title: Prognostic value of intrathecal heme oxygenase-1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients.
  
  
  METHODS
  Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed.
  
  
  RESULTS
  The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy).
  
  
  CONCLUSIONS
  The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.
authors.affiliation: Division of Neurosurgery, Department of Surgery, and.
authors.forename: Kuo-Chuan
authors.initials: KC
authors.lastname: Wang
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.forename: Jing-Er
authors.initials: JE
authors.lastname: Lee
authors.forename: Dar-Ming
authors.initials: DM
authors.lastname: Lai
authors.forename: Sheng-Jean
authors.initials: SJ
authors.lastname: Huang
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Jeng
authors.forename: Yong-Kwang
authors.initials: YK
authors.lastname: Tu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005293:Ferritins / Q000134:cerebrospinal fluid; D051547:Heme Oxygenase-1 / Q000134:cerebrospinal fluid*; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010108:Oxyhemoglobins / Q000134:cerebrospinal fluid; D011379:Prognosis; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010108:Oxyhemoglobins; D005293:Ferritins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001663:Bilirubin
keywords: DIND = delayed ischemic neurological deficit; GAM = generalized additive model; GOS = Glasgow Outcome Scale; HO-1; HO-1 = heme oxygenase–1; IVH = intraventricular hemorrhage; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies; bilirubin; cerebrospinal fluid; lactate; subarachnoid hemorrhage; vascular disorders