Fluorescent molecular peroxidation products: a prognostic biomarker of early neurologic deterioration after thrombolysis

Stroke. 2014 Feb;45(2):432-7. doi: 10.1161/STROKEAHA.113.003431. Epub 2013 Dec 12.

Abstract

Background and purpose: 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.

Keywords: biomarkers; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Biomarkers / blood*
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / etiology*
  • Disease Progression
  • Endpoint Determination
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Fluorescence
  • Humans
  • Male
  • Nervous System Diseases / etiology*
  • Oxidative Stress
  • Peroxides / blood*
  • Prognosis
  • Stroke / complications*
  • Stroke / drug therapy*
  • Thrombolytic Therapy / adverse effects*
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use
  • Tomography, X-Ray Computed

Substances

  • Biomarkers
  • Fibrinolytic Agents
  • Peroxides
  • Tissue Plasminogen Activator