Page 837 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster
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Figure 22–14 Myelomeningocele. Both meninges and spinal cord Congenital Malformations and Perinatal Brain Injury 823
parenchyma are included in the cystlike structure visible just above the
buttocks. to a smooth-surfaced brain. The cortex is abnormally
thickened and usually has only four layers. Many forms
encephalocele is a diverticulum of malformed CNS tissue of lissencephaly are associated with defects in genes that
extending through a defect in the cranium. It most often control neuronal migration.
involves the occipital region or the posterior fossa. When • Polymicrogyria is characterized by an increased number
it occurs anteriorly, brain tissue can extend into the sinuses. of irregularly formed gyri that result in a bumpy or
cobblestone-like surface. These changes can be focal or
Forebrain Malformations widespread. The normal cortical architecture can be
altered in various ways, and adjacent gyri often show
In certain malformations, the volume of the brain is fusion of the superficial molecular layer.
abnormally large (megalencephaly) or small (microencephaly). • Holoprosencephaly is characterized by a disruption of the
Microencephaly, by far the more common of the two, normal midline patterning. Mild forms may just show
usually is associated with a small head as well (micro- absence of the olfactory bulbs and related structures
cephaly). It has a wide range of associations, including (arrhinencephaly). In severe forms the brain is not
chromosome abnormalities, fetal alcohol syndrome, and divided into hemispheres or lobes, and this anomaly
human immunodeficiency virus type 1 (HIV-1) infection may be associated with facial midline defects such as
acquired in utero. The unifying feature is decreased gen- cyclopia. Holoprosencephaly as well as polymicrogyria
eration of neurons destined for the cerebral cortex. During can be the result of acquired or genetically determined
the early stages of brain development, as progenitor cells disruption of normal development. Several single-gene
proliferate in the subependymal zone, the balance between defects including mutations in sonic hedgehog have
cells leaving the progenitor population to begin migration been linked to holoprosencephaly.
to the cortex and those remaining in the proliferating pool • Other examples are focally disordered cortex (confus-
affects the overall number of neurons and glial cells gener- ingly called dysplastic cortex) and neurons stranded
ated. If too many cells leave the progenitor pool prema- beneath the cortex, sometimes as nodules and other
turely, there is inadequate generation of mature neurons, times as bands.
leading to a small brain.
Posterior Fossa Anomalies
Disruption of neuronal migration and differentiation
during development can lead to abnormalities of gyration The most common malformations in this region of the
and the six-layered neocortical architecture, often taking brain result in misplacement or absence of portions of the
the form of neurons ending up in the wrong anatomic cerebellum. The Arnold-Chiari malformation (Chiari type II
location. Various mutations in genes that control migra malformation) combines a small posterior fossa with a mis-
tion result in these malformations, which include the shapen midline cerebellum and downward extension of
following: the vermis through the foramen magnum; hydrocephalus
• Lissencephaly (agyria) or, with more patchy involvement, and a lumbar myelomeningocele typically are also present.
The far milder Chiari type I malformation has low-lying cer-
pachygyria, is characterized by absent gyration leading ebellar 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.
Syndromes characterized by “missing” cerebellar tissue
include Dandy-Walker malformation, characterized by an
enlarged posterior fossa, absence of the cerebellar vermis,
and a large midline cyst, and Joubert syndrome, in which
there is absence of the vermis and brain stem abnormalities
resulting in eye movement problems and disrupted respi-
ratory patterns. A range of recessive genetic lesions have
been found to cause Joubert syndrome, with many involv-
ing alterations of the primary cilium.
Spinal Cord Abnormalities
In addition to neural tube defects, structural alterations of
the spinal cord can occur that are not associated with
abnormalities of the bony spine or overlying skin. These
include expansions of the ependyma-lined central canal of
the cord (hydromyelia) or development of fluid-filled cleft-
like cavities in the inner portion of the cord (syringomyelia,
syrinx). These lesions are surrounded by dense reactive
gliosis, often with Rosenthal fibers. A syrinx also may
develop after trauma or with intramedullary spinal tumors.
