Neurosurgery Commons^™

Autologous Peripheral Nerve Tissue Grafts Implanted Into The Nucleus Basalis Of Meynert And Substantia Nigra At The Time Of Bilateral Deep Brain Stimulation In Parkinson Disease: A Report Of 2 Cases, Samuel R. Daly, Jorge E. Quintero, Lisa M. Koehl, Elizabeth Roslyn Wallace, Zain Guduru, Julie A. Gurwell, Tripp Hines, Jaimie Hixson, Saad Hulou, John T. Slevin, Frederick A. Schmitt, Greg A. Gerhardt, Craig G. Van Horne

Neurosurgery Faculty Publications

Background and Objectives: Cholinergic degeneration in the nucleus basalis of Meynert (NBM) is implicated in the cognitive impairment seen in Parkinson disease (PD) and is being examined as a potential therapeutic target. We have previously shown the safety of delivering investigational autologous cell-based therapy, ie, peripheral nerve tissue (PNT), to the substantia nigra (SN) at the time of deep brain stimulation (DBS) surgery in PD (DBS-Plus). In this study, we assessed the safety and feasibility of simultaneously delivering that PNT to both the NBM and SN at the time of DBS.

Methods: Two patients with idiopathic PD and mild cognitive …

Association Between Perioperative Patient-Reported Outcomes And Upper Extremity Functional Performance In Degenerative Cervical Myelopathy, Harshit Arora, Hassan Darabi, Vishwajeet Singh, Aysha Alsahlawi, Jared T. Wilcox, Francis Farhadi

Neurosurgery Faculty Publications

Background: Degenerative cervical myelopathy (DCM) is caused by chronic compression of the cervical spinal cord. Individuals usually present with a combination of upper extremity dysfunction, imbalance, and bladder dysfunction, which impact overall quality of life. Various questionnaires like mJOA, Nurick, NDI, and DCM-72 have been used for disease stratification. Our study aims to evaluate the clinical correlation between self-reported measures and objective upper extremity assessments and to derive the minimal clinically important difference (MCID) for individuals with DCM.

Methods: A prospective two-center study of consecutive patients diagnosed with DCM was undertaken. A comprehensive assessment of upper extremity functioning including dexterity, …

Converting “Nonlesional” Imaging Occult Epilepsy Into A Focal Lesional Entity Using Advanced Imaging Techniques: Illustrative Case, Muhammad Usman Khalid, Flavius D. Raslau, Valentinos Zachariou, David Powell, Zachary Winder, Ryan Cloyd, Sarah Helen Thomas, John Kuipers, Rachel Ward Mitchell, Riham H. El Khouli, Timothy J. Ainger, Sally Mathias, Farhan A. Mirza

Neurosurgery Faculty Publications

BACKGROUND To achieve the best possible outcome in surgical refractory epilepsy, the seizure onset zone must be accurately identified prior to treatment.

OBSERVATIONS A 38-year-old man presented with tonic-clonic and focal seizures 2–3 times per month, refractory to antiseizure medications. Scalp EEG, MRI, PET, ictal SPECT, magnetoencephalography, and stereo-EEG (SEEG) did not provide conclusive seizure onset zone localization. Subsequently, the patient was included in the authors’ ongoing postictal arterial spin labeling (ASL) study and additional postprocessing was performed with a morphometric analysis program (MAP) and texture analysis. Using these results, the authors reexamined the original structural MR images, with attention …

Efficacy Of Deferoxamine Mesylate In Serum And Serum-Free Media: Adult Ventral Root Schwann Cell Survival Following Hydrogen Peroxide-Induced Cell Death, Yee Hang Ethan Ma, Abhinay R. Putta, Cyrus H. H. Chan, Stephen R. Vidman, Paula V. Monje, Giles W. Plant

Neurosurgery Faculty Publications

Schwann cell (SC) transplantation shows promise in treating spinal cord injury as a pro-regenerative agent to allow host endogenous neurons to bridge over the lesion. However, SC transplants face significant oxidative stress facilitated by ROS in the lesion, leading to poor survival. deferoxamine mesylate (DFO) is a neuroprotective agent shown to reduce H₂O₂-induced cell death in serum-containing conditions. Here we show that DFO is not necessary to induce neuroprotection under serum-free conditions by cell survival quantification and phenotypic analysis via immunohistochemistry, Hif1α and collagen IV quantification via whole cell corrected total cell fluorescence, and cell death …

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 …

Assessment Of Cerebrospinal Fluid And Blood-Based Biomarkers In Degenerative Cervical Myelopathy: Systematic Review And Meta-Analysis, Harshit Arora, Hassan Darabi, Cassandra C. Wolsh, Kelsey N. Karnik, John C. Gensel, Francis Farhadi

Neurosurgery Faculty Publications

Study Design: Systematic Review and Meta-Analysis.

Objectives: Degenerative cervical myelopathy (DCM), the leading cause of spinal cord injury globally, may clinically manifest with hand numbness and tingling, loss of hand dexterity and impaired balance and gait. Biomarkers have been identified as disease indicators with recent studies exploring the role of structural and inflammatory biomarkers in diagnostic and treatment outcome prediction. The review aims to identify relevant cerebrospinal fluid (CSF) and blood-based biomarkers associated with DCM diagnosis and prognostication.

Methods: The systematic review was conducted as per PRISMA guidelines. A comprehensive search strategy was devised to identify articles evaluating biomarkers in …

Frailty Indices In Patients Undergoing Functional Neurosurgical Procedures: A Systematic Review, Carmelo Venero Jr., Joanna M. Roy, Nirbha Ghurye, Akshay Warrier, Muhammad Usman Khalid, Niels Pacheco-Barrios, Farhan A. Mirza, Christian A. Bowers

Neurosurgery Faculty Publications

Introduction: Functional neurosurgery covers a wide array of neurological disorders with an equally vast array of treatment modalities, including neuromodulation, decompressive, and ablative therapies for disparate pathologies such as pain, neuromodulation, disconnection, and refractory epilepsy. One of the most common functional treatments is deep brain stimulation for movement disorders and select psychiatric diseases. Functional neurosurgery treats patients with reduced quality of life from pathological neuronal pathways. Optimal patient selection by preoperatively identifying high-risk patients is critical for avoiding as many operative complications as possible, in addition to managing complications better once they occur. Frailty indices have demonstrated superior discrimination in …

Short Chain Fatty Acids Taken At Time Of Thrombectomy In Acute Ischemic Stroke Patients Are Independent Of Stroke Severity But Associated With Inflammatory Markers And Worse Symptoms At Discharge, Nicholas Henry, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Andrew J. Morris, Jianzhong Chen, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks.

Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem …

Can Activated Titanium Interbody Cages Accelerate Or Enhance Spinal Fusion? A Review Of The Literature And A Design For Clinical Trials, Nathaniel Toop, Connor Gifford, Rouzbeh Motiei-Langroudi, Arghavan Farzadi, Daniel Boulter, Reza Forghani, H. Francis Farhadi

Neurosurgery Faculty Publications

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale …

Cessation And Resumption Of Elective Neurointerventional Procedures During The Coronavirus Disease 2019 Pandemic And Future Pandemics, Tim W. Malisch, Sameer A. Ansari, Gary R. Duckwiler, Kyle M. Fargen, Steven W. Hetts, Franklin A. Marden, Athos Patsalides, Clemens M. Schirmer, Allan Brook, Justin F. Fraser

Neurosurgery Faculty Publications

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on …

Intra-Arterial Combination Therapy For Experimental Acute Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Amanda A. Gorman, Gregory J. Bix, Justin F. Fraser

Neurosurgery Faculty Publications

Acute ischemic stroke continues to devastate millions of individuals worldwide. Current treatments work to restore blood flow but not rescue affected tissue. Our goal was to develop a combination of neuroprotective agents administered intra-arterially following recanalization to target ischemic tissue. Using C57Bl/6J male mice, we performed tandem transient ipsilateral middle cerebral/common carotid artery occlusion, followed by immediate intra-arterial pharmacotherapy administration through a standardized protocol. Two pharmacotherapy agents, verapamil and lubeluzole, were selected based on their potential to modulate different aspects of the ischemic cascade; verapamil, a calcium channel blocker, works in an acute fashion blocking L-type calcium channels, whereas lubeluzole, …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Smoking-Induced Sex Differences In Clinical Outcomes In Patients Undergoing Mechanical Thrombectomy For Stroke, Jacqueline A. Frank, Kara Jo Swafford, Jill M. Roberts, Amanda L. Trout, Ann M. Stowe, Douglas E. Lukins, Stephen Grupke, Keith R. Pennypacker, Justin F. Fraser

Neurology Faculty Publications

OBJECTIVE: Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke.

METHODS: Subjects (N = 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Gait And Balance Changes With Investigational Peripheral Nerve Cell Therapy During Deep Brain Stimulation In People With Parkinson’S Disease, Geetanjali Gera, Zain Guduru, Tritia R. Yamasaki, Julie A. Gurwell, Monica Chau, Anna Krotinger, Frederick A. Schmitt, John T. Slevin, Greg A. Gerhardt, Craig G. Van Horne, Jorge E. Quintero

Physical Therapy Faculty Publications

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the …

Method Of Intra-Arterial Drug Administration In A Rat: Sex Based Optimization Of Infusion Rate, Sarah J. Messmer, Justin F. Fraser, Keith R. Pennypacker, Jill M. Roberts

Center for Advanced Translational Stroke Science Faculty Publications

BACKGROUND: Endovascular thrombectomy is the process of removing a blood clot and re-establishing blood flow in patients with emergent large vessel occlusion. The technique provides an opportunity to deliver therapeutics directly to the site of injury. The intra-arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. Here, we adapted the IA method for use in rats, by investigating various flow rates to optimize the IA injection through the internal carotid artery (ICA).

METHODS: Male and female Sprague-Dawley rats (∼4 months of age) were subjected to placement …

Machine Intelligence Identifies Soluble Tnfa As A Therapeutic Target For Spinal Cord Injury, J. R. Huie, A. R. Ferguson, N. Kyritsis, J. Z. Pan, K.-A. Irvine, J. L. Nielson, P. G. Schupp, M. C. Oldham, John C. Gensel, A. Lin, M. R. Segal, R. R. Ratan, J. C. Bresnahan, M. S. Beattie

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Commentary: Use Of Bactrac Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke, Gabriella-Salome K. Armstrong, Jacqueline A. Frank, Christopher J. Mclouth, Ann M. Stowe, Jill M. Roberts, Amanda L. Trout, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle's loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI> 25) and its relationship to stroke in patients.

Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent …

Treatment Of Headache In Aneurysmal Subarachnoid Hemorrhage: Multimodal Approach, Garrett B. Hile, Aaron M. Cook

Pharmacy Practice and Science Faculty Publications

Sudden severe headache is a cardinal symptom and the most common complaint amongst patients presenting with aneurysmal subarachnoid hemorrhage. The multifactorial etiology of these headaches makes pharmacotherapy problematic. Current aneurysmal subarachnoid hemorrhage guidelines have limited or no recommendations for headache treatment. Our institution utilizes a multimodal pharmacotherapy protocol in the management of aneurysmal subarachnoid hemorrhage headache. The purpose of this study was to evaluate the efficacy of the current aneurysmal subarachnoid hemorrhage headache treatment approach at our institution. This was a retrospective cohort study of patients presenting with aneurysmal subarachnoid hemorrhage. A multimodal aneurysmal subarachnoid hemorrhage headache treatment protocol was …

The Relationship Between Sport-Related Concussion And Sensation-Seeking, Spencer W. Liebel, Kathryn L. Van Pelt, Gian-Gabriel P. Garcia, Lauren L. Czerniak, Michael A. Mccrea, Thomas W. Mcallister, Steven P. Broglio, Care Consortium Investigators

Sanders-Brown Center on Aging Faculty Publications

Sensation-seeking, or the need for novel and exciting experiences, is thought to play a role in sport-related concussion (SRC), yet much remains unknown regarding these relationships and, more importantly, how sensation-seeking influences SRC risk. The current study assessed sensation-seeking, sport contact level, and SRC history and incidence in a large sample of NCAA collegiate athletes. Data included a full study sample of 22,374 baseline evaluations and a sub-sample of 2037 incident SRC. Independent samples t-test, analysis of covariance, and hierarchical logistic regression were constructed to address study hypotheses. Results showed that (1) among participants without SRC, sensation-seeking scores were …

Current Role Of Laser Interstitial Thermal Therapy In The Treatment Of Intracranial Tumors, Farhan A. Mirza, Rida Mitha, Muhammad Shahzad Shamim

Neurosurgery Faculty Publications

Laser interstitial thermal therapy (LITT) is gaining popularity in the treatment of both primary and secondary intracranial tumors. The goal of LITT is to deliver thermal energy in a predictable, controlled, and minimally invasive fashion. It can be particularly valuable in patients with recurrent tumors who, due to previous radiation or surgery, may have a potentially higher risk of wound breakdown or infection with repeat craniotomy. Deep-seated lesions that are often inaccessible through open approaches (thalamus, hypothalamus, mesial basal temporal lobe, brainstem) may also be suitable targets. The experience and data published thus far on this modality is limited but …

Biomarker Application For Precision Medicine In Stroke, Alexis N. Simpkins, Miroslaw Janowski, Helieh S. Oz, Jill Roberts, Gregory Bix, Sylvain Doré, Ann M. Stowe

Neurosurgery Faculty Publications

Stroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies …

Expression Of Cytokines And Chemokines As Predictors Of Stroke Outcomes In Acute Ischemic Stroke, Sarah R. Martha, Qiang Cheng, Justin F. Fraser, Liyu Gong, Lisa A. Collier, Stephanie M. Davis, Doug Lukins, Abdulnasser Alhajeri, Stephen Grupke, Keith R. Pennypacker

Institute for Biomedical Informatics Faculty Publications

Introduction: Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and …

Early Acid/Base And Electrolyte Changes In Permanent Middle Cerebral Artery Occlusion: Aged Male And Female Rats, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Sarah J. Goodwin, David Powell, Doug Lukins, Justin F. Fraser, Keith R. Pennypacker

Neurosurgery Faculty Publications

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model.

METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways, Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric M. Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Neuroscience Faculty Publications

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

The Effect Of Haptoglobin Phenotypes On Markers Of Neuroinflammation In Patients With Aneurysmal Subarachnoid Hemorrhage, Kevin Hatton

Theses and Dissertations--Clinical and Translational Science

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of hemorrhagic stroke resulting from the spontaneous rupture of an intracranial aneurysm and release of oxygenated blood into the subarachnoid space. In the United States alone, aSAH occurs in approximately 30,000 patients each year and occurs, primarily, in otherwise healthy adults, frequently without warning. Sadly, approximately 40% of patients with aSAH will die in the first 30 days. Of those who survive, only about 75% will be able to live semi-independently again and only about 60% will be able to return to work.

Delayed brain injuries (DBI), which may affect up to …

Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …