Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts.
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2013-01
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Cerebral palsy (CP) is a heterogeneous group of non-progressive motor disorders caused by injury to the developing fetal or infant brain. Although the defining feature of CP is motor impairment, numerous other neurodevelopmental disabilities are associated with CP and contribute greatly to its morbidity. The relationship between brain structure and neurodevelopmental outcomes in CP is complex, and current evidence suggests that motor and developmental outcomes are related to the spatial pattern and extent of brain injury. Given that multiple disabilities are frequently associated with CP, and that there is increasing burden of neurodevelopmental disability with increasing motor severity, global white matter (WM) connectivity was examined in a cohort of 17 children with bilateral CP to test the hypothesis that increased global WM damage will be seen in the group of severely affected (Gross Motor Function Classification Scale (GMFCS) level of IV) as compared to moderately affected (GMFCS of II or III) individuals. Diffusion tensor tractography was performed and the resulting fibers between anatomically defined brain regions were quantified and analyzed in relation to GMFCS levels. Overall, a reduction in total WM connectivity throughout the brain in severe versus moderate CP was observed, including but not limited to regions associated with the sensorimotor system. Our results also show a diffuse and significant reduction in global inter-regional connectivity between severity groups, represented by inter-regional fiber count, throughout the brain. Furthermore, it was also observed that there is a significant difference (p = 0.02) in long-range connectivity in patients with severe CP as compared to those with moderate CP, whereas short-range connectivity was similar between groups. This new finding, which has not been previously reported in the CP literature, demonstrates that CP may involve distributed, network-level structural disruptions.
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Englander, ZoĆ« A, Carolyn E Pizoli, Anastasiya Batrachenko, Jessica Sun, Gordon Worley, Mohamad A Mikati, Joanne Kurtzberg, Allen W Song, et al. (2013). Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts. NeuroImage. Clinical, 2(1). pp. 440ā447. 10.1016/j.nicl.2013.03.006 Retrieved from https://hdl.handle.net/10161/24676.
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Scholars@Duke
Jessica Muller Sun
Gordon Worley
Dr. Gordon Worley specializes in Neurodevelopmental Disabilities, a sub-specialty of Pediatrics focusing on the management of the medical problems of children with physical disabilities. The principal diagnoses he treats are cerebral palsy, spina bifida, and Down syndrome. HIs research pertains to clinical problems of children with these conditions. Current research interests include genetic factors influencing outcomes of Extremely Low Birth Weight Infants using analyses of a large data set; comparison of outcomes of prenatal (in utero) surgery vs postnatal for lesion closure in meningomyelocele using the National Spina Bifida Patient Registry; Down Syndrome Disintegrative Disorder; and associations of ADHD with high risk sexual behaviors using analyses of a large data set.
Mohamad Abdul Mikati
Mohamad A. Mikati M.D., is the Wilburt C. Davison Professor of Pediatrics, Professor of Neurobiology, and Chief of the Division of Pediatric Neurology. Dr. Mikatiās clinical research has centered on characterization and therapy of pediatric epilepsy and neurology syndromes, describing several new pediatric neurological entities with two carrying his name (POSSUM syndromes # 3708 and 4468), developing novel therapeutic strategies for epilepsy and related disorders particularly Alternating Hemiplegia of Childhood, and applying cutting edge genetic and Magnetic Resonance Imaging techniques to drug resistant pediatric epilepsy. In the laboratory he has elucidated mechanisms of seizure related neuronal injury, particularly those related to the ceramide pathway, and demonstrated neuroprotective effects of several agents including erythropoietin. Most recently he has concentrated his laboratory research on the pathophysiology of ATP1A3 dysfunction in the brain as model for epilepsy and of Alternating Hemiplegia of Childhood. He has more than 290 peer reviewed publications, 400 abstracts 41 chapters one book and two booklets. He also has more than 10,497 citations in the literature with an h-index of 58 and an i-10index of 190. Dr. Mikati has written chapters on epilepsy and related disorders in the major textbooks of Pediatrics and Pediatric Neurology including Swaimanās Pediatric Neurology and Nelsonās Pediatrics. Before joining Duke in 2008 he had completed his M.D. and Pediatric training at the American University of Beirut, his Neurology at the Massachusetts General Hospital, his Neurophysiology at Boston Childrenās Hospital and had been on the Faculty at Harvard as Director of Research in the Epilepsy Program at Boston Childrenās Hospital and then as Professor and Chairman, Department of Pediatrics, Founder and Director of the Adult and Pediatric Epilepsy Program at the American University of Beirut. Dr. Mikati has had several international leadership roles including being President of the Union of the Middle Eastern and Mediterranean Pediatric Societies, on the Standing Committee of the International Pediatric Association (IPA), Chair of the Strategic Advisory Group on Early Childhood Development of the IPA, Officer of the International Child Neurology Association, Consultant to UNICEF, WHO, and the American Board of Pediatrics. He was selected to organize and chair the American Epilepsy Society's Merritt-Putnam Symposium and was one of only two Pediatric Neurologists, initially chosen worldwide, on the WHO advisory committee for the International Classification of Disease. He has received several national and international honors including, among others, Merritt Putnam American Epilepsy Society Fellowship Award, Harvard Community Health Plan Peer recognition Award, Debs Research Award, Hamdan Award for contributions to Medicine, Hans Zellweger Award for contributions to Pediatric Neurology, Patient Choice Award and the Michael Frank Award for research and lifetime contributions to the field of Pediatric Neurology.
Joanne Kurtzberg
Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine. Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University. The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program. The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.
Dr. Kurtzbergās research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury ā hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.
In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA. She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.
Allen W Song
The research in our lab is concerned with advancing structural and functional MRI methodologies (e.g. fast and high-resolution imaging techniques) for human brain imaging. We also aim to improve our understanding of functional brain signals, including spatiotemporal characterizations of the blood oxygenation level dependent contrast and alternative contrast mechanisms that are more directly linked to the neuronal activities. Additional effort is invested in applying and validating the developed methods to study human functional neuroanatomy.
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