Clinical Neurosciences Center
Leaders in Hydrocephalus Research
One in 500 individuals requires management of intracranial pressure (ICP) resulting from hydrocephalus
Hydrocephalus can result from head injury, brain tumor, infection, congenital defect, intraventricular hemorrhage, or brain tissue deterioration associated with dementia. Treatment includes diverting excess cerebrospinal fluid (CSF) to the peritoneum or the atria, or for some, endoscopic third ventriculostomy. Programmable shunts may be used to noninvasively adjust CS F flow and intracranial pressure(ICP) parameters.
Seeking to Improve Outcomes
“Our goals are to prevent brain damage and promote brain repair,” says James P. (Pat) McAllister II, PhD, Professor of Neurosurgery and Director of Basic Hydrocephalus Research at The University of Utah School of Medicine. “To do this, we provide pathophysiological data for clinical decision-making, develop supplemental drug therapies, and seek to improve diagnostic and treatment tools through biomedical engineering.”
Dr. McAllister and his colleagues have been studying the pathophysiology of hydrocephalus for more than 25 years. His recent addition to the multidisciplinary team at The University of Utah Clinical Neurosciences Center and the Division of Pediatric Neurosurgery has created a unique group that seeks to identify major injury and genetic mechanisms via broad studies into neuroinflammation, gliosis, biomarkers, intracranial pressure and pulsatility, clearance of toxins and proteins, and the role of the lymphatic system in CS F absorption.
A major effort is devoted to determining the efficacy of anti-inflammatory agents as supplements to CSF shunting. Preliminary studies using the microglial cell inhibitor minocycline in an experimental model of congenital neonatal hydrocephalus have been very promising. Given systemically, this drug has prevented the proliferation of neuroinflammatory cells and reduced the size of the cerebral ventricles without shunting.
With regard to other injury mechanisms, Dr. McAllister says, “Surprisingly—because so many of the clinical problems facing the treatment of hydrocephalus involve shunt malfunction—no basic research has been performed on the effects of repetitive bouts of ventricular enlargement. We can model this situation in the lab, however, and should know soon if the damage is additive and preventable.”
The effort toward improving diagnostic and treatment tools includes high-power magnetic resonance imaging (MRI) to detect changes in CS F flow, Diffusion Tensor Imaging (DTI) to identify progressive tissue damage in white matter tracts, proteomic approaches that correlate CSF biomarkers of cytological changes with neurological outcome, as well as bioengineering approaches to minimize cell adhesion and tissue obstruction in shunt catheters and provide real-time measurements of ICP using implantable pressure sensors.
Clinical and basic studies also are underway on new biomarkers that could dramatically improve diagnoses of infection and the extent of brain damage for pediatric and adult patients. In particular, Ramin Eskandari, MD, a Neurosurgery Resident, will conduct a study to determine if intermittent drainage of CSF creates more damage than continuous drainage through a permanent shunt. This study will correlate white matter damage from the 7-Tesla MRI for DTI, cerebral metabolism using positron emission tomography (PET), and the new micro-PE T scanner with histopathology and CS F biomarkers of neuroinflammation and cellular damage.
A Model for Collaborative Research
Researchers and clinicians across the United States and in Canada pool information to advance treatment for children with hydrocephalus.
Driven by a vision of dramatically improving children’s lives, John R. W. Kestle, MD, Chief of the Division of Pediatric Neurosurgery and Director of the Residency Training Program of the Clinical Neurosciences Center at The University of Utah and several key colleagues co-founded the Hydrocephalus Clinical Research Network (HCRN ) to pool and coordinate data from larger patient populations. Principal investigators at member institutions in Texas, Alabama, Toronto, and Seattle joined the team in Salt Lake City to establish a registry of all patients with hydrocephalus at their institutions and investigate ways to reduce and treat shunt-related infections, identify patients most likely to benefit from endoscopic third ventriculostomy, utilize ultrasound guidance for shunt placement, and compare surgical management strategies affecting premature infants.
“Everyone here is involved in this network,” says Dr. Kestle. “This collaboration is unique and provides an excellent opportunity to do cutting edge research in hope of seeing our patients enjoy longer, better lives. As pediatric neurosurgeons, we are all involved in clinical research and clinical trials. Working with other pediatric hospitals through the Hydrocephalus Clinical Research Network expands the number of patients involved and helps us answer essential clinical questions.
To learn more about the Hydrocephalus Clinical Research Network, visit www.hcrn.org
For more information on research at the Clinical Neurosciences Center contact Neurosciences Public Affairs at 801-585-7777.