The "cortical invagination sign": a midtrimester sonographic marker of unilateral cortical focal dysgyria in fetuses with complete agenesis of the corpus callosum.

BACKGROUND: Agenesis of the corpus callosum (ACC) is associated with several malformations of cortical development. Recently, features of focal cortical dysgyria have been described in fetuses with ACC.

OBJECTIVES: To describe the "cortical invagination sign", a specific sonographic feature of focal cortical dysgyria, which is consistently seen at midtrimester axial brain ultrasound in fetuses with complete agenesis of the corpus callosum (ACC).

STUDY DESIGN: Retrospective analysis of prospectively collected data from 2018 to 2021, including patients referred to five fetal medicine centers in the second trimester (19+0 - 22+0 weeks of gestation) with suspected complete ACC. All those cases with the diagnosis of complete ACC were submitted to an axial sonographic assessment of the fetal brain on the transventricular plane. On this scanning section, the mesial profile of both cerebral hemispheres at the level of the frontal-parietal cortex was investigated. In this area, the operator looked for an abnormal invagination of the cortical surface along the widened interhemispheric fissure, which was referred to as the "cortical invagination sign". All fetuses were submitted to dedicated antenatal magnetic resonance imaging (MRI) to reassess the ultrasound findings. Cases with additional brain anomalies which did not involve the cortex were excluded. The final diagnosis was confirmed at postnatal brain MRI or postmortem examination, for cases undergoing termination of pregnancy (TOP). The primary outcome of this study was to evaluate the presence and laterality of the "cortical invagination sign" in fetuses with complete ACC at antenatal ultrasound and MRI.

RESULTS: During the study period, 64 cases of complete ACC were included, of those 50 (78.1%) underwent TOP and 14 (21.9%) resulted in a live birth. The "cortical invagination sign" was detected at ultrasound in 13/64 (20.3%) cases, and at targeted brain MRI in two additional cases (23.4%), all of which were electively terminated. Moreover, the "cortical invagination sign" was found to be exclusively unilateral and on the left cerebral hemisphere in all the cases. There was a predominant majority, albeit non-significant, of male fetuses (80.0% of the cases, P=0.06) in the group of complete ACC with "cortical invagination sign".

CONCLUSIONS: The "cortical invagination sign" is a specific marker of focal cortical dysgyria which seems to characterize at mid-trimester a large group of fetuses with complete ACC. The etiology, pathophysiology and prognostic significance of this finding remains to be elucidated.