Neurology Commons^™

A T-Cell Engaging Bispecific Antibody With A Tumor-Selective Bivalent Folate Receptor Alpha Binding Arm For The Treatment Of Ovarian Cancer, Brian C Avanzino, Kirthana Prabhakar, Pranjali Dalvi, Sharon Hartstein, Hannes Kehm, Aarti Balasubramani, Andrew A Boudreau, Ben Buelow, Karen Chang, Laura M Davison, Suhasini Iyer, Vidyut Kalwit, Kristin Lewis Wilson, Harbani K Malik-Chaudhry, Will Pierson, Geovanni Pineda, Udaya S Rangaswamy, Sowmya Saiganesh, Ute Schellenberger, Harshad S Ugamraj, Rodolfovan D Yabut, Roland Buelow, Jocelyn Chapman, Nathan D Trinklein, Katherine E Harris

Faculty, Staff and Student Publications

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density …

A Hybrid Unsupervised And Supervised Learning Approach For Postictal Generalized Eeg Suppression Detection, Xiaojin Li, Yan Huang, Samden D Lhatoo, Shiqiang Tao, Laura Vilella Bertran, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Sudden unexpected death of epilepsy (SUDEP) is a catastrophic and fatal complication of epilepsy and is the primary cause of mortality in those who have uncontrolled seizures. While several multifactorial processes have been implicated including cardiac, respiratory, autonomic dysfunction leading to arrhythmia, hypoxia, and cessation of cerebral and brainstem function, the mechanisms underlying SUDEP are not completely understood. Postictal generalized electroencephalogram (EEG) suppression (PGES) is a potential risk marker for SUDEP, as studies have shown that prolonged PGES was significantly associated with a higher risk of SUDEP. Automated PGES detection techniques have been developed to efficiently obtain PGES durations for …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Stereotactic Radiosurgery For Pituitary Adenomas: A Review Of Literature, Kaynat Siddiqui, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.

Uncertainty Estimation In Classification Of Mgnt Using Radiogenomics For Glioblastoma Patients, W. Farzana, Z. A. Shboul, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors among all high-grade brain cancers. Temozolomide (TMZ) is the first-line chemotherapeutic regimen for glioblastoma patients. The methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) gene is a prognostic biomarker for tumor sensitivity to TMZ chemotherapy. However, the standardized procedure for assessing the methylation status of MGMT is an invasive surgical biopsy, and accuracy is susceptible to resection sample and heterogeneity of the tumor. Recently, radio-genomics which associates radiological image phenotype with genetic or molecular mutations has shown promise in the non-invasive assessment of radiotherapeutic treatment. This study proposes a machine-learning framework …

A Novel Framework To Estimate Cognitive Impairment Via Finger Interaction With Digital Devices, Ashley A Holmes, Shikha Tripathi, Emily Katz, Ijah Mondesire-Crump, Rahul Mahajan, Aaron Ritter, Teresa Arroyo-Gallego, Luca Giancardo

Faculty, Staff and Student Publications

Measuring cognitive function is essential for characterizing brain health and tracking cognitive decline in Alzheimer's Disease and other neurodegenerative conditions. Current tools to accurately evaluate cognitive impairment typically rely on a battery of questionnaires administered during clinical visits which is essential for the acquisition of repeated measurements in longitudinal studies. Previous studies have shown that the remote data collection of passively monitored daily interaction with personal digital devices can measure motor signs in the early stages of synucleinopathies, as well as facilitate longitudinal patient assessment in the real-world scenario with high patient compliance. This was achieved by the automatic discovery …

Advancements In The Quest To Map, Monitor, And Manipulate Neural Circuitry, Jessica L Swanson, Pey-Shyuan Chin, Juan M Romero, Snigdha Srivastava, Joshua Ortiz-Guzman, Patrick J Hunt, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors …

Recurrent Liponeurocytoma: A Case Report And Systematic Review Of The Literature, Darsh S Shah, Himanshu Sharma, Prem Patel, Arya Shetty, Collin William English, J Clay Goodman, Ashwin Viswanathan, Akash J Patel

Duncan NRI Faculty and Staff Publications

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma.

Methods: A systematic review exploring …

Qu-Brats: Miccai Brats 2020 Challenge On Quantifying Uncertainty In Brain Tumor Segmentation - Analysis Of Ranking Scores And Benchmarking Results, Raghav Mehta, Angelos Filos, Ujjwal Baid, Chiharu Sako, Richard Mckinley, Michael Rebsamen, Katrin Dätwyler, Raphael Meier, Piotr Radojewski, Gowtham Krishnan Murugesan, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Fang F. Yu, Baowei Fei, Ananth J. Madhuranthakam, Joseph A. Maldjian, Laura Daza, Catalina Gómez, Pablo Arbeláez, Chengliang Dai, Shuo Wang, Hadrien Reynaud, Yuan-Han Mo, Elsa Angelini, Yike Guo, Wenjia Bai, Subhashis Banerjee, Lin-Min Pei, Murat Ak, Sarahi Rosas-González, Ilyess Zemmoura, Clovis Tauber, Minh H. Vu, Tufve Nyholm, Tommy Löfstedt, Laura Mora Ballestar, Veronica Vilaplana, Hugh Mchugh, Gonzalo Maso Talou, Alan Wang, Jay Patel, Ken Chang, Katharina Hoebel, Mishka Gidwani, Nishanth Arun, Sharut Gupta, Mehak Aggarwal, Praveer Singh, Elizabeth R. Gerstner, Jayashree Kalpathy-Cramer, Nicholas Boutry, Alexis Huard, Lasitha Vidyaratne, Md. Monibor Rahman, Khan M. Iftekharuddin, Joseph Chazalon, Elodie Puybareau, Guillaume Tochon, Jun Ma, Mariano Cabezas, Xavier Llado, Arnau Oliver, Liliana Valencia, Sergi Valverde, Mehdi Amian, Mohammadreza Soltaninejad, Andriy Myronenko, Ali Hatamizadeh, Xue Feng, Quan Dou, Nicholas Tustison, Craig Meyer, Nisarg A. Shah, Sanjay Talbar, Marc-André Weber, Abhishek Mahajan, Andras Jakab, Roland Wiest, Hassan M. Fathallah-Shaykh, Arash Nazeri, Mikhail Milchenko1, Daniel Marcus, Aikaterini Kotrotsou, Rivka Colen, John Freymann, Justin Kirby, Christos Davatzikos, Bjoern Menze, Spyridon Bakas, Yarin Gal, Tal Arbel

Electrical & Computer Engineering Faculty Publications

Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. …

Radiomic Texture Feature Descriptor To Distinguish Recurrent Brain Tumor From Radiation Necrosis Using Multimodal Mri, M. S. Sadique, A. Temtam, E. Lappinen, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Despite multimodal aggressive treatment with chemo-radiation-therapy, and surgical resection, Glioblastoma Multiforme (GBM) may recur which is known as recurrent brain tumor (rBT), There are several instances where benign and malignant pathologies might appear very similar on radiographic imaging. One such illustration is radiation necrosis (RN) (a moderately benign impact of radiation treatment) which are visually almost indistinguishable from rBT on structural magnetic resonance imaging (MRI). There is hence a need for identification of reliable non-invasive quantitative measurements on routinely acquired brain MRI scans: pre-contrast T1-weighted (T1), post-contrast T1-weighted (T1Gd), T2-weighted (T2), and T2 Fluid Attenuated Inversion Recovery (FLAIR) that can …

Neuromotor Changes In Participants With A Concussion History Can Be Detected With A Custom Smartphone App, Christopher K. Rhea, Masahiro Yamada, Nikita A. Kuznetsov, Jason T. Jakiela, Chanel T. Lojacono, Scott E. Ross, F. J. Haran, Jason M. Bailie, W. Geoffrey Wright

Rehabilitation Sciences Faculty Publications

Neuromotor dysfunction after a concussion is common, but balance tests used to assess neuromotor dysfunction are typically subjective. Current objective balance tests are either cost- or space-prohibitive, or utilize a static balance protocol, which may mask neuromotor dysfunction due to the simplicity of the task. To address this gap, our team developed an Android-based smartphone app (portable and cost-effective) that uses the sensors in the device (objective) to record movement profiles during a stepping-in-place task (dynamic movement). The purpose of this study was to examine the extent to which our custom smartphone app and protocol could discriminate neuromotor behavior between …

In Alzheimer-Prone Brain Regions, Metabolism And Risk-Gene Expression Are Strongly Correlated, Fengdan Ye, Quentin Funk, Elijah Rockers, Joshua M Shulman, Joseph C Masdeu, Belen Pascual

Duncan NRI Faculty and Staff Publications

Neuroimaging in the preclinical phase of Alzheimer’s disease provides information crucial to early intervention, particularly in people with a high genetic risk. Metabolic network modularity, recently applied to the study of dementia, is increased in Alzheimer’s disease patients compared with controls, but network modularity in cognitively unimpaired elderly with various risks of developing Alzheimer’s disease needs to be determined. Based on their 5-year cognitive progression, we stratified 117 cognitively normal participants (78.3 ± 4.0 years of age, 52 women) into three age-matched groups, each with a different level of risk for Alzheimer’s disease. From their fluorodeoxyglucose PET we constructed metabolic …

Typical Sounding Atypical Diagnostic Conundrum -- A Rare Case Of Mycobacterium Avium Complex (Mac) Presenting With Multiple Cranial Nerve Involvement, Ashwini Kini, Karl Echiverri, Edward J. Escott, Padmaja Sudhakar

Neurology Faculty Publications

Background

MAC infections rarely cause symptomatic systemic infection in immunocompetent healthy individuals. This case brings to light a rare such presentation that gives us a learning point about keeping a strong pre-clinical suspicion for this condition in patients whom lung imaging reveals suspicious cavitary lesions. Starting empiric therapy while awaiting culture results may be considered after weighing risks and benefits in order to achieve the morbidity and mortality associated with the disease.

Case report

A 54 year-old white male presented for evaluation of progressively worsening vertigo, imbalance, vertical diplopia, facial diplegia, bilateral hyperacusis followed by hearing loss, dysphagia, and dysarthria …

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

Intensive Care Bundle With Blood Pressure Reduction In Acute Cerebral Hemorrhage Trial (Interact3): Study Protocol For A Pragmatic Stepped-Wedge Cluster-Randomized Controlled Trial, Lili Song, Xin Hu, Lu Ma, Xiaoying Chen, Menglu Ouyang, Laurent Billot, Qiang Li, Paula Muñoz-Venturelli, Carlos Abanto, Mohammad Wasay

Section of Neurology

Background: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH.
Methods: INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 …

Filled/Non-Filled Pairs: An Empirical Challenge To The Integrated Information Theory Of Consciousness, Amber R. Hopkins, Kelvin J. Mcqueen

Philosophy Faculty Articles and Research

Perceptual filling-in for vision is the insertion of visual properties (e.g., color, contour, luminance, or motion) into one’s visual field, when those properties have no corresponding retinal input. This paper introduces and provides preliminary empirical support for filled/non-filled pairs, pairs of images that appear identical, yet differ by amount of filling-in. It is argued that such image pairs are important to the experimental testing of theories of consciousness. We review recent experimental research and conclude that filling-in involves brain activity with relatively high integrated information (Φ) compared to veridical visual perceptions. We then present filled/non-filled pairs as …

A Literature Review Of Mild Traumatic Brain Injury Research, Brindlea Peterson

Honors Theses

Mild traumatic brain injuries (mTBI) are a type of traumatic brain injury (TBI) usually sustained from an injury to the head and are hard to diagnose due to the lack of physical evidence seen in diagnostic radiology. The estimated worldwide rate of incidence each year is 42 million, making mTBIs rather common. In the US armed forces, that rate of incidence is even higher due to the dangerous nature of the work being done. Many complications can come from not properly addressing an mTBI after it happens which makes being able to determine an appropriate return-to-play or return-to-duty time very …

Transition Program To Postsecondary Education For Students With Traumatic Brain Injury, Eung Gyeong Park, Susan Macdermott, Becki Cohill, Karen Park

Fall 2021 Virtual OTD Capstone Symposium

Traumatic brain injury (TBI) is a condition that occurs due to an external blow to the skull that damages the brain (Carulli et al., 2018). According to the Centers for Disease Control and Prevention, 2.5 million TBI have been reported each year. Many students with TBI face physical, cognitive, environmental, and social challenges in their transition to post-secondary education (Bedell et al., 2017). Individuals with TBI experience social and behavioral changes that interfere with their participation as they face difficulties initiating, regulating their social behaviors, and experiencing increased introversion (Bedell et al., 2017). Physical challenges include fatigue, headaches, sleep disturbances, …

Dementia Risk Reduction: Why Haven't The Pharmacological Risk Reduction Trials Worked? An In-Depth Exploration Of Seven Established Risk Factors, Ruth Peters, John Breitner, Sarah James, Gregory A. Jicha, Pierre-Francois Meyer, Marcus Richards, A. David Smith, Hussein N. Yassine, Erin L. Abner, Atticus H. Hainsworth, Patrick G. Kehoe, Nigel Beckett, Christopher Weber, Craig Anderson, Kaarin J. Anstey, Hiroko H. Dodge

Neurology Faculty Publications

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need …

Reduced Risk Of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From A United States Claims Database, Chengyuan Wu, Sean J Nagel, Rahul Agarwal, Monika Pötter-Nerger, Wolfgang Hamel, Ashwini Sharan, Allison T Connolly, Binith Cheeran, Paul S Larson

Department of Neurosurgery Faculty Papers

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States.

Design: Retrospective, contemporaneous cohort study.

Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018.

Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, …