Medicine and Health Sciences Commons^™

Neurosurgical Applications Of Magnetic Resonance Diffusion Tensor Imaging, Daniel D. Hirsch, Bs, Benjamin M. Zussman, Bs, Adam E. Flanders, Md, Ashwini D. Sharan, Md

JHN Journal

Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) is a rapidly evolving technology that enables the visualization of neural fiber bundles, or white matter (WM) tracts. There are numerous neurosurgical applications for MR DTI including: (1) Tumor grading and staging; (2) Pre-surgical planning (determination of resectability, determination of surgical approach, identification of WM tracts at risk); (3) Intraoperative navigation (tumor resection that spares WM damage, epilepsy resection that spares WM damage, accurate location of deep brain stimulation structures); (4) Post-operative assessment and monitoring (identification of WM damage, identification of tumor recurrence). Limitations of MR DTI include difficulty tracking small and crossing …

Complications Of Decompressive Craniectomy, Sandra Ho, Bs, Yinn C. Ooi, Md, Muhamad A. Sheikh, Mbbs, Mitchell Maltenfort, Phd, Jack Jallo, Md, Phd

JHN Journal

Introduction:

Persistent elevation of intracranial pressure (ICP), if untreated, may lead to brain ischemia or lack of brain oxygen and even brain death.1-6,10 When standard treatments for elevated ICP are exhausted without any signs of improvement, decompressive craniectomy can be an effective alternative solution.7,19 Decompressive craniectomies (DC) have been used as a method of controlling intracranial pressure in patients with cerebral edema secondary to cerebral ischemia, subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), among others. 8-10 Several studies over the years have demonstrated the efficacy of this procedure.7-9,11,35,36 However, consensus is still lacking in the utility of DC as …

Undergraduate Neurosurgical Learning Opportunities At Jefferson, Leadership Committee Neurosurgery Student Interest Group

JHN Journal

On the evening of November 29, 2011, Jefferson’s Neurosurgery Interest Group (NSIG) hosted fourteen Jefferson Medical College students for a technical course entitled “Foundations in Neurosurgery” taught by Dr. Ashwini Sharan, Associate Professor of Neurosurgery and Director of the Division of Functional Neurosurgery, and Dr. Joshua Heller, Assistant Professor of Neurosurgery at Thomas Jefferson University Hospital. Additional instructors included Jefferson neurosurgery residents Rohan Chitale (PGY5), Chengyuan Wu (PGY4), and Karl Balsara (PGY2). Stryker MedED provided equipment, models, and instructors Ryan Dugan and Devin Opdendyk (Figure 1).

Anatomical Relationships Of The Anterior Blood Vessels To The Lower Lumbar Intervertebral Discs: Analysis Based On Magnetic Resonance Imaging Of Patients In The Prone Position., Alexander R Vaccaro, Christopher K Kepler, Jeffrey A Rihn, Hidekazu Suzuki, John K Ratliff, James S Harrop, William B Morrison, Worawat Limthongkul, Todd J Albert

Rothman Institute Faculty Papers

BACKGROUND: Intra-abdominal vascular injuries are rare during posterior lumbar spinal surgery, but they can result in major morbidity or mortality when they do occur. We are aware of no prior studies that have used prone patient positioning during magnetic resonance imaging for the purpose of characterizing the retroperitoneal iliac vasculature with respect to the intervertebral disc. The purpose of this study was to define the vascular anatomy adjacent to the lower lumbar spine with use of supine and prone magnetic resonance imaging.

METHODS: A prospective observational study included thirty patients without spinal abnormality who underwent supine and prone magnetic resonance …

Egr-1 Induces Darpp-32 Expression In Striatal Medium Spiny Neurons Via A Conserved Intragenic Element., Serene Keilani, Samira Chandwani, Georgia Dolios, Alexey Bogush, Heike Beck, Antonis K Hatzopoulos, Gadiparthi N Rao, Elizabeth A Thomas, Rong Wang, Michelle E Ehrlich

Farber Institute for Neuroscience Faculty Papers

DARPP-32 (dopamine and adenosine 3', 5'-cyclic monophosphate cAMP-regulated phosphoprotein, 32 kDa) is a striatal-enriched protein that mediates signaling by dopamine and other first messengers in the medium spiny neurons. The transcriptional mechanisms that regulate striatal DARPP-32 expression remain enigmatic and are a subject of much interest in the efforts to induce a striatal phenotype in stem cells. We report the identification and characterization of a conserved region, also known as H10, in intron IV of the gene that codes for DARPP-32 (Ppp1r1b). This DNA sequence forms multiunit complexes with nuclear proteins from adult and embryonic striata of mice and rats. …

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

Rajanikanth Vadigepalli

Poster Presentation.

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 …

The Appropriateness Of Long-Term Opioids To Treat Chronic Back Pain, Thomas Watanabe, Michael Salino, Adam Schreiber

Department of Rehabilitation Medicine Faculty Papers

Point/Counterpoint Case Scenario: A 55-year old man presents to a pain clinic upon referral from his primary care physician. His symptom is axial low back pain. His pain started approximately 1 year earlier without a specific inciting event. He denies radiation of pain into the lower extremities. There is no bowel or bladder involvement. There is no directional preference. He reports pain "all the time," with minimal specific exacerbating or relieving factors. There is no medical-legal involvement. His medical history is significant for hypertension, hypercholesterolemia, obesity, and sleep apnea. He is a divorced father of 2 adult children. He is …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis), Michael G. Fehlings, Alexander Vaccaro, Jefferson R. Wilson, Anoushka Singh, David W. Cadotte, James S. Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M. Massicotte, Stephen Lewis, Raja Rampersaud

Department of Neurosurgery Faculty Papers

Background: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (,24 hours after injury) versus late ($24 hours after injury) decompressive surgery after traumatic cervical SCI.

Methods: We performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was …

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 …

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 …

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 …

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 …

Surgical Management Of Fungal Vertebral Osteomyelitis, Benjamin M. Zussman, Bs, David L. Penn, Ms, James S. Harrop, Md

JHN Journal

Fungal vertebral osteomyelitis (FVO) is an uncommon but aggressive disease that may cause spinal instability, neurological insult, and possible death. Little data about treatment strategies and patient outcomes exist. A retrospective review of medical and surgical management with follow-up of this disease was performed.

Mis Posterior Cervical Spine Surgery: Five-Level Fusion Through A Novel Cervical Tube, Ashwini Sharan Md, Mitchell A. Hardenbrook, Md, John K. Ratliff Md, James Harrop, Md

JHN Journal

Minimally invasive surgical (MIS) techniques to the spine have focused mainly on the lumbar region. Many reports exist on the ability to decompress the neural structures in the lumbar and thoracic spine both via an anterior and posterior approach. Familiarity with these techniques now allows one or two level interbody and pedicle fusions, and treatment of trauma through MIS approaches. Controversy exists as to the efficacy of these techniques because direct studies comparing MIS approaches with open techniques are lacking. However, proponents of these techniques site smaller incision, less muscle retraction, less blood loss, shorter length of stay and better …

Bevacizumab: A Controversial Agent Against High-Grade Gliomas, Sussan Salas, Md, Miguel Guzman, Md, Kevin Judy, Md

JHN Journal

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Despite the current regimen of surgical resection with subsequent external beam radiotherapy and temozolomide, mean survival is 14.6 months and 2-year survival is 26%. GBM is a highly vascular tumor, a result of its increased expression of vascular endothelial growth factor (VEGF) compared to other brain tumors. VEGF promotes endothelial cell proliferation, and is thought to have a pivotal role during tumor progression. Multiple treatment modalities have targeted VEGF and VEGF receptors (VEGFTs) due to their essential roles in the regulation of angiogenic processes. Bevacizumab is a …

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 …

Is The Quality Of Neurosurgical Literature Improving?, James Harrop, Md, Mitchell Maltenfort, Phd

JHN Journal

Introduction:

The advent of evidence-based medicine has resulted in higher quality journal manuscripts in numerous medical disciplines. However, the impact in the neurosurgical literature has not been reported.

Objective:

To quantify the impact of evidence-based medicine on the quality of articles published in the Neurosurgery literature.

Methods:

Articles published in the journal Neurosurgery (founded in 1977) were reviewed for 1978, 1988, 1998, and 2008. Each decade’s sample was classified as therapeutic, diagnostic and prognostic based on a published system for determining level of evidence.

Results:

438 articles were reviewed. Articles not considered included any published under the heading “Case Report” …

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 …