Fetal Central Nervous System Imaging

Definition

Cephaloceles are cranial defects along bony sutures in which there is a herniation of the brain and/or meninges. Cephaloceles can be occipital, parietal, or frontal; in the Western Hemisphere, 80% are occipital. If the cephalocele sac contains brain tissue, it is termed an encephalocele ; if only cerebrospinal fluid (CSF) is present, it is termed a meningocele .

Incidence and Pathogenesis

• Incidence ranges from 1:3500 to 1:5000 live births. Occipital encephalocele is most common.

• Usually isolated, but in a small percentage of cases may be a part of a chromosomal or nonchromosomal syndrome.

• The exact pathogenesis of cephalocele is unclear. However, there is failure of closure of the neural tube no later than 26 days after conception, at the time when the anterior neural tube closes.

• Prenatal diagnosis at 11 0/7–13 6/7 weeks is possible, and the sonographic appearance is similar to that described during the second trimester.

Key Diagnostic Features

• Saclike structure adjacent or posterior to fetal head

• Brain tissue seen in sac covered by skin

• Skull defect

• Hydrocephaly in 80% of occipital encephaloceles

• Microcephaly (20%)

Differential Diagnosis

• Midline scalp masses, such as cysts, hemangiomas, nuchal tumors, cephalohematomas, cystic teratomas, scalp edema, cystic hygromas, branchiogenic cysts, and fetal hair (during the third trimester)

• Amniotic band syndrome

• Autosomal recessive syndromes that feature a cephalocele: Meckel syndrome (cephalocele, renal cystic dysplasia, and postaxial polydactyly); Walker-Warburg or HARD ± E syndrome ( h ydrocephaly, a gyria, r etinal d ysplasia, with or without e ncephalocele); and Knobloch syndrome (vitreoretinal degeneration and occipital encephalocele)

Associated Anomalies

• Approximately 65% of fetuses and infants with cephalocele have at least one additional major malformation, whereas 35% have isolated cephalocele.

• Extracranial malformations: cardiovascular (ventricular septal defect [VSD], coarctation of the aorta, single umbilical artery); urogenital tract (urinary tract dilatation [pyelectasis], ureteral agenesis); malformations of the extremities (talipes equinovarus); malformations of the thorax and abdominal wall (gastroschisis, diaphragmatic hernia, costal malformations).

• CNS anomalies include microcephaly (up to 25%), hydrocephaly (30%–50%), agenesis of the corpus callosum, Dandy-Walker malformation, holoprosencephaly (lobar), Arnold-Chiari type II malformation, and cerebral dysgenesis.

• Trisomy 18, trisomy 13, mosaic trisomy 20; various deletions and duplications also described.

Imaging

Management

Definition

Choroid plexus cysts (CPCs) are well-demarcated, anechoic, fluid-filled structures within the choroid plexus of the lateral ventricles of the brain. They are not true cysts in the pathologic sense. CPCs are often called “soft sonographic signs” or “markers” of aneuploidy because some studies have found an association between them and fetal chromosomal abnormalities. However, as more knowledge has accumulated, the initial importance attributed to this common sonographic finding has diminished. When CPCs are isolated, some consider them an anatomic variant. ^,

Incidence and Pathogenesis

• Incidence is 0.18%–3.6% of fetuses scanned in second trimester. ^{, ,}

• Pathogenesis is not clear but may be caused by filling of neuroepithelial folds with cerebrospinal fluid. CPC results from fluid trapped within this spongy layer of cells.

Key Diagnostic Features

• Unilateral or bilateral sonolucent cystic structures within glomus of choroid plexus of the lateral ventricles.

• Well-delineated borders.

• Size, shape, and number variable; heterogeneous appearance.

• Usually small, measuring <10 mm in diameter (range, 3–20 mm); should be at least >2 mm to meet criteria. Therefore, not every “dropout” seen in the choroid plexus is a true CPC.

• They regress, spontaneously disappearing during third trimester. ^{, ,}

Differential Diagnosis

• Ventriculomegaly

• Choroid plexus papilloma

• Intraventricular hemorrhage

• Periventricular leukomalacia

Associated Anomalies

• CPCs may be an isolated finding or associated with fetal anomalies.

• Associated anomalies are typically those seen with trisomy 18 and include congenital heart disease, clenched hands, single umbilical artery, intrauterine growth restriction, and rocker-bottom feet.

• Chromosomal aneuploidy: trisomy 18.

• Rare cause of obstructive hydrocephaly.

Imaging

Management

Definition

Holoprosencephaly (HPE) encompasses a spectrum of brain abnormalities in which there is failure of the forebrain to properly divide along the midline. The three classic forms are alobar, semilobar, and lobar; a fourth mild form, middle interhemispheric variant (MIHV), is also recognized. In alobar HPE, the most severe type, there is complete lack of division of the forebrain with absent midline structures. In semilobar HPE, there is some posterior separation. In lobar HPE, there is lack of separation of the ventral neocortex and agenesis of the corpus callosum. In MIHV, the mildest form, failure of separation involves the posterior frontal and parietal lobes, with incomplete separation of the thalami and caudate nuclei and absent body of the corpus callosum. HPE is associated with a spectrum of facial abnormalities, with more severe abnormalities seen with the most severe type (i.e., alobar).

Incidence and Pathogenesis

• HPE is the most common malformation involving the forebrain. It occurs in 1:250 embryos and 1:10,000 live births. It is estimated that spontaneous demise and abortion will occur in >90% of affected embryos.

• HPE is a primary defect of induction and patterning that leads to partial or complete failure of division of the prosencephalon into two separate hemispheres between 18 and 28 days after conception. However, no splitting actually occurs; instead, there is budding of the telencephalon.

• Genetic and environmental factors play a role in development of HPE.

Key Diagnostic Features

• In alobar HPE, there is a monoventricle; absence of the interhemispheric fissure, falx cerebri, corpus callosum, and cavum septi pellucidi; fusion of the thalami and cerebral hemispheres; and possibly various facial anomalies (e.g., cyclopia, proboscis, median clefts). In the first trimester (11 0/7–13 6/7 weeks), there is failure to image the two choroid plexuses (“butterfly” appearance) in the axial plane.

• In semilobar HPE, there is absence of the interhemispheric separation, but posteriorly there is some separation. The anterior horns are fused; the septi pellucidi and the anterior part of the corpus callosum are absent; and there is partial separation of the thalami, a rudimentary third ventricle, and facial anomalies (e.g., hypotelorism).

• In lobar HPE, there is absence of the cavum septi pellucidi and corpus callosum in the affected area.

• In MIHV, there is incomplete separation of the thalami and caudate nucleus, absent body of the corpus callosum, and brain heterotopias.

• Microcephaly is commonly seen.

Differential Diagnosis

In alobar and semilobar HPE:

• Hydrocephaly

• Schizencephaly

• Arachnoid cyst

• Agenesis of the corpus callosum

In lobar HPE:

• Septo-optic dysplasia

In middle interhemispheric variant (MIHV):

• Dysgenesis of the corpus callosum

Associated Anomalies

• CNS abnormalities: most commonly neural tube defects (exencephalies, meningoencephaloceles, myelomeningoceles, and myeloceles), Dandy-Walker malformation (DWM), rhombencephalosynapsis.

• Facial abnormalities seen with the most severe cases may include cyclopia, synophthalmia, or microphthalmia; proboscis; severe hypotelorism; midline cleft lip and palate; flat nasal bridge; and single or barely separated nostrils. ^,

• 25%–45% of newborns with HPE have a karyotype abnormality (trisomy 13, trisomy 18, triploidies). Mutations in 21q22.3, sonic hedgehog ( SHH ), Zic2 , SIX3 , and TGIF genes are also seen.

• About 25% have syndromes such as Smith-Lemli-Opitz and Pallister-Hall syndromes.

Imaging

Management

Definition

Porencephalic cyst is a pathologic brain cavity filled by cerebrospinal fluid (CSF); it is not a true cyst because it does not have a cyst wall. The cyst is the end result of an insult occurring between the second trimester of pregnancy and the early postnatal period. Areas affected by the insult undergo tissue necrosis and resorption, leaving behind a cavity in the brain (porencephalic cavity). Schizencephaly and porencephaly may share similar pathologies.

Incidence and Pathogenesis

• Porencephaly is a rare disorder that is the end result of a prenatal or perinatal ischemic stroke caused by an arterial or venous infarction, intraparenchymal hemorrhage, or in utero infection. These insults result in focal or multifocal areas of brain necroses that subsequently undergo dissolution and cavity formation.

• The fetal incidence is unknown; however, in term neonates the estimated incidence of a perinatal arterial ischemic stroke (PAIS) is 1:2500 to 1:5000.

Key Diagnostic Features

• Cyst or cavity within the brain parenchyma that communicates with the ventricles and/or subarachnoid space

• Ventriculomegaly on the same side as cyst

• No mass effect present

• Cyst seen along distribution of the middle cerebral artery or other arteries

• Typically seen late in gestation

Differential Diagnosis

• Unilateral schizencephaly

• Arachnoid cysts

• Hydranencephaly

• Ependymal cyst

• Encephalomalacia

• Brain tumor

Associated Anomalies

• Ventriculomegaly.

• Polymicrogyria may border cysts.

• Thrombophilias—high rate compared with general population.

• In one study, 64% of infants with perinatal arterial stroke had at least one thrombophilic marker, and 68% of the mothers were carriers of a thrombophilia.

• Factor V Leiden mutation, protein C deficiency, and presence of antiphospholipid antibodies were significant factors for perinatal stroke.

• Mutation in collagen IV A1 (COL4A1) gene in autosomal dominant porencephaly.

Imaging

Management

Definition

The terms ventriculomegaly (VM) and hydrocephaly are used interchangeably in the literature, but they are different entities. Ventriculomegaly should be preferred because it identifies the abnormal sonographic finding independently from the etiology. Most commonly, ventriculomegaly is used when the ventricles are mildly enlarged, and hydrocephaly is used when they measure >15 mm. Aqueductal stenosis (AS) results from the narrowing of the aqueduct of Sylvius, which connects the third and fourth ventricles.

Incidence and Pathogenesis

• The incidence of congenital dilation of the lateral ventricles is 3–15:10,000 births.

• AS is the most common cause of fetal VM, accounting for 30%–40% of cases.

• The aqueduct may become stenotic as a result of mass effect or from intrinsic pathology.

• In approximately 75% of patients, the etiology of the disorder is not known (idiopathic AS). ^, Causes of AS include genetic (X-linked or L1) syndromes, MASA syndrome ( m ental retardation, a phasia, s huffling gait, a dducted thumbs), and spastic paraplegia 1 (SPG1) syndrome; bacterial and viral infections (e.g., cytomegalovirus [CMV], influenza A); hemorrhage (direct obstruction of aqueduct by blood or clot); and CNS anomalies (e.g., Chiari I, Dandy-Walker malformation). ^,

• Incidence of X-linked hydrocephaly is 1:30,000 males.

Key Diagnostic Features

• AS is a diagnosis of exclusion, and other causes of VM need to be ruled out.

• Severe bilateral VM with lateral ventricles measuring >15 mm with dangling choroid plexus and dilation of third ventricle.

• VM is usually progressive.

• Macrocephaly.

• The brain mantle may be thin or compressed.

• The corpus callosum may be thin or undetectable because of compression from the dilated ventricles.

• Agenesis of the corpus callosum.

• Absent or fenestrated cavum septi pellucidi.

• Posterior fossa structures (cerebellum, vermis, and cisterna magna) are normal.

• Periventricular calcification if AS is caused by intracranial infection.

• Hemorrhage or masses.

• Abducted thumbs.

• More common in male fetuses.

Differential Diagnosis

• Holoprosencephaly

• Porencephaly

• Schizencephaly

• Hydranencephaly

Associated Anomalies

• Extracranial abnormalities (30% of cases).

• 25% of cases have multiple anomalies.

• Anomalies include macrocephaly, agenesis of the corpus callosum, and bilateral abducted thumbs (50%–60% of cases) (Online Mendelian Inheritance in Man [OMIM] database #307000).

• Can be part of MASA syndrome.

• Chromosomal aberrations (11% of cases).

• L1CAM mutation.

• In utero infection (e.g., CMV).

Imaging

Management