Neurology Commons^™

Linking Kindling To Increased Glutamate Release In The Dentate Gyrus Of The Hippocampus Through The Stxbp5/Tomosyn-1 Gene, Seth R. Batten, Elena A. Matveeva, Sidney W. Whiteheart, Thomas C. Vanaman, Greg A. Gerhardt, John T. Slevin

Psychology Faculty Publications

Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling.

Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1^−/− (Tom^−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA).

Results: Naïve Tom^−/− mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as …

Stress Increases Peripheral Axon Growth And Regeneration Through Glucocorticoid Receptor-Dependent Transcriptional Programs, Jessica K. Lerch, Jessica K. Alexander, Kathryn M. Madalena, Dario Motti, Tam Quach, Akhil Dhamija, Alicia Zha, John C. Gensel, Jeanette Webster Marketon, Vance P. Lemmon, John L. Bixby, Phillip G. Popovich

Physiology Faculty Publications

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult …

Burden Of Arrhythmias In Epilepsy Patients: A Nationwide Inpatient Analysis Of 1.4 Million Hospitalizations In The United States, Rupak Desai, Chintan Rupareliya, Upenkumar Patel, Syeda Naqvi, Smit Patel, Abhishek Lunagariya, Zabeen Mahuwala

Neurology Faculty Publications

Arrhythmias have been one of the common complications in epilepsy patients and have also been the reason for death. However, limited data exist about the burden and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating the burden and differences in outcomes of various subtypes of arrhythmias in epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from 2014 was examined for epilepsy and arrhythmias related discharges using appropriate International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes. The frequency of arrhythmias, gender differences in arrhythmia by subtypes, in-hospital outcomes and mortality predictors was analyzed. A …

Impact Of Cocaine Use On Acute Ischemic Stroke Patients: Insights From Nationwide Inpatient Sample In The United States, Rupak Desai, Upenkumar Patel, Chintan Rupareliya, Sandeep Singh, Manan Shah, Rikinkumar S. Patel, Smit Patel, Zabeen Mahuwala

Neurology Faculty Publications

Cocaine is the third most common substance of abuse after cannabis and alcohol. The use of cocaine as an illicit substance is implicated as a causative factor for multisystem derangements ranging from an acute crisis to chronic complications. Vasospasm is the proposed mechanism behind adverse events resulting from cocaine abuse, acute ischemic strokes (AIS) being one of the few. Our study looked into in-hospital outcomes owing to cocaine use in the large population based study of AIS patients. Using the national inpatient sample (NIS) database from 2014 of United States of America, we identified AIS patients with cocaine use using …

Functionally Pathogenic Ears2 Variants In Vitro May Not Manifest A Phenotype In Vivo, Nathan Mcneill, Alessia Nasca, Aurelio Reyes, Benjamin Lemoine, Brandi Cantarel, Adeline Vanderver, Raphael Schiffmann, Daniele Ghezzi

Neurology Faculty Publications

Objective: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC).

Methods: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity.

Results: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K). This gene has previously been implicated in the autosomal recessive leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In silico analysis supported pathogenicity …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

A Retrospective Review Of Paediatric Head Injuries In Asia - A Pan Asian Trauma Outcomes Study (Patos) Collaboration, Shu-Ling Chong, Uzma R. Khan, Indumathy Santhanam, Jun Seok Seo, Quan Wang, Sabariah Faizah Jamaluddin,, Quoc Ai Hoang Quoc, Su Yah Chew, Marcus Eng Hock Ong

Department of Emergency Medicine

Objective: We aim to examine the mechanisms of head-injured children presenting to participating centres in the Pan Asian Trauma Outcomes Study (PATOS) and to evaluate the association between mechanism of injury and severe outcomes.
Design and Setting: We performed a retrospective review of medical records among emergency departments (EDs) of eight PATOS centres, from September 2014 - August 2015.
Participants: We included children <16 years old who presented within 24 hours of head injury and were admitted for observation or required a computed tomography (CT) of the brain from the ED. We excluded children with known coagulopathies, neurological co-morbidities or prior neurosurgery. We reviewed the mechanism, intent, location and object involved in each injury, and the patients' physical findings on presentation.
Outcomes: Primary outcomes were death, endotracheal intubation or neurosurgical intervention. Secondary outcomes included hospital and ED length of stay.
Results: 1438 children were analysed. 953 children (66.3%) were male and the median age was 5.0 years (IQR …

Speech Processing Approach For Diagnosing Dementia In An Early Stage, Roozbeh Sadeghian, J. David Schaffer, Stephen A. Zahorian

Faculty Works

The clinical diagnosis of Alzheimer’s disease and other dementias is very challenging, especially in the early stages. Our hypothesis is that any disease that affects particular brain regions involved in speech production and processing will also leave detectable finger prints in the speech. Computerized analysis of speech signals and computational linguistics have progressed to the point where an automatic speech analysis system is a promising approach for a low-cost non-invasive diagnostic tool for early detection of Alzheimer’s disease.

We present empirical evidence that strong discrimination between subjects with a diagnosis of probable Alzheimer’s versus matched normal controls can be achieved …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Quantitative Anterior And Posterior Clinoidectomy Analysis And Mobilization Of The Oculomotor Nerve During Surgical Exposure Of The Basilar Apex Using Frameless Stereotaxis., Aclan Dogan, Justin S Cetas, Gregory J Anderson, Andy Rekito, Johnny B Delashaw

Articles, Abstracts, and Reports

No abstract provided.

A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib

Articles, Abstracts, and Reports

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease., David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne Mccormick, Susan M Mccurry, James D Bowen, Eric B Larson, Paul K Crane

Articles, Abstracts, and Reports

INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS: …

Role Of Surgery In Brain Metastases, Altaf Ali Laghari, Syed Ijlal Ahmed, Muhammad Shahzad Shamim

Department of Surgery Docs

Abstract Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

Variant Prevertebral Muscle: Unique Cadaveric Findings., Jocelyn R Gonzales, Joe Iwanaga, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The levator scapulae muscle typically runs from the transverse process of the atlas to the superior angle of the scapula. In this paper, we describe a rare finding identified during a dissection of a male cadaver, wherein a continuation of the right levator scapulae ran past its normal attachment to the C1 transverse process, fusing with the inferior attachment of the rectus capitis lateralis muscle. No variants were found on the opposite side, and the innervation of the levator scapulae muscle variant was typical of that of a normal levator scapulae. We also describe other related variants of the cranial …

A Randomized Controlled Trial Of Disclosing Genetic Risk Information For Alzheimer Disease Via Telephone, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

Purpose: Telephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.Methods: In a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.Results: Data from 257 participants showed that telephone disclosure occurred 7.4 days sooner and was 30% shorter, on average, than in-person disclosure (both P < 0.001). Anxiety and depression scores were well below cutoffs for clinical concern across protocols. Comparing telephone and in-person disclosure protocols, 99% confidence intervals of mean differences were within noninferiority margins on scales assessing anxiety, depression, and test-related distress, but inconclusive about positive impact. No differences were observed on measures of recall and subjective impact. Subanalyses supported noninferiority on all outcomes among apolipoprotein E (APOE) I 4-negative participants. Subanalyses were inconclusive for APOE I 4-positive participants, although mean anxiety and depression scores were still well below cutoffs for clinical concern. Conclusion: Telephone disclosure of APOE results and risk for Alzheimer disease is generally safe and helps providers meet demands for services, even when results identify an increased risk for disease.

Macrophage Type 2 Differentiation In A Patient With Laryngeal Squamous Cell Carcinoma And Metastatic Prostate Adenocarcinoma To The Cervical Lymph Nodes., Michael C. Topf, Madalina Tuluc, Larry A. Harshyne, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes.

CASE PRESENTATION: We report a 59-year-old male with recurrent T4 squamous cell carcinoma …

Ruptured Mycotic Aneurysms: Report And Outcomes Of Two Surgically Managed Patients, Aleena Khan, Muhammad Waqas, Waseem Mehmood Nizamani, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Mycotic aneurysm is a rare potentially life-threatening complication of infective endocarditis (IE). Little data is available on the management and outcomes of ruptured mycotic aneurysms with large intracerebral hematoma. Few cases have been described on the management of mycotic aneurysm in the presence of life-threatening hematoma and mass effect.
Case description: We are presenting two cases of ruptured mycotic aneurysm with intracerebral hematoma and impending brain herniation. Both patients had signs of high intracranial pressure and required urgent surgical evacuation of clot. One patient survived while the other patient expired soon after surgery.
Conclusion: Mycotic aneurysm of middle cerebral …

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug …

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …