Neil Osterweil

October 24, 2014

BOSTON — Serum levels of several common metabolites appear to be good biomarkers for estimating the severity of traumatic brain injury (TBI) and may serve as predictors of prognosis, Finnish investigators report.

A study comparing serum metabolite levels in adults with acute TBI with those of patients with acute orthopedic trauma but no acute or previous brain trauma showed that expression patterns of 43 metabolites significantly differed between TBI cases and controls, and that the differences were most pronounced among patients with severe TBI, said Jussi Posti, MD, PhD, a neurosurgeon at Turku University Hospital in Finland.

"These metabolic biomarkers found to be associated with a diagnosis of TBI also scaled with outcome, and were strongly associated with the worst patient outcomes. The metabolic patterns observed were unique to the TBI and showed no strong correlations with extracranial injuries," he said at the Congress of Neurological Surgeons (CNS) 2014 Annual Meeting here.

Dr Posti and colleagues looked at blood metabolite levels and patterns in 256 consecutive, nonselected adults with acute TBI and in 36 patients with acute orthopedic trauma without acute or previous brain disorders (controls).

The investigators collected blood samples at presentation and at 1, 2, 3, and 7 days after the injury.

Using two-dimensional gas chromatography coupled to time-of-flight mass spectrometry, they measured a total 851 metabolites, 43 of which differed significantly in expression patterns between TBI cases and controls.

The metabolites of note included small fatty acids such as decanoic and octanoic acid, amino acids such as serine and 1H-indole-3-acetic acid, and sugar derivatives such as glycerol.

The authors then conducted univariate and multivariate analyses to investigate correlations between metabolic patterns and TBI severity, clinical descriptors of TBI, and extracranial injury.

They found that the largest differences in metabolite levels were between patients with severe TBI and controls; the differences were "much smaller" between patients with moderate of mild TBI and controls, Dr Posti said.

They also found evidence of significant upregulation of several metabolites in the cerebrospinal fluid and brain microdialysate samples of newly arrived patients with severe TBI, suggesting that blood-brain barrier had been disrupted. These included decanoic acid, octanoic acid, glycerol serine, and 1H-Indole-3-acetic acid.

Samples taken the day after the injury continued to show marked differences between patients with severe TBI and controls, metabolite profiles similar to those seen in the samples obtained at patient presentation.

The investigators also created a statistical model to see whether serum metabolites could predict patient outcomes, determined by a Glasgow Outcomes Scale (extended) score of 4 (upper severe disability) vs greater than 4. They found a strong association between metabolic profiles and outcome, with an area under the curve of 0.88 (95% confidence interval, 0.78 - 0.96).

"These results show that metabolic patterns could provide an objective means of estimating TBI severity, based on the host metabolic response to injury," Dr Posti said.

These results show that metabolic patterns could provide an objective means of estimating TBI severity Dr Jussi Posti

Premature for Practice

However, two clinicians who heard the data presented but were not involved in the study say they are not ready to embrace metabolic studies in patients with TBI.

"Decanoic acid and some of these other metabolites that they're looking at are not traditional biomarkers," said Donald Marion, MD, MSc, senior consultant with the Defense and Veterans Brain Injury Center in Silver Spring, Maryland.

"I think it premature to change practice at this stage, because the infrastructure to gather all that metabolite data is not available at present, so it's really more of a scientific finding at this stage," said Shelly D. Timmons, MD, PhD, a neurotrauma and neurocritical care specialist at the Geisinger Medical Center in Danville, Pennsylvania. Dr Timmons co-moderated the session.

The study was partially funded by the European Commission. Dr Posti and Dr Marion have disclosed no relevant financial relationships. Dr Timmons disclosed relationships with Synthes and Solway Pharmaceuticals.

Congress of Neurological Surgeons (CNS) 2014 Annual Meeting. Abstract 155. Presented October 21, 2014.


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