Current and Recent Research Projects

This is a CPARF-funded study within the Cerebral Palsy Research Network.

Pain management is a priority for adults with CP, and the biggest barrier to this is the pervasive lack of pain screening and classification of pain by physicians. There is an urgent need to fill this gap to serve the increasing number of adults with CP.

This study standardizes procedures for screening and classifying pain in adults with CP within four Cerebral Palsy Research Network institutions across the US by identifying a set of procedures and employing these procedures at centers to gather a sample of more than 200 adults with CP.

Researchers aim to characterize pain types to advance collective knowledge and compile a straightforward protocol that can be applied across institutions. The results from this study will create the foundation for establishing, testing, and improving treatment options for pain in adults with CP.

This study seeks to develop a data-driven perspective on the functional health, well-being, and presence of chronic pain in adults with CP. 

This grant allowed the CP Research Network to test additional recruitment methods to increase the enrollment in our longitudinal study of adult well-being and chronic pain. 

This qualitative study of low back pain uses our community registry to recruit people with different levels of low back pain and then interviews them to learn more about their experience with this most common difficulty. 

Chronic low back pain is a common problem in many adults with cerebral palsy, leading to increasing disability and functional decline. Improving pain management strategies is critical to improving quality of life as people with CP age. However, participants’ perspectives on living with low back pain have not been thoroughly examined. This study proposal will use interviews combined with survey data to explore how pain interferes with daily function as well as how adults with CP experience seeking treatment for low back pain. 

Developing evidence for the best way to treat dystonia in CP is crucial to improving outcomes. This study is a multi-arm randomized control trial to test the range of medications used with patients with dystonia in CP. 

The current standard of care monitoring (pulse oximetry) for premature infants provides inadequate information to guide ventilator and oxygen management for optimal neuroprotection. Near-infrared spectroscopy (NIRS) is a light-based non-invasive device, approved for use in neonates, which provides information about oxygen levels in the brain, something not
easily available in any other way.

There are an increasing number of reports which link low oxygen levels to brain injury and it is a high-priority target for intervention.

This project will randomize preterm infants to either a “standard of care” group or a “NIRS-directed”group. In this second group, the infants will have NIRS monitoring for the first 72 hours after birth. If their brain oxygen level goes outside of the normal range, a standardized treatment protocol using evidence-based strategies will be employed. The primary outcome of this study will be a reduction in death or severe brain injury.

This project was piloted in a group of 166 infants with a remarkable 25% reduction in this outcome, suggesting significant potential benefits.

Stroke is the most common cause of hemiparetic cerebral palsy. Ischemic stroke occurs when a blood vessel to the brain is blocked, resulting in brain cell death. Stroke affects ~5,000 children in the USA yearly. The risk of stroke is highest around the time of birth (perinatal), occurring in ~1 in 4000 live births. Up to 70-80% of children who suffer perinatal stroke develop cerebral palsy.

Currently, the only treatment for stroke is restoring blood flow through the blocked vessel. Unfortunately, >90% of children and all babies with stroke are not eligible for these treatments. Thus, new treatments are needed.

Mitochondria are the “energy powerhouse” of the body. In stroke, mitochondria become dysfunctional and cause harm, leading to brain cell death. We aim to identify mitochondrial targets for new treatments. In order to design effective treatments, we first need to understand the changes that occur within mitochondria during stroke and how these cause cell death. This study uses a novel mouse model of childhood stroke to investigate the effect of mitochondrial dysfunction in two main brain cell types (neurons and astrocytes).

Using genetic engineering, we will induce mitochondrial mutations in neurons and astrocytes, separately, and measure stroke size and motor disability. We postulate that selective mitochondrial dysfunction in neurons will be protective by reduction of damaging oxidative stress. In contrast, we hypothesize that selective mitochondrial dysfunction in astrocytes will be harmful due to the loss of cues that keep brain cells alive. Thus, a treatment that indiscriminately affects mitochondria in all cell types would be unlikely to work. We will test a potential cell-selective therapeutic strategy to
reduce stroke severity. This study has high potential to illuminate new approaches for treatments to reduce brain injury and improve stroke-related disability, including cerebral palsy.

This study is an international collaboration between the United States, Australia, and Italy.

The international guidelines for the early detection of cerebral palsy (CP) established a decision-making framework to facilitate earlier and more accurate diagnosis of CP in infancy. The Prechtl General Movement Assessment (GMA) is a clinical tool that was recommended as one of the best motor assessments to identify CP in infants less than five months old. While the GMA has been proven to be a robust predictor of CP, the age at which the test is most accurate is less clear.

The presence of “fidgety movements,” an age-specific marker of typical motor development, was traditionally believed to be present and detectable at 12 weeks post-term age. However, in the years since the guidelines have been published, new evidence has emerged challenging this time frame. The emergence of fidgety movements should be studied rigorously as there may be variation among high-risk groups. This has not yet been tested in a large, diverse sample of infants.

Our objective is to understand the time at which the GMA is most effective to improve accuracy of early detection of cerebral palsy. We will compare the onset of fidgety movements in children with medically complex histories to a healthy control group. Parents will be able to obtain GMA data at six time points in development (10, 12, 14, 16, 18, 20 weeks post-term age), using the Baby Moves smartphone application.

Over the course of two years, infants from Europe, Australia, and North America will be enrolled in the study. The movements will be analyzed by expert GMA assessors to determine the time when fidgety movements are most clearly present.

It is imperative that clinicians following the early detection guidelines understand the optimal time to use the GMA in order to accurately identify infants with CP.

This study is an international collaboration between the United States, Australia, and Italy.

The international guidelines for the early detection of cerebral palsy (CP) established a decision-making framework to facilitate earlier and more accurate diagnosis of CP in infancy. The Prechtl General Movement Assessment (GMA) is a clinical tool recommended as one of the best motor assessments to identify CP in infants less than 5 months old. While the GMA has been proven to be a robust predictor of CP, the age at which the test is most accurate in predicting later outcomes is less clear. In the years since the guidelines have been published, new evidence suggests that the presence of “fidgety movements,” an age-specific marker of typical motor development, may be seen more clearly at a different age window than was originally recommended.

With initial funding from the Cerebral Palsy Alliance Research Foundation, our international team of interdisciplinary healthcare researchers is now studying the timeline of emerging fidgety movements in a large, diverse sample of children between 2- and 5-months corrected age. We would next like to understand how this timeline relates to the children’s development over the first few years of life.

Our objective in this proposal is to understand the time at which the GMA is most effective at predicting long-term outcomes to improve accuracy of early detection of cerebral palsy. Currently, we are collecting the GMA at 6 timepoints in early infancy, to understand when fidgety movements are most detectably present in children with both typical and medically complex histories. Next, in this proposal, we plan to measure the development of these children at one- and two-years of age and compare their development with the initial timing of their fidgety movements.

It is imperative that clinicians following the early detection guidelines understand the
optimal time to use the GMA in order to accurately identify infants with CP.

This study examines the knowledge gap about which clinical tools can best determine the prognosis for a child with cerebral palsy. It compares a specific behavioral assessment at six timepoints in early infancy with two-year neurodevelopmental outcomes in a large population of children with and without medical complexity. It aims to further improve upon early detection, which will ultimately improve individual prognosis and open the door to earlier and targeted therapeutic interventions for children with CP.

Investigators throughout Egypt, Tunisia, Jordan, and Saudi Arabia are evaluating the practicality and affordability of a multicenter CP registry in different settings and developing nationally driven evidence-based guidelines to follow children with CP in Arabic-speaking countries. This study will help develop a multicenter registry in Arabic-speaking countries and has the potential to greatly improve public health policies and clinical practice by narrowing the knowledge gap around CP characteristics. A registry of this caliber will serve as a foundation for ethically entering, storing, and sharing information reliably among participating institutions and Arabic-speaking countries.

This study is funded through CPARF’s partnership with the American Academy of Cerebral Palsy and Developmental Medicine.

Cerebral palsy (CP) is a major neurodevelopment disorder and the most common lifelong physical disability. Although CP is commonly associated with prematurity or prenatal brain injury, accumulating evidence suggests that deleterious genetic variants may contribute to CP, in addition to environmental insults. However, the genetic causes of most CP cases remain unclear. Further, attempts to measure the effects of genetic variations have been limited.

We will analyze genetic information from CP families to identify genetic risk factors and perform functional studies to provide mechanistic insight into identified genetic variations. This work can identify novel genetic causes for therapeutic intervention and increase precision in genetic counseling, outcome prognostication, and treatment stratification, while informing future clinical trial design.

Dystonia affects one in six people with cerebral palsy, making it very difficult and sometimes impossible to control movement. Deep brain stimulation, a cutting-edge form of neuromodulation in which electrodes are strategically placed in the brain, is proven to be a dramatically effective treatment in many people with dystonic cerebral palsy. However, there are some cases in which individuals do not respond at all to the treatment, making outcomes extremely difficult to predict and presenting challenges to both families and physicians when deciding to prescribe and proceed with the invasive procedure. This study will test a novel approach that combines genomic findings with detailed clinical data to predict which individuals are top candidates for Deep Brain Stimulation and most likely to see significant improvements.

Instead of one disorder, researchers are finding that cerebral palsy (CP) includes a mix of genetic disorders. This creates both a need and opportunity for personalized medicine in CP. However, many of these genes are unknown, uncharacterized, or lack treatments. Where treatments are known, patients who would benefit are missed because of lack of access to genetic testing.

A feature of CP that needs better treatment options is dystonia. Dystonia is abnormal muscle contractions causing unwanted movements or postures that can cause pain and profound impairments in daily tasks. The genes and cell changes that cause dystonia are mostly unknown, which has made it very difficult to develop treatments.

This project focuses on creating a list of genes found in dystonic CP patients and adults with dystonia.

Some genetic causes of CP have known treatments that would improve patient outcomes. These can be missed since many clinicians and healthcare decisionmakers don’t know how genetic testing could benefit patients with CP.

Clinicians, scientists, and geneticists on this project will bridge this gap by creating a report of genes found in patients from clinical testing and research studies. This project also entails the search for treatments known to be effective for these genetic causes in peer-reviewed clinical studies.

A group of neurologists within the CP Research Network are exploring the possibility of using natural history, genetic biomarkers of CP to prepare for clinical trials for rare forms of CP. 

This study seeks to find the genetic causes of cerebral palsy which have already been found to be much higher than originally predicted.  Finding genetic causes opens the door to better clinical interventions to improve outcomes. 

This competitive renewal of Dr. Kruer’s original genetic causes of CP is being developed to take the learning from the first five years and use new methods to enhance discovery. 

People with CP who walk need a wearable device that can be used as a gait aid and rehabilitation tool in their home and community, rather than solely in therapeutic or medical settings. This study’s primary aim is to determine the effectiveness of a lab-proven ankle-powered exoskeleton device to activate ankle muscles for people with CP while they walk. Researchers believe that people with CP will experience improved walking in the community, and the results will shape the ways this device and others are used for future at-home rehabilitation.

SpineX Inc. is an early stage bioelectric medtech company developing noninvasive neuromodulation devices. SpineX is committed to helping individuals with unmet clinical needs. Our goal is to use rigorously tested neuromodulation technologies to aid recovery and restoration of several functions for people with cerebral palsy, including bladder, bowel, and sensorimotor function.

CPARF’s current grant supports ongoing clinical and device development for Spinal Cord Innovation in Pediatrics (SCIP) to enable voluntary movement and control for children with cerebral palsy. SCIP is recognized by the FDA as a breakthrough device.

New strategies to improve motor function in young children with cerebral palsy (CP) are needed. Our goal is to bring children with CP to the forefront of the implementation of robotic exoskeleton technology. We will conduct the first study of robotic exoskeleton training in children with delayed motor skills or a diagnosis of CP at ages 1-2 years.

We will recruit 10 children to participate in an exoskeleton-training program to determine the acceptability and feasibility of robotic rehabilitation. We will evaluate whether the exoskeleton improves range of motion, strength and/or motor function. To learn how robotics may address the needs and rehabilitation goals of participating children, we will conduct interviews and focus groups with parents of participants and clinicians.

The long-term goal of this study is to apply what we learn to the design of a clinical trial that can
determine if exoskeleton rehabilitation is more effective than standard rehabilitation.

This project is funded by CPARF’s Accelerator Grant to the Cerebral Palsy Research Network. It implements GOAL and CPCHILD reports as an external service on the CP Research Network to enable shared decision making. 

This planning grant is intended to demonstrate the feasibility of building an anonymized video library extension to our registry to enable the application of shared expertise to diagnose dystonia. 

This registry extension is intended to capture essential data points from the NICU for infants diagnosed with hypoxic-ischemic encephalopathy, which often leads to CP and other co-morbidities often experienced by people with CP, like epilepsy. 

This infrastructure grant is intended to support the development of an imaging database linked to the clinical registry.  The funds would be used to build the infrastructure to de-identify images at the site and then transmit them to the data coordinating center.  The initial study concept includes the mapping of brain lesions on to known brain network maps to diagnose dystonia. 

This study will use machine learning to read, improve, and categorize MRIs in correlation with the clinical registry to predict outcomes. 

This qualitative study sought to better understand the practice for two common interventions to reduce spasticity — chemical denervation (typically with Botulinum Toxin A) and selective dorsal rhizotomy. 

This study will provide guidance about which children with CP are the best candidates for selective dorsal rhizotomy (SDR). The project will also support understanding of how much and focus of physical therapy after SDR. 

This project will describe the variation in surgeries (orthopedic, neurosurgery) that are done in children with cerebral palsy. Understanding the variability of when surgery happens will guide understanding of the best timing of surgery. 

Children with more involved cerebral palsy have higher risks for complications after surgery, including longer hospital stays and time to recovery. We do not fully understand why children with CP are more likely to have surgical complications, but one of the causes may be due to malnutrition, which is common in this population. In a 2019 survey, medical providers and surgeons said that improving nutrition was the most important target to improve surgical care, but we still do not know the best way to do this. In this study, we combine the expertise of developmental-behavioral pediatricians, pediatric gastroenterologists, and pediatric orthopedic surgeons to find a solution to this problem. We aim to identify markers of malnutrition that may lead to poorer surgical outcomes (Aim 1) and understand changes in body composition in children with CP after surgery (Aim 2). This will help identify nutritional interventions that will improve surgical care for this growing population of children. 

This secondary analysis of our registry seeks to examine the trends between patient weight and weight percentile on a CP curve and their clinical outcomes. 

This survey tool will help parents and physicians capture the complexity of CP and co-morbid conditions in their patients to improve the assessment of patients. 

This multisite study funded by the Canadian Institutes of Health Research seeks to determine if two popular patient reported outcome measures, the Gait Outcomes Assessment List (GOAL) and CPCHILD, can be effective shared decision-making tools for clinicians, patients, and families prior to medical or surgical intervention. The participating sites include Children’s of Alabama, Gillette Children’s, Nationwide Children’s and the coordinating site at SickKids. 

This infrastructure grant added standard questions about epilepsy to the registry so that clinicians could better understand and treat individuals with both CP and epilepsy.

This secondary analysis of the CP Research Network registry seeks to describe the variation in both surgical technique and patient selection for a neurosurgical procedure called selective dorsal rhizotomy. 

This study aims to further understand the growth of children with CP to help families and providers support nutritional support across the lifespan. 

This secondary analysis of CP Research Network registry seeks to determine if there is a correlation between the etiology of CP and the person’s gross motor functional ability.