia with a poor prognosis for neurologic recovery. The management of symptoms is dependent primarily upon timely diag nosis and treatment of the underlying neoplasm. Herein, we present the diagnostic and treatment course of a patient with paraneoplastic cerebellar degeneration. Case: A 72-year-old woman with a past medical history of left mastectomy for high grade ER/PR negative Her2 positive invasive ductal carcinoma presented with progressively worsening dysarthria and ataxia over two months. A metabolic work up by her primary care physician was unrevealing. Breast MRI did not show recurrence of …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor

Faculty, Staff and Students Publications

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma …

Comparative Analysis Of Aav Serotypes For Transduction Of Olfactory Sensory Neurons, Benjamin D W Belfort, Johnathan D Jia, Alexandra R Garza, Anthony M Insalaco, J P Mcginnis, Brandon T Pekarek, Joshua Ortiz-Guzman, Burak Tepe, Hu Chen, Ascent-Pd Investigators, Zhandong Liu, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Olfactory sensory neurons within the nasal epithelium detect volatile odorants and relay odor information to the central nervous system. Unlike other sensory inputs, olfactory sensory neurons interface with the external environment and project their axons directly into the central nervous system. The use of adeno-associated viruses to target these neurons has garnered interest for applications in gene therapy, probing olfactory sensory neuron biology, and modeling disease. To date, there is no consensus on the optimal AAV serotype for efficient and selective transduction of olfactory sensory neurons

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Sujal Manohar, Jennifer Jacobe, Rebecca Berger, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …