Neurology 2020 Projects

Project Title: Management and Outcomes of Cerebral Vasculopathy in Children with Sickle Cell Disease: a Retrospective Registry

Faculty Mentor: Philipp Aldana

Student: Emily Beydler

Research Project Description:

Sickle Cell Disease (SCD) causes vasculopathies in several organs, including the central nervous system. This may result in arterial stenosis (which may result in ischemic stroke) or dilatation (which may result in aneurysm or intracranial hemorrhage). These cerebrovascular pathologies affect up to 63% of patients with sickle cell disease, and are a serious cause of morbidity and mortality.

Conventional treatment consists of monthly blood transfusions to reduce the hemoglobin S content in the blood of high risk pediatric patients. Chronic transfusion therapy has been shown to reduce risk of ischemic stroke, but it has also been associated with various complications such as iron overload and compliance issues. Additionally, transfusions do not reduce the risk of hemorrhagic stroke.

Children with SCD with additional significant vasculopathy, such as in Moyamoya Syndrome (MMS), are at an even greater risk for stroke. MMS is characterized by progressive stenosis of the arteries of the Circle of Willis. This causes compensatory development of a network of capillaries for collateral blood flow. This network can fail to supply the necessary blood and oxygen to the brain, thus children with SCD with MMS are 5 times more likely to experience recurrent cerebrovascular events compared to patients with SCD without MMS.

Cerebral revascularization surgery (CRS) has been shown to decrease the risk of stroke in patients with primary MMS, but its efficacy in patients with MMS secondary to SCD is unknown.

Project Title: Diabetes Driven Systems of Care for Stroke Prevention

Faculty Mentor: Alexis Simpkins 

Student: Hannah Branstetter 

Research Project Description:

Acute ischemic stroke patients often present with hyperglycemia on admission and this is linked with worse outcomes thought to be due to a pro-oxidative and procoagulant state (Baird et al. 2003). Furthermore it has been shown that chronic hyperglycemia is an independent predictor of poor outcome in acute ischemic stroke.(Luitse et al. 2017). Wang et al confirmed that acute ischemic stroke patients experienced less functional independence with higher hemoglobin A1c levels than did those who had lower hemoglobin A1c levels on admission, even after other risk factors were adjusted for. (Wang et al. 2019) These studies support the idea that hemoglobin A1c is an important marker not only for predicting outcomes, but for targeting when it comes to secondary stroke prevention. One of the best opportunities to help patients assess and control risk factors such as hemoglobin A1c is during hospitalization following acute ischemic stroke. It is known that people with diabetes are at higher risk for stroke, and several studies have been published looking at the best antidiabetic agents to employ to lower this risk. Lim et al performed a metanalysis looking at the efficacy of conventional versus intensive glucose lowering treatment post-stroke, and found that overall the evidence for intensive glycemic control post stroke is limited however that pioglitazone is likely to reduce the occurrence of cerebrovascular disease. (Lim et al. 2019). This was showcased specifically in the IRIS trial in which 3876 patients with insulin resistance and recent stroke or TIA were studied and pioglitazone was found to reduce the risk of stroke and cardiovascular disease compared to placebo. However, patients who arrive with acute ischemic stroke at our institution are not routinely transitioned to pioglitazone, not even after receiving an endocrinology consult. It is also unknown whether these patients subsequently follow up with a neurologist, endocrinologist, or primary care provider after their hospital stay and whether or not the issue of their hemoglobin A1c is readdressed or their diabetic medication regimen adjusted. There is currently no standardized way to manage hyperglycemia and uncontrolled diabetes in the stroke population.
In addition to management with medication, diabetes education also plays an important role in glycemic control. A joint position paper of the American Diabetes Association, American Association of Diabetes Educators, and Academy of Nutrition and Dietetics (Powers, et al 2017) asserts that diabetes self-management education and support can lower hemoglobin A1C up to 1%, prevent the progression of diabetes-related complications, mitigate distress and depression among patients, and empower patients to embrace lifestyle changes. Although diabetes self-management education historically has been conducted in a formal classroom-style setting, the format and setting are becoming increasingly flexible and accessible (Powers 2017). Of primary importance are communication, collaboration, and a patient-centered approach. The position paper identifies diabetes-related complications and diagnosis of new conditions as “critical indicators for diabetes education” that require “immediate attention” (Powers 2017). Thus, the occurrence of a stroke in a patient with diabetes would imply a crucial need for self-management education. While it is generally agreed that the outpatient setting is the ideal venue for comprehensive, ongoing diabetes training and support, inpatient diabetes education lays the foundation for effective continuity of care. A large academic teaching hospital recently published results from their initiative to integrate inpatient diabetes education into the interprofessional care model (Hardee 2015). Given that patients in the hospital are typically not feeling well and under a great deal of stress, a brief, targeted, “survival-skills” approach was used, with promising results. Every patient was given a one-page handout on the basics of diabetes, and the messages were reinforced by bedside nurses, registered dietitian nutritionists, certified diabetes educators, and pharmacists (when indicated). The new model did not increase length of stay or 30-day readmission rate, and it yielded significant costs savings of over $400,000 (Hardee 2015).Another important consideration in diabetics who sustain acute ischemic stroke are body mass index and obesity. It is widely known that being overweight contributes to the development of diabetes mellitus through impaired glucose tolerance and insulin resistance, and this in turn contributes to the increased risk for acute ischemic stroke. There is an entity known as the obesity paradox in which adults who are lean have worse outcomes than overweight or obese adults, specifically when looking at cardiovascular health. This finding has been most applicable to Class I obesity (BMI 30-34.9), however several caveats remain as body mass index is only a rough guide for body fat composition and patients with a similar BMI may have differing degrees of adiposity (Elagizi et al. 2018). However, obesity remains an important risk factor in the development of ischemic stroke, heart disease, and type II diabetes mellitus and while recovery profiles have been shown to be different for lean versus obese patients, obese patients are more likely to develop cerebrovascular and cardiovascular illnesses to begin with. According to Dearborn et al, current guidelines regarding helping patients manage obesity are uncertain and tend to emphasize for screening of readiness to lose weight and then providing support to achieve that goal, and first line therapy is counselling on lifestyle. Her team analyzed changes in weight after recent ischemic stroke or TIA and found that only 25% of patients were able to lose a clinically significant amount of weight in 2 years, and 19% of patients actually gained weight. (Dearborn et al. 2019) One reason for this postulated by the writers was that there is a lack of prioritization of weight management by physicians in office visits and furthermore, lack of training amongst physicians on how to address these issues. We plan to evaluate post stroke care as it applies to the specific risk factors of diabetes and obesity by focusing on medication management and lifestyle/dietary changes after a patient with acute ischemic stroke is discharged from the hospital. Is the patient following up with a vascular neurologist, endocrinologist, or primary care physician? Did dietary counselling or an endocrinology consult occur while in the hospital, and were medications changed? While there are studies that have focused on post discharge care and secondary stroke prevention in the context of a clinical trial, there are few studies specifically addressing population-based outcomes with current therapies available for glucose control and in the context more recent insurance payer models. The American Heart Association secondary stroke prevention guidelines do not provide any recommendations of systems of care that should be standard for optimizing glucose control in patients that have had an ischemic stroke. In our current model, patients admitted to the stroke service with a hemoglobin A1c > 8% have both an endocrinology consultation and consultation with a diabetes educator prior to the patient being discharged from the hospital. To date, the effectiveness of this model on patient care has not be assessed.

  1. Baird, T. A., M. W. Parsons, T. Phan, T. Phanh, K. S. Butcher, P. M. Desmond, B. M. Tress, P. G. Colman, B. R. Chambers & S. M. Davis (2003) Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke, 34, 2208-14.
  2. Dearborn, J. L., C. M. Viscoli, L. H. Young, M. J. Gorman, K. L. Furie & W. N. Kernan (2019) Achievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity. Stroke, 50, 713-717.
  3. Elagizi, A., S. Kachur, C. J. Lavie, S. Carbone, A. Pandey, F. B. Ortega & R. V. Milani (2018) An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases. Prog Cardiovasc Dis, 61, 142- 150.
  4. Hardee S. G., K. C. Osborne, N. Njuguna, et al. (2015) Interdisciplinary Diabetes Care: A New Model for Inpatient Diabetes Education. Diabetes Spectr, 28, 276-282.
  5. Lim, S., T. J. Oh, J. Dawson & N. Sattar (2019) Diabetes drugs and stroke risk: Intensive versus conventional glucose-lowering strategies, and implications of recent cardiovascular outcome trials.
  6. Diabetes Obes Metab. Luitse, M. J., B. K. Velthuis, L. J. Kappelle, Y. van der Graaf, G. J. Biessels & D. S. Group (2017) Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke. Int J Stroke, 12, 180- 186.
  7. Powers, M. A., J. Bardsely, M. Cypress, et al. (2017) Diabetes Self-management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, ad the Academy of Nutrition and Dietetics. Diabetes Educ, 43, 40-53.
  8. Wang, H., Y. Cheng, S. Chen, X. Li, Z. Zhu & W. Zhang (2019) Impact of Elevated Hemoglobin A1c Levels on Functional Outcome in Patients with Acute Ischemic Stroke. J Stroke Cerebrovasc Dis, 28, 470-476

Project Title: Utilizing Dual Energy CT Imaging to Evaluate for Hemorrhage and Blood Brain Barrier Disruption in Stroke Patients

Faculty Mentor: Alexis Simpkins 

Student: Tri Huynh and Niran Vijayaraghavan 

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.

Project Title: Stroke Survivors Perception of Their Ischemic Stroke and Transient Ischemic Attack and Navigation of the Healthcare System

Faculty Mentor: Alexis Simpkins 

Student: Rondalyn Dickens 

Research Project Description:

There are multiple health behavior theories where risk perception is a central focus. They include the Health Belief Model (Rosenstock, 1974), Protection Motivation Theory (Rogers, 1975), Extended Parallel Process Model (Witte, 1992), the Theory of Reasoned Action (Ajzen & Fishbein, 1980) and others. Overall, these theories propose that preventative health behaviors are associated with higher risk perception. Risk perception has been conceptually defined as an individual’s belief about his or her chances of becoming ill (Hay et al., 2007), people’s perceptions about their susceptibility to various ailments and diseases (Rimal, 2001), and the likelihood and severity of losses or negative outcomes (van der Plight, 1996).

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 (Kulshreshtha et al., 2013; Mozaffarian et al., 2016). But, most of the population lacks awareness of their personal stroke risk which therefore changes their risk reduction behaviors. Recently, there has been a call for the development of theory-based interventions for the reduction of stroke through behavior change (Boden-Albala & Quarles, 2013). Thus, there have been new studies looking at the perception of an individual’s risk of stroke to create prevention models based on these perceptions. Moreover, many of these studies primarily look at healthy individuals and occasionally stroke survivors. On the other hand, there does not seem to be a focus on an individual’s perception of their illness after a stroke and what they believe will help aid their return to baseline. For risk management and communication to be successful between the provider and patient, the patient’s perceptions must first be assessed.

  1. Ajzen, I., & Fishbein, M. (1980). Understanding attitudes and predicting behavior. Englewood Cliffs, NJ: Prentice Hall.
  2. Aycock, D. M., & Clark, P. C. (2016). Incongruence between perceived long-term risk and actual risk of stroke in rural African Americans. Journal of Neuroscience Nursing, 48, 35-41.
  3. Aycock, D. M., Clark, P. C., & Araya, S. (2019). Measurement and Outcomes of the Perceived Risk of Stroke: A Review. Western Journal of Nursing Research, 41(1), 134–154.
  4. Aycock, D. M., Kirkendoll, K. D., Coleman, K. C., Clark, P. C., Albright, K., & Alexandrov, A. W. (2015). Family history of stroke among African Americans and its association with risk factors, knowledge, perceptions, and exercise. Journal of Cardiovascular Nursing, 30, E1-E6.
  5. Boden-Albala, B., Carman, H., Moran, M., Doyle, M., & Paik, M. C. (2011). Perception of recurrent stroke risk among Black, White and Hispanic ischemic stroke and transient ischemic attack survivors: The SWIFT study. Neuroepidemiology, 37, 83-87.
  6. Boden-Albala, B., & Quarles, L. (2013). Education strategies for stroke prevention. Stroke, 44(6, Suppl. 1), S48-S51.
  7. Kulshreshtha, A., Vaccarino, V., Judd, S., Howard, V., McClellan, W., Muntner, P., . . . Cushman, M. (2013). Life’s simple 7 and risk of incident stroke: The Reasons for Geographic and Racial Differences in Stroke Study. Stroke, 44, 1909-1914
  8. Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., . . . Turner, M. B. (2016). Executive summary: Heart disease and stroke statistics—2016 update. A report from the American Heart Association. Circulation, 133, 447-454.
  9. Rogers, R. (1975). A protection motivation theory of fear appeals and attitude change. Journal of Psychology, 91, 93-114.
  10. Rosenstock, I. M. (1974). Historical Origins of the Health Belief Model. Health Education Monographs, 2, 328-335.
  11. Witte, K. (1992). Putting the fear back into fear appeals: The extended parallel process model. Communications Monographs, 59, 329-349.

Project Title: A New Technique for Implanting Deep Brain Stimulation Leads: “Macro off the Micro”

Faculty Mentor: Michael Okun

Student: Sina Aghili-Mehrizi 

Research Project Description:

Deep brain stimulation (DBS) is an FDA approved treatment for select neurologic disorders including Parkinson’s disease, essential tremor, obsessive-compulsive disorders, and dystonia. It involves implanting an electrode into a precisely targeted area of the brain based on a patient’s specific disease, symptoms and neuroanatomy. Specific brain areas can be electrically modulated to improve symptoms (Miocinovic et al. 2013). Numerous studies have shown significant improvements in both clinical outcomes and quality of life in patients receiving DBS (Deep-Brain Stimulation for Parkinson’s Disease Study Group et al. 2001) (Weaver et al. 2009).

Since its discovery, DBS techniques have steadily improved (Benabid et al. 1993). Despite these improvements, there remains a lack of consensus for pre-surgical planning, intraoperative techniques and post-operative quality control. Thus, DBS outcomes in the community remain suboptimal given the multitude of variables in a patient experience (Okun et al. 2005). Studies have shown the critical role for precise lead placement on outcome (Okun et al. 2005). The goal of the present study is to evaluate a novel technique to optimize microelectrode recording (MER), confirmatory macrostimulation and lead placement. We will analyze impact on outcomes and operative time.

  1. Benabid, A. L., P. Pollak, E. Seigneuret, D. Hoffmann, E. Gay, and J. Perret. 1993. “Chronic VIM Thalamic Stimulation in Parkinson’s Disease, Essential Tremor and Extra-Pyramidal Dyskinesias.” Acta Neurochirurgica. Supplementum 58: 39–44.
  2. Deep-Brain Stimulation for Parkinson’s Disease Study Group, J. A. Obeso, C. W. Olanow, M. C. Rodriguez-Oroz, P. Krack, R. Kumar, and A. E. Lang. 2001. “Deep-Brain Stimulation of the Subthalamic Nucleus or the Pars Interna of the Globus Pallidus in Parkinson’s Disease.” The New England Journal of Medicine 345 (13): 956–63.
  3. Miocinovic, Svjetlana, Suvarchala Somayajula, Shilpa Chitnis, and Jerrold L. Vitek. 2013. “History, Applications, and Mechanisms of Deep Brain Stimulation.” JAMA Neurology 70 (2): 163–71.
  4. Okun, Michael S., Michele Tagliati, Michael Pourfar, Hubert H. Fernandez, Ramon L. Rodriguez, Ron L. Alterman, and Kelly D. Foote. 2005. “Management of Referred Deep Brain Stimulation Failures: A Retrospective Analysis From 2 Movement Disorders Centers.” Archives of Neurology 62 (8): 1250.
  5. Weaver, Frances M., Kenneth Follett, Matthew Stern, Kwan Hur, Crystal Harris, William J. Marks, Johannes Rothlind, et al. 2009. “Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients with Advanced Parkinson Disease: A Randomized Controlled Trial.” JAMA 301 (1): 63–73.

Project Title: Global and Focal Attention with Monocular Viewing / Painting Laterality and its Influence on Valence

Faculty Mentor: Kenneth Heilman

Student: Karly Landvay 

Research Project Description:

Global and Focal Attention with Monocular Viewing
This project is a continuation of a project that David Drunker MS2 conducted in 2019.
In a recent study, it was discovered that when healthy participants attempt to bisect vertical lines, there is an upward bias (1). In addition, when lines were eccentrically placed on a paper (ex: toward the top or bottom) but the middle of the paper was at eye level, healthy young participants were distracted by the page. Their attempted bisections deviated toward the middle of the page and this deviation was greater when the lines were placed toward the top of the page than when placed toward the bottom of the page (1).
Prior lesions studies have revealed that the injury to the ventral visual stream induces upward vertical neglect and lesions to the dorsal stream produce downward vertical neglect (2,3). It is, therefore, possible that the upward deviation seen with vertical line bisections when the line is placed in the middle of the page is related to greater activation of the ventral “What” allocentric visual stream. When the sheets of paper on which the lines on the page are displaced toward the bottom, participants are distracted by the space between the top of the line and the upper margin of the paper and therefore deviate further upward. In contrast, when the lines on the sheets of paper are displaced toward the top of the page, the participants appear be distracted toward the bottom of the line.
In addition, healthy participants are more distracted when the lines are placed higher than when the lines are placed lower. One possible explanation of this asymmetry (greater downward than upward distractibility) may be related to the dorsal “What” stream being more responsible for the allocation of global attention than the ventral “What” stream, as well as being responsible for allocating downward attention. Since the right hemisphere appears to be dominant for mediating global attention and allocating left focal attention, it is possible that asymmetrical activation of the right versus left hemisphere could alter distractibility (greater with right hemisphere activation).

Painting Laterality and its Influence on Valence
The valence hypothesis describes emotional hemispherical asymmetry in which the left hemisphere mediates positive emotions (positive valence) and the right hemisphere mediates negative emotions (negative valence). There have been numerous studies that support the valence hypothesis (1,2, 3). Additionally, it is known that a wide range of human emotion can be evoked by observing a painting or picture. Therefore, it is possible that laterality in paintings may influence visual works of art and the way in which they are perceived by humans, explaining how subtle spatial differences may alter human perception.
Studies have shown that in portraiture, subjects of paintings are more likely to show the left side of their face (4, 5) and that the left side of the face is often more expressive than the right side (5). While it is not agreed on why this happens (5), it is clear that laterality is an important influence on art. Hence, the way in which the main subject of a painting is positioned, facing, or interacting with may contribute to the overall ambiance of the painting. Indeed, one study showed that paintings of Jesus’ crucifixion, an emotionally negative event, were more likely to show the left side of Jesus’s face than found in other portraits (4). Additionally, a follow-up study showed that the left side of the face of Jesus is less commonly depicted in portraits of the Resurrection, an emotionally positive event, than the Crucifixion, an emotionally negative event (6). Therefore, the aim of this study is to further analyze potential correlations between the valence hypothesis and works of art. I propose that painting valence will correlate with subject position relating to the viewer; paintings that contain a main character positioned, interacting, or facing to the viewer’s left side will be viewed more by the viewer’s right hemisphere, and as a result, will tend to have more negative valence than painting with subjects positioned, interacting, or facing to the viewer’s right side.

Global and Focal Attention with Monocular Viewing

  1. Rodriguez Jr, J. A., Lamb, D. G., Salazar, L., Correa, L. N., Mosquera, D. M., Schwartz, Z. J., … & Heilman, K. M. (2018). Background distraction during vertical solid and character line bisections. Journal of clinical and experimental neuropsychology, 40(9), 887-894.
  2. Rapcsak, S. Z., Cimino, C. R., & Heilman, K. M. (1988). Altitudinal neglect. Neurology, 38(2), 277-277.
  3. SHELTON, P. A., BOWERS, D., & HEILMAN, K. M. (1990). Peripersonal and vertical neglect. Brain, 113(1), 191-205.
  4. Roth, H. L., Lora, A. N., & Heilman, K. M. (2002). Effects of monocular viewing and eye dominance on spatial attention. Brain, 125(9), 2023-2035.
  5. Heilman, K. M., Valenstein, E., & Watson, R. T. (1984, June). Neglect and related disorders. In Seminars in neurology (Vol. 4, No. 02, pp. 209-219). © 1984 by Thieme Medical Publishers, Inc..

Painting Laterality and its Influence on Valence

  1. Davidson, R. J. (1992). Emotion and affective style: Hemispheric substrates.
  2. Adolphs, R., Jansari, A., & Tranel, D. (2001). Hemispheric perception of emotional valence from facial expressions. Neuropsychology, 15(4), 516–524.
  3. Silberman, E. K., & Weingartner, H. (1986). Hemispheric lateralization of functions related to emotion. Brain and cognition, 5(3), 322-353.
  4. Acosta, L. M. Y., Williamson, J. B., & Heilman, K. M. (2013). Which cheek did Jesus turn?. Religion, Brain & Behavior, 3(3), 210-218.
  5. Powell, W. R., & Schirillo, J. A. (2009). Asymmetrical facial expressions in portraits and hemispheric laterality: A literature review. Laterality, 14(6), 545-572.
  6. Acosta, L. M. Y., Williamson, J. B., & Heilman, K. M. (2015). Which Cheek did the Resurrected Jesus Turn?. Journal of religion and health, 54(3), 1091-1098.
  7. Richardson, Joel. “Random Art Gallery.” Random Classic Art Gallery – Randomize,
  8. Duerksen, K. N., Friedrich, T. E., & Elias, L. J. (2016). Did Buddha turn the other cheek too? A comparison of posing biases between Jesus and Buddha. Laterality: Asymmetries of Body, Brain and Cognition, 21(4-6), 633-642.