Medicine and Health Sciences Commons^™

Pulmonary Function Decline In Amyotrophic Lateral Sclerosis, Terry D. Heiman-Patterson, Ossama Khazaal, Daohai Yu, Michael E. Sherman, Edward J. Kasarskis, Carlayne E. Jackson, Peg Niv Study Group

Neurology Faculty Publications

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each …

Review Of Alterations In Perlecan-Associated Vascular Risk Factors In Dementia, Amanda L. Trout, Ibolya Rutkai, Ifechukwude J. Biose, Gregory J. Bix

Neurology Faculty Publications

Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan's influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer's disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes …

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …

Development Of A Non-Invasive Device For Swallow Screening In Patients At Risk Of Oropharyngeal Dysphagia: Results From A Prospective Exploratory Study, Catriona M. Steele, Rajat Mukherjee, Juha M. Kortelainen, Harri Pölönen, Michael Jedwab, Susan L. Brady, Kayla Brinkman Theimer, Susan Langmore, Luis F. Riquelme, Nancy B. Swigert, Philip M. Bath, Larry B. Goldstein, Richard L. Hughes, Dana Leifer, Kennedy R. Lees, Atte Meretoja, Natalia Muehlemann

Neurology Faculty Publications

Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, …

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 …

Commentary: Ganglion Cell Complex Of Retinal Layer Thickness By Optical Coherence Tomography In Cases Of Multiple Sclerosis Without Optic Neuritis Compared To Healthy Eyes, Padmaja Sudhakar

Neurology Faculty Publications

No abstract provided.

Rationale And Methods For A Multicenter Clinical Trial Assessing Exercise And Intensive Vascular Risk Reduction In Preventing Dementia (Rrad Study), Amanda N. Szabo-Reed, Eric Vidoni, Ellen F. Binder, Jeffrey Burns, C. Munro Cullum, William P. Gahan, Aditi Gupta, Linda S. Hynan, Diana R. Kerwin, Heidi Rossetti, Ann M. Stowe, Wanpen Vongpatanasin, David C. Zhu, Rong Zhang, Jeffrey N. Keller

Neurology Faculty Publications

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of …

A Pilot Study Identifying Brain-Targeting Adaptive Immunity In Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury, Sterling B. Ortega, Poornima Pandiyan, Jana Windsor, Vanessa O. Torres, Uma M. Selvaraj, Amy Lee, Michael Morriss, Fenghua Tian, Lakshmi Raman, Ann M. Stowe

Neurology Faculty Publications

OBJECTIVES: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

DESIGN: A single center prospective observational study.

SETTING: Pediatric and cardiac ICUs at a single tertiary care, academic center.

PATIENTS: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Venous blood samples were …

Pediatric Cardioembolic Stroke In Midaortic Syndrome, Ana C. Albuja, Mauricio F. Villamar, Alejandra M. Stewart, Donita D. Lightner

Neurology Faculty Publications

No abstract provided.

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …

Influence Of Dietary Salt Knowledge, Perceptions, And Beliefs On Consumption Choices After Stroke In Uganda, Martin N. Kaddumukasa, Elly Katabira, Martha Sajatovic, Svetlana Pundik, Mark Kaddumukasa, Larry B. Goldstein

Neurology Faculty Publications

Background

Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices.

Purpose

Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda.

Methods

Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships …

Linking Tuberous Sclerosis Complex, Excessive Mtor Signaling, And Age-Related Neurodegeneration: A New Association Between Tsc1 Mutation And Frontotemporal Dementia, Nicholas T. Olney, Carolina Alquezar, Eliana Marisa Ramos, Alissa L. Nana, Jamie C. Fong, Anna M. Karydas, Joanne B Taylor, Melanie L. Stephens, Andrea R. Argouarch, Victoria A. Van Berlo, Deepika R. Dokuru, Elliott H. Sherr, Gregory A. Jicha, William P. Dillon, Rahul S. Desikan, Mary De May, William W. Seeley, Giovanni Coppola, Bruce L. Miller, Aimee W. Kao

Neurology Faculty Publications

No abstract provided.

Peripheral (Deep) But Not Periventricular Mri White Matter Hyperintensities Are Increased In Clinical Vascular Dementia Compared To Alzheimer's Disease, Charles D. Smith, Eleanor S. Johnson, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Richard J. Kryscio, Richard R. Murphy, Clinton V. Wellnitz

Neurology Faculty Publications

Background and purpose: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. Methods: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Sex Differences In Clinical Features Of Early, Treated Parkinson's Disease, Erika F. Augustine, Adriana Pérez, Rohit Dhall, Chizoba C. Umeh, Aleksandar Videnovic, Franca Cambi, Anne-Marie A. Wills, Jordan J. Elm, Richard M. Zweig, Lisa M. Shulman, Martha A. Nance, Jacquelyn Bainbridge, Oksana Suchowersky

Neurology Faculty Publications

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.

METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between …

Ferritin Levels In The Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes And Are Regulated By Apoe, Scott Ayton, Noel G. Faux, Ashley I. Bush, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Alzheimer's Disease Neuroimaging Initiative

Neurology Faculty Publications

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. …

The Relationship Of Cpe To Hiv Dementia: Slain By An Ugly Fact?, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

No abstract provided.

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

Spontaneous Intracranial Arterial Dissection In The Young: Diagnosis By Ct Angiography, William C. Robertson, Curtis A. Given

Neurology Faculty Publications

BACKGROUND: Spontaneous carotid artery dissections have been rarely reported in children. Diagnosis has traditionally been confirmed by catheter arteriography. More recently diagnosis has been made by magnetic resonance imaging and magnetic resonance angiography; however the sensitivity of these techniques has yet to be determined. The authors are unaware of reports of carotid dissection confirmed by dynamic computed tomography (computerized tomographic arteriography) in the young.

CASE PRESENTATION: We recently evaluated a fourteen year-old male following the development of transient neurologic symptoms. There was no antecedent illness or trauma. Dynamic computed tomography revealed an intracranial dissection involving the supraclinoid segment of the …

Estrogen Protects Against The Synergistic Toxicity By Hiv Proteins, Methamphetamine And Cocaine, Jadwiga Turchan, Caroline Anderson, Kurt F. Hauser, Qinmiao Sun, Jiayou Zhang, Ying Liu, Phyllis M. Wise, Inna Kruman, William Maragos, Mark P. Mattson, Rosemarie Booze, Avindra Nath

Neurology Faculty Publications

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by …