Report
Pediatric Neurotrauma Center (PNTC)
University of Pittsburgh
June, 2011
Summary
Over the past 3 years, the Pediatric Neurotrauma Center (PNTC) of the University of
Pittsburgh has continued to provide excellent care for children with traumatic brain
injury (TBI) and advance its other goals in research, education and advocacy.

The multidisciplinary clinical team cared for over 300 children demonstrating
superior outcomes as a result of the hard work from Neurosurgical residents,
Critical Care Fellows, Nurse Coordinators, Pediatric ICU nurses and the
combined efforts of faculty members from Critical Care Medicine,
Neurosurgery, Trauma Surgery, Pediatrics and other departments.

Research is expanding at a vigorous pace, with the completion of the “Cool
Kids” trial, the implementation of a new phase I/II clinical trial, the start of a
comparative effectiveness study to discern barriers to implementation of
evidenced-based guidelines, the continuing support of a T32-training grant in
pediatric neurocritical care.

Educational opportunities are myriad within the Center with weekly journal
clubs, case conferences and lectures to staff within the hospital and across
the country.

Important advocacy initiatives were also completed including the
development of a local community advisory board, leading the writing of new
guidelines for medical management of traumatic brain injury for children and
establishing common data elements necessary for future studies.

Continuing challenges include developing long-term neuropsychological
follow-up for children who are not on study protocols and continuing to
search for therapies to mitigate injuries in this vulnerable patient population.
Cover photographs of star patients
Left – 18 month old who had a TV fall on her head (pictured with her mom). She suffered
nearly fatal injuries to her skull base on Christmas Eve (including complete fracture of her
clivus), enrolled in “Cool Kids” study, required multiple surgical procedures, pentobarbital
coma and maximal medical therapies for months. In this picture, she is back for removal of
her tracheostomy at approximately 6 months after injury and tests at only 1 month behind
her age-group on neuropsychological evaluation.
Right – 15 year old who suffered severe TBI by falling from his motorcycle. He suffered an
intracerebral hemorrhage and subdural hematoma, enrolled in “Cool Kids” study, required a
medically-induced coma for 3 weeks and left the hospital with hemiparesis. Now 2 years
after injury, he is getting excellent grades in high school and has fully regained strength in
his extremities so that he can participate in sports.
Leadership
Michael Bell, Associate Professor, Critical Care Medicine and Neurological Surgery –
Director, PNTC
Senior Advisors
Robert Friedlander, Chairman, Neurological Surgery
Derek Angus, Chairman, Critical Care Medicine
Ian Pollack, Chief, Pediatric Neurological Surgery
Robert Clark, Chief, Pediatric Critical Care Medicine
Senior Contributors
Jeff Balzer, Assistant Professor, Neurological Surgery
Hülya Bayır, Associate Professor, Critical Care Medicine
Sue Beers, Associate Professor, Psychiatry
Rachel Berger, Associate Professor, Pediatrics
Ericka Fink, Assistant Professor, Critical Care Medicine
Barbara Gaines, Associate Professor, Surgery; Director, Trauma Surgery
Stephanie Greene, Assistant Professor of Neurological Surgery
Miguel E. Habeych, Assistant Professor of Neurological Surgery
Elizabeth Tyler-Kabara, Assistant Professor, Neurological Surgery
Patrick Kochanek, Professor, Critical Care Medicine
Mioara Manole, Assistant Professor, Emergency Department
Samuel Poloyac, Assistant Professor, Pharmacy
Mandeep Tamber, Assistant Professor, Neurological Surgery
Stephen Wisniewski, Professor, School of Public Health
Contributors
Alicia Au, Critical Care Medicine Clinical Instructor, NRSA Fellow
Chris Bonfield, Neurosurgery Resident
Philip Empey, Research Faculty, Pharmacy
Nikki Miller Ferguson, Critical Care Medicine Fellow
Kim Foster, Neurosurgery Resident
Allison Hricik, Outcomes Coordinator, Neurological Surgery
Peter Kim, Clinical Instructor, Neurological Surgery
Katherine Kirk, Medical Student III
Sandy Lam, Clinical Instructor, Neurological Surgery
Amit Mehta, Critical Care Medicine Fellow
Chris McKenna, Trauma Coordinator, Pediatric Surgery
Pawel Ochalski, Neurosurgery Resident
Veronica Ortiz, Medical Student IV
Rosanne Salonia, Critical Care Medicine Clinical Instructor, NRSA Fellow
Laurie Silfies, Data Manager, School of Public Health
Rebecca Smith, Critical Care Medicine Clinical Instructor, NRSA Fellow
Steve Shein, Critical Care Medicine Fellow, NRSA Fellow
Erik Su, Critical Care Medicine Clinical Instructor, NRSA Fellow
Research Coordinators
Rachelle Bell, RN
Maria Sidoni, RN
The Pediatric Neurotrauma Center (PNTC) was formed to comprehensively provide
care for children with traumatic brain injury in the catchment area that includes
western Pennsylvania, West Virginia and eastern Ohio and to merge this effort in
advanced care with research, education and advocacy efforts both within the
Pittsburgh region and throughout the world. As one of the most established and
comprehensive programs in the country, the PNTC has led the country in
establishing clinical guidelines for caring for children and performing trials to
improve outcomes.
Clinical Care/Education Summary
Clinical care of children with traumatic brain injury continues to be at the
cutting edge within the Center at Children’s Hospital of Pittsburgh of UPMC. The
physician care team is organized based on Pediatric Intensivists (including our
Neurocritical Care team), Neurosurgeons, Trauma Surgeons, Pediatricians,
Neuropsychologists and a host of other consultants required for the care of these
patients with complex illnesses. All of these physicians (Drs. Pollack, Tyler-Kabara,
Greene, Tamber, Bayir, Clark, Fink, Bell along with Dr. Gaines and the entire
Surgery Faculty) have worked tirelessly to provide care for these children within the
Center. In the past 3 years, we treated 351 children with moderate-severe TBI
within the PNTC. Unfortunately, we had 13 fatalities within this group - 4 children
who could not be resuscitated from multiple injuries (including presumed TBI) and
died upon arrival to the ED/PICU and 1 had support withdrawn after surviving his
moderate TBI with an unrecoverable high spinal cord injury. As a result, we have
observed a mortality rate of 2.3% for children with TBI.
There were many educational sessions within the PNTC in the last several
years. Rachelle Bell, RN and Maria Sidoni, RN provided in-services for the PICU
nursing and respiratory staff regarding administration of hypothermia and providing
consistent care to the head-injured child. Several lectures were given to the
Benedum Trauma Center and as a part of Critical Care Orientation for Nursing Staff.
Dr. Bell performed several visiting professorships to promote the work of the Center
(Cornell University, New York, NY; Massachusetts General Hospital, Boston MA;
New York Pediatric Critical Care Society, New York, NY; Children’s National Medical
Center, Washington, DC, Department of Pediatrics of the University of Pittsburgh
School of Medicine) among many other talks given by Senior Contributors to the
PNTC. Several lectures were given to provide an orientation to Surgery,
Neurosurgery and Critical Care Medicine trainees on the care for children with
severe TBI. A unique T32 training grant from the NIH focused on pediatric
neurocritical care supports our program was successfully renewed this year. Multidepartmental (critical care, neurological surgery, child neurology, pediatrics,
neuroradiology, emergency medicine, and physical medicine and rehabilitation) and
multidisciplinary investigation in traumatic brain injury in children is a central facet
of this grant. And a vibrant journal club schedule and case conference series (Safar
Journal Club, 9am Fridays at the Safar Center; Safar Rounds, 7am Wednesdays at
CHP) has been implemented to discuss the latest advances of care. As a result, the
clinical care and educational opportunities within the PNTC are broad and very
active. We hope to recruit a dedicated fellow in Neurocritical Care from the
specialties of Pediatric Neurosurgery, Pediatric Neurology and/or Pediatric Critical
Care Medicine in the future to offer a broadened educational and clinical experience
to talented young practitioners. Another remaining challenge for the PNTC is to
obtain neuropsychological outcomes from children who are not enrolled in clinical
studies, as insurance providers have not been universally willing to support these
vital tests for all children with moderate-to-severe TBI.
Research Summary
The ongoing research within the PNTC continues to be amongst the most
active and productive of any center across the country. Dozens of important
projects are ongoing, including observational and interventional trials. In the past
several months, the Center completed work on the Pediatric Traumatic Brain Injury
Consortium: Hypothermia Trial (the “Cool Kids Trial”). That trial, of which our
center enrolled nearly one-third of all the subjects (24 patients enrolled within the
PNTC out of the 78 total patients across 36 clinical sites in 3 countries), was
stopped due to the inability of the trial to detect a difference in the primary
outcome (overall mortality). Nevertheless, a clearer understanding on the role of
hypothermia after TBI was discerned and several other advances were made in
organizing interventional clinical trials and several ancillary studies performed
within the PNTC.
Two additional funded studies have begun in the past year. A phase I/II trial
of combinational drug therapy for TBI (using Probenecid and N-acetyl cysteine)
began enrollment in January 2011. In this study, 20 children will be randomized to
receive the combination of drugs or placebos, with the hypothesis that the
combination therapy will not cause increased adverse events but will lead to
increased anti-oxidant reserve within the serum and CSF. Another study
(Implementation Science to Increase Implementation of Evidenced-Based
Guidelines in Pediatric TBI: PI, Monica Vavilala, University of Washington) has
begun in the past year as well. In this study, adherence to the TBI Guidelines will
be measured and barriers to implementation of these guidelines at several sites
(including the PNTC) will be identified. The ultimate goal of this study is to increase
the utilization of evidenced-based care across the country.
Grants Currently Funded within PNTC
U01 NINDS – “Pediatric Traumatic Brain Injury Consortium: Hypothermia”; PI:
Adelson; Site PI: Bell – 2007 - 2012
R01, NINDS – “Overcoming Membrane Transporters to Improve CNS Drug
Therapy”; PI: Clark; Clinical PI: Bell - 2009 – 2014
R01, NINDS - “Implementation Science to Increase Implementation of EvidencedBased Guidelines in Pediatric TBI”; PI: Vavilala, University of Washington, Site PI:
Bell, 2010 – 2015
T32, NICHD – “Training in Pediatric Neurointensive Care and Resuscitation
Research”; PI: Kochanek, 2011-2016
R01, NICHD - "Novel approaches to Screening for Inflicted Childhood
Neurotrauma"; PI; Berger, 2009-2014
R01, NINDS – “Oxidative Lipidomics in Pediatric Traumatic Brain Injury”; PI: Bayir,
2008 – 2013
Selected Papers from the PNTC
Bell MJ and Kochanek PM. “Traumatic brain injury in children: Recent advances in
management”. Indian J Pediatr 75(11): 1159-1165, 2008.
Fink EL, Lai Y, Zhang X, Janesko-Feldman K, Adelson PD, Szabó C, Berger RP,
Sarnaik AA, Kochanek PM, Clark RS. “Quantification of poly(ADP-ribose)-modified
proteins in cerebrospinal fluid from infants and children after traumatic brain
injury”. J Cereb Blood Flow Metab 28 (9):1523-9, 2008.
Kochanek PM, Bell MJ, Adelson PD. “Critique of Traumatic Brain Injury Trial by
Hutchison et. al.”. N Engl J Med 359(11):1179, 2008.
Ochalski PG, Okonkwo DO, Bell MJ, Adelson PD. “Reversal of coma with flumazenil
in a child following a traumatic brain injury”. J Neurosurg Pediatr 3: 240-243, 2009.
Berger RP, Ta’asan S, Rand A, Lokshin A, Kochanek P. ”Multiplex assessment of
serum biomarker concentrations in well-appearing children with inflicted traumatic
brain injury”. Ped Research 65(1):97-102, 2009.
Fink EL, Beers S, Russell ML, Bell MJ. “Acute Brain Injury and Therapeutic
Hypothermia in the PICU: A Rehabilitation Perspective”. J Pediatr Rehab Med 2(4):
309-19, 2009.
Kochanek PM, Fink EL, Bell MJ, Bayir H, Clark RSB. “Therapeutic hypothermia:
Applications in pediatric cardiac arrest”. J Neurotrauma 26(3):421-7, 2009.
Sanchez de Toledo J, Adelson PD, Watson RS, Gaines B, Brown SD, Kochanek PM,
Wisniewski S, Fink EL, Bayir H, Clark RSB, Bell MJ. “Relationship Between Increases
in Pancreatic Enzymes and Cerebral Events in Children after Traumatic Brain
Injury”. Neurocrit Care 11: 322-329, 2009.
Exo J, Smith R, Smith C, Bell MJ. “Emergency Treatment Options for Pediatric
Traumatic Brain Injury”. Ped Health 3 (6): 533.541, 2009
Bayir H, Adelson PD, Wisniewski SR, Shore P, Lai Y, Brown D, Janesko-Feldman KL,
Kagan VE, Kochanek PM. “Therapeutic hypothermia preserves antioxidant defenses
after severe traumatic brain injury in infants and children” Crit Care Med 2009; 37:
689-95.
Fink EL, Kochanek PM, Clark RSB, Bell MJ. “How to Cool Children in Neurointensive
Care”. Neurocrit Care 12(3): 414-20, 2010.
Kochanek PM, Bell MJ, Bayır H. “Quo Vadis Carpe Diem: Challenges and
opportunities in pediatric traumatic brain injury”. Dev Neurosci. 32:335-42, 2010
Salonia R, Empey PE, Poloyac SM, Wisniewski SR, Klamerus M, Ozawa H, Wagner
AK, Ruppel1 R, Bell MJ, Feldman K, Adelson PD, Clark RSB and Kochanek PM.
“Endothelin-1 is Increased in Cerebrospinal Fluid and Associated with Unfavorable
Outcomes in Children after Severe Traumatic Brain Injury”. J Neurotrauma 27(10):
1819-25, 2010.
Berger RP, Bazaco MC, Wagner AK, Kochanek PM, Fabio A. ”Trajectory analysis of
serum biomarker concentrations facilitates outcome prediction after pediatric
traumatic and hypoxemic brain injury”. Dev Neurosci 32:396-405, 2010.
Mehta A, Kochanek PM, Tyler-Kabara E, Adelson PD, Wisniewski S, Berger RP,
Sidoni MD, Bell RL, Clark RSB and Bell MJ. “The Relationship Between Intracranial
Pressure (ICP) and Cerebral Perfusion Pressure with Outcome in Young Children
after Severe Traumatic Brain Injury”. Dev Neurosci 32(5-6): 413-9, 2010.
Su E, Bell MJ, Wisniewski SR, Adelson PD, Janesko-Feldman KL, Kochanek PM,
Kagan VE and Bayir H. “Alpha Synuclein Levels are Elevated in Cerebrospinal Fluid
Following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic
Hypothermia”. Dev Neurosci 32 (5-6): 385-95, 2010.
Sarnaik A, Conley YP, Okonkwo DO, Barr T, Fink EL, Szabo C, Kochanek PM, Clark
R. Influence of PARP-1 Polymorphisms in Patients after Traumatic Brain Injury. J
Neurotrauma, 27(3):465-71, 2010.
Berger R, Bell MJ. “Serum Biomarkers in Pediatric Traumatic Brain Injury” Current
Concepts in Pediatric Critical Care 2010, 21 - 30.
Exo J, Kochanek PM, Adelson PD, Greene S, Clark RSB, Bayir H, Wisniewski SR and
Bell MJ. “Intracranial Pressure Monitoring Systems in Children with Traumatic Brain
Injury: Combining Therapeutic and Diagnostic Tools”. Pediatr Crit Care 2011 (in
press).
Smith CM, Adelson PD, Chang Y-F, Brown SD, Kochanek PM, Clark RSB, Bayir H,
Hinchberger J and Bell MJ. “Brain-Systemic Temperature Gradient is Temperature
Dependent in Children with Severe Traumatic Brain Injury (TBI)”. Pediatr Crit Care
2011 (in press).
Fink EL, Kochanek PM, Clark RSB, Bell MJ. “Fever Control and Application of
Hypothermia Using Cold Intravenous Saline”. Pediatr Crit Care Med 2011 (in press).
Au A, Carcillo JA, Clark RSB, Bell MJ. “Brain Injuries and Neurological System
Failure are the Most Common Proximate Cause of Death in Children Admitted to a
Pediatric Intensive Care Unit”. Pediatr Crit Care 2011 (in press).
Malakouti A, Sookplung P, Siriussawakul A, Phillip S, Bailey N, Brown N, Farver K,
Zimmerman JJ, Bell MJ, Vavilala M. “Nutrition Support and Deficiencies in Children
with Severe Traumatic Brain Injury”. Pediatr Crit Care Med 2011 (in press).
Smith RL, Lin JC, Adelson PD, Kochanek PM, Fink EL, Wisniewski S, Bayır H, TylerKabara E, Clark RSB, Brown SD, Bell MJ. “Relationship Between Hyperglycemia and
Outcome in Children with Severe Traumatic Brain Injury”. Pediatr Crit Care Med
2011 (in press).
Berger RP, Hayes RL, Houle J-F, Mondello S, Wang K, Bell MJ. “Translating
Biomarkers Research to Clinical Care: Applications and Issues for Rehabilomics”
PM&R 2011 (in press).
Berger RP, Beers SR, Papa L, Bell MJ. “Common Data Elements for Pediatric
Traumatic Brain Injury: Recommendations from the Biospecimens and Biomarkers
Workgroup”. J Neurotrauma 2011 (in press).
Adelson PD, Pineda J, Bell MJ, Abend N, Berger RP, Giza C, Hotz G, Wainwright M..
“Common Data Elements for Pediatric Traumatic Brain Injury: Recommendations
from the Working Group on Demographics and Clinical Assessment”. J Neurotrauma
2011 (in press).
Adelson PD, Srivnas R, Chang Y-F, Bell MJ, Kochanek PM. “Cerebrovascular
Response in Children Following Severe Traumatic Brain Injury”. Child Nerv System
2011 (in press).
Kochanek PM, Fink EL, Bell MJ. “Re-warming after mild therapeutic hypothermia:
Clinical considerations” International Consensus Conference in Intensive Care
Medicine Symposium Program 2011 (in press).
Kochanek PM and Bell MJ. ”Neurological Emergencies and Stabilization”. In Nelson’s
Pediatrics 2011 (in press).
Weinstein S and Bell MJ. “Traumatic Brain Injury – Basic Review and Implications
for Epilepsy”. Curr Opin Neurol 2011 (in press).
Bell MJ. “Pediatric Neurocritical Care” in Pediatric Critical Care. Fuhrman BP and
Zimmerman J Ed. Mosby Elsevier Publishing, Philadelphia, PA, 2011 (in press).
Kochanek PM, Bell MJ, Bayir H, Forbes ML, Ruppel R, Adelson PD, Clark RSB.
“Severe Traumatic Brain Injury in Infants and Children” in Pediatric Critical Care.
Fuhrman BP and Zimmerman J Ed. Mosby Elsevier Publishing, Philadelphia, PA,
2011 (in press).
Advocacy Summary
Members of PNTC have been deeply involved national and international
efforts to develop standards for children with TBI. In winter of 2011, the NIH
developed working groups to standardize data collection methods for both clinical
care and for biomarkers for studies in pediatric TBI. The results of these efforts
were recently published in the Journal of Neurotrauma with the goal of
standardizing basic data collection within clinical trials so that the trials can be
rigorously compared. In addition, the Brain Trauma Foundation sponsored an effort
to re-consider the published Guidelines for Medical Management of Severe TBI for
Infants, Children and Adolescents (previously published in 2003). These new
recommendations are to be published in the spring of 2011 and will set standards
for caring for children with TBI.
Locally, a Community Advisory Board for the PNTC has been organized under
the leadership of Mr. Mark Napodano (parent of one of our patients from 2008). He
is actively recruiting other family members to join this group and it is expected that
they will advise us on how we can improve the care for the family of children with
TBI. Lastly, members of the PNTC continue to work with the Sarah Jane
Foundation, an effort started by Patrick Donohue in New York to advocate for
funding for children with inflicted traumatic brain injury and other acquired brain
disorders. Rachel Berger is leading the effort at the University of Pittsburgh and we
have been named the Pennsylvania Lead Center for the Pediatric Acute Brain Injury
Plan (PABI). We look forward to working with this national organization in
increasing awareness of brain injuries in children across the US and in our
community.
Future Plans and Goals

We plan to continue to provide state-of-the-art care for children with TBI and
incorporate new therapies and technologies into the Center. In order to
determine the full effectiveness of these new interventions, a comprehensive
program of neuropsychological testing of children who are not necessarily
enrolled in clinical trials will need to be implemented.

We plan to build a network of investigators within the US and in Europe in
order to study the effectiveness of the medical therapies for intracranial
hypertension and other care variables known to have important impact on
outcomes. While 25 US sites have already agreed to join our consortium, a
meeting is planned in Brussels in October 2011 where the collaboration will
be extended to European sites in conjunction with an NIH and European
Union initiative.

We plan on expanding the educational opportunities within the PNTC by
providing additional experience to NRSA-funded fellows in caring for children
with severe TBI and establishing TBI-specific simulation experiences for
trainees of all levels of experience.

We plan on recruiting at least 10 parents/families to join the Community
Advisory Board and develop a list of improvements that could be made to
improve the experiences of families who have children that suffer TBI.

A national meeting of the Pediatric Neurocritical Care Research Group, a
group of 40 centers from across the country that specialize in treating
children with brain injuries from trauma and other conditions, will be hosted
by the Pediatric Critical Care Medicine Division, Department of Critical Care
Medicine, University of Pittsburgh School of Medicine through generous
support from the Children's Hospital of Pittsburgh of UPMC on October 22 and
23rd, 2011.