Brain Imaging

Microlissencephaly.

Microlissencephaly is used to describe children with severe microcephaly, a simplified sulcal pattern, and a thickened cortex. Different causative factors have been implicated including cytomegalovirus (CMV) infection and mutations of the RELN gene. Children with microlissencephaly tend to present with seizures and profound developmental delay.

Hemimegalencephaly.

Hemimegalencephaly refers to hamartomatous overgrowth of all or part of a cerebral hemisphere. Hemimegalencephaly refers to a heterogeneous group of conditions and may occur in isolation or in association with hemihypertrophy and neurocutaneous disorders. In some cases, there is a familial predisposition.

Children with hemimegalencephaly may present with macrocephaly, hemiplegia, seizure disorder, and developmental delay. MRI reveals diffuse enlargement of an entire cerebral hemisphere or a specific lobe of the brain [ Fig. 8.1 ]. Other anomalies such as polymicrogyria (PMG), lissencephaly, or gray matter heterotopia may be present. The ipsilateral lateral ventricle tends to be enlarged. In patients with intractable seizures, anatomic or functional hemispherectomy may be performed. Surgery may be contraindicated if there are contralateral malformations. Therefore a careful assessment of the contralateral “normal” hemisphere is especially important when reviewing MRI studies in these patients.

Focal Cortical Dysplasias.

Focal cortical dysplasias (FCD) are not associated with a single, known genetic abnormality and most likely arise because of mutations in a number of different genes. Histologically, FCD is divided into three main categories based on cortical delamination, disruption of cell architecture, cell composition, and any associated destructive brain lesions. The most common clinical presentation of children with FCD is medication-refractory, focal epilepsy.

Identification of FCD on MRI can be challenging. High-resolution T1, T2, and FLAIR images need to be scrutinized carefully for subtle cortical thickening with or without T1 shortening, abnormal gyration with an indistinct interface between the cortex and subcortical white matter, and the presence of adjacent white matter signal abnormality [ Fig. 8.2 ]. The transmantle sign has been described in type II FCD and refers to T2 prolongation (hyperintensity) within the subcortical white matter underlying the cortical abnormality extending to the ventricle. The signal abnormality is due to the presence of balloon cells and ectopic neurons along the radial glial pathway. Because MR delineation of a lesion for resection strongly correlates with surgical outcome, identification of FCD is critically important in patients, with intractable epilepsy being considered for operative intervention. FCD can be clinically occult and is occasionally seen on MRIs performed for an indication other than seizure. The differential diagnosis for an FCD on MRI often includes low-grade neoplasm. Follow-up imaging to assess stability of the lesion may help differentiate FCD, which should not change over time, from a slowly growing neoplasm.

Lissencephaly.

Lissencephaly means “smooth brain” and is characterized by reduced gyral and sulcal development. It is also referred to as the agyria-pachygyria complex. Agyria is defined as absence of the gyri in association with a thickened cortex; pachygyria is defined as the presence of a few broad, flat gyri. Lissencephaly encompasses a number of heterogeneous disorders that can be grouped into two major types: type 1 (classic) lissencephaly and type 2 (cobblestone lissencephaly).

Type 1 (classic) lissencephaly occurs in 1 in 500,000 live births and is caused by disruption of neuronal migration between the 10th and 14th weeks of gestation. Up to 70% of patients with type 1 lissencephaly have mutations of either LIS1 or doublecortin ( DCX ) gene. LIS1 type 1 lissencephaly includes the Miller-Dieker syndrome and results from a de novo mutation in 80% of affected children. DCX has an X-linked pattern of inheritance. Males with the DCX mutation have lissencephaly, whereas heterozygous females have subcortical laminar heterotopia referred to as “band heterotopia.”

Children with type 1 lissencephaly are typically hypotonic at birth with a normal or small head circumference. They subsequently experience development of seizures, hypertonia, and hyperreflexia. On imaging, type 1 lissencephaly consists of a diffusely thickened and abnormally smooth cerebral cortex. Band heterotopia or “double cortex” is characterized by a layer of incompletely migrated neurons and more normally gyrated appearance of the outer cortex [ Fig. 8.3 ]. The clinical phenotype tends to be much less severe in band heterotopia.

Type 2 (cobblestone) lissencephaly occurs because of excessive neuronal migration. It represents a heterogeneous group of disorders characterized by morphological abnormalities in the brain and merosin-negative or merosin-deficient congenital muscular dystrophy including Fukuyama disease, muscle-eye-brain disease, and Walker-Warburg syndrome. A combination of clinical findings, elevated serum creatine kinase levels, brain imaging, muscle and skin biopsy, and molecular genetic testing helps make the specific diagnosis. The imaging appearance on MRI can vary from mild pachygyria and a lack of normal sulcation to a highly abnormal, “cobblestone” appearance to the cortex, particularly anteriorly [ Fig. 8.4 ]. Because of overmigration of neurons, the CSF spaces surrounding the brain are typically reduced. The reduction in CSF surrounding the brain can be one of the earliest signs of cobblestone lissencephaly on fetal MR. Abnormalities can also be seen in the brainstem and in the cerebellum, and occipital cephalocele may be present in Walker-Warburg syndrome.

Gray Matter Heterotopia.

Gray matter heterotopia are focal collections of gray matter that arise because of interruption of normal neuronal migration. Heterotopia can be seen in isolation or in association with other anomalies. They can be subdivided into three groups: periventricular/subependymal, focal subcortical, and leptomeningeal; periventricular heterotopia are the most common. The majority of cases are sporadic. An X-linked dominant filamin-1 gene mutation is associated with extensive periventricular heterotopia and is seen mostly in girls. Heterotopia may cause seizures; with seizures usually more severe in children with multiple heterotopia. On all imaging modalities, heterotopia appear as nodules with the same imaging features as gray matter [ Fig. 8.5 ]. fMRI and blood oxygenation level–dependent imaging can demonstrate activation in epileptogenic heterotopia. Contrast enhancement should not be present.

Polymicrogyria.

PMG occurs because of disruption of late neuronal migration and cortical organization. It results in abnormalities in the deeper cortical cell layers and the formation of small and overly convoluted gyri. PMG can be unilateral or bilateral and focal or diffuse. The peri-Sylvian region is the most commonly involved [ Fig. 8.6 ]. Patients can present with developmental delay, focal neurological signs/symptoms, or seizures depending on the cortical area involved. PMG can be sporadic and isolated, associated with other genetic syndromes or related to CMV infection or cerebral ischemia.

The most constant feature of PMG is cortical thickening. High-resolution imaging better depicts the small abnormal gyri and bumpy contour. A volumetric acquisition with multiplanar evaluation is often helpful to diagnose subtle irregularities of the gray-white matter junction, which may be the only evidence of PMG. In unmyelinated areas, the abnormal cortex may appear thin and bumpy, as opposed to myelinated areas where it can appear thicker and relatively smooth. Perisylvian PMG is often accompanied by an abnormally vertical orientation of the Sylvian fissure [see Fig. 8.8 ]. The abnormality of the Sylvian fissure may be one of the first clues to the presence of PMG on fetal MR. Subtle cases of PMG may be difficult to diagnose in the neonate because of the high water content in the inner cell layers of the cortex, and follow-up imaging later in infancy may be required to detect or confirm PMG.

Schizencephaly.

Schizencephaly refers to congenital clefts in the cerebral hemisphere extending from the ventricular ependyma to the pia mater overlying the cerebral cortex. Schizencephaly is a disorder of neuronal organization and the clefts are lined with heterotopic gray matter, usually PMG. This is in contrast with porencephaly, which is a cystic lesion lined by white matter that occurs secondary to an encephaloclastic insult such as trauma or infarction.

The incidence of schizencephaly is estimated at 1.5 in 100,000 live births. Patients may be asymptomatic but usually present with seizures or developmental delay.

MRI is the imaging modality of choice. The lips (margins) of the cleft may be in apposition (closed-lip) or separated (open-lip). Closed-lip schizencephaly produces a nipple-like outpouching at the ependymal surface [ Fig. 8.7 ]. In open-lip schizencephaly, the CSF cleft can be seen extending from ventricular ependyma to the cortical surface. Schizencephaly may be associated with absence of the septum pellucidum and small optic nerves in patients with septooptic dysplasia (SOD).

Joubert syndrome.

Joubert syndrome is a hindbrain malformation with underdevelopment of the cerebellar vermis. Symptoms include hyperpnea, hypotonia, abnormal eye movements, ataxia, and developmental delay. On imaging, the cerebellar vermis is extremely underdeveloped or completely absent, the cerebellar hemispheres are apposed to one another in the midline, and there is enlargement of the superior cerebellar peduncles (“molar tooth sign”) [ Fig. 8.17 ]. Cleft lip and palate may also be present.

Rhombencephalosynapsis.

Rhombencephalosynapsis is a rare disorder in which the cerebellar vermis does not form and there is fusion of the cerebellar hemispheres across the midline producing a diamond-shaped fourth ventricle [ Fig. 8.18 ]. Associated supratentorial anomalies including hypoplasia of the corpus callosum, optic nerves, and agenesis of the posterior lobe of the pituitary gland may be present.

Dandy-Walker spectrum.

Classification of the Dandy-Walker spectrum anomalies continues to be controversial. The term Dandy-Walker spectrum may variably be used to encompass a number of anomalies including the classic Dandy-Walker malformation, the Dandy-Walker variant (less dilatation of the fourth ventricle and less enlargement of the posterior fossa), retrocerebellar arachnoid cysts, Blake pouch cysts (ballooning of the superior medullary velum into the cisterna magna), and mega cisterna magna. The classic Dandy-Walker malformation consists of an enlarged posterior fossa, elevated torcular Herophili, severe hypoplasia or agenesis of the cerebellar vermis, and a dilated, cystic-appearing fourth ventricle [ Fig. 8.19 ]. These anomalies are seen in approximately 1 in 30,000 live births. A number of different gene and modes of inheritance have been implicated.

Other anomalies associated with Dandy-Walker spectrum include hydrocephalus (70–90%), callosal abnormalities (30%), PMG or gray matter heterotopias (5–10%), and occipital encephaloceles in up to 16%. Clinical presentation varies depending on the severity of the abnormality. Eighty percent of patients with classic Dandy-Walker malformation present in the first year of life with symptoms secondary to hydrocephalus.

Chiari I Malformation.

The Chiari I malformation is defined as caudal extension of the cerebellar tonsils below the level of the foramen magnum [ Fig. 8.20 ]. The most common type of Chiari I malformation is related to a congenitally small, bony posterior fossa. Chiari I can also develop in patients with premature closure of the sutures as seen in Crouzon syndrome and Pfeiffer syndrome, and in some infants with ventriculoperitoneal shunts for hydrocephalus. Children with a Chiari I malformation may be asymptomatic or present with irritability (in younger children), headaches, lower cranial nerve palsies, or dissociated extremity anesthesia secondary to syringohydromyelia.

Potentially significant tonsillar descent in Chiari I should be distinguished from milder tonsillar ectopia, which is likely an incidental, clinically silent finding. Although the imaging findings distinguishing “Chiari I” from “tonsillar ectopia” historically focused on the extent of tonsillar ectopia present, clinical symptoms are related to the degree of obstruction of CSF flow at the foramen magnum, and surgical decompression is directed at relieving the obstruction. In Chiari I malformation, the tonsils extend to a variable degree (typically >6 mm), have a “pointed” configuration, and obstruct the flow of CSF at the foramen magnum. Clinically asymptomatic tonsillar ectopia may occur when the tonsils extend into the upper cervical canal, retain a rounded configuration, and do not significantly impede CSF flow. Hydromyelia is present in 20% of patients with a Chiari I malformation. The hydromyelic cavity usually, although not exclusively, involves the cervical spinal cord and extends a variable distance into the thoracic spinal cord. Hydromyelia produces a typical, partially “septated” appearance that serves to differentiate it from syringomyelia [ Fig. 8.21 ]. The demonstration of hydromyelia in the spinal cord should prompt evaluation of the cervicomedullary junction for the Chiari I malformation that will usually be present.

Chiari II Malformation.

The Chiari II malformation is a complex malformation of the hindbrain and skull that occurs in association with an open neural tube defect. This pathogenesis of Chiari II malformations remains controversial, but the anomaly arises in combination with different genetic polymorphisms and in association with environmental factors, including deficient maternal folate intake and abnormalities of folate metabolism. It is relatively common with an incidence of approximately 1 in 1000 live births. Almost all patients with a Chiari II malformation have a myelomeningocele. The hindbrain abnormalities are thought to occur secondary to the failure of closure of the posterior neuropore. This leads to a pressure gradient between the intracranial (higher pressure) and intraspinal (lower pressure spaces) with resultant inferior herniation of the developing structures of the posterior cranial fossa. Most of the hindbrain findings can be thought of as resulting from a normal-sized cerebellum developing in a small posterior fossa with a low-lying tentorium [ Fig. 8.22 ].

Features commonly seen in Chiari II include hydrocephalus, dysplastic tentorium, a small, bony posterior fossa, and a characteristic skull dysplasia known as Lückenschädel skull. Lückenschädel skull results from mesodermal dysplasia, which gives rise to the characteristic scalloped appearance. These dysplastic foci ossify and normalize by 6 months of age.

Other stigmata of Chiari II malformation include inferior displacement and elongation of the brainstem, kinking of the cervicomedullary junction, upward cerebellar herniation, an enlarged massa intermedia, elongated cranial nerves, tectal beaking, and callosal hypogenesis. Approximately 50% of patients have syringohydromyelia. Many patients have small-appearing gyri with shallow sulci in the posterior and medial aspects of the cerebral hemispheres; this pattern is known as stenogyria. Subependymal heterotopia are often present along the trigones of the lateral ventricles.

Chiari II malformations are being more frequently diagnosed antenatally. The classic antenatal sonographic appearance includes the lemon sign (which describes an indentation of the frontal bone) and the banana sign (which describes the appearance of the cerebellum tightly wrapped around the brainstem with obliteration of the cisterna magna). Fetal MRI can add diagnostic information regarding the intracranial abnormalities [ Fig. 8.23 ].

Early neonatal repair of the myelomeningocele and shunting of hydrocephalus has been the standard management of children born with Chiari II. Prenatal surgical repair of the myelomeningocele is now being performed at some centers and has been reported to reduce hydrocephalus, reduce requirement for postnatal ventriculoperitoneal shunt placement, and improve motor outcomes at 30 months. The long-term impact on neurocognitive development of fetal repair of the myelomeningocele has not yet been established.

Chiari III malformation was originally used to describe herniation of posterior fossa contents through a low occipital calvarial defect or high cervical spinal dysraphism. Chiari III malformations are rare.

Anencephaly.

Complete failure of early closure of the cephalic end of the neural tube results in anencephaly in which the forebrain, skull, and scalp are absent. It is associated with raised maternal serum alpha-fetoprotein. It is easily detected on antenatal ultrasound [ Fig. 8.24 ]. In the first trimester, neural tissue is still present; however, the normal head contour is absent and crown rump length is less than expected. As the pregnancy continues, neural tube superior to the orbits dissolves and the absent calvarium becomes more apparent. MRI is not required for diagnosis. Anencephaly is invariably lethal within a few days of delivery.

Cephalocele.

A cephalocele refers to herniation of CNS tissue through a defect in the skull. Most cephaloceles are midline in location. They are classified according to their contents and the location of the skull defect. A herniation containing CSF lined by meninges is referred to as a meningocele. A meningoencephalocele contains CSF and brain tissue, and a meningoencephalocystocele contains CSF, brain, and ventricle [ Figs. 8.25 and 8.26 ].

Occipital cephaloceles are the most common. Additional anomalies can be seen in up to 50% of cases including aneuploidy, Dandy-Walker spectrum, and Meckel-Gruber syndrome. Occipital encephaloceles often contain dysplastic occipital or cerebellar tissue, and anomalies of the adjacent dural venous sinuses are common.

Frontal and frontoethmoidal encephaloceles are more common in Asian populations. These may present with hypertelorism or a glabellar mass [ Fig. 8.27 ]. Failure of closure at the foramen cecum may result in a nasofrontal cephalocele, dermoid-epidermoid, or nasal “glioma” (isolated ectopic, dysplastic brain tissue) [ Fig. 8.28 ]. Rare sphenoidal cephaloceles can result in a nasopharyngeal mass.

Cephaloceles can be seen on prenatal ultrasound or fetal MR; they may appear cystic or solid depending on their contents. In postnatal patients, MRI is the best modality for delineating the composition of the contents and intracranial relationships. Thin-section CT with multiplanar reformats can be used for more accurate assessment of the osseous anatomy.

Craniosynostosis.

Craniosynostosis is the term applied to the premature fusion of a calvarial suture. It can affect the whole or part of a suture and can involve a single or multiple sutures. Failure of growth at the closed sutures causes increased growth along open sutures and resultant craniofacial abnormality [ Table 8.2 ]. Craniosynostosis can be either primary, caused by abnormal suture fusion, or secondary, caused by a failure of brain growth. Isolated single-suture synostosis does not restrict brain development and is usually only of cosmetic importance.

Primary craniosynostosis is relatively common with an estimated incidence of 1 in 2000 to 2500 live births. Most cases of craniosynostosis are isolated, but 15% are syndromic and associated with other developmental abnormalities.

Embryologically, the cranial vault is derived from the mesodermal neurocranium. The ossification centers begin to ossify around the 13th gestational week. By the 18th gestational week, the borders of the mineralizing bones have approached each other and begun to form the nonossified sutures. The presence of nonossified sutures and open fontanels at term allows overlap and deformation of the skull bones during parturition. The sutures permit further remodeling during rapid phases of brain and skull growth during the first few years of life.

Sutures normally close from back to front and from lateral to medial. The metopic suture is the exception; it closes from the glabella to the anterior fontanelle and is the first to close (9–11 months). The fontanels normally close by the second year of life. The coronal, lambdoid, and sagittal sutures may remain open until the fourth decade of life.

Sagittal synostosis is the most common isolated synostosis. It is four times more common in males than in females. It clinically manifests as a long, narrow head shape with sagittal ridging, restricted growth the parietotemporal regions, frontal bossing, and occipital protrusion. The long, narrow skull has been described as scaphocephalic, which means “boat-shaped” [ Fig. 8.30 ].

Unicoronal synostosis is the second most common form of craniosynostosis. Two-thirds of affected patients are female. The clinical features include a flattened ipsilateral forehead, a flattened ipsilateral occipital area, the “harlequin eye” deformity (caused by superior displacement of the ipsilateral orbital roof and lesser sphenoid wing), ipsilateral temporal bulging and cheek protrusion, contralateral forehead bossing, and deviation of the nose to the contralateral side [ Fig. 8.31 ].

Bicoronal synostosis causes a short, wide head that can be described as brachycephalic. There is depression of the supraorbital rims with bitemporal and upper forehead bulging. In bicoronal synostosis, the frontosphenoidal and frontozygomatic sutures are typically fused as well.

Bilambdoid synostosis causes a shallow posterior fossa and towering skull known as turricephaly. In a more severe form when bicoronal and bilambdoid synostoses are combined, the skull can adopt a characteristic towering and narrow shape, with bulging temporal areas and shallow orbits known as cloverleaf or Kleeblattschädel skull.

Metopic synostosis, when it occurs before the age of 6 months, is associated with a triangular wedding of the forehead ( trigonocephaly ), hypotelorism, narrow anterior cranial fossa, hypoplasia of the ethmoids, and a metopic ridge. After 6 months of age, premature closure of the metopic suture is associated with minimal deformity.

More than 180 described syndromes are associated with craniosynostosis. The management of syndromic craniosynostosis is complicated by associated skull base, facial, and brain abnormalities. Children with one of the syndromic craniosynostoses are at risk for raised intracranial pressure (ICP), hydrocephalus, optic atrophy, cleft palate, respiratory problems, and hearing disorders [ Table 8.3 ]. The most common of the syndromic causes of craniosynostosis affect the coronal sutures. Bicoronal synostosis may be associated with hydrocephalus, most often caused by jugular foraminal stenosis and venous hypertension.

Apert syndrome (also known as type I acrocephalosyndactyly) is an autosomal dominant condition that results from mutations of the FGFR2 gene. It is characterized by bicoronal craniosynostosis, midface hypoplasia, hypertelorism, exorbitism, and severe complex syndactyly of fingers and toes [ Fig. 8.32 ].

Crouzon syndrome is also due to mutations of the FGFR2 gene. Crouzon syndrome has similar calvarial deformities, facial anomalies, and exorbitism but is not associated with hand and foot abnormalities.

Pfeiffer syndrome (also known as type V acrocephalosyndactyly) can occur because of mutations in FGFR1 or FGFR2. It is characterized by craniosynostosis affecting multiple sutures, midfacial hypoplasia, severe exorbitism, and hypertelorism. The clinical findings in the periphery include broad and medially deviated great toes, broad thumbs, and soft-tissue syndactyly.

Muenke syndrome is caused by a mutation in the FGFR3 gene and is strongly associated with coronal synostosis. The hands and feet are often affected but with mild abnormalities such as thimble-like middle phalanges, carpal or tarsal coalition, and coned epiphyses that may not be clinically significant. All patients with Muenke syndrome should be tested for sensorineural hearing loss, but only a few are actually affected.

Imaging plays an important role in confirming the diagnosis and management of craniosynostosis, evaluating the extent of involvement, which is difficult with clinical examination alone. CT is the primary imaging modality used to evaluate the sutures. The closed suture is demonstrated by bone bridging across the suture, loss of architecture, or ridging. A very-low-dose technique can be used when the primary concern is osseous anatomy, and 3D reconstructions can depict the abnormalities exquisitely and are critical for operative planning.

Imaging can also help differentiate lambdoid craniosynostosis from positional plagiocephaly, which is an abnormal skull shape caused by infant positioning and not by premature fusion of the sutures [ Fig. 8.33 ]. There has been an increase in occipital plagiocephaly over the past two decades because of “back to back” campaigns encouraging that infants sleep in the supine position to reduce the risk for sudden infant death syndrome. In positional plagiocephaly, in addition to the lambdoid sutures being open, the ear on the flattened side is “pushed” forward; but in lambdoid synostosis, the ipsilateral ear is “pulled” posteriorly toward the fused suture.

In complex cases, dedicated magnetic resonance venography (MRV) or computed tomographic venography (CTV) imaging may be performed preoperatively to assess for associated dural venous sinus anomalies. In bicoronal synostosis with jugular foraminal stenosis, enlarged transosseous emissary veins (sinus pericranii) may be present. MRI may be required if there is a need to assess for underlying parenchymal abnormalities inadequately imaged using the low-dose CT technique.

Surgical intervention is unique to each type of synostosis. Surgery may be undertaken to correct cosmetic deformity in single-suture synostosis or may be required to permit normal brain growth or prevent complications such as raised ICP in multisutural synostosis.