INTRODUCTION: Intraventricular fibrinolytic therapy with plasminogen activators is an experimental treatment for posthemorrhagic hydrocephalus (PHH), but some infants do not respond. The objectives of this study are to investigate whether the levels of the main inhibitor of fibrinolysis (PAI-1) correlate with treatment outcome, whether there is a difference between the levels of PAI-1 before and after treatment, and between patients with PHH and normal controls.

METHODS: CSF samples from 16 infants with PHH (median 1065 gm, range 805-2600) and 7 controls (median 1300 gm, range 750-3010) were analyzed for PAI-1, using an ELISA technique. Pre treatment CSF was available from 12 infants; pre and post treatment CSF was available from 6. Six are now home without shunts, 9 are shunted, and 1 unshunted infant died with hydrocephalus.

RESULTS: Table PAI-1 levels were significantly higher in PHH patients who were shunted or died than in those not shunted. There was no significant change in CSF PAI-1 levels before and after administration of plasminogen activator. There was a highly significant difference between the PAI levels of patients with PHH compared with normal controls. PAI-1 was undetectable (<6 ng/ml) in the CSF of all control patients, but detectable in the CSF of all but one of the PHH patients.

Table 1
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CONCLUSION: PAI-1 is not detectable in normal neonatal CSF. PAI-1 is seen in the presence of PHH, and higher PAI-1 levels are associated with failure of intraventricular fibrinolytic therapy.