The central nervous system (CNS)
is the most complex organ in the human body comprising a highly
organized anatomic scaffold of billions of cells and a network of
trillions of connections. Structural brain development proceeds
through an integrated series of often rapid developmental events
from early embryogenesis through fetal life and into early adulthood.
It is therefore not surprising that many common childhood neurologic
and developmental disorders have their origins in genetic or environmental
perturbations of embryonic or fetal brain development.
Advances in genetics and diagnostic imaging, including prenatal
imaging, have led to earlier and more complete diagnosis and enhanced prognostication
for CNS malformations and the ability to counsel effectively regarding
recurrence. The diagnosis of malformations has been revolutionized
by magnetic resonance imaging (MRI), and the challenge for the pediatrician
is often to translate the imaging diagnosis to effectively counsel
the family and plan further care and management for the child. Modern
neonatal neurologic and neurosurgical intensive care together with
progress in early intervention and pediatric rehabilitation means
children with malformations of the brain or spinal cord may now
survive longer and with improved quality of life.
Malformations of the CNS are among the most common problems in
child neurology. Brain development is abnormal in an estimated 25% of
conceptions and is responsible for a high percentage of miscarriage
and stillbirth. Brain malformations are, together with congenital
heart disease, the leading cause of neonatal and postneonatal mortality
in the developed world. Brain malformations are after cerebral palsy,
the leading cause of childhood morbidity and mortality related primarily
to consequent neurologic disability and epilepsy. Brain malformations
frequently coexist with other malformations of organ systems, in
particular the eye, heart, kidneys, gut, and skeleton.
The neuraxis develops following the fate decision of several
early embryonic cells to become neural progenitors and by the second week
of embryogenesis the three primary layers of ectoderm, mesoderm,
and endoderm are formed. It subsequently proceeds through the dorsal
and ventral induction to form the neural tube, lower spinal cord
and eventually the prosencephalon (forebrain), mesencephalon (midbrain),
and rhombencephalon (hindbrain). This is followed by massive cellular
proliferation of both neuronal and glial precursors and later differentiation
into specific neuronal and glial types. Cortical development occurs
with migration of neuronal and glial precursors away from the ventricular
and subventricular zone towards the pial surface to form the neocortex
and major commissures such as the corpus callosum. This is followed
by cortical organization that includes alignment, orientation, and
layering of cortical neurons together with synaptogenesis. From
the end of the second trimester into early childhood late glial
differentiation and myelination, together with programmed and experience-dependent
synaptic formation and pruning predominate.
The range of known malformations is almost as complex as the
series of developmental events that lead to the formation of the brain.
They are perhaps best understood as the effects of insults—regardless
of type—at key points in the development of the brain. Although ...