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Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus
1Joint Program in Neonatology, Children's Hospital, Boston, MA, USA.
Insights
Plasminogen activator inhibitor-1 (PAI-1) in cerebrospinal fluid predicts treatment failure for posthaemorrhagic hydrocephalus in infants receiving fibrinolytic therapy. Higher PAI-1 levels indicate poor response to this experimental treatment.
Area of Science:
- Neonatal Neurology
- Biochemistry
- Pediatric Neurosurgery
Background:
- Intraventricular fibrinolytic therapy using plasminogen activators is an experimental treatment for posthaemorrhagic hydrocephalus (PHH).
- Treatment response varies, with some infants not benefiting from this intervention.
- Understanding factors influencing treatment efficacy is crucial for optimizing care.
Purpose of the Study:
- To determine if plasminogen activator inhibitor-1 (PAI-1) is present in neonatal cerebrospinal fluid (CSF) in normal and posthaemorrhagic conditions.
- To investigate the association between neonatal CSF PAI-1 concentrations and the failure of fibrinolytic therapy in infants with PHH.
Main Methods:
- Analysis of CSF samples from 7 control infants and 16 infants with PHH.
- Fifteen of the PHH infants received exogenous fibrinolytic agents.
- Quantification of PAI-1 levels in CSF using laboratory analysis.
Main Results:
- PAI-1 was undetectable in control CSF samples.
- PAI-1 was detectable in nearly all posthaemorrhagic CSF samples.
- Significantly higher median PAI-1 levels were found in treatment failures (94 ng/ml) compared to treatment successes (25 ng/ml).
Conclusions:
- Elevated PAI-1 levels in neonatal CSF are predictive of fibrinolytic therapy failure in posthaemorrhagic hydrocephalus.
- High PAI-1 concentrations offer a potential biological explanation for non-response to intraventricular fibrinolysis.
- PAI-1 measurement may aid in identifying infants unlikely to benefit from this treatment.
Abstract:
Intraventricular fibrinolytic enhancement with plasminogen activators is an experimental treatment for posthaemorrhagic hydrocephalus, but some infants do not respond. The objectives of this study were to investigate whether plasminogen activator inhibitor-1 is detectable in normal or posthaemorrhagic neonatal cerebrospinal fluid and whether higher neonatal cerebrospinal fluid concentrations of plasminogen activator inhibitor-1 are associated with failure of fibrinolytic therapy. Cerebrospinal fluid samples from 7 controls and 16 infants with posthaemorrhagic hydrocephalus (15 treated with exogenous fibrinolytic agents) were analysed for plasminogen activator inhibitor-1. Plasminogen activator inhibitor-1 was not detectable in any of the control samples but was detectable in all but one of the posthaemorrhagic samples, and at significantly higher levels in the treatment failures (median 94 ng ml(-1)) than in the treatment successes (median 25 ng ml(-1)). High levels of plasminogen activator inhibitor-1 in the cerebrospinal fluid are predictive of, and provide a plausible biological explanation for, failure of intraventricular fibrinolytic therapy.