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Embryonic development of the nervous system is a series of overlapping processes.1 To understand neural development, a traditional view of morphogenesis must be integrated with what we know about molecular genetic programming of the neural tube and fetal brain. Understanding these normal ontogenetic processes is necessary to comprehend neural malformations, which arise as disturbances in one or more of these processes. Malformations of the brain and spinal cord may be caused by genetic mutations or by environmental or acquired influences. Examples of acquired and environmental causes are teratogenic toxins and drugs, fetal ischemia and infarcts, intrauterine trauma from maternal trauma or invasive procedures, cerebral hemorrhages, and infections affecting the fetal brain.

Knowledge of neuroembryology provides insight into the pathogenesis and mechanisms of neural malformations and how the brain determines dysgeneses of many non-neurological structures, such as developmental craniofacial disorders. Molecular genetics has profoundly changed our understanding of the mechanisms of both normal and abnormal development of the nervous system. These advances, combined with medical advances in neuroimaging, clinical neurophysiology, and neuropathologic tissue examination, provide a way to understand malformations of the nervous system. Thus, this chapter is not presented as a traditional list of various known neural malformations, each with their clinical, radiologic, and pathologic findings; nor is it intended as a tabulation of known genetic mutations and deletions associated with specific dysgeneses. It is presented as a modern approach to better understand malformations in the context of development, a new neuroembryology that integrates descriptive morphogenesis and genetic programming.

Neural development is better thought of as a set of simultaneously occurring processes than as a set of sequential steps.

Traditional classifications list a series of developmental processes as a linear sequence of events, one following another. Some processes are indeed step-wise, each dependent upon the preceding one. Among these are:

  • Gastrulation
  • Establishment of the body axes
  • Curling of the primitive neuroepithelium or neural plate to form the neural tube

All of these processes occur before maturation of individual cells and structural organization of the neural tube.

Other neurodevelopmental processes occur late in embryonic development. Synaptogenesis can only occur after the formation of dendrites and dendritic spines, maturation of the neuronal membrane to form synapses, and the synthesis of neurotransmitters and their release at axonal terminals. Myelination of axons does not occur during the projection phase of axonal growth before the axon has reached its target and initiated synapse formation.

However, most processes occur simultaneously, such that they must be considered in relation to one another. Among these are:

  • Neuroblast migration
  • Maturation of the neuroblast membrane capable of developing a resting membrane potential
  • Projection of the axonal growth cone from the migratory neuroblast
  • Vascular perfusion of the brain
  • The formation of glial cells in relation to capillaries to form a blood–brain barrier

Nevertheless, it is useful both for classification and ...

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