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2024 Fetal Care Center Frontiers in Fetal Neurology Day 1 - Dr. Jose Peiro
With Dr. Jose Peiro · hosted by Dr. Kara Markham
Chapter 1 of 9 · Fundamentals
Introduction
Introduction of Dr. Peiro
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Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.
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What the experts said
CSF produced in the choroid plexus circulates through the ventricular system via the aqueduct of Sylvius and fourth ventricle, then around the brain for reabsorption.
Aqueductal stenosis blocks normal CSF circulation, causing fluid buildup in lateral and third ventricles, representing a pure obstructive problem in fetuses and babies.
Progressive ventricular enlargement in obstructive hydrocephalus causes increased intracranial pressure, cortical mantle thinning, rupture of septum pellucidum, and denudation of ependyma, producing problems in brain development.
Ventriculomegaly and hydrocephalus can be detected very early in gestation using prenatal ultrasound, classified as mild, moderate, or severe.
MRI is a very good tool to complete prenatal hydrocephalus evaluation and identify isolated aqueductal stenosis with genetic testing.
Aqueductal stenosis is probably the most important cause of obstructive congenital hydrocephalus.
Fetal hydrocephalus is associated with potentially poor outcomes including intellectual disabilities, spasticity, and seizures.
Postnatal treatment of congenital hydrocephalus almost consistently requires CSF diversion, mostly with VP shunts, which have problems including malfunction and infection.
Any postnatal treatment probably arrives late because progressive brain deterioration occurs during the intrauterine period, including denudation, astrocytosis, and microgliosis.
The first attempts at fetal hydrocephalus treatment were performed in fetal monkeys and chimp models using ventriculo-amniotic shunts approximately 40 years ago.
The first human case of fetal hydrocephalus treatment was described by Birnholz, and 44 cases were collected in a registry and discussed at a 1982 fetal medicine and surgery meeting.
Experts in fetal surgery decided on a moratorium on fetal hydrocephalus intervention after the 1982 meeting, likely due to suboptimal clinical outcomes and patient selection.
Modern technology, better imaging, and genetic tools for patient selection make it sensible to reconsider fetal hydrocephalus treatment, specifically fetal ETV without hardware.
In the fetal lamb model, kaolin injected into the cisterna magna creates moderate hydrocephalus but causes a meningitis-like irritation reaction.
Comparing kaolin, bioglue, and onyx for creating fetal lamb hydrocephalus, bioglue was determined to be the best agent.
A severity scale for fetal lamb hydrocephalus was developed with mild, moderate, and severe categories based on ventricular measurements.
Only bioglue allowed creation of severe hydrocephalus cases in the fetal lamb model, with significant cortical thinning.
The fetal lamb hydrocephalus model shows ependymal denudation with loss of cilia, likely due to ventricular distension.
The percentage of ependymal denudation is higher with severe category hydrocephalus and occurs very early in gestation until delivery.
Astrocytes replace ependymal cells and create scar tissue in areas of denudation.
Activated microglia indicating neuroinflammation are present in areas of ependymal denudation, putting neuroprogenitor cells in the subventricular zone at risk of maldevelopment.
Fetal ETV in the lamb model is performed using a 7 French rigid fetoscope or cystoscope inserted through the coronal suture approximately 1 centimeter to the midline to enter the lateral ventricle.
The fetal lamb brain anatomy is more elongated than human, with a narrow foramen of Monro and other anatomical differences that create technical difficulties.
In the fetal lamb model, the septum pellucidum is absent in hydrocephalus, allowing visualization of both lateral ventricles.
The interthalamic adhesion in fetal lambs is very large, making the anatomy different from human.
A rigid plastic fiber (laser without energy) is used to create a blunt opening in the third ventricle floor to avoid energy-related damage to the basilar artery in mid-gestation fetuses.
Fetal ETV in the lamb model reduced ventricular size from severe to moderate-mild and from moderate to normal in most cases.
A fetal surgeon in Brazil has performed percutaneous fetal ETV in 10 human cases with no deaths, demonstrating feasibility and safety.
Fetal ETV improved cortical thickness (reduced compression) in treated fetal lambs.
In most cases, fetal ETV recovered ependymal denudation, though it is unknown whether this represents prevention or regeneration after ventricular deflation.
A multi-center U.S. clinical trial is planned, starting with phase 1 in 10 human cases to assess safety and feasibility, followed by phase 2 in 50-60 cases to assess efficacy.
Endoscopic third ventriculostomy can be performed postnatally to recirculate CSF as an alternative to shunting.