Exencephaly is a rare fetal anomaly that is incompatible with extrauterine life. In exencephaly, the bones of the cranial vault are absent (acrania), but the facial structures and the base of the skull are preserved (Casellas et al., 1993). The terms exencephaly and acrania are used interchangeably in this chapter. Exencephaly is a precursor to anencephaly (the so-called fetal acrania-anencephaly sequence); it differs from anencephaly in that residual brain tissue is present and floating free in the amniotic fluid.

Exencephaly is frequently noted in animal teratogen studies. Human exencephaly appears to be confined to early gestation. Only rare reports exist of a third trimester diagnosis of an exencephalic fetus (Wilkins-Haug and Freedman, 1991). Anencephaly, however, is more common in humans than in animals. The greater prevalence of anencephaly in humans is attributed to a longer gestational period, which presents the opportunity for destruction of the free-floating brain matter.

Exencephaly is due to the failure of the anterior neuropore to close during the 4th week of embryonic development. The underlying defect is due to a failure in mesenchymal migration (Stagiannis et al., 1995). In pathologic studies, the exencephalic brain is noted to be covered by a highly vascular epithelial layer. In exencephaly, two relatively equivalent cerebral hemispheric remnants are present within a reddish mass of disorganized tissues, remnants of deep cerebral neural elements, blood vessels, fibrous tissues, and fluid-filled spaces (Hendricks et al., 1988). The remaining brain has been termed the “anencephalic area cerebrovasculosa.” In exencephalic brain tissue, the gyri and sulci are shallow, flattened, and disorganized. All surfaces of the brain are highly vascular. The remaining central nervous system tissue is dysplastic, with little or no neuronal differentiation, and very little normal cortex (Hendricks et al., 1988).

Papp et al. (1986) reviewed cases of neural tube defect detected by maternal serum α-fetoprotein (AFP) screening. In 36,075 screened pregnancies, 10 cases of exencephaly were detected. This equals an incidence of 3 cases per 10,000 screened pregnancies. The same population had 14 cases of anencephaly per 10,000 screened pregnancies. In this report from Hungary, the mean age of the mothers of fetuses with exencephaly was 22 years. Of the 10 affected pregnancies detected, 9 were singletons and 1 was a twin gestation. In eight of the nine cases described, the maternal serum AFP levels were greater than 2.5 multiples of the median.

In experimental animals, there is an increased incidence of exencephaly in fetuses of female mice injected with clomiphene citrate prior to ovulation (Dziadek, 1993). In addition, hyperglycemia in mice induces exencephaly (Sadler, 1980). The phenomenon in mice is similar to the inhibition of neural tube closure seen in infants of mothers with diabetes.

Exencephaly/acrania can be detected early and late in gestation. In the normal fetus, echogenic areas can be seen that correspond to calcification of the cranial bones at approximately 11 weeks. If calcification is absent at this point in gestation, exencephaly should be considered. Another finding can be lateral widening of the cerebral hemispheres with clear delineation of the interhemispheric fissure, the “Mickey Mouse” sign. Later in gestation, the most common finding in exencephalic fetuses is the presence of a large quantity of disorganized brain tissue that is not covered by the bones of the skull, with concomitant preservation of facial structures and bones at the base of the skull (Figure 13-1).

The first prenatal sonographic diagnosis of exencephaly was made at 39 weeks and described by Cox et al. in 1985. Subsequently, the gestational age at diagnosis has decreased considerably. Multiple case reports have contributed to the information available regarding sonographic diagnosis. In one report, in a routine sonographic examination performed at 29 weeks of gestation, the flat bones of the skull were noted to be absent with only a small part of the occipital bone present (meroacrania). Disorganized brain tissue was noted to be floating free in the amniotic cavity. In addition, no evidence of cerebral ventricles was seen, and the gyri were noted be extremely disorganized (Casellas et al., 1993).

Exencephaly is often associated with other major malformations, most commonly omphalocele, amniotic band syndrome, limb–body wall complex, and pentalogy of Cantrell.

First trimester diagnosis of exencephaly is possible (Nishi and Nakano, 1994; Bognoni et al., 1999). In a case diagnosed at 9 weeks, the following sonographic features were observed: the cranial pole was smaller than the chest, the cranial pole bulged dorsally, and the surface of the cranium was irregular (Becker et al., 2000). In another report at 10 weeks, a vaginal sonogram demonstrated absence of the calvarium, choroid, and echolucent areas normally seen in the brain at that point in gestation (Kennedy et al., 1990). In the affected fetus, the brain appeared echodense, with a pulsatile prominence in the area of the forebrain. Because of the concern regarding lack of cranial calcification, repeat sonography was performed at 14 weeks of gestation. At this later time, the cranium was noted to be absent above the occipital bones, a widened cervical spine was present, and fragments of neural tissue were seen attached but floating in the amniotic fluid in the process of degeneration (Kennedy et al., 1990).

More recently, Cafici and Sepulveda (2003) described an indirect sonographic sign of acrania/exencephaly, echogenic amniotic fluid. It is hypothesized that after 10 weeks of gestation, the exposed fetal brain rubs against the uterine wall. This mechanical trauma results in the exfoliation of blood and neural tissue into the amniotic fluid, which can be identified as echogenic free-floating particles.

Three-dimensional (3-D) scanning in the diagnosis of acrania–anencephaly sequence has also been described (Liu et al., 2005).