Neurology

Novel Insights in the Pathophysiology of A-Synuclein Dysregulation of Dopamine Neurons

Faculty Mentor’s Name: Dr. Habibeh Khoshbouei
Email: Habibeh@ufl.edu 
Phone Number: (352) 273-8115 
Project Category: Clinical
International Component or Travel: No

Research Project Description:
Pathophysiological damages and loss of function of dopamine neurons precedes their demise and contributes to the early phases of Parkinson’s disease. The presence of aberrant intercellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed multiple complementary approaches in molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein levels alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission prior to neuronal demise. These studies demonstrate that α-synuclein dysregulation of D2 receptor autoinhibition contributes to the vulnerability of dopaminergic neurons, and that modulation thereof can ameliorate the resulting pathophysiology. These novel findings provide mechanistic insights in the insidious loss of dopaminergic function and neurons that characterize Parkinson’s disease progression with significant therapeutic implications.

Emergency Management of Acute Neurological Emergencies in a Live High-Fidelity Multidisciplinary Simulation Setting

Faculty Mentor’s Name: Dr. Marc-Alain Babi
Email: m.babi@ufl.edu
Phone Number: (802) 777-2880
Project Category: CQI
International Component or Travel: No

Research Project Description:
This study is IRB APPROVED . Protocol: IRB202000255

The aim of this study is to describe the development of a high-fidelity multidisciplinary simulation program that uses evidence-based medicine and guidelines, focused on the management of acute neurological emergencies in the NeuroICU (live simulation). In this study, we will review the technical, cognitive and effective teamwork skillsets in a controlled multidisciplinary simulation, identify risk factors for non-adherence to treatment guidelines, and identify threats, misses and near-misses.

Management of acute neurological emergencies is often a stressful and emergent situation that requires proper medical knowledge, training, and the ability to quickly function and adapt in a multidisciplinary setting.

The purpose of this study is to develop a high-fidelity multidisciplinary simulation program that uses evidence-based medicine and guidelines, focused on the management of acute neurological emergencies in the Neurology ICU (live simulation). In this study, we will review the technical, cognitive and effective teamwork skill sets in a controlled multidisciplinary simulation, identify risk factors for non-adherence to treatment guidelines, and identify threats, misses and near-misses. Simulation-training programs are an effective method of education for emergency-medical care teams, with the aim to reduce adverse-events related to these non-technical skills, thus improving patient safety. The participants in this study are house staff trainees (residents, fellows), advanced practice providers (APPs-nurse practitioners, physician assistants), and other clinical team members (ie: nursing staff, respiratory therapist) who will be running a mock educational clinical scenario (an acute neurological emergency) in a controlled clinical setting. This involves a mannequin (simulator). The process involves: a developed clinical vignette, a mock paper-based chart containing a clinical (educational) scenario of a patient’s history and physical exam notes, progress notes, nursing kardex, medication orders, physician orders, vital signs record, and simulation mannequin. The simulation leader will be adjusting the mannequin vitals and medical parameters based on the written educational/clinical script and as the clinical scenarios evolve.
During the process, the simulation leader will be reviewing the technical, cognitive and effective teamwork skill sets as well as identify risk factors for non-adherence to treatment guidelines, as well as identify threats, misses and near-misses.
The specific aims of this study are:
1. Provide leadership training and improve communication skills for acute neurological emergencies.
2. Provide participants with experience in simulation, leadership in coordination of care, understanding self-organization principles, tools for delegation and diffusing conflict.
3. Develop situational awareness and critical thinking skills.
The scenarios are conducted in the Neurological ICU (Neurocritical care unit, Neuromedicine tower, unit 47). A room is designed to be the “simulation/education lab”, with an interactive mannequin and actors playing the roles of patients and family members. The simulation room is configured as a trauma/emergency/intensive care room where the team responds to an urgent acute neurological situation. Each team will consist of four to eight healthcare member, and each scenario will be video recorded. A briefing and debriefing will be conducted prior to and following the scenario. The simulation will start with brief introductions, overview of the exercise, and expectations. It will be emphasized that strict confidentiality and professionalism will be upheld among the participants, the simulation staff and investigators. Follow up simulation will be conducted six months and one year after the initial course to evaluate retention of knowledge and skills. The investigators will fill out the Performance Observation Tool, from TeamSTEPPS to assess the study participants for leadership and teamwork skills. Upon completion, the participants will complete a post simulation survey to assess effectiveness of the training (Teamwork Perceptions Questionnaire, from TeamSTEPPS) (See attachment). After undergoing the initial scenario, the participants will be debriefed and coached in the proper teamwork skills like closing the loop, delegation and speaking up. Following the debriefing and coaching, the participants will be provided an opportunity to practice what they just learned and train in established best practices for teamwork such as those developed by AHRQ in the TeamSTEPPS program. These sessions will be recorded and evaluated for cohesiveness of the study participants as a team in the same manner as the first scenario. Participants will be asked to participate in simulation exercises during their rotation in the NeuroICU. The evaluation tools and pre and post training surveys used in the study, will not be linked to an individual nor be used to assess competency for physician in training involved in the scenario.

Emergency Endotracheal Intubation by Non-Anesthesiologists in a Neuroscience ICU in a Large Academic University Hospital – Airway Outcomes and Complications

Faculty Mentor’s Name: Dr. Marc-Alain Babi
Email: m.babi@ufl.edu
Phone Number: (802) 777-2880
Project Category: Clinical
International Component or Travel: No

Research Project Description:
This study is IRB APPROVED. PROTOCOL: IRB202000687
There are limited outcome data regarding emergency non-operative intubation by non-anesthesiologists in intensive care units, and no data that address airway outcomes in Neuro-intensive care units when performed by non-anesthesiologists. The aim of this study is to retrospectively (observational study) evaluate the factors associated with endotracheal intubation in the NeuroICU, evaluate the complication rates and predictors of complication in this setting.
The primary aims of this study:
1. To determine the factors associated with endotracheal intubation (emergency) in a neuroscience ICU at a large single academic center by non-anesthesiologists
1a. Determine the incidence and complications in acute airway management by non-anesthesiologists in a neuroscience ICU
1b. Determine the predictors of complications in this setting compared to emergency management of airway by anesthesiologists (based on published large studies)
This study is of retrospective design. The database will be queried to identify patients who required endotracheal intubation by non-anesthesiologist in the neuroscience ICU (by CPT code 31500) by one of the non-anesthesiology providers. We will be retrospectively collecting data only on patients treated at the University of Florida, Neurosciences (Neurocritical care unit) Shands hospital. Inclusion criteria include admission to UF Health Shands Neurosciences ICU in the period between January 2017 and August 01, 2020, Age>18, admission, endotracheal intubation in the neurosciences ICU. Exclusion criteria will be: age<18 yr, pre-existing endotracheal tube or location other than the neurosciences ICU. Patients in the emergency department (ED) in whom induction/intubation was performed prior to the arrival to the Neurosciences ICU will also be excluded. The study will use previously recorded retrospective defined data points listed on the data collection page. Medico-legal documentation of emergent airway management using this system is an institutional standard of care, consistent with accepted national guidelines. The clinical information system is available at bedside workstations throughout the institution. The emergent intubation documentation is typically completed by the performing clinician (ie: housestaff/trainee/mid-level provider) and is by the supervising attending physician for review and final co-sign. The attending physician reviews the documentation, modifies it as necessary, and cosigns the note, locking it from further editing. Within each airway management record, required fields are designed with a drop-down menu without default settings. Each element is required and allows selection of one or more options and a comment section for free text if the options provided are not adequately descriptive.
ur primary outcome will be a composite variable that includes:
1. Factors associated with emergency endotracheal intubation in a neuroscience ICU at a large single academic center by non-anesthesiologists
1a. The incidence and complications in acute airway management by non-anesthesiologists in the neuroscience ICU
1b. The predictors of complications in this setting compared to emergency management of airway by anesthesiologists (the latter, based on previously published studies)

Statistical analysis will be performed in house using SPSS (R).

The Artificial Intelligence Learns Optimal Treatment Strategies for Hypotension in Surgery

Faculty Mentor’s Name: Dr. Azra Bihorac
Email: abihorac@ufl.edu
Phone Number: (352) 273-9009
Project Category: Clinical
International Component or Travel: No

Research Project Description:
Patients and physicians make essential decisions on which diagnostic and therapeutic interventions should be performed or deferred under time constraints and uncertainty regarding patients’ diagnoses and predicted response to treatment which may lead to cognitive and judgment errors. We aim to develop a deep reinforcement learning model that would provide individualized and clinically interpretable treatment decisions that could help balance blood pressure during surgery and decrease postoperative complications, and improve patient outcomes in patients undergoing surgery. Current practices in the administration of intravenous fluids and vasopressors during surgery as a treatment of hypotension are suboptimal. Reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making. We aim to develop a deep RL model that would provide individualized and clinically interpretable treatment decisions that could help balance blood pressure during surgery and decrease postoperative complications in patients undergoing surgery.

A Historical Review of Stroke Care and New Context of Stroke in 2021

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Literature Review
International Component or Travel: No

Research Project Description:
Stroke care has changed dramatically over the last 25 years since the first thrombolytic was approved for use in patients. Not only do we have new drugs available for treating acute stroke, but also now have methods for screening for reperfusion therapy by using imaging to select patients when duration of symptoms or degree of severity of ischemia is unknown with clinical history alone. With this great progress, it is a time to reflect back on the origins of stroke care from the time of Hippocrates and as far back as the Egyptian era to the 21st century.

Patient and Healthcare Givers Perceptions of Health Care After Stroke

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Clinical
International Component or Travel: No

Research Project Description:
As one of the leading causes of death and disability, stroke is primarily preventable. Maintaining low cardiovascular and vascular risk by living a healthy lifestyle can prevent most strokes, but most of the population lacks awareness of their personal stroke risk, which leads to changes in their risk reduction behaviors. Recently, there has been a call for the development of theory-based interventions for the reduction of stroke through behavior. Studies to evaluation patient’s and health care givers perception of an individual’s risk of stroke is an important part of stroke care. Current studies, mostly have looked at healthy individuals and, occasionally, stroke survivors. There is a knowledge gap related to individual’s and healthcare givers perception of their illness after a stroke and what they believe will help aid their return to baseline. For optimal secondary stroke prevention to be successful between the provider and patient, the patient’s perceptions must first be assessed and mutually understood. Here we will be focusing on ways of evaluating patients and caregivers perception of healthcare after stroke. Students will work on projects as part of the CREST Initiative, which is a team science and career development program for trainees with interest in stroke.

Global Stroke and Health Care Disparities

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Clinical
International Component or Travel: Yes – The data has already been collected under an approved IRB. The study involved retrospective database analysis. The students role would be with writing and literature review.

Research Project Description:
Stroke has a significant global impact. It has remained a leading cause of mortality and long-term disability in adults. Although stroke systems of care are adapted to each region, disparities in health care outcomes are prevalent world wide. In the United States, rates of hypertension and diabetes have been reported to be more prevalent in minority groups such as African Americans. It is unclear how much the prevalence of these risk factors is associated with genetic and how much may be attributed to social and economic impact. Our international collaboration with Ghanaian stroke investigators will look at differences in stroke outcomes between our stroke registries. Students will work on projects as part of the CREST Initiative, which is a team science and career development program for trainees with interest in stroke.

Stroke Imaging Biomarkers

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Clinical
International Component or Travel: No

Research Project Description:
Acute stroke treatment has evolved greatly over the past few years. Imaging is now a significant driver factor for patient selecting patients for acute treatments and driving healthcare outcomes. The goal of this project is to learn about MRI processing and analysis for stroke research and database creation. Students will work on projects as part of the CREST Initiative, which is a team science and career development program for trainees with interest in stroke.

Biomakers for Neurologic Complications of COVID-19

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Translational
International Component or Travel: No

Research Project Description:
Patients with COVID-19 are well recognized to be at risk of developing a wide range of neurologic manifestations of the disease. Patients can develop ischemic stroke, intracerebral hemorrhage, epilepsy, neuromuscular disease, and cognitive deficits. Currently, there is limited data regarding appropriate biomarkers that will allow for prediction of who will develop neurologic manifestations and prognosis. We will be conducting a collaborative project evaluating for blood biomarkers in COVID-19 patients with neurologic complications. Students will work on projects as part of the CREST Initiative, which is a team science and career development program for trainees with interest in stroke.

Computed Tomography Contrast Extravasation: A Novel Marker of Blood Brain Barrier Disruption and Reperfusion Injury in Acute Ischemic Stroke

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Translational
International Component or Travel: No

Research Project Description:
Initial management of acute stroke is guided by rapid neuroimaging to help differentiate between stroke subtypes and assess eligibility for revascularization. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two primary imaging modalities used by clinicians to guide therapy, with MRI having higher sensitivity and CT being more cost-effective and more widely available. Both imaging modalities are used to identify the presence of hyperintense intracerebral hemorrhage (ICH) for acute ischemic stroke. MRI also allows for identification of cerebrospinal fluid hyperintensities, or contrast extravasation, on post-contrast MRIs, which are referred as hyperintense acute reperfusion marker (HARM). In the setting of acute stroke, HARM is associated with the degradation of the blood brain barrier (BBB), and has been linked to increased mortality and risk for major disability, therefore it is critical that patients with comprised barriers are identified. HARM occurs after a patient has been treated with thrombolysis and occurs when there is blood brain barrier disruption and the contrast previously given prior to the patient receiving thrombolysis. Because the integrity of the blood brain barrier is compromised secondary to the stroke and reperfusion injury, contrast can leak out of the arterial compartment into the tissue and stain the tissue. While HARM is traditionally identified on MRI because of MRIs ability to differentiate between acute hemorrhage from contrast extravasation, dual-energy CT (DECT) also provides this capability. DECT has not yet been explored as an alternative for MRI HARM in acute post-revascularization management but warrants further investigation due to its easier accessibility and cost-effectiveness compared to MRI.

Factors Influencing Aging Related Alterations of Vertical Spatial Attention

Faculty Mentor’s Name: Dr. Kenneth Heilman
Email: heilman@neurology.ufl.edu
Phone Number: (352) 514-4580
Project Category: Clinical
International Component or Travel: No

Research Project Description:
The National Council on Aging stated, “Falls are the leading cause of fatal and nonfatal injuries for older people… and these falls are often caused by collisions with obstacles during walking.” (Di Fabio et al. 2005). In people with normal or corrected vision, spatial inattention may be responsible for collisions with obstacles and tripping.  When performing activities, such as walking, we have a ‘window’ of attention and are aware of the stimuli inside, but not outside this window. With aging, there are changes in the brain that may induce alterations in the spatial allocation of attention. In a preliminary study, we examined older and younger healthy participants’ allocation of spatial attention using a vertical line bisection task. Both younger and older participants had an upward bias; however, the aging participants had a significantly greater upward attentional bias (Mańkowska et al., 2018).  This aging related lower vertical inattention might be a factor in the increased frequency of accidents experienced by aging people. Learning about the behavioral and neuroanatomic factors that can influence this vertical inattention, may help with the development of successful management and treatment strategies and that is the goals of this program.  

1-Allocation of Focal Attention:When performing a variety of activities, people often have to focus their attention on specific objects in their environment, but they must most also be aware of other objects and activities in their environment (global attention). The posterior inferior parietal cortex mediates global attentional processing (Boksem et al., 2012; Volberg & Hübner, 2004) and with aging there may be a reduction in functions mediated by the parietal cortex. .  In a pilot study, with healthy participants, we examined how the allocation of focal attention alters the global attentional window by using vertical line quadrisection and bisection tasks (Falchook et al., 2013). A line quadrisection task requires a person to focus their attention toward one end of the line and thus, when allocating focal attention to a line segment particpants might be less aware of the full extent of the line.   We found that there was relatively greater deviation (attentional bias) with quadrisection than bisection, suggesting that activation of the brain networks that mediate focal allocentric attention can interrupt the function of the networks mediating global attention.  In this study (1A), we therefore want to learn if aging participants have a greater reduction in the allocation of global attention, when quadrisecting vertical lines, and if focusing on the top or bottom of an object (line) has a greater influence in altering the allocation of global spatial attention.   

2-Allocation of Global Attention-Searching: One of the tests performed to assess for unilateral spatial neglect is the cancellation test, where targets are distributed over a page and the patient is asked to cancel all the targets. Healthy aging people perform normally on this test.  We have developed a new cancellation test where before each trial begins the participant fixates on a center point on a screen and is provided with the target letter that must be touched.  The screen then displays multiple circles with different letters and one circle has the target letter.  This target letter can be displayed on the top, bottom, right or left of the screen in a variety of locations. In each trial, the target is in a different location, as are the distracting targets. Using this test we will be able to learn if there are vertical as well as as horizontal changes in search that occur with aging 

3-Distraction:   Healthy people’s allocation of attention to an entire object can also be distracted by a part of this object that are not the focus of attention. In a pilot study, we found that when asked to bisect horizontal lines, made of two physically different segments, healthy participants are distracted by the larger segment (Mosquera.et al., 2018).  In addition, when attempting to bisect just the larger segment of a compound line, participants are distracted by the entire (global) line.   We want to learn if when attending to an entire compound vertical line (made of a longer and shorter segment), distraction by the longer segment will be greater less with aging than with the younger participants, and if there is a difference when the larger segment is on top than on the bottom (e.g., will aging participants be less distracted with the distraction segment is lower?)  We also want to learn if when attending to the longer line segment in upper vs lower space, aging participants will be more distracted by the entire line.  

 4-Habituation: Attended stimuli appear to have a greater magnitude than less attended stimuli. The attentional resources allocated to stimuli that are not novel or meaningful, also decreases over time, i.e., habituation. In a pilot study with healthy participants, we found that attending to an end of a horizontal line and then immediately bisecting the line induced a bias to the attended end.  After 20 seconds of sustained allocation of attention to one end, there was a greater increase in the bias toward the attended portion (Lamb et al., 2018).   In this study, we want to learn the effects of aging on habituation when allocating attention to the top or bottom ends of vertical lines.         

Using Novel Anticoagulants to Treat Cerebral Venous Thrombosis

Faculty Mentor’s Name: Dr. Alexis Simpkins
Email: alexis.simpkins@neurology.ufl.edu
Phone Number: (352) 273-5550
Project Category: Clinical
International Component or Travel: No

Research Project Description:
Cerebral venous thrombosis (CVST) is a rare cerebrovascular disorder in which a clot forms in the veins in the brain blocking the normal flow patterns of blood and cerebral spinal fluid drainage. CVST can result in significant sequela and critical illness including, stroke, headache, cerebral edema, and even vision loss. The current treatment for CVST rapid initiation of anticoagulation. The rarity of this disorder makes conducting randomized clinical trials to identify effective and easy to use anticoagulants very difficult. The current gold standard therapy for CVST is anticoagulation with coumadin. Unlike many other medications, coumadin is more labor intense to manage for the patient and providers. There are now other oral anticoagulants that do not requiring blood level monitoring and dietary restrictions, but there is a knowledge gap regarding potential efficacy of these anticoagulants for CVST treatment. If these medications are non-inferior to coumadin, this would make treatment of CVST significantly easier for patients and potential more cost effective. This project involves participating in a multi-center study evaluating the patient outcomes in patients with CVST that were treated with a novel oral anticoagulant versus those treated with coumadin. Also, in participating in this project, students will be able to benefit from all the learning initiatives and career development opportunities within the CREST Initiative in the Stroke Division at University of Florida.

Factors Affecting Recovery and Long-term Prognosis Following Acute Motor (AMAN) and Motor-sensory Axonal Neuropathy (AMSAN) Guillain-Barre Syndrome Variants

Faculty Mentor’s Name: Dr.
Email:miguel.chuquilin@neurology.ufl.edu
Phone Number: (314) 322-6363
Project Category: Case Review
International Component or Travel: No

Research Project Description:
A retrospective chart review of patients admitted to Shands from 1990 to 2019 for AMAN and AMSAN. Prognostic factors of age, preceding illness, time from onset to admission, autonomic and bulbar dysfunction, time to maximum weakness, presence of mechanical ventilation and duration, treatment type, CSF findings, and ganglioside auto-antibodies will be correlated to MRC and GBS disability score at admission and follow-up visits (1, 2, 6, 9, 12, 24 mos).

Disclaimer: The images on this page were taken prior to the national guidelines of face coverings and social distancing.