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Intracerebral haemorrhage (ICH) accounts for approximately 10% of strokes and is a life threatening condition with a 30 day mortality rate of about 45%.1 The adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are proinflammatory parameters for the activation of the immune system.2,3 They have been correlated with acute inflammation in several systemic and neurological inflammatory diseases. Recently, it was suggested that an inflammatory reaction is responsible for reperfusion damage leading to brain damage and tissue destruction after acute ischaemia and subarachnoid haemorrhage.3,4 In this study, we investigated whether ventricular cerebrospinal fluid (CSF) and serum concentrations of adhesion molecules can be used as prognostic markers for the clinical outcome of patients with ICH.
For this purpose, we studied prospectively 10 patients with acute ICH and ventricular tamponade. Estimated blood volume of the ICH was between 40 and 60 ml in all patients. Initial intubation and mechanical ventilation due to coma were required in all patients. All of them were being treated at the neurological intensive care unit after neurosurgical application of a ventricular drainage to treat acute hydrocephalus. Paired serum and CSF samples from the ventricular drainage were obtained within eight hours after the first symptoms attributed to ICH and within three hours after operation. Concentrations of soluble ICAM-1 (sICAM-1) and sVCAM-1 were determined by enzyme linked immunosorbent assay (ELISA). In corresponding clinical examinations, the Scandinavian stroke scale and Glasgow coma scale scores were determined. The patients were categorised into two groups: patients who survived (n = 6) and patients who died (n = 4) from cerebral causes within eight weeks after the onset of ICH. Patients with prior cerebrovascular diseases and patients who subsequently died of non-cerebral causes were excluded from this pilot study. Data were analysed using the SPSS statistical program (SPSS, Chicago, Illinois, USA). The Wilcoxon test was applied to compare the two patient groups.
The two patient groups (surviving versus non-surviving) did not differ statistically with regard to age, sex, location and size of ICH, and initial Glasgow coma scale and Scandinavian stroke scale scores. As fig 1 shows, the CSF concentrations of sICAM-1 were below 13.7 ng/ml (mean (SD) 8.7 (4.7) ng/ml) and of sVCAM-1 below 35.4 ng/ml (11.5 (13.1) ng/ml) in the group of patients who survived (n = 6). However, in patients with a lethal outcome (n = 4), initial ventricular CSF concentrations of sICAM-1 were above 18.3 ng/ml (25.5 (9.3) ng/ml) and of sVCAM-1 were above 44.5 ng/ml (76.8 (45.0) ng/ml). These differences were significant for the CSF concentrations of sICAM-1 (p < 0.01) and of sVCAM-1 (p < 0.01). However, the concentrations of adhesion molecules in serum did not differ significantly (non-surviving: 444 (152) ng/ml for sICAM-1, 1422 (465) ng/ ml for sVCAM-1; surviving: 463 (110) ng/ml for sICAM-1, 1147 (382) ng/ ml for sVCAM-1).
This is the first study to investigate soluble adhesion molecules in CSF and serum in patients with ICH with ventricular tamponade. We found a strong correlation between clinical outcome and the concentrations of soluble adhesion molecules in the CSF of patients with acute ICH and ventricular drainage. Moreover, we found more than threefold increases of sICAM-1 and of sVCAM-1 in the CSF of patients with lethal outcome as compared with CSF concentrations from patients with multiple sclerosis (s-ICAM-1: 2.8 ng/ml, range 0.9–12.7; sVCAM-1: 4.2 ng/ml, range 0–21.5) and from healthy donors (sICAM-1: 5.2 (2.2) ng/ ml) as determined in our laboratory by identical test systems.2,5 The finding that the soluble adhesion molecules were increased in CSF but not in serum may indicate that the process leading to poor outcome occurs predominately in the brain. There are two possible explanations for the origin of increased CSF concentrations of soluble adhesion molecules. Firstly, brain tissue destruction may lead primarily to the release of adhesion molecules due to necrotic destruction. Secondly, ICH may initiate an inflammatory process leading to secondary brain damage, as has been suggested in human ischaemic stroke,4 as well as for experimental ICH and subarachnoid haemorrhage in animal models.1,3 With regard to the second hypothesis, it would be interesting to investigate the effects of early anti-inflammatory treatment in patients with ICH and an initial highly increased concentration of adhesion molecules in their ventricular CSF samples. In this condition, early application of corticosteroids may be useful to suppress the deviating inflammatory reaction.2 The blockage of ICAM-1 and VCAM-1 by systemic treatment with monoclonal antibodies would probably not be helpful, as the pathogenetic concept is to block the migration of inflammatory cells into the central nervous system.1 However, based on our results, it can be speculated that these cells are already inside the central nervous system and thus out of reach of these antibodies.
With these data of only 10 patients, it cannot finally be concluded whether the increased soluble adhesion molecules in CSF are indicators of the fatal process or are responsible for the initiation of secondary brain damage.
Dr B Engelhardt is gratefully acknowledged for critically discussing the manuscript.