Nervous System Diseases Commons^™

Fatty Acid Therapy And Implications For Spinal Cord Injury Treatment: A Literature Review, Philippe J. Dentino

MEDI 9331 Scholarly Activities Clinical Years

Introduction: Spinal Cord Injuries (SCI) are catastrophic injury to spinal neurons that cause a tremendous socioeconomic and public health burden on individuals globally. The role of fatty acids in treatment of SCI is not well understood and poorly standardized across treatment provision. This review seeks to explore the role of fatty acids in neurorecovery and propose emerging themes in SCI treatment with fatty acids.

Methods: A PICO was designed and online databases were searched for relevant articles. A total of 55 studies were deemed appropriate for the review and summarized into thematic elements including ) Cellular Transport 2) Neuroprotection 3) …

Vulnerability And Adaptation Of Neocortical Neuron Subtypes In Models Of Concussive Traumatic Brain Injury And Multiple Sclerosis, Alan C. Harris Jr.

Theses and Dissertations

The pathognomonic sequela of traumatic brain injury is traumatic axonal injury, the

burden of which correlates with less favorable outcomes. Elucidation of

the intrinsic variables that endow delineated neuronal subgroups and microanatomical domains with outsized vulnerability to injury represents a critical domain of inquiry toward the successful translation of disease-modifying therapeutics. To this end, we studied mild traumatic brain injury (mTBI) within the central fluid percussion model to examine the consequences of mTBI on the morphology and functional integrity of the axon initial segment (AIS) and the relative contributions to network homeostasis mediated by distinct populations of inhibitory interneurons. One …

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Seizures, Vitamin D Deficiency, And Severe Hypophosphatemia: The Unique Presentation Of A Sars-Cov-2 Case

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV), which is related to the SARS-CoV-1 virus that caused the 2002-2004 SARS outbreak. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). It has been associated with electrolyte abnormalities. In this report, we discuss the case of a SARS-CoV-2-infected person presenting with recurrent seizure episodes resulting from hypophosphatemia. A 52-year-old male patient with questionable prior seizure history presented to the emergency department (ED) twice within eight days with recurring seizure episodes. While the physical examination at the first presentation was significant for …

Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Jane H Brice

Faculty, Staff and Student Publications

OBJECTIVE: Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.

METHODS: This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based …

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Defining The Impact Of Clinically Modeled Hindlimb Stretching, Exercise, & Inactivity On Functional Recovery After Spinal Cord Injury., Greta Cesarz

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life altering event that affects approximately 282,000 Americans. The most obvious side effect of SCI is paralysis due to damage to the spinal cord that disrupts ascending and descending pathways as well as central pattern generating circuitry. In addition to paralysis, patients suffer from other debilitating side effects including altered cardiovascular function, autonomic dysreflexia, neuropathic pain, spasticity, and contractures. In contrast to humans, rodents display spontaneous locomotor recovery following incomplete SCI due to in-cage activity/training. Previously, our laboratory has studied the effect of lack of in-cage training by utilizing custom designed rodent wheelchairs. …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Exploring Risk Factors Of Alzheimer’S Disease Using Mouse Models, Xian Han

Theses and Dissertations (ETD)

Mouse models of Alzheimer’s disease (AD) that accurately recapitulate pathology and molecular changes are crucial for understanding disease mechanisms and subsequent therapeutic development. We examined five commonly used mouse models of AD (5xFAD, J20, APPNL-F, APPNL-G-F, Tau P301S) and compared their whole- and phosphoproteomes with human AD (the integration of three published datasets) to study whether they can mimic protein/RNA expression discrepancies, molecular changes, and enriched pathways found in human AD cases. The mouse models especially 5xFAD and APPNL-G-F show proteomic signatures similar to human AD but lack human-specific AD progressions, such as dysregulation of synaptic pathways and networks. Integration …

The Uncertainty And Psychological Health Of Family Caregivers Of Patients With Delirium In Intensive Care Units, Amal Shokri Haji Assa

Theses and Dissertations (ETD)

Each year, more than 5 million patients are admitted to an intensive care unit (ICU) in the United States, and up to 80 % of these patients develop delirium. Delirium is a common indicator of acute brain dysfunction in the ICU and a predictor of mortality, longer ICU/hospital stay, and long-term cognitive impairment. Family caregivers are a valuable resource in preventing, detecting, and managing delirium in the ICU. However, witnessing delirium episodes can generate adverse psychological symptoms in family caregivers that may compromise their health and well-being. Research in this area has demonstrated a gap in the literature regarding how …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Thanila A Macedo

Faculty, Staff and Student Publications

No abstract provided.

Massive Macroglossia, A Rare Side Effect Of Covid-19: Clinical, Histologic, And Genomic Findings In Covid-19-Positive Versus Covid-19-Negative Patients, Victoria A Mañón, David Chubb, Laura S Farach, Rachid Karam, Mary C Farach-Carson, Karan Saluja, Mark Wong, James C Melville

Faculty, Staff and Student Publications

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia.

METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples.

RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, …

Identifying Voice-Based Digital Biomarkers Of Parkinson's Disease, Rachelle Beshay, Madison Gill, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Introduction: Parkinson's disease is a disorder in the central nervous system that causes tremors, abnormal gait and balance, and muscle rigidity due to loss of function in parts of the brain. Traditionally, Parkinson's is identified by the physical symptoms seen in a patient's gait and motor skills, but irregular speech patterns (hypokinetic dysarthria) is one of the first symptoms to be derived from the disease. Objective: The goal of this ongoing study is to use Mel Frequency Centrum Coefficients (MFCC), to diagnose Parkinson's in the early stages by identifying hypokinetic dysarthria. MFCC's process speech recognition patterns and produce …

Effects Of Transcranial Direct Current Stimulation On Adults With Post-Acute Covid-19 Syndrome, Isaac Min, Aaron Schurger

Student Scholar Symposium Abstracts and Posters

Since its detection in December 2019, coronavirus disease 2019 (COVID-19), the viral disease caused by the SARS-CoV-2 novel coronavirus, has had prominent effects on human health and mortality. Studies in previous infections of SARS-CoV and MERS-CoV have found evidence of persistent symptoms in recovered patients, such as lethargy and shortness of breath. Similar residual symptoms have also been seen in recovered COVID-19 patients beyond four weeks of the initial onset of symptoms — collectively termed post-acute COVID-19 syndrome (PACS). These symptoms include deficits in working memory. Preliminary studies done in the United States and Europe have shown a significant portion …

Understanding Parkinson’S Disease Through Gait Initiation And Center Of Pressure, Mira Ananthanarayanan, Kiara Salceda, Michael Shiraishi, Rahul Soangra

Student Scholar Symposium Abstracts and Posters

Parkinson's disease is a neurological disorder that causes tremors and freezing of gait in diagnosed patients. Freezing of gait can be difficult to identify and intervene without laboratory based instruments data collection. Force plates have been proven to show viable results in identifying gait events such as heel contact and toe off. The complete gait cycle consists of a right-heel strike, right heel-to-toe shift, simultaneous right-toe off/left heel strike, left heel-to-toe shift, and a simultaneous left-toe off/right heel strike. This study will investigate center of pressure trajectories when initiating gait between healthy and Parkinson's participants. It is predicted that the …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

Living With Multiple Sclerosis As A Former Marathon Runner: Impact Of Attitude And Past Behaviour On Self-Care Maintenance And Perseverance, Michael Stephanou

Patient Experience Journal

As healthcare professionals, we have a duty to promote the wellbeing of individuals living with chronic diseases and this could be accomplished through the establishment of self-care strategies that are both collaborative and self-directed. Insight into the complex behaviours and backgrounds of individuals who show initiative in dealing with chronic disease could help achieve this by revealing drivers of health-seeking and engaging behaviours. Therefore, by deducing the complex interactions between attitude, past experiences and disease outlook, broader patient welfare could be championed through the implementation of targeted interventions which promote self-care in chronic disease. This article aims to explore these …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.