Gianluigi Pilu, MD

Bologna, Italy pilu@mbox.queen.it

Synonyms: ventriculomegaly, hydrocephalus, acqueductal stenosis, communicating hydrocephalus

Definition: overt enlargement of the lateral ventricles (atrial width > 15 mm) in the absence of other sonographically demonstrable central nervous system anomalies.

Prevalence: The incidence of congenital cerebral lateral ventriculomegaly ranges between 0.3 to 1.5 in 1000 births in different series.[1] Isolated ventriculomegaly accounts for 30%-60% of fetuses with enlarged lateral cerebral ventricles.[2]

Pathogenesis: In the majority of cases, isolated cerebral lateral ventriculomegaly is the consequence of an obstruction along the normal pathway of the cerebrospinal fluid (obstructive hydrocephalus).

Etiology: Congenital ventriculomegaly is a heterogeneous disease for which genetic, infectious, teratogenic and neoplastic causes have been implicated. A multifactorial pattern of inheritance is probably responsible for most cases of congenital hydrocephalus.[3] 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. Mutations in this gene are also responsible for other syndromes with clinical overlap that are frequently referred to as the X-linked hydrocephalus spectrum and include MASA (mental retardation, aphasia, 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.[4] Infections implicated in the determination of congenital ventriculomegaly include toxoplasmosis, syphilis, cytomegalovirus, mumps and influenza virus.

Pathology: Overt lateral ventriculomegaly can result from different pathological entities. Fetuses with isolated ventriculomegaly diagnosed in utero at our institution were usually found at birth to have either aqueductal stenosis or communicating ventriculomegaly. Progression from communicating ventriculomegaly to aqueductal stenosis has been documented and it is uncertain whether these two conditions are separate clinical entities. Communicating hydrocephalus may however derive from acute events such as subarachnoid hemorrhage, or be caused by overproduction of cerebro-spinal fluid by a choroid plexus papilloma. 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. This phase has been considered reversible. Later, there is proliferation of astrocytes and fibrosis of the white matter. The gray matter seems to be spared during the initial staged of the process.

Recurrence risk: apart from X-linked hydrocephalus (recurrence risk 50% of males) congenital ventriculomegaly is mostly multifactorial. Couples with a previously affected child have a recurrence risk of 4%.[5]^,[6]

Associated anomalies: extra-cranial abnormalities occur in 30% 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).[7] The X-linked hydrocephalus spectrum is frequently associated with abduction of the thumbs, abnormal facies and absence of the septum pellucidum. [8]^,[9]

Diagnosis: Different approaches have been proposed for the diagnosis of fetal lateral cerebral ventriculomegaly. A qualitative approach has been suggested. Under normal condition, the large fetal choroid plexus entirely fills the cavity of the lateral ventricle at the level of the atria, being closely apposed to both the medial and the lateral wall, irrespective of gestational age. In even early stages of ventriculomegaly, the choroid plexus is shrunken anteriorly displaced, thus being clearly detached from the medial wall (Figure 1).[10] However, in a finite number of normal fetuses some disproportion between the choroid plexus and the atrial lumen is found.[11] Normal values for virtually all portions of the lateral ventricles throughout gestation are available.[12]^,[13],[14] Measurement of the width of atrium is however favored. Between 15 and 40 weeks’ gestation, the mean value is consistently about 7 mm and the standard deviation about 1 mm in most studies. Some degree of asymmetry of the lateral ventricles exists in human fetal brain[15] and is detectable in utero.[16] A measurement of less than 10 mm is indicative of normalcy.[17]^,[18] Overt lateral cerebral ventriculomegaly is defined as a measurement of 15 mm or more. Sonographic demonstration of abducted thumbs in combination with ventriculomegaly and other intracranial abnormalities should prompt the diagnosis of X-linked hydrocephalus spectrum.[19]

Figure 1: Fetal hydrocephalus: gross enlargement of the lateral ventricles, thinning of the cortex, asymmetric choroid plexuses.

Differential diagnosis: The main problem is distinguishing isolated ventriculomegaly from more complex abnormalities of the fetal brain that have frequently a different prognosis (e.g. holoprosencephaly, porencephaly, etc). We recommend careful multiplanar examination of the fetal brain, performed if possible with a high-resolution vaginal probe, and a detailed evaluation of the spine.

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 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.[20] The patients at risk for 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 DNA analysis, as the recurrence rate is high and midtrimester sonography is frequently unsuccessful.[21]

Implications for sonographic screening: In all standard sonographic examinations, a view of the lateral ventricles should be obtained, and at least one of the atria should be visualized and assessed. A qualitative evaluation is acceptable, and the presence of the choroid plexus filling the cavity of the atrium, being closely apposed to both the medial and lateral wall of the ventricle, is indicative of normalcy.  A quantitative approach is however favored, and a measurement less than 10 mm is considered normal between 15-40 weeks. Congenital ventriculomegaly may develop late in gestation, and a normal midtrimester exam does not exclude this condition.

Prognosis: In a recent review, isolated ventriculomegaly diagnosed in utero was associated with a postnatal survival rate of 70% and 59% of the survivors had normal developmental quotient at follow-up.[22] These results may be biased however by the inclusion of cases with borderline enlargement of the ventricles. In one of the largest pediatric series, excluding cases with X-linked hydrocephalus and congenital toxoplasmosis, 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.[23]  Macrocrania at birth, ventricular size and age at surgery had no influence on the outcome. X-linked hydrocephalus spectrum carries a severe prognosis, being usually associated with severe neurological deficits and premature death.

Obstetrical management: A search for associated congenital anomalies, including fetal karyotyping) and a workup for congenital infections associated with hydrocephalus (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. Cephalocentesis is indeed associated with a perinatal mortal­ity in excess of 90 percent.[24] Intrauterine treatment consist­ing of the implantation of a ventriculoamniotic shunt for the relief of intracranial pressure during gestation has been attempted.Although experience in ani­mal models appears encouraging,the clinical appli­cation of these procedures remains undetermined. In a group of 39 treated fetuses, the perinatal mortality rate was 18 percent, and moderate to severe handicaps affected 66 percent of the survivors.[25]

References