Congenital infections are acquired by the maternal hematogenous-transplacental route or by exposure to organisms during passage through the birth canal. Most fetal bacterial infections are due to the ascent of organisms from the cervix into the amniotic fluid. Congenital infections of the central nervous system (CNS), however, are usually transmitted transplacentally. The TORCH organisms cause most of these CNS infections: Toxoplasma, other (coxsackievirus, syphilis, varicella-zoster, human immunodeficiency virus, and parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus type 2 (HSV). These organisms can cause chorioretinitis, microcephaly, and focal cerebral calcification.
The stage of fetal development at which the infection occurs is a crucial factor in determining the sequelae. In general, CNS infections that occur during the first 2 trimesters tend to cause developmental malformations, whereas those occurring during the third trimester lead to destructive brain lesions. Migration abnormalities are the most common developmental manifestations of congenital CNS infections. Because the fetal brain has limited capacity for astroglial reaction, necrotic tissue caused by a congenital infection is completely removed by the immune response. The resultant defect may persist as a fluid-filled cavity (i.e., porencephaly) or be replaced by expansion of adjacent normal tissue.
Cytomegalovirus is the most common organism involved in congenital infections. This infection occurs in approximately 40,000 infants in United States per year (approximately 1% of all births). Approximately 10% of infants congenitally infected with cytomegalovirus have clinical manifestations of disease at birth (i.e., cytomegalic inclusion disease). These infants may have hepatosplenomegaly, petechiae, microcephaly, cerebral atrophy, ventriculomegaly, chorioretinitis, or sensorineural hearing loss. Neuronal migration anomalies are common. Approximately 90% of children who survive symptomatic congenital cytomegalovirus infection have long-term neurological sequelae, such as intellectual impairment, seizures, and sensorineural hearing loss. Infants with congenital cytomegalovirus infection born to mothers who have preexisting immunity to the virus are usually asymptomatic at birth, but may go on to exhibit subtle neurodevelopmental sequelae. Up to 20% of these infants have unilateral or bilateral sensorineural hearing loss.1–3
The major neuroimaging findings of congenital cytomegalovirus infection include generalized periventricular calcifications, cerebral underdevelopment, white matter thinning, porencephaly, cerebellar hypoplasia, cortical dysplasia, and delayed myelination (Figure 16-1). With severe involvement, there is hydranencephaly. Infections occurring early during pregnancy may lead to lissencephaly, cerebellar hypoplasia, delayed myelination, and marked ventriculomegaly. White matter involvement occurs in the form of diffuse thinning or multifocal areas of damage. Cysts may develop in the involved white matter. Infections occurring around the time of the mid-second trimester are usually associated with less severe global brain malformations. Polymicrogyria is common in these children. Schizencephaly can occur. Infections occurring near the end of gestation generally do not result in altered gyral patterns. Periventricular calcifications and white matter changes are common, whereas ventriculomegaly and cortical thinning are relatively mild. White matter involvement in these children tends to spare the periventricular and subcortical regions.4–8