Medicine and Health Sciences Commons^™

Conditions For Combining Gene Therapy With Bone Marrow Transplantation In Murine Krabbe Disease., Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

No abstract provided.

Molecular Treatment Effects Of Alemtuzumab In Skeletal Muscles Of Patients With Ibm., Karsten Schmidt, Konstanze Kleinschnitz, Goran Rakocevic, Marinos Dalakas, Jens Schmidt

Department of Neurology Faculty Papers

BACKGROUND: Mechanisms of inflammation and protein accumulation are crucial in inclusion body myositis (IBM). Recent evidence demonstrated that intravenous immunoglobulin failed to suppress cell-stress mediators in IBM. Here we studied the molecular changes in skeletal muscle biopsies from patients with IBM before and after treatment with alemtuzumab.

METHODS: Relevant inflammatory and degeneration-associated markers were assessed by quantitative-PCR and immunohistochemistry in repeated muscle biopsy specimens from patients with IBM, which had been treated in a previously published uncontrolled proof-of-concept trial with alemtuzumab.

RESULTS: There were no significant changes of the mRNA expression levels of the pro-inflammatory chemokines CXCL-9, CCL-4, and the …

Determinants Of Activity Levels In African Americans With Mild Cognitive Impairment., Barry W. Rovner, Md, Robin J. Casten, Phd, Benjamin E. Leiby, Phd

Department of Neurology Faculty Papers

Engaging in cognitive, social, and physical activities may prevent cognitive decline. In a sample of older African Americans with mild cognitive impairment (MCI; N=221), we investigated the cross-sectional relationships between activity levels and participants' demographic, clinical, and neuropsychological characteristics. The average age of participants was 75.4 years (SD, 7.0); 177 (80.1%) were women. Participation in cognitive/social activities was positively associated with education, depression, literacy, mobility, instrumental activities of daily living (IADL), verbal learning, and subcomponents of executive function. A linear regression identified IADLs, education, depression, and verbal learning as independent predictors. Participation in physical activities was positively associated with sex, …

Predicting The Laterality Of Temporal Lobe Epilepsy From Pet, Mri, And Dti: A Multimodal Study., Dorian Pustina, Brian Avants, Michael R Sperling, Richard Gorniak, Xiaosong He, Gaelle Eve Doucet, Paul Barnett, Ms, Scott Mintzer, Ashwini Sharan Md, Joseph I Tracy

Department of Neurology Faculty Papers

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the …

Plumbing And Wiring: Atherosclerosis In Epilepsy., Scott Mintzer, Md

Department of Neurology Faculty Papers

Over the long term, epilepsy is clearly associated with cognitive impairment. This has been demonstrated functionally, using neuropsychological testing, and reinforced by structural studies showing progressive atrophy in patients with chronic epilepsy ^1-3. The prevailing explanation for this, of course, has been the direct and cumulative effects of seizures on the brain. The basic science literature is chock full of studies showing impairment of neuronal function after seizures, both acutely and chronically. And for those of us who see patients, the progressive memory complaints and clear-cut decline in function seen in those with drug-resistant epilepsy — particularly temporal lobe …

Regulation Of L1 Expression And Retrotransposition By Melatonin And Its Receptor: Implications For Cancer Risk Associated With Light Exposure At Night., Dawn Deharo, Kristine J Kines, Mark Sokolowski, Robert T Dauchy, Vincent A Streva, Steven M Hill, John P Hanifin, George Brainard, David E Blask, Victoria P Belancio

Department of Neurology Faculty Papers

Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian …

Converging Evidence For The Processing Costs Associated With Ambiguous Quantifier Comprehension., Corey T Mcmillan, Danielle Coleman, Robin Clark, Tsao-Wei Liang, Rachel G Gross, Murray Grossman

Department of Neurology Faculty Papers

Traditional neuroanatomic models of language comprehension have emphasized a core language network situated in peri-Sylvian cortex. More recent evidence appears to extend the neuroanatomic network beyond peri-Sylvian cortex to encompass other aspects of sentence processing. In this study, we evaluate the neuroanatomic basis for processing the ambiguity in doubly-quantified sentences. For example, a sentence like "All the dogs jumped in a lake" can be interpreted with a collective interpretation (e.g., several dogs jumping into a single lake) or a distributive interpretation (e.g., several dogs each jumping into a different lake). In Experiment 1, we used BOLD fMRI to investigate neuroanatomic …

The Stigma Of Migraine, William B. Young, Jung E. Park, Iris X. Tian, Joanna Kempner

Department of Neurology Faculty Papers

Background

People who have a disease often experience stigma, a socially and culturally embedded process through which individuals experience stereotyping, devaluation, and discrimination. Stigma has great impact on quality of life, behavior, and life chances. We do not know whether or not migraine is stigmatizing.

Methods

We studied 123 episodic migraine patients, 123 chronic migraine patients, and 62 epilepsy patients in a clinical setting to investigate the extent to which stigma attaches to migraine, using epilepsy as a comparison. We used the stigma scale for chronic illness, a 24-item questionnaire suitable for studying chronic neurologic diseases, and various disease impact …

Inhibitory Effect Of Matrine On Blood-Brain Barrier Disruption For The Treatment Of Experimental Autoimmune Encephalomyelitis., Su Zhang, Quan-Cheng Kan, Yuming Xu, Guang-Xian Zhang, Lin Zhu

Department of Neurology Faculty Papers

Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement …

Pulmonary Complications In Patients With Severe Brain Injury., Kiwon Lee, Fred Rincon

Department of Neurology Faculty Papers

Pulmonary complications are prevalent in the critically ill neurological population. Respiratory failure, pneumonia, acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), pulmonary edema, pulmonary contusions and pneumo/hemothorax, and pulmonary embolism are frequently encountered in the setting of severe brain injury. Direct brain injury, depressed level of consciousness and inability to protect the airway, disruption of natural defense barriers, decreased mobility, and secondary neurological insults inherent to severe brain injury are the main cause of pulmonary complications in critically ill neurological patients. Prevention strategies and current and future therapies need to be implemented to avoid and treat the development …

Life History Theory And Social Psychology., Donald F Sacco, Karol Osipowicz

Department of Neurology Faculty Papers

No abstract provided.

Rituximab Induces Sustained Reduction Of Pathogenic B Cells In Patients With Peripheral Nervous System Autoimmunity., Michael A Maurer, Goran Rakocevic, Carol S Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal …

Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE:

Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET-positive, MRI-negative patients and compared them with those of patients with MTS.

METHODS:

We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI-). We compared …

Conversion From Enzyme-Inducing Antiepileptic Drugs To Topiramate: Effects On Lipids And C-Reactive Protein., Scott Mintzer, Christopher T Skidmore, Sara J Rankin, Inna Chervoneva, Edward Pequinot, David M Capuzzi, Michael R Sperling

Department of Neurology Faculty Papers

PURPOSE: We previously demonstrated that converting patients from the enzyme-inducers phenytoin or carbamazepine to the non-inducers levetiracetam or lamotrigine reduces serum lipids and C-reactive protein (CRP). We sought to determine if the same changes would occur when patients were switched to topiramate, which has shown some evidence of enzyme induction at high doses. We also examined the effects of drug switch on low-density lipoprotein (LDL) particle concentration.

METHODS: We converted 13 patients from phenytoin or carbamazepine monotherapy to topiramate monotherapy (most at doses of 100-150 mg/day). Fasting lipids, including LDL particle concentration, and CRP were obtained before and ≥6 weeks …

The Prevalence Of Cervico-Arterial Dissection In Sub-Arachnoid Hemorrhage In The United States, Ali Seifi, Md, Fred Rincon, Md, Msc, Mitchell Maltenfort, Phd, Pascal Jabbour, Md, Rodney Bell, Md, Michael Moussouttas, Md

Department of Neurology Faculty Papers

Objectives: In this study, we sought to determine the prevalence of cervico-arterial dissection in aubarachnoid hemorrhage (SAH) using a large administrative database.

The Prevalence And Risk Factors Of Acute Myocardial Infarction (Ami) After Acute Ischemic Stroke (Ais) In The United States, Ali Seifi, Md, Fred Rincon, Md, Msc, Michael Moussouttas, Md, Mitchell Maltenfort, Phd, Matthew Vibbert, Md, Rodney Bell, Md, Maria Carissa Pineda, Md, Diana Tzeng, Md, Jacqueline Urtecho, Md, Anish Koka, Md, William Mcbride, Md

Department of Neurology Faculty Papers

Objectives: To determine the prevalence and risk factors for, and the association with in-hospital mortality of, AMI after AIS, and to study the effect of intravenous recombinant tissue plasminogen activator (r-tPA) in this setting. We hypothesized that AMI would be associated with lower survival rate at hospital discharge but that intravenous r-tPA would be associated with lower risk of AMI.

Psychological And Cognitive Determinants Of Vision Function In Age-Related Macular Degeneration., Barry W. Rovner, Robin J Casten, Robert W Massof, Benjamin E Leiby, William S Tasman

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD.

METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Clinical And Diagnostic Features Of Patients With Compound Heterozygous A467t/W748s Polg1 Mutations: A Case Report And Review Of Previous Cases, David Roshal, D.O., Andro Zangaladze, Md, Phd

Department of Neurology Faculty Papers

Introduction

Mutations in the POLG1 gene are considered to be the most common gene defect identified in autosomal recessive mitochondrial DNA depletion disorders. POLG1 is a gene encoding the 195kDa catalytic (alpha) subunit of the mitochondrial (gamma) DNA polymerase, located on chromosome 15q25 and is responsible for mtDNA replication. Mutations in POLG1 are associated with chronic progressive external ophthalmoplegia (CPEO). Other genes that have been implicated in causing syndromic and non-syndromic mitochondrial disorders have been found on both mtDNA (3243A>G, 8344A>G, 8993T>G, and 11778A>G) and nDNA (SURF1, POLG1, TWINKLE, and ANT1).

We report a patient with …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …

Involvement Of Beta-Chemokines In The Development Of Inflammatory Demyelination., Ileana Banisor, Thomas P Leist, Bernadette Kalman

Department of Neurology Faculty Papers

The importance of beta-chemokines (or CC chemokine ligands - CCL) in the development of inflammatory lesions in the central nervous system of patients with multiple sclerosis and rodents with experimental allergic encephalomyelitis is strongly supported by descriptive studies and experimental models. Our recent genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing the genetic associations, we also detected a distinct regional expression regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in multiple sclerosis brains. These observations are in consensus with previous studies, and add new …