Medicine and Health Sciences Commons^™

Manifestations Of Rheumatoid Arthritis: Epidural Pannus And Atlantoaxial Subluxation Resulting In Basilar Invagination., Adam L Schreiber, Do, Ma

Department of Rehabilitation Medicine Faculty Papers

Presented in part at the AAPMR 71st Annual Assembly Meeting, Seattle, WA, November 4-7, 2010.

Atlantoaxial instability results from cartilaginous destruction, periarticular erosions, and ligament and tendon attenuation. Instability affects 19%-70% of patients, and basilar invagination from vertical odontoid subluxation through the foramen magnum occurs in 38% of patients. This phenomenon occurs twice as often in women than men, whose age at diagnosis typically ranges from 30-50 years. Along with bony compression, the pannus further decreases the space available for the cord by 3mmor more in approximately 66% of patients (Figures 1-7). The earliest and most common symptom of cervical …

Mir-128 Inhibits Tumor Growth And Angiogenesis By Targeting P70s6k1., Zhu-Mei Shi, Jing Wang, Zhiping Yan, Yong-Ping You, Chong-Yong Li, Xu Qian, Yu Yin, Peng Zhao, Ying-Ying Wang, Xie-Feng Wang, Ming-Na Li, Ling-Zhi Liu, Ning Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating …

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 …

Functional Recovery Of Untreated Human Immunodeficiency Virus-Associated Guillain-Barré Syndrome: A Case Report, Adam L. Schreiber, John W. Norbury Iii, Eduardo A. De Sousa

Department of Rehabilitation Medicine Faculty Papers

HIV-associated Guillain-Barré Syndrome is a well-documented phenomenon, typically occurring at seroconversion. GBS may result in functional impairment treated with a combination of medications, plasmapheresis, and rehabilitation. The quantified functional recovery of HIV-associated GBS with or without HIV treatment is not well-described. Utilizing serial FIM scoring, we describe a patient’s recovery from HIV-associated GBS after treatment with IVIg and acute inpatient rehabilitation without HIV treatment.

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.

Treatment Of Cerebrospinal Fluid Leak During Spinal Cord Stimulator Implantation With Epidural Blood Patches, Farid Kia, Md, Linqiu Zhou, Md, Jason Berk, Md

Department of Rehabilitation Medicine Faculty Papers

Conclusion:

Our data is consistent with prior studies in demonstrating that the incidence of dural puncture and CSF leak with SCS procedures is rare. Based on our experiences, performing an epidural blood patch intra-operatively on the contra-lateral side under fluoroscopy could prevent PDPH. This treatment should especially be considered in patients undergoing SCS trials in order to accurately assess the level of pain reduction. Patients with prior spine surgeries might pose higher risks for dural puncture and more extensive pre-operative assessment could be beneficial.

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 …

Multiple Courses Of Stereotactic Re-Irradiation In Recurrent Oligodendroglioma: A Case Report., Shannon Fogh, Charles Glass, David W Andrews, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit.

CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 …

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 …

A New Frontier For Headache., Stephen Silberstein

Department of Jefferson Headache Center papers and presentations

No abstract provided.

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 …

Interaction Of The Mu-Opioid Receptor With Gpr177 (Wntless) Inhibits Wnt Secretion: Potential Implications For Opioid Dependence., Jay Jin, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Wade Berrettini, Robert Levenson

Department of Neurosurgery Faculty Papers

BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy

Department of Cancer Biology Faculty Papers

BACKGROUND: The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.

METHODOLOGY/PRINCIPAL FINDINGS: Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies …

Transverse Myelitis In Pregnancy: A Case Report, Brian P. Mcdonald, Do, Nethra S. Ankam, Md

Department of Rehabilitation Medicine Faculty Papers

Objective: Describe the clinical course and treatment of a patient with paraplegia secondary to transverse myelitis during her pregnancy.

Setting: Acute Inpatient Rehabilitation Unit, University Hospital.

Participant: 36 year old Caucasian woman at 18 weeks gestation.

Interventions: Provided education and training on basic childcare tasks at a wheelchair level, and on how to obtain wheelchair accessible baby furniture. Provided availability of a peer who sustained a spinal cord injury prior to pregnancy. Maintained a close working relationship with maternal fetal health department regarding management of nausea and pain management, and educated team members about the possibility of autonomic …

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Utilization Of Dantrolene In Stiff-Person Syndrome: A Case Report, John M. Vasudevan, Md, S. Kamal Fetouh, Md,, Nethra S. Ankam, Md, Adam L. Schreiber, Do, Ma

Department of Rehabilitation Medicine Faculty Papers

Setting: University hospital-based acute rehabilitation.

Patient: 75-year-old woman with Stiff-Person Syndrome (SPS) with a recent fall and Colles fracture.

Case Description: Four months prior to admission, the patient was diagnosed with SPS, negative for anti-GAD antibodies. Diagnosis was based on a 3-year history of progressive rigidity leading to frequent falls and fractures. Anxiety and fear of falling limited her mobility, and she sustained a sacral pressure ulcer during acute hospitalization. On admission, history was remarkable for unsteady gait and muscle cramps exacerbated when startled or excited. Examination was remarkable for rigidity in her axial and limb muscles. She presented …

Early And Late Treatment Of Migraine With Dhe Ns (Migranal®), Meryl Latsko, Md, Mph, Stephen D. Silberstein, Md

Department of Jefferson Headache Center papers and presentations

To examine the use of DHE NS (Migranal®) in the early and late treatment of migraine in subjects with a history of cutaneous allodynia.

Frovatriptan As Preemptive Treatment For Fasting-Induced Migraine, Meryl Latsko, Md, Mph, Stephen D. Silberstein, Md

Department of Jefferson Headache Center papers and presentations

To examine frovatriptan's efficacy as preemptive treatment for fasting-induced migraine.

Intravenous Inoculation Of A Bat-Associated Rabies Virus Causes Lethal Encephalopathy In Mice Through Invasion Of The Brain Via Neurosecretory Hypothalamic Fibers., Mirjam A R Preuss, Marie-Luise Faber, Gene S Tan, Michael Bette, Bernhard Dietzschold, Eberhard Weihe, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

The majority of rabies virus (RV) infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown …

The Efficacy Of Surgical Decompression Before 24 Hours Versus 24 To 72 Hours In Patients With Spinal Cord Injury From T1 To L1--With Specific Consideration On Ethics: A Randomized Controlled Trial., Vafa Rahimi-Movaghar, Soheil Saadat, Alexander R Vaccaro, Seyed Mohammad Ghodsi, Mohammad Samadian, Arya Sheykhmozaffari, Seyed Mohammad Safdari, Bahram Keshmirian

Department of Neurosurgery Faculty Papers

BACKGROUND: There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24-72 hours) surgical decompression in terms of neurological …

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 …

Near Fatal Posterior Reversible Encephalopathy Syndrome Complicating Chronic Liver Failure And Treated By Induced Hypothermia And Dialysis: A Case Report., Rashmi Chawla, Daniel Smith, Paul E Marik

Division of Pulmonary and Critical Care Medicine Faculty Papers

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinico-neuroradiological entity characterized by headache, vomiting, altered mental status, blurred vision and seizures with neuroimaging studies demonstrating white-gray matter edema involving predominantly the posterior region of the brain. CASE PRESENTATION: We report a 47-year-old Caucasian man with liver cirrhosis who developed posterior reversible encephalopathy syndrome following an upper gastrointestinal hemorrhage and who was managed with induced hypothermia for control of intracranial hypertension and continuous veno-venous hemodiafiltration for severe hyperammonemia. CONCLUSION: We believe this is the first documented case report of posterior reversible encephalopathy syndrome associated with cirrhosis as well as the first report …

Multi-Scale Modeling Of Angiotensin Ii Induced Neuronal Regulatory Mechanisms In The Brain, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Poster Presentation.

A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon

Department of Cancer Biology Faculty Papers

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …

Developing "Human Functioning And Rehabilitation Research" From The Comprehensive Perspective., Gerold Stucki, Jan Dietrich Reinhardt, Gunnar Grimby, John Melvin

Department of Rehabilitation Medicine Faculty Papers

With the International Classification of Functioning, Disability and Health (ICF) the World Health Organization (WHO) has prepared the ground for a comprehensive understanding of Human Functioning and Rehabilitation Research, integrating the biomedical perspective on impairment with the social model of disability. This poses a number of old and new challenges regarding the enhancement of adequate research capacity. Here we will summarize approaches to address these challenges with respect to 3 areas: the organization of Human Functioning and Rehabilitation Research into distinct scientific fields, the development of suitable academic training programmes and the building of university centres and collaboration networks.

Evidence Against Roles For Phorbol Binding Protein Munc13-1, Adam Adaptor Eve-1, Or Vesicle Trafficking Phosphoproteins Munc18 Or Nsf As Phospho-State-Sensitive Modulators Of Phorbol/Pkc-Activated Alzheimer App Ectodomain Shedding., Annat F Ikin, Mirsada Causevic, Steve Pedrini, Lyndsey S Benson, Joseph D Buxbaum, Toshiharu Suzuki, Simon Lovestone, Shigeki Higashiyama, Tomas Mustelin, Robert D Burgoyne, Sam Gandy

Farber Institute for Neuroscience Faculty Papers

ABSTRACT: BACKGROUND: Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on …

A Turner Syndrome Neurocognitive Phenotype Maps To Xp22.3., Andrew R Zinn, David Roeltgen, Gerry Stefanatos, Purita Ramos, Frederick F Elder, Harvey Kushner, Karen Kowal, Judith L Ross

Department of Pediatrics Faculty Papers

BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. METHODS: Subjects were recruited from North American genetics and …