Gianluigi Pilu*, Gustavo Malinger**

From the Department of Obstetrics and Gynecology of the University of Bologna, Italy*,and the Fetal Neurology
Clinic, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.*

Synonyms
hydrocephalus

Definition and diagnosis

Measurement of the atria of lateral ventricles in excess of 15 mm without evidence of other cerebral malformations (1-
5)

Incidence
Severe fetal cerebral ventriculomegaly is a rare finding, and no specific figures are available. Some of these infants
develop neonatal hydrocephalus, that is reported in 0.3-1.5 in 1000 births.(6)

Pathogenesis

Most frequently severe ventriculomegaly is part of complex cerebral abnormalities. Isolated ventriculomegaly is seen
in a distinct minority of cases and is usually the consequence of obstructed cerebrospinal fluid turnover. When this is
associated with intracranial hypertension, the term obstructive hydrocephalus is commonly utilized.(7)

Etiology

Congenital severe ventriculomegaly is a heterogeneous disease for which genetic, infectious, teratogenetic and
neoplastic causes have been implicated. X-linked hydrocephalus comprises approximately 5% of all cases. This
condition is caused by mutations in the gene at Xq28 encoding for L1, a neural cell adhesion molecule (L1CAM).
Mutations in this gene are also responsible for other syndromes with clinical overlap and those are frequently referred
to as the X-linked hydrocephalus spectrum or L1 spectrum and include MASA (mental retardation, aphasias, shuffling
gait, adducted thumbs), complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb
(MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum.(8-11) A multifactorial pattern of
inheritance is probably responsible for most other cases of congenital hydrocephalus.(9) Infections implicated in the
determination of congenital ventriculomegaly include toxoplasmosis, syphilis, cytomegalovirus, mumps and influenza
virus.
Pathology

Severe lateral ventriculomegaly can result from different pathological entities. In our experience fetuses with this
finding usually have other neural and extra-neural malformations. Even those with presumably isolated ventricular
dilatation were found in the majority of cases to have complex abnormalities including. In a large series, only 10% of
fetuses with severe ventricular dilatation were found not to have associated malformations.(12) Only in a small
proportion fetuses are found to have isolated obstructive hydrocephalus, either acqueductal stenosis or
communicating hydrocephlaus. In these cases, the degree of ventricular enlargement is variable. Knowledge about
the pathogenesis of congenital ventriculomegaly is largely incomplete. Thinning of the cortex, macrocrania and
symptoms of intracranial hypertension are frequently found. Studies performed in experimental animals and based on
biopsies of brain tissue obtained in children at the time of shunting seem to demonstrate the following sequence of
events: initially there is disruption of the ependymal lining, followed by edema of the white matter and proliferation of
astrocytes and fibrosis of the cortex.

Recurrence risk

Isolated congenital ventriculomegaly is mostly multifactorally determined. Couples with a previously affected child
have a recurrence risk of 4%.(13). X-linked hydrocephalus has a recurrence risk 50% of males.

Associated anomalies

Extra-cranial abnormalities occur in 30-60% of cases.(7, 12) Chromosomal aberrations are found in 11% of cases (6%
of fetuses with ventriculomegaly as the only antenatal finding, 25% of cases with multiple anomalies).(14) The X-
linked hydrocephalus spectrum is frequently associated with abduction of the thumbs, abnormal facies and absence of
the septum pellucidum.(15)

Differential diagnosis

The main problem is to differentiate isolated ventriculomegaly from more complex abnormalities of the fetal brain that
have frequently a different prognosis, including intracranial hemorrage (16) cortical malformations,(17) Walker-
Warburg syndrome (18) or X-linked hydrocephalus spectrum.(15) Identifying such conditions is usually a major
challenge. When severe isolated ventriculomegaly is identified, genetic analysis for X-linked hydrocephalus should be
offered. Ventriculomegaly may be associated with cortical malformations and the diagnosis of these conditions is
frequently difficult or impossible. In particular, it has been recently demonstrated that ventriculomegalic brains have a
delayed cortical maturation (figure 2) and it is unclear whether this has an impact on the final outcome or not.(19).
Several authors have suggested that MR can be helpful in the assessment of ventriculomegalic fetuses particularly in
advanced gestation.(20, 21)
Implications for targeted examinations
For patients at risk for fetal cerebral ventriculomegaly (e.g. because of a previously affected child, or because of
TORCH infection), we recommend careful multiplanar examination of the fetal brain, performed if possible with a high
resolution vaginal probe, including visualization and assessment of both lateral ventricle. It has been our experience,
and it has been reported in a handful of cases that ventriculomegaly may develop only in late gestation or after birth,
particularly with the X-linked hydrocephalus spectrum.(9) The patients at risk should be informed that a normal
midtrimester sonogram does not rule out this condition. Couples with a previously affected child should receive
genetic counseling, because sometimes a generic diagnosis of congenital hydrocephalus may hinder a more complex
anomaly with significant genetic implications. For example, patients at risk for X-linked hydrocephalus spectrum
should be offered genetic testing, as the recurrence rate is high and midtrimester sonography is frequently
unsuccessful. (8)

Implications for sonographic screening

Assessment of the size of the lateral ventricles is an essential component of the evaluation of fetal anatomy in second
and third trimester sonographic examinations (22) Different approaches have been proposed but measurement of the
width of the atrium, or posterior horn is favoured by many.(4, 22-24) Congenital ventriculomegaly may develop late in
gestation, and a normal midtrimester exam does not exclude this condition.

Prognosis

Isolated ventriculomegaly diagnosed in utero is associated with a postnatal survival rate of 70% and 59% of the
survivors had normal developmental quotient at follow-up.(25) In most albeit not in all cases with isolated progressive
ventriculomegaly intracranial hypertension develops after birth and a shunting procedure is necessary. In a large
pediatric series (excluding cases with X-linked hydrocephalus and congenital infections) the survival rate was 62% at
10 years, and 50% of survivors had a low developmental quotient (< 60). Only 29% of infants attending school
reached a normal academic level. Macrocrania at birth, ventricular size and age at surgery had no influence on the
outcome.(26) The X-linked hydrocephalus spectrum carries a severe prognosis, being usually associated with severe
neurological deficits and premature death.(8, 10, 11)

Obstetrical Management

A search for associated congenital anomalies, including fetal karyotyping and a workup for congenital infections
associated with hydrocephaly (i.e., toxoplasmosis, cytomegalovirus, rubella) is indicated. Before viability, the option of
pregnancy termination should be offered to the parents. Little data exist to support any specific management plan in
continuing pregnancies. There is no evidence that anticipation of delivery is beneficial. Most infants with
ventriculomegaly do not have macrocrania, and therefore a trial of labor is indicated in vertex presentation. Cesarean
section should be reserved for standard obstetrical indications. Whether cephalocentesis should be offered in cases
with macrocrania to overcome cephalo-pelvic disproportion is debated. In one series cephalocentesis resulted in
perinatal mortality in over 90% of cases.(27) Careful aspiration with fine needles guided with high resolution
ultrasound equipment, trying to limit as much as possible damage to brain parenchyma and cerebral vessels may
cause however much less harm than these rather old data indicate. Intrauterine treatment consisting of the
implantation of a ventriculo-amniotic shunt for the relief of intracranial pressure during gestation has been attempted.
Although preliminary experience in animal models was encouraging, the clinical application of these procedures
remains undetermined. In a group of 39 treated fetuses, the perinatal mortality rate was 18 percent, and 66 percent of
the survivors were affected by moderate to severe handicaps.(28) However, the new fetal endoscopic technique may
provide a different approach to the problem in the future.(29)

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Pilu G, Malinger G: A. Severe fetal cerebral ventriculomegaly. Visual Encyclopedia of Ultrasound in Obstetrics and
Gynecology. www.isuog.org, 24 June 2013