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Critically ill patients may suffer delirium, encephalopathy or other neurobehavioral abnormalities, often with lasting effects. This is thought to be a result of systemic inflammation which compromises the blood brain barrier and leads to neural damage. The hippocampus is particularly sensitive to inflammatory and hypoxic change, both common sequelae to acute severe illness and/or chronic debilitating disease. Brain imaging studies demonstrate that patients suffering dementia, post traumatic stress disorder and depression characteristically show hippocampal atrophy, thought to be related to inflammation.
The correlation between serum inflammatory biomarkers and atrophic brain changes on imaging scans led researchers at the University of Bonn to investigate the plausibility of using these inflammatory markers as predictors of brain anomalies. In a retrospective study involving 22 critically ill patients hospitalized (ICU) between 2004 and 2006, the investigators examined several aspects of the brain in conjunction with inflammatory markers: systemic inflammatory response syndrome (SIRS) criteria (body temperature, heart rate, respiratory rate, white blood cell count), C-reactive protein (CRP), pro-calcitonin (PCT), interleukin-6 (IL-6) and two ICU scoring systems. Serum inflammatory biomarkers were obtained from hospital files and MRI scans were conducted within 6 to 24 months after hospitalization. Patients could have no history of dementia, stroke, head trauma, renal failure, hepatic disease, or other illness that would add variability to results. They were hospitalized with pancreatitis, coronary by-pass, pneumonia, aortic aneurysm, meningitis, intestinal surgery, and non-head trauma. Thirty gender-matched healthy subjects were used for controls.
MRI scans on all participants evaluated whole brain, white matter, grey matter, hippocampus and cerebrospinal fluid (CSF) volumes, corrected for age differences and total intracranial volume. Analyze software was used to compute volume measures for all structures.
Hippocampal volume and white matter volume were statistically significantly reduced in critically ill patients compared to normal subjects. Serum inflammatory biomarker, PCT was highly statistically associated with hippocampal volume, and IL-6 less markedly so. High levels of PCT and IL-6 were significant predictors of lowered hippocampal volume, but no other brain parameters were dependent upon these two markers. Higher CRP predicted reduced grey matter. SIRS criteria and the ICU scoring systems did not correlate with any brain volume changes.
The small sample size, use of matched healthy subjects for MRI controls rather than baseline scans, and potential contributions to brain volume decrease from other factors such as hypoxia, medications, electrolyte imbalance or dehydration, could have influenced the results of the Bonn study. However, the findings are corroborated by a couple of large epidemiological studies which found similar correlations between serum inflammatory markers and brain atrophy. For example, IL-6 and CRP were related to increased white matter hyperintensities volume and lower grey matter volume in the 3-C Dijon Study, an examination of almost 2,000 dementia-free elderly patients. In the Framingham Heart Study, IL-6 and CRP were associated with greater incidence of brain atrophy. Neither of theses studies included PCT. The Bonn research suggests that high serum levels of PCT, IL-6 and CRP may signal damaging effects to the brain, especially the hippocampus, while other ICU scoring systems are unable to detect such brain alterations. Such information may hold great advantage for identifying critically ill patients who could benefit from neuroprotective interventions.
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Tags: Brain Studies, Brain Volume, Hippocampal Atrophy, Hippocampus