Active Projects

New Research (FY 2014)

Exploratory Research Grants – $500,000 ($50,000/year for two years)

Glen Lichtwark, University of Queensland (“The Relationship between Muscle Quality, Functional Capacity and Functional Performance through the Adult Lifespan in Cerebral Palsy”) Email: g.lichtwark@uq.edu.au

As people with cerebral palsy age, they often experience greater challenges in mobility due to muscle weakness, increased joint stiffness, and reduced control of muscles. We do not know how the natural effects of aging interact with the musculoskeletal adaptations that occur due to CP. Is there deterioration in muscle quality in adults with CP and does this limit the ability to perform daily activities like walking? To answer this question we need to examine the structure and function of muscles in CP and relate this to the ability to perform functional tasks or participate in physical activity. This information will enable us to recommended interventions that slow decline in function, improve health and reduce risk of falls.

Alexander Hoon, John Hopkins University School of Medicine (“Quantitative Mapping of the Basal Ganglia and Related Structure In Children with Dyskinetic Cerebral Palsy”) Email: hoon@kennedykrieger.org

Brain injury affecting the brain’s basal ganglia (BG), due to low oxygen at birth or genetic metabolic disorders, result in movement disorders called dyskinetic cerebral palsy. Quantitative Susceptibility Mapping (QSM) is a new neuroimaging technique that has never been applied to the study of brain structure and basal ganglia injury in children with dyskinetic CP. The aim of this study which is being co-funded by the Cerebral Palsy Alliance in Australia is to map injury to basal ganglia (BG) and related structures in 15 children with dyskinetic cerebral palsy (CP) and 15 unaffected children. More precise quantifications of basal ganglia structures and their connections in children with dyskinetic cerebral palsy will help refine targets for therapeutic interventions such as Deep Brain Stimulation (DBS).

An Massaro, The George Washington University School of (“Quantifying Basal Ganglia Thalamic Injury i n Neonatal Hypoxic Ischemic Encephalopathy – A Method for Early Assessment of CP Risk”) Email: ANguyenM@cnmc.org

Hypoxic ischemic encephalopathy (HIE) refers to brain injury resulting from reduced blood and oxygen delivery to a baby’s brain near the time of birth. Advanced magnetic resonance imaging (MRI) is a safe, non-invasive tool that can be used to measure tissue health and blood flow in deep brain structures. Using brain MRI measurements in newborns to predict later childhood disability can advance clinical care by providing means to assess the immediate effects of treatments for brain injury. This project aims to evaluate advanced MRI tools that can help prevent or ameliorate disability due to cerebral palsy that is often a consequence of HIE and other neurologic disorders in the newborn.

Ming Wu, Rehabilitation Institute of Chicago (“Robotic Pelvis Manipulation Improves Dynamic Balance and Walking in Children with Cerebral Palsy”) Email: w-ming@northwestern.edu

Horseback riding (hippotherapy) has been shown to improve balance in children with CP. However, this beneficial therapy is not available for a majority of patients because of limited access to horses, weather conditions, and the relatively high cost due to the need for multiple professional staff during a hippotherapy session. As a result, there is a need to develop a novel robotic system to make this type of therapy more widely available for children with CP. We propose to test whether providing controlled 3D movement (similar to that of a horse) astride a cable-driven robotic system will improve dynamic balance and walking function in children with CP.

Bernadette Gillick, University of Minnesota Program in Physical Therapy Medical School (“Application of Non-Invasive Brain Stimulation (NBS) in Children with Hemiparesis to Improve Hand Function”) Email: gillick@umn.edu

Weakness on one side of the body due to cerebral palsy, or hemiparesis, affects the functional ability of an individual during childhood and throughout the lifespan. Using a specific form of stimulation, transcranial direct current stimulation or tDCS, brain cells that were inactive due to injury have the potential to become instrumental in function. tDCS is painless, cost-effective, and portable and has shown no evidence of seizure or other serious adverse event. The proposed research combines tDCS with constraint-induced movement therapy (CIMT) to investigate their benefit on hand function in children with hemiparetic cerebral palsy.

Hausman Clinical Scholars Award – $225,000 ($75,000/year for three years)

Kathryn Connaghan, Northeastern University (“Prosodic Differences and Their Impact on Speech Intelligibility in Cerebral Palsy”) Email: k.connaghan@neu.edu

The clinical presentation of cerebral palsy frequently includes motor speech impairments which can substantially impair communication. Even in its mildest forms, atypical speech can impact social interactions and quality of life. Through a series of speaking and listening studies we will examine the interaction of perception and production of prosody (rhythm and pattern of sounds) and its impact on speech intelligibility in CP. In addition to contributing to the scientific and clinical knowledge base, findings from this work may challenge current clinical assumptions and lead to novel, more efficacious inventions that address the complex communication needs of individuals with CP.

Cerebral Palsy Research Center of Excellence – $600,000 ($200,000/year for three years)

“Prevention and/or Cure of White Matter Injury among Preterm Infants”

The purpose of this research funding ($1 million over five years) initiative is to support innovative research and/or infrastructural needs leading to prevention and/or cure of cerebral palsy due to white matter injury among preterm infants. The proposed research aims should address one or more novel approaches to prevention and/or cure and lead to a human application within the project period (i.e. five years or less). Importantly, this project should serve as the foundation of the establishment of an integrated, interdisciplinary Cerebral Palsy Center of Research Excellence (CPCRE), focused on prevention and/or cure of cerebral palsy, which will endure and flourish beyond the timeframe of this particular project.

Proposals have been submitted and are under review by an international panel of experts. Announcement of the winner of this competition is expected in late Spring, 2014.

Deep Brain Stimulation Registry – $210,000 ($70,000 per year for three years)

Deep brain stimulation (DBS) is a new neurosurgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain. DBS in select brain regions has provided remarkable therapeutic benefits for otherwise treatment-resistant movement disorders such as Parkinson disease, tremor and dystonia.

To date there has been minimal exploration of the utility of DBS in cerebral palsy (CP). Before DBS becomes more widely utilized in CP, with the risk of inappropriate use and even harm, it is imperative that it be subjected to rigorous scientific scrutiny.

CPIRF has facilitated and funded two meetings regarding establishment of a DBS in CP registry to which neurologists and neurosurgeons around the world would contribute data regarding their patients with CP who undergo DBS. Such a registry would provide invaluable guidance regarding optimal patient candidates, best sites of electrode implantation, complications, and outcomes. Based on the collective experience in various medical centers globally, an informed prospective clinical trial of DBS in CP can be implemented. The DBS in CP registry will be operational in early 2014.

Continuing Research Programs of FY 2013

Advancing Neuroimaging and Educational Training $225k ($75k/year for three years)

Christopher D. Smyser, MD, Assistant Professor of Neurology at Washington University/St. Louis Children’s Hospital is continuing his research as an Ethel & Jack Hausman Clinical Research Scholar Award recipient.

Dr. Smyser’s research award is in its second year with funding support by the Hearst Foundation. Dr. Smyser is utilizing an innovative advanced neuroimaging approach, in an investigation of prematurely born infants to provide insight into the earliest forms of functional brain development and further define the effects of cerebral injury. Award funds are designed to specifically help Dr. Smyser improve neurological care for infants and management of neurodevelopment disorders at St. Louis Children’s Hospital. Funding will additionally enable Dr. Smyser to provide medical students, resident physicians and fellow physicians with the knowledge and clinical skills necessary to assess infants with neurological concerns and neurodevelopmental disabilities and develop comprehensive management plans for patient care.

Improving Pain Treatment in Adults $400k ($200k/year for two years)

A special project research grant was awarded to Dr. David Roye and Dr. Joseph Dutkowsky at Cerebral Palsy Center at Columbia University Medical Center in New York for their research platform on Pain in the Adult with Cerebral Palsy. The purpose of this two-year project is to address the scarcity of data related to the experience of pain for adults with cerebral palsy, to ultimately devise better pain treatment in these adults, providing a transformative addition to medical knowledge and patient care. The current published data deals mainly with prevalence and few articles discuss treatment efficacy or etiology. Contributing is the relatively subjective nature of pain coupled with the difficulty of assessing pain, especially in non-communicative or cognitively impaired people with CP. The specific aim of this research platform is to ultimately produce tangible and influential advances in the evaluation and understanding of pain in the entire population of adults with CP.

Voice and Speech Treatment in Spastic CP $100k ($50k for two years)

A pilot research grant was awarded to Carol A. Boliek, PhD, Associate Professor, Department of Speech Pathology and Audiology Faculty of Rehabilitation Medicine at the University of Alberta in Canada. The study, funded in part by F.M. Kirby Foundation, focuses on the effects of a specific speech treatment in children with CP. The hope is that this work will lead to National Institute of Health and Canadian Institutes for Health Research grant applications to fund large-scale treatment studies, the results of which have the potential to significantly affect voice and speech treatment delivery to children with CP.

This pilot study focuses on speech deficits in spastic CP, the most common type of CP, which causes a high degree of muscle tightness. It affects approximately 50% of cases. Speech deficits associated with CP can have significant functional consequences on children, affecting their potential for academic advancement, social and emotional development, and eventual independence and participation in the work force. Trial and error interventions characterize current best practice in voice and speech treatment with this population, resulting in frequent mismatches. This study will generate insight on how to enhance treatment outcomes and extend the duration of treatment effects. Ultimately the goal will be to predict which types of structural and functional brain profiles respond best to a complex continuum of treatment approaches.

Brain Manipulation & Medication to Improve Motor Function $100k ($50k/year for 2 years)

A pilot research grant, supported by The Hearst Foundation, was awarded to Hsiu-Ling Li, Research Assistant Professor, Department of Physiology and Pharmacology at SUNY downstate Medical Center in Brooklyn, N.Y. This grant is vigorously testing the hypothesis of how maladaptive plasticity (a non-typically developed brain, inflexible to change) could exacerbate motor deficits in children with congenital hemiplegia (a condition affecting one side of the body caused by brain damage before, during or soon after birth). To date, causes remain elusive and effective treatments are in critical need. This study will combine optogenetics, which probes neural circuits at the high speeds needed to understand brain information processing, and live-imaging to directly investigate the progressive component of hemiplegic CP that occurs during early development. A better understanding of the cellular basis of this maladaptive plasticity will help the design of new therapies involving manipulation of specific cortical area activity. The study will also aid in identifying new medications to correct mal-development after early brain injury.

Using a Mouse Model to Understand Brain Reorganization$100k ($50k/year for two years)

More than half of cerebral palsy patients have brains showing some disorganization of the cortex as do many related conditions, including intellectual disability and epilepsy. Research fellow Sung-Jin Jeong at Children’s Hospital in the Boston Department of Medicine is the recipient of a research grant to enrich the understanding of the pathogenesis (disease development process) of cerebral palsy and other neurological disorders resulting from disrupted neural migration by studying brain specimens in mice. The hope is that better understanding will lead to effective treatments.

Robots Assisting in Movement $100k ($50k/year for two years)

Dr. Adam Kirton, Associate Professor, Pediatrica & Clinical Neuroscience at Calgary Pediatric Stroke Program, Alberta Children’s Hospital in Canada is conducting a study using children between the ages of 6 – 18 and robots to provide a unique opportunity to better understand sensory dysfunction in the developing brains of children with CP. Proprioception – the sensation of position, motion, and force – is essential for limb function but remains unquantifiable in perinatal stroke and CP. Improved therapeutic strategies could benefit tens of thousands of children globally with hemiplegic CP (a condition affecting one side of the body).

The Role of Genetics $100k ($50k/year for two years)

Neuropsychologist John Connolly of the Center for Applied Genomics at the Children’s Hospital of Philadelphia was awarded a grant with funding support by The Hearst Foundation, to outline a powerful methodology aimed at delivering important insights into the genetic causes of CP. He predicts that genetic defects collectively constitute a substantial proportion of all CP cases and that recent developments in genomic technology now offer an unprecedented opportunity to acquire a sophisticated understanding of the genetic causes of CP, and ultimately, reduce its impact and prevalence.