Research Investment by Program
Conquer Chiari takes every dollar it receives in donations very seriously. In order to maximize the impact of your donations, Conquer Chiari has established a Research Agenda, and a structured research program to achieve it.
The Research Agenda lays out the Goals and Objectives which, when achieved, will go a long way towards Conquering Chiari. To accomplish this, Conquer Chiari established the Conquer Chiari Research Center at the University of Akron (CCRC). The CCRC acts as the focal point for Chiari research and has quickly built a reputation as the premier Chiari research institution in the world.
In addition, to organize and structure our funding of projects, Conquer Chiari has launched several Research Programs:
Quantitative Measures (15 projects, $1,364,000 funded, $1,000,000 external grant)
Program Advisor: Dr. Francis Loth
Pathophysiology (10 projects, $686,000 funded)
Program Advisor: Dr. Francis Loth
Infrastructure (6 projects, $1,962,000 funded)
Program Advisor: Rick Labuda
Quality of Life (5 projects, $283,000 funded)
Program Advisor: Dr. Phil Allen
If you are a scientist or medical professional interested in Chiari research and have a project you would like to discuss, please call Rick Labuda at 724-940-0116 or email: director@conquerchiari.org
Agenda
Goal 1: Reduce the average time to an accurate diagnosis to less than 3 months from time of first symptoms.
Objectives:
- Develop a standard, simple, objective definition and test of symptomatic Chiari
- Enable the introduction of new technologies, such as inexpensive, portable imaging, which will reduce the barriers to diagnosis
Goal 2: Develop an effective, widely adopted, and minimally traumatic standard of care.
Objectives:
- Design, and encourage the adoption of, a standard outcome measure, such that the results from different studies can be compared and combined
- Establish whether the surgical variations that currently exist have a significant effect on long-term patient outcomes, and further develop a standardized surgical approach
- Encourage the development of minimally invasive surgical techniques
- Pursue non-surgical treatment approaches which don't just address symptoms, but are targeted at the core problem(s)
Goal 3: Minimize the impact that Chiari has on the quality of life of patients.
Objectives:
- Develop, and encourage the adoption of, a Chiari Impact Measure, which takes into account patient focused issues such as career, family, economics, recreation, and socialization
- Understand, and develop treatments for, the neuropsychological effects of Chiari, including both cognitive and emotional manifestations
- Develop widely accepted protocols for physical, occupational, and other types of therapies designed to maximize functional capabilities
- Enable the development of innovative technologies and treatments targeted at the neuropathic pain and loss of function associated with Chiari
Goal 4: Understand the pathophysiology, natural history, and epidemiological characteristics of Chiari.
Objectives:
- Establish, with reasonable accuracy, the incidence and prevalence of Chiari and Chiari related syringomyelia
- Characterize, and quantify, the Chiari experience, such as average age of diagnosis, time to diagnosis, number of doctors seen, major symptoms, etc.
- Develop a sound theoretical model for the pathophsyiology of Chiari, which explains how symptoms develop, and will enable predictions about who needs surgery, who will develop syringomyelia, etc.
- Identify and characterize the genetic basis of Chiari
Quantitative Measures
Why It's Important
One of the primary challenges of Chiari is the lack of objective tests and measures. While Chiari is defined by the degree of cerebellar tonsillar herniation, it has been shown that this is not a strong measure of symptom severity or eventual treatment outcome. Further complicating the picture is the fact that many Chiari symptoms can be vague and subjective. Developing objective, quantitative measure of Chiari and its symptoms would be a tremendous advance for patients.
Goal:
Develop accurate and reliable quantitative measures and markers of Chiari presence and severity, allowing the ability to:
- provide a faster, more accurate diagnosis
- objectively assess symptom severity
- objectively assess surgical success/failure
- objectively assess the effectiveness of new treatments
- classify patients into sub-groups
- contribute to the fundamental understanding of Chiari
Active Projects (7)
Clinical Imaging Database $50,000
Dr. Rafeeque Bhadelia
Building on the tremendous success of the Chiari1000, Dr. Bhadelia will build a clinical version of the database which will be used to explore the physical mechanisms underlying common Chiari symptoms such as cough headache, dizziness, and numbness/tingling.
Are Surgical Outcomes Linked To Morphological Changes? $38,800
Dr. Francis Loth
The primary goal of the proposed study is to quantify the brain and cranio-cervical morphology, specifically crowding measures, of Chiari Type I malformation (CM) patients before and after decompression surgery to determine if individual patient morphology, and/or the morphological changes that result from surgery, are predictive of surgical outcomes.
Morphometric Projects and Publications Based on Chiari1000 Data | $87,000 (Year One); $59,300 (Coordinator); $36,400 (Year Two); $28,000 (Coordinator Year 2); $50,000 (Year 3)
Dr. Francis Loth
The Chiari1000 project has generated an enormous amount of data. This grant is for the continued analysis of that data and the generation of journal publications. It is expected the CCRC will publish 6-8 papers based on the Chiari1000 in 2019.
Measuring brain displacement with DENSE MRI in patients with Chiari Malformation | $99,500
Dr. John Oshinski
Dr. John Oshinski, working with researchers at the CCRC will use a new type of MRI scan, DENSE, to measure the actual movement of brain tissue in Chiari patients as compared to healthy controls. Once the tissue movement is captured, the strain being placed on the brains of Chiari patients can be determined and mapped. This could be a valuable diagnostic too.
Automated Morphometric Analysis for Diagnosis & Research
$49,783 (Year One), $86,505 (Year Two) $115,511 (Year 3)
Dr. Francis Loth
The goal of this project is to develop semi and fully automated techniques to quantify MR based morphometric measurements. Fully automating these measurements would have an enormous research and potentially clinical impact.
Morphometrics | Part of Chiari1000
Dr. Francis Loth
The CCRC team will use the MRI’s and other data collected from the Chiari 1000 project to identify unique features of the skull and brains of Chiari patients. They hope to develop useful clinical parameters (beyond tonsillar herniation) and also to shed light on gender differences in Chiari and differences between pediatric and adult onset Chiari.
Cough Associated Changes in CSF Flow in CMI Evaluated by Real-Time MRI | $24,200
Dr. Rafeeque Bhadelia
With this project Dr. Bhadelia continues his work in using real time MRI as a way to quantitatively assess symptomatic Chiari. He hopes to show that after coughing, CM patients have a distinct pattern of spinal fluid flow the junction between the skull and spine.
Brain Damage in Chiari 1 Malformation | $142,000 | $48,000 (Additional Funds)
Dr. Phil Allen
Dr. Allen (CCRC) is working to understand how damage to brain tissue occurs in Chiari and the cognitive and/or emotional impacts this damage may impart. This project utilizes detailed psychological tests (32-lead electroencephalogram and others) and MRI diffusion tensor imaging and brain motion analysis tools to quantify brain damage in Chiari. This interdisciplinary study is being conducted in partnership with Cleveland Clinic Foundation (Stephen Dombrowski PhD and Mark Luciano PhD, MD) and Vanderbilt University (Seth Smith, PhD). Results from this study will help to identify the location of damage that occurs in Chiari and new information about the specific neural circuits involved.
Completed Projects (7)
Metabolic and Inflammatory Alterations in Patients with Chiari Malformation | $60,000
Dr. Leah Shriver
Many neurological conditions, such as MS, have been shown to involve significant changes in brain metabolism with indications of an inflammatory response. Dr. Leah Shriver, a professor in the Department of Chemistry and Biology at the University of Akron, is exploring her hypothesis that Chiari patients, due to the tonsillar herniation and disrupted flow of cerebrospinal fluid (CSF) will show significant alterations in the metabolic profile associated with the central nervous system. Dr. Shriver is an expert in metabolomics and has studied the metabolic response associated with MS.
Gait Assessment in Chiari Malformation | $6,084
Dr. Brian Davis
Conducted at the CCRC Open House 2018, Dr. Davis used a treadmill, cameras, and sensors to capture and analyze the gait of Chiari patients and controls. This will be used to assess coordination, stiffness, and stability. In the future, this type of testing might be used as part of the diagnostic process and to evaluate surgical outcomes.
Physiology-based Quantitative Assessment of CSF Flow Obstruction at the Foramen Magnum in Patients with Chiari I Malformation | $30,000
Dr. Rafeeque Bhadelia
Dr. Bhadelia (Beth Israel Deaconess Medical Center) conducted a pilot study to quantitatively assess the degree of CSF flow obstruction at the foramen magnum in patients with Chiari I malformation (CM) using fast CSF flow imaging with MRI and physiological challenges such as Valsalva maneuver. His findings confirmed his hypothesis that he could identify Chiari patients by the CSF flow pattern after Valsalva or cough. His results were recently published and Conquer Chiari has awarded him additional money to collect more data.
Cognitive Functioning in CM1 | $75,000
Cognitive Interventions in Children with CM1 | $75,000
Dr. David Frim
Dr. Frim and his team at the University of Chicago utilized neuropsychological testing on both children and adults and found that while overall intelligence was normal, there was a specific, identifiable pattern of weakness in certain types of verbal memory and executive function. In the children, these weaknesses improved significantly after decompression surgery, but with adults not as much. Based on these results, Dr. Frim was awarded a second grant to investigate the effects of two types of cognitive intervention therapies designed to improve working memory and attention (one computer based and one based on more traditional face-to-face therapy) on neurocognitive performances of children diagnosed with CM1. Their hypothesis was that CM1 patients with below average executive function and memory would show improvement in those functions after one or both of the intervention. The results are being analyzed and prepared for publication.
MRI Based Classification of Chiari Malformation | $33,000
Dr. Malena Espanol
Dr. Espanol (U of Akron) applied what is known as Machine Learning to the problem of objectively diagnosing Chiari. Basically, the idea was to input a large amount of data - in this case morphometric measurements from the MRIs of Chiairi patients and healthy controls - into a computer analysis, so the computer can learn how to distinguish between symptomatic and asymptomatic Chiari. Dr. Espanol's preliminary results were encouraging and identified a few morphometric measurements as potentially very significant. This project will continue by analyzing the much larger dataset from the Chiari 1000 project.
Dynamic MRI and Quantitative MR CSF Flow Studies in Chiari I Malformations | $50,000
Dr. Rajeev Bapuraj
Dr. Bapuraj (U of Michigan) studied the effect of neck position on tonsillar crowding and CSF flow in children with Chiari. While he didn't find any significant data in this regard, as often happens with research, he did observe some interesting dynamics and is currently working on a publication.
Hydrodynamics of Chiari | $120,000
Dr. Frank Loth
Dr. Loth (CCRC used advanced MRI and engineering techniques to measure 3 different hydrodynamic parameters in symptomatic Chiari patients, asymptomatic Chiari patients, and healthy controls. Their work produced strong enough preliminary results that Dr. Loth was arded a $500,000 NIH grant to continue and expand this line of research, with the goal of providing objective, quantitative data to aid in Chiari diagnosis. The most promising result showed that Longitudinal Impedance, a measure of the resistance to CSF flow in the spine, is significantly different between Chiari patients and healthy people, and may also be able to discriminate between symptomatic Chiari and asymptomatic tonsillar herniation.
Pathophysiology
Why It's Important
Pathophysiology refers to the study of the physical manifestation of a disease in a person. In other words, what is wrong and why. Understanding the pathophysiology of Chiari should address important questions such as:
- Are pediatric and adult Chiari the same or different?
- Why are more women affected than men?
- Why do symptoms vary so much from person to person?
- What causes symptoms to start in the first place?
- Why do people respond differently to treatment?
- Understanding the pathophysiology of Chiari is critical to advancing the care that patients receive. Unfortunately, studying the pathophysiology of a disease involves work in basic science, which is expensive, takes a long time to develop, and is high risk.
Goal
Develop a complete, practical, and accurate disease model of Chiari, which would answer fundamental questions, enable the categorization of patients, and suggest new techniques for diagnosis and treatment.
Active Projects (4)
Biomechanical Assessment of Brain Deformation in Chiari Malformation | (Year One) $40,326, (Year Two) $29,812
Dr. Rouzbeh Amini
Based on the data collected by Dr. Oshinski using DENSE scans, Dr. Amini will perform a biomechanical analysis to determine the forces that the brains of Chiari patients are exposed to. This may provide clues as to the underlying causes of Chiari and the link to specific symptoms.
Identification of novel MRI parameters and genetic factors for the diagnosis of classical Chiari | $47,179
Dr. Allison Ashley-Koch
Using samples acquired through the Chiari 1000, Dr. Ashley-Koch will perform targeted genetic sequencing looking for known connective tissue genetic variants among Chiari patients.
Targeting Syrinx Transporters for Syringomyelia Treatment Strategies | $142,200
Dr. Nic Liepzig
With this project, Dr. Liepzig’s team will continue their work in understanding syrinxes at the cellular level (using a rat model) and work to identify compounds that may slow or stop syrinx growth.
Biomarkers of surgical success in females with Chiari Malformation Type I | Part of Chiari1000
Dr. Phil Allen
A key part of the Chiari 1000 project, Dr. Phil Allen and his team will try to explain some of the variation in surgical outcomes among adult women. Specifically they will look at hormone levels to identify markers of an altered stress response which could account for why so many patients do not improve even after what is considered a medically successful surgery.
Completed Projects (6)
Genetic Traits of CM Across Age and Gender | Part of Chiari1000
Dr. Aintzane Urbizu
As part of the larger Chiari 1000 project, Dr. Urbizu, a visiting researcher from Europe, is collecting saliva samples from Chiari 1000 participants in order to look for genetic factors that are associated with specific skull and brain features commonly found in Chiari.
Molecular Biology Assessment of Syringomyelia | $97,000
Dr. Nic Leipzig
Dr. Liepzig is conducting research into nerve damage and healing, specifically looking at the molecular processes that are involved in syringomyelia. In this project, Dr. Liepzig successfully created a syringomyelia model in rats and was able to analyze the molecular processes associated with syrinx growth. Based on these published results, Conquer Chiari has funded Phase II of this work which will begin to look at ways to reduce or reverse the processes which lead to so much damage associated with syrinxes.
Cellular and Molecular Processes Affecting Posterior Fossa Volume (Phase III) | $150,000
Dr. Georgy Koentges
Dr. Koentges' team made tremendous strides in identifying the underlying mechanisms involved in the development of the bony structures that are affected in classical Chiari. Through painstaking work which followed the fate of specific cells as mice developed, he identified some potential pathways which could explain the undersized posterior fossa in classical Chiari. His results will compared to what is found in the Morphometrics project associated with the Chiari 1000.
Molecular Neural Crest-mesoderm Interactions and Control Networks Affected in Chiari (Phase II) | $75,000
Dr. Georgy Koentges
Extending his previous project, Dr. Koentges used advanced cell fate mapping techniques to study abnormal skull base development as seen with Chiari. His work was very well received at the 2010 Conquer Chiari research conference and holds significant implications for further research.
Microarray-based discovery of genes active in post-otic neural crest at critical stages and places of head morphogenesis affected in Chiari I/II (Phase I) | $50,000
Dr. Georgy Koentges
Dr. Georgy Koentges employed a mouse model to identify what genes are active at critical stages of embryological development which are believed to correspond to when the defects associated with Chiari occur. According to Dr. Koentges, “As a direct results of this grant, our investigations into PONC cells has led to the establishment of the molecular development of the tissues implicated in the variety of symptoms of Chiari.”
Characterization of Chiari Clinical Subtypes by Expression Analysis | $54,000
Dr. Simon Gregory
Dr. Simon Gregory, a geneticist at Duke University, performed genetic analysis on pediatric Chiari patients undergoing surgery, in order to identify clinical sub-groups. Dr. Gregory examined blood and tissue samples from the patients and correlated the genetic expression(s) with clinical indicators, such as skull dimensions and the presence of a syrinx. This work developed several promising leads for further genetic research.
Infrastructure
Why It's Important
Building an effective research program involves more than just funding individual projects. To be truly impactful for the Chiari community, top researchers – from a variety of disciplines - must be attracted to the field; easy access to patients and patient data must be established; and results must be disseminated effectively through conferences and journals.
Conquer Chiari is committed to doing more than just funding projects; we are committed to having a positive impact on patient outcomes and experiences. Therefore, we have committed a significant amount of resources to building a Chiari research environment, the centerpiece of which is the Conquer Chiari Research Center (CCRC).
The CCRC has quickly proven that our commitment to building a research infrastructure is paying dividends.
Goal
Develop the research infrastructure necessary to create a vibrant Chiari research ecosystem.
Active Projects (3)
Chiari 1000 | $368,644 (Year One), $207,205 (Year Two), $110,262 (Year Three)
Dr. Francis Loth
The Chiari 1000 is the largest project Conquer Chiari has funded to date. The goal is to collect uniform data from 1,000 Chiari patients, including demographics, medical information, neuropsychological scales, MRI’s, and for some people biological samples, such as saliva and blood. Conquer Chiari believes that by collecting data on such a large number of patients, the researchers at the CCRC will be able to make significant progress in answering key questions surrounding Chiari and have a major impact on the standard of care. The Chiari 1000 includes several sub-projects, such as morphometrics, biomarkers, and genetics. Just six months into this multi-year project, over 500 people have completed all of the on-line questionnaires and hundreds of MRIs have been received. If you are interested in participating in this ground breaking project, visit: https://chiari1000.uakron.edu/. See the results at http://chiari1000results.info/
Conquer Chiari Research Center | $881,064
Dr. Francis Loth
The CCRC is the world's first research laboratory dedicated solely to advancing the medical and scientific understanding of Chiari malformation in order to improve the experiences and outcomes of patients. The Conquer Chiari Research Center (CCRC) at the University of Akron is a state of the art facility, staffed with distinguished researchers, working diligently to: Apply the latest engineering techniques and analyses to improve diagnoses and treatment options, Leverage the Conquer Chiari Patient Registry to study the epidemiology and natural history of Chiari, Foster collaborations with leading clinicians and scientists to advance the Conquer Chiari Research Agenda and act as a focal point for the Chiari research community and attract more researchers to the study of Chiari.
Conquer Chiari Research Conference | $107,532
Dr. Francis Loth & Rick Labuda
The Conquer Chiari Research Conference is a bi-annual, professional meeting which brings together the top Chiari clinicians and scientists world-wide to present new developments in Chiari research, discuss issues, and form new collaborations.
Completed Projects (3)
Chiari Imaging Database | $48,000
Dr. Francis Loth
The CCRC has teamed with Akron General Hospital (who is offering MRI time at a greatly reduced cost) to build an MRI database of Chiari patients. The CCRC is working to establish a broad set of protocols which will be used on a wide variety of Chiari patients. The goal is to gather as much information as possible and to provide a platform for future research.
Conquer Chiari Patient Database | $149,000
Rick Labuda
Administered by Conquer Chiari itself, the Conquer Chiari Patient Database was a web based, secure database of demographic and health related information about Chiari patients. Patients entered their own data on topics ranging from diagnostic history, to surgical history, to the impact Chiari has had on their lifestyle. Information was collected on more than 1,000 patients. An interactive infographic was created to explore the results: http://registry.conquerchiari.org/
Voices of Chiari: Advancing Chiari Research Through a National Patient Registry | $90,000
Dr. Michelle Chyatte
Dr. Michelle Chyatte and her colleagues at NEOMED analyzed the data in the patient registry and generated several interesting publications from it and have presented at research conferences. In addition, they created an interactive infographic for the general public to explore the registry data (see link above).
Quality of Life
Why It's Important
A lot of medical research involves basic science, which can take years and cost a tremendous amount of money.
The QoL research program is focused on addressing specific questions, in a timely fashion, which will directly improve patients’ daily experience. For example:
- How can Chiari kids participation in the educational experience be maximized?
- What therapies can be used to minimize residual symptoms after surgery?
- Can physical and/or cognitive therapy improve surgical recovery and outcomes?
- How prevalent are suicidal thoughts and tendencies among the Chiari population and how can those patients be helped?
Goal
Minimize the impact of Chiari on patients and their families, by maximizing patients’ physical, mental, emotional, vocational, recreational, and interpersonal quality of life.
Active Projects (2)
Suicidal Ideation in Chiari Malformation $45,700
Dr. Phil Allen
A number of factors, such as chronic pain, headaches, EDS and depression place Chiari imply Chiari patients may be at a higher risk for suicidal ideation and self-harm behaviors. This project will explore the prevalence of these in the Chiari community through surveys and validated assessments. It is important to understand the scope of the problem in order to both bring attention to it and begin to address it.
Predicting Educational, Employment, Social, and Quality of Life Outcomes in Emerging and Young Adults with Chiari Malformation $17,900
Dr. David Tokar
Little is known about the school-to-work transition and other developmental milestones of adolescents and young adults with CM. Important questions remain about the impact of CM on emerging and young adults’ decisions to pursue higher education or other formal training (e.g., trade/professional school), enter the work force, leave their parental home, marry or become involved in a committed relationship, and become a parent. This project will explore the impact of CM on young adults and what role, if any, personality plays in mediating the impact of CM.
Completed Projects (4)
Career Development Experiences of Individuals with Chiari Malformation | $19,932
Dr. David Tokar
Until quite recently, almost nothing was known about the effects of Chiari malformation (CM) on work outcomes and other aspects of people’s work lives. The major purpose of this research is to illuminate the impact of CM on various work-related experiences, including workers' employability, career goals, job satisfaction and performance, absenteeism/presenteeism, change in job duties, coworker and employer relationships, experiences of discrimination, and work-related functional limitations.
Career Development Experiences of Individuals with Chiari Malformation | $16,670
Dr. David Tokar
Dr. David Tokar will build on the data collected through the Chiari 1000 to study the impact of Chiari on employment and careers.
Non-invasive Therapies for the Treatment of Chronic Pain in Chiari | $129,973
Dr. Phil Allen
Dr. Allen, along with Dr. Johnson and Dr. Otterstetter, will compare two type of interventions for Chiari patients dealing with chronic pain. Specifically, they will compare a controlled, water based exercise program with a specific type of cognitive therapy.
The Developmental and Psychoeducational Impact of Chiari Malformation | $53,000
Dr. Kevin Kaut
Dr. Kevin Kaut, a professor in the Psychology Department at the University of Akron, and a former school psychologist is examining in depth the impact Chiari has on school age children and adolescents. Specifically, Dr. Kaut will interview and assess Chiari patients in different age groups to gather data on their cognitive abilities and school experiences. By scientifically examining how Chiari affects children in school, Dr. Kaut believes he can then develop materials and guides for both parents and school officials to maximize Chiari children's participation in the school environment.