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DEVELOPMENTAL DISEASES OF THE NERVOUS SYSTEM
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stem, and spinal cord retain their normal dimensions The cranium may be misshapen or enlarged but is normal in size in some cases Rarely, the face and body are enlarged on the side of the enlarged hemisphere The cortex of the giant hemisphere is thick and disorganized Neurons are in disarray and some are enlarged; in some places the natural lamination of the cortex is effaced Nothing is known about causation, but apparently embryogenesis has been deranged at the stage of neuroblast formation Clinically, most affected individuals have been mentally retarded and some are epileptic A degree of hemiparesis may be present, but severe hemispheral neurologic de cits are generally not reported The hemimegalencephaly has been discovered at autopsy in a few individuals who had no mental or neurologic de cits Craniostenoses Some of the most startling cranial deformities are caused by premature closure of the cranial sutures (membranous junctions between bones of the skull) Such conditions are estimated to occur in 1 of every 1000 births, with a predominance in males (Lyon and Evrard) The growth of the cranium is inhibited in a direction perpendicular to the involved suture(s), with a compensatory enlargement in other dimensions, as allowed by the patent sutures For example, when the lambdoid and coronal sutures are both affected, the thrust of the growing brain enlarges the head in a vertical direction (tower skull, or oxycephaly, also referred to as turricephaly and acrocephaly) The orbits are shallow, the eyes bulge, and skull lms show islands of bone thinning (Luckenschadel) When only the sagittal suture is involved, the head is long and narrow (scaphocephalic), and the closed suture projects, keel-like, in the midline With premature closure of the coronal suture, the head is excessively wide and short (brachycephalic) The nervous system is usually normal in these restricted craniostenoses If this condition is recognized before 3 months of age, the surgeon can make arti cial sutures that may permit the shape of the head to become more normal (Shillito and Matson) Once brain growth has been completed, little can be done aside from complex reconstructive surgery When several sutures (usually coronal and sagittal) are closed, so as to diminish the cranial capacity, intracranial pressure may increase, impairing cerebral function and causing headache, vomiting, and papilledema Obviously an operation is then needed to increase the capacity of the skull In acrocephalosyndactyly or Apert syndrome, craniostenoses that are combined with syndactyly (fused, or webbed, ngers or toes), there are often added complications mental retardation, deafness, convulsions, and loss of sight secondary to papilledema The so-called clover-shaped skull is the most severe and lethal of the craniostenoses because of the associated developmental anomalies of the brain (see further on) When, for any reason, an infant lies with the head turned constantly to one side (because of a shortened sternomastoid muscle or hemianopia, for example), the occiput on that side becomes attened, as does the opposite frontal bone The other occipital and frontal bones bulge, so that the maximum length of the skull is not in the sagittal but in the diagonal plane This condition is called plagiocephaly, or wry head Craniostenosis of one-half of a coronal suture may also distort the skull in this way
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ferentiation, and connectivity Certain developmental anomalies have been traced to one or another of these stages of cytogenesis and histogenesis in the rst trimester of gestation and to the growth and differentiation that take place in the second and third trimesters During the rst trimester of gestation, postmitotic neurons that will ultimately reside in the cortex arise in the ventricular zone adjacent to the ventricles They then migrate along the scaffold of radial glia to form the multilayered cortex It is striking that neurons moving up the scaffold must pass through neurons that are already in position in the cortex, leading to an inside-out lamination in which the most recently born and arrived neurons reside on the outermost surface of the forming cortex Originally there is an excess of neurons, many of which degenerate during development a process properly called apoptosis There are recorded instances in which the full complement of neuroblasts and neurons fails to be generated Or the emergence of two separate cerebral hemispheres may not occur (holoprosencephaly), or the bihemispheral brain may remain small (microcephaly) In other described specimens, a diminished number of neurons is less obvious than their failure to migrate to the cortical surface; they remain scattered through the mantle zone in sheets and heterotopic aggregates One type of focal band-shaped subcortical heterotopia is termed double-cortex Micropolygyria refers to an excessive number of abnormally small gyri It is expressed by a syndrome of mental retardation, seizures, delayed speech, and motor abnormalities Or, the cortex may fail to become sulcated ie, 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 38-1) These migrational disorders, particularly these heterotopias, are just now being recognized by MRI and are found to have a possible functional signi cance in such states as mental retardation, epilepsy, and dyslexia Finally, the cortex may be normally formed and structured but there is a failure of differentiation of intra- and intercor-
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