Microencephaly describes the group of malformations in which the volume of brain is too small; usually it is associated with a small head as well (microcephaly). It has a wide range of associations, including chromosome abnormalities, fetal alcohol syndrome, and human immunodeficiency virus (HIV) and Zika virus infection acquired in utero. The unifying feature is decreased generation of neurons destined for the cerebral cortex. During the early stages of brain development, as progenitor cells proliferate in the subependymal ventricular zone, the balance between cells leaving the progenitor population to form the cortex and those remaining in the proliferating pool affects the overall number of neurons and glial cells generated. If too many cells leave the progenitor pool prematurely, there is inadequate generation of mature neurons, leading to a small brain. Megalencephaly, excessive brain volume that is always associated with a large head, is far less common and is mostly associated with rare genetic disorders.
Disruption of neuronal migration and differentiation during development can lead to abnormalities of gyration and neocortical architecture, often taking the form of neurons ending up in the wrong location. Mutations in various genes that control migration result in a variety of malformations. A representative example is holoprosencephaly, characterized by disruption of normal midline patterning. Mild forms show absence of the olfactory bulbs and related structures (arrhinencephaly). In severe forms, the brain is not divided into hemispheres or lobes, and there may be facial midline defects such as cyclopia. The best known genetic causes involve acquired or inherited loss of function mutations in components of the Hedgehog signaling pathway.
Other examples include loss of gyri, which may be complete (lissencephaly) or partial, and increased number of irregularly formed gyri (polymicrogyria).
The most common malformations in this region of the brain result in misplacement or absence of portions of the cerebellum.
Arnold-Chiari malformation (Chiari type II malformation) combines a small posterior fossa with a misshapen midline cerebellum and downward extension of the vermis through the foramen magnum; hydrocephalus and a lumbar myelomeningocele typically are also present.
The far milder Chiari type I malformation has low-lying cerebellar tonsils that extend through the foramen magnum. Excess tissue in the foramen magnum results in partial obstruction of CSF flow and compression of the medulla, with symptoms of headache or cranial nerve deficits often manifesting only in adult life. Surgical intervention can alleviate the symptoms.
Dandy-Walker malformation is characterized by an enlarged posterior fossa, absence of the cerebellar vermis, and a large midline cyst.
Brain injury occurring in the perinatal period is an important cause of childhood neurologic disability. Cerebral palsy is a term for nonprogressive neurologic motor deficits characterized by spasticity, dystonia, ataxia or athetosis, and paresis attributable to injury occurring during the prenatal and perinatal periods. Signs and symptoms may not be apparent at birth and only declare themselves later, well after the causal event.
The two major types of injury that occur in the perinatal period are hemorrhages and infarcts. These differ from the otherwise similar lesions in adults in terms of their locations and the tissue reactions they engender. In premature infants, there is an increased risk for intraparenchymal hemorrhage within the germinal matrix, most often adjacent to the anterior horn of the lateral ventricle. Hemorrhages may extend into the ventricular system and from there to the subarachnoid space, sometimes causing hydrocephalus. Infarcts may occur in the supratentorial periventricular white matter (periventricular leukomalacia), especially in premature infants. The residua of these infarcts are chalky yellow plaques consisting of discrete regions of white matter necrosis and dystrophic calcification (