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Focal Cerebral Arteriopathy Steroid (FOCAS)
Principal Investigators: Heather Fullerton, Mitchell Elkind, Jordan Elm
Focal cerebral arteriopathy (FCA) is a disease that causes inflammation and narrowing of blood vessels in the brain of a child. Doctors currently use steroids to treat FCA and prevent stroke, but they do not know when the best time to start steroid treatment is.
The purpose of the FOCAS trial is to compare two steroid treatment options and determine the best time to treat children who may have FCA.
Seizures and Children's Outcomes after Stroke (SCOUTS)
Principal Investigator: Christine Fox
The purpose of SCOUTS is to understand how children recover after stroke and why some children develop epilepsy. In this study, we will gather information about seizures and stroke recovery from children who took part in one of two previous childhood stroke studies: Vascular Effects of Infection in Pediatric Stroke I (VIPS I) or Vascular Effects of Infection in Pediatric Stroke II (VIPS II). We will ultimately use the knowledge gained from this study to 1) give a more accurate prognosis about epilepsy after a child has a stroke and 2) plan future research for epilepsy prevention.
The specific aims for SCOUTS are:
1. To determine the inflammatory signaling pathways activated by acute seizures using banked blood collected from children enrolled in VIPS II, validating preliminary work from the VIPS I cohort.
2. To identify changes in inflammatory signaling pathways in children who later develop epielpsy. Epilepsy outcomes will be ascertained in both cohorts. Banked blood will be utilized to determine differential expression of analytes in those who develop epilepsy compared to those who do not.
3. To use lesion-symtom mapping and lesion-network mapping to identify the brain regions and functional networks associated with post-stroke epilepsy. Machine learning techniques will be used to integrate results from these three aims.
American Heart Association Bugher Foundation Center of Excellence in Hemorrhagic Stroke Research
Project 1: Predictors of Growth, Recurrence, and High-risk Features in Pediatric Brain Arteriovenous Malformation
Principal Investigator: Helen Kim
Brain arteriovenous malformations (AVMs) are abnormal tangles of blood vessels that can rupture and bleed, sometimes causing hemorrhagic stroke.
The purpose of Project 1 is to understand how and why brain AVMs develop and rupture in pediatric patients. In this study, imaging characteristics and blood tests will be used to identify potential genetic and protein biomarkers that can explain how abnormal blood vessels grow and change over time. Understanding the mechanism of how brain AVMs develop will eventually allow doctors to better monitor brain AVMs and develop drugs to prevent them from rupturing.
Project 2: Predicting Outcomes in Pediatric Hemorrhagic Stroke with Personalized Connectomics
Principal Investigator: Pratik Mukherjee
The purpose of Project 2 is to gather information on the functional networks of pediatric patients with hemorrhagic stroke by analyzing their resting-state fMRI scans. Understanding these patients' functional networks will eventually allow us to predict the effects of hemorrhagic stroke and guide surgical planning to improve treatment outcomes and recovery.
Project 3: Epidemiology Of Pediatric Hemorrhagic Stroke And Arteriovenous Malformations In A Multicenter, International Cohort
Prinical Investigators: Christine Fox, Nomazulu Dlamini
The purpose of Project 3 is to examine the epidemiology of pediatric hemorrhagic stroke, with a particular focus on epidemiology and health disparities based on race/ethnicity, geography and socioeconomics. Researchers will also collect longitudinal outcomes and work with collaborating investigators in physical and occupational therapy to develop improved outcome measures. This project will enroll a large number of children across the United States and internationally and broaden the understanding of pediatric hemorrhagic stroke at a population level.
Pediatric Neurovascular Registry
Principal Investigator: Christine Fox
The Pediatric Neurovascular Registry is a registry of pediatric patients who have been seen for stroke, risk of stroke, or other neurovascular disease at the Pediatric Brain Center in Benioff Children's Hospital - San Francisco. The study involves conducting retrospective and prospective chart review on pediatric patients with vascular disease of the brain and spine. Data regarding demographics, clinical and imaging characteristics, risk factors for stroke, and outcomes is collected and stored in the registry.
The specific aim for this study is to gain further insight into the risk factors and outcomes of pediatric cerebrovascular disease by analysis of clinical data (including imaging data) through chart review.
Radiation induced Arteriopathy and Stroke Risk in Children with Cancer treated with Cranial Radiation Therapy (RadArt)
Principal Investigator: Sabine Mueller
The primary aims for RadArt are:
- To estimate the rate and predictors of large-vessel vasculopathy defined as any irregularity noted on MRA in children who received/did not receive radiation to the brain and/or neck for underlying cancer diagnosis prior to enrollment.
- To estimate the rate and predictors of small-vessel vasculopathy defined as: 1. MRI based T2 lesions related to vascular injury (White Matter Hyperintensities (WMH)) and 2. Cerebral microbleeds based on gradient recalled echo (GRE) sequences in children who received radiation and who did not receive radiation to the brain and/or neck for underlying cancer diagnosis prior to enrollment.
- To estimate the rate and predictors of stroke and stroke recurrence in children who were treated/not treated with radiation to the brain and/or neck prior to study enrollment.
The secondary aims for RadArt are:
- To assess QOL in children with evidence of stroke and stroke recurrence who were treated/not treated with radiation to the brain and/or neck for underlying cancer prior to study enrollment.
- To assess neuro-cognitive function in children who were treated/not treated with radiation to the brain and/or neck prior to study enrollment via a computerized testing battery: CogState Research Battery and/or BRIEF (Behavior Rating Inventory of Executive Function).
- To test feasibility of collecting blood for DNA and RNA isolation for future analysis.
Data Analysis
Vascular Effects of Infection in Pediatric Stroke II (VIPS II)
Principal Investigator: Heather Fullerton
VIPS II began in 2017 and ended in June 2022. The purpose of VIPS II was to expand on the results from VIPS I. In VIPS I, we discovered that 1) clinical infection acts as a stroke trigger, 2) the upper respiratory tract is the most common location of preceding infection, and 3) routine childhood vaccines protect against stroke. However, we did not know the full spectrum of pathogens that contribute to childhood stroke risk.
Therefore, the specific aims of VIPS II were:
1. To identify known and novel pathogens in children with arterial ischemic stroke (AIS) and determine whether different pathogens (including unusual strains or combinations of pathogens) are associated with arteriopathic versus cardioembolic or idiopathic stroke.
2. To determine whether children with arteriopathic AIS have a distinct analyte signature consistent with an alternative pathway of inflammation compared to children with cardioembolic or idiopathic stroke.
3. To obtain and analyze the childhood stroke transcriptome and identify molecular correlates of stroke heterogeneity.
Seizures in Pediatric Stroke II (SIPS II)
Principal Investigator: Christine Fox
SIPS II started in 2016 and ended in 2020. The specific aims of SIPS II were:
1. To determine the extent to which acute seizures after pediatric stroke are associated with stroke-related death, neurologic recovery, and 5-year epilepsy risk.
2. To identify neuroimaging biomarkers associated with acute seizures and epilepsy.
3. To identify EEG biomarkers associated with severe neurologic outcomes and epilepsy.
