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Ventriculomegaly/Hydrocephalus


Isolated Mild Ventriculomegaly
Marked Hydrocephalus

Findings:

The case on the left demonstrates mild ventriculomegaly with a maximum atrial diameter of 11.0 mm. No other neural axis or non-CNS abnormalities were detected. The case on the right demonstrates marked hydrocephalus due to aqueductal stenosis.

Discussion:

The history of the sonographic evaluation of fetal intracranial ventricular anatomy and hydrocephalus is fascinating. It is interesting that despite the fact that many early investigators were mistaken about the normal sonographic anatomy of the brain (cavum septum pellicudum interpreted as third ventricle, deep medullary white matter veins misinterpreted as the lateral ventricular wall) clinical diagnoses were reasonably accurate. It is also interesting that some of the criteria used to detect an abnormality of the fetal neural axis (upper limit in size for the lateral ventricle being 10 mm) have remained for more than 20 years.

In the 1970's ultrasound examinations were performed predominantly with static articulated-arm scanners. The major structures depicted were the cranium and reflections from the ventricular system. It was recognized that enlargement of the fetal head was a late sign in fetuses with hydrocephalus. The diagnosis of hydrocephalus was made when a ratio of the measurement of the midline to lateral ventricular wall (LVW) compared to a measurement of the hemicranium (HW) was abnormal. The normal ratio (LVW/HW) was high early in development with a mean of 71% and decreased with advancing gestation with a mean of 28% at term. This measurement was used for over a decade. Most investigators realized that the actual lateral ventricle was not being measured. However, what they did not realize, until the late 1980's, was that what was often utilized as the lateral wall of the lateral ventricle in this ratio were in fact, reflections from the deep medullary draining veins. These veins drain the white matter and converge near the angles of the lateral ventricles. This explains why this measurement, though anatomically incorrect, was often successful in defining the presence or absence of hydrocephalus. In the mid 1980's the observation of four structures in the fetal cranium accounted for major strides in the advancement of our understanding of the normal and abnormal neural axis: the choroid plexus, the meninges, the medial wall of the lateral ventricle and the recognition that the normal cerebrum was poorly echogenic.

Veins in the deep white matter simulating the ventricular wall

Normal lateral ventricular wall angling laterally and posteriorly

An understanding of the development of the normal fetal brain as depicted sonographically is important in attempting to diagnose hydrocephalus or other pathologic intracranial abnormalities. An excellent discussion of the embryology of the ventricular system appeared in a report by Pilu et al. As they describe: " the lateral ventricles originate from the telocele, the primitive neural cavity contained in the telencephalon or primordium, of the forebrain. At about the sixth week, cleavage of the telencephalon along the sagittal plane results in a symmetrically paired division of the internal telocele, forming two distinct cavities. In the following weeks, the medial wall of the primitive lateral ventricles bulges within the cavity, forming a fold which is rapidly covered by pseudostratified epithelium and molded into a villous structure by the proliferation of underlying blood vessels. this structure develops into the choroid plexus. The atrium, or trigone, is the triangular portion of the lateral ventricles that is connected anteriorly to the body, posteriorly to the occipital horn, and inferiorly to the temporal horn". At the end of the first trimester the choroid plexus normally fills the entire lateral ventricle bilaterally. Early in the second trimester it begins to recede posteriorly but remains in close contact with the medial and lateral walls of the bodies and atria of the ventricles. Likewise, the lateral cerebral ventricle is large relative to the cerebral hemispheric width. Due to the already large, but normal size of the developing ventricle, the most likely explanation for readily perceived hydrocephalus is medial displacement of the medial wall of the lateral ventricle as well as an alteration in the size of the choroid plexus. It is known experimentally that increased CSF pressure will result in atrophy of the choroid plexus. It is the small choroid plexus surrounded by CSF that is readily perceptible as evidence of ventricular dilatation.

Ventriculomegaly Criteria

If the lateral ventricle dramatically increased in size throughout gestation, the diagnosis of hydrocephalus might be difficult. In fact, early studies by Siedler and Filly and confirmed by others have demonstrated that the size of the atrium of the lateral ventricle changes little throughout gestation. In their study, mean measurements increased only 2 mm from 5 mm at 15 weeks to 7 mm at 35 weeks. The measurement of the atrium of the lateral ventricle as it becomes the occipital horn has been chosen by most authors as a standard reference structure in assessing ventricular size for a variety of reasons. First, the occipital horn of the lateral ventricle appears to dilate first, and most severely in the presence of hydrocephalus. Thus, this measurement should be the most sensitive for detection of ventriculomegaly rather than measurement of the frontal horn. Second, the walls of the ventricular atrium are perpendicular to the ultrasound beam in the transaxial plane and can be identified in virtually 100% of fetuses. Third, the echogenic choroid plexus is readily identified in most patients and serves as a marker for the lateral ventricular wall. In a later study by Cardoza et al the mean atrial diameter in 100 patients from 14 to 38 weeks was 7.6 mm with a standard deviation of 0.6 mm and was age independent. A ventricular atrial measurement exceeding 10 mm (greater than 4 standard deviations from the mean) should suggest ventriculomegaly. This was in contrast to earlier investigators who demonstrated an increase in the distance of the lateral ventricular wall from the midline with increasing gestational age. The most likely explanation is that the medial brain in addition to the ventricle were being measured in these earlier studies.

Normal ventricular atrial measurement. Note the choroid fills the ventricle at the atrium from its medial to its lateral wall

Since the above mentioned studies, there have numerous reports with larger series in an attempt to define the upper limits of normal for lateral ventricular atrial measurements. Values have ranged from a low of a mean of 5.4 mm with a SD of 1.2 mm to a high of 6.6 mm with a SD of 1.4 mm. While these studies validate the use of the upper limit of 10 mm for the atrium of the lateral ventricle, this would be at a maximum standard deviation of 2.5 . If 4 SD were used as the upper limit of normal the maximum acceptable atrial size would increase to 12 mm in several of these studies. From a practical perspective, it is probably most reasonable to leave the upper limit of normal at 10 mm, as will be discussed below. When ventriculomegaly is pronounced the choroid plexus will no longer lie in an almost parallel fashion against the lateral ventricular wall.Tethered at the Foramen of Monroe it will "hang down" and appear to "dangle" within the dilated ventricle. This appearance described as the "dangling choroid" plexus sign was described by Cardoza et al and also serves to confirm ventricular dilatation and differentiate it from pseudo-hydrocephalus.

Two cases of marked ventriculomegaly with "dangling" of the choroid plexus (arrows) in a gravity dependent manner

The diagnosis of ventriculomegaly and hydrocephalus are important for several reasons: the abnormal dilatation may impact adversely, the normal development of the fetal brain; the dilatation may be part of or the result of other neural axis abnormalities or the dilatation may be part of or signal the presence of other syndromic or non-neural axis abnormalities. The causes of ventricular dilatation are varied including: central nervous system abnormalities such as the Chiari II malformation, Dandy-Walker Malformation, agenesis of the corpus callosum, aqueductal stenosis, infection, hemorrhage or teratogens to name a few.

Mild Ventriculomegaly

While there is no question that moderate or severe hydrocephalus can have a dismal prognosis (fetal mortality between 55% and 91%) if progressive and associated with other abnormalities (neonatal survival rates as low as 15%-28%); the impact of the finding of mild ventriculomegaly is less clear. There have been numerous reports evaluating the impact of mild ventriculomegaly on the developing fetus and neonate. The emphasis has been on cases in which the ventricle measures between 10 and 15 mm and in which no other abnormalities are observed sonographically (isolated mild ventriculomegaly). A study by Mahony et al of 20 fetuses with mild ventricular dilatation and no other CNS abnormalities seen at ultrasound found that 60% of these fetuses at follow-up either had an "uncertain prognosis" or perinatal death. In this study the mild ventriculomegaly group had ventricles measuring between 9 - 15 mm but also had separation of the medial border of the choroid plexus from the medial ventricular wall of 3 mm or greater. Another study by Goldstein et al found an 83% mortality rate when ventriculomegaly ( 9-15 mm) was associated with other abnormalities and a 38% mortality rate when isolated. In the study by Bromley et al mild ventriculomegaly (10-12 mm) had a high rate of fetal mortality and morbidity and a normal outcome in only 59% of fetuses.

Mild Ventriculomegaly - The atrium of the lateral ventricle measured 11 mm.

Mild ventriculomegaly - The distance (arrow) from the medial aspect of the choroid plexus to the medial wall of the lateral ventricle was 5.5 mm

Isolated mild ventriculomegaly is said to occur in approximately 25% of fetuses with mild ventriculomegaly. Studies that have examined the "miss rate" of other abnormalities when fetuses were stated to have isolated mild ventriculomegaly have demonstrated false negative rates of approximately 10%. In the study of isolated mild ventriculomegaly by Patel et al there 44 patients with this diagnosis of which follow-up was available in 37 patients (beyond 1 year in 28 patients). Twenty-two (79%) of patients were developing normally at follow-up, whereas six (21%) were developmentally delayed. There was no difference between the subcategory of patients with dilated ventricles less than 11 mm and those 11-15 mm and abnormal outcome. One of 44 fetuses (2%) had a chromosomal abnormality (trisomy 21). With the exclusion of six children with limited follow-up, 78% of boys older than one year were developmentally normal compared with only 50% of girls. In a follow-up study Patel et al reexamined the issue of differing ventricle sizes in female and male fetuses.They evaluated the ventricular atrial measurements in 219 fetuses and found that the mean atrial diameter measured 5.8 mm (1.3 mm SD) in female fetuses and the mean atrial diameter measured 6.4 mm (1.3 mm SD) in male fetuses. Thus if the same upper limit of normal (10 mm) is used for both sexes, it is expected that more healthy male (0.28%) than healthy female (0.06%) fetuses would be above the limit.

A recent study by Bloom et al., with perhaps the most rigorous follow-up to date, also evaluated fetuses diagnosed antenatally with isolated mild ventriculomegaly. Young children (average age = 22 months) with the aforementioned diagnosis as fetuses were administered both the Bayley Scales of Infant Development, Second Edition, and the Vineland Adaptive Behavior Scales, Interview Edition, Survey Form. From a group of 94 fetuses diagnosed with mild ventriculomegaly between 1990 and 1996, 22 patients met the appropriate criteria and agreed to participate in the study and were matched with an appropriate comparison group. "The ventriculomegaly subjects scored significantly lower on the Bayley mental and psychomotor development development indices than did the children in the comparison group. In contrast, no such difference was found between the two groups on the Vineland Scales." While female subjects achieved significantly higher scores than male subjects on the motor scale testing in both the affected and comparison group, "the sex of the subject did not interact with the presence of mild isolated ventriculomegaly to affect psychomotor development index score significantly." In this study, eight (36.4%) of the 22 children with antepartum mild isolated ventriculomegaly were delayed, whereas only one (4.5%) of the 22 children in the comparison group were delayed. Of the eight children in the affected group who were developmentally delayed, two demonstrated resolution of the ventriculomegaly on subsequent antenatal ultrasound examinations, two revealed persistence or worsening and the remaining four did not have further sonographic studies. Only two children were diagnosed with significant mental developmental delay and in one of these the ventriculomegaly progressed antenatally. There was a linear correlation between the size of the ventricle and decreased performance on the mental developmental index.

Recently Vergani et al prospectively evaluated 11,864 patients over a 7 year period from 1990 to 1996 for the sonographic diagnosis of mild ventriculomegaly. A total of 82 cases fulfilled the criteria (prevalence 0.7%). It should be noted that theirs was a referral center. Mild ventriculomegaly was defined as the presence of a transverse diameter of the atria of the lateral ventricles between 10 and 15 mm inclusive. All fetuses underwent a detailed fetal survey of the brain (corpus callosum) and other non CNS-fetal structures including a fetal echocardiogram. Maternal serologic studies were performed as well as cytogenetic analysis for maternal indications or the presence of ventriculomegaly in the presence of other sonographic abnormalities. Follow-up sonographic examinations as well as, autopsy or neonatal follow-up including developmental testing was performed. In addition a literature search was performed for the prognostic significance of isolated mild ventriculomegaly.

Of the 82 cases, 34 (41%) were associated with other abnormalities, whereas 48 (59%) were isolated. The median atrial size was larger among cases with associated anomalies than in cases of isolated mild cerebral ventriculomegaly (12 vs 10 mm). An atrial size of between 12 and 14.9 mm was present in 19 of 34 (56%) cases of mild cerebral ventriculomegaly associated with anomalies and in 3 of 48 cases (6%) of isolated mild ventriculomegaly. 13 of 48 cases of isolated mild ventriculomegaly (24%) while 19 of 34 cases (56%) of mild ventriculomegaly associated with other findings were diagnosed prior to 24 weeks. Of the 35 cases of isolated mild ventriculomegaly diagnosed after 24 weeks, 19 (40%) had a normal sonographic examination prior to diagnosis. In this series isolated mild ventriculomegaly occurred more frequently in male fetuses (male/female ratio 2.2/1). The rate of female fetuses was significantly greater among mild cerebral ventriculomegaly cases associated with other anomalies than among isolated cases (62% vs 31%).

Karyotype analysis was performed in all cases of associated mild ventriculomegaly and seven chromosomal anomalies (20%) were identified (three cases of trisomy 21). Two cases of trisomy 21 were seen in cases of isolated mild ventriculomegaly (both of advanced maternal age). Among surviving euploid fetuses 10 of 16 (62%) had normal motor and neurologic development. Isolated mild ventriculomegaly remained stable throughout pregnancy in 28 of 48 cases (58%), resolved in utero in 16 of 48 cases (33%) and worsened in only 4 cases (8%).(2/4 had trisomy 21, 1 with aqueductal stenosis, and one was normal).

When the authors used previously published data in addition to their own to assess the rate of developmental delay they found that it was significantly lower in the presence of atria < 12 mm than in those equal to or greater than 12 mm (3% vs 23%).

The authors make a point several times in this report of the importance of making sure that cases of isolated mild ventriculomegaly are truly isolated prior to counseling regarding prognosis. Careful evaluation of the fetal brain for other associated abnormalities (agenesis of the corpus callosum was seen in 7 cases), as well as serologic testing for infection and echocardiography are all important. While not stated in this report, magnetic resonance imaging of the fetal brain may ultimately also prove useful in detecting other CNS abnormalites not seen at ultrasound. The presence of a male fetus with an ventricular size of <12 mm usually implies a good prognosis. In the presence of isolated mild ventriculomegaly and a normal karyotype the incidence of motor or neurologic developmental delay (preedominanly mild when present) is approximately 9% (range 0% to 19%). While the authors' reported rate of developemental delay is somewhat less than others there follow-up may not be as long as in some reports.

A recent report by Pilu et al stated their experience with borderline (mild) isolated ventriculomegaly as well as a review of the English literature. This study assessed the clinical significance of fetal isolated borderline cerebral lateral ventriculomegaly defined as a width of the atrium of the lateral cerebral ventricles of 10-15 mm in the absence of other sonographically demonstrable malformations. Of 31 fetuses, two had chromosomal aberrations (trisomy 21 and trisomy 13) and three had neurological complications (one infant developed shunt-dependent hydrocephalus, one lissencephaly and one cerebral hemorrhage and periventricular leukomalacia). The literature search revealed eight independent studies. Including the present series, 234 cases were available for analysis. An abnormal outcome was documented in 22.8% of cases. Perinatal death occurred in 3.7%. Chromosomal aberrations, mostly trisomy 21, were present in 3.8%, malformations undetected at a second-trimester sonogram in 8.6% and neurological sequelae, mostly a mild to moderate delay in cognitive and/or motor development, were present in 11.5%. The risk of an abnormal neurological outcome was increased in females versus males (22.6% versus 4.6%, relative risk 4.892; 95% confidence interval 1.356-1 7.656), when the atrial width was 12 mm or more (13.9% versus 3.8%, relative risk 3.6, 95% confidence interval 1.035-12.846) and when the diagnosis was made in the second trimester versus later in gestation. The authors conclusions were that: "in most cases, isolated borderline cerebral lateral ventriculomegaly has no consequence. However, this finding carries an increased risk of cerebral maldevelopment, delayed neurological development and, possibly, chromosomal aberrations. The optimal management of these cases remains uncertain."

Mild Idiopathic Ventriculomegaly and Chromosomal Abnormalities

In 1988 Mahony et al, and subsequently other investigators, noted a relationship between mild idiopathic ventricular dilatation and fetal trisomies. A prospective study by Achiron et al evaluated this relationship. From 5400 fetuses screened between 1989 and 1991 eight cases (0.15%) of mild ventriculomegaly were detected. Mild idiopathic ventriculomegaly was defined when the width of the ventricular atrium ranged between 10 and 15 mm or when the distance between the medial aspect of the choroid plexus and the medial wall of the lateral ventricle was greater than 4 mm. Six of the eight fetuses had karyotypic assessment of which two were abnormal (25%). Trisomy 18 was diagnosed in one fetus who also demonstrated clenched fists and the other fetus had trisomy 21. Of the four live births in their series, three (75%) were developmentally normal as neonates.

When these authors reviewed the literature, they found 92 cases of isolated mild ventriculomegaly. Eleven fetuses (12%) had an abnormal karyotype. The authors then calculated the risk of trisomy 21 in a fetus with mild ventriculomegaly. They used data from Nyberg's study in which it was reported that 3% of fetuses with trisomy 21 demonstrated the finding of mild ventriculomegaly, the rate of of mild idiopathic lateral ventriculomegaly in the general population to be 1 in 675 and the prevalance of trisomy 21 to be 1 in 600. From this the authors calculated the risk of trisomy 21 in a fetus with mild idiopathic lateral ventriculomegaly to be 3.3%. While this number may be a bit high, it clearly corroborates other studies showing an increased risk of fetal trisomy with isolated mild ventriculomegaly that far exceeds the risk of amniocentesis.

References:

Denkhaus H, Winsberg F. Ultrasonic measurement of the fetal ventricular system. Radiology 131:781-787, 1979

Hadlock FP, Deter RL, Park SK. Real-time sonography: Ventricular and vascular anatomy of the fetal brain in utero. Amer J Neuroradiol 1:507-511, 1980

Garrett WJ. Gray-scale examination of the brain in children. In:White D, Brown RE., eds. Ultrasound in Medicine, vol 3A. New York:Plenum 821-828, 1977

Fiske CE, Filly RA, Callen PW. Sonographic measurement of lateral ventricular width in early ventricular dilatation. J Clin Ultrasound 9:303-307, 1981

Crade M, Patel J, McQuown D. Sonographic imaging of the glycogen stage of the fetal choroid plexus. Amer J Roentgenol 137:489-491, 1981

Chinn DH, Callen PW, Filly RA. The lateral cerebral ventricle in early second trimester. Radiology 148:529-531, 1983

Hertzberg BS, Bowie JD, Burger PC et al. The three lines: Origin of sonographic landmarks in the fetal head. Amer J Roentgenol 149:1009-1012, 1987

Siedler DE, Filly RA. Relative growth of the higher fetal brain structures. J Ultrasound Med 6:573-576, 1987

Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly with a single measurement: the width of the lateral ventricular atrium. Radiology 169:711-714, 1988

Cardoza JD, Filly RA, Podrasky AE. The dangling choroid plexus: a sonographic observation of value in excluding ventriculomegaly. Amer J Roentgenol 151:767-770, 1988

Pilu G, Reece EA, Goldstein I, Hobbins JC, Bovicelli L. Sonographic evaluation of the normal developmental anatomy of the fetal cerebral ventricles:II The atria. Obstet Gynecol 73:250-256, 1989

Tennyson VM, Pappas GD. The fine structure of the developing telencephalic and myelencephalic choroid plexus in the rabbit. J Comp Neurol 123:379-412, 1964

Bromley B, Frigoletto FD, Benacerraf BR. Mild fetal lateral cerebral ventriculomegaly: clinical course and outcome. Am J Obstet Gynecol 164:863-867, 1991

Mahony BS, Nyberg DA, Hirsch JH, Petty CN, Hendricks SK, Mack LA. Mild idiopathic lateral cerebral ventricular dilatation in utero: sonographic evaluation. Radiology 169:715-720, 1988

Heiserman J, Filly RA, Goldstein RB. Effect of measurement errors on sonographic evaluation of ventriculomegaly. J Ultrasound Med 10:121-124, 1991

Alagappan R, Browning PD, Laorr A, McGahan JP. Distal lateral ventricular atrium: reevaluation of normal range. Radiology 193:405-408, 1994

Farrell TA, Hertzberg BS, Kliewer MA, Harris L, Paine SS. Fetal lateral ventricles: Reassessment of normal values for atrial diameter at ultrasound. Radiology 193:409-411, 1994

Goldstein RB, LaPidus AS, Filly RA, Cardoza J. Mild lateral cerebral ventricular dilatation in utero: clinical significance and prognosis. Radiology 176:237-242, 1990

Patel MD, Filly AL, Hersh DR, Goldstein RB. Isolated mild fetal cerebral ventriculomegaly: clinical course and outcome. Radilology 192:759-764, 1994

Patel MD, Goldstein RB, Tung S, Filly RA. Fetal cerebral ventricular atrium: difference in size according to sex. Radiology 194:713-715, 1995

Bloom SL, Bloom DD, Dellanebbia C, Martin LB, Lucas MJ, Twickler DM. The developmental outcome of children with antenatal mild isolated ventriculomegaly. Obstet Gynecol 90:93-97, 1997

Achiron R, Schimmel M, Achiron A, Mashiach S. Fetal mild idiopathic lateral ventriculomegaly: is there a correlation with fetal trisomy? Ultrasound Obstet Gynecol 3:89-92, 1993

Vergani P, Locatelli A, Strobelt N, Cavallone M, Ceruti P, Paterlini G, Ghidini A. Clinical Outcome of Ventriculomegaly Am J Obstet Gynecol 178:218-222, 1998

Pilu G, Falco P, Gabrielli S, Perolo A et al. The clinical significance of fetal isolated cerebral borderline ventriculomegaly:report of 31 cases and review of the literature. Ultrasound Obstet Gynecol 14:320-26, 1999

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Peter W. Callen, M.D.
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University of California Medical Center, San Francisco, California