"This study is the first to document high levels of glutamate in children who have suffered head injury," said Patrick M. Kochanek, M.D., associate professor of anesthesiology and critical care medicine and director, Safar Center for Resuscitation Research. "Our findings suggest directions for future research, including learning about the effects of glutamate on the developing brain in children and finding ways to block the injurious effect of toxic levels of glutamate and other neurochemicals and thus limit damage from traumatic brain injury, particularly among child abuse victims. In addition, this research suggests the possibility that specific biochemical markers in brain fluid may aid in the diagnosis of child abuse or shaken baby syndrome."

Head injury is the most common cause of childhood death and disability in the United States. Brain injury occurs in two stages. Initial or primary damage results from the direct impact of the trauma itself. Secondary damage occurs after the initial trauma—as brain tissue around the impact site swells, pressure inside the skull rises and a variety of chemical imbalances occur.

Child abuse is an important public health problem in the United States, with more than three million cases of child abuse or neglect reported in 1997. More than one million of these cases, or 15 out of every 1,000 children, was confirmed.

The study examined 37 patients treated at Children’s Hospital of Pittsburgh. The study group consisted of 18 children who had sustained severe traumatic brain injury. The normal comparison group consisted of 19 children who had undergone a spinal tap to rule out the diagnosis of meningitis. A spinal tap is a procedure where a needle is inserted into the spinal canal to obtain a sample of cerebrospinal fluid.

All of the children in the study group had drainage tubes placed as part of their care to allow physicians to monitor the pressure inside the skull and to remove fluid in and around the brain. High pressure within the skull, which can cause secondary injury to the brain by restricting blood flow, can be relieved in part by draining fluid. The drained fluid was then analyzed for neurochemicals, such as glutamate, aspartate and glycine, which can cause nerve cell injury. While all children with traumatic brain injury had toxic levels of neurochemicals, very young children and shaken-baby patients had extremely high levels of glutamate.

Researchers hypothesize that in shaken baby syndrome both direct impact injury and the violent force of shaking injure the brain. The shaking causes delicate brain tissues and blood vessels of infants to tear. Often, the entire brain is affected by the shaking. In addition, there is often delay in seeking medical attention for the infant.

The higher glutamate levels seen in younger patients than in older children or adults may also reflect, in part, an immature response to injury of an infant’s developing brain. Previous research has shown that the effects of glutamate on immature brain cells change as those cells age. Understanding these age-related differences is critical for the development of effective treatments to limit or prevent secondary brain damage caused by glutamate.

The study was led by Dr. Kochanek, with important contributions by Donald Marion, M.D., professor of neurologic surgery, director, UPMC Brain Trauma Research Center, and director, Center for Injury Research and Control (CIRCL); David Adelson, M.D., assistant professor of neurologic surgery, and director, pediatric neurotrauma, Children’s Hospital of Pittsburgh; Randall Rupell, M.D., fellow, Safar Center and department of pediatric critical care medicine, Children’s Hospital of Pittsburgh; and Stephen Graham, M.D., Ph.D., associate professor of neurology, University of Pittsburgh School of Medicine.

The study was funded through UPMC’s Center for Injury Research and Control (CIRCL), which earlier this year received a $4 million award from the Centers for Disease Control (CDC). CIRCL is one of only nine such programs in the United States with the official CDC designation as an injury control research center. CIRCL’s goals include the prevention of long-term disability caused by intentional and unintentional injuries through effective prevention programs and novel therapies; educational programs for health care providers, the general public and future injury prevention professionals; and development of better methods of injury surveillance.