Neurology Commons^™

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …

Repurposing Ms Immunotherapies For Cidp And Other Autoimmune Neuropathies: Unfulfilled Promise Or Efficient Strategy?, Felix Kohle, Marinos Dalakas, Helmar C Lehmann

Department of Neurology Faculty Papers

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Regional Fa Values And Loss Of Consciousness In Mild Traumatic Brain Injury, Alexander Asturias, Thomas Knoblauch, Alan Rodriguez, Cheryl Vanier, Caroline Le Tohic, Brandon Barrett, Michael Eisenberg, Rachelle Gibbert, Lennon Zimmerman, Shaunaq Parikh, Anh Nguyen, Sherwin Azad, Leo Germin, Enrico Fazzini, Travis Snyder

Far West Division GME Research Day 2023

No abstract provided.

A Case Of Thrombolytic Associated Ich In The Setting Of Infective Endocarditis, Priscilla Yan, Lama Al-Khoury

Far West Division GME Research Day 2023

No abstract provided.

Cardiac Tamponade In The Setting Of Severe Sepsis And Adrenal Insufficiency, Ayesha Choudhry, Matthew Cardeiro, Angelina Hong, Adekunle Bamgboye

East Florida Division GME Research Day 2023

Introduction: Pericardial effusions can have various etiologies, including infectious, autoimmune, drug induced, endocrinologic, among others. Cardiac tamponade occurs when large effusions compress the heart and can lead to obstructive shock.

Case Description: A 48-year-old female with a history of hypothyroidism and pituitary adenoma resection presented with subjective fevers and generalized weakness for the past 5 days. She was lethargic with muffled heart sounds on exam. Vitals showed a heart rate 95 beats per minute, blood pressure 63/51, respiratory rate 18 breaths per minute, with normal temperature. Labs on admission were significant for white blood cell count of 11,500/L, hemoglobin 10.8 …

Ticagrelor Plus Aspirin Vs Clopidogrel Plus Aspirin In Mild Non-Cardioembolic Ischemic Stroke: A Protocol Of A Randomized, Controlled, Active Comparator Arm, Outcome Assessor Blind, Feasibility Study, Athena Sharifi-Razavi, Amir Moghadam Ahmadi, Nasim Tabrizi, Razieh Daz

Farber Institute for Neuroscience Staff Papers and Presentations

Background & Objectives: The risk of recurrence after a transient ischemic attack (TIA) or minor stroke is high especially within three months after first event. The aim of study is assessing the efficacy of ticagrelor plus aspirin in reduction of mild non-cardioembolic ischemic stroke or high risk TIA recurrence during first 3 months.

Methods: This is a randomized, controlled, active comparator arm, outcome assessor blind, parallel group, feasibility study design on 90 patients with diagnosis of non-cardioembolic minor ischemic stroke or high risk TIA admitted in Bou-Ali Sina Hospital, Sari, Iran. After meeting all inclusion and exclusion criteria, patients will …

Evaluating Digital Cognitive Biomarkers As A Noninvasive Diagnostic Tool For Alzheimer's Disease: Correlations With Classic Csf Biomarkers, Kasey Corripio

Honors Undergraduate Theses

Alzheimer's Disease (AD) is a neurodegenerative disorder affecting over 35 million people. Early diagnosis and intervention are crucial for improving outcomes. Digital Cognitive Biomarkers (DCBs) offer a promising approach for early detection and disease management, quantifying cognitive processes of encoding and retrieval through a hierarchical Bayesian cognitive processing model using wordlist memory tests. We hypothesize that DCBs will correlate with classic AD cerebrospinal fluid (CSF) biomarkers (Aβ42, T-tau, p-tau) in patients with varying cognitive decline levels compared to healthy elderly controls. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) data and paired Pearson correlation coefficient analysis, our results support the hypothesis, indicating …

Wernicke Encephalopathy: Interplay Between Magnesium And Thiamine, Richard Allen Gorman Ii, Mark Stine, Rafael Vaello, Patrick J. Stocker

West Florida Division GME Research Day 2023

No abstract provided.

Risk Factors For Depression Progression In Parkinson's Disease: A Retrospective Cohort Study, David Kosoy, James Cassuto, Gregory Kurgansky

East Florida Division GME Research Day 2023

Introduction: Depression is a common non-motor symptom in Parkinson's disease (PD) with a significant impact on quality of life and overall prognosis. Despite the availability of effective treatments, many PD patients with depression do not receive timely diagnosis and appropriate intervention. This study aimed to identify risk factors for depression progression in PD to inform clinical practice and future research.

Methods: We conducted a retrospective cohort study of PD patients using registry data from the Parkinson's Progression Markers Initiative (PPMI) dataset. The primary outcome was depression progression, defined as a 2-point or greater increase in the MDS-UPRDS depression score within …

Anti-Nmda Encephalitis In A Patient With Active Covid-19 Infection, Ali Abu-Alya, Janita Sidhu, Hamza Hansoti, Tyler Voss-Hamrick, Venkatachalam Veerappan, Ruhin Sidhu

Far West Division GME Research Day 2023

No abstract provided.

Microvascular Compression Causing Strokes From Subdural Hematoma Treated By Middle Meningeal Artery Embolization, Roy S. Escobar, Ali Abu-Alya, Vishnu Halthore, Julia Collins, Tanvir Khosla, Hamza Hansoti, Janite Sidhu, Venkatachalam Veerappan, Cyndi Tran

Far West Division GME Research Day 2023

No abstract provided.

Case Based Review On Headaches And Cerebral Venous Thromboembolism Post Covid-19 Infection, Aishwarya Raich, Tanvir Khosla, Vishnu Halthore, Ali Abu-Alya, Venkatachalam Veerappan

Far West Division GME Research Day 2023

No abstract provided.

Sudden Onset Ams, Focal Weakness, Fever And Aphasia Due To Intracranial Subdural Empyema In Left Temporo-Parietal Lobe, Lily Hyunjung Lim, Menachem M. Nagar, Pallavi Aneja

East Florida Division GME Research Day 2023

Intracranial subdural empyema (ISE) is a rare infection of brain, which occurs when pus is collectively located in the space between dura and arachnoid matter. In the past, its mortality was nearly 100%, if it was not treated appropriately within 24-48 hours. Thanks to improvement of diagnostic modalities and treatment, its mortality has dramatically decreased. Though, it can still cause a devastating consequence if it is not managed in a timely manner. The common etiology of ISE is different depending on the age group. In younger patients, it occurs frequently as a complication of infection in neighboring structures like sinusitis …

Evaluating The Impact Of Using A Wound-Specific Oral Nutritional Supplement To Support Wound Healing In A Rehabilitation Setting, Rya K Clark, Argyrios Stampas, Kirk W Kerr, Jeffrey L Nelson, Suela Sulo, Luis Leon-Novelo, Esther Ngan, Dehuti Pandya

Faculty, Staff and Student Publications

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein-energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non-healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound-specific oral nutritional supplementation (WS-ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard …

A Umls-Based Investigation Of Laterality In Biomedical Terminologies, Rashmie Abeysinghe, Xubing Hao, Licong Cui, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Laterality is an important anatomic directional property indicating the sidedness of body structures, diseases, and procedures. Errors in laterality could have catastrophic consequences in patient care. In this paper, we investigate how different biomedical terminologies organize terms indicating laterality. We leverage the Unified Medical Language System (UMLS) to identify lateral terms in different terminologies. For each lateral term, we attempt to obtain other matched lateral terms and further analyze how they are interrelated. Our results indicated that only 1.68% of the matched lateral term-pairs are hierarchically related. It was also seen that 44.24% of matched-pairs were siblings. We found that …

Extracting Temporal Expressions Of First Seizure Onset From Epilepsy Patient Discharge Summaries, Shiqiang Tao, Rashmie Abeysinghe, Blanca Talavera De La Esperanza, Samden Lhatoo, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Early onset of seizure is a potential risk factor for Sudden Unexpected Death in Epilepsy (SUDEP). However, the first seizure onset information is often documented as clinical narratives in epilepsy monitoring unit (EMU) discharge summaries. Manually extracting first seizure onset time from discharge summaries is time consuming and labor-intensive. In this work, we developed a rule-based natural language processing pipeline for automatically extracting the temporal information of patients’ first seizure onset from EMU discharge summaries. We use the Epilepsy and Seizure Ontology (EpSO) as the core knowledge resource and construct 4 extraction rules based on 300 randomly selected EMU discharge …

Lack Of Better Functional Outcome In Young Border Hispanic Patients With Acute Ischemic Stroke After Endovascular Thrombectomy Compared To Older Patients: A Retrospective Chart Review, Saisree Ravi, Sohum Desai, Sherief Ghozy, Wondwossen Tekle, Ameer E. Hassan

MEDI 9331 Scholarly Activities Clinical Years

Shortened Abstract:

Previous data indicates that young acute ischemic stroke patients have better prognosis after endovascular thrombectomy, while Hispanic patients are associated with poorer outcomes. Our goal is to study the interaction between age and Hispanic status to assess functional outcomes after endovascular thrombectomy in young versus older patients in a predominantly Hispanic population with a high prevalence of diabetes mellitus and obesity.

Our Hispanic population demonstrates no differences in sICH, mortality, and functional independence between young and older acute ischemic stroke patients after endovascular thrombectomy.

Examining A Blood Biomarker Approach To Blood-Brain Barrier Disruption, Samantha Ford

Theses and Dissertations--Medical Sciences

Blood-brain barrier disruption has been identified to associate with the pathogenesis several neurological diseases such as dementia [1, 2], multiple sclerosis[3, 4], acute or chronic cerebral ischemia[5], brain trauma[5], meningitis[5], encephalitis[5], stroke[6], and seizures[7]. Being able to effectively identify blood-brain barrier disruption is limited in methodology. The current standard is using a cerebrospinal fluid (CSF) albumin to serum albumin index, which requires the use of a lumbar puncture. A novel method of identifying blood-brain barrier disruption utilizing blood biomarkers is proposed in this study. Participants in this study had previously collected blood and CSF samples, which were analyzed to compare …

Lipids And Lipoproteins May Play A Role In The Neuropathology Of Alzheimer’S Disease, Omer Akyol, Sumeyya Akyol, Mei-Chuan Chou, Shioulan Chen, Ching-Kuan Liu, Salih Selek, Jair C Soares, Chu-Huang Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the …

Parental Instincts: The Neurological And Biological Factors Associated With Parenthood, Jared Reeder

Undergraduate Honors Theses

The following project involves a systematic review of the scientific literature on neural and biological changes of mothers and fathers in parenthood. Until very recently, little scientific research was devoted to studying how bearing children affects a man or woman’s long-term biology. Over the last twenty years, studies of neuroplastic changes in new mothers show specific neural mechanisms responsible for altering the behaviors of mothers during and after pregnancy. These changes in neuroplasticity alter behavior in such a way that led to mothers requiring less sleep and being more prone to hearing the cries of their children. In addition to …

A Story Of Hope: How A Community Project Is Transforming The Lives Of Filipino Children With Intellectual And Developmental Disabilities, Lance Vincent C. Sese, Ma Celina L. Guillermo

Ateneo School of Medicine and Public Health Publications

The issue of social inequality became more prevalent during the pandemic and with it, the call for preferential option toward the vulnerable. 1 Not only do we protect them from sickness and death, but we are also called to improve their quality of life. Thus, it is imperative that in this call for inclusivity, we address the gap, one group at a time—for example, children with special needs. The project discussed in this perspective article exemplifies the importance of collaboration in bridging the gap to create a more holistic environment for Filipino children with special needs. This article then serves …

Combined 3d Bioprinting And Tissue-Specific Ecm System Reveals The Influence Of Brain Matrix On Stem Cell Differentiation, Martina Zamponi, Peter A. Mollica, Yara Khodour, Julie S. Bjerring, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures …

Prospective Investigation Of Insomnia Symptoms And Sleep Duration As Risk Factors For Stroke Incidence And All-Cause Mortality In U.S Adult, Wendemi Sawadogo

Theses and Dissertations

Background and Objectives: Stroke is the second leading cause of death in the world. In the United States, on average, someone has a stroke every 40 seconds and someone dies as a result of stroke every 3.5 minutes. Identifying modifiable risk factors of stroke is therefore a public health priority. The purpose of this study was to investigate the extent to which insomnia symptoms and sleep duration contribute to stroke incidence, all-cause mortality, and explore potential causal pathways.

Methods: The Health and Retirement Study (HRS) and the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were …

Serum Neurofilament Light-Chain Levels And Long-Term Treatment Outcomes In Relapsing-Remitting Multiple Sclerosis Patients: A Post Hoc Analysis Of The Randomized Combirx Trial, Gary Cutter, Richard A Rudick, Carl De Moor, Carol M Singh, Elizabeth Fisher, Thijs Koster, Fred D Lublin, Jerry S Wolinsky, Henry Mcfarland, Steven Jacobson, Maria L Naylor

Faculty, Staff and Student Publications

BACKGROUND: CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies.

OBJECTIVE: This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse.

METHODS: RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. …

Exploring The Reduction Of Ipap Below Epap In The Therapy Of Obstructive Sleep Apnea, William Noah, Sue Lynn Myhre

TriStar Division Research Day 2023

No abstract provided.

Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Srihari V Chari, Eric R Cui, Haylie E Fehl, Antonio R Fernandez, Jane H Brice, Mehul D Patel

Faculty, Staff and Student Publications

OBJECTIVE: Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.

METHODS: This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based …