Brain
Sanjay P. Prabhu
Savvas Andronikou
Sara O. Vargas
Richard L. Robertson
INTRODUCTION
Imaging plays a crucial role in the evaluation of neurologic disease in children. During the past several decades, rapid advances in imaging have contributed to a greater understanding of the structural and functional changes that occur in a child’s brain throughout childhood. Additionally, imaging provides noninvasive tools to help diagnose the cause of neurologic impairment in pediatric patients. It is important for the radiologist to consider changes of normal brain development from gestation through adolescence when performing and interpreting neuroimaging studies in pediatric patients. Furthermore, it is important to be familiar with agespecific diagnoses and have a clear understanding of the normal appearance and normal variations that characterize each stage of brain development.
This chapter provides an overview of imaging evaluation of pediatric brain disease. First, the role of currently available imaging modalities for assessing the pediatric brain is reviewed. Following this, normal anatomy and development are discussed. Finally, an overview of selected essential pediatric brain disorders is provided with emphasis on the underlying pathophysiology, clinical manifestations, key imaging features with pathologic correlation, and treatment approaches.
IMAGING TECHNIQUES
Radiography
Very few indications remain for performing radiographs to evaluate the brain parenchyma in an acutely ill child. Radiographs, however, continue to have a role in evaluating the skull: (1) as part of a skeletal survey in a victim of suspected child abuse, (2) for detection of osseous abnormalities in metastatic or metabolic disease, (3) as a screening tool for craniosynostosis in a child with an abnormally shaped skull, and (4) for evaluation of shunt catheter integrity and programmable shunt valve settings in pediatric patients with hydrocephalus.
Standard skull radiography technique consists of frontal, lateral, and Townes projections. These views have been discussed in more detail in Chapter 1 of this book.
Ultrasound
Ultrasound (US) of the infant brain is a noninvasive, radiation-free procedure that can be performed at the bedside, in the intensive care unit, or on an intubated, ventilated infant following delivery. It has a number of advantages including ready access, portability, real-time and multiplanar capabilities, and reproducible results.
Currently, US is mainly used in neonates (1) to screen for suspected intracranial hemorrhage and periventricular leukomalacia (PVL) in the premature infant, (2) to monitor progression or resolution of the pathologic process, and (3) to detect the subsequent complications of ventriculomegaly and progressive hydrocephalus. Cranial US also has a role in detecting focal infarcts and hemorrhagic lesions in the term or near-term infant; in screening for congenital midline anomalies, intracranial cystic lesions, vascular malformations, and intracranial calcifications; and in delineating extra-axial fluid collections. Because of its portable nature, it remains the modality of choice for use at the bedside, obviating the need for transportation of the unstable or critically ill child. In older children, transcranial Doppler is used to correlate resistive indices with elevated intracranial pressure in cases
of head trauma and assess blood flow in cases of cerebrovascular disease. A sonographic finding or suspected lesion can be further characterized with computed tomography (CT) or magnetic resonance imaging (MRI) when the patient is more stable.
of head trauma and assess blood flow in cases of cerebrovascular disease. A sonographic finding or suspected lesion can be further characterized with computed tomography (CT) or magnetic resonance imaging (MRI) when the patient is more stable.
Sonographic scanning in premature infants should be performed using higher-frequency transducers operating between 7 and 10 MHz because of their higher spatial resolution.1,2 Lower-frequency transducers (3.5 to 5 MHz) are often used in larger infants to obtain adequate penetration of sound waves. Sector transducers with a 120-degree imaging field are ideal to image through the anterior and posterior fontanelles.3
To ensure optimal coverage of the brain, scanning should include a series of standardized coronal and sagittal images through the anterior fontanelle (Fig. 2.1). Coronal images are acquired by placing the transducer transversely across the fontanelle and moving it in an arc in an anteroposterior direction to cover the entire brain. The transducer should be carefully positioned to produce symmetrical imaging of both hemispheres. Six to eight angled images should be obtained, with the most anterior image acquired anterior to the frontal horns of the lateral ventricles at the level of the orbits, the second image through the anterior horns of the lateral ventricles at the level of the suprasellar cistern, the third image more posteriorly through the body of the lateral ventricles at the level of the paired foramina of Monro and brainstem, the fourth image with the transducer angled slightly more posteriorly, the fifth image further posteriorly at the level of the prominent paired echogenic choroid plexus in the atria of the lateral ventricles, and the final coronal image posterior to the lateral ventricles.
 FIGURE 2.1 A: Positions of the transducer for coronal ultrasound images through the brain. B: Positions of the transducer for sagittal ultrasound images through the brain. |
Sagittal images are obtained by placing the transducer longitudinally along the anterior fontanelle, with one acquired along the midline and two to three acquired on each side by angling the transducer laterally. The true midline-imaging plane is obtained by identifying the comma-shaped fluidfilled cavum septum pellucidum, the curved hypoechoic corpus callosum cephalad to it, and the echogenic cerebellar vermis in the infratentorial region. The cingulate gyrus is located cephalad to the corpus callosum, and the echogenic line between them is the pericallosal sulcus. The cingulate gyrus is separated from the other gyri by the cingulate sulcus. Note that the normal gyri and sulci never extend to the ventricles. The medial aspect of the paired thalamic nuclei, the
tectum of the midbrain, and fourth ventricle can be identified on this midline image.
tectum of the midbrain, and fourth ventricle can be identified on this midline image.
The first parasagittal image obtained with the anterior portion of the probe angled more medially than the posterior portion produces a sagittal image showing the frontal horn and body of the lateral ventricle. On this image, attention should be directed in particular to the caudothalamic groove, which is seen as thin echogenic line at the junction of the slightly more echogenic caudate nucleus anteriorly and the relatively less echogenic thalamus posteriorly. The caudothalamic groove is contiguous with the choroid plexus in the roof of the third ventricle. Further lateral angulation provides images through the entire lateral ventricle, and more laterally, through the peripheral brain parenchyma, the Sylvian fissure, and the cerebral convolutions, which increase with gestational age.
In addition to the coronal and sagittal planes, four additional approaches through the midline posterior fontanelle, the squamosal suture, the posterolateral or mastoid fontanelle, and the foramen magnum are used as additional problem-solving tools in some patients with suspected posterior fossa and midbrain anomalies and abnormalities.
Color Doppler is used to investigate the pericallosal segment of the anterior cerebral artery (ACA) in a midline sagittal projection using 7 to 8 MHz vector transducer.2 Two views are obtained, each for a maximum of 3 to 5 seconds. The first view of baseline Doppler spectrum is obtained without exerting pressure over the fontanelle. Then, the second view is obtained by completely depressing the transducer until further depression of the fontanelle generates no additional pressure. During compression, the Doppler range gate is repositioned over the same portion of the ACA, and a second Doppler spectrum is obtained. Flow velocity and resistive index (RI), which is defined as the peak systolic velocity (PSV) minus the end-diastolic velocity divided by PSV, are the most commonly used spectral Doppler measures used to quantify the cerebral blood flow. All intracranial arteries display a low-resistance flow pattern with continuous forward flow during systole and diastole. Because these arteries usually have a diameter of <5 mm, the spectral lines are broad and the spectral window is filled.4 In premature babies, the intracerebral RI is high; an RI of up to 1 may be normal.4 Variations in cerebral blood flow that occur as adaptations to postnatal life are poorly reflected in the RI and PI; hence, they are less informative in the first few months of life. Elevation of RIs is nonspecific, but serial measurements are used to follow pediatric patients with raised intracranial pressures, shunted hydrocephalus, or indomethacin administration.
Computed Tomography
CT remains the neuroimaging modality of choice in the acutely ill child because of its widespread availability and fast image acquisition speeds. Although CT is still used in many institutions around the world for investigation of children with a variety of suspected brain abnormalities, it is best suited for detecting acute intracranial hemorrhage, cerebral edema, hypoxic-ischemic injury (HII), infarction, hydrocephalus/shunt dysfunction, neoplasm, or abnormal collections. Modern multidetector CT scanners can acquire submillimeter thick images, which can be manipulated to produce multiplanar reformats and 3D images, thereby facilitating rapid detection of calvarial and facial fractures. CT remains the modality of choice in the workup of children with suspected craniosynostosis. When performed with iodinated contrast media, CT provides information about inflammatory and infectious lesions and resultant complications such as abscess.
CT angiography (CTA) provides excellent detail of the vascular structures and helps diagnose a variety of arterial and venous abnormalities in the acute setting. CTA also compares favorably with MR angiography (MRA) in evaluating vertebral artery dissection, as shown in a number of adult studies. CT venography (CTV) remains the initial modality of choice in many pediatric centers for assessing pediatric patients with suspected dural venous sinus thrombosis.
However, CT requires use of ionizing radiation, which has the potential to adversely affect tissues in the pediatric patient, particularly when used for multiple studies. Therefore, it is important to consider alternatives to CT, particularly in infants and young children. Once CT is chosen as the imaging modality, the ALARA (As Low As Reasonably Acceptable) principle must be always adhered to. This entails the use of appropriate age- and weight-based dose adjustment parameters available on modern CT scanners and limitation of the scan to the area of concern.
Magnetic Resonance Imaging
More recently, MRI has become the modality of choice for imaging the pediatric brain in almost all elective medical conditions and, more recently, even in the acute setting. The capability of MRI to acquire images in multiple planes with excellent anatomic detail and superb tissue contrast, without the harmful effects of ionizing radiation, makes MRI an ideal tool for imaging the brain in children of all ages. MRI is substantially better than CT for evaluating the brain parenchyma, assessing the posterior fossa, and detecting microhemorrhages. The increasing availability of higher field strength magnets (most commonly 3-Tesla scanners) and multichannel head coils in pediatric institutions provides excellent detail and has improved diagnostic accuracy for many conditions affecting the central nervous system (CNS). MRI can provide vital functional and physiologic information about the brain that cannot be generated by other imaging modalities.
Advanced MR imaging sequences including diffusionweighted and diffusion tensor imaging (DWI and DTI), susceptibility-weighted imaging (SWI), magnetic resonance spectroscopy (MRS), and perfusion imaging including arterial spin labeling (ASL) are now part of routine pediatric neuroimaging protocols in many institutions.
Two major disadvantages of MRI are longer scan acquisition times and sensitivity to patient motion, which are more relevant in the pediatric age group than in adults. These
factors necessitate use of sedation or general anesthesia in a proportion of young pediatric patients. Various techniques have been used to reduce the need for sedation, including mock MRI, which acclimatizes the child to the MRI scanner, and technologies that decrease acquisition times, such as multichannel head coils, parallel imaging, and motion compensation techniques. In order to ensure that the information required to answer the clinical question is acquired in the shortest possible time before lack of patient cooperation becomes problematic, it is important to acquire the most important sequences at the start of the examination and actively monitor the MRI exam in a pediatric patient.
factors necessitate use of sedation or general anesthesia in a proportion of young pediatric patients. Various techniques have been used to reduce the need for sedation, including mock MRI, which acclimatizes the child to the MRI scanner, and technologies that decrease acquisition times, such as multichannel head coils, parallel imaging, and motion compensation techniques. In order to ensure that the information required to answer the clinical question is acquired in the shortest possible time before lack of patient cooperation becomes problematic, it is important to acquire the most important sequences at the start of the examination and actively monitor the MRI exam in a pediatric patient.
Nuclear Medicine
Nuclear medicine studies are most commonly used to evaluate pediatric epilepsy and brain tumors. In addition, nuclear medicine studies have a role in the assessment of inflammatory brain diseases such as Rasmussen encephalitis and brain death in the pediatric population. Furthermore, nuclear medicine studies have been used to study the pathophysiology underlying various childhood disorders including posttraumatic brain injury, Rett syndrome, and the phacomatoses. As the use of nuclear medicine studies in modern clinical practice primarily involves the evaluation of epilepsy and brain tumors, techniques used in these areas are briefly discussed here.
Radiopharmaceuticals such as 99mTc-hexamethylpropylene amine oxime (HMPAO) and 99mTc-bicisate (ECD) are taken up by brain parenchyma in proportion to regional brain perfusion. These agents are used to perform ictal and interictal single positron emission computed tomography (SPECT) studies in pediatric patients with temporal and extratemporal lobe epilepsy. Similarly, 18F-fluorodeoxyglucose-positron emission tomography (18F FDG-PET) is used in the interictal state to highlight the epileptogenic area in the brain. In temporal lobe epilepsy, the sensitivity of ictal SPECT ranges between 60% and 90%, whereas a positive FDG-PET scan can show the epileptogenic focus in up to 85% of cases.5 Subtraction ictal SPECT coregistered to MRI (SISCOM) is a valuable diagnostic tool used to accurately localize the seizure onset zone in nonlesional and extratemporal epilepsies (Fig. 2.2).
Nuclear medicine studies continue to play an important role in the management of childhood brain tumors. FDG-PET is widely used for metabolic studies of brain tumors. The utilization of FDG-PET in evaluating pediatric brain tumors is based on the assumption that malignant tumors have increased FDG uptake and benign tumors have reduced FDG uptake compared to normal brain parenchyma. Indeed, FDG uptake is increased in the majority of malignant tumors, and the uptake is positively correlated with tumor grade in childhood CNS tumors.
Other tracers such as 11C-methionine PET (MET-PET) have been used in the management of pediatric brain tumors and in the localization of active tubers in pediatric patients with tuberous sclerosis. However, their limited availability has prevented widespread adoption of these tracers in routine clinical practice.
 FIGURE 2.2 A 3-year-old boy with temporal lobe epilepsy. Axial subtraction ictal SPECT coregistered to MRI (SISCOM) image demonstrates a left temporal lobe epileptogenic focus (arrow). |
Conventional Cerebral Angiography
Advances in cross-sectional imaging and its ever-increasing availability have improved resolution of angiographic anatomy and led to a progressive decline in the need for diagnostic conventional cerebral angiograms in the pediatric population. However, catheter angiograms are able to resolve small vessels with a spatial resolution of 0.2 mm and temporal resolution of 0.25 seconds, which are superior to CTA and MRA.6 This technique helps diagnose and plan management of a number of pediatric neurovascular diseases, including intracranial hemorrhage, aneurysms, vascular malformations, dural venous fistulae, trauma, and arteriopathies. Four-vessel catheter neuroangiography remains the “gold standard” modality for the assessment of various disorders including vasculitis, arteriopathies, small aneurysms, arteriovenous malformations (AVMs), and fistulae. The availability of microcatheters has enabled superselective catheterization even in small infants and aids the percutaneous management of various vascular lesions by neurointerventionalists. Catheter size and contrast dose are determined by patient size and age. Disadvantages of this modality include its relatively invasive nature, challenges in obtaining arterial access in children, small risk of lasting neurologic deficits (0.06% to 0.1%), and the small number of trained personnel with pediatric angiographic experience.7
EMBRYOLOGY AND NORMAL ANATOMY
Developmental Biology
The change that occurs in the brain from the time of conception to the adulthood is complex, and a detailed discussion of this process is beyond the scope of this chapter. However, a fundamental knowledge of the various steps involved in the development of the brain is essential in order to understand the pathogenesis of various developmental malformations of the pediatric brain and their classification. These steps can be summarized as follows:
In the 3rd week of gestation, the embryo becomes three layered (trilaminar) via a process called gastrulation, following formation of a thick, linear band along the dorsal caudal surface of the epiblast called the primitive streak. The primitive node forms at the cranial end of the streak, and a depression develops along the streak called the primitive groove. As cells begin to migrate between the epiblast and the hypoblast, the layers of the trilaminar embryo are renamed as the ectoderm (epiblast), mesoderm (migrated mesenchymal epiblastic cells), and endoderm (hypoblast). Some mesenchymal cells migrate cranial to the primitive node between the ectoderm and endoderm and form the notochord. The notochord grows in a caudal to cranial direction between 17 and 21 days of gestation. It induces a portion of the ectoderm to become the neural plate. Around 19 to 21 days of gestation, the neural plate differentiates into the neural tube, which gives rise to the CNS, and the neural crest, which gives rise to the peripheral nervous system.
 FIGURE 2.3 Brain development: formation of the various parts of the brain. |
Subsequently, during the 4th week of gestation, the neural tube develops a cranial opening called the rostral neuropore and a caudal opening called the caudal neuropore. Both neuropores normally close by ˜24 to 25 days of gestation. Following cranial neuropore closure, the neural tube undergoes segmentation into neuromeres and rhombomeres. The neuromeres then give rise to the prosencephalon (forebrain), which divides into the telencephalon (cerebral hemispheres) and the diencephalon. The rhombomeres give rise to the mesencephalon (midbrain) (Fig. 2.3A) and the rhombencephalon (hindbrain) (Fig. 2.3B and C).
Cerebral cortical formation occurs through a complex process involving a group of neurons that are induced in a neuroepithelial layer and subsequently differentiate, migrate, and organize into a functioning cerebral cortex. This process is controlled by interaction between intrinsic genetic mechanisms and extrinsic information relayed to the cortex by thalamocortical input and other less known factors. Neuronal precursors migrate from the ventricular zone to the cortical plate. Cells begin to migrate centrifugally from the ventricular zone to form the cerebral cortex. Radially oriented glial cells extending between the ventricular margin and the cortex were previously thought to act as scaffolding along which the neurons migrate. More research into this process has helped define that radial glial cells have a more important role in neurogenesis. They have been shown to give rise to cortical neurons as well as glial cells. Once the neurons reach the surface,
they differentiate to form the normal six-layered cortex (Fig. 2.4).
they differentiate to form the normal six-layered cortex (Fig. 2.4).
 FIGURE 2.4 Cortical development. |
Based on the patterns of migration, various classifications of malformations of cortical development (MCD) have been proposed. The latest classification by Barkovich et al., describes three primary groups based on the overlapping stages of neuronal migration8: (I) malformations caused by abnormal neuronal and glial proliferation, (II) malformations caused by abnormal neuronal migration, and (III) malformations caused by abnormal cortical organization. These disorders are described in a subsequent section of this chapter.
Myelination
The brain parenchyma is composed of gray matter and white matter, which differ in composition (water content and macromolecules) and gross morphology. Although the gray matter consists mainly of neurons, the white matter is composed predominantly of myelinated bundles of axons. The brain of a neonate consists of a large amount of water (89% in gray matter and 82% in white matter), compared to the mature adult brain (82% in gray matter and 72% in white matter).9
Myelination of the CNS is primarily a postnatal process. The myelin sheath is a tightly wrapped, multilayered membrane composed of a repeating structure characterized by lipid-cytoplasm-lipid-water surrounding the axons. It is produced by the oligodendroglial cell membranes. Lipid components of myelin in the white matter include cholesterol, galactocerebrosides, sphingomyelin, and phospholipids. They are essential for ensuring stability and strength of the myelin sheath. The other constituents of myelin are a number of proteins including proteolipid protein (PLP), myelin basic protein, myelin-associated glycoprotein, 2′, 3′-cyclic-nucleotide 30-phosphodiesterase? and myelin oligodendrocyte glycoprotein. Alterations in the genes controlling the production of these proteins can result in abnormal white matter structure.
Myelination progresses in the human brain in a predictable sequential pattern. Myelination, which starts in the second trimester of gestation, continues postnatally, and lasts into adulthood. The sequence of progression of myelination has been shown to relate to psychomotor development. Certain rules can be used to define the progression of normal myelination. These include progression of myelination in a posterior-to-anterior direction (in keeping with the development of occipital regions and visual areas prior to auditory and speech areas) and in a caudocranial pattern (in keeping with development of the brainstem and cerebellum followed by sensorimotor and higher functions including emotions and abstract thoughts). The corpus callosum also myelinates in a posterior-to-anterior fashion, in keeping with the sequence of myelination in the areas connected by its various sections.
The appearance of the brain parenchyma on MRI changes according to the myelin content. White matter relaxation times, which determine the MR appearance of white matter,
are affected by a number of factors, including changes in the structure and chemical composition of the axon and the surrounding myelin and the degree of axonal ensheathment by myelin. Most authors believe that signal changes on T1-weighted MR images correspond with the increase in the certain lipids occurring during myelin formation. The changes on T2-weighted MR images can be explained by myelin sheath maturation and decrease in the water content of the white matter indicated in vitro by thickening and tightening of the spiral of myelin around the axon.
are affected by a number of factors, including changes in the structure and chemical composition of the axon and the surrounding myelin and the degree of axonal ensheathment by myelin. Most authors believe that signal changes on T1-weighted MR images correspond with the increase in the certain lipids occurring during myelin formation. The changes on T2-weighted MR images can be explained by myelin sheath maturation and decrease in the water content of the white matter indicated in vitro by thickening and tightening of the spiral of myelin around the axon.
On a practical note, T1-weighted MR images are considered useful for assessment of the state of myelination in the first 6 months of life, and T2-weighed MR images are utilized in older age groups. However, in our experience, on modern 3-Tesla scanners, T2-weighted MR images in the neonate and young infant are as valuable as the T1-weighted MR images to assess myelination. A series of milestones can be used to assess the appropriateness of myelination, as detailed in Table 2.1. As myelination continues well into the teenage years, we do not deem myelination “complete” but prefer to use the term “age appropriate” if the milestones in Table 2.1 are present at a particular age. Myelination is essentially complete by around 2 years of age, except for some areas of persistent nonmyelinated white matter in the parietooccipital regions. These are called the terminal zones of myelination and should not be confused with areas of white matter injury of prematurity, which can have a similar distribution. The various stages of myelination are summarized on Figure 2.5.
TABLE 2.1 Milestones of Myelination | ||||||||||||||||||||||||||||||
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 FIGURE 2.5 Summary of the stages of myelination from the newborn period to 24 months of age on T1- and T2-weighted MR images. |
SPECTRUM OF BRAIN DISORDERS
Congenital and Developmental Anomalies
Several classification systems have been proposed to describe congenital and developmental brain anomalies, in order to incorporate details of morphology, neuropathology, genetics, and clinical findings. Although many of these comprehensive classification systems succeed in incorporating most of the known malformations, they are not always practicable for use in daily clinical practice.
In this section, we use a practical location-based approach that includes the details of morphology and genetics used by some of the more modern classification systems to analyze brain anomalies. Although this is not fully comprehensive, we believe that this is practicable to grasp and use in daily clinical practice. The classification system is summarized in Table 2.2.
TABLE 2.2 Classification of Congenital Brain Malformations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Supratentorial Anomalies
Malformations of Cortical Development
MCDs encompass a heterogeneous group of cortical lesions resulting from abnormalities during development and formation of the cortical mantle. This process has been summarized in an earlier section in this chapter. The classification of MCDs undergoes periodic revision based upon advances in our understanding of the molecular pathways and genes involved in brain development and the ways in which this complex process can go awry. The latest classification used at the time of drafting this chapter, described by Barkovich et al., is based upon the stage of cortical development that is affected.8
The three major stages of cortical development are proliferation, neuronal migration, and postmigrational development. Note that there is temporal overlap between these stages. For instance, neuronal proliferation continues while migration commences and neurons continue to migrate as postmigrational development begins. Further, cells resulting from abnormal proliferation often fail to migrate and organize properly. It is important to recognize that the classification does not encompass every single constellation of abnormalities, but should be seen as a guide.
Using this classification, MCDs are divided into four major groups:
Group I: is defined by abnormalities of neuronal and glial proliferation or apoptosis (resulting in either too many or too few cells) and is divided into three subgroups: (A) reduced proliferation or accelerated apoptosis (resulting in congenital microcephalies), (B) increased proliferation or decreased apoptosis (resulting in conditions such as megalencephalies), and (C) abnormal proliferation (with resultant focal and diffuse dysgenesis and dysplasia).
Group II: is defined by abnormalities of neuronal migration and is divided into four subgroups: (A) abnormalities in the neuroependymal cell (ventricular zone epithelium) during initiation of migration (resulting in periventricular nodular heterotopia), (B) generalized abnormalities of transmantle migration (resulting in lissencephalies), (C) localized abnormalities of transmantle migration (resulting in subcortical heterotopia), and (D) terminal migration anomalies and defects in the pial-limiting membranes (resulting in the cobblestone malformations).
Group III: consists of abnormalities of postmigrational development. These malformations result from injury to the cortex during later stages of development and include late prenatal and perinatal insults.
Group IV: is defined as MCD, not otherwise specified. This chapter includes some of the more important anomalies that come under this classification with helpful information to identify them on imaging, along with notes about their clinical relevance.
Lissencephaly (Agyria With or Without Pachygyria)
Lissencephaly refers to a “smooth brain” with a paucity of gyri and sulci on the brain surface. Agyria is defined as an absence of gyri with a thickened cortex and is synonymous with “complete lissencephaly.” On the other hand, pachygyria refers to the presence of a few broad, flat gyri with thickened cortex and is synonymous with “incomplete lissencephaly.”
In classic lissencephaly, the cortex is abnormally thick (12 to 20 mm; normal: 3 to 4 mm) and poorly organized with four layers, namely, a thin outer cortical layer, a thin molecular layer adjacent to the pia, a “cell-sparse zone” medial to the outer cortical layer, and a thickest deep cortical layer.10 MRI in patients with complete lissencephaly shows a smooth brain surface, with absent gyri and shallow, vertically oriented Sylvian fissures, which results in the “figure-of-eight” appearance on axial images. Callosal dysgenesis with a vertically oriented splenium is seen in severe lissencephaly. The brainstem is usually small.
In patients with incomplete lissencephaly, pachygyria is seen along with agyria or areas of normal brain. Imaging studies show presence of broad gyri and shallow sulci (Fig. 2.6). Gross anatomy demonstrates a paucity of gyri over the surface (Fig. 2.7). Use of high-resolution images helps differentiate between the smooth gray and white matter junction in pachygyria and the irregular, nodular outline in polymicrogyria.
Polymicrogyria
Polymicrogyria is one of the most common MCDs. It refers to the pathologic finding of overfolding and abnormal
lamination of the cortex. The overfolding is usually microscopic, and the abnormal lamination either unlayered or four-layered in most described cases. Polymicrogyria is most commonly seen in the perisylvian cortex, but almost all cortical regions can be involved. Polymicrogyria is a highly heterogeneous disorder in terms of its pathogenesis, distribution, pathologic appearance, and clinical and imaging features. The clinical presentation is varied, and patients present at all ages from the neonatal period until late adulthood.
lamination of the cortex. The overfolding is usually microscopic, and the abnormal lamination either unlayered or four-layered in most described cases. Polymicrogyria is most commonly seen in the perisylvian cortex, but almost all cortical regions can be involved. Polymicrogyria is a highly heterogeneous disorder in terms of its pathogenesis, distribution, pathologic appearance, and clinical and imaging features. The clinical presentation is varied, and patients present at all ages from the neonatal period until late adulthood.
 FIGURE 2.6 Incomplete lissencephaly (pachygyria) in a 3-year-old boy. Axial T2-weighted MR image (on the left) shows lissencephaly characterized by broad gyri and shallow sulci more pronounced in the frontal and temporal lobes. Note the T2 hyperintense cell-sparse zone in the parietal lobes (white arrows). Sagittal T1-weighted MR image (on the right) shows a vertically oriented Sylvian fissure (white arrow). |
 FIGURE 2.7 Pachygyria in an 11-year-old girl with microcephaly. The cerebral cortex shows pachygyria, characterized by a paucity of gyri (black arrows). |
Polymicrogyria is classified as an abnormality occurring during late neuronal migration or early cortical organization, with both genetic and nongenetic factors involved in its pathogenesis. Ischemic injury, congenital infections (cytomegalovirus [CMV] being the most common), chromosomal deletion and duplication syndromes (e.g., 22q11.2 deletion), and peroxisomal disorders like Zellweger syndrome are among the common causes implicated in the development of polymicrogyria. Various modes of inheritance, including X-linked and autosomal recessive pedigrees, have been identified. Mutations in genes such as the TUBB2B gene have been identified recently. Imaging should be directed toward defining the regional distribution of the polymicrogyria, elaborating additional abnormalities in the white matter, correlating with the head circumference, and identifying clues that point to a possible infective or ischemic etiology such as periventricular calcification or encephalomalacia.11
On MRI, polymicrogyria is characterized by an irregular cortical surface and “stippled” gray-white junction with regions of apparent cortical thickening (Figs. 2.8 and 2.9).
On MRI, polymicrogyria is characterized by an irregular cortical surface and “stippled” gray-white junction with regions of apparent cortical thickening (Figs. 2.8 and 2.9).
 FIGURE 2.8 Bilateral perisylvian polymicrogyria. Axial T2-weighted MR image shows the irregular nodular cortical-white matter junction (arrows) in the bilateral perisylvian regions, right more than left. |
Pitfalls to avoid include mistaking deformational changes because of perinatal injury for polymicrogyria and underestimating the abnormality in the cortical outline in patients with incomplete myelination of the white matter.
 FIGURE 2.9 Polymicrogyria in a 13-year-old boy with holoprosencephaly. Superior aspect of the brain shows polymicrogyria of the frontal (right) and anterior parietal lobes (arrows). |
Schizencephaly
Schizencephaly is a full-thickness cleft lined with gray matter and connecting the subarachnoid cerebrospinal fluid (CSF) spaces with the ventricular system. The cleft is lined by abnormal infolded gray matter extending from the cortex into the ventricles, with associated fusion of the cortical pia and ventricular ependyma within the cleft.12 Gray matter heterotopias and areas of polymicrogyria are frequently found within and near the cleft. Schizencephaly results from injury to the entire thickness of the developing hemisphere during cortical organization because of prenatal infection, ischemia, or chromosomal abnormalities. Clinical manifestations of schizencephaly most often include varying degrees of developmental delay, motor impairment, and seizures.
On imaging studies, schizencephaly is seen as a full-thickness CSF-containing cleft extending medially from the subarachnoid space into the lateral ventricle. The wall of the cleft is lined with abnormal gray matter, which sometimes extends into the lateral ventricle in the form of subependymal heterotopias. Clefts may be small or large, unilateral or bilateral. The anomaly may be of the open-lip or closed-lip type. In closed-lip schizencephaly, the gray matter-lined lips are in contact with each other. The walls of the cleft in openlip schizencephaly are separated, and a cleft of CSF can be seen extending to the underlying ventricles (Fig. 2.10).
 FIGURE 2.10 Open-lip schizencephaly. Axial MPRAGE (magnetization-prepared rapid acquisition gradient-echo) MR image demonstrates a large right-sided full-thickness cleft (asterisk), lined by abnormal polymicrogyric gray matter (straight arrows), that communicates with the lateral ventricle. Also, note absence of the septum pellucidum in this child with septooptic dysplasia and polymicrogyria (curved arrow) without schizencephaly in the left cerebral hemisphere. |
In addition to defining the schizencephalic cleft, imaging should be directed to identifying additional abnormalities that may coexist in these pediatric patients. The more common associated abnormalities include variable components of septooptic pituitary dysplasia (including optic nerve hypoplasia, absence of septum pellucidum, and ectopic/absent neurohypophysis), pachygyria, polymicrogyria, heterotopia, and arachnoid cysts.
Hemimegalencephaly
Hemimegalencephaly is a rare malformation of cortical development characterized by defective cellular organization and neuronal migration, with resultant hamartomatous overgrowth of a hemisphere. This condition is rare, representing <5% of MCD diagnosed on imaging studies.13 Affected patients typically present in infancy with macrocrania, developmental delay, and seizures. Hemihypertrophy of part or all of the ipsilateral body may be associated. Seizures are difficult to treat, and severe developmental delay is common.
On imaging studies, hemimegalencephaly is characterized by an enlarged, dysplastic-appearing hemisphere with an abnormal gyral pattern, cortical thickening, and white matter signal abnormalities (Fig. 2.11). The ipsilateral lateral ventricle usually appears enlarged, and the frontal horn points anteriorly on the involved side. Focal or localized type is also described. On CT, there is an enlarged hemisphere and hemicranium, with contralateral displacement of the posterior falx. Dystrophic calcifications are common. On MRI, the dysplastic cortex appears thickened and undulating on T1-weighted MR images. Myelination is accelerated with resultant T1 hyperintensity. Gray matter heterotopias are commonly seen. The ipsilateral ventricle is usually enlarged and deformed. Pachygyria and polymicrogyria are seen in the involved hemisphere. White matter signal is of heterogeneous signal intensity on T2-weighted and FLAIR MR images, with cysts and patchy hyperintensity.
 FIGURE 2.11 Hemimegalencephaly. Coronal T2-weighted MR image shows the abnormal dysplastic-appearing left hemisphere with an abnormal gyral pattern, cortical thickening, white matter hyperintensity (asterisks), and polymicrogyria (arrows). |
Heterotopia
Gray matter heterotopia is a relatively common form of neuronal migration disorder in which collections of cortical neurons are found in an abnormal location. It results from an in utero arrest of radial migration of neurons from the germinal matrix in the wall of the lateral ventricle to the developing cerebral cortex between 6 and 16 weeks of gestation. It is usually discovered during the evaluation of children or young adults with epilepsy and children with neurodevelopmental abnormalities or as an incidental finding. The pathogenic mechanisms are not fully understood, but they lead to distinct clinicoradiologic syndromes. Based on the location of the ectopically located gray matter, various subtypes are described including band heterotopia, subcortical heterotopia, and subependymal (periventricular) heterotopia.
Band heterotopia is considered the mildest form of classic lissencephaly. It refers to a band of heterotopic gray matter located just beneath the cortex, which lends a typical “double cortex” appearance. The overlying gyral pattern is normal or demonstrates mildly simplified shallow sulci, and a normal cortical ribbon is present. Affected pediatric patients are almost exclusively female. They usually present in childhood with seizure disorders and developmental delay. On imaging studies, band heterotopia is seen as a homogenous band of gray matter between the lateral ventricles and the cerebral cortex separated from the overlying cortex and the underlying lateral ventricles by a layer of normal-appearing white matter (Fig. 2.12).
Subcortical heterotopias are malformations characterized by large, focal, mass-like collections of neurons that are found in the deep cerebral white matter anywhere from the ependyma to the cortex. The involved portion of the affected hemisphere is small, and the overlying cortex is thin with shallow sulci and may be dysplastic.
Subependymal (periventricular nodular) heterotopias are characterized by gray matter nodules lining the ventricular margins and can be divided into two main groups. The first group is characterized by a few scattered heterotopic nodules at the trigones and the temporal and occipital horns. They may be associated with other brain anomalies such as Chiari II malformation, callosal agenesis, and cerebellar hypoplasia. The second smaller group has a large number of nodules that completely or nearly completely line the walls of the lateral ventricles. This group is more likely to be familial, with X-linked and autosomal recessive patterns of inheritance. Mutations in the gene filamin-A (FLNA) at chromosome Xq28 have been identified in a subset of these patients.14
In other types of heterotopia, focal ectopic masses of gray matter occur in linear or swirling curved columns of neurons that extend through normal-appearing white matter from the
ependyma to the pia. The overlying cortex is thin, and the underlying ventricle often appears distorted. These foci follow gray matter on all sequences, do not demonstrate edema, and do not enhance, which differentiates them from glioneuronal tumors like gangliocytomas.
ependyma to the pia. The overlying cortex is thin, and the underlying ventricle often appears distorted. These foci follow gray matter on all sequences, do not demonstrate edema, and do not enhance, which differentiates them from glioneuronal tumors like gangliocytomas.
 FIGURE 2.12 Subcortical band heterotopia. Axial T2-weighted (on the left) and axial SPGR (spoiled gradient recalled) (on the right) MR images demonstrate the double cortex appearance caused by an inner band of heterotopic gray matter (white arrows) separated from the outer cortex by a thin zone of normal white matter (black arrows). |
Focal Cortical Dysplasia
Focal cortical dysplasia (FCD) is one of the more common MCDs. It is the most common cause of medically refractory epilepsy in the pediatric population. The most recent classification of FCDs proposed by the International League Against Epilepsy describes three types15.
FCD type I includes abnormalities of cortical lamination (type Ia), abnormal tangential cortical lamination (type Ib), and abnormal radial lamination (type Ic). FCD type II includes abnormal cortical dyslamination and dysmorphic neurons without balloon cells (type IIa) and with balloon cells (type IIb). FCD type III describes those with an associated lesion. The associated lesion can be hippocampal sclerosis (type IIIa), an epilepsy-associated tumor (type IIIb), vascular malformation (type IIIc), or other lesions (type IIId).15
On high-resolution MRI, features of FCD include cortical thickening (which should ideally be confirmed in at least two planes and on two different imaging sequences), blurring of the junction between the white matter and the cortex, T2 and FLAIR hyperintensity in the cortex and adjacent subcortical white matter, T1 shortening in the cortex, and abnormal sulcal/gyral pattern.
In practice, it may be possible to distinguish between type I and type II dysplasias.16 MRI is able to show abnormalities in the majority of type II dysplasias but only in some of the type I cortical dysplasias. The typical appearance of FCD type IIb (with balloon cells) is a band of hyperintensity on T2-weighted and FLAIR MR images extending from the gray and white matter interface to the surface of the ventricles (Fig. 2.13). In order to visualize this often subtle finding optimally, multiplanar thin-section images should be performed. On modern 3-Tesla MR scanners, a three-dimensional FLAIR sequence with reformats is an excellent method for visualizing these malformations.
Clinical symptoms are more severe in the type II cortical dysplasia usually seen in children. In this type, abnormalities may be seen outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with an additional lesion such as hippocampal sclerosis, tumor, vascular malformation, or pathology acquired during early life.
A complete resection of the epileptogenic zone is required for seizure freedom, or at least seizure control with medications. High-resolution MRI is helpful in identifying those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However,
the abnormalities may also involve eloquent areas, and resection may not be an option in these cases. Therefore, other diagnostic imaging techniques such as FDG-PET, magnetoencephalography (MEG), DTI, and intracranial electroencephalography (EEG) are widely used to establish the diagnosis and plan management.
the abnormalities may also involve eloquent areas, and resection may not be an option in these cases. Therefore, other diagnostic imaging techniques such as FDG-PET, magnetoencephalography (MEG), DTI, and intracranial electroencephalography (EEG) are widely used to establish the diagnosis and plan management.
 FIGURE 2.13 Focal cortical dysplasia type IIb. Coronal T2-weighted MR image shows a band of hyperintensity (arrows) extending from the gray and white matter interface to the surface of the ventricles in the right frontal lobe. |
Commissural, Midline, and Septal Anomalies
Corpus Callosum Anomalies (Complete and Partial Agenesis). Agenesis of the corpus callosum (ACC) is a relatively frequent malformation. If the normal developmental process of the corpus callosum is disturbed, it may be completely absent (agenesis) or partially formed (hypogenesis).17 Two types of ACC can be distinguished morphologically: type 1 ACC, in which axons are present but are unable to cross the midline, forming large aberrant longitudinal fiber bundles (Probst bundles) (Figs. 2.14 and 2.15); and the less common type 2 ACC, in which axons fail to form (no Probst bundles).
Callosal dysgenesis is defined as malformation of the corpus callosum as a result of an injury during the formation of its precursors, rather than from an injury to the corpus itself.17 This failure may result from extrinsic causes (lipoma, interhemispheric cyst, etc.), from disorders in neuronal migration, or an intracortical disposition linked with a gyral anomaly. Formation of most of the cerebrum and cerebellum occurs at the same time as that of the corpus callosum, between 8 and 20 weeks of gestational age. Therefore, callosal anomalies are often associated with other anomalies in the cerebrum and cerebellum, including holoprosencephaly (HPE), encephalocele, and posterior fossa anomalies. HPE shows a spectrum of callosal anomalies from agenesis to the dysgenesis associated with lobar types. This entity is discussed in the next section of this chapter.
 FIGURE 2.14 Agenesis of the corpus callosum. Axial T2-weighted (on the left) and sagittal MPRAGE (magnetization-prepared rapid acquisition gradient-echo) (on the right) MR images show the parallel orientation of the lateral ventricles (arrows) in the axial plane and absence of the corpus callosum in its expected position (asterisk) in the sagittal plane. |
Interhemispheric cysts are classified into various types based on morphology and clinical features. Loculated cyst without ventricular communication, known as a type II cyst, is associated more commonly with brain anomalies, including those of the corpus callosum. Intracranial lipomas are congenital malformations resulting from abnormal, persistent maldifferentiation of the formal primordium of the meninges during subarachnoid cistern development. They are associated with up to 40% to 50% of callosal anomalies. Lipomas are most common in the pericallosal area. Anterior pericallosal lipomas are associated with more severe corpus callosal anomalies than posterior pericallosal lipomas.
 FIGURE 2.15 Agenesis of the corpus callosum. Coronal section at the level of the basal ganglia shows an absent corpus callosum (arrow) in an 11-month-old boy with Vici syndrome, which is also called immunodeficiency with cleft lip/palate, cataract, hypopigmentation, and absent corpus callosum. |
 FIGURE 2.16 Lobar holoprosencephaly in an infant girl. Coronal T2-weighted MR image (on the left) and cut surface of the brain (on the right) show fusion of the cortex across the midline (black arrows), absent fornices and septum pellucidum (asterisks), and a thin corpus callosum (white arrows). |
Holoprosencephaly. HPE is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 fetuses.18 Three subtypes, in order of increasing severity, are described: lobar (Fig. 2.16), semilobar, and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant or syntelencephaly is also described.
Facial anomalies are seen in a proportion of patients with alobar or semilobar HPE, such as cyclopia, proboscis, median or bilateral cleft lip/palate, hypotelorism, or solitary median maxillary central incisor in minor forms. These midline defects can occur without the cerebral malformations. Clinical features include developmental delay, feeding difficulties, seizures, and an inability to maintain temperature, heart rate, and respiration. Endocrine disorders including diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia, and growth hormone deficiency are frequent. A number of genes have been implicated in HPE. Gene sequencing and allele quantification are currently available for the four main genes SHH, ZIC2, SIX3, and TGIF.19
Prenatal diagnosis is based on US and MRI rather than on molecular diagnosis. Treatment is symptomatic and supportive and requires a multidisciplinary management. Outcome depends on the severity of HPE and the medical and neurologic complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and live a normal life.
Septooptic (Pituitary) Dysplasia. Septooptic dysplasia (SOD) is a syndrome characterized by an absence of the septum pellucidum, optic nerve hypoplasia, and varying degrees of pituitary gland dysfunction. In order to avoid emphasis on the absence of the septum and optic nerve hypoplasia, the term septooptic pituitary dysplasia is currently preferred. Only ˜30% of SOD cases have complete manifestations, 62% have the complication of hypopituitarism, and 60% have an absent septum pellucidum.20 The incidence of SOD is 1 in 10,000 live births.21 SOD can be caused by mutations in HESX1 and SOX2. A genetic diagnosis can currently be made in only <1% of the patients.22 Affected pediatric patients present with a variety of symptoms including developmental delay, seizures, visual impairment, sleep disturbance, precocious puberty, obesity, anosmia, sensorineural hearing loss, and cardiac anomalies.
MRI findings vary among affected pediatric patients. However, classically, MRI shows hypoplastic optic nerves (unilateral or bilateral) and optic chiasm, partial or complete septum pellucidum agenesis, corpus callosal agenesis or hypogenesis, ectopic or absent posterior pituitary bright spot, and varying degrees of anterior pituitary hypoplasia (Fig. 2.17). Associated lesions to be looked for include schizencephaly and cortical malformations, which can be seen in a substantial proportion of affected patients.
Treatment includes regular ongoing follow-up by a multidisciplinary team, including optimal hormonal replacement for any hormonal insufficiencies, regular ophthalmologic follow-up, and neurodevelopmental support. Close monitoring should be instituted to assess for other associated features such as autism and obesity.
Infratentorial Anomalies
Cerebellar Aplasia, Dysplasia, or Hypoplasia
Cerebellar hypoplasia represents a spectrum of abnormalities ranging from a virtually empty posterior fossa (i.e., cerebellar aplasia) to milder variants with a small hypoplastic
cerebellum (i.e., cerebellar hypoplasia). In the severe variant, both hemispheres and vermis are almost completely absent. The brainstem, particularly the pons, is hypoplastic.
cerebellum (i.e., cerebellar hypoplasia). In the severe variant, both hemispheres and vermis are almost completely absent. The brainstem, particularly the pons, is hypoplastic.
 FIGURE 2.17 Septooptic dysplasia. Axial T2-weighted (on the left) and sagittal T1-weighted (on the right) MR images show absent septum pellucidum (asterisk), ectopic posterior pituitary bright spot (black arrow), and hypoplastic optic chiasm (white arrow). |
Other unclassified focal or diffuse dysplasias involve the cerebellar hemispheres and/or vermis. They demonstrate asymmetry or focal disruption of cerebellar folia and sulcal morphology. On MRI, a dysmorphic appearance to the cerebellum is seen, with enlarged, vertically oriented fissures or clefts, disordered foliation, abnormal white matter arborization, malformed cortical lining, gray matter heterotopias, and small cyst-like areas in the white matter (Fig. 2.18). It is important to define the difference between cerebellar hypoplasia and atrophy. Cerebellar hypoplasia refers to a congenitally small cerebellum with normal-sized fissures compared
to the folia and is usually associated with hypoplasia of the pons. In contrast, cerebellar atrophy refers to a small cerebellum with prominent cerebellar fissures or evidence of progressive volume loss shown on serial imaging.
to the folia and is usually associated with hypoplasia of the pons. In contrast, cerebellar atrophy refers to a small cerebellum with prominent cerebellar fissures or evidence of progressive volume loss shown on serial imaging.
 FIGURE 2.18 Cerebellar hypoplasia. Coronal (on the left) and axial (on the right) T2-weighted MR images demonstrate marked right cerebellar hypoplasia, with milder hypoplasia of the left cerebellar hemisphere (asterisks) and small inferior vermis with a small flattened pons (arrow). Note the abnormal cortical outline in the hypoplastic cerebellar hemispheres. |
 FIGURE 2.19 Dandy-Walker malformation in a 2-year-old infant boy with severe hydrocephalus. Axial (on the left) and sagittal (on the right) T2-weighted MR images show a markedly enlarged CSF-filled posterior fossa, which communicates with an enlarged fourth ventricle (4V), upward rotated hypoplastic vermis (white straight arrow), high tentorium, hypoplastic brainstem (curved arrow), and elevation of the confluence of the venous sinuses (asterisk). |
Dandy-Walker Malformations
Dandy-Walker malformation is a rare congenital malformation characterized by aplasia or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa (Fig. 2.19). A large number of concomitant problems may be present, but Dandy-Walker malformation is recognized whenever these three features are found. Approximately 70% to 90% of affected pediatric patients have hydrocephalus, which often develops postnatally. Dandy-Walker malformation may be associated with atresia of the foramen of Magendie and, possibly, the foramina of Luschka.
Rhombencephalosynapsis
Rhombencephalosynapsis is a rare midline brain malformation characterized by absence of the cerebellar vermis and apparent fusion of the cerebellar hemispheres. The degree of fusion is variable and ranges from partial absence of the nodulus and anterior and posterior vermis in the mild type to complete absence of the vermis on the severe end of the spectrum. Continuity of the cerebellar hemispheres across the midline dorsally is typical.
On MRI, sagittal images show an upwardly convex fastigial recess of the fourth ventricle and absence of the normal midline foliar pattern of the vermis. On coronal MR images, transverse folia are seen with continuity of the cerebellar white matter across the midline (Fig. 2.20). Absence of the vermis is best seen in the axial plane. Aqueductal stenosis and hydrocephalus are common. Partial or complete fusion of the
thalami, fornices, and tectum may be present. Other midline and forebrain anomalies including absent cavum septum pellucidum, absent olfactory bulbs, and corpus callosum dysgenesis can be also seen.
thalami, fornices, and tectum may be present. Other midline and forebrain anomalies including absent cavum septum pellucidum, absent olfactory bulbs, and corpus callosum dysgenesis can be also seen.
 FIGURE 2.20 Rhombencephalosynapsis. Coronal T2-weighted MR image shows apparent fusion of the cerebellar hemispheres with transversely oriented folia and continuity (arrows) of the cerebellar white matter across the midline. |
Chiari Malformations
The Chiari malformations are a group of defects associated with congenital caudal “displacement” of the cerebellum and brainstem. Initial descriptions were based on autopsy observations. Three types were described, with a fourth added later. Types II and III are likely to be related to each other.
Chiari I Malformation
Chiari I malformation is the most common type. It is characterized by a peg-like configuration of the cerebellar tonsils, which are displaced into the upper cervical canal through the foramen magnum (Fig. 2.21). Traditionally, the cerebellar tonsillar tips are considered low-lying if they measure at least 5 mm below the foramen magnum. However, recent studies have shown that reliance on a single measurement does not define the malformation or correlate with symptomatology. It is now thought that describing the configuration of the cerebellar tonsils (rounded or peg-like), the amount of CSF around them, the degree of crowding at the foramen magnum, and the configuration of the dens (angled posteriorly or not) is important to define Chiari type I malformations and avoid overdiagnosis. CSF flow studies utilizing cine phase contrast images have been shown to have some value in the assessment of these patients. Many pediatric patients diagnosed with this condition are asymptomatic. When symptoms do occur, affected pediatric patients present with headaches (commonly occipital in location and accentuated by bending forward), neck pain, sleep apnea, and balance problems.
 FIGURE 2.21 Chiari I malformation. Sagittal T1-weighted MR image shows pointed cerebellar tonsils (arrow) extending inferiorly to the mid C2 level, with resultant effacement of the CSF spaces at the level of the foramen magnum and associated kinking (asterisk) of the cervicomedullary junction. |
The upper cervical cord should be examined closely for evidence of syringomyelia or presyrinx (potentially reversible edema within the cord caused by alteration in CSF flow dynamics caused by obstruction to CSF flow at the foramen magnum). MRI characteristics of the presyrinx include T2 prolongation, subtle T1 prolongation, and cord expansion without frank cavitation.
Chiari II Malformation
Chiari II malformation is characterized by herniation of the vermis through the foramen magnum, a smooth cerebellar vermis, small brainstem, beaked tectum (due to collicular fusion), absent fourth ventricle, small cerebellum, and crowded posterior fossa (Fig. 2.22). It is almost invariably associated with a lumbosacral spinal myelomeningocele. Approximately two-thirds of affected pediatric patients display a medullary “kink” dorsal to the upper cervical spinal cord, which has been associated with a more symptomatic clinical course. Other features seen on imaging include large massa intermedia, cortical abnormalities including gray matter heterotopia, callosal hypogenesis, and colpocephaly.23 Interdigitation of the cerebral gyri across the midline is another commonly seen finding. Skull malformations including enlargement of the foramen magnum, scalloping of the petrous pyramid, Luckenschadel, or lacunar skull (round-, oval-, or finger-shaped pits on the inner surface of the membranous part of the skull vault, separated by ridges of bone), and clival shortening are noted on CT performed in these patients.
Given that CM II is associated in almost all cases with myelomeningocele, the initial presenting symptom is an open neural tube defect. A symptomatic CM II is the most common cause of death in patients with myelomeningocele <2 years of age. Around one-third of affected pediatric patients with CM II develop signs and symptoms of brainstem compression by the age of 5 years, and more than one-third of these patients do not survive.
The first consideration in evaluating symptomatic CM II is the degree of hydrocephalus and the shunt, if present. Untreated hydrocephalus or a malfunctioning shunt may increase the intracranial pressure with subsequent downward herniation of an already caudally displaced brainstem and vermis. It is imperative to ensure that the shunt catheter is working optimally and any untreated hydrocephalus is appropriately managed.
Affected pediatric patients younger than the age of 2 years present most frequently with cranial nerve and brainstem signs and must be evaluated urgently, because a symptomatic CM II in these patients can be a neurosurgical emergency. Respiratory difficulties with or without inspiratory stridor are signs of brainstem dysfunction and should prompt
urgent evaluation. Vocal cord abduction, paresis, or paralysis resulting from dysfunction of the vagus nerve causes the inspiratory stridor. Cranial nerve dysfunction is attributed to various causes including caudal traction on the nerve by the herniated medulla/medullary kink, lower brainstem compression, or an abnormally formed dorsal motor nucleus within the brainstem.
urgent evaluation. Vocal cord abduction, paresis, or paralysis resulting from dysfunction of the vagus nerve causes the inspiratory stridor. Cranial nerve dysfunction is attributed to various causes including caudal traction on the nerve by the herniated medulla/medullary kink, lower brainstem compression, or an abnormally formed dorsal motor nucleus within the brainstem.
 FIGURE 2.22 Chiari II malformation. Axial (on the left) and sagittal (on the right) T2-weighted MR images show a small posterior fossa, herniation of the cerebellar tonsils (curved arrow) to the C4 level with mild kinking of the cervicomedullary junction, tectal beaking (black arrows), and associated subependymal gray matter heterotopia (white arrows). |
Chiari III Malformation
Chiari III malformation is characterized by features similar to Chiari II, but with an occipital and/or high cervical encephalocele (Fig. 2.23).
Chiari IV Malformation
Chiari IV malformation refers to a constellation of findings including marked cerebellar hypoplasia without displacement of the cerebellum through the foramen magnum. It is considered as a possible variation of cerebellar hypoplasia.
Mesenchymal Origin Anomalies
Cephaloceles (Encephalocele, Meningocele, and Related Malformations)
A cephalocele is defined as an outward protrusion of the intracranial contents through an osseous defect in the cranial vault or skull base (Fig. 2.24). Cephaloceles can be either congenital or acquired lesions and can be open or skin covered. The most common cephaloceles are named according to their location: occipital, parietal, or frontoethmoidal/frontonasal (at the skull base).
Cephaloceles can be subdivided based upon the contents of the lesion into meningoencephaloceles (containing brain tissue, meninges, and CSF), meningoceles (meninges and CSF, but without brain tissue), glioceles (glia-lined outpouching
containing only CSF), and atretic cephaloceles (containing dura, fibrous tissue, and degenerated brain tissue).
containing only CSF), and atretic cephaloceles (containing dura, fibrous tissue, and degenerated brain tissue).
 FIGURE 2.23 Chiari III malformation. Sagittal T1-weighted MR image demonstrates an occipital encephalocele (black arrow), which spontaneously decompressed partially after spinal fusion, low lying cerebellar tonsils (asterisk), and thinned posterior half of corpus callosum (white arrow). |
 FIGURE 2.24 Frontoethmoidal encephalocele. Axial T2-weighted MR (on the left), sagittal T1-weighted MR (in the center), and 3D reconstructed CT (on the right) images show a large frontoethmoidal cephalocele (arrows) containing dysplastic brain tissue, associated agenesis of corpus callosum, marked hypertelorism, abnormal nose, and cleft palate and lip. |
The role of imaging is to define the osseous defect, delineate the contents, map out the vascular structures within the cephalocele, and assess any coexisting intracranial anomalies. The brain parenchyma within a congenital cephalocele is often abnormal. It is important to recognize that affected pediatric patients may also have extracranial abnormalities such as cleft lip and palate, cardiac abnormalities, and chromosomal anomalies (e.g., trisomies 13 and 18).
Intracranial Lipomas
Intracranial lipomas are rare congenital malformations of the brain parenchyma that are thought to arise from abnormal persistence and maldifferentiation of the meninx primitiva during the development of the subarachnoid cisterns. They are usually found incidentally. They are located most commonly in the pericallosal cistern and are associated with other parenchymal or brain vascular malformations in up to half of cases. Callosal dysgenesis is commonly associated with pericallosal lipomas.
They are usually asymptomatic, but have been associated with seizures (20% to 30%), headaches (25%), and raised intracranial pressure.24,25 The reported increased incidence of epilepsy in patients with intracranial lipomas may be related to higher incidence of associated intracranial abnormalities and malformations compared with the general population.
Intracranial lipomas have a characteristic appearance on unenhanced CT, with low attenuation values (between −39 Hounsfield Units [HU] and −80 HU) (Fig. 2.25). Calcifications are seen commonly in midline interhemispheric lipomas. On MRI, intracranial lipomas are characterized by T1 hyperintensity and intermediate signal on T2-weighted spin-echo sequences, which nulls on fat-saturated MR images.
Histologically, intracranial lipomas consist of mature adipose tissue. Management is usually conservative and surgical treatment is very rarely needed.
Intracranial Cysts
Primary intracranial cysts are usually benign disorders of development. They may also develop secondarily as a complication of surgery, trauma, or infection. They are often seen as incidental findings on neuroimaging studies, but may occasionally cause focal neurologic deficits. Hemorrhage into the cystic lesions may result in a sudden increase in size and cause obstructive hydrocephalus.
The three most common intracranial cysts are arachnoid cysts, neuroepithelial cysts, and leptomeningeal cysts.
Arachnoid cysts and neuroepithelial cysts are discussed in the following section. The information regarding leptomeningeal cysts is included in Chapter 1 of this book.
Arachnoid cysts and neuroepithelial cysts are discussed in the following section. The information regarding leptomeningeal cysts is included in Chapter 1 of this book.
 FIGURE 2.25 Corpus callosum lipoma. Sagittal reformatted CT image shows a low attenuation (-50 HU) lesion (straight arrows) in the midline in the pericallosal cistern with a small amount of calcification (curved arrow) along its posterior aspect near the splenium, consistent with a callosal lipoma. |
Arachnoid Cysts
Arachnoid cysts are benign, fluid-filled lesions located between the dura and the pia mater and lined by a thin layer of the arachnoid membrane. The fluid within arachnoid cysts resembles CSF. These lesions are therefore similar to CSF on all imaging modalities. US demonstrates an anechoic or hypoechoic lesion with well-defined margins and smooth borders. On CT, these lesions are isodense to CSF and may be associated with remodeling and resultant scalloping of the inner surface of adjacent calvarium. MRI is the ideal imaging modality to define the lesion and identify any septations within the lesion. FLAIR MR images may demonstrate a rim of high signal around the lesion, which represents gliosis in the white matter. Suprasellar arachnoid cysts can be challenging to diagnose, especially on CT. Thin-section T2-weighted MR images can be very helpful in defining the thin walls of arachnoid cysts (Fig. 2.26).
The main differential diagnosis is an epidermoid cyst, which characteristically shows decreased diffusion, whereas an arachnoid cyst does not. It is also important to differentiate arachnoid cysts from cephaloceles and a careful evaluation of the surrounding dural and bony outlines should be made, particularly in cases of lesions close to the skull base.
 FIGURE 2.26 Arachnoid cyst in a 3-year-old boy with multiple sulfatase deficiency. Coronal T2-weighted MR image (on the left) and postmortem brain specimen (on the right) show a CSF signal intensity thin-walled translucent cyst (black and white arrows) overlying the left inferior surface of the cerebellum, with associated cerebellar asymmetry. Note the abnormal diffuse white matter signal intensity (asterisks) and volume loss in the supratentorial brain on MR image, which is a manifestation of the underlying metabolic disease. |
Neuroepithelial Cysts
Neuroepithelial cysts are benign, fluid-filled cysts lined by a single layer of cells resembling ependymal cells that occur in various sites within the brain. They are named based on their location as choroid plexus cysts, intraventricular ependymal cysts, and choroid fissure cysts. They are usually seen as incidental findings on imaging studies and do not cause clinical symptoms. Diagnosis is based on characteristic location and signal intensity that resembles CSF (Fig. 2.27).
Infectious Disorders
Congenital Infections (TORCH)
TORCH (toxoplasmosis, other, rubella, cytomegalovirus (CMV), and herpes) infections result from the transfer of infection to the fetus via the placenta or the birth canal. Congenital malformations result from insults in the first two trimesters, and destructive lesions occur when the infection is transmitted in the third trimester.
Toxoplasmosis
Congenital toxoplasmosis is rare compared to CMV. Hydrocephalus, chorioretinitis, and intracranial calcifications are common presenting features. Infection acquired in early gestation (<20 weeks) causes severe neurologic impairment. Findings seen on imaging studies include intracerebral and periventricular calcifications, with hydrocephalus in some cases (Fig. 2.28).
 FIGURE 2.27 Neuroepithelial cyst incidentally found in a 10-year-old boy. Axial FLAIR MR image (on the left) and coronal postcontrast T1-weighted SPACE (Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) MR image (on the right) show a cystic CSF signal intensity lesion (arrows) in the cerebellum closely related to the margins of the fourth ventricle. |
 FIGURE 2.28 Congenital toxoplasmosis in an 11-month-old boy. Coronal reformatted unenhanced CT image (on the left) shows multiple foci of intraparenchymal and subependymal calcification. The child also had hydrocephalus (asterisk), which had been shunted by this time. Axial unenhanced CT image (on the right) shows a right frontal shunt catheter (arrow) and hydrocephalus (asterisk). |
Other Infections
This category includes a number of organisms that cause congenital infections including Coxsackie virus, varicella (chickenpox), parvovirus B19, chlamydia, HIV, Zika virus, human T-lymphotropic virus, and syphilis. They are relatively less common in the United States and their manifestations are summarized in Table 2.3.
Congenital Rubella
Congenital rubella is rare in the United States. However, during the critical first 12 weeks of pregnancy, the fetal infection rate can be as high as 80%. Features of congenital rubella include congenital heart disease in more than half, deafness in approximately half because of damage to the organ of Corti, and ocular abnormalities such as cataracts in ˜40%.26,27 Further, ˜40% of survivors have developmental delay.28 Some cases of autism have been linked to rubella infection. Neurologic symptoms are related to viral invasion and replication in brain tissue. Rubella appears to have an antimitotic effect on brain cell multiplication with microcephaly being a common outcome of fetal infection. The main brain tissue cell types infected with in utero rubella virus are the astrocyte and, occasionally, the neuron.
TABLE 2.3 Other Congenital TORCH Infections | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Rubella virus preferentially involves the placental and fetal vascular endothelia. Abnormalities of the cerebral vascular system are present on pathologic specimens in more than half of cases. Focal destruction of the vascular walls, with thickening and proliferation, results in luminal narrowing. Imaging findings in survivors include mineralizing microangiopathy with arterial occlusion and stroke. Follow-up studies demonstrate hydranencephaly, microcephaly, cerebellar atrophy, and cerebral parenchymal calcification. Brain ultrasound in neonates with congenital rubella shows a “branched candlestick” appearance of the vessels.
Cytomegalovirus
Of the TORCH infections, CMV is the most common serious viral infection to affect newborns, occurring in nearly 1% of all live births in the United States.29 The usual route of fetal infection is transplacental, occurring during a primary infection of the mother. Fetal infection results in up to 40% of cases of maternal primary infection.30 Gestational age at time of infection has little correlation with rate of transmission or severity of disease expression. Of note, maternal antibodies, which protect the fetus in rubella and toxoplasmosis, do not
prevent fetal transmission of the CMV virus, but do play a role in reducing severity of disease. Most infants have silent infections following recurrent rather than primary maternal infection. CMV is considered the leading infectious cause of sensorineural hearing loss in the post-rubella vaccination era. Sensorineural hearing loss occurs in around 10% of infected neonates.30 Additional clinical manifestations in affected infants include microcephaly, chorioretinitis, and seizures.
prevent fetal transmission of the CMV virus, but do play a role in reducing severity of disease. Most infants have silent infections following recurrent rather than primary maternal infection. CMV is considered the leading infectious cause of sensorineural hearing loss in the post-rubella vaccination era. Sensorineural hearing loss occurs in around 10% of infected neonates.30 Additional clinical manifestations in affected infants include microcephaly, chorioretinitis, and seizures.
Prenatal imaging evaluations may show evidence of atrophy including ex vacuo ventricular dilatation and prominent CSF spaces. Periventricular calcification and subependymal cysts are seen on pre- and postnatal imaging studies. “Ringlike” areas of periventricular lucency have been shown to precede the development of subependymal calcification and are felt to represent foci of subependymal degeneration and inflammation. Subsequent glial scarring and dystrophic calcification occur. Increased echogenicity of the thalamostriate arteries has been described on cranial sonography in the presence of congenital CMV, but this feature is not specific. Periventricular and basal ganglia calcifications are the most common finding on US (Fig. 2.29) or CT performed in the neonatal period and correlate with a poor neurodevelopmental outcome.
On MRI, periventricular foci of signal abnormality can be difficult to differentiate from hemorrhage. Other features of congenital CMV infection on MRI include lissencephaly with a thinned cerebral cortex, enlarged lateral ventricles, white matter volume loss, delayed myelination, and a small cerebellum. These features are thought to result from an insult to the germinal matrix and reflect infection between 16 and 18 weeks of gestation.29 Localized polymicrogyria with thickened irregular cortices (usually in a perisylvian distribution) and diminished white matter indicates infection late during the phases of neuronal migration or organization between 18 and 24 weeks of gestation (Fig. 2.30). Normal gyral pattern with abnormal white matter hyperintensity indicates infection in the third trimester. However, it should be noted that it is not always possible to predict the pattern of brain abnormality based on the timing of the maternal infection.
 FIGURE 2.29 Congenital cytomegalovirus infection in a 2-day-old boy. Parasagittal ultrasound image shows areas of increased echogenicity consistent with periventricular calcifications (arrows). |
 FIGURE 2.30 Congenital cytomegalovirus (CMV) infection. Axial T2-weighted MR image shows extensive frontal polymicrogyria (white arrows) and subcortical heterotopia (black arrows) as a manifestation of congenital CMV. |
Herpes Simplex Virus
Neonatal herpes simplex virus 2 (HSV2) occurs usually from transvaginal transmission during passage through the birth canal. Presenting features of HSV2 meningoencephalitis in infants in the first month of life include seizures, lethargy, and fever. It should be noted that HSV1 encephalitis, which affects older children and adults, is different from neonatal herpes infection.
CT in early disease is either normal or demonstrates subtle areas of low attenuation. MRI shows decreased diffusion resulting from infarction in multiple areas and evidence of necrosis, atrophy, encephalomalacia, demyelination, and gliosis (Fig. 2.31). Decreased diffusion may be seen within the brain, predominantly involving the temporal lobes, brainstem, or cerebellum. Later, patchy T2 prolongation may be seen in the white matter, which becomes more pronounced, as the disease progresses. Enhancement of the leptomeninges can demonstrate the disease extent. Increased areas of density in the cerebral cortex are seen on CT, with corresponding T1 and T2 shortening on MRI. Sequela of HSV2 infection includes mental retardation, severe neurologic deficits, or even death secondary to virulent destruction of the brain. Follow-up imaging studies show evidence of encephalomalacia and atrophy of the cerebral parenchyma and cerebellum.
 FIGURE 2.31 Neonatal herpes encephalitis in a 12-day-old girl. Axial diffusion-weighted MR images show increased signal (indicating decreased diffusion [arrows]) in the periventricular and deep frontal white matter (on the left), corona radiata, basal ganglia, and internal capsule (on the right). |
Acquired Infections
Viral Meningitis and Meningoencephalitis
In an immunocompetent child, HSV type 1 is the most common cause of viral encephalitis. Other viruses such as Epstein-Barr virus, influenza viruses, West Nile virus, and Eastern equine encephalitis have emerged as causative viruses in the pediatric population in the United States in recent years. The list of causative viruses is longer in the immunocompromised child.
MRI is the imaging modality of choice in pediatric patients with suspected encephalitis. In the older child with herpes encephalitis, signal abnormalities resulting edema, hemorrhage, and necrosis are seen primarily in the inferomedial temporal lobes (Fig. 2.32). When findings are bilateral, they are usually asymmetric. Signal changes may also be seen in the limbic system, insular cortex, cingulate gyrus, basal ganglia, and parietooccipital cortex. Small petechial foci of hemorrhage are typically seen in HSE in older children. Diffusion-weighted MR images show evidence of cytotoxic edema that resolves over the next 10 to 14 days.31 Follow-up studies may demonstrate atrophy or ventricular enlargement.29
Bacterial Infections
Bacterial Meningitis and Meningoencephalitis
Meningitis refers to inflammation of the subarachnoid space and leptomeninges surrounding the brain and spinal cord (arachnoid mater and pia mater). Most cases of meningitis have an infective etiology. The causative organisms are specific to particular age groups, seasonality, geography, and underlying host factors. After the introduction of the Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the infant immunization schedule, the incidence of bacterial meningitis declined in all age groups except children younger than 2 months. The peak incidence continues to occur in children younger than 2 months. Group B streptococcus remains the predominant bacterial pathogen in the neonatal population. Streptococcus pneumoniae and Neisseria meningitidis remain relatively common pathogens in older children and adolescents.
Acute bacterial meningitis has two patterns of presentation. In the first type, meningitis develops progressively over one or several days and may be preceded by a febrile illness. The second type is characterized by an acute and fulminant course, with manifestations of sepsis and meningitis developing rapidly over several hours. The rapidly progressive form is frequently associated with severe brain edema.
The primary role of imaging studies in pediatric patients with bacterial meningitis is identifying and monitoring complications including cerebritis, abscess formation, infarcts, subdural empyema, and epidural abscess. The role of a CT at presentation in pediatric patients with suspected bacterial meningitis needs some clarification. Although there may be a role for CT to exclude contraindications for lumbar
puncture, it is important to recognize that normal CT findings may not be sufficient to indicate normal intracranial pressure in pediatric patients with bacterial meningitis. Review of the literature indicates that herniation is unlikely in children with bacterial meningitis unless they have focal neurologic findings or coma.32 In addition, the results of an imaging study do not exclude or prove the presence of acute meningitis. Diagnosis should therefore be made based on clinical history, examination findings, and results of laboratory tests.
puncture, it is important to recognize that normal CT findings may not be sufficient to indicate normal intracranial pressure in pediatric patients with bacterial meningitis. Review of the literature indicates that herniation is unlikely in children with bacterial meningitis unless they have focal neurologic findings or coma.32 In addition, the results of an imaging study do not exclude or prove the presence of acute meningitis. Diagnosis should therefore be made based on clinical history, examination findings, and results of laboratory tests.
 FIGURE 2.32 Herpes simplex virus encephalitis in a 9-year-old girl. Axial FLAIR MR image (on the left) and axial diffusion-weighted MR image (on the right) demonstrate signal abnormality in the left thalamus (black arrow) and diffusion restriction in the left hippocampus (white arrow). The distribution of findings is most suggestive of herpes encephalitis, which was proven by polymerase chain reaction analysis of CSF. |
CT findings are often normal in the early phase of meningitis. Leptomeningeal enhancement may be seen on contrast administration, a finding that is more pronounced in the later stages of the disease. Imaging studies can help in identifying causes of meningitis. For instance, CT can help identify skull fractures and infections within the paranasal sinuses, mastoid air cells, and the petrous temporal bone, which can spread by direct extension into the brain. Dermal sinus tracts may be the primary source of infection affecting the meninges, leading to intracranial complications (Fig. 2.33).
The diagnostic value of MRI in uncomplicated bacterial meningitis is also low. Findings include leptomeningeal FLAIR hyperintensity and enhancement as well as subarachnoid space distention with widening of the interhemispheric fissure in early meningitis. However, the absence of leptomeningeal enhancement on MRI does not exclude the diagnosis of meningitis. Diffusion-weighted MR images should be utilized, as presence of decreased diffusion can help characterize the fluid within extra-axial collections, differentiate between vasogenic and cytotoxic edema, and reveal early cerebritis and small abscess cavities. The presence of T1 and FLAIR hyperintensity within the sulci suggests protein or pus accumulation.33
Tuberculous Infection
Although relatively uncommon in the United States, tuberculous meningitis remains an important cause of morbidity and mortality in children around the world. The pandemic of acquired immunodeficiency syndrome has resulted in an increased incidence of central nervous system tuberculosis worldwide. Infection may occur by either hematogenous seeding of the meninges or release of the organism into the meningeal space. This results in a severe granulomatous inflammatory reaction within the basal cisterns, which can lead to death (if untreated) in a few weeks.
Tuberculomas are space-occupying masses of granulomatous tissue, which form a large percentage of intracranial mass lesions in developing countries. They are single or multiple and can be formed within the meninges, at the gray-white junction, and in the spinal cord, or rarely, in the choroid plexus. Children develop infratentorial tuberculomas
more commonly than adults. Organisms from these foci are released into the subarachnoid space causing meningitis. Meningitis is typically most severe in the basal cisterns and leads to secondary complications, including multiple cranial nerve palsies, vasculitis of the lenticulostriate and thalamoperforating vessels resulting in secondary infarction of the basal ganglia, and hydrocephalus secondary to blockage of the fourth ventricular outlet foramina. It is important to note that hydrocephalus in patients with tuberculous meningitis may need to be treated surgically. This can be determined with an emergent CT at presentation, followed by MRI later.34 Imaging using diffusion-weighted MRI is important to document the presence of infarcts, which correlates with poor outcome. In particular, bilateral basal ganglia infarcts have a poor prognosis. Border zone necrosis seen in these patients needs to be differentiated from necrosis in older children with herpes, which is most often seen at the insular cortex.35
more commonly than adults. Organisms from these foci are released into the subarachnoid space causing meningitis. Meningitis is typically most severe in the basal cisterns and leads to secondary complications, including multiple cranial nerve palsies, vasculitis of the lenticulostriate and thalamoperforating vessels resulting in secondary infarction of the basal ganglia, and hydrocephalus secondary to blockage of the fourth ventricular outlet foramina. It is important to note that hydrocephalus in patients with tuberculous meningitis may need to be treated surgically. This can be determined with an emergent CT at presentation, followed by MRI later.34 Imaging using diffusion-weighted MRI is important to document the presence of infarcts, which correlates with poor outcome. In particular, bilateral basal ganglia infarcts have a poor prognosis. Border zone necrosis seen in these patients needs to be differentiated from necrosis in older children with herpes, which is most often seen at the insular cortex.35
 FIGURE 2.33 Recurrent meningitis in a 3-year-old girl. Axial CT image (on the left) shows posterior fossa dermoid (white arrow). A tract (black arrow) passing through occipital bone on to the overlying scalp is also seen (in the middle). This was not noticed at the time of the CT study, and at a subsequent presentation, axial postcontrast T1-weighted MR image (on the right) shows infected material within the dermoid (curved arrow) and an adjacent abscess (A) in the cerebellar hemispheres. |
 FIGURE 2.34 Tuberculous meningitis and meningoencephalitis in a 17-year-old girl. Axial and coronal postcontrast T1-weighted MR images show abnormal linear and nodular meningeal enhancement (arrows) in the bilateral temporal lobes and basal cisterns (on the left and in the middle), and multiple foci of ring enhancement (arrows) in the right cerebellar hemisphere with surrounding encephalomalacia (on the right). |
On CT, the presence of hyperdensity within the basal cisterns indicates an exudate resulting from TB meningitis. This is considered a very specific sign for TB meningitis in children.36 During the initial stages of the disease, noncontrast MRI sequences usually show little or no evidence of meningeal abnormality. As the disease progresses, mild shortening of T1 and T2 relaxation times compared to normal CSF is seen within the affected subarachnoid spaces.36 Postcontrast T1-weighted MR images show abnormal meningeal enhancement, most marked in the basal cisterns (Fig. 2.34). The interpeduncular fossa, pontine cistern,
perimesencephalic cisterns, suprasellar cisterns, and sulci over the convexities are commonly affected.
perimesencephalic cisterns, suprasellar cisterns, and sulci over the convexities are commonly affected.
Intracranial tuberculomas appear as low- or high-density round or lobulated masses with irregular walls showing homogeneous enhancement after contrast administration on CT. They can be either solitary or multiple and are common in the frontal and parietal lobes. The imaging characteristics depend on whether the lesion is noncaseating, caseating with a solid center, or caseating with a liquid center. Edema around the lesion is inversely proportional to duration of the lesion. The presence of the “target sign,” a central nidus of calcification with a surrounding ring of enhancement, which was previously thought to be diagnostic of tuberculomas, has been subsequently shown to be nonspecific.37
On MRI, intracranial tuberculomas are characterized by hypo- or isointensity or central hyperintensity with a hypointense rim on T2-weighted MR images and isointensity and/or hypointensity on T1-weighted MR images. The appearance of a tuberculoma varies on MRI based on its stage of maturation.38 A noncaseating tuberculoma usually appears hyperintense on T2-weighted and slightly hypointense on T1-weighted MR images, with homogeneous enhancement after injection of paramagnetic contrast on T1-weighted MR images. Solid caseating tuberculomas appear relatively iso- to hypointense on both T1-weighted and T2-weighted MR images, with an iso- to hyperintense rim on T2-weighted MR images. In the presence of edema, the rim may be difficult to delineate on T2-weighted MR images. Tuberculomas may show rim enhancement on postcontrast T1-weighted MR images.
 FIGURE 2.35 Enterobacter cerebral abscess. Coronal cranial ultrasound image (on the left) shows heterogeneous left frontoparietal intraparenchymal lesions (A) with surrounding increased echogenicity and sulcal effacement, consistent with cerebral abscess. Also noted is an echogenic lesion (arrow) in the left lateral ventricle representing intraventricular pus. Subsequently obtained axial postcontrast MR image (on the right) shows a rim-enhancing lesion (asterisk) with adjacent subdural fluid collection (SFC) overlying the left frontal lobe. |
Differential diagnosis of tuberculomas includes lesions in the healing stage of neurocysticercosis, fungal granulomas, chronic pyogenic brain abscesses, metastases, and lymphoma. Sometimes, large tuberculomas mimic neoplastic lesions on MRI, as they appear predominantly hyperintense on T2-weighted MR images, with mixed intensity on T1-weighted MR images and, possibly, heterogeneous enhancement on postcontrast MR images. Quantitative magnetization transfer imaging and in vivo proton MRS have been shown to be helpful in differentiating tuberculomas from entities like cysticercosis.39
Complications of Bacterial Infections
Cerebral Abscess
Cerebral abscess is defined as a focal suppurative process within the brain parenchyma. Pediatric patients with a brain abscess often present with new-onset acute headaches or first-time seizure, with fever and focal neurologic signs on examination. The young infant or neonate with brain abscess usually presents with irritability, a bulging fontanelle, and a rapid increase in head circumference. US in this age group may be used if the child is too unwell to undergo crosssectional imaging evaluation. Cerebral abscesses are seen as heterogeneous intraparenchymal lesions with surrounding increased echogenicity and sulcal effacement (Fig. 2.35).
Ring-enhancing lesions can be seen on contrast-enhanced CT. However, MRI is the optimal imaging modality in this situation. Abscesses in the brain parenchyma are characterized by central T2 prolongation and T1 hypointensity and
demonstrate enhancement of the walls of the lesion following gadolinium-based contrast administration (Fig. 2.35). Diffusion-weighted MR imaging is helpful to differentiate between an abscess and a necrotic tumor. Therefore, it must be performed in all cases of suspected CNS infection because almost all pyogenic abscesses demonstrate decreased apparent diffusion coefficient (ADC) values, indicating decreased water diffusion compared with nonpyogenic lesions.
demonstrate enhancement of the walls of the lesion following gadolinium-based contrast administration (Fig. 2.35). Diffusion-weighted MR imaging is helpful to differentiate between an abscess and a necrotic tumor. Therefore, it must be performed in all cases of suspected CNS infection because almost all pyogenic abscesses demonstrate decreased apparent diffusion coefficient (ADC) values, indicating decreased water diffusion compared with nonpyogenic lesions.
Subdural and Epidural Empyema
Subdural empyema is a collection of pus in the subdural space, which is a naturally occurring space between the dura and arachnoid mater. It accounts for ˜15% to 25% of pyogenic intracranial infections, and most often results as a complication of head and neck infections like sinusitis, otitis media, or mastoiditis.40 Abnormal signal in the bone adjacent to empyemas should be recognized on MRI, as this is an early sign of osteomyelitis and needs a longer course of antibiotics.33
Epidural empyema is a collection of pus between the dura and the inner table of the skull. Visualization of displaced dura, indicated by a hypointense rim between the collection and brain, suggests that the collection is epidural rather than subdural. Surrounding white matter edema, mass effect, and cortical signal changes can be seen. Empyemas can be identified on CT as fluid collections that are slightly hyperdense compared to CSF; however, it is not always possible to define the exact location and nature of the collection. On MRI, empyemas are slightly hyperintense relative to CSF on T1-weighted MR images and hyperintense relative to CSF and white matter on T2-weighted MR images, with peripheral enhancement after contrast administration (Fig. 2.36). Diffusion-weighted MR imaging can help characterize extra-axial collections as empyemas, typically demonstrating restricted diffusion (Fig. 2.36).
 FIGURE 2.36 Subdural empyema as a complication of sinusitis in a 7-year-old girl. Axial postcontrast T1-weighted MR image (on the left) and axial diffusion-weighted MR image (on the right) show a rim-enhancing collection with restricted diffusion, consistent with a right frontal parafalcine subdural empyema (arrows). |
Vascular Complications
Arterial or venous infarcts may be seen on cross-sectional studies in pediatric patients with meningitis, resulting from secondary inflammation of contiguous blood vessels (Fig. 2.37). In pediatric patients with dural venous sinus thrombosis, contrast-enhanced CT venography can show filling defects within the affected sinus and may show hemorrhagic infarcts as areas of low density that do not correspond to an arterial distribution. MR venography used in conjunction with evaluation of flow voids on coronal T2-weighted MR images and postcontrast SPGR or MPRAGE images are used to diagnose dural venous sinus and cortical vein thrombus on MRI. MR angiography can be added to conventional MRI sequences to identify arterial thrombus.
Other Complications
In cases of pneumococcal meningitis, postcontrast imaging of the petrous temporal bones can help detect early labyrinthitis, indicated by enhancement within the labyrinthine structures (Fig. 2.38). In the subacute stage, CT and MRI can
detect early fibrosis within the inner ear structures and labyrinthitis ossificans33 (Fig. 2.38).
detect early fibrosis within the inner ear structures and labyrinthitis ossificans33 (Fig. 2.38).
 FIGURE 2.37 Pneumococcal meningitis in a 22-month-old girl. Axial postcontrast T1-weighted MR image (on the left) shows leptomeningeal enhancement (straight arrow) and small frontal enhancing subdural collections (curved arrow). Axial diffusion-weighted MR image (on the right) shows multiple foci of decreased diffusion (straight arrows) in the basal ganglia and frontal white matter, without corresponding enhancement on postcontrast MR images, indicating that these are infarcts secondary to meningitis. Note decreased diffusion in the bifrontal subdural empyemas (curved arrows). |
Fungal Infections
Fungal infection of the CNS is rare in the immunocompetent child. Fungal meningitis or meningoencephalitis must be considered in immunocompromised children (usually chemotherapy-related) presenting with signs of a systemic fungal infection. Manifestations of various fungal infections are summarized in Table 2.4.
 FIGURE 2.38 Labyrinthine enhancement in an 8-month-old boy with pneumococcal meningitis. Axial postcontrast T1-weighted fat-saturated MR image obtained at initial presentation (on the left) shows enhancement (arrows) within the inner ear structures bilaterally. Subsequently obtained CT 2 months later, just before cochlear implantation (on the right), shows subtle increased density (arrow) in the right lateral semicircular canal, consistent with early labyrinthitis ossificans. |
Neoplastic Disorders
Brain tumors are the most common solid tumors and are the leading cause of death from solid tumors in the pediatric population.41 The incidence of all primary brain and CNS
tumors in childhood is ˜4.5 cases per 100,000 person-years.42 In young children <3 years of age, supratentorial tumors are more common than infratentorial tumors.42 In children between 4 years and 10 years of age, infratentorial tumors occur more frequently. Supra- and infratentorial tumors occur equally after 10 years old age.42
tumors in childhood is ˜4.5 cases per 100,000 person-years.42 In young children <3 years of age, supratentorial tumors are more common than infratentorial tumors.42 In children between 4 years and 10 years of age, infratentorial tumors occur more frequently. Supra- and infratentorial tumors occur equally after 10 years old age.42
TABLE 2.4 Clinical Manifestations and Central Nervous System Imaging Features of Fungal Infections | |||||||||||||||
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Classification of tumors by location in conjunction with the appearance of the lesion on conventional and advanced MR imaging techniques helps limit the differential diagnosis. Table 2.5 summarizes the classification of pediatric brain tumors used to organize this chapter.
TABLE 2.5 Common Anatomic Locations of Pediatric Brain Tumors | |||||||||||||||||||||||||||||||||||||||||||||
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Supratentorial Tumors
Tumors of the Cerebral Hemispheres
Hemispheric Astrocytoma
Astrocytomas are the most common childhood tumors of the CNS, constituting approximately one-third of all pediatric supratentorial tumors. Their peak incidence is between 2 and 4 years of age and during early adolescence. They originate from the cerebral hemispheres, thalamus, hypothalamus, and basal ganglia. As discussed later in this chapter, astrocytomas are more common in pediatric patients with NF1. Most astrocytomas are low-grade and classified as WHO grade I neoplasms. However, high-grade neoplasms also occur, and their imaging characteristics are similar to high-grade primary brain tumors seen in adults. Although most low-grade lesions present with seizures, higher-grade tumors present more acutely with symptoms resulting from mass effect, hemorrhage, and raised intracranial pressure.
On CT, low-grade hemispheric astrocytomas have a mixed solid and cystic appearance, with the solid components typically being hypodense. On MRI, various imaging patterns have been described. These include (1) a mass with a nonenhancing cyst and an intensely enhancing mural nodule (typical of pilocytic astrocytoma), (2) a mass with an enhancing cyst wall and an intensely enhancing mural nodule, (3) a necrotic mass with a central nonenhancing zone, and (4) a predominantly solid mass with minimal to no cyst-like component. Some cyst walls may enhance avidly. However, cyst wall enhancement is not necessarily indicative of the presence of tumor cells. The solid areas are typically hyperintense on T2-weighted MR images relative to brain parenchyma, and vary from homogenous to heterogeneous on contrastenhanced images (Fig. 2.39). On diffusion-weighted MR images, low-grade astrocytomas have relatively high diffusivity, reflecting the relatively low cell density or nuclear-to-cytoplasmic ratio seen on histology.
Surgical resection is the definitive curative treatment for hemispheric astrocytoma in the pediatric population, although location near eloquent areas may preclude complete resection.
High-Grade Glioma (Gliomatosis Cerebri and Glioblastoma Multiforme)
Gliomatosis cerebri is a rare diffuse infiltrating high-grade glial tumor of astrocytic origin that can rarely occur in the first two decades of life, but is more common in adults. In children, it is nearly always fatal, with a length of survival spanning from 6 months to 3 years after initial presentation. Gliomatosis cerebri can present with a wide variety of symptoms including headaches, vomiting, seizures, and focal neurologic deficits. On CT, it can be difficult to resolve apart from the presence of mild mass effect, especially on noncontrast studies. On MR, gliomatosis cerebri initially presents as T2 and FLAIR hyperintense unihemispheric lesions that progress to become bihemispheric with time. There is general preservation of the anatomic architecture. Mass effect is generally mild, and enhancement is typically absent in the early stage (Fig. 2.40).
 FIGURE 2.39 Hemispheric pilocytic astrocytoma. Axial FLAIR MR image (on the left), postcontrast coronal T1-weighted MR image (in the middle), and single voxel MR spectroscopy image (on the right) show a rounded enhancing T2 hyperintense lesion (curved arrows) in the right parietal white matter, with elevated choline peak on MR spectroscopy (straight arrow). |
Glioblastoma multiforme is a highly malignant tumor that comprises ˜3% of tumors in children.43 This tumor typically crosses the midline across the commissural tracts, giving rise to a “butterfly glioma” lesion that involves the contralateral hemisphere (Fig. 2.41). Clinical presentation includes seizures, signs of raised intracranial pressure, and focal neurologic deficits. On MRI, these lesions are hypo- to isointense to white matter on T1- and hyperintense on T2-weighted MR images. Irregular and heterogeneous enhancement of the margins is a common finding. A central necrotic core may
be seen (Fig. 2.42). Intratumoral bleeding is also common because of the abnormal, rich vasculature that characterizes these tumors. Histologically, glioblastoma multiforme consists of poorly differentiated glial cells, often with pronounced variation in nuclear size and shape (anaplasia or pleomorphism).
be seen (Fig. 2.42). Intratumoral bleeding is also common because of the abnormal, rich vasculature that characterizes these tumors. Histologically, glioblastoma multiforme consists of poorly differentiated glial cells, often with pronounced variation in nuclear size and shape (anaplasia or pleomorphism).
 FIGURE 2.40 Gliomatosis cerebri in a 7-year-old girl who presented with confusion and left-sided weakness. Axial T2-weighted MR image (on the left) and coronal postcontrast T1-weighted MR image (on the right) show a large mass (arrows) characterized by abnormal T2 signal occupying large portions of the right cerebral hemisphere with mass effect. |
 FIGURE 2.41 Glioblastoma multiforme in a 16-year-old boy. Axial T2-weighted MR image (on the left) and axial postcontrast T1-weighted MR image (on the right) show a large frontal lobe mass (black arrows) with a T2 hyperintense central necrotic core and enhancing margins. In addition, there is an extensive surrounding T2 hyperintense lesion extending across the midline (white arrows), consistent with the “butterfly glioma” characteristic of glioblastoma multiforme. |
Oligodendroglioma
Oligodendrogliomas are glial neoplasms that occur most frequently in adults (peak incidence is in the fourth and fifth decades of life), accounting for only 1% of CNS tumors in the pediatric population.45 They are slow-growing neoplasms with a peripheral location. Traditional subtyping of oligodendrogliomas based on whether or not they are anaplastic has been supplemented by testing for IDH1 or IDH2 mutation and for codeletion of chromosomal arms 1p and 19q. “Pediatric-type” oligodendroglioma lacks these genetic changes, suggesting that it is a quite different genetic and biologic entity than adult-type oligodendroglioma.
On MRI, oligodendrogliomas are predominantly solid masses located along the periphery of the cerebral hemispheres. The solid components are T2 and FLAIR hyperintense (Fig. 2.43). Presence of prominent cortical thickening is a characteristic feature. Calcification is seen commonly on CT and on susceptibility-weighted sequences on MRI. Chunky nodular calcification is described as a typical feature, but this occurs more commonly in adults. Lesions enhance variably following contrast administration. As with other
slow-growing peripherally located lesions, remodeling of the inner table of the skull is a common finding.
slow-growing peripherally located lesions, remodeling of the inner table of the skull is a common finding.
 FIGURE 2.42 Glioblastoma multiforme in a 16-month-old boy who was diagnosed 3 months antemortem. The cut surface shows a large mass (arrows) with multiple areas of yellow-hued necrosis and an ill-defined border. |
 FIGURE 2.43 Oligodendroglioma in a 15-year-old boy. Axial FLAIR MR image (on the left) and axial T1-weighted SPGR (spoiled gradient recalled) MR image (on the right) demonstrate a FLAIR hyperintense lesion in the right temporal lobe that does not enhance following contrast administration (arrows). Histology of the resected specimen revealed an oligodendroglioma. |
The current treatment of oligodendrogliomas includes surgical resection with adjuvant radiotherapy and chemotherapy. Local recurrence is common, and close attention should be paid to the resection site on follow-up studies, noting that the recurrent tumors can be nonenhancing, particularly when the presenting lesion was nonenhancing.46
Ependymal Tumors
Ependymomas constitute ˜6% of all primary intracranial tumors in children.42 Of these, supratentorial ependymomas typically occur in children <6 years old and account for up to 40% of all ependymomas.47 These tumors are thought to arise from embryonic rests of ependymal tissue trapped in the developing cerebral hemispheres.
Ependymal tumors are T1 hypointense and isointense to hyperintense to gray matter on T2-weighted MR images, and generally enhance moderately after contrast administration on both CT and MRI (Fig. 2.44). Ependymomas are heterogeneous and often contain calcification and cystic areas. On MRI, there is usually avid enhancement of the soft tissue components of the tumor, intermixed with poorly enhancing or nonenhancing areas.
Grossly, ependymomas are often soft, tan, and distinct from the surrounding normal brain. Microscopically, they consist of cellular collections of round cells within an abundant fibrillary background. The nuclei are often arranged around the fibrillary material in ependymal rosettes or perivascular pseudorosettes (Fig. 2.45).
Embryonal Tumor Other Than Medulloblastoma (formerly known as CNS PNET)
Embryonal tumor other than medulloblastoma, formerly known as central nervous system primitive neuroectodermal tumor (CNS PNET), is relatively rare, accounting for 5% of all supratentorial tumors in childhood.48 These tumors are more common in the first decade of life, with a peak incidence from birth to 5 years of age. At presentation, supratentorial embryonal tumors are often large and fairly well-defined, occurring either in the cerebral hemispheres or in the lateral ventricles. They may be solid and homogenous or heterogeneous with cyst formation. Calcification is often seen on CT. Following contrast administration, heterogeneous enhancement is seen within regions of necrosis. On MR, solid areas have restricted diffusion and T2-hypointense areas (Fig. 2.46), reflecting high nuclear-to-cytoplasmic ratio and increased cellularity (Fig. 2.47), as well as increased CBV values on perfusion imaging. Hemorrhage can also occur in these lesions. CNS embryonal tumors are a more heterogeneous group of tumors than peripheral PNET and may show differentiation along neuronal, astrocytic, or ependymal lines. They lack the EWSR1 gene rearrangement characteristic of peripheral PNET/Ewing sarcoma.49
 FIGURE 2.44 Supratentorial ependymoma in a 5-month-old girl. Axial T2-weighted MR image (on the left) and coronal postcontrast T1-weighted MR image (on the right) show a large heterogeneous mass (arrows) containing a large cystic component and heterogeneous enhancement in the right cerebral hemisphere, with vasogenic edema and marked mass effect on surrounding brain. Histology of the resected specimen was consistent with an anaplastic ependymoma. |
Neuronal and Neuronal-Glial Neoplasms
Ganglioglioma and Gangliocytoma
Ganglioglioma and gangliocytoma are both tumors that contain neoplastic mature ganglion cells (neuronal cells). Gangliocytomas are composed solely of neuronal elements, whereas gangliogliomas contain neoplastic glial cells as well (Fig. 2.48). Ganglioglioma and gangliocytoma comprise ˜6% of supratentorial tumors in children.48 Ganglioglioma and gangliocytoma arise most commonly in adolescents and
in young adults. Both tumors arise in the cerebral cortex, most commonly in the temporal lobe. Presenting symptoms depend upon the size and location of tumors and usually include seizures. In particular, complex partial seizures are commonly associated with temporal lobe tumors.
in young adults. Both tumors arise in the cerebral cortex, most commonly in the temporal lobe. Presenting symptoms depend upon the size and location of tumors and usually include seizures. In particular, complex partial seizures are commonly associated with temporal lobe tumors.
 FIGURE 2.45 Ependymoma in a 6-year-old girl. Histology from a mass resected from the frontal lobe shows monotonous round cells in a fibrillary background. Tumor cell nuclei are often arranged around hypocellular fibrillary areas with central vessels (arrows), forming “perivascular pseudorosettes” (hematoxylin and eosin, original magnification, 200×). |
 FIGURE 2.46 Central nervous system (CNS) embryonal tumor (diagnosed as “CNS PNET” before WHO nomenclature was changed) in an 8-year-old boy. Coronal postcontrast T1-weighted MR image demonstrates a large, partially necrotic, enhancing mass (arrows) in the right cerebral hemisphere causing marked mass effect and midline shift. |
 FIGURE 2.47 Embryonal tumor from the temporal lobe of a 3-year-old girl. Poorly differentiated densely packed cells with high nuclear-to-cytoplasmic ratio are present (hematoxylin and eosin, original magnification, 400×). Genetic findings may permit specific classification, such as “embryonal tumor with multilayered rosettes, C19MC-altered”; when not further classifiable, the designation “CNS embryonal tumor, not otherwise specified” is appropriate, as the old term “CNS PNET” is now defunct. |
 FIGURE 2.48 Ganglioglioma in a 14-year-old boy. This mass resected from the parietal lobe is moderately cellular with a spindled glial component and admixed dysplastic, occasionally multinucleate (arrows) ganglion cells (hematoxylin and eosin, original magnification, 400×). |
 FIGURE 2.49 Ganglioglioma in an 11-month-old girl who presented with seizures. Coronal T2-weighted MR image (on the left) and coronal postcontrast T1-weighted MR image (on the right) show a poorly-defined, nonenhancing, heterogeneous mass (arrows) that is hyperintense to gray matter expanding the right temporal lobe, suggestive of a ganglioglioma. |
On imaging studies, the appearance of ganglioglioma and gangliocytoma is virtually identical. Both are seen as intra-axial tumors located peripherally in the cortex with a mixed solid and cystic appearance. The solid components are hyperintense to gray matter on T2-weighted MR images and variably enhance following contrast administration (Fig. 2.49). Presence of mineralization and absence
of enhancement may suggest the diagnosis of these tumors, although the appearance is still nonspecific.
of enhancement may suggest the diagnosis of these tumors, although the appearance is still nonspecific.
 FIGURE 2.50 Desmoplastic infantile ganglioglioma in an asymptomatic 9-month-old boy who presented with increasing head circumference. Axial T2-weighted MR (on the left) and axial postcontrast T1-weighted MR image (on the right) show a large mixed solid and cystic lesion (arrows) in the right cerebral hemisphere, with enhancement of some of the solid components. Mass effect from the tumor and leftward midline shift are also present. |
Surgical resection is the definitive treatment of ganglioglioma and gangliocytoma in the pediatric population.
Desmoplastic Infantile Ganglioglioma
Desmoplastic infantile gangliogliomas (DIG) are rare intracranial tumors that typically occur in the first 2 years of life.50 They are characterized by both astrocytic and ganglionic differentiation and a prominent desmoplastic stroma. Clinical presentation is usually with rapid and progressively increasing head circumference.
DIGs are typically seen as large mixed solid and cystic masses in the cerebral hemispheres, most commonly in the frontal and parietal lobes. On CT, the solid portion of these large masses is slightly hyperdense compared to normal gray matter and typically located along the cortical margin of the mass. Calcification is not commonly seen. On MRI, the solid components of the lesions are isointense to brain parenchyma on T1- and T2-weighted MR images. As on CT, the solid components enhance avidly following contrast administration on MRI (Fig. 2.50).
Treatment of DIGs is best accomplished by surgical resection, which can often be challenging because of large size and firm attachment to the dura. Chemotherapy may be considered if gross total resection cannot be accomplished. In spite of the aggressive appearance, overall prognosis is good for most pediatric patients.
Dysembryoplastic Neuroepithelial Tumor
Dysembryoplastic neuroepithelial tumors (DNET) are WHO grade I benign, slow-growing mixed neuronal-glial tumors arising from either cortical or deep gray matter (Fig. 2.51). Average age of presentation is 9 years, and most affected pediatric patients present with a longstanding history of often-intractable partial seizures. They comprise <1% of
CNS tumors in childhood.42 DNETs are located most commonly in the temporal and parietal lobes. Most lesions arise from the cortical gray matter, and associated cortical dysplasia has been reported in more than 80% cases.51,52
CNS tumors in childhood.42 DNETs are located most commonly in the temporal and parietal lobes. Most lesions arise from the cortical gray matter, and associated cortical dysplasia has been reported in more than 80% cases.51,52
 FIGURE 2.51 Dysembryoplastic neuroepithelial tumor in a 15-year-old boy. Tumor resected from the temporal lobe shows round oligodendrocyte-like cells with occasional interspersed neurons, present in a pale blue myxoid background (hematoxylin and eosin, original magnification, 400×). |
 FIGURE 2.52 Dysembryoplastic neuroepithelial tumor in a 10-year-old boy who presented with seizures. Axial T2-weighted MR image (on the left) and axial postcontrast T1-weighted MR image (on the right) show a large cortically based lesion (asterisks) with cyst-like areas (arrows) along the medial aspect, which does not enhance on the postcontrast MR image. |
On CT, the lesion is hypodense to gray matter. On MRI, classic DNETs are seen as cortically based lesions with a gyriform configuration and cyst-like areas on T2-weighted MR images (Fig. 2.52). These areas are hyperintense on FLAIR images. Classic DNETs do not enhance following contrast administration on either CT and MRI. A subtype of DNET involves the subcortical white matter in addition to the cortex and enhances variably following contrast administration. Typically, there is no evidence of surrounding edema or mass effect. Also, their longstanding nature is indicated by the presence of scalloping of the inner table of the calvarium.
Surgical resection is currently the definitive treatment of DNETs.
Extraventricular Neurocytoma
Neurocytomas are rare WHO grade 2 neuroepithelial tumors that account for 0.1% to 0.5% of all CNS tumors.53 Most neurocytomas are located within the intracerebral ventricular system (in which case they are called “central neurocytomas”) in or near the midline, usually attached to the septal leaflets. However, “extraventricular neurocytomas” in cerebral and spinal cord locations have been reported. These tumors are uncommon in childhood and seen most often in young adults in the second to fourth decades.
On CT, neurocytomas are mixed solid and cystic. The solid components are usually hyperdense to the cortex (Fig. 2.53). Calcification is seen in ˜50%.54 Moderate heterogeneous enhancement of solid components is seen following contrast administration. On MRI, these tumors are heterogeneous. They are isointense to the cortex on T1-weighted MR images. On T2-weighed MR images, the lesion has a “bubbly” appearance because of the presence of cysts within the lesion that null on FLAIR MR images. Prominent vascular flow voids may be seen, corresponding to the choroidal vessels supplying the mass. Mild to moderate heterogeneous enhancement of solid components is seen following contrast administration.
Surgical resection is curative in a vast majority of cases. Microscopically, the tumor consists of uniform histologically benign round cells with interspersed areas of neuropil (Fig. 2.54).
Sellar and Suprasellar Tumors
Chiasmatic and Hypothalamic Glioma
Some preferred sites of pilocytic astrocytomas (WHO grade I) include the optic nerve (“optic nerve glioma”) and the optic chiasm/hypothalamus. Pilocytic astrocytomas of the optic pathways represent 15% of supratentorial tumors.55 Moreover,
bilateral optic nerve tumors are virtually pathognomonic of this diagnosis. Optic pathway gliomas may involve the optic nerves, optic chiasm, optic tract, lateral geniculate bodies, and/or optic radiations. Optic gliomas occur with increasing frequency in patients with NF1 (20% to 50%).56 On the other hand, up to 24% of patients with NF1 have optic pathway gliomas.57 Tumors in children with NF1 are reportedly less aggressive than those in children without NF1 and tend to be bilateral.
bilateral optic nerve tumors are virtually pathognomonic of this diagnosis. Optic pathway gliomas may involve the optic nerves, optic chiasm, optic tract, lateral geniculate bodies, and/or optic radiations. Optic gliomas occur with increasing frequency in patients with NF1 (20% to 50%).56 On the other hand, up to 24% of patients with NF1 have optic pathway gliomas.57 Tumors in children with NF1 are reportedly less aggressive than those in children without NF1 and tend to be bilateral.
 FIGURE 2.53 Neurocytoma in a 14-year-old girl. Axial noncontrast CT image (on the right) and axial postcontrast T1-weighted MR image (on the left) show a hemorrhagic, partially enhancing tumor (arrows) arising from the left head of caudate with intraventricular extension. |
 FIGURE 2.54 Neurocytoma. This intraventricular mass from the same patient (Figure 2.53) shows round uniform cells interspersed with “nucleus-free” zones of fibrillary neuropil (hematoxylin and eosin, original magnification, 400×). |
Optic pathway gliomas are usually T1 isointense to hypointense. On T2-weighted MR images, the lesions demonstrate mixed signal intensity. Intense enhancement is common on postcontrast MR images (Fig. 2.55). The use of axial and coronal postcontrast thin-section T1-weighted fat-suppressed MR images and inversion recovery or T2-weighted MR images with fat suppression enables optimal visualization of the optic pathways. The presence of mass effect and contrast enhancement differentiates tumors from myelin vacuolization seen along the optic tracts in NF1 patients.
Diencephalic syndrome may be seen in pediatric patients with hypothalamic/chiasmatic astrocytomas presenting with failure to thrive. These tumors are often larger, occur at a younger age, are more aggressive than others at presentation, and may seed throughout the CSF pathways.
Craniopharyngioma
Craniopharyngiomas are slow-growing, benign, nonglial tumors arising in the sellar and parasellar regions. They comprise between 3% and 5% of all pediatric brain tumors58. Craniopharyngiomas are classified as WHO grade I tumors and arise from ectodermal remnants of the Rathke pouch, with a bimodal incidence in the first and fifth decades of life.
The adamantinomatous type is more common in children, whereas the squamous-papillary variant tends to occur in adults.59,60 Although they are benign, they can invade surrounding structures in the sellar and parasellar regions, eliciting a gliotic response and making resection challenging.
The adamantinomatous type is more common in children, whereas the squamous-papillary variant tends to occur in adults.59,60 Although they are benign, they can invade surrounding structures in the sellar and parasellar regions, eliciting a gliotic response and making resection challenging.
 FIGURE 2.55 Optic pathway glioma in a 6-month-old girl who presented with increased irritability and was diagnosed with diencephalic syndrome. Axial T2-weighted MR image (on the left) and postcontrast sagittal 3D SPGR (spoiled gradient recalled) MR image (on the right) show an avidly enhancing suprasellar and sellar intermediate T2 signal intensity lesion (arrows) extending to the prepontine region and splaying the cerebral peduncles (asterisks) consistent with a large optic pathway glioma with secondary obstructive hydrocephalus (H). |
On imaging studies, craniopharyngiomas have a mixed cystic and solid appearance, with 90% of tumors showing calcification and 90% containing cystic areas61 (Fig. 2.56). On MRI, high signal intensity on both T1- and T2-weighted MR images is seen in areas of lesions with high protein content or in lesions containing subacute hemorrhage.62 Hypointensity on T1-weighted MR images may reflect the presence of keratin. CT is often used to demonstrate calcification in the lesion, which is important for diagnosis and surgical planning.
Surgical resection remains the mainstay of treatment of craniopharyngiomas, with radiotherapy having a role in cases that are not amenable to gross total resection. Greater than 85% of patients survive 3 years after diagnosis, and subtotal resection and radiation therapy are associated with prolonged survival.63 The resected specimen is often spongy and variably gritty, and its cysts may contain dark fluid resembling “machine oil.” Microscopically, they are composed of squamous epithelium that may, in the adamantinomatous variant, have prominent peripheral palisading and areas of differentiation into stellate reticulum, resembling adamantinomas derived from dental epithelium (Fig. 2.57). Follow-up imaging is directed toward identifying recurrence, second tumors, and associated moyamoya syndrome.
Pituitary Tumor
Macroadenoma and Microadenoma
Pituitary adenomas account for ˜3% of all supratentorial tumors in childhood.64 Clinical presentation is variable and depends on tumor size, hormonal activity, and extrasellar extent. Most adenomas are hormonally active, with most secreting prolactin. Most lesions are microadenomas (<1 cm in diameter) and present with neuroendocrine symptoms. Prolactin secreting or hormonally inactive macroadenomas (>1 cm in diameter) have more variable symptomatology, including neuroendocrine abnormalities, visual field cuts, or headache.
On MRI, adenomas may be isointense or hypointense compared with the normal pituitary gland on T1- and isointense to hyperintense on T2-weighted MR images. On postcontrast images, microadenomas are relatively hypoenhancing compared to normal pituitary tissue (Fig. 2.58). Macroadenomas present as heterogeneous masses that tend to involve the sella and suprasellar region. Hemorrhage into a macroadenoma is a relatively common complication.
Surgical removal is indicated for macroadenomas that cause optic chiasmal compression in children. For macroadenomas without chiasmal compression, surgery is considered for lesions larger than 2 cm and with prolactin levels > 600
ng/mL.65 Functioning microadenomas are usually treated with medical therapy, although some surgeons prefer upfront operative management in pediatric patients. Microscopically, pituitary adenomas may be classified based on their architectural pattern and hormonal content as assessed by immunohistochemical staining (Fig. 2.59).
ng/mL.65 Functioning microadenomas are usually treated with medical therapy, although some surgeons prefer upfront operative management in pediatric patients. Microscopically, pituitary adenomas may be classified based on their architectural pattern and hormonal content as assessed by immunohistochemical staining (Fig. 2.59).
 FIGURE 2.56 Craniopharyngioma in a 17-year-old boy who presented with hypopituitarism. Axial T2-weighted MR image (on the left) and sagittal postcontrast T1-weighted MR image (on the right) shows a large, partially calcified, heterogeneous, suprasellar mass (arrows) with mass effect upon the optic chiasm and involvement of the pituitary gland. |
Rathke Cleft Cyst
Another lesion commonly encountered in the sella or in the suprasellar region is a Rathke cleft cyst. These lesions are congenital, nonneoplastic cysts derived from remnants of Rathke pouch. Rathke cleft cysts are most commonly discovered incidentally, as they are usually not large enough to be symptomatic by compressing surrounding structures. Symptoms result from compression of the optic chiasm, hypothalamus, or pituitary gland and are indistinguishable from those caused by other sellar masses, such as craniopharyngioma or pituitary adenoma.
 FIGURE 2.57 Craniopharyngioma in a 3-year-old girl. This adamantinomatous variant of a craniopharyngioma was a large cystic hypothalamus-centered mass. Gross examination (on the left) shows spongy and somewhat chalky pale tan tissue with occasional cysts containing dark, greasy fluid. Microscopically (on the right), squamous cells with basal palisading (B) and stellate reticulum (S) alternate with calcifying keratinous debris (K) and cystic spaces (C) (hematoxylin and eosin, original magnification, 400×). |
On MRI, Rathke cleft cysts are typically characterized by high signal intensity on unenhanced T1-weighted
MR images. Intracystic nodules have also been described, but may be difficult to visualize because of similar signal intensity of the cyst fluid and the nodule. Although imaging findings may be helpful for differentiating these lesions from other sellar or suprasellar lesions, radiologic findings can be nonspecific, and features can overlap with cystic craniopharyngiomas or cystic pituitary adenomas. Follow-up imaging is required in many cases, and occasionally, cyst aspiration may be required to establish a diagnosis.
MR images. Intracystic nodules have also been described, but may be difficult to visualize because of similar signal intensity of the cyst fluid and the nodule. Although imaging findings may be helpful for differentiating these lesions from other sellar or suprasellar lesions, radiologic findings can be nonspecific, and features can overlap with cystic craniopharyngiomas or cystic pituitary adenomas. Follow-up imaging is required in many cases, and occasionally, cyst aspiration may be required to establish a diagnosis.
 FIGURE 2.58 Pituitary macroadenoma in a 16-year-old boy who presented with growth hormone deficiency. Sagittal precontrast T1-weighted MR image (on the left) and sagittal postcontrast T1-weighted MR image (on the right) through the sella show a large, heterogeneous, partially-enhancing macrolobulated lesion (arrows) expanding the sella and extending superiorly into the suprasellar cistern and inferiorly into the sphenoid sinus. |
 FIGURE 2.59 Pituitary adenoma in a 13-year-old boy who presented with Cushing disease. Resected mass demonstrates characteristic nests of cells showing abundant variably granular cytoplasm (left, hematoxylin and eosin, original magnification, 400×). Immunohistochemical staining shows brown cytoplasmic reactivity for adrenal corticotropic hormone (right, ACTH immunostain, original magnification, 400×). |
Hypothalamic Hamartoma
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