Fluorescent molecular peroxidation products: a prognostic biomarker of early neurologic deterioration after thrombolysis
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Published on: September 25, 2016
Víctor Llombart1, Carmen Dominguez, Alejandro Bustamante
1From 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.).
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.
Insights
Fluorescent molecular peroxidation products (FMPPs) can predict neurological worsening after stroke treatment. Higher FMPP levels indicate a greater risk of poor outcomes and symptomatic intracranial hemorrhage in acute ischemic stroke patients.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Oxidative Stress Research
Background:
- Fluorescent molecular peroxidation products (FMPPs) are potential indicators of molecular oxidative damage.
- FMPPs may increase blood-brain barrier permeability and disruption.
- Early identification of neurological worsening in stroke patients is crucial.
Purpose of the Study:
- To evaluate FMPPs as a biomarker for predicting neurological worsening.
- To assess the relationship between FMPPs and early hemorrhagic transformation after stroke.
- To determine the predictive value of FMPPs in acute ischemic stroke patients receiving tissue plasminogen activator (tPA).
Main Methods:
- Measured baseline FMPP levels in 186 acute ischemic stroke patients before tPA.
- Assessed serial FMPP levels at multiple time points post-treatment in 100 patients.
- Utilized computed tomography scans for monitoring and defined symptomatic intracranial hemorrhage.
Main Results:
- Patients with neurological worsening had significantly higher baseline FMPP levels (P=0.035).
- FMPP levels >48.2 Uf/mL, along with age, hypertension, and systolic blood pressure, predicted worsening at 48 hours.
- Baseline FMPP levels effectively distinguished between patients who worsened and those who did not (P=0.0004).
Conclusions:
- FMPPs show promise as a biomarker for poor early neurological outcomes in tPA-treated stroke patients.
- Elevated FMPP levels may be linked to the development of symptomatic intracranial hemorrhage.
- FMPPs could aid in identifying patients at risk for severe complications after stroke thrombolysis.
