Severe Ventriculomegaly

Hydrocephalus

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

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

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

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.

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.

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.

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

The main problem is to differentiate isolated ventriculomegaly from more complex abnormalities of the fetal brain that have frequently a different prognosis, including intracranial hemorrage¹⁶ cortical malformations,¹⁷ Walker-Warburg syndrome¹⁸ 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}

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

Assessment of the size of the lateral ventricles is an essential component of the evaluation of fetal anatomy in second and third trimester sonographic examinations²² 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.

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}

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%, and 66% 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

Please note that the maximum upload size is 5MB, and larger images and video clips can be sent to [email protected].