Neurology Commons^™

Recovery After Human Bone Marrow Mesenchymal Stem Cells (Hbm-Mcs)-Derived Extracellular Vesicles (Evs) Treatment In Post-Mcao Rats Requires Repeated Handling, Yolanda Gomez-Galvez, Malvika Gupta, Mandeep Kaur, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi, Amit K. Srivastava, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form …

Endovascular Therapy Versus Medical Management In Isolated Posterior Cerebral Artery Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Weighted Study, Hamza Adel Salim, Benjamin Pulli, Vivek Yedavalli, Basel Musmar, Nimer Adeeb, Dhairya Lakhani, Muhammed Amir Essibayi, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Inayat Grewal, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, 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, Max Wintermark, Adrien Guenego, Adam A Dmytriw

Faculty, Staff and Student Publications

Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo.

Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified …

Characterizing The Progression From Mild Cognitive Impairment To Dementia: A Network Analysis Of Longitudinal Clinical Visits, Muskan Garg, Sara Hejazi, Sunyang Fu, Maria Vassilaki, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

Faculty, Staff and Student Publications

Background: With the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.

Objective: We aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, …

“Ups And Downs, Joys And Sorrows” – Assessment And Clinical Relevance Of Patient Priorities In An Interdisciplinary Parkinson’S Disease Clinic, Esme D. Trahair, Allison M. Allen, Sneha Mantri

Journal of Patient-Centered Research and Reviews

Purpose: Barriers to communication and inaccurate provider assumptions about patient priorities limit the delivery of comprehensive, high-quality, patient-centered care (PCC) to people with Parkinson’s (PWP). This study aimed to analyze priorities of PWP using a qualitative, unstructured single-question survey and to test associations with validated quality of life (QOL) measures.

Methods: During appointments at a subspecialty, interdisciplinary clinic, PWP (n = 139) provided written responses to the prompt: “What is important for your care team to know about you?” Patient Health Questionnaire, Montreal Cognitive Assessment, and Hoehn and Yahr scales were obtained through retrospective chart review. Key qualitative themes were …

Integrated Electrophysiological And Genomic Profiles Of Single Cells Reveal Spiking Tumor Cells In Human Glioma, Rachel N Curry, Qianqian Ma, Malcolm F Mcdonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci

Faculty, Staff and Students Publications

Prior studies have described the complex interplay that exists between glioma cells and neurons, however, the electrophysiological properties endogenous to tumor cells remain obscure. To address this, we employed Patch-sequencing on human glioma specimens and found that one third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia by firing single, short action potentials. To define these hybrid cells (HCs) and discern if they are of tumoral origin, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate each cell individually. SCRAM revealed that HCs represent tumor and non-tumor cells that …

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Simulated Resections And Responsive Neurostimulator Placement Can Optimize Postoperative Seizure Outcomes When Guided By Fast Ripple Networks, Shennan Aibel Weiss, Michael R Sperling, Jerome Engel, Anli Liu, Itzhak Fried, Chengyuan Wu, Werner Doyle, Charles Mikell, Sima Mofakham, Noriko Salamon, Myung Shin Sim, Anatol Bragin, Richard Staba

Department of Neurology Faculty Papers

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure-onset zone and incorporation of neuroimaging findings from MRI, PET, single-photon emission CT and magnetoencephalography modalities. Resecting cortical tissue generating high-frequency oscillations has been investigated as a more efficacious alternative to targeting the seizure-onset zone. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz …

A Virtual In Vivo Dissection And Analysis Of Socioaffective Symptoms Related To Cerebellum-Midbrain Reward Circuitry In Humans, Linda J. Hoffman, Jula M. Foley, Josiah K. Leong, Holly Sullivan-Toole, Blake L. Elliot, Ingrid R. Olson

Psychological Science Faculty Publications and Presentations

Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. …

Il-7rα On Cd4+ T Cells Is Required For Their Survival And The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Gholamreza Azizi, Bram Van Den Broek, Larissa Ishikawa, Hamed Naziri, Reza Yazdani, Guang-Xian Zhang, Bogoljub Ciric, Mohamad Rostami

Department of Neurology Faculty Papers

BACKGROUND: The IL-7 receptor alpha (IL-7Rα) binds both IL-7 and thymic stromal lymphopoietin (TSLP). IL-7Rα is essential for the development and survival of naive CD4+ T cells and their differentiation to effector/memory CD4+ T cells. Mice lacking IL-7Rα have severe lymphopenia and are resistant to experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. However, it has been reported that IL-7Rα on peripheral CD4+ T cells is disposable for their maintenance and EAE pathogenesis, which does not align with the body of knowledge on the role of IL-7Rα in the biology of CD4+ T cells. Given that a definitive study …

Alzheimer’S Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Matea Pavešković, Ruth B De-Paula, Shamsideen A Ojelade, Evelyne K Tantry, Mikhail Y Kochukov, Suyang Bao, Surabi Veeraragavan, Alexandra R Garza, Snigdha Srivastava, Si-Yuan Song, Masashi Fujita, Duc M Duong, David A Bennett, Philip L De Jager, Nicholas T Seyfried, Mary E Dickinson, Jason D Heaney, Benjamin R Arenkiel, Joshua M Shulman

Duncan NRI Faculty and Staff Publications

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in …

The Fundamentals Of Antiseizure Medications: A Through Z, Timothy E Welty, Jeannine M Conway, Jacquelyn Bainbridge, Kristen Park, David G Vossler, Archana A Patel, Alica Goldman

Faculty, Staff and Students Publications

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these …

Identification Of An Ionic Mechanism For Erα-Mediated Rapid Excitation In Neurons, Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V Jossy, Megan L Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

The major female ovarian hormone, 17β-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα …

Generalized Spike-Waves In Idiopathic Generalized Epilepsies: Does Their Frequency Matter?, Ali A. Asadi-Pooya, Mohsen Farazdaghi

Department of Neurology Faculty Papers

OBJECTIVES: We hypothesized that the frequency (in Hertz) of generalized spike-waves (GSWs) in patients with idiopathic generalized epilepsy (IGE) has associations with the syndromic diagnosis as well as with the prognosis of patients (their response to medical treatment). METHODS: This was a retrospective study of a prospectively developed database. All patients with a diagnosis of IGE were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Patients were classified into four IGE syndromes: childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and generalized tonic-clonic seizures alone. RESULTS: Five hundred and eighty-three …

Arid1a-Baf Coordinates Zic2 Genomic Occupancy For Epithelial-To-Mesenchymal Transition In Cranial Neural Crest Specification, Samantha M. Barnada, Aida Giner De Gracia, Cruz Morenilla-Palao, Maria Teresa López-Cascales, Chiara Scopa, Francis J. Waltrich, Harald M.M. Mikkers, Maria Elena Cicardi, Jonathan Karlin, Davide Trotti, Kevin A. Peterson, Samantha A. Brugmann, Gijs W.E. Santen, Steven B. Mcmahon, Eloísa Herrera, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The BAF chromatin remodeler regulates lineage commitment including cranial neural crest cell (CNCC) specification. Variants in BAF subunits cause Coffin-Siris syndrome (CSS), a congenital disorder characterized by coarse craniofacial features and intellectual disability. Approximately 50% of individuals with CSS harbor variants in one of the mutually exclusive BAF subunits, ARID1A/ARID1B. While Arid1a deletion in mouse neural crest causes severe craniofacial phenotypes, little is known about the role of ARID1A in CNCC specification. Using CSS-patient-derived ARID1A induced pluripotent stem cells to model CNCC specification, we discovered that ARID1A-haploinsufficiency impairs epithelial-to-mesenchymal transition (EMT), a process necessary for CNCC delamination and migration from …

Default Mode Network Electrophysiological Dynamics And Causal Role In Creative Thinking, Eleonora Bartoli, Ethan Devara, Huy Q Dang, Rikki Rabinovich, Raissa K Mathura, Adrish Anand, Bailey R Pascuzzi, Joshua Adkinson, Yoed N Kenett, Kelly R Bijanki, Sameer A Sheth, Ben Shofty

Faculty, Staff and Students Publications

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by …

Leptomeningeal Metastases From Solid Tumors: A Society For Neuro-Oncology And American Society Of Clinical Oncology Consensus Review On Clinical Management And Future Directions, Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O'Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire

Faculty, Staff and Students Publications

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, …

Neuron-Glial Interactions: Implications For Plasticity, Behavior, And Cognition, Mauricio Rangel-Gomez, Cristina M Alberini, Benjamin Deneen, Gabrielle T Drummond, Tiina Manninen, Mriganka Sur, Aleksandra Vicentic

Faculty, Staff and Students Publications

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, to include a diversity of other functions, such as regulation of complex behaviors. Astrocytes, the most abundant glial cells in the central nervous system (CNS), have been shown to modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling and behavioral functions. Contemporary studies further highlight astrocytes' involvement in complex cognitive functions. For instance, inhibiting astrocytes in the hippocampus can lead to memory deficits, suggesting their integral role in memory processes. Moreover, astrocytic calcium activity and astrocyte-neuron metabolic coupling have …

The Alzmatch Pilot Study - Feasibility Of Remote Blood Collection Of Plasma Biomarkers For Preclinical Alzheimer’S Disease Trials, S. Walter, O. Langford, G. A. Jimenez-Maggiora, S. Abdel-Latif, R. A. Rissman, J. D. Grill, J. Karlawish, A. Atri, S. Bruschi, K. Hussen, M. C. Donohue, G. A. Marshall, Gregory Jicha, M. Racke, R. S. Turner, C. H. Van Dyck, V. Venkatesh, K. E. Yarasheski, R. Sperling, J. Cummings, Paul Aisen, R. Raman

Neurology Faculty Publications

BACKGROUND: Advances in plasma biomarkers to detect Alzheimer’s disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer’s Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.

OBJECTIVES: The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based …

Global, Regional, And National Burden Of Stroke And Its Risk Factors, 1990–2021: A Systematic Analysis For The Global Burden Of Disease Study 2021, Gbd 2021 Stroke Risk Factor Collaborators

Ateneo School of Medicine and Public Health Publications

Background

Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021.

Methods

We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, …

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

Clinical Outcome-Guided Deep Temporal Clustering For Disease Progression Subtyping, Dulin Wang, Xiaotian Ma, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Objective: Complex diseases exhibit heterogeneous progression patterns, necessitating effective capture and clustering of longitudinal changes to identify disease subtypes for personalized treatments. However, existing studies often fail to design clustering-specific representations or neglect clinical outcomes, thereby limiting the interpretability and clinical utility.

Method: We design a unified framework for subtyping longitudinal progressive diseases. We focus on effectively integrating all data from disease progressions and improving patient representation for downstream clustering. Specifically, we propose a clinical Outcome-Guided Deep Temporal Clustering (OG-DTC) that generates representations informed by clustering and clinical outcomes. A GRU-based seq2seq architecture captures the temporal dynamics, and the model …

The Grenada Learning And Memory Scale: Psychometric Features And Normative Data In Caribbean Preschool Children, Karen Blackmon, Roberta Evans, Lauren Mohammed, Kemi Burgen, Erin Ingraham, Bianca Punch, Rashida Isaac, Toni Murray, Jesma Noel, Cora Belmar-Roberts

Brain and Mind Institute

Objective: Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially pertinent in low- and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. The Grenada Learning and Memory Scale (GLAMS) was created for use in limited resource settings and includes a shopping list and face-name association test. Here, we present psychometric and normative data for the GLAMS in a Grenadian preschool sample.

Methods: Typically developing children between 36 and 72 months of age, primarily English speaking, were recruited from public preschools in …

Improving Adherence Amongst Post-Stroke Patients In The Outpatient Setting, Olivea Adetu

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This quality improvement (QI) project aimed to enhance medication adherence and follow-up rates through structured, personalized phone calls to recently discharged post-stroke patients. The project was implemented at an outpatient neuroscience clinic in Greater Houston.

BACKGROUND

Low medication adherence and poor attendance at the first neurology follow-up appointment among post-stroke patients contribute to increased morbidity and higher risk of recurrent stroke. Despite receiving discharge instructions, many patients do not consistently take their prescribed medications or attend their initial neurology visit.

METHODOLOGY

Guided by the Plan-Do-Study-Act (PDSA) cycle, this project engaged a medical assistant to call recently discharged stroke patients …

Considerations For Widespread Implementation Of Blood-Based Biomarkers Of Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali

Brain and Mind Institute

Diagnosing Alzheimer's disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimer's Disease BBM Workgroup convened to address these challenges …

Recommendations For Clinical Implementation Of Blood-Based Biomarkers For Alzheimer's Disease, Michelle Mielke, Matthew Anderson, Wesson Ashford, Andreas Jeromin, Pei-Jung Lin, Allyson Rosen, Jamie Tyrone, Lawren Vandevrede, Deanna Willis, Zul Merali, Chinedu Momoh

Brain and Mind Institute

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational …

Cerebrovascular Disease Is Associated With Alzheimer's Plasma Biomarker Concentrations In Adults With Down Syndrome, Andreas Engvig, Karl Trygve Kalleberg, Lars T. Westlye, Esten Høyland Leonardsen, Alzheimer’S Disease Neuroimaging Initiative Consortium

Neurology Faculty Publications

DNA methylation age (MA), brain age (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship and combined potential for prediction of cognitive impairment and future dementia risk using the ADNI database. Of several MA algorithms, DunedinPACE and GrimAge2, associated with memory, were combined in a composite MA alongside BA and a data-driven FI in predictive analyses. Pairwise correlations between age- and sex-adjusted measures for MA (aMA), aBA, and aFI were low. FI outperformed BA and MA in all diagnostic tasks. A model including age, sex, and aFI achieved an area under the …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Simultaneous Ipsilateral Hip And Knee Dislocation: Management And Outcome – A Case Report, Christian G Falgons, Stephen J Warner

Faculty, Staff and Student Publications

Case: This clinical case report presents a 40-year-old male who sustained an ipsilateral hip and knee dislocation with ipsilateral femoral head fracture and incomplete femoral neck fracture following a motorcycle collision.

Conclusion: This report describes acute and later definitive orthopedic care and management, with focus on urgent interventions and timing of immediate treatments. Given the presented patient's favorable clinical outcomes, return to baseline activities, and absence of significant sequelae following injury, the considerations from the acute management and surgical planning of this patient's injuries can be used as a reference for treating the rare injury of ipsilateral knee and hip …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

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

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high …