Medicine and Health Sciences Commons^™

Telemedicine For The Spine Surgeon In The Age Of Covid-19: Multicenter Experiences Of Feasibility And Implementation Strategies., Daniel Franco, Thiago Montenegro, Glenn A Gonzalez, Kevin Hines, Aria Mahtabfar, Melvin D Helgeson, Rakesh Patel, James Harrop

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Multicenter study.

OBJECTIVES: The COVID-19 pandemic has obligated physicians to recur to additional resources and make drastic changes regarding the standard physician-patient encounter. In the last century, there has been a substantial improvement in technology, which over the years has opened the door to a new form of medical practicing known as telemedicine.

METHODS: Healthcare workers from three hospitals involved in the care for COVID-19 patients in the united states were invited to share their experience using telemedicine to deliver clinical care to their patients.

RESULTS: Since the appearance of this worldwide outbreak, social distancing has been a …

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.

A Delayed H3k27me3 Accumulation After Dna Replication Of Embryonic Stem Cells Opens Chromatin For Lineage Specific Transcription Factors To Bind And Initiate Differentiation, Jingli Cai, Svetlana Petruk, Robyn Sussman, Sina K. Kovermann, Samantha Mariani, Bruno Calabretta, Steven B Mcmahon, Hugh W. Brock, Lorraine Iacovitti, Alexander Mazo

Department of Neuroscience Faculty Papers

Introduction

Pluripotent stem cells (PSCs) have been useful to generate differentiated progenies for cell replacement therapy, and disease models. The Parkinson’s Disease (PD) field was arguably one of the first to have embraced the promise of stem cells. However, regardless of the differentiation protocols used, cultures and grafts continue to contain multiple cell types with midbrain dopamine (mDA) neural progenitors (NPs) and neurons representing only a fraction of total cells in the dish or graft. During cell differentiation, recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs, which is impeded by condensed …

Socioeconomic Status And Stroke Outcome, Sophia Dang, Jonathan C. Li, Kimon Bekelis, Md, Stavropoula Tjoumakaris, Md

Sigma Xi Student Research Day

Introduction

• International studies find socioeconomic status (SES) to be predictive of functional impairment after stroke.^1,2
• Lower socioeconomic status (LSE) is associated with increased severity of stroke onset, higher incidence of risk factors, and worse outcomes.³
• We sought to confirm the predictive significance of SES on acute ischemic stroke patient outcomes at a large urban, U.S. stroke center.

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 …

Dysregulation Of Kv3.4 Channels In Dorsal Root Ganglia Following Spinal Cord Injury., David Ritter, Benjamin M Zemel, Tamara J Hala, Michael E O'Leary, Angelo C Lepore, Manuel Covarrubias

Farber Institute for Neuroscience Faculty Papers

Spinal cord injury (SCI) patients develop chronic pain involving poorly understood central and peripheral mechanisms. Because dysregulation of the voltage-gated Kv3.4 channel has been implicated in the hyperexcitable state of dorsal root ganglion (DRG) neurons following direct injury of sensory nerves, we asked whether such a dysregulation also plays a role in SCI. Kv3.4 channels are expressed in DRG neurons, where they help regulate action potential (AP) repolarization in a manner that depends on the modulation of inactivation by protein kinase C (PKC)-dependent phosphorylation of the channel's inactivation domain. Here, we report that, 2 weeks after cervical hemicontusion SCI, injured …

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 …

Management Of Head And Neck Pseudoaneurysms: A Review Of 33 Consecutive Cases., Eliza Anderson, Nohra Chalouhi, Md, Aaron Dumont, Stavropoula Tjoumakaris, Mario Zanaty, Robert H. Rosenwasswer Md, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

Background. Endosaccular coiling, vessel occlusion, stenting, stent-assisted coiling, and flow diversion are all endovascular treatment options for pseudoaneurysms (PAs) of the head and neck. We explore different clinical situations in which these were selected for PA management at a single institution. Methods. Over a period of ten years, 33 patients presented to our hospital with PAs of the head and neck. Their outcomes and procedural complications are discussed. Results. We observed a complication rate of 18.2% (6 of 33), consisting predominantly of infarcts following vessel occlusion. As measured by the modified Rankin Scale, 25 (75.8%) patients had achieved favorable outcomes …

Persistent At-Level Thermal Hyperalgesia And Tactile Allodynia Accompany Chronic Neuronal And Astrocyte Activation In Superficial Dorsal Horn Following Mouse Cervical Contusion Spinal Cord Injury., Jaime L Watson, Tamara J Hala, Rajarshi Putatunda, Daniel Sannie, Angelo C Lepore

Department of Neuroscience Faculty Papers

In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal …

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 …

Advances In Neurovascular Treatments., Robert M Starke, Stephen J Monteith, Nohra Chalouhi, Dale Ding, Ricky Medel, David Hasan, Aaron S Dumont

Department of Neurosurgery Faculty Papers

No abstract provided.

Letter To Alliance For Headache Disorders Advocacy, William B. Young, Md

Department of Jefferson Headache Center papers and presentations

Several years ago the Centers for Medicare and Medicare Services (CMS) decided it would not pay for oxygen for the treatment of cluster headache. This is a serious hardship for many people with cluster headache. The American Headache Society and the Alliance for Headache Disorders Advocacy appealed to CMS to reverse this decision but they refused.

In February, we went to Congress, asking them to encourage CMS to reconsider this appeal. As a result of these efforts, Nebraska Senator Johanns and Delaware Senator Coons are circulating a letter for all Senators to sign urging CMS to re-evaluate this situation. To …

A Prospective, Multicenter, Phase I Matched-Comparison Group Trial Of Safety, Pharmacokinetics, And Preliminary Efficacy Of Riluzole In Patients With Traumatic Spinal Cord Injury., Robert G Grossman, Michael G Fehlings, Ralph F Frankowski, Keith D Burau, Diana S L Chow, Charles Tator, Angela Teng, Elizabeth G Toups, James Harrop, Bizhan Aarabi, Christopher I Shaffrey, Michele M Johnson, Susan J Harkema, Maxwell Boakye, James D Guest, Jefferson R Wilson

Department of Neurosurgery Faculty Papers

A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice-daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and …

Sociocultural Influences On Diabetes Self-Management Behaviors In Older African Americans, Barry W. Rovner, Robin J. Casten, Lynn Fields Harris

Department of Psychiatry and Human Behavior Faculty Papers

Objective. The purpose of this observational study was to describe the associations between cultural beliefs that are prevalent in older African Americans and adherence to diabetes self-management (DSM) behaviors.

Methods. In a community population of 110 older African Americans with type 2 diabetes, the investigators administered surveys that assess present time orientation (PTO), future time orientation (FTO), and religiosity, as well as exercising habits, reading food labels, and checking blood glucose.

Results. Participants who reported regularly exercising had significantly lower PTO scores and higher FTO and religiosity scores than participants who did not regularly exercise. Similarly, participants who reported reading …

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 …

Key Neurological And Neurochemical Features In A Model Of Repetitive Concussions: Implications For Post-Concussion Headache, C. Macolino, B. Daiutolo, A. Tyburski, Melanie B. Elliott

Department of Neurosurgery Faculty Papers

Introduction

Incidence rates for concussion will continue to grow along with the increasing awareness and improvements in diagnosis. Headache is a hallmark feature of post-concussion syndrome. Post-concussion headache (PCH) is highly prevalent in the military with as high as 97.8% reporting having headaches¹. occurring in up to 85% of athletes following ^2-4. In the Military and sports, return to duty or play guidelines state that a soldier/player should be asymptomatic before returning to physical activity. However, headache following concussion is commonly dismissed. PCH can be a new headache resulting from head trauma or worsening of pre-existing headache …

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 …

Hyperosmolar Therapy For Raised Intracranial Pressure., Ethan A Benardete

Department of Neurosurgery Faculty Papers

No abstract provided.

Metabolic Syndrome And Migraine., Amit Sachdev, Michael J Marmura

Department of Jefferson Headache Center papers and presentations

Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogenesis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and …

Neurophysiological Impact And Modeling-Independent Elucidation Of Inactivation Pathways In A-Type K+ Channels, J.D. Fineberg, David Ritter, Manuel Covarrubias

Department of Molecular Physiology and Biophysics Faculty Papers

Poster presented at Society for Neuroscience

Abstract:

A-type voltage-gated K⁺ channels auto-regulate their function by undergoing fast inactivation. Independent of molecular mechanisms, this inactivation can proceed after channel opening (open-state inactivation, OSI) or from a closed state prior to opening (closed-state inactivation, CSI). We hypothesize that the specific neurophysiological roles of A-type Kv channels depend on whether they undergo OSI, CSI or both (CSI+OSI). To explore these possibilities, we introduced Markov kinetic schemes of the A-type Kv4 conductance into a computational model of the hippocamcal CA1 neuron assuming either CSI or CSI+OSI and compared the properties of the somatic …

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 …

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. …

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 …