Allison Gandey

May 06, 2009

May 6, 2009 (San Diego, California) — A new study using invasive monitoring techniques suggests that glutamate may play an important role in the pathophysiology of traumatic brain injury (TBI) and that changing glutamate levels may be indicative of prognosis after injury.

Presenting here at the American Association of Neurological Surgeons 77th Annual Meeting, the study authors showed that glutamate levels are correlated with mortality and 6-month functional outcome.

"We found multiple changes in glutamate levels over time," presenter Roukoz Chamoun, MD, from the Baylor College of Medicine, in Houston, Texas, said at the meeting. "A delayed increase carried the worst prognosis."

Dr. Roukoz Chamoun presenting at the meeting.

Session moderator Michael Fehlings, MD, from the Toronto Western Hospital, in Ontario, called the work interesting but left the details to discussant Geoffrey Manley, MD, from the University of California, San Francisco.

Dr. Manley praised the study, saying it is "stellar work from a great group." He pointed to a number of strengths, including the study's prospective design, its use of a large number of patients, and a 120-hour monitoring period. "This is an enormous amount of work," he emphasized.

"This study is asking a great question," Alex Valadka, MD, from the University of Texas Medical School, in Houston, told Medscape Neurology & Neurosurgery. "We know that too much glutamate is a bad thing, and we've already seen this in stroke as well as in trauma," he noted.

Invasive Monitoring

Investigators conducted a prospective study of 165 patients with traumatic brain injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous oxygen saturation, and cerebral microdialysis.

All patients had a Glasgow Coma Score of 8 or less within 48 hours of injury. The researchers treated patients according to a standard protocol at Ben Taub General Hospital in Houston.

They report that high glutamate values were predictive of poor outcome.

Table 1. Mortality Rate by Glutamate Level

Glutamate Level (µmol/L) Mortality Rate (%)
> 20 30.3
< 20 18

The researchers identified multiple patterns of glutamate changes over time and observed that these had different prognostic values. In pattern 1, glutamine levels tended to normalize over the monitoring period. In pattern 2, the levels tended to increase with time or remain abnormally high.

Table 2. Changes in Glutamate Level and Outcome

Glutamate Mortality (%) Improvement in Functional Outcome (%)
Pattern 1: Levels normalize 17.1 41.2
Pattern 2: Levels increase or remain high 39.6 20.7

"Glutamate levels and patterns measured by microdialysis appear to have an important role in traumatic brain injury," Dr. Chamoun told the meeting.

Dr. Manley said that future targeted clinical trials are warranted, but he raised some technical concerns. He wondered, for example, whether the placement of the probes during microdialysis might interfere with the glutamate levels and help explain the spike.

Dr. Chamoun acknowledges that many questions remain. During his presentation, he described a recent Cochrane review exploring the use of antiglutamate therapy. The work, he points out, suggests the benefits remain unproven.

This study was funded by the National Institutes of Health. The researchers have disclosed no relevant financial relationships.

American Association of Neurological Surgeons 77th Annual Meeting: Abstract 646. Presented May 4, 2009.