The development of the Sylvian fissure is one of the major brain maturational processes occurring in fetal life. Using magnetic resonance imaging (MRI), abnormalities in this process, leading to aberrant operculization, have been diagnosed increasingly in infants and children with developmental delay.
Although the maturational phases of the operculum have been defined by neuropathological evaluation of fetuses1, relatively few papers have described ultrasonographic imaging of normal operculization2–5. Since the introduction of ultrasound for evaluation of the fetal brain, emphasis has been on the ventricular system and surrounding structures and the study of the cortex has lagged behind. This fact can be explained mainly by technical issues that have precluded visualization of the proximal hemispheric surface and by the rapid developmental changes in cortical milestones through pregnancy that are difficult to standardize and remember during real-time scanning.
The seminal study by Chen et al.6 in 1995 describing the normal topography of the cerebral operculum on MRI led to papers describing its abnormal formation7–10 and paved the way to the in-utero identification of related conditions. In this issue of the Journal, two papers are evidence of the recent interest in operculization and advance our knowledge of this process. Quarello et al.11 suggest a standardized approach to following fetal Sylvian fissure development and Guibaud et al.12 present their experience with the prenatal diagnosis of abnormal development of this structure and correlate their imaging findings with neuropathological and postnatal data.
Quarello et al.11 defined six gross landmarks in the normal operculization process based first on the angle between the insula and the temporal lobe and then on the extent of overriding of the posterior half of the insula by the temporal lobe; these landmarks and the stages in between them were scored between 0 and 10. In our opinion, this method, although described as being reproducible and reliable, is cumbersome, time-consuming and relatively difficult to apply in daily practice and is unnecessary during the performance of a routine examination. This opinion is strengthened by the fact that all cases with abnormal operculization described by Guibaud et al.12 were referred for associated findings, including ventriculomegaly, abnormal head circumference and other central nervous system (CNS) and non-CNS anomalies. Dedicated neurosonography and MRI later defined the abnormal operculization and added information regarding the presence of malformations of cortical development (MCD), such as lissencephaly and polymicrogyria. Chen et al.13 divided abnormal operculization into five types. Isolated abnormal operculization was found only among patients with Type 5 (normal-appearing insula with underdeveloped operculum consistent with the developing operculum found after 32 weeks of gestation). This group included children with abnormal head circumference, metabolic diseases and trisomy 21 and children with non-specific developmental delay. The authors suggested that the abnormal operculization in some of these children could signify delayed maturation, similar to delayed myelination, that would improve with time with concomitant improvement of the developmental delay. Therefore, we may conclude that initial evaluation, even in the hands of a sonographer without proficiency in neurosonography, will usually be sufficient to identify most at-risk fetuses, enabling referral for consultation at a fetal neurology clinic, where the scoring method described in this issue will be very useful for accurate definition of the brain anomaly.
Since Kuzniecky et al.14 first described congenital bilateral perisylvian syndrome in 1989, abnormal operculum formation has been considered almost synonymous with polymicrogyria. However, the paper by Guibaud et al.12 highlights the fact that most children with abnormal operculization will not have an associated MCD (10 out of 15 cases). These results are consistent with the findings of Chen et al.13, that only 14 out of 86 patients had an MCD. In these 14 patients, the operculum was either unformed or abnormally formed.
Combining the knowledge obtained from the papers in this issue with the literature on normal and abnormal formation of the operculum, we can conclude that: when the operculum is unformed or abnormally formed, it carries a uniformly bad prognosis and usually signifies an underlying MCD; when the operculum is underdeveloped for gestational age, it is usually associated with abnormal head circumference, brain anomalies (especially of the midline, such as callosal dysgenesis, cerebellar hypoplasia and holoprosencephaly), neural tube defects, multiple malformations or intrauterine infection (cytomegalovirus); when it is an isolated finding, the prognosis is unclear. In this situation, it may represent a metabolic disease (glutaric aciduria Type 1, Canavan disease, mitochondrial disorder), a chromosomal anomaly (trisomy 21, 22q11 deletion) or a neurogenetic syndrome (Sotos syndrome, Treacher–Collins), it could signify benign delayed maturation of the operculum, or, when combined with macrocephaly, it could be part of benign enlargement of the subarachnoid spaces15 (Figure 1).
Based on the differential diagnosis, the protocol for prenatal investigation after ultrasound has identified abnormal operculum formation should include: parents' head circumference measurement, complete fetal ultrasound examination including neurosonography and echocardiography, brain MRI, amniocentesis for karyotype, fluorescent in-situ hybridization for chromosome 22q11 deletion, amniotic fluid organic acids assessment and TORCH.
The papers by Quarello et al.11 and Guibaud et al.12 shed new light on the normal and abnormal development of the fetal operculum and are likely to facilitate prenatal diagnosis and counseling. However, in our opinion, the possible benefits of routine evaluation of the Sylvian fissure as part of the second-trimester ultrasound examination remain to be proven.