In our laboratory, we study disorders of cerebrospinal fluid (CSF) physiology such as hydrocephalus and Chiari-associated syringomyelia. We employ a broad range of experimental methodologies—from CSF analysis to advanced MRI—to examine these common and important clinical problems. We work to bring together complementary expertise and experience to conduct multi-modality, multi-disciplinary, and often multi-institutional collaborative research.
In our laboratory, we focus on cerebrospinal fluid physiology, both under normal conditions and in pathological states such as hydrocephalus and syringomyelia. We have built two main study lines unified by disturbances in cerebrospinal (CSF) hydrodynamics. The first study line focuses on hydrocephalus, specifically post-hemorrhagic hydrocephalus of prematurity and congenital hydrocephalus. Our translational research efforts are directed toward characterizing CSF markers of hydrocephalus and evaluating protein mediators of neurodevelopment. In partnership with the Hydrocephalus Clinical Research Network (HCRN), we have developed a multi-institutional CSF repository to facilitate the study of CSF biomarkers with detailed clinical and neurodevelopmental data. Our second study line, primarily a clinical and image-based research project, focuses on syringomyelia associated with Chiari type I malformation (CM+SM). With generous philanthropic support, we have created the Park-Reeves Syringomyelia Research Consortium (PRSRC), a 28-center North American research collaboration designed to identify the best neurosurgical practices for the treatment of CM+SM.
For both the hydrocephalus and Chiari-associated syringomyelia study lines, we are actively engaged in the application of novel and advanced imaging techniques, such as MRI diffusion tensor imaging, resting state functional connectivity, elastography, cine phase contrast, and TRUE FISP to better understand the pathophysiology of both conditions.
Hydrocephalus Study Line David Limbrick, M.D., Ph.D. Pat McAllister, Ph.D. Diego Morales, M.S. Leandro Castaneyra-Ruiz, Ph.D. Brandon Baksh Former Lab Members: Haejun Ahn Matt Rantfle Shawgi Silver Gakwaya Habiyaremye Clint Morgan Miya Smith Daniel Berger Chiari-associated Syringomyelia Study Line David Limbrick, M.D., Ph.D. Michael Lehmkuhl, Clinical Research Nurse Jacob Greenberg, M.D. and M.S.C.I. TL-1 student Former Lab Members: David Kim, M.D. student Jake Godzik, M.D. student
- Hydrocephalus Clinical Research Network
- Park-Reeves Syringomyelia Research Consortium
- The Washington University Proteomics Core Facility
- The Hope Center for Neurological Disorders, Washington University
- Hope Center Program on Protein Aggregation and Neurodegeneration (HPAN)
- Terrie Inder, Brigham and Women’s Hospital, Harvard University
Limbrick, D.D.J. and Park, T.S. Occult hydrocephalus in children with cerebral palsy. Neurosurgery 58(3):E590, 2006. Miller, J.H., Limbrick, D.D.J., Callen, M., and Smyth M.D. Spontaneous resolution of Chiari type I malformation in monozygotic twins. J Neurosurg Peds 2: 317-19, 2008. Limbrick, D.D.J., Mathur, A., Munro, R., Johnston, J.M., Sagar, J., Inder, T., Park, T.S., Leonard, J.R., Smyth, M.D. Neurosurgical treatment of progressive post-hemorrhagic ventricular dilatation in preterm infants: a 10-year single-institution study. J Neurosurg Peds 6:224-30, 2010. Yarbrough, C.K., Powers, A.K., Park, T.S., Leonard, J.R., Limbrick, D.D., Smyth, M.D. Type 1 Chiari Malformation Patients Presenting with Acute Neurological Deficits: Case Series and Review of Literature. J Neurosurg Peds 7:244-7, 2011. Morales, D.M., Townsend, R. LeDuc, R., Malone, J.P., Ewersmann, C.A., Inder, T.E., and Limbrick, D.D.J. Alterations in Protein Regulators of Neurodevelopment in the Cerebrospinal Fluid of Infants with Post-hemorrhagic Hydrocephalus of Prematurity. Molecular and Cellular Proteomics 11:M111.011973, 2012. Buckley, R.T., Yuan, W., Mangano, F.T., Phillips, J.M., Powell, S., McKinstry, R., Rajagopal, A., Jones, B.V., Holland, S., and Limbrick, D.D.J. Longitudinal comparison of diffusion tensor imaging parameters and neuropsychological measures following endoscopic third ventriculostomy for hydrocephalus. J Neurosurg: Pediatrics 9:630-35, 2012. Srinivasakumar, P., Limbrick, D., Munro, R., Inder, T., and Mathur, A.M. Timing And Mode Of Neurosurgical Intervention in Progressive Post Hemorrhagic Ventricular Dilatation (PPHVD). J Perinatology 30:207-14, 2013. Yuan, W., McKinstry, R.C., Shimony, J.S., Altaye, M., Powell, S., Phillips, J.M, Limbrick, D.D.J., Holland, S.K., Jones, B.V., Rajagopal, A., Simpson, S., Mercer, D., Mangano, F.T. Diffusion Tensor Imaging Properties and Neurobehavioral Outcomes in Children with Hydrocephalus. Am J Neuroradiol 34:439-45, 2013. Limbrick, D.D.J., Lake, S., Talcott, M., Alexander, B., Wight, S., Willie, J., Richard, D., Genin, G., Leuthardt, E.C.The Baric Probe: a novel long-term implantable intracranial pressure monitor with ultrasound-based interrogation. J Neurosurg: Pediatrics 10:518-24, 2012. Akbari, S.H., Limbrick, D.D. Jr., Kim, D.H., Narayan, P., Leonard, J.R., Smyth, M.D., Park, T.S. Surgical Management of symptomatic Chiari II malformation in infants and children. Childs Nerv Syst 2013 Feb 7. [Epub ahead of print] He, Y., Murphy, R.K., Roland, J.L., Limbrick, D.D. Jr. Interactions between programmable shunt valves and the iPad3 with Smart Cover. Childs Nerv Syst29:531-3, 2013. Wellons, J.C. 3rd, Holubkov, R., Browd, S.R., Riva-Cambrin, J., Whitehead, W., Kestle, J., Kulkarni, A.V.; Hydrocephalus Clinical Research Network. The assessment of bulging fontanel and splitting of sutures in premature infants: an interrater reliability study by the Hydrocephalus Clinical Research Network. J Neurosurg Pediatr 11:12-4, 2013. Ranalli, N.J., Limbrick, D.D.J., and Park, T.S. Outcomes for the surgical management of Chiari I and Chiari II malformations, in Oakes W.J. and Tubbs, R.S. (eds.) The Chiari Malformations Springer, 2012. Leonard, J.R. and Limbrick, D.D.J. Intraventricular Hemorrhage and Post-Hemorrhagic Hydrocephalus, in Albright A.L. (ed.) Principles and Practice of Pediatric Neurosurgery Thieme New York, 2013. Kulkarni, A.V., Riva-Cambrin, J., Butler, J., Browd, S.R., Drake, J.M., Holubkov, R., Kestle, J.R.W., Limbrick, D.D., Simon, T.D., Tamber, M., Wellons, J.C. III, Whitehead, W.E. for the Hydrocephalus Clinical Research Network. Outcome of CSF shunting in children within a North American multicenter collaborative: results from the Hydrocephalus Clinical Research Network (HCRN) compared to historical controls. J Neurosurg Pediatr In press. Rajagopal, A., Shimony, J.S., McKinstry, R.C., Altaye, M., Maloney, T., Mangano, F.T., Limbrick, D.D., Holland, S.K., Jones, B.V., Simpson, S., Mercer, D., Yuan, W. White matter microstructural abnormality in children with hydrocephalus detected by probabilistic diffusion tractography. Am J Neuroradiol In press. Godzik, J., Kelly, M.P., Lenke, L.G., Park, T.S., Leonard, J.R., Limbrick, D.D.J. Relationship between Syringomyelia Size and Spinal Deformity in Patients with Chiari I Malformation. J Neurosurg Pediatr In press. Akbari, S.H.A., Holekamp, T.F., Murphy, T.M., Mercer, D., Leonard, J.R., Smyth, M.D., Park, T.S., and Limbrick, D.D.J. Surgical management of complex, multiloculated hydrocephalus in infants and children. Childs Nervous Syst In press. Whitehead, W.E., Riva-Cambrin, J., Wellons, J.C. III, Kulkarni, A.V., Browd, S., Limbrick, D.D.J., Rozzelle, C., Tamber, M., Simon, T., Holubov, R., Oakes, W.J., Luerssen, T.G., Walker, M.L., Drake, J.M., and Kestle, J.R.W. for the Hydrocephalus Clinical Research Network. Factors associated with ventricular catheter movement and inaccurate catheter location in the ultrasound study. J Neurosurg Pediatr In press. Morales D.M., Holubkov, R. Ahn H., Inder T.E., Limbrick, D.D.J. Cerebrospinal fluid levels of APP correlate with ventricular size in post-hemorrhagic hydrocephalus of prematurity. PLoSOne In press. Akbari, S.H.A., Limbrick, D.D.J., Yuan, W., Holland, S.K., Jones, B.V., Mangano, F.T., McKinstry, R.C., Shimony, J. Periventricular Hyperintensity in Children with Hydrocephalus. Pediatr Radiol In press.