This can be caused by factors extrinsic to the brain tissue, such as hydrocephalus and hydrancephaly (as defined below), or excessive brain growth (megaloor macroencephaly; Table 37-2). The hydrocephalic head is distinguished by several features: frontal protuberance, or bossing; a tendency for the eyes to turn down so that the sclerae are visible between the upper eyelids and iris (sunset sign); thinning of the scalp and prominence of scalp veins; separation of the cranial sutures; and a “cracked pot” sound on percussion of the skull. Infantile hydrocephalus usually comes to medical attention because of an expanding cranium that exceeds normal dimensions for age. The usual causes are type II Chiari malformation, hereditary aqueductal stenosis, and prenatal infections, for example, toxoplasmosis. These disorders are discussed further on.
Hydranencephaly, defined as hydrocephalus and destruction or failure of development of parts of the cerebrum, is often associated with enlargement of the skull. When the cranium is transilluminated with a strong flashlight in a darkened room, the fluid-filled region of the cranium glows like a jack-o’-lantern. It can be caused by cerebral infarction from intrauterine vascular occlusion or by diseases such as toxoplasmosis and cytomegalovirus (CMV), which destroy parts of each cerebral hemisphere. The lack of brain tissue reduces resistance to intraventricular pressure, permitting great enlargement of both lateral ventricles; it is especially marked if there is an added hydrocephalic state because of interference with cerebrospinal fluid circulation. This type of destruction of the cerebral mantle in the embryonal period may lead to the formation of large brain defects with apposition of ventricular and pial surfaces (porencephaly) and subsequent failure of development of that part of the brain. Yakovlev and Wadsworth referred to the localized failure of evagination as schizencephaly and postulated that it was the result of a focal developmental defect in the wall of the cerebral mantle. They based their interpretation on the finding of malformed cortex in the margins of the defect (in distinction to porencephaly) but this might indicate only that the lesion preceded neuronal migration. Levine and coworkers attributed it to a destructive, possibly ischemic, lesion occurring in the first few weeks of gestation, at a time when neuronal migration was incomplete. However, at least some forms have been traced to genetic defects as detailed further on.
The macrocephalic head (a large head with normal or only slightly enlarged ventricles) may be indicative of an advancing metabolic disease that enlarges the brain, as in Alexander disease, Canavan spongy degeneration of infancy, and later phases of Tay-Sachs disease, all of which are described in Chap. 36. Agenesis of the corpus callosum, a common congenital defect, may be associated with macrocephaly and varying degrees of mental impairment, optic defects, and seizures. In a series of 56 patients with agenesis of the corpus callosum, Taylor and David reported the presence of epilepsy in 32 and varying degrees of developmental delay in 28; only 9 had no recognizable neurologic defects. Also noted was a high incidence of psychiatric disturbances in these patients. In such cases, CT and MRI reveal the characteristic “bat-wing” deformity of the ventricles. There is also asynchrony of electrical activity of the two cerebral hemispheres on the electroencephalogram (EEG). In a few of these patients, an autosomal dominant inheritance was found (Lynn et al). Agenesis of the corpus callosum is also part of the Aicardi syndrome (see further on) and the Andermann syndrome, and it has been noted, without explanation, in some cases of nonketotic hyperglycinemia.