On completion of this chapter, you should be able to:
Describe the embryology of the neural tube fetal brain development
Discuss the anomalies that can occur in the fetal head and spine
Recognize the sonographic appearance of fetal head and spine anomalies
The central nervous system (CNS) arises from the ectodermal neural plate at around 18 gestational days. The cephalic neural plate develops into the forebrain, and the caudal end forms the spinal cord. The midbrain and hindbrain then form, and the neural plate begins to fold. The cranial and caudal neuropores represent unfused regions of the neural tube that will close between 24 and 26 gestational days. The forebrain will continue to develop into the prosencephalon, the midbrain will become the mesencephalon, and the hindbrain will form the rhombencephalon.
At the end of the third week, the cephalic end of the neural tube will bend into the shape of a C (cephalic flexure), with the area of the mesencephalon having a very prominent bend. The brain then folds back on itself, and by the beginning of the fifth week another prominent bend, the cervical flexure, appears between the hindbrain and the spinal cord. The brain that originally was composed of three parts has now further divided into five parts. The prosencephalon divides into the telencephalon, which becomes the cerebral hemispheres, and the diencephalon, which eventually develops into the epithalamus, thalamus, hypothalamus, and infundibulum. The rhombencephalon also subdivides into the metencephalon, which ultimately becomes the cerebellum and pons, and the myelencephalon, which transforms into the medulla. The fundamental organization of the brain is represented in these five divisions that persist into adult life.
The primitive spinal cord divides into two regions. The alar plate region matures into the sensory region of the cord, and the basal plate region develops into the motor region of the cord. These regions further subdivide into specialized functions. Initially, the spinal cord and the vertebral column extend the length of the body. After the first trimester, the posterior portion of the body grows beyond the vertebral column and spinal cord, and growth of the spinal cord lags behind that of the vertebral column. At birth, the spinal cord terminates at the level of the third lumbar vertebra, although by adulthood, the cord will end at the level of the second lumbar vertebra.
Neural function begins at 6 weeks of gestation and commences with primitive reflex movements at the level of the face and neck. By 12 weeks of gestation, sensitivity has spread across the surface of the body except at the back and top of the head. The fetus begins to have defined periods of activity and inactivity at the end of the fourth month. Between the fourth and fifth months, the fetus can grip objects and is capable of weak respiratory movements. At 6 months of gestation, the fetus displays the sucking reflex, and by about 28 weeks, significant changes in brain wave patterns have occurred.
Many of the congenital malformations of the CNS result from incomplete closure of the neural tube. A wide range of defects may affect the spine and/or brain. The remainder of this chapter presents anomalies of the CNS ( Table 60-1 ).
|Spina bifida||Deformed cranium “lemon sign”; usually disappears in third trimester|
|Obliteration of cisterna magna|
|Open spinal defect|
|Cephalocele||Open cranial defect; usually occipital skull base|
|Obliteration of the cisterna magna|
|Occasional lemon sign|
|Single ventricular cavity|
|Dandy-Walker complex||Midline posterior fossa cyst|
|Defect in cerebellar vermis|
|Agenesis of corpus callosum||Absent cavum septi pellucidi|
|Elevated third ventricle|
|Arachnoid/glioependymal cyst||Intracranial cyst with regular contours displacing/compressing cortex|
|Porencephaly||Intracranial cyst with jagged outline often communicating with lateral ventricles|
|Schizencephaly||Clefts in cortical mantle|
|Intracranial hemorrhage||Echogenic/complex mass in lateral ventricles/brain parenchyma|
|Vascular malformations||Fluid-filled lesion with blood flow at Doppler examination|
|Craniostenosis||Abnormal skull shape|
|Lissencephaly||Absent/reduced cerebral convolutions|
Correctly identifying anomalies of the fetal head and spine can be a complex task. Some of the distinguishing characteristics that help define specific anomalies are listed in Table 60-2 .
|Anomaly||Sonographic Findings||Differential Considerations||Distinguishing Characteristics|
|Anencephaly||Absence of brain and cranial vault||Microcephaly||No calvarium above vault orbits|
|Cephalocele||Extracranial mass||Cystic hygroma||Defect in skull|
|Bony defect in calvarium|
|Dandy-Walker malformation||Posterior fossa cyst |
Splaying of cerebellar hemispheres
|Arachnoid cyst |
|Cerebellar hemispheres will be splayed|
|Vein of Galen aneurysm||Midline cystic structure||Arachnoid cyst||Doppler flow in the cystic space|
|Turbulent Doppler flow||Porencephalic cyst|
|Porencephalic cyst||Cyst within brain parenchyma |
No mass effect
Communication with ventricle
|Arachnoid cyst |
Cyst communicating with ventricle
|No mass effect|
|Hydranencephaly||Absence of brain tissue||Hydrocephaly||Lack of intact falx|
|Fluid-filled brain||Holoprosencephaly||No rim of brain tissue|
|Absent or partially absent falx|
Anencephaly, also known as aprosencephaly or atelencephaly, is the most common neural tube defect, with an overall incidence of approximately 1 in 1000 pregnancies. The incidence varies with geographic location, with a much higher prevalence in the United Kingdom. The incidence also varies with gender and race, with a female prevalence of 4 to 1 over males, and a prevalence of white over black of 6 to 1. A significant recurrence risk of 2% to 5% for subsequent pregnancies has been documented for a woman with a history of a prior pregnancy with an open neural tube defect. The recurrence risk can be reduced by 50% to 70% with use of folic acid supplements beginning 1 month before pregnancy.
Anencephaly, which means absence of the brain, is caused by failure of closure of the neural tube at the cranial end. The result consists of absence of the cranial vault, complete or partial absence of the forebrain, which may partially develop and then degenerate, and presence of the brainstem, midbrain, skull base, and facial structures. The remnant brain is covered by a thick membrane called angiomatous stroma or cerebrovasculosa.
Anencephaly is a lethal disorder, with up to 50% of cases resulting in fetal demise. The remainder die at birth or shortly thereafter. Because of the severity of this disorder, early diagnosis is preferred. Prenatal diagnosis is often made with ultrasound following referral for increased maternal serum alpha-fetoprotein levels, which are extremely high with this defect because of the absent skull and exposed tissue.
Causes of neural tube defects, including anencephaly, are numerous. Anencephaly may result from a syndrome, such as Meckel-Gruber (i.e., cystic kidneys, occipital encephalocele and/or polydactyly [postaxial], microcephaly, microphthalmia, cleft palate, and genitourinary anomalies), or a chromosomal abnormality, such as trisomy 13 and trisomy 18. Risk is increased in patients with diabetes mellitus, including those whose disorders are well controlled. Environmental and dietary factors, including hyperthermia, folate and vitamin deficiencies, and teratogenic levels of zinc, may also increase the prevalence of neural tube defects. Other teratogens associated with neural tube defects include valproic acid, methotrexate, and aminopterin. Another cause of neural tube defects is amniotic band syndrome, which may manifest with clefting defects.
Anencephaly may be detected with ultrasound as early as 10 to 14 weeks of gestation, although the only sonographic feature may be acrania. The crown-rump length may be normal because degeneration of the fetal brain is progressive, leading to a reduction in the crown-rump length with advancing gestation. Second-trimester identification of anencephaly is more obvious, with absent cerebral hemispheres evident, along with absence of the skull.
Sonographic features of anencephaly include the following:
Absence of the brain and cranial vault ( Figure 60-1 )
Rudimentary brain tissue characterized as the cerebrovasculosa ( Figure 60-2 )
Bulging fetal orbits, giving the fetus a froglike appearance ( Figure 60-3 )
Other sonographic findings associated with anencephaly include polyhydramnios, which is commonly seen but may not be present until after 26 weeks of gestation, although oligohydramnios may occasionally be identified. Coexisting spina bifida and/or craniorachischisis may be identified in fetuses with anencephaly. Additional anomalies include cleft lip and palate, hydronephrosis, diaphragmatic hernia, cardiac defects, omphalocele, gastrointestinal defects, and talipes.
When severe, microcephaly may be confused with anencephaly, although the presence of the cranium should aid in a definitive diagnosis. Other defects that may mimic anencephaly include acrania (brain is abnormal but present), cephalocele (brain herniation), and amniotic band syndrome (usually asymmetric cranial defects).
Acrania , also known as exencephaly, is a lethal anomaly that manifests as absence of the cranial bones with the presence of complete, although abnormal, development of the cerebral hemispheres. This anomaly occurs at the beginning of the fourth gestational week, when the mesenchymal tissue fails to migrate and does not allow bone formation over the cerebral tissue. The prevalence of acrania is rare, with only a few cases reported in the literature. In addition, acrania usually progresses to anencephaly as the brain slowly degenerates as a result of exposure to amniotic fluid.
Acrania may be confused with anencephaly, although the presence of significant brain tissue and the lack of a froglike appearance should establish the diagnosis. Other disorders that may mimic acrania include hypophosphatasia and osteogenesis imperfecta, both of which result in hypomineralization of the cranium. Identification of additional findings, such as long bone fractures, should help to distinguish these disorders from acrania. In addition to the lack of other skeletal anomalies, lack of a calvarium allows differentiation of the cerebral hemispheres within the amniotic fluid, giving the fetal head a bilobed appearance. This bilobed brain is best identified in the first trimester and has been described as a “Mickey Mouse” appearance.
Sonographic features of acrania include the following:
The presence of brain tissue without the presence of a calvarium ( Figure 60-4 )
Disorganization of brain tissue
Prominent sulcal markings ( Figures 60-5 to 60-7 )
Acrania may be associated with other anomalies, including spinal defects, cleft lip and palate, talipes, cardiac defects, and omphalocele. Acrania has also been associated with amniotic band syndrome (see Figure 60-4 , B ).
A cephalocele is a neural tube defect in which the meninges alone or the meninges and brain herniate through a defect in the calvarium. Encephalocele is the term used to describe herniation of the meninges and brain through the defect; cranial meningocele describes the herniation of only meninges ( Figure 60-8 ). Cephaloceles occur at a rate of 0.8 to 4 in 10,000 live births.
Cephaloceles most commonly involve the occipital bone ( Figure 60-9 ) and are located at the midline, although they may also involve the parietal, frontal, and temporal regions or other bones of the calvarium.
The prognosis for the infant with a cephalocele varies based on the size, location, and involvement of other brain structures. The presence of brain in the defect dictates a poor prognosis. Microcephaly and other associated anomalies worsen the outcome. An infant with an isolated cranial meningocele has a chance of normal mentation.
The sonographic appearance of a cephalocele largely depends on the location, size, and involvement of brain structures. Cephaloceles containing meninges only; brain tissue only; meninges and brain tissue; and meninges, brain tissue, and lateral ventricles are referred to as meningocele, encephalocele, encephalomeningocele, and encephalomeningocystocele, respectively. According to the size of the lesion, cephaloceles are classified as occipital cephaloceles, which occur when the defect lies between the lambdoid suture and the foramen magnum; parietal cephaloceles, which occur between the bregma and the lambda; and anterior cephaloceles, which lie between the anterior aspects of the ethmoid bone. Anterior cephaloceles are further classified into frontal and basal varieties. The frontal cephaloceles are always external lesions that occur near the root of the nose. Basal cephaloceles are internal lesions that occur within the nose, the pharynx, or the orbit.
Sonographic features of cephaloceles include the following:
An extracranial mass ( Figure 60-10 ), which may be fluid filled (cranial meningocele) or contain solid components (encephalocele)
A bony defect in the skull
Ventriculomegaly, which is more commonly identified with an encephalocele
Another sonographic finding associated with cephaloceles is polyhydramnios. Coexisting anomalies include microcephaly, agenesis of the corpus callosum, facial clefts, spina bifida, cardiac anomalies, and genital anomalies. Chromosomal anomalies and syndromes have been identified with cephaloceles, including trisomy 13 and Meckel-Gruber syndrome, which is an autosomal recessive disorder characterized by encephalocele, polydactyly, and polycystic kidneys ( Figure 60-11 ). Other syndromes linked with cephalocele include Chemke, cryptophthalmos, Knobloch, dyssegmental dysplasia, von Voss, Roberts’, and Walker-Warburg. Cephaloceles located off midline are usually the result of amniotic band syndrome and may be further distinguished by associated limb anomalies and abdominal wall defects.
Cephaloceles may be confused with cystic hygromas, although they lack a cranial defect. Anencephaly may be difficult to distinguish from encephaloceles of significant size, and the presence of the cranial vault with encephalocele should establish the diagnosis. Frontal encephaloceles may be difficult to distinguish from a facial teratoma.
Spina bifida encompasses a wide range of vertebral defects that result from failure of neural tube closure. The meninges and neural elements may protrude through this defect. The defect may occur anywhere along the vertebral column but most commonly occurs along the lumbar and sacral regions. The incidence of this defect has declined as a result of campaigning by the U.S. Public Health Service, which encourages women to increase their intake of folic acid before becoming pregnant, and the subsequent mandate by the Food and Drug Administration to add folic acid to cereal grain products. Decreases in the prevalence of anencephaly and encephalocele have been noted.
The term spina bifida means that there is a cleft or opening in the spine ( Figure 60-12 ). When covered with skin or hair, it is referred to as spina bifida occulta, an anomaly that is associated with a normal spinal cord and nerves and normal neurologic development. Spina bifida occulta is extremely difficult to detect in the fetus. Because the defect is covered by skin, the maternal serum alpha-fetoprotein level will be normal.
When the defect involves only protrusion of the meninges, it is termed a meningocele. More commonly, the meninges and neural elements protrude through the defect. This is called a meningomyelocele. If the defect is very large and severe, it is termed rachischisis. These defects are commonly associated with increased maternal serum alpha-fetoprotein.
Spina bifida is also associated with varying degrees of neurologic impairment, which may include minor anesthesia, paraparesis, or death. Fetuses with myelomeningoceles often present with cranial defects associated with the Arnold-Chiari (type II) malformation, which is identified in 90% of patients. The Arnold-Chiari II malformation presents invariably with hydrocephalus caused by the cerebellar vermis, which becomes displaced into the cervical canal. This changes the shape of the cerebellum, giving it a “banana” appearance, and leads to obliteration of the cisterna magna. In addition, caudal displacement of the cranial structures causes scalloping of the frontal bones of the skull, making the fetal head resemble a lemon.
Management of a fetus with spina bifida usually includes serial ultrasound examinations to monitor progression and extent of ventriculomegaly and to follow fetal growth. Fetuses may be delivered early for ventricular shunting, usually by cesarean section to preserve as much motor function as possible. Surgical repair of these defects in utero is being performed in a randomized clinical trial to determine whether surgery decreases the incidence of hindbrain herniation, thus decreasing the incidence of hydrocephalus and subsequent shunting. Risks incurred with this procedure include premature delivery, maternal morbidity, and fetal mortality.
The prognosis for an infant with spina bifida varies greatly according to the type, size, and location of the defect. Three-dimensional sonographic imaging can assist in identifying the upper level of the defect, which predicts neurologic function and mortality. Rachischisis is invariably lethal, and higher lesions ( Figure 60-13 ) tend to have a worse prognosis. When intervention is desired, surgical closure of the defect is performed to preserve existing neurologic function. In addition to management of the actual defect, attention to any hydrocephalus, urinary tract anomalies or dysfunction, and orthopedic issues may be part of the long-term care required for this child.