Neurology Commons^™

Safety, Pharmacodynamics, And Potential Benefit Of Omaveloxolone In Friedreich Ataxia, David R. Lynch, Jennifer Farmer, Lauren Hauser, Ian A. Blair, Qing Qing Wang, Clementina Mesaros, Nathaniel Snyder, Sylvia Boesch, Melanie Chin, Martin B. Delatycki, Paola Giunti, Angela Goldsberry, Chad Hoyle, Michael G. Mcbride, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S. H. Subramony, George R. Wilmot, Theresa A. Zesiewicz, Colin Meyer

Neurology Faculty Publications

Objective Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435).

Methods Sixty-nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5–300 mg/day.

Results Omaveloxolone was well tolerated, and adverse …

Central Pain Mimicking Trigeminal Neuralgia As A Result Of Lateral Medullary Ischemic Stroke, Abinayaa Ravichandran, Kareem S. Elsayed, Hussam A. Yacoub

Neurology Faculty Publications

Background. Central pain mimicking trigeminal neuralgia (TN) as a result of lateral medullary infarction or Wallenberg syndrome has been rarely reported. Case Report. We discuss a patient who presented with a lateral medullary infarct and shortly after developed facial pain mimicking TN. We also elaborate on the anatomical pathway of the trigeminal nerve explaining facial pain as a result of a lateral medullary lesion. Discussion. Clinicians should be aware of this typical complication of lateral medullary infarct in order to attain proper management and work-up.

Protocol For Arest: Apixaban For Early Prevention Of Recurrent Embolic Stroke And Hemorrhagic Transformation—A Randomized Controlled Trial Of Early Anticoagulation After Acute Ischemic Stroke In Atrial Fibrillation, David Z. Rose, John N. Meriwether, Michael G. Fradley, Swetha Renati, Ryan C. Martin, Thomas Kasprowicz, Aarti Patel, Maxim Mokin, Ryan Murtagh, Kevin Kip, Andrea C. Bozeman, Tara Mctigue, Nicholas Hilker, Bonnie Kirby, Natasha Wick, Nhi Tran, W. Scott Burgin, Arthur J. Labovitz

Neurology Faculty Publications

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.

Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and …

Addressing Stroke Patient And Family Reasons For Not Calling 911, Maygret Ramirez, Rodney Bedgio, Virginia Ramos, Ivis Gonzalez, Yaima Miro Gonzalez, Amy Starosciak, Daniel D'Amour, Jayme Strauss, Felipe De Los Rios La Rosa

All Publications

No abstract provided.

The Effects Of Matrix Metalloproteinase-9 On Cx3cl1 Shedding And Axon Retraction, Lauren A. Dobrie

Honors Undergraduate Theses

Spinal cord injury (SCI) often leads to irreversible damage, and permanent paralysis inferior to the injury is common (Leibinger et al., 2013). Injury to the spinal cord occurs in two phases. In the first phase, components of the spinal cord are subject to mechanical trauma causing direct damage. In the second phase, damage spreads from the area of injury through molecular processes. Several studies have linked M1 "pro-inflammatory" macrophages to exacerbation of damage by inducing dieback of dystrophic axons, but not healthy axons, through direct cellular contact. Several studies have identified the presence of macrophage subtypes at specific time. A …

Role Of Amyloid Precursor Protein In Neuroregeneration On An In Vitro Model In Alzheimer's Patient-Specific Cell Lines, Lina S. Bedoya Martinez

Honors Undergraduate Theses

Alzheimer's disease (AD) leads to neurodegeneration resulting in cognitive and physical impairments. AD is denoted by accumulation of intracellular neurofibrillary tangles, known as tau, and extracellular plaques of the amyloid beta protein (Aβ). Aβ results from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and gamma-secretases in the amyloidogenic pathway. Although, Aβ has been widely studied for neurodegeneration, the role of APP in both, the healthy and diseased conditions, has not yet been entirely understood. The function that APP has in neural stem cell (NSC) proliferation, differentiation, and migration during adult neurogenesis has been previously studied. Additionally, …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Human Papillomavirus And Human Cytomegalovirus Infection And Association With Prognosis In Patients With Primary Glioblastoma In Pakistan, Syed Adnan Ali, Yumna Mirza, Zubair Ahmad, Nida Zahid, Ather Enam

Department of Surgery

Objective: Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. Human cytomegalovirus (HCMV) has been studied for the past decade, and conflicting results have been reported with no conclusive role established yet. Human papillomavirus (HPV) is involved in the pathogenesis of many cancers and has a high prevalence in patients with cervical and oral cancer in Pakistan. The objective of our study was to identify the prevalence of HCMV and HPV in Pakistani patients with primary GBM.
Methods: In total, 112 primary GBM biopsies were analyzed. HCMV and HPV infection was investigated using nested and conventional polymerase chain …

Postoperative Intracranial Migration Of A C2 Odontoid Screw: A Case Report And Literature Review., Ankush Chandra, Seong-Jin Moon, Blake Walker, Emre Yilmaz, Marc Moisi, Robert Johnson

Articles, Abstracts, and Reports

Background: Intracranial migration of odontoid screws is a rare but serious complication of anterior odontoid screw fixation not often reported in literature by neurosurgeons. Here, we describe the second case in literature of intracranial migration of an odontoid screw.

Case Description: A 64-year-old neurologically intact patient with a type II odontoid fracture secondary to trauma underwent anterior odontoid screw fixation without any intraoperative complications. He tolerated the procedure well, and postoperative imaging demonstrated near anatomic correction of the fracture with satisfactory placement of the lag screw. Unfortunately, the patient was subsequently lost to follow up and he presented 7 months …

Primary Cardiac Sarcoma: A Rare, Aggressive Malignancy With A High Propensity For Brain Metastases., Brittany L Siontis, Lili Zhao, Monika Leja, Jonathan B Mchugh, Maryann M Shango, Laurence H Baker, Scott M Schuetze, Rashmi Chugh

Articles, Abstracts, and Reports

Introduction: Primary cardiac sarcoma (PCS) has a poor prognosis compared to other sarcomas due to late presentation, challenging resection, incidence of metastases, and limited efficacy of systemic therapies.

Methods: A medical record search engine was queried to identify patients diagnosed with PCS from 1992 to 2017 at the University of Michigan.

Results: Thirty-nine patients with PCS had a median age of 41 years (range 2-77). Common histologies were angiosarcoma (AS, 14), high-grade undifferentiated pleomorphic sarcoma (UPS, 10), and leiomyosarcoma (LMS, 5). Sites of origin were left atrium (18), right atrium (16), and pericardium (5). AS was the most common right-sided …

A Systems Thinking Approach For Eliciting Mental Models From Visual Boundary Objects In Hydropolitical Contexts: A Case Study From The Pilcomayo River Basin, Riveraine S. Walters, Erin S. Kenzie, Alexander E. Metzger, William Jesse Baltutis, Kakali B. Chakrabarti, Shana Lee Hirsch, Bethany Laursen

Systems Science Faculty Publications and Presentations

Transboundary collaborations related to international freshwater are critical for ensuring equitable, efficient, and sustainable shared access to our planet’s most fundamental resources. Visual artifacts, such as knowledge maps, functioning as boundary objects, are used in hydropolitical contexts to convey understandings and facilitate discussion across scales about challenges and opportunities from multiple perspectives. Such focal points for discussion are valuable in creating shared, socially negotiated priorities and integrating diverse and often disparate cultural perspectives that naturally exist in the context of international transboundary water resources. Visual boundary objects can also represent the collective mental models of the actor countries and transboundary …

Are There Mortality Risks For Patients With Epilepsy Who Use Cannabis Treatments As Monotherapy?, Devon M Kollmyer, Kyla E Wright, Nicole M Warner, Michael J Doherty

Articles, Abstracts, and Reports

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.

The Role Of Neck Musculature In Traumatic Brain Injuries In Older Adults: Implications From Sports Medicine, Tyler A. Wood, Steven Morrison, Jacob J. Sosnoff

Rehabilitation Sciences Faculty Publications

Traumatic brain injuries (TBIs) are common and serious injuries to older adults. The majority of TBIs in older adults are sustained when the head impacts the ground or other surface during a fall. While several non-modifiable risk factors have been identified for fall-related TBIs in older adults, there still remains a dearth of knowledge surrounding modifiable risk factors. Thus, this significant knowledge gap warrants an investigation into research across disciplines. The sports medicine literature has examined several modifiable risk factors to prevent a mild form of TBI known as concussion. While this research has identified several risk factors, one particular …

Randomized Trial Of Polychromatic Blue-Enriched Light For Circadian Phase Shifting, Melatonin Suppression, And Alerting Responses., J. P. Hanifin, S. W. Lockley, K. Cecil, K. West, M. Jablonski, B. Warfield, M. James, M. Ayers, B. Byrne, E. Gerner, C. Pineda, M. Rollag, G. C. Brainard

Department of Neurology Faculty Papers

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis., Sean J O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A S Reyes, Jon Gorky, Rajanikanth Vadigepalli, Elisabeth J Van Bockstaele, James S Schwaber

Articles, Abstracts, and Reports

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Altering Brain Dynamics With Transcranial Random Noise Stimulation, Onno Van Der Groen, Jason B. Mattingley, Nicole Wenderoth

Research outputs 2014 to 2021

Random noise can enhance the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. Here we used a computational model to predict the effect of noise on perceptual dominance durations. Subsequently we compared the model prediction to a series of experiments where we measured …

Characterizing Whole Brain Temporal Variation Of Functional Connectivity Via Zero And First Order Derivatives Of Sliding Window Correlations., Flor A Espinoza, Victor M Vergara, Eswar Damaraju, Kyle G Henke, Ashkan Faghiri, Jessica A Turner, Aysenil A Belger, Judith M Ford, Sarah C Mcewen, Daniel H Mathalon, Bryon A Mueller, Steven G Potkin, Adrian Preda, Jatin G Vaidya, Theo G M Van Erp, Vince D Calhoun

Articles, Abstracts, and Reports

Brain functional connectivity has been shown to change over time during resting state fMRI experiments. Close examination of temporal changes have revealed a small set of whole-brain connectivity patterns called dynamic states. Dynamic functional network connectivity (dFNC) studies have demonstrated that it is possible to replicate the dynamic states across several resting state experiments. However, estimation of states and their temporal dynamicity still suffers from noisy and imperfect estimations. In regular dFNC implementations, states are estimated by comparing connectivity patterns through the data without considering time, in other words only zero order changes are examined. In this work we propose …

Down Syndrome Associated Moyamoya May Worsen Epilepsy Control And Can Benefit From Surgical Revascularization., Sarah R Garson, Stephen J Monteith, Sheila D Smith, Bart P Keogh, Ryder P Gwinn, Michael J Doherty

Articles, Abstracts, and Reports

Objectives: To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya.

Materials and methods: Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls.

Results: Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life.

Conclusion: In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures.

Regeneration Enhances Metastasis: A Novel Role For Neurovascular Signaling In Promoting Melanoma Brain Metastasis., Roshini Prakash, Sivan Izraely, Nikita S Thareja, Rex H Lee, Maya Rappaport, Riki Kawaguchi, Orit Sagi-Assif, Shlomit Ben-Menachem, Tsipi Meshel, Michal Machnicki, Shuichi Ohe, Dave S B Hoon, Giovanni Coppola, Isaac P Witz, S Thomas Carmichael

Articles, Abstracts, and Reports

Neural repair after stroke involves initiation of a cellular proliferative program in the form of angiogenesis, neurogenesis, and molecular growth signals in the surrounding tissue elements. This cellular environment constitutes a niche in which regeneration of new blood vessels and new neurons leads to partial tissue repair after stroke. Cancer metastasis has similar proliferative cellular events in the brain and other organs. Do cancer and CNS tissue repair share similar cellular processes? In this study, we identify a novel role of the regenerative neurovascular niche induced by stroke in promoting brain melanoma metastasis through enhancing cellular interactions with surrounding niche …