March 2010 Fact Sheet

Leading neuroscientists, clinicians, radiologists, neurobiologists, and pediatric neurologists came together for a symposium  entitled “Injury to the Preterm Brain and Cerebral Palsy” in conjunction with the 37th Annual Meeting of the Child Neurology Society on November 5th, 2008.  The symposium  was supported by the National Institutes of Health, the Child Neurology Society, the Kennedy Krieger Institute, and the Cerebral Palsy International Research Foundation. Recently a summary of the symposium was published in the Journal of Child Neurology by Michael Babcock, Felina Kostova and Drs. Donna Ferriero, Michael Johnson, Jan Brunstrom, Henrik Hagberg and Bernard Maria. The first session was on clinical aspects of injury to the preterm brain.

Current Knowledge of Preterm Injury

Dr. Joseph Volpe of the Children’s Hospital in Boston discussed the current state of knowledge regarding injury to the preterm brain. Of the 60,000 infants born each year in the US weighing less than 1,500 grams, up to 10% develop motor dysfunction and up to 50% have cognitive, behavioral and social deficits. Due to advances in neonatal care, 90% of these extremely low birthweight infants survive.  Periventricular leukomalacia (PVL) is the most common pathology, occurring in up to 50 % of these infants.  PVL has two components, one being a focal component, the other being a diffuse cell-specific  component characterized by injury to the preoligodendrocyte (precursor of the cell responsible for myelinating the neuronal axon), and the occurrence of astrocytosis, and microgliosis (nerve cells that are activated after a CNS injury).  Injury to preoligodendrocytes can result in cell death or loss of cell processes.  After insult, there is a replenishment of preoligodendrocytes that are unable  to mature into oligodendrocytes capable of myelination.

It is believed that there are interacting factors that contribute to PVL  in the premature infant . They include cerebral ischemia, infection and inflammation and a maturation dependent vulnerability of the preoligodendrocyte. Premature infants are susceptible to ischemia because of impaired vascular autoregulation, generating reactive oxygen and nitrogen species. These reactive species accumulate and cause injury in the preoligodendrocytes as they have not yet acquired an antioxidant defense system.  In addition, there is also clearly a link between infection/inflammation and PVL.  Infection and inflammation are associated with release of pathogen-associated molecular products that activate microglia. These activated microglia lead to production of free-radicals that cause injury to the preoligodendrocyte as well.

Thus there are upstream mechanisms of ischemia, reperfusion, and inflammation that activate downstream mechanisms of excitotoxicity (pathological process by which nerve cells are damaged and killed by glutamate and similar substances) and free radical attack that can all potentially be targeted for prevention of injury.  There are many animal studies demonstrating efficacy of various compounds blocking action of reactive species thus preventing injury and many of these appear to be ready for trials in premature infants.

Neuroimaging in Cerebral Palsy

Dr. David Edwards of the Hammersmith Hospital in London, England discussed recent technological advances and clinical usefulness of imaging.  He stated that conventional MRI does not have a lot of value in predicting health outcomes in premature infants.  Another type of imaging, called diffusion tensor imaging (DTI) has shown promise in that it can reveal  the structural integrity of white matter as well as white matter tracts throughout the brain demonstrating connections between various  regions.  Using DTI and tract-based spatial statistics, researchers have demonstrated a good correlation between health outcomes of 2 years old with white matter lesions and measures of microscopic white matter integrity.  DTI has revealed that in children with white matter lesions, not only is there decreased volume of the thalamus, but there is decreased connectivity between the thalamus and the cortex.  It is believed that use of DTI with functional MRI can be combined to give very precise structure-function relationships of various regions of the brain.

Fetal Inflammatory Response

Dr. Olaf Dammann of the University of Hanover in Germany discussed the fetal inflammatory response and brain injury.  It is now believed that premature birth is sometimes the result of some exposure during pregnancy (such as intrauterine infection) and that this exposure causes white matter damage in the infant.  Thus prematurity and cerebral palsy are associated but not necessarily causal in some instances.  In addition, it is now believed that it is not exposure to the pathogen itself that causes the damage, but rather exposure to substances produced by the fetal inflammatory response to the pathogen.

Further, Dr Dammann stated that it is likely that fetal white blood cells are involved in brain injury by going through the fetal blood-brain barrier once activated by cytokines, which in turn, activate microglia and astrocytes that damage the preoligodendrocytes.  He also suggested that brain injury and long-term disability results not just from a single event, but from an ongoing exposure to persistent inflammation as evidenced by the presence of a marker of inflammation present in the blood of children with cerebral palsy at age 10.

The Today Show featured a segment on cerebral palsy and robotic therapy. The segment showed footage from CPIRF’s project at Blythedale Children’s Hospital in Valhalla, NY featuring upper extremity robotic therapy and from the Rehabilitation Institute of Chicago where we held a joint workshop on ‘Transformational Technologies’, to get the research community interested in using technologies shown to be effective in stroke rehabilitation for use in cerebral palsy therapy. Additionally, Meredith Vieira interviewed Dr. Nancy Synderman about the increasing prevalence of CP, the reasons why, and new therapies on the horizon.

Please find below a link to the Today Show website that contains the CP segment aired this morning.

Click Here to watch the Today Show Segment!

Stay tuned for our posting of the video segment!

CPIRF will award $30,000 to Dr. Yvonne Wu of the University of California at San Francisco and William M. Gilbert, MD at Sutter Medical Center, Sacramento, to study factors associated with the occurrence of CP in term infants. Much of this funding was raised from CPIRF’s Power Heroes Gala held last year in Los Angeles.

Her previous work found that black ethnicity is associated with a 40% increased risk of CP among term and near-term infants. In a follow up study, Wu et al confirmed her earlier finding of increased risk of CP among black infants, although the relative risk did not reach statistical significance as in the previous study. These findings are consistent with research conducted by the Centers for Disease Control. They found a higher prevalence of cerebral palsy in black 8-year old children as compared to other racial groups in three different geographical areas of the country: metropolitan Atlanta, Northern Alabama and Southeastern Wisconsin . The prevalence of CP was highest among 8 year old black children in all three regions and was 30% higher overall than the prevalence found in white non-Hispanic children.

Drs. Wu and Gilbert are going to use a database maintained by the Office of Statewide Health Planning and Development (OSHPD) of California. This database contains 10 years of birth certificate information from the whole state of California and is linked with another database maintained by the California Department of Developmental Services that contains all diagnoses of cerebral palsy in the same time period. She will test the following hypotheses: 1) Infants born to black mothers experience an increased risk of cerebral palsy that is only partially explained by increased rates of prematurity and other potential confounders; and 2) Infants born to mothers of Hispanic origin demonstrate a lower risk of cerebral palsy. Dr Wu hopes to complete her study by the end of next year.

The Developmental Medicine and Child Neurology  Supplement on “Adults with CP workshop” is now available. Please go to this link to download entire content:

The Developmental Medicine and Child Neurology  Supplement on “Adults with CP workshop”

Dr. Mindy Aisen gave a plenary talk at the 63rd AACPDM Annual Meeting on September 26th in Scottsdale, Arizona. Her talk was entitled ‘ Updating Research Priorities for Cerebral Palsy’.

Download her Power Point Presentation here.
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Gary Lynn, CPRIF’s Ambassador at Large, was chosen by the City of Houston to receive the 2009 Mayor’s Disability Advocate of the Year Award. The award committee noted his ‘efforts to remove barriers for people with disabilities and to be a voice for those unable to effectively represent themselves’. They went on to state ‘your work on behalf of the disabled community demonstrates your commitment to ideals that are key to equal participation and full inclusion of people with disabilities in Houston’.  Gary will be honored by Houston’s Mayor and Council Member Wanda Adams on Tuesday October 13, 2009 at 1:30 p.m. at the Council Chambers, City Hall, 901 Bagby.

Gary Lynn from Houston, TX  regularly holds events to raise money for cerebral palsy research. He has donated almost $12,000 to CPIRF because he understands the importance of research in preventing CP and improving the quality of life for both children and adults who have this condition. Gary, who has spastic, quadriplegic cerebral palsy, started his own foundation, the Gary J. Lynn Foundation because of his desire to help others with cerebral palsy who may not have been as blessed as Gary to help achieve their hopes and dreams and to enhance their lives.  Please visit Gary’s website www.thegaryjlynnfoundation.org to learn more about his Foundation and his many great fund-raising activities.

Three new research awards were made in 2009 by the CPIRF Board. The first award was made to Dr. Ahamed Hossain of the Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Dr. Ahamed Hossain

He plans to study neuronal pentraxin 1 (NP1), a novel neuronal protein and a member of a newly recognized subfamily of “long pentraxins”. His goal is to determine the role and function of this protein in the molecular cascade of neuronal death in neonatal brain injury triggered by a hypoxia-ischemic (HI) event, an important risk factor for the development of cerebral palsy. His previous work has shown that NP1 is induced in neonatal HI and that anti-sense oligonucleotides directed at NP1 mRNA prevent neuronal loss. The long term goal is to develop a molecular target (NP1) that will prevent hypoxic-ischemic brain injury in infants.

Dr. Greg Wilson

The second award was made to Dr. Greg Wilson of the Riley Hospital for Children in Indianapolis, IN. He will be studying the effectiveness of robots developed by Dr. Igo Krebs of MIT for both the shoulder and wrist of children with moderate to severe hemiplegic cerebral palsy in improving upper extremity function. In addition he and his team will determine if the random presentation of targets in the accompanying video portion of the robotic therapy leads to better transfer and retention of motor skills than an ordered presentation of targets in children with cerebral palsy. Motor learning literature suggests that random presentation leads to increased motor learning but this has not yet been studied in children with CP. This project will be conducted in the newly established robotics center at Riley which was made possible by the efforts of CPIRF Board Member Margaret Goldsmith and the Executive Director of UCP Indy, Donna Roberts.

Dr. Simona Bar-Haim

The third award was made to Dr. Simona Bar-Haim of the Assaf Harofeh Medical Center in Zerifin, Israel. Dr. Bar-Haim along with her Moroccan, Jordanian and Palestinian colleagues will be studying the effectiveness of shoes that employ the theory of “chaotic perturbation” in improving the walking ability of adolescents with spastic diplegic/tetraplegic cerebral palsy.

PIRF will award Diane Damiano, PT, PhD with the 2009 Weinstein-Goldenson Award at the American Academy of Cerebral Palsy and Developmental Medicine 63rd annual meeting on Friday, August 24th at the Celebration Dinner in Phoenix, AZ. The Weinstein-Goldenson Award is presented by CPIRF annually to a clinician-scientist for outstanding contributions in medical research which enhance the lives of persons with cerebral palsy and their families.

Dr. Diane Damiano

Dr. Damiano is currently the Director of Biomechanics at the NIH Clinical Center in Washington DC where she conducts research to investigate the neural and biomechanical mechanisms that underlie the motor disorder that is the hallmark of cerebral palsy and to identify and evaluate potential interventions to improve motor performance in individuals with CP. Dr. Damiano’s particular interest is in the effects of exercise on functional abilities and participation in those with CP. Regular and intense physical activity is an especially important concern for those with motor disabilities such as CP because they are at higher risk for activity limitation, face greater challenges in trying to stay active, and may suffer more devastating consequences over the lifespan if they are not active. Dr. Damiano, has been awarded numerous grants from the NIH for her research and has authored numerous papers and book chapters. She is asked to speak all over the world on her work as she was the first researcher to recognize that spastic muscles were, in fact, weak and needed strengthening. Dr. Damiano is a former Hausman Awardee, the career award given by CPIRF to support clinician-researchers while they pursue research in an area relevant to cerebral palsy while continuing to spend time providing hands-on clinical care to the developmentally disabled.

Dr. Hermano Igo Krebs

CPIRF will award the 2009 Isabelle and Leonard H. Goldenson Technology and Rehabilitation Award to Dr. Hermano Igo Krebs at the American Congress of Rehabilitation Medicine and the American Society of Neurorehabilitation Joint Educational Conference on Friday October 9th in Denver, Colorado. This award is presented annually to a scientist for outstanding contributions in the development and use of technology and rehabilitation methodologies that enhance the quality of life for individuals with cerebral palsy and other disabilities and their families. Dr. Krebs joined MIT’s Mechanical Engineering Department in 1997 where he is a Principal Research Scientist and Lecturer – Newman Laboratory for Biomechanics and Human Rehabilitation. He also holds an affiliate position as an Adjunct Research Professor of Neuroscience a Weill Medical College of Cornell University. He is a pioneer in the design, development, and testing of robots used to administer rehabilitation therapy to patients with stroke, multiple sclerosis, Parkinson’s Disease, and acquired brain injury for the improvement of upper and lower extremity function. Hermano Igo Krebs’ team has now focused on robotic devices to help cerebral palsy patients with upper body therapy, and they have also initiated a project to design a pediatric robot for the ankle. Results from three published pilot studies conducted by Dr. Krebs involving 36 children suggest that cerebral palsy patients can greatly benefit from robotic therapy. The studies indicate that robot-mediated therapy helped the children reduce impairment and improve the smoothness and speed of their reaching motions.