Abstracts

Rationale: We previously found that the concentration of soluble Intercellular Adhesion Molecule 5 (sICAM5) is low in epilepsy patient plasma compared to control patient plasma. We hypothesized that plasma concentrations of sICAM5 would be altered in patients with anoxic brain injury in status epilepticus and could be used as a biomarker for this condition.Methods: Patients were diagnosed as having hypoxic brain injury with cardiac arrest requiring hospitalization and hypothermia treatment protocol. Informed consent was obtained and plasma was collected from consecutive patients. Up to two samples of blood were obtained from patients, one on admission and one within 48 hours after being rewarmed. The plasma was isolated and stored at -80°C. We analyzed each sample in duplicate with a custom ICAM5 high-throughput ELISA on the Meso Scale Discovery (MSD) System at Cognizance Biomarkers, LLC.Results: 10 consecutive patients were enrolled, and 19 samples were collected. We found that the plasma of anoxic brain injury patients had mean sICAM5 concentrations of 280 +/- 194 pg/ml (range 65-843 pg/ml). Two patients had EEG diagnosed status epilepticus with EEGs showing diffuse voltage attenuation and GPEDs 107 hours and 150 hours after cardiac arrest. The sICAM5 levels for the status patients were almost identical to the patients who were not in status epilepticus with the mean for the four samples in status 272 +/- 198 pg/ml vs. 282 +/- 200 pg/ml for the patients not in status (p=0.9325 in two-tailed unpaired t test). In addition there was no difference in sICAM5 levels between those patients who ultimately survived (n=7) and those who did not (n=3) (p=0.9965). When four samples from the two patients who had neuroimaging that confirmed diffuse cortical injury (367 +/- 200 pg/ml) were compared to samples from seven patients that did not have evidence of diffuse brain injury on imaging(215 +/- 108 pg/ml), a p value of 0.0556 was obtained. For comparison purposes, cross-institutional non-neurological disease controls were assayed during the same MSD ELISA run and mean sICAM5=756+/-262 pg/ml (range 354-1197).Conclusions: sICAM5 plasma concentrations in patients who experienced status epilepticus during their admission for anoxic brain injury were no different from those in anoxia patients who did not experience status. Even in the most severely affected patients, the sICAM5 levels did not exceed historical control values, suggesting that even massive neuronal injury that might be expected to release sICAM5 intracranially did not result in an increase in plasma sICAM5; however no CSF sICAM5 concentrations were obtained, so we are unable draw conclusions about the mechanism of transfer of sICAM5 from the CNS to the plasma. We conclude that sICAM5 is not a useful biomarker for status epilepticus in patients with anoxic brain injury. However, given the strong trend towards relatively elevated values in those with radiologically confirmed diffuse cortical injury, further study of its usefulness in evaluating anoxic brain injury is warranted.