Polymicrogyria refers to an excessive number of abnormally small gyri. It is expressed by a syndrome of cognitive impairment, seizures, delayed speech, and motor abnormalities. The cortex may fail to become sulcated—that is, it is lissencephalic or may be defectively convoluted, forming microgyric and pachygyric (broad gyral) patterns. In yet other brains, neuronal migration is normal for the most part, but small groups of neurons in particular regions may lag or present in regional heterotopias (focal dysgeneses; Fig. 37-1). These migrational disorders, particularly heterotopias, are now being recognized more often by MRI and are found to have a functional significance in epilepsy but also possibly in states of nonspecific developmental delay as well as in dyslexia. Finally, the cortex may be normally formed and structured but there is a failure of differentiation of intraand intercortical and interhemispheral connections, the most obvious one being agenesis of the corpus callosum.
The timing of embryogenesis of the main visceral organs and of the coincident stages of neural tube closure were given in the introduction. With these elementary facts of neuroembryology in mind, the bases of the following clinical states are readily conceptualized: anencephaly, lissencephaly, holoprosencephaly, polymicrogyria and pachygyria, microcephaly, and combinations of cranial and somatic abnormalities. Each is described below.
In regard to disorders of brain development, there are also certain tumors that are the consequence of abnormal neuronal or glial development. These are variously termed gangliomas, or gangliocytomas, dysembryoplastic neuroepitheliomas (DNETs), and low-grade astrocytomas. Sometimes they become manifest in the first year of life or even before birth. Their relatively slow growth and benign character suggest that some of them represent hamartomas rather than true neoplasms (see Chap. 30). Among the ones encountered in adults is the Lhermitte-Duclos type of dysplastic cerebellar gangliocytoma that is characterized by a “tigroid” appearance on MRI (see Fig. 30-16).
Genetics of cerebral disorders of neuronal migration (Table 37-3) Because each phase of cerebral development is under genetic control, it comes as no surprise that aberrant development might have a genetic basis. A singular advance in this field has been the identification of large numbers of genetic defects that underlie disorders of neuronal migration. These mutations, and what is known of their effects on the developing nervous system, were reviewed extensively by Mochida and Walsh, by Kato and Dobyn, and by Barkovich and colleagues; a summary is given in Table 37-3. The reader will notice that several quite different mutations may give rise to the same type of maldevelopment and that any given gene can cause malformations of varying severity but in most cases, the affected gene is active at a stage in brain development that makes the nature of the malformation understandable.
It should at the same time be noted that metabolic disturbances may also give rise to malformations of cerebral development. For example, in their review of the inborn errors of metabolism those are linked to cerebral dysgeneses. Nissenkorn and colleagues point out that disorders such as Zellweger syndrome and disorders of fatty oxidation, phenylketonuria (PKU), hyperglycinemia, and pyruvate dehydrogenase deficiency cause aberrant neuronal migration and dysgenesis of the corpus callosum.