Predictive Value of S100-B and Copeptin for Outcomes following Seizure: The BISTRO International Cohort Study

Predictive Value of S100-B and Copeptin for Outcomes following Seizure: The BISTRO International Cohort Study

Yonathan Freund1,2*, Benjamin Bloom3,10, Jerome Bokobza2, Nacera Baarir4, Said Laribi5, Tim Harris3,10, Vincent Navarro6, Maguy Bernard7,9, Rupert Pearse8,10, Bruno Riou1,2, Pierre Hausfater1,2, the BISTRO investigators.

Source : 1 Sorbonne universités, UPMC Univ Paris 06, UMRS INSERM 1166, IHU ICAN, Paris, France, 2 Emergency Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France, 3 Emergency Department, Royal London Hospital, London, United Kingdom, 4 Emergency Department, Hôpital Tenon, APHP, Paris, France, 5 Emergency Department, Hôpital Lariboisière, APHP, Paris, France, 6 Neurology Department, Hôpital Pitié-Salpêtrière, APHP, Paris, France, 7 Biochemistry Department, Hôpital Pitié-Salpêtrière, APHP, Paris, France, 8 Adult critical care unit, Royal London Hospital, London, United Kingdom, 9 Université Paris 5 Paris Cité, Paris, France, 10 Queen Mary University of London, London, United Kingdom. PLoS ONE 10(4): e0122405. doi:10.1371/journal.pone.0122405

Abstract : Objective : To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. Methods : We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. Results : Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 ?g/l [95% CI 0.07–0.20] vs 0.09 ?g/l [0.07–0.14]) and copeptin (23 pmol/l [9–104] vs 17 pmol/l [8–43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51–0.64] and 0.59 [0.54–0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1–1.5]), provoked seizure (OR 4.93 [2.5–9.8]), complex partial seizure (OR 4.09 [1.8–9.1]) and first seizure (OR 1.83 [1.1–3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80–18.9] copeptin OR 1 [1.00–1.00]). Conclusion : The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes.