Diagnostic ultrasound ( PDFDrive )

1194 PART IV Obstetric and Fetal Sonography
and can result from intrinsic factors, as mutations in genes
controlling brain development, or extrinsic insults including
syndromes, maternal diseases (phenylketonuria), teratogens
(anoxia, drugs, x-rays), metabolic abnormalities, and fetal infections,
but oten a cause cannot be found. Changes oten relect
time of insult rather than its speciic nature. 91,186-188 he responsible
genes oten function at many developmental stages and in many
diferent body structures apart from the brain. Diferent mutations
of the same gene may result in diferent syndromes. Abnormalities
may be found in seemingly unrelated organs, as in thanatophoric
skeletal dysplasia, in which abnormal function of the FGFR3
gene causes both cortical brain malformations and skeletal
abnormalities. 189
Cerebral changes with malformations of cortical development
are heterogeneous. VM is common. hey generally share
variable degrees of thickened, disorganized cortical neuronal
layers and alterations in sulcal, gyral, and white matter patterns
and abnormal corpus callosum or posterior fossa. Cortical
abnormalities may be diicult to detect until sulcal development
becomes visible at about 24 weeks. Some may not be detectable
in utero and may become evident only as symptoms (and abnormalities)
develop in later life. Detailed classiication of these
disorders is complex and based variously on genetics, biologic
pathways, neuroimaging features, and irst-afected developmental
stage. he past few years have shown a dramatic increase
in the understanding of the genetic and molecular basis of these
malformations. he current classiication is acknowledged to be
neither perfect nor complete and is subject to updating with new
genetic discoveries. In practice they are described by the general
conspicuous patterns they present, including microcephaly,
macrocephaly, lissencephaly, polymicrogyria (PMG), periventricular
nodular heterotopia, and schizencephaly. 91,190-192
For all these conditions, investigation requires detailed
examination including MRI, which can help focus further directions
for more targeted testing. Multidisciplinary consultation
is important for optimal prenatal assessment and counseling.
Additional investigations depend on individual situations and
can include detailed family and pregnancy history, infection
screening, amniocentesis for karyotype and array-comparative
genomic hybridization (CGH), commonly called microarray,
other testing for speciic gene mutations, and other speciic testing
as suggested by clinical and imaging appearances. Prognosis
varies depending on the severity of the condition and associated
abnormalities, and epilepsy and developmental delay are
common. 193-195
Microcephaly
Microcephaly describes a disproportionately small head for fetal
age and body size. Precise diagnostic deinition is diicult, but
in general, microcephaly is diagnosed if the head circumference
less than 3 SDs below the expected mean and intrauterine growth
restriction (IUGR) has been excluded. Some suggest using 2
SDs, but this would include many normal individuals. Incidence
at birth ranges from 1 per 1360 to 10,000. he diagnosis implies
failure of brain development (micrencephaly). Etiology is
heterogeneous and can be related to a great variety of prenatal
causes including genetic factors, environmental issues, asphyxia,
Classiication of Malformations of Cortical
Development
ABNORMAL NEURONAL PROLIFERATION OR
APOPTOSIS
Abnormal Brain Size
Microcephaly
Megalencephaly (macrocephaly)
Hemimegalencephaly
Abnormal Proliferation
Nonneoplastic or neoplastic
ABNORMAL NEURONAL MIGRATION
Classical lissencephaly and subcortical band heterotopia
Cobblestone lissencephaly and complex or congenital
muscular dystrophy
Heterotopia
ABNORMAL CORTICAL ORGANIZATION
Polymicrogyria
Schizencephaly
NOT OTHERWISE CLASSIFIED
Secondary to inborn errors of metabolism (mitochondrial,
pyruvate)
Peroxisomal disorders
Modiied from Raybaud 191 and Barkovich. 196
infections (Zika virus), 197 maternal conditions (phenylketonuria),
drugs (e.g., fetal alcohol syndrome), diverse syndromes (e.g.,
Smith-Lemli-Opitz, Cornelia de Lange), and irradiation. On
pathologic examination, the brain may be small but normal in
appearance, or it may have diverse indings, including simpliied
gyri, porencephaly, absent corpus callosum, and VM. Associated
CNS and non-CNS abnormalities are common. 91,188,198
Microcephaly should be suspected if the head size is smaller
than expected. Measurements alone have only a limited ability
to diagnose microcephaly. In one study, only 4 of 24 fetuses with
small measurements had the diagnosis conirmed at delivery.
Other indings include brain abnormality, abnormal head-toabdomen
circumference ratio, sloping forehead, and small frontal
lobe size (Fig. 34.22).
Microcephaly is usually is not evident until late in pregnancy
when the head size fails to grow normally, but it has been seen
as early as 15 weeks. When a smaller-than-expected fetal head
is encountered, there should be a careful search for cerebral and
other anomalies that would help to conirm clinical importance.
Ultrasonography of the brain can be diicult because the cranial
bones become closely approximated and hinder visibility. MRI
is helpful in evaluation of the cerebral parenchyma and associated
abnormalities. 7,199 Small head size can be associated with subnormal
mental ability; the smaller the head circumference, the
lower the performance level. Prognosis varies with CNS and
associated abnormalities.
Macrocephaly and Megalencephaly
Macrocephaly implies a large head with circumference of 2 SDs
or greater or at the 98th percentile for gestational age. It excludes