Neurocutaneous Syndromes: Developmental Dysplasias of the Early Period of Gestation. A Clinical and MRI Study

Abstract

The neurocutaneous syndromes, also called phakomatoses or hamartomatous syndromes, are a highly variable and heterogenic group of dermatologic, somatic and nervous system disorders. Much attention is paid to these syndromes by neurologists because they are usually accompanied by epilepsy and mental retardation. Dermatological symptomatology is relatively variable, and somatic disturbances are very common, but nervous system disorders, both in clinical and in MRI pictures, are regularly observed. The normal process of neural crest formation in the 4th week of gestation is characterized by a period of rapid proliferation and differentiation of the neuroependymal cells and this process of neuroblast migration is often considered to be the most important developmental period of the brain. This process continues between the 10th and 22nd weeks of gestation and ends with the cellular apoptosis of 30–50% of participating neuroblasts. In some cases, the neuroblasts will not reach their predetermined site within the cerebral cortex and abnormal layers or bands of heterotopias in the subependymal or subcortical spaces may form. These defects in the cortical grey matter manifest themselves as flat cortex (lissencephaly or agyria), pachygyria (macrogyria) or polymicrogyria. The process of neuroblast migration is intertwined with the earlier stages of brain embryogenesis. After four weeks of gestation, in 5–6 mm sized embryos, two branches of the carotid artery are visible, and in 15–16 mm sized embryos two branches of the vertebro-bazilar arterial system are identifiable. The most frequent cause of malformations is genetic chromosomal defects, but similar developmental disturbances are seen in sporadic cases where the developing embryo has been subjected to harmful exogenic influences (i.e. congenital mononucleosis infections, drug dependence, or fetal alcohol syndrome). Here we demonstrate MRI changes in some typical cases of neurocutaneous diseases generally accepted as denoting lissencephaly. Together with lissencephaly some other ventricular (hydrocephalus, mid-line defects) and vascular system abnormalities with variable skin phacomas are observed. In some cases of undiagnosed idiopatic epilepsy, variable skin morphas may be found which serves to emphasize the importance of MRI examination as a diagnostic tool. We frequently observed lissencephaly combined with vascular dysplasias or abnormal ventricular configurations.