Neurology Commons^™

The Synergy Of Bet Inhibitors With Aurora A Kinase Inhibitors In Mycn-Amplified Neuroblastoma Is Heightened With Functional Tp53, Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson

Faculty, Staff and Students Publications

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared …

Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.

METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.

RESULTS: Among 175 patients enrolled by October 31, 2019, …

Postdischarge 24/7 Hotline Service For Neurology And Neurosurgery Patients And 1-Year Impact On Readmission Rates, Unplanned Emergency Department Visits, And Patient Satisfaction, Shafqat Bibi, Rida Mitha, Kiran Bano, Farida Datoo, Nadia Karim, Muhammad Shahzad Shamim

School of Nursing & Midwifery

Objective: Telephone triage is a system in which trained nurses use standardized protocols to evaluate symptoms over the phone and determine the appropriate course of action.
Materials and methods: We implemented a protocol for systematic follow up phone calls and telephonic triage to families of neurology and neurosurgery patients after discharge, primarily to improve care transition and to assess its impact on the ratio of visits in the emergency department, readmissions, and overall satisfaction of patients and families. The intervention comprised the implementation of nurse led telephone triage and postdischarge follow up phone calls. After implementing hotline services in mind …

Aggressive Herpes Zoster In Young Patients With Multiple Sclerosis Under Dimethyl Fumarate: Significance Of Cd8, Maria Anagnostouli, Georgios Velonakis, Marinos Dalakas

Department of Neurology Faculty Papers

Dimethyl fumarate (DMF), approved for relapsing-remitting multiple sclerosis (RRMS), exerts immune-mediated mechanisms crucial for T-cell survival and migration, preferentially reducing CD8+ T cells.1 Although baseline absolute lymphocyte count (ALC) is considered the most critical predictor of developing lymphopenia,2 it was recently concluded that lymphocyte subset monitoring is not required for safety vigilance because T-cell subset reduction does not increase risks for serious infections.3 We present 2 young patients with RRMS, under DMF treatment, negative for HIV and SARSCoV-2 (by RT-PCR in nasal swab) and with normal follow-up white blood cell (WBC)/ALC counts, who developed severe herpes zoster (HZ) infection with …

Tolerability Of Switching Cholinesterase Inhibitors To Memantine Monotherapy Versus Adding Memantine As Combination Therapy For All-Cause Neurodegenerative Disorders, Estevana Isaac, Md, Mijail Serruya, Md, Phd, Keith Scott, Phd, Michael R. Sperling, Md, Carol Lippa, Md

Health Equity and Quality Improvement (HEQI) Summit

Background: Prior studies have focused on the clinical efficacy of combination therapy, Donepezil and Memantine, for patient’s diagnosed with Alzheimer’s disease. However, the potential adverse drug reactions while described as mild can have serious sequelae in older adults who are already managing the side effects of polypharmacy.

Objective: This study looks to explore the tolerability of switching cholinesterase inhibitors to memantine monotherapy versus adding memantine as combination therapy for all-cause neurodegenerative disorders.

Methods: The study is a retrospective chart review that includes 175 patients aged 50 and older diagnosed with neurocognitive disorders (ICD 10 F00-F03.91 and ICD10 G30-G31.84) managed on …

Addressing Health Disparities And Access In The Department Of Neurology Outpatient Setting In The Era Of The Covid-19 Pandemic: A Quality Improvement Initiative, V. Wang, M. Rehman, K. Burda, L. Liao, M. Braslavsky, T. Chuang, J. Diep, Md, E. Isaac, E. Wong

Health Equity and Quality Improvement (HEQI) Summit

Neurology, a largely outpatient specialty, has joined many other fields in the endeavor of incorporating telemedicine.^4,6,7 We present the results of analysis of the Epic Electronic Medical Record (EMR) of all outpatient visits from the Thomas Jefferson University Hospital Department of Neurology from 2019 to 2020 in order to identify areas of ethnic minority and geographic disparities with regards to usage of telemedicine. For our analyses, we have included Neurology patients across the General Neurology (JUP Neurology 909 Walnut NEU), Headache Center (HA), and Multiple Sclerosis Center (MS). Additionally, based on patient surveys from a subset of our outpatient …

Evaluating Advance Care Planning In Patients With Amyotrophic Lateral Sclerosis: A Retrospective Chart Review, Zachary Klock, Md, Stephanie Dobak, Rd, Gail Houseman, Rn, Margaret Kreher, Md, Facp

Health Equity and Quality Improvement (HEQI) Summit

• ALS is a progressive, degenerative neurologic disorder with inevitable decline in function and ultimately death.
• Most patients and families will be faced with decisions regarding mechanical ventilation and artificial nutrition.
• Prior studies have showed low rates of ACP completion in this population (<50%) and high rates of opt out in programs to aid ACP (nearly 40%).
• By reviewing charts of patients with ALS, we can analyze the impact of ACP on care utilization including artificial nutrition, mechanical ventilation and hospice utilization to help to guide efforts regarding ACP in the outpatient setting.

Alteplase Administration For Acute Ischemic Stroke (Ais) In Er - A 5-Year Review, Ali A. Saherwala, Md, Diana Tzeng, Md, Robin Dharia, Md

Health Equity and Quality Improvement (HEQI) Summit

• ER visits for AIS grown in last 10 years by 25%
• Ongoing effort by AHA/ASA to improve access to care with early stroke recognition and awareness
• Time is brain; rate of thrombolysis with alteplase (ALT) should increase with better EMS systems, awareness, and education

Improving Understanding Of And Compliance With Anti-Shivering Protocols During Therapeutic Hypothermia With Just-In-Time Training, Brittany Heckel, Md, Eunice Lee, Md, Courtney Curran, Md, Kasun Navarathna, Md, Henry Lee, Md, Lucy Maguire, Md, Phd, Malissa Pynes, Md, Shyam Majmundar, Md, Alexander Buslov, Md, Syed Shah, Md, Mba, Matthew Vibbert, Md

Health Equity and Quality Improvement (HEQI) Summit

• Therapeutic hypothermia after cardiac arrest has been demonstrated to improve neurologic outcomes and survival rates following cardiac arrest.
• Shivering during hypothermia increases metabolic demand, increases oxygen consumption and increases difficulty maintaining desired temperatures.
• Gaps in knowledge can lead to inadequate management of shivering, leading

Aims for Improvement

To improve understanding of and compliance with anti-shivering protocols during therapeutic hypothermia post-cardiac arrest.

Inflammatory Regulation Of Cns Barriers After Traumatic Brain Injury: A Tale Directed By Interleukin-1, Colleen N. Bodnar, James B. Watson, Emma K. Higgins, Ning Quan, Adam D. Bachstetter

Neuroscience Faculty Publications

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during …

Explicit Training To Improve Affective Prosody Recognition In Adults With Acute Right Hemisphere Stroke, Alexandra Zezinka Durfee, Shannon M. Sheppard, Erin L. Meier, Lisa Bunker, Erjia Cui, Ciprian Crainiceanu, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Difficulty recognizing affective prosody (receptive aprosodia) can occur following right hemisphere damage (RHD). Not all individuals spontaneously recover their ability to recognize affective prosody, warranting behavioral intervention. However, there is a dearth of evidence-based receptive aprosodia treatment research in this clinical population. The purpose of the current study was to investigate an explicit training protocol targeting affective prosody recognition in adults with RHD and receptive aprosodia. Eighteen adults with receptive aprosodia due to acute RHD completed affective prosody recognition before and after a short training session that targeted proposed underlying perceptual and conceptual processes. Behavioral impairment and lesion characteristics were …

Long Term Safety, Tolerability, And Efficacy Of Intracutaneous Zolmitriptan (M207) In The Acute Treatment Of Migraine., Stephanie J. Nahas, Nada Hindiyeh, Deborah I. Friedman, Nada Elbuluk, Donald J. Kellerman, Pamela K. Foreman, Peter Schmidt

Department of Neurology Faculty Papers

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.

BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.

METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a …

Use Of Artificial Intelligence To Identify Predictors Of Functional Outcomes In Patients With Facioscapulohumeral Muscular Dystrophy, Natalie K. Katz

Research Days

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy characterized by slowly progressive muscle weakness. Symptoms initially involve the facial and shoulder girdle muscles, with later involvement of the distal lower extremities, pelvic girdle and proximal lower extremities. FSHD type 1 (FHSD1) is the most common form (~95% of individuals) and is caused by deletion of microsatellite repeats in the D4Z4 region on chromosome 4 (4q35). Normal individuals have >10 repeats whereas individuals with FSHD1 have 1-10 repeats. There is significant variability in regards to disease severity, rates of progression and functional outcomes, but …

Lessons Learned After 760 Neurointerventions Via The Upper Extremity Vasculature: Pearls And Pitfalls., Ahmad Sweid, Joshua H. Weinberg, Omaditya Khanna, Somnath Das, Julie Kim, Darcy Curtis, Batoul Hammoud, Kareem El Naamani, Rawad Abbas, Shyam Majmundar, Kalyan C. Sajja, Nohra Chalouhi, Fadi Al Saiegh, Nikolaos Mouchtouris, Elias Atallah, M. Reid Gooch, Nabeel A. Herial, Stavropoula Tjoumakaris, Victor Romo, Robert H. Rosenwasswer, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: The radial approach has been gaining more widespread use by neurointerventionalists fueled by data from the cardiology literature showing better safety and overall reduced morbidity.

OBJECTIVE: To present our institution's experience with the radial approach for neuroendovascular interventions in 614 consecutive patients who underwent a cumulative of 760 procedures.

METHODS: A retrospective analysis was performed and identified neuroendovascular procedures performed via the upper extremity vasculature access site.

RESULTS: Amongst 760 procedures, 34.2% (260) were therapeutic, and 65.7% (500) were nontherapeutic angiograms. Access sites were 71.5% (544) via a conventional radial artery, 27.8% (211) via a distal radial artery, 0.5% …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Neural Regions Underlying Object And Action Naming: Complementary Evidence From Acute Stroke And Primary Progressive Aphasia, Bonnie L. Breining, Andreia V. Feria, Brian Caffo, Erin L. Meier, Shannon M. Sheppard, Rajani Sebastian, Donna C. Tippett, Argye E. Hillis

Communication Sciences and Disorders Faculty Articles and Research

Background: Naming impairment is commonly noted in individuals with aphasia. However, object naming receives more attention than action naming. Furthermore, most studies include participants with aphasia due to only one aetiology, commonly stroke. We developed a new assessment, the Hopkins Action Naming Assessment (HANA), to evaluate action naming impairments.

Methods >& Procedures: Participants (N = 138 PPA, N = 37 acute stroke) completed the BNT and HANA. Behavioural performance was compared. A subset of participants (N = 31 PPA, N = 37 acute stroke) provided neuroimaging data. The whole brain was automatically segmented into regions of interest (ROIs). …

Cerebral Venous Thrombosis Associated With Covid-19 Infection: An Observational, Multicenter Study, Sajid Hameed, Mohammad Wasay, Bashir A. Soomro, Ossama Mansour, Foad Abd-Allah, Tianming Tu, Raja Farhat, Naila Shahbaz, Husnain Hashim, Wasim Alamgir

Section of Neurology

Background and purpose: Coronavirus disease 2019 (CO-VID-19) has an increased propensity for systemic hypercoagulability and thromboembolism. An association with cerebrovascular diseases, especially cerebral venous thrombosis (CVT), has been reported among these patients. The objective of the present study was to identify risk factors for CVT as well as its presentation and outcome in COVID-19 patients.
Methods: This is a multicenter and multinational observational study. Ten centers in 4 countries (Pakistan, Egypt, Singapore, and the United Arab Emirates) participated in this study. The study included patients (aged >18 years) with symptomatic CVT and recent COVID-19 infection.
Results: Twenty patients (70% men) …

Automated Analysis Of Risk Factors For Postictal Generalized Eeg Suppression, Xiuhe Zhao, Laura Vilella, Liang Zhu, M R Sandhya Rani, Johnson P Hampson, Jaison Hampson, Norma J Hupp, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Luke Allen, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo, Nuria Lacuey

Department of Neurology Faculty Papers

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We …

Rule Out Screening For Undiagnosed Dementia And Alzheimer’S Disease Using An Ehr Based Machine Learning Solution, Branum Stephan, David A. Julovich, Dustin Bracy, Jeff Nguyen

SMU Data Science Review

Abstract. Current detection methods for Dementia and Alzheimer’s disease include cerebral spinal fluid (CSF) markers and/or the use of positron emission tomography (PET) imaging, both being high-cost, highly invasive testing methods. The need for low-cost, minimally invasive methods to prescreen individuals for cognitive impairment has been a challenge for many years. Today’s costs associated with an annual screen for all adults 65 and above using current methods (CSF, PET) reach well beyond trillions of dollars per year. Motivated by the limited accessibly and high costs, an alternative tool presented within this paper demonstrates an effective rule out screening for Dementia …

The Effect Of Polyunsaturated And Saturated Fatty Acids On Seizure Presence And Severity In A Cohort Of Subjects In An Epilepsy Monitoring Unit, Jana K. Wells

Theses & Dissertations

Ketogenic diet therapies (KDTs) have been used to treat epilepsy for nearly 100 years. Although effective, restrictive diet patterns and unknown impacts on long-term health outcomes often prevent their use as first-line therapy. To date, a distinct mechanism of action for KDTs has not been determined and evidence suggests fatty acids (FAs) may play a role in eliciting anti-seizure effects. This dissertation aimed to provide insights into the effect of polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) on seizure presence and severity through the analysis of dietary intake in a cohort of patients admitted to an epilepsy monitoring …