PHASE-I STUDY OF INTRAVENTRICULAR RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR FOR TREATMENT OF POSTHEMORRHAGIC HYDROCEPHALUS

Aim-Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of cle aring blood fi om the cerebrospinal fluid, and thus preventing permane nt hydrocephalus. Methods-Twenty two preterm infants, aged 7 to 26 day s, with progressive posthaemorrhagic ventricular dilatation (ventricul ar width > 4 mm over 97th centile) received one to five intraventricul ar bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to sev en days. Results-The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 mu g/ml. The half life of tPA in cerebrospin al fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55 %) without shunt surgery. One infant had secondary intraventricular ha emorrhage. Conclusion-Intraventricular tPA resulted in survival withou t a shunt for most of the infants, but with some risk. Failure may hav e been due to plasminogen deficiency, an inhibitor, or late interventi on.