title: Fluorescent molecular peroxidation products: a prognostic biomarker of early neurologic deterioration after thrombolysis.
abstract: OBJECTIVE
  Fluorescent molecular peroxidation products (FMPPs) are considered potential markers of molecular oxidative damage and may provoke increased permeability and disruption of the blood-brain barrier. This study aimed to determine the value of FMPPs as a biomarker to predict neurological worsening related to early hemorrhagic transformation.
  
  
  METHODS
  Baseline FMPP levels were measured in 186 consecutive acute ischemic stroke patients before tissue plasminogen activator treatment was administered. A serial FMPP profile (baseline before tissue plasminogen activator treatment, and 1, 2, 12, and 24 hours from treatment) was determined in a subset of 100 patients. Computed tomographic scans were performed at admission and repeated at 24 to 48 hours or after neurological worsening occurred. Symptomatic intracranial hemorrhage was defined as blood at any site in the brain associated with neurological deterioration.
  
  
  RESULTS
  Patients who worsened had higher median FMPP levels compared with those who did not (59.68 [48.63-85.73] versus 44.87 [36.37-58.90] Uf/mL; P=0.035) at baseline. After logistic regression multivariate analysis, FMPP >48.2 Uf/mL together with age, hypertension, and systolic blood pressure remained baseline predictors of worsening at 48 hours. Moreover, baseline FMPP determination helped to distinguish between patients who worsened and those who did not (Integrated Discrimination Improvement index, 5.7%; P=0.0004). Finally, within patients who had worsened at 48 hours, those with symptomatic intracranial hemorrhage had higher FMPP levels (P=0.038).
  
  
  CONCLUSIONS
  FMPPs might be a valuable biomarker of poor early neurological outcome and be related to the appearance of symptomatic intracranial hemorrhage in tissue plasminogen activator-treated patients, one of the most feared neurological complications after thrombolytic treatment of acute ischemic stroke.
authors: From Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Barcelona, Spain (V.L., A.B., T.G.-B., A.P., M.H.-G., D.G., A.R., J.M.); Biochemistry and Molecular Biology Research Centre for Nanomedicine, Hospital Universitari Vall d'Hebron, Instituto de Salud Carlos III, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain (C.D., V.R.-S., P.M.-G., A.V.); Neurovascular Unit, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain (M. Rubiera, M. Ribó, C.A.M., J.A.-S.); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (C.E.); and Department of Neurology, University Hospital of Schleswig-Holstein, Kiel, Germany (C.E.).
authors: Víctor
authors: V
authors: Llombart
authors: Carmen
authors: C
authors: Dominguez
authors: Alejandro
authors: A
authors: Bustamante
authors: Victor
authors: V
authors: Rodriguez-Sureda
authors: Pilar
authors: P
authors: Martín-Gallán
authors: Angel
authors: A
authors: Vilches
authors: Teresa
authors: T
authors: García-Berrocoso
authors: Anna
authors: A
authors: Penalba
authors: Mar
authors: M
authors: Hernández-Guillamon
authors: Marta
authors: M
authors: Rubiera
authors: Marc
authors: M
authors: Ribó
authors: Christoph
authors: C
authors: Eschenfelder
authors: Dolors
authors: D
authors: Giralt
authors: Carlos A
authors: CA
authors: Molina
authors: José
authors: J
authors: Alvarez-Sabín
authors: Anna
authors: A
authors: Rosell
authors: Joan
authors: J
authors: Montaner
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D005453:Fluorescence; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology*; D018384:Oxidative Stress; D010545:Peroxides / Q000097:blood*; D011379:Prognosis; D020521:Stroke / Q000150:complications* / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D010545:Peroxides; D010959:Tissue Plasminogen Activator
keywords: biomarkers; stroke