A 26-year-old primiparous woman was admitted for evaluation to our ultrasound unit at 11 weeks' gestation because of suspected primary cytomegalovirus (CMV) infection. The woman was generally healthy. Her husband was also healthy, although he was a carrier of beta-thalassemia minor, which he had inherited from his father.
The initial findings on routine serology at 8 weeks' gestation had revealed a very low level of CMV-immunoglobulin (Ig)-G (6 arbitrary units (AU)/mL) and positive CMV-IgM, indicating a recent primary infection. At 13 weeks, there was a significant elevation in IgG level (62 AU/mL), and the IgM remained positive. An avidity test could not be performed because of the low level of IgG antibodies. Ultrasound examination at 13 weeks showed normal nuchal translucency thickness (1.2 mm). An early anomaly scan performed at 15 weeks showed a male fetus appropriate in size for gestational age, with no detectable abnormalities.
Sonography at 21 weeks revealed a hyperechogenic lesion measuring 12 mm in diameter occupying most of the right cerebellar hemisphere (Figure 1). The cisterna magna was normal, but there was mild asymmetry of the ventricles (width of 7 and 9 mm). The corpus callosum, vermis, and posterior fossa were visible. Mild pyelectasis (5 mm) of the left kidney was noted. Due to the possibility of primary infection of CMV, amniocentesis was performed at 22 weeks' gestation. Quantitative polymerase chain reaction (PCR), shell-vial assay and CMV culture were negative, excluding CMV infection. The karyotype was normal male (46,XY). A repeat scan at 23 weeks demonstrated a decrease in the right hyperechogenic lesion to 7–8 mm in diameter and suspected hyperechogenic lesion in the left hemisphere. At 24 weeks' gestation, significant hypoplasia of the right cerebellar hemisphere was diagnosed and was interpreted as being a consequence of hemorrhagic infarction (Figure 2). Following consultation with a pediatric neurologist, the parents decided to terminate the pregnancy and refused to delay their decision until after the magnetic resonance imaging examination that was scheduled for a few days later. The termination was carried out at 25 weeks by intracardiac injection of 5 mL potassium chloride, followed by induction of delivery with a balloon catheter and extra-amniotic prostaglandin.
At autopsy, the 760-g male fetus was appropriate-for-gestational age in all measurements. No dysmorphic facial features were noted. Grossly, the cerebellar hemispheres were asymmetric: the right cerebellar hemisphere was smaller and covered with blood clots (Figure 3a). A transverse (axial) section through the cerebellum and pons, revealed an irregular hemorrhagic mass that partially replaced the diminutive right cerebellar hemisphere and involved the overlying leptomeninges (Figure 3b). The cerebral hemispheres were normal and the ventricles were not dilated. Histological sections revealed a rich network of small capillaries as well as larger vessels, without intervening parenchyma. The lesion was not clearly circumscribed, and involved predominantly the right cerebellar hemisphere with overlying leptomeninges and extended focally to the left hemisphere, pons and midbrain (Figure 3c). The lesion was consistent with cerebral cavernous malformation, and was associated with recent hemorrhages, organizing hematoma, hemosiderin deposits and degeneration of surrounding cerebellar tissue. The rest of the autopsy disclosed mild dilatation of the left renal pelvis. No other gross or histological vascular anomaly was found.
Fetal cerebellar hyperechogenic lesions are rarely detected on prenatal ultrasound imaging. The differential diagnosis includes parenchymal hemorrhage, possibly from vascular anomaly, space-occupying lesion, or a result of viral infection.
Some cases may present initially with cerebellar hypoplasia, which may be global or focal1. The diffe- rential diagnosis should then include prenatal viral infection, exposure to teratogens, chromosomal aberrations, metabolic disorders, isolated (genetic) migration disorders, congenital muscular dystrophies or pontocerebellar hypoplasia2. Focal hypoplasia, as in our case (i.e. affecting one hemisphere), is highly suggestive of a clastic origin due to vascular disruption leading to ischemia or hemorrhage1, 3, 4.
In our case, the combination of the positive CMV-IgM and the sonographic image of a hyperechogenic cerebellar lesion first suggested a cerebellar insult due to CMV infection. Cerebellar hypoplasia has been reported in congenital CMV infection, but it is usually reported with other brain anomalies (microcephaly, lissencephaly, polymicrogyria, ventriculomegaly, periventricular calcification)5–10. The negative results of the PCR, shell-vial, and culture studies ruled out CMV, raising the possibility of a parenchymal hemorrhage due to arteriovenous malformation or a space-occupying lesion.
Congenital and neonatal tumors are extremely rare, with a reported rate of 1 in 25 000 liveborn infants. About 0.5–1.5% of all brain tumors are congenital, and most are diagnosed before 2 years of age11, 12. Tumors of the posterior fossa include astrocytomas, medulloblastomas, ependymomas, gliomas, teratomas and hemangioblastomas. Brain tumors may be suspected prenatally on findings of a hypo- or hyperechogenic lesion, distortion or hydrocephalus.
Vascular lesions are diverse and their nomenclature is confusing. They are derived from vessels, somewhere from the continuum of artery–capillary vein. They involve an increased number of normal or abnormal vessels13. Some lesions consist of only one type of vessel, while others are made up of several components (e.g. capillaries and venules). The most widely used classification of vascular central nervous system (CNS) anomalies includes: capillary telangiectasia, venous angioma, cavernous angioma malformation and arteriovenous malformation. Mixed and transitional lesions are also described14. It appears that cerebral cavernous malformation (angioma) is a distinct clinical-radiological-pathological entity15. Histologically, it consists of dilated capillary-like endothelial channels, lacking intervening parenchyma and lacking smooth muscle or elastic fibers in their walls16. The fate of vascular lesions (especially in the CNS) is highly dependent on location, extension, multiplicity, accompanying hemorrhages with tissue destruction and underlying disorders. In our case, the final diagnosis was made at autopsy. Massive cerebellar hemorrhage was associated with a poorly circumscribed vascular lesion whose predominant component was capillaries, without intervening parenchyma. These findings are consistent with a transitional form between venous and capillary malformation. It was detected sonographically during the second trimester, probably because of its secondary hemorrhage and tissue destruction.
Prenatal cerebrovascular anomalies are rarely described in the literature. There have been reports of some cases associated with intracranial hemorrhage6, 17, 18. Hemorrhage probably facilitates early diagnosis. Vascular anomalies of the cerebellum are also rare. Among four cases described by Thrash, one was a case similar to ours, in a premature baby. The cerebellar vascular malformation was composed of dilated capillaries and involved leptomeninges and the contralateral hemisphere19. Cases of capillary telangiectasia4, 20 and venous angioma6 have also been described.
In summary, we have described a rare case of cerebellar vascular malformation in the second-trimester fetus. There was a recent maternal CMV infection, but this was probably not related to the lesion. Extensive hemorrhaging with tissue destruction, as in previous reported cases, complicated the primary lesion and facilitated the sonographic detection. In such cases, the possibility of familial occurrence or a syndrome involving CNS vascular anomaly should be considered.