Objectives

• Name the three standard imaging planes to visualize fetal cranial anatomy

• List the sonographic characteristics of anencephaly

• List the sonographic characteristics of encephalocele

• Define the sonographic characteristics suggestive of microcephaly

• Describe ventriculomegaly

• List the sonographic characteristics of aqueductal stenosis

• Describe the three types of holoprosecncephaly

• List the sonographic characteristics of agenesis of the corpus callosum

Introduction

Congenital anomalies of the brain and skull are commonly encountered by the sonographer. Each year in the United States, approximately 6000 neonates are afflicated with one of these central nervous system (CNS) anomalies. These embryonic defects may be the most devastating for the infant, if not lethal. Using prenatal ultrasound, many anomalies of the brain may be detected. The brain has varying appearances, depending on the fetal age at the time of sonographic inspection. To recognize an abnormality in development, one should have a comprehensive understanding of the normal developmental appearance of the brain.

Many clinicians will refer their patients for a targeted examination once a fetal anomaly has been found or if there are increased risk factors in the patient's background. For example, a woman who had delivered a previous child with a neural tube defect has an increased risk of delivering another child with the same or similiar defect. The early recognition of a CNS anomaly may provide the counseling, support, and delivery plan that are necessary for the well-being of the mother and fetus.

Sonographic Techniques

Most major brain malformations are recognizable when the three standard imaging planes of fetal neuroanatomy are used. The coronal, axial (transverse), and sagittal planes should be imaged by the sonographer to demonstrate the fetal anatomy in a systematic approach.

Abnormalities Altering Cranial Shape

The normal fetal cranium has smooth borders and assumes the shape of a circle at the top of the skull and an oval at lower levels. The echogenicity of the skull table is extremely dense and will appear as an intact echogenic circle. This section describes congenital anomalies that in some manner change or alters cranial shape.

Anencephaly

Anencephaly is the single most common neural tube defect. The incidence of anencephaly is 1 per 1500 births in North America, with a higher incidence in the United Kingdom. Anencephaly results from failure of the rostral neuropore to close at the cranial end by 38 menstrual days. As a consequence, the cerebral hemispheres (forebrain) only partially develop and then degenerate, resulting in the presence of the brain stem, midbrain, and skull base. The remnant brain is covered by tissue called angiomatous stroma or cerebrovasculosa.

Anencephaly is a lethal disorder and early diagnosis is preferred. Maternal serum alpha-fetoprotein levels are exceedingly high with this defect because of the absent skull and exposed tissue.

The causes of neural tube defects are multiple. They may be part of a syndrome resulting from a single gene defect (Meckel-Grueber syndrome), or occur with a chromosomal abnormality, or by a teratogenic insult, or by maternal diabetes mellitus. Other causes include the amniotic band syndrome, dietary deficiencies, teratogenic levels of zinc, and hyperthermia, which affects the closure of the neural tube.

Anencephaly, for instance, is a neural tube defect usually considered to result from multifactorial influences. Anencephaly may occur as part of a monogenic syndrome, chromosome anomaly, teratogenic insult (e.g., hyperthermia, folate deficiency), or secondary to amniotic bands.

Anencephaly is usually detected by ultrasound, which may be performed following high alpha-fetoprotein levels in maternal serum. The anencephalic fetus may be recognized as early as the twelfth week of gestation, at which time cranial ossification is complete. A definitive diagnosis may not be possible until a few weeks later. The inability to see the cranial bones on any fetal scan should prompt the scanner to exclude this problem.

Click on image to view full size

Normal Fetal Profile	Fetus with anencephaly; note the absence of cranial tissue.

Sonographic Characteristics Of Anencephaly

• Absent skull and brain above the orbits.

• Rudimentary brain tissue (cerebrovasculosa) herniating from the open defect

• Bulging fetal orbits because of the absent frontal bone

• Hydramnios occurs in 50% after 25 weeks of gestation because of depressed or ineffective swallowing, excessive urination, or reabsorption deficiencies of cerebrospinal fluid.

• Coexisting spina bifida, craniorachischisis (extensive opening of cranium and spine), or both.

• Nonneural tube anomalies that may be present include cleft lip and palate, hydronephrosis, diaphragmatic hernia, cardiac defects, omphalocele, gastrointestinal problems, and clubfeet.

• Increased fetal activity because of irritative effects of exposed meninges and neural tissue.

When anencephaly has been diagnosed, measurements of head size are not possible. Other dating parameters are used to assess fetal age. When the cranium appears to be located deep in the pelvis, a full maternal bladder or use of a vaginal probe often aids in the confirmation of this defect.

Other brain defects may be confused with anencephaly. These include severe microcephaly (cranium present), acrania (brain is abnormal but present), cephalocele (brain herniation but brain is present), or amniotic band syndrome (usually asymmetric cranial defects with amputation defects of limbs).

Acrania (Exencephaly)

Acrania is a serious malformation that occurs because of abnormal migration of mesenchymal tissue, which normally covers the cerebral hemispheres. This faulty migration results in the faulty formation of the cranial bones, muscles, and dura mater. Acrania may manifest as a partial or complete absence of the skull, with complete but abnormal development of the cerebral hemispheres.

Acrania occurs more infrequently than anencephaly and in some cases may be the embryonic precursor to the development of anencephaly. The abnormal brain tissue of acrania is destroyed by amniotic fluid exposure and atrophy and becomes the rudimentary brain found in anencephaly.

Sonographic Characteristics Of Acrania

• Development of brain tissue with no evidence of a calvarium. In partial acrania, portions of the skull may be observed.

• Brain tissue may appear to be unorganized and have irregular echogenicities.

• Prominent sulcal markings.

Coexisting anomalies include spinal defects, cleft lip and palate, and clubfoot. The conditions hypophosphatasia and osteogenesis imperfecta, type II, must be differentiated from acrania. These two disorders result in hypomineralization of the cranium, which may be confused with acrania. Acrania is a lethal cranial abnormality.

Encephalocele (Cephalocele)

Cephaloceles are neural tube defects caused by the herniation of the brain (cerebellum) and meninges (encephalocele or meningoencephalocele), meninges and cerebrospinal fluid alone (meningocele), or brain, meninges, and ventricles (meningohydroencephalocele) through a defect in the skull. Cephaloceles occur in 1 per 5000 to 10,000 births. Cephaloceles occur because of a congenital defect in the skull.

Cephaloceles most commonly involve the occipital bone and are usually located in the midline. Other sites for cephaloceles include the parietal, nasopharyngeal, and frontal bones.20 The sonographic appearance of a cephalocele largely depends on the location, size, and involvement of brain structures.

Sonographic Characteristics Of Cephaloceles

• An extracranial mass. When cystic, probably a meningocele. When solid with brain tissue, an encephalocele or meningoencephalocele, and when the ventricle is found within the encephalocele sac, a meningohydroencephalocele is present.

• Ventriculomegaly (dilation of the ventricle) may be seen.

• Bony defect in the skull (small defects may be undetected). Location of cephalocele in relationship to interhemispheric fissure and face. Check for midline location and other sites of orientation (occipital, parietal, nasopharyngeal, or frontal areas).

Other congenital anomalies that should be distinguished from cephaloceles are anencephaly, cystic hygroma, teratoma, branchial cleft cyst, and hemangioma.

The prognosis for the infant with a cephalocele varies based on the size, location, and involvement of other brain structures and the presence of microcephaly and associated syndromes. The fetus with a meningocele (without brain tissue) may have a normal outcome after surgical repair of the defect, but the mortality rate approaches 11%. When brain tissue is herniated within the defect, the mortality rate is as high as 71%.

Microcephaly

Microcephaly is an abnormally small head caused by an overall reduction in the size of the brain, resulting from a developmental defect of the cerebrum. Microcephaly is of major clinical concern because it is usually associated with a small brain and mental retardation. About 85% of children with microcephaly have mental retardation. The incidence of microcephaly is reported from 1 per 6200 to 1 per 8500 births.

Causes of microcephaly include inheritance (autosomal-dominant microcephaly), chromosomal aberrations, and severe prenatal radiation exposure. Other causes include maternal viral infections (rubella, cytomegalovirus, toxoplasmosis), maternal alcoholism, heroin addiction, mercury poisoning, and maternal phenylketonuria.

The detection of microcephaly by ultrasound is difficult. First, in fetuses at risk for genetically transmitted microcephaly, it is generally unknown when the condition manifests; therefore diagnosis before the twenty-fourth week of gestation may be impossible. Second, insults in later pregnancy (e.g., viral infection) may not affect cranial growth until late in gestation. Third, diagnosis relies solely on estimations of cranial growth.

Often a coexisting intracranial anomaly may be the underlying cause of microcephaly. In the majority of cases, sonography fails to appreciate these anomalies (cortical atrophy). Ventriculomegaly may be found in fetuses with cortical atrophy. Agenesis of the corpus callosum may be a cause of microcephaly.

Sonographic Features of Microcephaly. Several investigators have used biparietal diameter (BPD), occipitofrontal diameter, and head perimeter (HP) to evaluate the fetus at risk for microcephaly. Other parameters which may suggest this condition are head area and ratios comparing head perimeter with abdominal perimeter (HC/AC) and femur length with biparietal diameter.

Microcephaly has been described as a BPD value more than 3 standard deviations below the mean. Accurate assessment of gestational age is imperative. Head circumference has been used to describe this condition when less than or equal to 3 standard deviations below the mean. Furthermore, the diagnosis of impaired cranial growth should coincide with appropriate growth of the abdominal circumference and femur length. Campbell and Thoms observed that in fetuses with microcephaly the HC/AC ratio decreases significantly as a result of slowed cranial growth.

Serial measurements for fetuses at risk for microcephalus are commonly performed at monthly intervals.

Sonographic characteristics suggestive of microcephalus

• Small biparietal diameter and head circumference.

• Head to abdomen disproportion.

• Disorganized brain tissue.

• Intracerebral calcifications suggestive of infection (parvovirus, cytomegalovirus).

• Ventriculomegaly.

• Congenital heart disease, such as ventricular septal defects and tetralogy of Fallot.

• Polycystic kidneys as seen in Meckel-Gruber syndrome.

• Limb disorders including micromelia (shortening), camptodactyly (permanent flexion of fingers or toes), syndactyly (fusion of digits), absent fifth finger, and arthrogyposis (joint contractures).

Abnormalities Altering Intracranial Anatomy

To appreciate the pathologic appearances of prenatally detectable brain anomalies, an understanding of normal anatomy is imperative. Fortunately, most major fetal brain anomalies are rare, but the sonographer must screen for major head anomalies during a basic survey of the fetal brain.

Ventriculomegaly (Hydrocephalus)

Physiologically, when an obstruction occurs within or outside of the ventricular system, the ventricles dilate as the flow of cerebrospinal fluid is blocked. This in turn causes the pressure within the obstructed ventricle to increase, leading to ventricle expansion. The abnormally enlarged ventricles exert pressure on the brain tissue, which may lead to irreversible brain damage.

The incidence of ventriculomegaly varies, from 0.5 to 1.8 per 1000 births, with the majority having an unknown cause. Common causes of ventriculomegaly include neural tube defects, such as spina bifida and encephaloceles. Dandy-Walker malformations, agenesis of the corpus callosum, and lissencephaly (absent gyral formation, "smooth brain") are other central nervous system associations.

The aqueduct of Sylvius may be blocked because of an inflammatory process (e.g., cytomegalovirus or parvovirus). Aqueductal stenosis may occur as a sporadic defect or as an X-linked recessive condition.

Neoplasms and arachnoid cysts may show signs of ventriculomegaly. Miscellaneous reasons for cerebrospinal fluid obstruction within the subarachnoid space include skeletal dysplasias, such as thanatophoric dysplasia, achondroplasia, and osteogenesis imperfecta. Inflammatory responses and hemorrhage may also contribute to the development of ventriculomegaly from a communicating obstruction. Vein of Galen aneurysms are known to occur with ventriculomegaly. Holoprosencephaly, porencephaly, hydranencephaly, and microcephaly are known defects with associated ventriculomegaly.

Coexisting malformations are reported in approximately 70% to 85% of fetuses with ventriculomegaly. Both intracranial and extracranial malformations are common. Ventriculomegaly has been described as the "tip of the iceberg" because of the high likelihood of additional fetal anomalies. Meningomyeloceles are found in 30% of fetuses with ventriculomegaly. Extracranial anomalies include defects involving the face, heart, kidneys, abdominal wall, thorax, and limbs. A systematic study of all organ systems is imperative to exclude any coexisting lesions of the central nervous system (CNS) or other organs.

Fetal ventriculomegaly typically progresses from the occipital horns (colpocephaly) into the temporal (atrial regions) and then to the frontal ventricular horns. Ventriculomegaly may be quantitated by measuring the size of the ventricular atria across the glomus of the choroid plexus. A dilated ventricle exceeds 10 mm in diameter. In some instances, the ventricle in the proximal hemisphere may be impossible to measure because of reverberation artifacts and head positioning. The sonographer may assume that, in most cases, the defect is bilateral. When ventriculomegaly is diagnosed, a targeted examination to detect coexisting malformations is indicated because pregnancy management, the delivery plan, and the prognosis for survival are based on all findings.

Serial scans often help in assessing the progression of ventriculomegaly and in isolating associated malformations. In fetuses at risk for developing ventriculomegaly during pregnancy, serial scanning is recommended because the natural history of some disorders is unknown.

Aqueductal Stenosis

Aqueductal stenosis is one of the most common causes of ventriculomegaly; flow of cerebrospinal fluid is impeded by stenosis, atresia, or blockage by a membrane. This disorder may be a primary malformation or occur secondary to acquired obstruction. Intrauterine infection (viral and bacterial), hemorrhage within the ventricle, and pressure by a cranial mass are causes of acquired forms of aqueductal stenosis. Primary aqueductal stenosis is usually X-linked, although family patterns consistent with autosomal-recessive inheritance have been described.

Sonographic Characteristics Of Aqueductal Stenosis

• Bilateral ventriculomegaly that may continue to enlarge to a severe degree.

• Third-ventricle dilation.

• No known intracranial or extracranial associated anomalies.

• Acquired obstruction (infection or hemorrhage) may occur any time during pregnancy.

The prognosis for infants born with aqueductal stenosis varies from relatively good to poor with intellectual deficits and handicaps. Infants with X-linked aqueductal stenosis have a poorer prognosis, all survivors showing intellectual impairment.

Hydranencephaly

Hydranencephaly is failure of cerebral hemisphere development caused by occlusion of the internal carotid arteries, which leads to a hemorrhage and infarction of the brain. The occipital lobes, midbrain, basal ganglia, cerebellum, and choroid plexuses are present because of preserved circulation from the posterior communicating arteries.

It is believed that hydranencephaly occurs later in pregnancy as the above-mentioned brain structures are normally formed. Progressive enlargement of the head (macrocephaly) occurs as the choroid plexus continues to produce cerebrospinal fluid. The prognosis for infants with hydranencephaly is extremely poor, most dying shortly after birth and rarely surviving beyond 3 months of age. There is no association with coexisting structural or chromosomal abnormalities.

Hydranencephaly may be confused with severe ventriculomegaly (where the falx is intact) and the pancake form of alobar holoprosencephaly. It is important to understand, however, that all three conditions have an extremely poor prognosis for survival.

Sonographic Characteristics Suggestive Of Hydranencephaly

• Brain tissue is replaced by a massive amount of cerebrospinal fluid.

• The interhemispheric fissure or falx is usually present but may be deviated. At times, the falx is absent or partially formed.

• Midbrain, basal ganglia, and cerebellum are encircled by cerebrospinal fluid.

• Choroid plexuses may be observed.

• Brain tissue is absent in all areas except the occipital lobes.

• Macrocephaly occurs as a result of production of cerebrospinal fluid.

• Hydramnios.

• Varying appearance of the cerebrospinal fluid. The appearance of evolving hemorrhage may change from echogenic to hypoechoic to anechoic.

Choroid Plexus Cysts

Choroid plexus cysts are commonly observed during antenatal examination of the brain in 1% to 2% of normal fetuses. These cysts are composed of cerebrospinal fluid and cellular debris, which become trapped within the neuroepithelial folds. When autopsies are performed in different age groups, small choroid plexus cysts are observed histologically. Choroid plexus cysts are observed prenatally from 15 to 26 weeks of pregnancy with resolution by the twenty-fourth week. Most choroid plexus cysts represent normal development, however, they may be associated with a chromosomal abnormality.

Normal development of the choroid plexus in the second trimester fetus; the choroid is homogeneous without cystic formation.

Sonographic Characteristics Of A Choroid Plexus Cyst

• Cyst size ranges from 0.3 to 2 cm.

• May be bilateral.

• May have irregular and multilocular appearance.

• Large cysts may cause ventricular expansion.

Genetic amniocentesis to exclude a chromosomal abnormality such as trisomy 18 may be offered to the patient. The sonographer should realize that even when a chromosomal abnormality exists, choroid plexus cysts may be small and resolve, as would occur in a fetus without a chromosome defect. When a choroid plexus cyst is found, surveys to exclude anomalies suggestive of a chromosomal abnormality are recommended.

Holoprosencephaly

Holoprosencephaly is a group of brain disorders that result from the abnormal cleavage of the prosencephalon or forebrain. The defect may affect the development of the midline facial plane, causing varying orbital and facial malformations (17% of fetuses). Facial defects vary in severity.

There are three forms of holoprosencephaly (alobar, semilobar, and lobar). The specific form depends on the degree of failed hemisphere division.

Alobar holoprosencephaly is the most severe form and may include the following:

• A single common ventricle that may appear in a "C"-shaped pattern because of absent temporal, occipital, and frontal horns.

• Brain tissue may be observed in a cup, ball, or pancake configuration.

• Fusion of the thalamus. Absent third ventricle

• Absent interhemispheric fissure.

• Dorsal sac (a cyst formed by the incomplete membranous covering of the prosencephalon.

• The presence of a supraorbital proboscis in cyclopia and midline proboscis with ethmocephaly.

• Orbital anomalies ranging from fused or nearly fused orbits with cyclopia. to hypotelorism (closely spaced orbits) seen in ethmocephaly and ce-bocephaly.

• Nasal anomalies from an absent nose to a single nostril may be present.

• Cleft lip and/or palate. Median facial clefting and/or bilateral clefts may be observed, usually in the most severe forms (alobar and semilobar).

• Other anomalies include renal cysts or dysplasia, omphalocele, cardiac defects, spina bifida, clubfeet, and gastrointestinal defects.

• Chromosomal abnormalities occur in 50%.

Cyclopia and ethmocephaly are fatal. It is unusual for an infant with other forms of alobar holoprosencephaly to survive beyond 1 year of age. These infants are severely mentally retarded.

Semilobar holoprosencephaly represents an intermediate form of holoprosencephaly and is manifested by partial separation of the ventricles and partial fusion of the thalamus. The pancake-, ball-, or cup-shaped brain tissue may be observed in semilobar holoprosencephaly.

In lobar holoprosencephaly, division of the ventricles and thalamus occurs, but the olfactory tracts and septum pellucidi are missing. Flattened frontal ventricular horns with absence of the septum pellucidum and corpus callosum may suggest this form of holoprosencephaly.

Agenesis of the Corpus Callosum

The corpus callosum is a band of white-matter tissue that connects the cerebral hemispheres. Agenesis of the corpus callosum occurs when the callosal fibers fail to cross the midline and form a normal connection between the two hemispheres. Concomitant cerebral and ventricular anomalies are common. The defect may be complete or partial.

Sonographic Characteristics Of Agenesis Of The Corpus Callosum

• Third ventricle dilation (interhemispheric cyst in many cases) and superior elevation.

• Lateral ventricle displacement in a more lateral and superior position. Lateral separation of frontal and temporal ventricles.

• Angulated frontal and lateral ventricular horns (steer sign).

• Occipital horn dilation.

• Probst bundles (radial array pattern of sulci) emanating from ventricles rather than coursing with the ventricle.

• High incidence of CNS and non-CNS anomalies.

Associated CNS anomalies include gyral defects, lipomata, encephalocele, Dandy-Walker malformation, holoprosencephaly, Arnold-Chiari malformation, septo-optic dysplasia, ventriculomegaly, and aqueductal stenosis. Non-CNS associated defects include facial, musculoskeletal, cardiac, bronchial, intestinal, and urinary tract disorders. Several rare syndromes are found in association with agenesis of the corpus callosum.

Dandy-Walker Malformation

Dandy-Walker malformation is a defect involving the cerebellar vermis, which may be partially or completely absent, with resulting dilation of the fourth ventricle (cyst formation). It is thought that the defect results from abnormal embryogenesis of the roof of the fourth ventricle. A milder form is termed the Dandy-Walker variant. This disorder may account for approximately 5% to 10% of cases of ventriculomegaly.

Sonographic Characteristics Of Dandy-Walker Malformation

• A cerebellar vermis defect (complete or partial). The defect is inferior in partial conditions.

• A posterior fossa cyst representing a dilated fourth ventricle.

• Enlargement of the cisterna magna (representing the fourth ventricle).

• Splaying of the cerebellar hemispheres

• Ventriculomegaly.

• Other anomalies include agenesis of the corpus callosum, aqueductal stenosis, microcephaly, encephalocele, gyral malformations and lipomas, cardiac, urinary tract anomalies, polydactyly (extra digits); facial malformations, and chromosomal problems.

Infants without other anomalies have a better prognosis than those with anomalies. Many infants with isolated Dandy-Walker malformation have a normal range of function. The differential diagnosis includes a posterior fossa arachnoid cyst and cerebellar dysgenesis.

Case Study

A 32 y.o. female presents, G2P1A0, at 34 weeks gestation with a history of size smaller than dates on physical examination. What would you look for to confirm this diagnosis?

Etiology:

• Failure of neural tube to close at cephalic end

• Occurs between 2nd and 3rd week of development

• No brain development after stem

Clinical, Laboratory, And Related Findings:

• Mother large for dates

• Increased AFP

• Associated with spina bifida (30%)

• Occurs in 1:1000-1500 births

• Open area of defect not covered by skin

• Lethal anomaly

Differential Diagnosis:

• Microcephaly

• Acrania

• Cephalocele

• Amniotic Band Syndrome

Disease Process: Anencephaly

References

Argo, Kara: "Congenital Anomalies" in Textbook of Diagnostic Ultrasonography, by Sandra Hagen-Ansert, 4th Ed., Mosby, St. Louis, 1995.

Callen DW, editor: Ultrasonography in obstetrics and gynecology, ed 3. Philadelphia, 1995, WB Saunders.

Chervenak FA, Isaacson G, Mahoney MJ, et al: Diagnosis and management of fetal cephalocele, Obstet Gynecol 64:86, 1984.

Chervenak FA, Jeanty P, Cantraine F, et al: The diagnosis of fetal microcephaly, Am J Obstet Gynecol 149:512, 1984.

Chung CS and Myrianthopoulos NC: Factors affecting risks of congenital malformations. I. Epidemiological analysis, Birth Defects 11:1, 1975.

Comstock CH, Culp D, Gonzalez J, and Boal DB: Agenesis of the corpus callosum in the fetus: Its evolution and significance, J Ultrasound Med 4:613, 1985.

Fleischer AC, Romero R, Manning FA, et al, editors: The principles and practice of ultrasonography in obstetrics and gynecology, ed 4, Norwalk, 1991, Appleton & Lange.

Hertzberg BS, Lile R, Foosaner DE, et al: Choroid plexus-ventricular wall separation in fetuses with normal-sized cerebral ventricles at sonography; Postnatal outcome, AJR Am J Roentgenol 163: 405, 1994.

Kurtz AB, Wapner RJ, Rubin CS, et al: Ultrasound criteria for in utero diagnosis of microcephaly, J Clin Ultrasound 8:11, 1980.

Mahoney B, Callen P, Filly R, et al: The fetal cisterna magna, Radiology 153:773, 1984.

Nyberg DA, Mahony BS, and Pretorius DH, editors: Diagnostic ultrasound of fetal anomalies: text and atlas. St. Louis, 1990, Mosby.

Romero R, Pilu G, Jeanty P, et al: Prenatal diagnosis of congenital anomalies, Norwalk, Conn, 1988, Appleton & Lange.

Sanders RC, editor: Clinical sonography: a practical guide, ed 2. Boston, 1991, Little, Brown and Company.

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