ULTRASOUND CLINICS

Diagnosing and managing mild fetal cerebral ventriculomegaly

By V. Ravishankar, MD, and Joshua A. Copel, MD

Thanks to advances in U/S technology, clinicians can now detect ventricular enlargement in its earliest stages. Unfortunately, a few fetuses with borderline ventriculomegaly still have chromosomal or structural malformations.

The good news is that most fetuses with mild fetal cerebral ventriculomegaly will not have birth defects. The bad news, unfortunately, is that a few do have chromosomal or structural malformations that carry a poor prognosis. Easily detected on ultrasound, mild cerebral ventriculomegaly is defined as an atrial width of the lateral ventricles that measures between 10 mm and 15 mm. Its prevalence ranges between 0.07% and 0.7%.^1,2 Although routine U/S will pick up most cases of mild ventriculomegaly, magnetic resonance imaging (MRI) is a valuable adjunct in diagnosing the fetal CNS malformations that sometimes accompany the abnormality. Our goals here are to discuss the prenatal diagnosis, differential diagnosis, and management of mild ventriculomegaly. And to emphasize the importance of parental counseling, which involves a coordinated team approach by obstetricians, pediatric neurologists, and neurosurgeons.

Embryology and cranial anatomy

The three primary brain vesicles that arise from the primitive neural tube are the forebrain or prosencephalon, the midbrain or mesencephalon, and the hindbrain or rhombencephalon. By 6 to 7 postmenstrual weeks, the forebrain divides into the telencephalon and the diencephalon and the hindbrain divides into the metencephalon and the myelencephalon, thereby forming five secondary brain vesicles. The midbrain does not divide (Figure 1).

The cerebral ventricles, which are interconnected cavities, develop from the neural tube and derive their names according to their locations in the brain. Early in their development, the ventricles are large relative to the brain tissue. With further development of the cerebral hemispheres, their cavities become the lateral ventricles, one situated in each cerebral hemisphere.³ These form the important sonographic landmarks for evaluating cranial anatomy. The lateral ventricles consist of three horns (anterior, posterior, and inferior), a body, and an atrium. On U/S, it is the atrium that's measured to assess ventricular size (Figure 2). By 8 to 9 postmenstrual weeks, the prominent choroid plexus occupies each lateral ventricle and is clearly seen in early scans.

Visualizing the ventricles sonographically

Sonographic characterization of the ventricles is used to identify ventriculomegaly. Over the years, the method of measuring the lateral ventricles by U/S described by Cardoza and colleagues has gained wide acceptance.⁴ The ventricular atrium on the far side of the fetal head relative to the transducer can be more clearly visualized, so its measurement is obtained in an axial plane through the thalamic nuclei. (This is parallel to the plane used for the biparietal diameter.) To measure it, you place the electronic calipers along the inner aspect of the medial and lateral walls of the lateral ventricle, which appear as linear echoes parallel to the midline (Figure 3). In this plane, you can also clearly visualize the posterior margin of the choroid plexus. (Note: Sonographers should no longer use previously described measurements of the ratio of lateral ventricular width to hemispheric width [LV/HW], which was prone to subjective variations, as it often included the measurement of the Sylvian fissure.)

Taking routine ventricular measurements

The average ventricular width measurements vary little throughout gestation. For example, measuring the ventricular diameters of 500 fetuses, researchers found a mean size of 6.6 mm with a standard deviation of 1.4 mm.⁵ They concluded that a measurement of 10 mm (corresponding to 2.5 SD) should be used as the upper limit of normal. Recently, other investigators took atrial measurements in 427 fetuses between 20 and 40 weeks and found that the ventricular diameter averaged 6.4 mm, with 3 standard deviations (SD) above that corresponding to 10 mm.⁶

Both the American Institute of Ultrasound in Medicine (AIUM), and the American College of Obstetricians and Gynecologists (ACOG) recommend routinely assessing lateral cerebral ventricles as part of the fetal anatomic survey.^{7, 8} The standard technique of lateral ventricular measurement is easily learned and reproducible, but don't forget to image the lateral ventricle nearer to the transducer. Failing to do so may lead to the false diagnosis of unilateral ventriculomegaly. Imaging the fetal brain in the coronal and sagittal planes should minimize this error.

Transvaginal neurosonography is increasingly gaining acceptance for evaluating the ventricular system. Monteagudo and her colleagues have constructed nomograms for quantitative assessment of the fetal cerebral ventricles by TVS.⁹ Among the advantages of the transvaginal approach is the ability to image both hemispheres, which can also be visualized clearly in the sagittal and coronal planes. The fact that in the vertex position, the fetal brain lies in close proximity to the vaginal transducer overcomes the limitations to abdominal sonography imposed by an obese patient or an abdomen scarred by previous surgeries. These researchers also recommend external cephalic version of the fetus, if it's in breech presentation, to perform a transvaginal scan.³

Distinguishing mild ventriculomegaly from hydrocephaly

Ventriculomegaly is defined as the dilation of the lateral ventricles without a raised intraventricular pressure. In hydrocephaly, the lateral ventricles are also dilated, but as a result of increased cerebrospinal fluid and raised intraventricular pressure. As we mentioned earlier, mild ventriculomegaly (also known as borderline ventriculomegaly) refers to a ventricular diameter measuring 10 mm or more but less than 15 mm on U/S (Figure 4). Thanks to advances in U/S technology, precise measurements of the lateral ventricles are now possible, permitting clinicians to detect ventriculomegaly at its earliest stages.

Keep in mind that fetal gender influences the ventricular measurement; males have larger ventricles.^{2, 11-14} Two groups of researchers have noted a preponderance of male fetuses with mild bilateral ventriculomegaly.^11,12 However, while fewer female fetuses have bilateral ventriculomegaly, they are more likely to suffer delayed development than males (23% vs. 5%).¹³ This gender difference does not uniformly hold true for fetuses with unilateral ventriculomegaly.^1,15

Isolated mild ventriculomegaly and bilateral ventriculomegaly

Isolated ventriculomegaly refers to an absence of associated intracranial or extra CNS malformations. Most ventricular enlargements identified prenatally are bilateral.¹⁶ Previous studies have relied only on the measurement of one ventricle seen in the hemisphere of the brain distal to the transducer in an axial section of the fetal head. However, if restricted to this view in the axial plane, the diagnosis of unilateral ventriculomegaly may be missed on the side of the head nearer to the transducer. It's therefore important to image the fetal head in both coronal and sagittal planes in addition to the standard axial plane to visualize both lateral ventricles as clearly as possible.

Fetal chromosomal anomalies occur with isolated mild ventriculomegaly in fewer than 5% of cases. However, because most of these are fetuses with trisomy 21, be sure to offer fetal karyotyping to all women with findings of isolated mild ventriculomegaly.¹⁷

A variety of structural and genetic disorders and syndromes can cause nonisolated ventriculomegaly. Whenever U/S identifies ventriculomegaly, search carefully for associated CNS and extracerebral malformations (Table 1). Combining their 31 cases with previous studies, Pilu and colleagues found structural anomalies in 19 out of 221 cases (8.6%) of "isolated" ventriculomegaly.¹³ CNS malformations were present in 4.1% of cases and extracerebral anomalies in 4.5%. Although these anomalies were not identified on the first scan, they were usually detected after birth. Perinatal infections are rarely associated with mild ventriculomegaly. Even though TORCH screening is routinely recommended in mild ventriculomegaly, no strong evidence currently suggests an infectious cause of this condition because only isolated cases of infections are reported with mild ventriculomegaly.

TABLE 1
Fetal anomalies associated with mild ventriculomegaly*

Unilateral mild ventriculomegaly

Precise measurement of ventricular size has improved the diagnostic accuracy of unilateral ventriculomegaly (UVM). Three studies have specifically looked into the outcomes of UVM,^{1, 18,19} which can be caused by congenital atresia of the foramen of Monro, as well as the foramen's obstruction by infection, hemorrhage, or neoplasm.^20-22 Following 26 cases with mild isolated UVM, one research team found that 25 infants had normal neurologic outcomes and one infant had petit mal seizures.¹⁸ Only one case of Down syndrome (which was not included in the study population) was diagnosed with UVM. Other studies with fewer cases have found favorable postnatal outcomes associated with UVM (Table 2).

TABLE 2
Mild isolated unilateral ventriculomegaly and neurodevelopmental outcome

As with fetuses having bilateral ventriculomegaly, they noted a preponderance of male fetuses with UVM. Interestingly, Senat and colleagues found that eight out of ten fetuses with isolated UVM had birthweights above the 90th percentile. Although in most cases the ventriculomegaly was isolated, there were some nonisolated cases with cerebral and extracerebral malformations. These included Weaver syndrome, arachnoid cyst, schizencephaly, and agenesis of the foramen of Monro. Toxoplasmosis and CMV infections accounted for two cases. Overall, no perinatal deaths were reported in 44 cases of isolated UVM from these three studies.

Degree of ventriculomegaly impacts developmental outcome

Several studies have used different methods to assess the neurodevelopmental outcome of children who were diagnosed with isolated mild ventriculomegaly in utero. It's encouraging to know that most infants had normal developmental outcomes. Developmental delay was seen in 2.3% of infants with unilateral ventriculomegaly (Table 2) and in 13.3% of infants (range 0%–36%) who had bilateral isolated mild ventriculomegaly (Table 3). To reiterate, although there seem to be more male fetuses with ventriculomegaly, affected females are more likely to have abnormal neurodevelopment.^{11, 13} The degree of ventriculomegaly seems to influence the neurodevelopmental outcome. Ventricular width of 12 mm or less has a more favorable outcome than a width exceeding 12 mm.¹³ Although the results are encouraging, pediatric follow-up in most studies was too short-term, and long-term evaluation is necessary to evaluate the significance of this prenatal finding.

TABLE 3
Mild isolated bilateral ventriculomegaly and neurodevelopmental outcome

Managing a fetus diagnosed with mild ventriculomegaly

Routine U/S identifies most cases of ventriculomegaly, whereupon patients are usually referred to a tertiary center for further management. Offer fetal karyotyping to rule out fetal chromosomal aberrations, and discuss pregnancy termination with those patients whose fetuses do have chromosomally abnormalities or associated cerebral malformations that are linked with adverse neurodevelopmental outcomes. Order maternal serologies IgM and IgG for toxoplasmosis and cytomegalovirus, and if an acute infection is found, begin appropriate counseling.

Many centers complement U/S findings with an MRI of the fetal brain because it provides additional information about fetal brain anatomy. In fact, fetal ventriculomegaly is one of the most common indications for MRI. Levine and colleagues reported 25 cases of ventriculomegaly diagnosed by U/S, followed by MRI evaluation of the fetal brain.²³ They found that MRI actually changed the diagnosis in ten cases (40%), identifying seven cases of agenesis of the corpus callosum and one case each of cerebellar hypoplasia, partial agenesis of the cavum septum pellucidum, and clastic lesions. Some experts contend, however, that dedicated transvaginal neurosonography done by experienced sonographers should minimize the need for MRI.²⁴ It's hard to say what's prompting this additional investigative approach—perhaps the increasing availability of ultrafast MRI, the lack of expertise in neurosonography, or concerns about lawsuits. MRI is a valuable tool for obstetricians and pediatric neurosurgeons who are jointly counseling parents. Our experience at Yale suggests that MRI is most valuable in the very late second and the third trimester because poorer image resolution and movement artifacts are seen earlier in pregnancy.

Fetuses with mild ventriculomegaly should be followed with serial U/S to evaluate the natural course of the enlargement. In utero resolution or stable ventricular dilatation is reassuring and seem to lead to more favorable neurodevelopmental outcomes. While you're closely monitoring progressive ventriculomegaly, pediatric neurology or neurosurgical consultations can help prepare parents for the possibility of postnatal interventions like shunting.

A multidisciplinary team approach to counseling parents should include a pediatric neurologist and a geneticist. Ventriculomegaly may also develop later in pregnancy, at which point it's frustrating for the parents to learn of this finding after a reassuring mid-trimester U/S. Even though long-term follow-up of infants with isolated mild ventriculomegaly is warranted, counsel these parents to expect a normal neurodevelopmental outcome, particularly if the measurement is less than 12 mm in a male fetus. Also discuss adequate plans for postnatal follow-up, including imaging studies. Vaginal delivery is not contraindicated in women with mild fetal ventriculomegaly.

Although mild ventriculomegaly is easily detected by U/S, sometimes ventriculomegaly doesn't appear until the third trimester and therefore will not be apparent in the mid-trimester scans.¹⁴ Perform imaging in both coronal and sagittal planes, in addition to the standard axial plane. Transvaginal scans have the advantage of detecting ventriculomegaly earlier and are not affected by maternal obesity or operative abdominal scars. When U/S detects this finding search carefully for related cerebral and extracerebral malformations. There's also a role for MRI, which may detect additional findings not apparent during U/S. You should offer fetal karyotyping, given that chromosomal aberrations can occur in about 4% of cases. Most fetuses with isolated mild ventriculomegaly have a favorable postnatal neurodevelopmental outcome and unilateral ventriculomegaly has a more favorable prognosis. Although you can expect to see more male fetuses with mild ventriculomegaly, female fetuses who have it will likely have more neurodevelopmental delays. Finally, when counseling patients, it's very important to use a multidisciplinary team approach involving geneticists and pediatric neurologists and, if the problem is severe and progressive, pediatric neurosurgeons.

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DR. RAVISHANKAR is Clinical Assistant Professor, Department of Obstetrics and Gynecology and Reproductive Sciences, SUNY at Stony Brook, Stony Brook, N.Y., and DR. COPEL is a Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Conn.

Department Editors are Joshua A. Copel, MD, and Ilan E. Timor-Tritsch, MD, Professor of Obstetrics and Gynecology at NYU School of Medicine and Director of the NYU Obstetrical and Gynecological Ultrasound Unit, New York, N.Y.

 

Viswanathan Ravishankar, Joshua Copel. U/S Clinics: Diagnosing and managing mild fetal cerebral ventriculomegaly. Contemporary Ob/Gyn Sep. 1, 2004;49:98-109.