Brain Imaging Findings Show Efficacy of Fetal Endoscopic Third Ventriculostomy as Prenatal Treatment for Induced Congenital Hydrocephalus in Fetal Lambs.

Background and objectives: Congenital obstructive hydrocephalus (HCP) causes progressive, irreversible fetal brain damage through ventricular enlargement and increasing fetal cerebral tissue compression. Postnatal treatments of choice include ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV). Intrauterine treatments, such as ventriculoamniotic shunting, were attempted unsuccessfully 4 decades ago and failed to improve postnatal outcomes, likely due to inadequate fetal patient selection. The aim of this study was to evaluate the efficacy of prenatal ETV for early ventricular decompression and potential prevention of fetal brain damage in hydrocephalic fetal lambs.

Methods: HCP was induced in 24 fetal lambs by injecting BioGlue into the cisterna magna at E85. Three weeks later (E105-110), fetal ETV was successfully performed on 8 fetuses using a small rigid cystoscope. Fetal brain lateral ventricular diameters and cerebral mantle thicknesses were monitored by prenatal and postnatal ultrasounds and fetal MRI.

Results: According to the Cincinnati HCP Severity Scale, moderate and severe HCP subgroups responded positively to fetal ETV with reduced cerebral ventricular diameters. Ten days post-ETV, severe HCP fetal lambs improved to moderate levels, whereas those with moderate HCP normalized by birth. A similar improvement pattern was seen for the mechanical compression threshold (ventricular diameters/biparietal diameter). Biparietal diameter values did not significantly differ among nontreated, treated, and normal control groups during pregnancy. MRI revealed a significant increase in brain mantle thickness in the prenatally treated fetuses.

Conclusion: Prenatal ETV is feasible in hydrocephalic fetal lambs and effectively reverses ventriculomegaly and brain compression in cases of severe or moderate fetal HCP in this ovine model.