Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility

Abstract

Introduction: Although endovascular techniques have improved outcomes in vein of Galen malformations (VOGM), there is still a high rate of morbidity and mortality, particularly among cases with decompensation in the neonatal period. The dimension of the draining venous sinus on fetal imaging correlates with the risk of neonatal decompensation. In fetuses within this high-risk group who do not have end-organ injury, there is a theoretical therapeutic opportunity to reduce the arteriovenous shunt before the normal physiological changes of birth precipitate decompensation. This study investigates the safety and potential benefit of treating a VOGM in utero, which has not been previously studied.

Methods and analysis: This study aims to enroll 20 subjects: pregnant women with a fetus harbouring a high-risk VOGM (defined on MRI by a narrowest medial-lateral width greater than 8 mm in the draining venous sinus). Unfortunately, the subset of fetuses with in utero end-organ injury is ineligible, because the late stage of pathology is not amenable to recovery from a cerebrovascular intervention, likely not even in utero. This study aims to alter the physiology before such developments accrue.At or after 23 weeks of gestation, a transuterine transposterior fontanelle needle puncture to the torcular allows ultrasound-guided deployment of coils to embolise the draining venous malformation.This study has 97.5% power to detect major safety events at 30% or greater, and 80% power to detect a reduction in the rate of neonatal intervention from 80% to 30%. In the staged study design, an interval evaluation after 11 patients invokes study termination if safety events occur above the allowed threshold.

Ethics and dissemination: The institutional review boards at Mass General Brigham and Boston Children's Hospital (BCH) reviewed and approved this protocol. The BCH Department of Radiology and a patient family philanthropic donation fund this study. The trial results will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number: NCT04434729.

Keywords: cerebral veins; fetal embolization; fetal therapies; vein of Galen malformations.

Conflict of interest statement

Competing interests: APS is on the scientific advisory board for Microbot Medical with CSF diverting implants. CSF diversion represents a rare intervention in infants with vein of Galen malformations, but every effort is made to avoid CSF diversion in the VOGM population, and this is not a component of the intervention studied or reported here.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Illustration of technique. This T2 sequence fetal MRI illustrates a patient with a vein of Galen malformation (VOGM). The procedure is completed by a collaboration between a high-risk Maternal Fetal Medicine specialist introducing a transuterine 19 G needle (red) under ultrasound guidance into the confluence of sinuses and allows access into the varix for a microcatheter (blue) to deliver coils for embolisation (green).

Figure 2

Plot of schedule of events. Grid of study activities at each study visit. CBCL, Child Behavior Checklist; REEL, Receptive-Expressive Emergent Language Test.

Figure 3

Participant timeline. A linear flow diagram describing each of the study visits and the assessments completed at each encounter. BWH, Brigham and Women’s Hospital; NICU, neonatal intensive care unit; REEL, Receptive-Expressive Emergent Language Test.