Cell Proliferation Disorders

A considerable number of central nervous system pathologies remain undiagnosed during the first two trimesters of pregnancy. This group of disorders includes anomalies of brain proliferation, migration and cortical organization. Due to the fact that a detailed ultrasound examination of the fetal brain is usually not performed during the third trimester the diagnosis of these disorders is usually only made in families with a previously affected child or in many cases be mere chance. In this article we review the feasibility of prenatal diagnosis of disorders of brain proliferation: microcephaly, macrocephaly, hemimegalencephaly and neoplastic and non-neoplastic abnormal cell types. We discuss the differential diagnosis and offer a stepwise approach to the diagnosis of the more common disorders. Review Thirty years have passed since the first prenatal diagnosis of a fetus with a brain malformation was made by ultrasound [1]. Since then, rapid development of new US machines and transducers have established the basis for a new field in Obstetrics: the diagnosis of congenital anomalies[2]. Shortly after the report by Campbell et al [1] Kratochwil et al diagnosed fetal hydrocephaly [3], Michell and Bradley-Watson described a case of fetal meningocele [4] and Karp et al reported the use of ultrasound for the exclusion of primary microcephaly [5]. During the second half of the 70's and during the 80's studies on the normal anatomy and biometry of the fetal brain enabled prenatal screening for CNS malformations [6-9]. By 1988 the now classical textbook on the prenatal diagnosis of congenital anomalies by Romero et al [2] included a comprehensive chapter on the normal anatomy and pathology of the fetal CNS. In their book they describe the ultrasonographic features of holoprosencephaly, agenesis of the corpus callosum, intracranial arachnoid cysts, and choroid plexus cysts. One year later, Filly et al suggested the use of 3 specific axial planes for the evaluation of the fetal CNS [10]. By routine visualization of the transventricular, transthalamic and transcerebellar planes, they were able to diagnose, retrospectively, most cases with CNS anomalie. Further progress was made after the introduction of high-resolution transvaginal probes. Transvaginal ultrasound permits the study of the brain in fetuses in vertex presentation in planes that are usually difficult to obtain with the transabdominal approach [11,12]. Recently, fetal magnetic resonance emerged as an additional potential useful method for the diagnosis of CNS anomalies [13]. The modern approach to the diagnosis of fetal CNS pathologies requires an in-depth knowledge of brain anatomy and embryology, expertise in the different imaging techniques and proficiency in the different genetic aspects of congenital brain disorders. Moreover, in order to establish the specific prognosis in a given case experience in pediatric neurology is essential. These requirements can only be met by a multidisciplinary team that includes experts in the fields of fetal medicine, neuroradiology, genetics, pediatric neurology, neonatology and pathology [14]. A cornerstone in the understanding of the development of the normal and pathologic brain is the understanding that the brain develops as a continuum during pregnancy and even after delivery and that different insults at a specific time may produce similar pathologies [15]. The current recommendation for screening of fetal anomalies is a second trimester ultrasound examination between 19 and 22 weeks of pregnancy. However a substantial amount of significant brain anomalies will remain undiagnosed at this gestational age [16]. We present a structured approach to the diagnosis of late manifesting fetal intracranial pathologies. In this first part we review the different aspects of cell proliferation disorders. Brain Development Volpe describes the sequential development of the human brain [15]. Early events include dorsal and ventral induction while later events, occurring from the second month of gestation through the postnatal period, include cell proliferation, migration, organization and myelination.