Neurology Commons^™

An Empirical Pipeline For Personalized Diagnosis Of Lafora Disease Mutations, M. Kathryn Brewer, Maria Machio-Castello, Rosa Viana, Jeremiah L. Wayne, Andrea Kuchtová, Zoe R. Simmons, Sarah Sternbach, Sheng Li, Maria Adelaida García-Gimeno, Jose M. Serratosa, Pascual Sanz, Craig W. Vander Kooi, Matthew S. Gentry

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations in either EPM2A, encoding the glycogen phosphatase laforin, or EPM2B, encoding the E3 ligase malin, cause LD. Whole exome sequencing has revealed many EPM2A variants associated with late-onset or slower disease progression. We established an empirical pipeline for characterizing the functional consequences of laforin missense mutations in vitro using complementary biochemical approaches. Analysis of 26 mutations revealed distinct functional classes associated with different outcomes that were supported by clinical …

The Efficacy Of A Sumatriptan And Naproxen Combination Pill In A Patient With Chronic Migraines Who Discontinued Triptan Therapy In The Past Due To A Self-Reported Poor Response To Sumatriptan Monotherapy, Ethan M. Cohen

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Mathew NT, Landy S, Stark S, et al. Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life. Headache. 2009;49(7):971-982. https://doi.org/10.1111/j.1526-4610.2009.01458.x

for a patient with chronic migraines who had self-reported poor response to sumatriptan monotherapy.

Neuroimaging Referral For Reassurance In Evaluation Of Headache With Low-Risk Features, Omar E. Fernandez

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Howard L, Wessely S, Leese M, et al. Are investigations anxiolytic or anxiogenic? A randomised controlled trial of neuroimaging to provide reassurance in chronic daily headache. J Neurol Neurosurg Psychiatry. 2005;76(11):1558-1564. https://doi.org/10.1136/jnnp.2004.057851

for a patient with daily headache.

Awake Craniotomy For Resection Of Intracranial Meningioma: First Case Series From A Low- And Middle-Income Country, Saqib Kamran Bakhshi, Noyan Jawed, Faraz Shafiq, Ather Enam

Section of Neurosurgery

Introduction: Awake craniotomy (AC) has emerged as a better modality for resection of intra-axial brain tumors. The advantages are not just related to the preservation of neurological function, but also include early recovery, short hospital stay and possibly lower costs. However, data on AC for meningioma resection is deficient, likely because of concerns related to intra-operative pain and blood loss.
Methods: All patients who underwent AC, using awake through-out technique for resection of meningioma, during the last five years, were included in the study. Non-probability consecutive sampling technique was employed. Variables for demographics, and details of diagnosis and surgical procedure …

Neuropsychological Symptoms Related To The Covid-19 Pandemic Experienced By The General Population And Particularly By The Healthcare Personnel, Alina Zorina Stroe, Alexandru Floris Stuparu, Silviu Docu Axelerad, Daniel Docu Axelerad, Aurelia Moraru

Journal of Mind and Medical Sciences

Undoubtedly, the outbreak of COVID-19 still represents an overanxious event for both society and population. The fear of getting infected is ubiquitous in the time of the pandemic. The population presented worrying thoughts related to the fact that the health care system was not able to provide enough services during the COVID-19 pandemic. The number of the hospital beds and ventilators was insufficient in order to ensure enough care, considering the increased number of COVID-19 cases that were admitted to the hospitals. Furthermore, people were fearful about the possibility of the global economy becoming decimated. The fright and also the …

Chronic Long-Covid Syndrome: A Protracted Covid-19 Illness With Neurological Dysfunctions, Abdul Mannan Baig

Department of Biological & Biomedical Sciences

After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in …

Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson’S Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram

Department of Neurosurgery Faculty Papers

Background: Neuronal loss in Parkinson’s Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.

Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.

Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the …

Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson's Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram

Department of Neurosurgery Faculty Papers

Background: Neuronal loss in Parkinson's Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.

Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.

Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the …

Terrorism In Your Brain: The Battles Of Multiple Sclerosis (Ms), Paul W. Asper

Student Publications

This paper is a review of Multiple Sclerosis (MS) looking at the phenotypes, epidemiology, etiology, pathology, and immunology. Additionally, this paper examines the clinical presentations and criteria for diagnosis along with the treatment and management of symptoms.

Prognostic Implications Of Epidermal And Platelet-Derived Growth Factor Receptor Alterations In 2 Cohorts Of Idh, Iyad Alnahhas, Appaji Rayi, Maria Del Pilar Guillermo Prieto Eibl, Shirley Ong, Pierre Giglio, Vinay Puduvalli

Department of Neurology Faculty Papers

Background: Glioblastoma remains a deadly brain cancer with dismal prognosis. Genetic alterations, including IDH mutations, 1p19q co-deletion status and MGMT promoter methylation have been proven to be prognostic and predictive to response to treatment in gliomas. In this manuscript, we aimed to correlate other mutations and genetic alterations with various clinical endpoints in patients with IDH-wild-type (IDHwt) glioblastoma.

Methods: We compiled a comprehensive clinically annotated database of IDHwt GBM patients treated at the Ohio State University Wexner Medical Center for whom we had mutational data through a CLIA-certified genomic laboratory. We then added data that is publicly available from Memorial …

Diversity In Alzheimer's Disease Drug Trials: The Importance Of Eligibility Criteria, Sanne Franzen, Jade Emily Smith, Esther Van Den Berg, Monica Rivera Mindt, Rozemarijn L. Van Bruchem-Visser, Erin L. Abner, Lon S. Schneider, Niels D. Prins, Ganesh M. Babulal, Janne M. Papma

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: To generalize safety and efficacy findings, it is essential that diverse populations are well represented in Alzheimer's disease (AD) drug trials. In this review, we aimed to investigate participant diversity in disease-modifying AD trials over time, and the frequencies of participant eligibility criteria.

METHODS: A systematic review was performed using Medline, Embase, the Cochrane Library, and Clinicaltrials.gov, identifying 2247 records.

RESULTS: In the 101 included AD trials, participants were predominantly White (median percentage: 94.7%, interquartile range: 81.0-96.7%); and this percentage showed no significant increase or decrease over time (2001-2019). Eligibility criteria such as exclusion of persons with psychiatric illness …

Management Of Coincident Pituitary Macroadenoma And Cavernous Carotid Aneurysm: A Systematic Literature Review., Keenan J. Piper, Michael Karsy, Blair Barton, Mindy Rabinowitz, Marc R. Rosen, Gurston G. Nyquist, James J. Evans, Stavropoula Tjoumakaris, Christopher J. Farrell

Department of Neurosurgery Faculty Papers

Introduction

Pituitary adenomas are a common intracranial pathology with an incidence of 15 to 20% in the population while cerebral aneurysms are less common with a prevalence of 1:50 patients. The incidence of aneurysms in patients with pituitary adenoma has been estimated at 2.3 to 5.4% of patients; however, this remains unclear. Equally, the management of concomitant lesions lacks significant understanding.

Methods

A case report is presented of a concomitant cerebral aneurysm and pituitary adenoma managed by minimally invasive endovascular and endoscopic methods, respectively. A systematic review of the literature for terms "pituitary adenoma" and "aneurysm" yielded 494 studies that …

Prion Disease: A Challenging Diagnosis, Jeffrey F. Spindel, Anita M. Fletcher, William T. Smith, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Introduction: Human prion diseases are a group of rare encephalopathies resulting in rapidly progressive dementia and ultimately death. While there are no effective treatments for any form of prion disease, prompt and efficient diagnosis is essential to prevent the spread of the self-propagating protein, which may occur through aerosols, and avoid unnecessary or invasive testing. Diagnosis relies largely on physical examination, with many nonspecific findings, and laboratory testing, which has wide ranges of reported accuracy and high false positive rates with diseases such as Alzheimer’s dementia.

Methods: Patients who underwent testing for prion disease were retrospectively identified from the electronic …

Longitudinal Cognitive Performance Of Alzheimer's Disease Neuropathological Subtypes, Madeline Uretsky, Laura E. Gibbons, Shubhabrata Mukherjee, Emily H. Trittschuh, David W. Fardo, Patricia A. Boyle, C. Dirk Keene, Andrew J. Saykin, Paul K. Crane, Julie A. Schneider, Jesse Mez

Sanders-Brown Center on Aging Faculty Publications

Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments.

Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive …

Usability Of Abattoir-Acquired Pig Eyes For Refractive Excimer Laser Research, Marius Topka, Yao Zhang, Antonia Bock, Peter Riedel, Johannes Lörner, Alexander Hammer, Eva Maier, Friedrich Paulsen, Christian M Hammer

Faculty, Staff and Student Publications

The purpose of this study was to elucidate, under which conditions abattoir-acquired pig eyes are suitable for refractive excimer laser experiments. Porcine eyes from tunnel-scalded (n = 5) and tank-scalded (n = 10) pigs were compared to unscalded eyes (n = 5) and to eyes scalded in the laboratory (n = 5). The corneal epithelium was removed before an excimer laser was used to perform a - 8.0 D photoablation. Corneal thickness was measured by optical coherence topography before and after photoablation. The ablation depth was determined with a contour measuring station, the morphology of the ablated areas was characterized …

Prevalence Of Soccer Heading In Middle School American Youth Club Soccer Players, Pedro Gonzalez-Cabrera, Mohan Ganesan, Julie Jameson, Deanna M. Hughes

Physical Therapy Collection

The purpose of this study was to evaluate the prevalence of soccer heading during a season in a youth soccer club competitive team

Heading events were recorded real time using a recording datasheet for a single team and their opponent teams during the 2014 season of a youth soccer league. Position on the field at the time of the heading event was also documented.

Mean heading events were 35.5 events/match. A paired sample t-test showed no statistically significant difference between observed team and opponent teams. Mean standardized assessment of concussion (SAC) score for the observed soccer team was 24.9±2.6 (out …

Combined Therapy With Avastin, A Paf Receptor Antagonist And A Lipid Mediator Inhibited Glioblastoma Tumor Growth, Valerie A. Cruz Flores, Hemant Menghani, Pranab K. Mukherjee, Luis Marrero, Andre Obenaus, Quan Dang, Larissa Khoutorova, Madigan M. Reid, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Glioblastoma multiforme (GBM) is an aggressive, highly proliferative, invasive brain tumor with a poor prognosis and low survival rate. The current standard of care for GBM is chemotherapy combined with radiation following surgical intervention, altogether with limited efficacy, since survival averages 18 months. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the dysregulation of numerous signaling pathways. Recently emerging therapies to precisely modulate tumor angiogenesis, inflammation, and oxidative stress are gaining attention as potential options to combat GBM. Using a mouse model of GBM, this study aims to investigate Avastin (suppressor of vascular endothelial …

Dysfunctional Tissue Correlates Of Unrelated Naming Errors In Acute Left Hemisphere Stroke, Erin L. Meier, Shannon M. Sheppard, Emily B. Goldberg, Catherine R. Kelly, Alexandra Walker, Delaney M. Ubellacker, Emilia Vitti, Kristina Ruch, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalised with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within …

Leveraging High-Resolution 7-Tesla Mri To Derive Quantitative Metrics For The Trigeminal Nerve And Subnuclei Of Limbic Structures In Trigeminal Neuralgia, Judy Alper, Alan C. Seifert, Gaurav Verma, Kuang-Han Huang, Yael Jacob, Ameen Al Qadi, John W. Rutland, Sheetal Patel, Joshua Bederson, Raj K. Shrivastava, Bradley N. Delman, Priti Balchandani

Publications and Research

Background: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal …

Genetic Variation In Padi6-Padi4 On 1p36.13 Is Associated With Common Forms Of Human Generalized Epilepsy, Russell J. Buono, Jonathan P. Bradfield, Zhi Wei, Michael R. Sperling, Dennis J. Dlugos, Michael D. Privitera, Jacqueline A. French, Warren Lo, Patrick Cossette, Steven C. Schachter, Heather Basehore, Falk W. Lohoff, Struan F.A. Grant, Thomas N. Ferraro, Hakon Hakonarson

Department of Neurology Faculty Papers

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10⁻⁸) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated …