Dorsal Induction

Under the rubric of dorsal induction, the brain undergoes primary and secondary neurulation; that is, turning a flat bed of cells into a round piece of brain and spinal cord.

Disorders of primary neurulation predominantly affect the spinal cord and include those due to adhesions between the inwardly oriented endoderm and the outer ectoderm. This is the presumed etiology for neurenteric cysts and diastematomyelia. If there is premature separation of the neuroectoderm and the cutaneous ectoderm, it is usually the fat that is left behind and fuses with the neuroectoderm. This produces the lipomyelocele, lipomyelomeningocele, and the intradural lipoma. If the separation never occurs, one gets persistent communication of the CNS with internal or external structures, hence cephaloceles, myeloceles, meningomyeloceles, anencephaly, exencephaly (brain outside the skull), craniorachischisis (congenital fissure of the skull and spine), and dermal sinus tracts. These entities may be associated with the Chiari II malformation because the posterior fossa calvarium is developing at the same time.

Disorders of secondary neurulation generally affect the conus medullaris, filum terminale, and cauda equina. Lipomas of the filum, short thickened tethered fila and tethered cords, and caudal regression syndrome with sacral agenesis are usually listed under this category.

Ventral Induction

Holoprosencephaly represents the signature anomaly associated with failure of ventral induction. Because the premaxillary facial structures are formed in association with ventral induction, it is not uncommon to see cyclopia and probosci in patients with ventral induction failures. Septo-optic dysplasia and pituitary anomalies are also disorders of ventral induction.

Cerebellar development also occurs at the 5- to 15-week period of fetal development. Just as there is cerebral hemispheric development from neural tissue derived from the germinal matrix around the lateral ventricles, so too is cerebellar development dependent on the germinal matrix about the fourth ventricle. Because hemispheric development occurs before vermian development and the superior vermis forms before the inferior vermis, it is rare to see hemispheric anomalies without vermian maldevelopments or superior vermian lesions without associated inferior vermian anomalies. Inferior vermian hypoplasia may be seen in isolation. Those entities associated with vermian dysgenesis include the Dandy-Walker complex lesions (Dandy-Walker malformation, Dandy-Walker variant, and giant cisterna magna), rhombenencephalosynapsis, and Joubert syndrome.

Disorders of hemispheric development include hemispheric hypoplasia, but this is a rare bird more commonly seen with other supratentorial and vermian anomalies.

Neuronal Proliferation, Differentiation, and Histogenesis

Disorders of neuronal proliferation, differentiation, and histogenesis are disorders that occur because of abnormal proliferation, such as microencephaly, macroencephaly, neurocutaneous syndromes, and aqueductal stenosis. Microencephaly and microlissencephaly occur because of too few neurons, less brain tissue. In megalencephaly, one has marked overproduction of neurons. Primary causes include achondroplasia, Soto syndrome, and Beckwith-Wiedemann syndrome.

Neuronal Migration

Neuronal migrational anomalies are based on the centrifugal movement of neuroblasts and glioblasts along radial glial fibers. From the periventricular region, the neuroblasts are first to migrate and they take up residence in the molecular layer of cortical zone 1, the most peripheral of the gray matter zones. Cells (glioblasts and neuroblasts) from the intermediate zone then migrate in fanlike waves along radial glial fibers out to the periphery and then double back on themselves to first fill the sixth deepest layer of the cortex, followed by cortical zones 5, 4, 3, and 2. Somehow, this is supposed to result in cortical organization, creating the many layers of the brain and mind. When this gets mixed up, one has classic lissencephaly, heterotopia, pachygyria, polymicrogyria, schizencephaly, and the like.

Myelination

White matter, when myelinated, is bright on a T1-weighted image (T1WI) and dark on a T2WI. The development of myelination is a complicated process but proceeds from posterior to anterior and from central to peripheral (Table 9-1 and Box 9-1). Barkovitch has done a good job in mapping normal myelination dates in term babies. In general, the white matter is seen to be myelinated earlier on T1WI than on T2WI for reasons that have to do with water content versus lipid content. It then takes a bit of wizardry to apply this to the premature infant. Table 9-1 is a good start for determining if there is delayed myelination.

Table 9-1 Timing of Myelination

Then along came fluid-attenuated inversion recovery (FLAIR) imaging. The signal intensity of white matter on FLAIR initially is dark because of the marked water content, turns brighter as the “watery brain” of infancy resolves, than again becomes dark as the white matter myelinates. The timing of these stages, summarized in Table 9-1, varies from structure to structure. The cerebellar peduncle and the posterior limb of the internal capsule show high signal intensity relative to gray matter at birth. Thereafter, the white matter loses signal intensity with time and shows low signal intensity at age 50 weeks and beyond. The unmyelinated white matter, including the frontal deep white matter, the occipital deep white matter, and the centrum semiovale, shows low signal intensity at birth, converts to high signal intensity at age 20 to 30 weeks, and back to low signal intensity after age 2 to 3 years.

It is useful to separate congenital disorders of the brain into those involving the supratentorial structures and those involving the infratentorial structures, because radiologists think in terms of anatomy rather than embryology. We synthesize information based on imaging findings and then think about developmental issues later.

Naturally, disorders can affect both spaces, but as an initial classification scheme, this may be helpful. In addition, in a newborn infant, separating the lesions into those that are cystic and those that are solid is of some help in arriving at a differential diagnosis. Clinical information is also useful in distinguishing among various congenital abnormalities, because several disorders also have associated cutaneous, ocular, or metabolic abnormalities.

Arachnoid Cysts

If you had to have a congenital lesion in the brain, this would be the lesion of choice. The arachnoid cyst is the most common congenital cystic abnormality in the brain. It consists of a cerebrospinal fluid (CSF) collection within layers of the arachnoid. The cyst may distort the normal brain parenchyma.

The arachnoid cyst is typically a serendipitous finding and may not be symptomatic. The most common supratentorial locations for an arachnoid cyst are (in decreasing order of frequency) (1) the middle cranial fossa, (2) parasellar cisterns, and (3) the subarachnoid space over the convexities (Fig. 9-1). Infratentorially (see Infratentorial Abnormalities later in this chapter), arachnoid cysts commonly occur in the (1) retrocerebellar cisterns, (2) cerebellopontine angle cistern, and (3) quadrigeminal plate cistern. Intraventricular cysts are rare but favor lateral and third ventricles (Fig. 9-2).

Figure 9-1 Arachnoid cyst. T2-weighted image at the level of the top of the lateral ventricle shows a cerebrospinal fluid intensity collection that remodels the bone (arrows) and causes mild midline shift.

Figure 9-2 Fetal imaging of an arachnoid cyst. A, The in utero magnetic resonance image defined an arachnoid cyst of the third ventricle, which was misinterpreted as hydrocephalus. Treated intrauterine and baby did well. B, There was hydrocephalus, but the ballooning of the third ventricle was the cyst itself.

Computed tomography (CT) scans demonstrate a CSF density mass that typically effaces the adjacent sulci and may remodel bone. The mass measures from 0 to 20 Hounsfield units (HU) and shows no enhancement. In those difficult cases where an arachnoid cyst and a dilated subarachnoid space must be distinguished, one can instill intrathecal contrast to differentiate the cyst (which does not immediately fill with contrast) from the subarachnoid space (which immediately fills) (Fig. 9-3). Be careful though. In time, the arachnoid cyst will imbibe contrast.

Figure 9-3 Arachnoid cyst of third ventricle. A, Initial unenhanced computed tomography (CT) scan showed a cystic mass widening the third ventricle. B, Sagittal T1-weighted image (T1WI) showed a mass with the same intensity as cerebrospinal fluid (CSF) that appears to communicate with the lateral ventricular system and extend into the sella. C, T2WI showed the lesion to have the same signal intensity as CSF. D, Intrathecal contrast was administered from a lumbar approach, and the contrast was allowed to flow superiorly to the intracranial compartment. The initial CT scan showed minimal filling of the cyst. Contrast material is in the subarachnoid space (arrows). E, On delayed axial scans the cyst filled with contrast. This is characteristic of an arachnoid cyst.

On magnetic resonance (MR) imaging the most common appearance is that of an extra-axial mass that has signal intensity identical to CSF on all pulse sequences. Occasionally, the signal intensity may be greater than that of CSF on proton density-weighted images (PDWI) because of the stasis of fluid within the cyst as opposed to the pulsatile CSF of the ventricular system and subarachnoid space. FLAIR and diffusion-weighted imaging (DWI) usually show a dark mass similar in intensity to CSF (again pulsation effects may cause some higher intensity). Rarely, the fluid within the arachnoid cyst may be of higher protein content than CSF, accounting for the difference in signal intensity.

The differential diagnosis of an arachnoid cyst is limited and generally revolves around three other diagnoses: a subdural hygroma, dilation of normal subarachnoid space secondary to underlying atrophy or encephalomalacia, and epidermoid (Table 9-2; see also Fig. 6-1). Although subdural hygromas have been thought to be due to chronic CSF leaks through traumatized leptomeninges, in most cases the trauma results in sufficient blood deposited within the “hygroma” so that the signal intensity on T1WI and FLAIR is different from that of CSF. In addition, subdural hygromas are typically crescentic in shape, whereas arachnoid cysts tend to have convex borders. Both efface sulci and show mass effect. In contradistinction, dilation of the subarachnoid space secondary to underlying encephalomalacia does not demonstrate mass effect and the adjacent sulci are enlarged. Another distinguishing feature is the fact that the cerebral veins in the subarachnoid space are seen to course through the CSF in the case of underlying encephalomalacia, as opposed to the subdural hygroma and arachnoid cyst, where the veins are displaced inward. An epidermoid may simulate an arachnoid cyst on CT and T2WI; however, FLAIR and DWI nicely show higher signal intensity than CSF. In fact, the T1WI will often also be brighter than CSF and will be obvious.

Table 9-2 Arachnoid Cyst vs. Subdural Hygroma, Epidermoid, Encephalomalacia

A feature, often seen in association with arachnoid cysts, that may suggest the diagnosis is bony scalloping. The bone may be thinned or remodeled, probably because of transmitted pulsations or slow growth. This would not be seen with hygromatous collections or atrophy. However, the finding may be seen occasionally in epidermoids or with porencephaly, where the ventricular pulsations may be transmitted through the porencephalic cavity to the inner table of the skull (see Fig. 8-21). When arachnoid cysts are seen in the middle cranial fossa, the temporal lobe may be hypoplastic. Absence of soft-tissue intensity or density, calcification, or fat distinguishes arachnoid cysts from those of the dermoid-epidermoid line.

Pineal cysts are discussed in Chapter 3.

Rathke Cleft Cysts

Rathke cleft cysts are embryologic remnants of Rathke’s pouch, the neuroectoderm that ascends from the oral cavity to the sellar region to form the pituitary anterior lobe and pars intermedia. These cysts are lined with a single layer of cuboidal or columnar cells and may arise within the sella, the suprasellar region, or most commonly both. They occur in up to 13% of autopsy studies of the sella. The cysts can compress normal posterior or anterior pituitary tissue to cause symptoms of hypopituitarism, diabetes insipidus, headache, and visual field deficits but are usually asymptomatic. The cysts are well-defined masses that on MR may have high or low signal intensity on T1WI and high signal intensity on T2WI, and on CT are hypodense and most often nonenhancing (see Fig. 11-31). Intracystic, yellow waxy solid nodules have recently been reported in Rathke cysts containing cholesterol or mucinous proteins probably accounting for the bright signal on T1WI in some cysts. The differential diagnosis is a craniopharyngioma or hemorrhagic pituitary gland; the presence of calcification, soft-tissue mass, or areas of enhancement would lead one away from Rathke cleft cyst as the diagnosis (see Chapter 11). Treatment is cyst aspiration or removal with little chance of recurrence.

Meningoencephaloceles

A meningocele is a congenital malformation in which the meninges protrude through the bony confines. As opposed to encephaloceles, meningoceles do not include brain tissue within the protrusion. Usually, an encephalocele also contains meninges, so it should really be called a meningoencephalocele. In fact, clinicians have become resigned to use the shortened noun cephalocele. The terms are used interchangeably in this chapter. Meningoceles are rarer than encephaloceles. The most common location for meningoencephaloceles associated with Chiari III malformations is the occipital region. These may also be associated with holoprosencephaly and aqueductal stenosis (Fig. 9-4). In the United States, parietal (10%) and frontal (9%) meningoencephaloceles are the next most common locations for this abnormality. Vietnamese and Southeast Asian women have a propensity for nasofrontal or sphenoethmoidal meningoencephaloceles (Fig. 9-5). Recent descriptions of meningoceles of Meckel’s cave account for the marked CSF enlargements sometimes seen in these locations. The diagnosis of meningoencephalocele is often made clinically when the protrusion is through the occipital, parietal, or frontal region. On the other hand, nasofrontal or sphenoethmoidal encephaloceles may be clinically occult and may have a wide clinical differential diagnosis when seen through a nasoscope. Otorhinolaryngologists will love you if you let them know that the polyp they plan to remove from the nasal vault is actually the frontal lobe. The anterior meningoencephaloceles have a higher rate of associated anomalies, such as agenesis of the corpus callosum, colobomas, and cleft lips.

Figure 9-4 Occipital encephalocele. Axial T2-weighted image shows protrusion of meninges (arrow) at the foramen magnum–C1 region. Patient had this lesion at birth.

Figure 9-5 Anterior basal encephalocele. Coronal T1-weighted image demonstrates inferior misplacement of the medial frontal lobes and gyrus rectus into the nasal cavity with hypertelorism. Wide frontal horns (arrows) suggest corpus callosum agenesis.

Encephaloceles may also be suspected when one sees enlargement of a basal neural foramen. An MR study will usually discern that there is herniated brain or CSF in the hole (Fig. 9-6). There often is a distortion of the adjacent brain tissue with maloriented white matter tracts.

Figure 9-6 Basal cephalocele. Seizures were the presenting symptom in this patient with a right temporal encephalocele, which was herniating (arrows) into the basisphenoid.

On CT the meningocele is seen as a CSF density protrusion through a bony defect in the calvarium (Fig. 9-7). MR scans demonstrate continuity of the meningocele with the underlying leptomeninges. The critical task is to find the abnormality; secondarily one should tell the surgeons whether brain tissue is protruding through the defect. For this reason MR, with its superior soft-tissue resolution, is the primary study in this evaluation. The brain tissue within the meningoencephalocele typically has the signal intensity of normal brain. However, occasionally one may see heterotopic or disorganized brain tissue, which has a more heterogeneous signal intensity.

Figure 9-7 Meningocele. Coronal computed tomography demonstrates a defect in the skull base on the left side (arrows) with remodeling of the bone, indicative of a long-standing process. This represented a meningocele coming from the floor of the left middle cranial fossa.

Neuroepithelial Cysts

Neuroepithelial cysts may arise within the ependyma of the ventricular system. Although lateral ventricular cysts are most common, often associated with the glomus of the trigone, they may also occur in the other ventricles. Typically, they follow CSF intensity; however, they may be bright on T1WI owing to high protein, mucin, cholesterol, or viscous content. The lining of this cyst is epithelial, and they are thought to arise from ectoderm. Occasionally one may see these cysts randomly in the brain parenchyma, where they may simulate cystic lacunar infarctions in atypical locations. Differential diagnoses might include epidermoid cysts, cysticercosis, or echinococcal cysts.

Anencephaly

Anencephaly means no brain. Anencephaly should now be a diagnosis made prenatally because most women are screened relatively early in pregnancy for elevated levels of serum α-fetoprotein, a marker of neural tube defects. The diagnosis by obstetric ultrasound (US) is made when the cranial vault is seen to be small, with only the fetus’s face and posterior fossa well seen (Fig. 9-8). Only a nubbin of tissue is seen at the skull base on US, and amniotic fluid α-fetoprotein levels are elevated. These babies do not do well and may be allowed to die if the diagnosis is not made prenatally. An association with spinal dysraphism exists.

Figure 9-8 Anencephaly. A, Obstetric ultrasound shows lack of development of the cranial vault (arrow) in this fetus. Eyes are marked by asterisks. B, Profile view of the face of the fetus shows nondevelopment of the skull (arrow) above the eye (E). N, nose; curved arrow, mouth. (Compliments of Peggy Brennecke, MD.)

Hydranencephaly

Hydranencephaly has the appearance of absence of that part of the brain supplied by anterior and middle cerebral arteries. The parts of the brain supplied by the posterior circulation are preserved, so the posterior temporal lobes, occipital lobes, thalami, and infratentorial structures are well formed. The brain stops there. In place of the remainder of the brain is a CSF-contained space (Fig. 9-9). The chief differential diagnosis is termed “maximal” hydrocephalus (severe hydrocephalus with a thin cortical mantle plastered against the sides of the calvarium) (Fig. 9-10). This will also usually affect the occipital region as opposed to hydranencephaly. To detect this thin rim of cortical tissue, MR is probably more accurate than CT. Shunting is the treatment for maximal hydrocephalus; some return of function may occur with shunting. With hydranencephaly, no treatment is effective. Bad brain: bad prognosis.

Figure 9-9 Hydranencephaly. Axial computed tomography shows absence of brain tissue in the anterior and middle cerebral artery distributions with preservation of the brain stem and cerebellum.

Figure 9-10 Maximal hydrocephalus. The presence of a cortical mantle peripherally and bilaterally suggests that this case represents maximal hydrocephalus and NOT hydranencephaly.

Holoprosencephaly

Holoprosencephaly (Table 9-3) refers to a constellation of congenital abnormalities where separation of the right and left cerebral hemispheres is incomplete (Fig. 9-11). The range of this disorder includes a minor form, lobar holoprosencephaly, in which separation of the cerebral hemispheres and lateral ventricles is near normal but formation of an interhemispheric fissure and cerebral falx is incomplete. Even in the mildest of forms you may see fusion of the hypothalamus, cingulum, and caudate nuclei. The frontal horns are closely apposed to each other, with partial fusion of frontal lobes. The most severe form is designated alobar holoprosencephaly, which demonstrates almost no separation of the cerebral hemispheres and ventricles. One is left with a single large ventricle with a horseshoe-shaped appearance (monoventricle) (Fig. 9-12). No interhemispheric fissure, falx, or significant separation of the hemispheric structures is identified. The basal ganglia and thalami are fused, and the septum pellucidum and corpus callosum are absent. Because one needs an interhemispheric fissure to form the corpus callosum, it is not surprising that this is commonly absent in patients with holoprosencephaly. Similarly, a dorsal cyst will interfere with callosal formation in holoprosencephaly. Between the two extremes of lobar and alobar holoprosencephaly is semilobar holoprosencephaly, in which there is partial development of the falx and the interhemispheric fissure (with partial separation of the lateral ventricles) (Fig. 9-13). The basal ganglia and thalami are still fused. These abnormalities are associated with rather severe mental retardation, microencephaly, hypotelorism, and abnormal facies. The finding of a solitary median maxillary central incisor is also indicative of holoprosencephaly.

Table 9-3 Holoprosencephaly Variants

Figure 9-11 Holoprosencephaly. A, Interhemispheric fissure anteriorly is well formed; however, poste-riorly the ventricles expand into a mono-ventricle with a shunt tube within it. Relatively well-developed anterior hemispheric fissure (arrows) suggests lobar holoprosencephaly. Note that no falx is seen. B, Monoventricle with no septum pellucidum or interhemispheric separation in a patient with alobar holoprosencephaly.

Figure 9-12 Alobar holoprosencephaly. A, The monoventricle is seen on computed tomography with a small cortical mantle peripherally. No falx or hemispheric separation is evident. B, Coronal T2-weighted image shows the absence of hemispheric separation except at the lamina terminalis level. C, Fusion of the thalami more posteriorly.

Figure 9-13 Semilobar holoprosencephaly. The posterior hemispheres are separated and the falx is implied to be present. The posterior ventricles look nearly normal but there is no development of the frontal horns. Fusion across the midline is seen anteriorly.

The CT findings in cases of holoprosencephaly include the absence or partial formation of the falx, interhemispheric fissure, and lateral ventricles. Patients typically have absence of the corpus callosum and an abnormally formed third ventricle. MR is a useful first study to examine patients with holoprosencephaly, because the evaluation of the corpus callosum, third ventricle, venous sinuses, vascular abnormalities, and septum pellucidum are better evaluated with MR. The olfactory bulbs and tracts are usually absent with lack of development of olfactory sulci and flat gyri recti. Associations with holoprosencephaly are listed in Box 9-2.

Often you must distinguish alobar holoprosencephaly from hydranencephaly and “maximal” hydrocephalus. If no cortical mantle is discernible around the dilated CSF space centrally, the diagnosis is hydranencephaly, especially if all that can be seen is a nubbin of occipital or posterior temporal cortex remaining with a falx present. If you see a well-formed falx, cortical mantle, and separated ventricles with a septum pellucidum, consider maximal hydrocephalus. If the thalami are fused, septum pellucidum or falx is absent, a cortical mantle is seen, and the ventricles have lost their usual shape, diagnose alobar holoprosencephaly.

A pearl: Holoprosencephaly is the one lesion in which the splenium and posterior portions of the corpus callosum may be formed, but the anterior corpus callosum is absent. Exception to this exceptional rule: The rostrum normally forms after the splenium.

Septo-optic Dysplasia (De Morsier Syndrome)

Septo-optic dysplasia is best considered as part of the spectrum of holoprosencephaly. As such, it represents a minor form of holoprosencephaly. The septum pellucidum is either absent (64%) or partially absent (36%), causing a squared-off appearance to the frontal horns of the lateral ventricles (Fig. 9-14). When the septum pellucidum is partially absent, usually the anterior portion is present. This is best seen on coronal MR. Agenesis of the corpus callosum and white matter hypoplasia may be associated with this abnormality. In general, patients with septo-optic dysplasia demonstrate small hypoplastic optic nerves and a small optic chiasm resulting from the dysplastic optic pathways. In some cases that dysplasia may be limited to the optic disk and the nerves/chiasm may not be small. Patients often (60%) have hormonal abnormalities (usually diminished levels of growth hormone) related to the hypothalamic-pituitary axis abnormality. Check for pituitary gland hypoplasia. Seizures coexist. Effects on the visual pathway may range from blindness to normal vision, nystagmus to normal eye movements.

Figure 9-14 Septo-optic dysplasia. Coronal T1-weighted image shows absence of the septum pellucidum with small optic tracts (arrows).

Schizencephaly (see section below) and neuronal migrational disorders may accompany septo-optic dysplasia in 50% of cases. Paradoxically, patients with the combination of schizencephaly and septo-optic dysplasia are more likely to have normal-sized ventricles, portions of the septum pellucidum spared, normal optic radiations, and seizures as a presentation. If schizencephaly does not coexist with septo-optic dysplasia, hypoplasia of the white matter (evidenced by corpus callosum thinning and ventricular enlargement), complete absence of the septum pellucidum, and worse hypothalamic-pituitary dysfunction usually are present.

Congenital Optic Nerve Hypoplasia

Congenital optic nerve hypoplasia commonly accompanies isolated growth hormone deficiency and multiple pituitary hormone deficiency syndromes. The absence of an anterior pituitary gland, a truncated pituitary stalk, and ectopic or absent posterior pituitary bright spot may also be found in this condition. Small optic nerves are a mandatory feature.

Schizencephaly

Schizencephaly refers to an abnormality of neuronal migration at the fifth to seventh week of gestation in which a cleft is seen coursing from the ventricular ependyma to the pial surface of the brain. This cleft has a gray matter lining (usually from polymicrogyric brain) and is usually seen in the supratentorial space (near the sylvian fissure) coursing to the lateral ventricles. The lips of the cleft may be apposed (closed-lipped) (Fig. 9-15) or gaping (open-lipped). The closed-lipped variety may be missed if the clefts are tightly apposed, but a dimple at the ventricle-cleft interface should suggest the diagnosis. At the ventricular junction there often is associated nodular heterotopia. Schizencephaly occurs most commonly in the frontal (44%), frontoparietal (30%), and occipital (19%) lobes. Bilateral involvement (35% to 67%) is associated with seizures, worse developmental delay, and developmental dysphasia. Motor dysfunction is more common with frontal lobe schizencephaly, open-lipped varieties, and wider gaps in the open lips. Anomalous venous drainage may also be associated with schizencephalic brain. The cause of this disorder is thought to be an ischemic watershed insult in utero that leads to infarction of the germinal matrix and radial glial fibers near the ventricles. If there is failure of the germinal matrix to form, there will be fusion of the pia and the ependymal lining of the ventricles. Normal migration to the cortex is impeded. Other theories espoused as to etiology include toxin exposure, viral infections, and genetic factors. Schizencephaly is often associated with focal cortical dysplasia (polymicrogyria), gray matter heterotopias, agenesis of the septum pellucidum (80% to 90%), and pachygyria. Some believe that focal cortical dysplasias are a form of schizencephaly or vice versa—just that the “cleft” never reaches the ventricle in the former. The lining of the cleft with gray matter, best seen on MR, is the differential point in this lesion and distinguishes it from encephalomalacic abnormalities (porencephaly), which are usually lined by white matter (Fig. 9-16). The inner surface of the cleft is pia-lined and communicates with the ependyma of the ventricle, which differentiates the lesion from an enlarged sylvian fissure seen in premature infants.

Figure 9-15 Schizencephaly. A, Can you find the evidence of the closed-lipped schizencephaly on this FLAIR scan? B, The nipple at the ventricular surface (arrow) on the T1-weighted image should eliminate any doubt.

Figure 9-16 Schizencephaly. Coronal T1-weighted image reveals an open-lipped schizencephaly (arrow) connecting to the lateral ventricle. Note the gray matter-lined lips (G) of the cleft.

Agenesis of the Corpus Callosum

Agenesis of the corpus callosum is one of the more common congenital abnormalities (occurring in 0.7% of all births). Patients with this anomaly often present with refractile seizures or mental retardation. The corpus callosum develops from anterior genu to posterior splenium, accounting for splenial absence in partial agenesis of the corpus callosum. The rostrum is the last portion of the corpus callosum to form, so the combination of absence of the splenium with rostrum agenesis should not put the neoneuroradiologist into a quandary. MR is ideal for the visualization of the corpus callosum because a midline sagittal image demonstrates all the portions of the corpus callosum (Box 9-3). Various degrees of corpus callosum agenesis may occur after complete agenesis; loss of the splenium is the next most common manifestation of this disorder (Fig. 9-17). If the splenium is absent, colpocephaly, dilation of the occipital horns of the lateral ventricles caused by a decrease in the posterior white matter mass, is seen. With complete agenesis, a high-riding, posteriorly oriented, dilated third ventricle; parallel and widely spaced orientation of the lateral ventricles; and impression on the medial aspect of the lateral ventricles because of Probst bundles are seen. The longitudinal Probst bundle is a parallel track of white matter that runs anteroposteriorly and is due to the alternative white matter tract development when the corpus callosum is absent (Fig. 9-18). As the fibers cannot cross, they redirect. The lateral ventricles (especially the occipital horns) are usually moderately dilated and concave medially, as is the third ventricle. Eversion of the cingulate gyrus is also present and the cingulate sulci are therefore not formed. This leads to a picture on the sagittal midline image where the medial hemispheric sulci extend down to the third ventricle. The third ventricle, in turn, extends into the interhemispheric fissure.

Figure 9-17 Agenesis of the corpus callosum. Sagittal T1-weighted image shows complete absence of the corpus callosum. Associated encephalocele in the basal region is identified by arrows.

Figure 9-18 Agenesis of the corpus callosum. A, Probst bundle in agenesis of corpus callosum. Coronal T1-weighted image shows the Probst bundle (P) causing lateral displacement of the frontal horns of the lateral ventricles. Cingulate gyri (C) are malformed. B, The shape of the ventricles suggests agenesis of the corpus callosum with colpocephaly (c). Probst bundles account for the inward bowing of the lateral wall of the lateral ventricle. Evagination of the cingulate sulcus (arrows) accounts for the high signal intensity medial to the lateral ventricles.

Other midline abnormalities may be associated with agenesis of the corpus callosum (see Box 9-3), such as an interhemispheric arachnoid cyst in the expected location of the corpus callosum or a pericallosal lipoma. A cyst would have low density on CT and signal intensity comparable to CSF on T1WI and T2WI. This can be distinguished from a lipoma (Fig. 9-19), which has fat intensity.

Figure 9-19 Agenesis of the corpus callosum with a fatty lipoma. Axial computed tomography reveals a low-density lipoma in the midline (asterisk) associated with agenesis of the corpus callosum. Lateral splaying of the lateral ventricles (arrows) is the tip-off to the agenesis.

Associated congenital abnormalities include agyria, pachygyria, heterotopias, Dandy-Walker syndrome, holoprosencephaly, septo-optic dysplasia, cephaloceles, and Chiari I and II malformations. Trisomy 13, 15, and 18; fetal alcohol syndrome; and Meckel syndrome (occipital encephalocele, microcephaly, polycystic kidneys, polydactyly) are also associated with agenesis of the corpus callosum (and also with holoprosencephaly).

Aicardi syndrome is seen in female patients and consists of the triad of agenesis of the corpus callosum, epilepsy, and choroidal abnormalities. Abnormal myelination, neuronal migrational abnormalities, colobomas, posterior fossa cysts, and microphthalmia may coexist.

Hamartomas

Hamartomas represent an abnormal proliferation of normal brain tissue in an abnormal location. Whereas the heterotopias are due to anomalous neuronal migration, hamartomas are a nonneoplastic proliferation of well-organized brain tissue. There is a propensity for hamartomatous formation in the hypothalamus (see Fig. 11-39). The patients typically present with precocious puberty; however, occasionally, visual disturbances may be present, because the hypothalamic hamartoma involves the optic pathways. Boys are more commonly affected than girls, and symptoms may also include seizures or laughing spells (gelastic seizures). Because the tissue that makes up a hamartoma is essentially normal brain substance, the hamartoma is isodense with gray matter on CT. On MR, the hamartoma is isointense to gray matter on T1WI and variable on T2WI. The abnormality is identified as a bulbous protrusion of the hypothalamic region in the midline. The hamartomas do not have an abnormal blood-brain barrier and are not expected to show enhancement on either CT or MR. Occasionally, mass effect may be associated with the hamartoma, as evidenced by displacement of the inferior portion of the third ventricle.

Hamartomas may occur in other locations. After the hypothalamic region, the next most common location for hamartomas is the cerebral cortex-subcortical region. Occasionally hamartomas may be seen in a periventricular location.

Fetus in fetu refers to duplication of brain structures, usually seen as an extra-axial frontal region mass. The signal intensity approaches that of normal brain. Case studies of ectopic brain in the nasopharynx or pterygopalatine fossa have also been reported.

Heterotopias

Heterotopic brain is disorganized brain tissue, usually gray matter, that is located in the wrong place because of a premature arrest in neuronal migration from the germinal matrix to the cerebral cortex (Fig. 9-20). Patients usually have seizures, weakness, spasticity, hyperreflexia, or developmental delay. Heterotopias form as a result of an abnormality in neuronal migration at the seventh to sixteenth week of gestation, when migration of the neuroblasts from the periventricular region to the pia is thwarted, possibly because of damage to the radial glial fibers, which orient migrating neurons. The classification of heterotopias is usually divided into two varieties: nodular and band types. Under nodular types, you will find subependymal/periventricular and subcortical variants. A subependymal location is very common, and these gray matter heterotopias are usually truly nodular in appearance (Fig. 9-21) and have the same signal intensity as gray matter. If there is hyperintensity on T1WI, it may be due to dystrophic microcalcifications, and these may show hyperdensity on CT. They may occur as an isolated anomaly or in association with other congenital lesions. A gene, responsible for the protein filamin-1, on the long arm of the X chromosome, has recently been implicated in some cases of nodular subependymal heterotopia. The favored sites are at the trigone or occipital horns of the lateral ventricles. They are bilateral in a high rate, but favor the right side over the left.

Figure 9-20 Brain tumor … NOT! The first-year fellow read the case as a low-grade glioma. No wonder our program is a two-year fellowship. The absence of edema and the isodensity to gray matter actually suggests a gray matter heterotopia. That is an OK miss in August (1 month into fellowship), but a May reprimand for a first-year fellow, and a “see you next year” at the CAQs.

Figure 9-21 Heterotopia. A, Axial unenhanced computed tomography shows nodular subependymal heterotopia (arrows) bilaterally lining the lateral ventricle. This patient did not have tuberous sclerosis. B, Sagittal T1-weighted image shows indentation of the lateral ventricle by gray matter nodules (arrows) from subependymal heterotopia. Tuberous sclerosis nodules have intensity similar to white matter.

Patients with subcortical heterotopias often have abnormal sulcation patterns superficial to the heterotopia. The hemisphere ipsilateral to the site of the subcortical heterotopia may be smaller with thinning of the overlying cortex. Subcortical heterotopias may be nodular or curvilinear in shape. The nodular variety of subcortical heterotopias is usually identified in a periventricular or subcortical location, whereas the diffuse (or laminar) heterotopias are seen more commonly in or close to the cortex. These lesions do not enhance and do not elicit edema.

The band type of heterotopias is associated with severe developmental delay and earlier onset of seizures than the focal type (Fig. 9-22). The X-linked gene doublecortin (DCX) predisposes to lissencephaly in men and band heterotopia in women (protected by two X chromosomes). Band heterotopias are isointense with cortical gray matter with well-defined smooth margins. A thin interface of white matter is located between the band (laminar) heterotopia and the cortex, creating the double-cortex sign. The heterotopic tissue may demonstrate mass effect and distort deep gray or white matter structures. The overlying cortex may be abnormal as well due to abnormal sulcation/gyration/migration. Band heterotopias are explained as anomalies arising because of arrest of neuronal migration in the intermediate zone between the germinal matrix and the outer cortex (where the cells belong).

Figure 9-22 Subcortical heterotopia. Axial T2-weighted image delineates gray matter signal intensity within the centrum semiovale and corona radiata on the left side (arrowheads). Note the distortion of the left lateral ventricle at the interface with heterotopic gray matter (arrows).

The abnormality is difficult to diagnose by CT but may be suggested when one identifies an island of higher density, nonenhancing tissue suggestive of gray matter in a white matter location. These abnormalities are much better demonstrated with MR, where one can distinguish the gray matter from the white matter on T2WI with a high degree of accuracy. Within the dark myelinated white matter, one typically finds a higher signal intensity island of irregular tissue representing the heterotopia. Look for gray, white, gray, white, ventricle as the pattern for band heterotopias—it is the second gray that is the rub.

Encephaloceles, holoprosencephaly, schizencephaly, Chiari malformations, and agenesis of the corpus callosum may coexist with gray matter heterotopias.

Pachygyria

Pachygyria (incomplete lissencephaly) is a condition of short, broad, fat gyri caused by abnormal sulcation and gyration of the cortical mantle. It is a congenital abnormality that occurs relatively late in gestation, at 12 to 24 weeks, because of neuroblastic migration not proceeding completely to the superficial layers of the cortex (Fig. 9-23). At its most extreme, no sulcation at all may occur, creating a smoothly outlined hourglass configuration to the brain. No sylvian fissures are formed. This condition is termed agyria or complete lissencephaly and is due to abnormal formation of the superficial cortex of the brain, where incomplete neuroblastic migration to the six-layered cortex has occurred, possibly from cortical laminar necrosis of the third cortical layer. A bright rim around the cortex may be seen on T2WI because of this laminar necrosis in the “cell-sparse layer” of the cortex (Fig. 9-24). Patients with congenital cytomegalovirus (CMV) infection have high rates of pachygyria. As opposed to hemimegalencephaly, white matter volume will be decreased; in both, gray matter appears thicker because of poor sulcation. Abnormal myelination may coexist.

Figure 9-23 Pachygyria. Bilateral symmetric pachygyric brain is seen in the parietal lobes on this FLAIR image. The white matter does not arborize in these regions.

Figure 9-24 Classic lissencephaly. A, On this sagittal T1-weighted image (T1WI) incomplete lissencephaly includes areas of agyria (more often parieto-occipital) and pachygyria (frontotemporal). B, On axial T1WI, the sylvian fissures are shallow and maloriented, causing a figure-eight appearance (in this case a bit topheavy). C, On this T2WI, one can identify posteriorly the unmyelinated white matter of the cell sparse layer (arrowheads) that separates the thin cortex from the deeper thickened gray matter in lissencephaly.

Two chromosomes have been associated with lissencephaly. With those from the X chromosome (DCX gene), you tend to see more severe involvement with a frontal lobe predominance, most commonly in females. Classic lissencephaly (type 1) associated with the LIS1 gene on chromosome 17 affects the parietal lobe more than the frontal lobe. Classic lissencephaly shows a smooth cortical surface with or without rudimentary gyral formation in the inferior frontal and temporal lobes and is due to arrest of cellular migration. High-intensity bands representing the cell-sparse layer are seen in the parieto-occipital regions. An hourglass configuration due to incomplete opercularization of the temporal lobes is representative.

Cobblestone lissencephaly (type 2) is seen in association with Fukuyama muscular dystrophy and Walker-Warburg syndrome. In this entity, you see nodular surface irregularities, ocular anomalies, and muscular disorders. The neuroblasts have migrated beyond the expected confines of the superficial cortex to protrude into the subarachnoid space. Walker-Warburg syndrome is characterized by macrocephaly, posterior encephaloceles, absent myelination, cerebellar hypoplasia, and microphthalmos.

Microlissencephaly and microcephaly with a simplified gyral pattern present with a small head, a smooth cortical surface, and thickening of the cortex with and without other associated anomalies.

Polymicrogyria

It is believed that polymicrogyria is due to ischemic laminar necrosis of the fifth cortical layer after the twentieth week of gestation, by which time the neurons have reached the cortical surface. CMV infection has been implicated as a cause, but other infections or vascular insults in utero may also lead to polymicrogyria. This disorder is frequently seen in patients with Chiari malformation and schizencephaly. Patients usually have developmental delay, spasticity, or seizures.

Grossly, one can see excessive numbers of small, disorganized cortical convolutions usually in the cortex subjacent to the sylvian fissures. The cortex appears thickened. The white matter thickness is normal (remember that it is increased in hemimegalencephaly and smaller in agyria). On MR, one may be able to distinguish pachygyria from polymicrogyria; the cortex is less thick with polymicrogyria (5 to 7 mm) than with true pachygyria (8 mm). On thin section images polymicrogyria is “bumpier” than pachygyria. Another distinguishing feature between pachygyria and polymicrogyria is the possible presence of abnormally bright white matter on T2WI deep to the latter. An association with developmental venous anomalies (anomalous venous drainage) is noted with polymicrogyria. When focal, some people use the term cortical dysplasia for polymicrogyria.

Congenital bilateral perisylvian (opercular) syndrome is recognized as an entity in which there is polymicrogyria involving the opercular cortex associated with abnormal sylvian fissure sulcation. Patients with congenital bilateral perisylvian syndrome disorder have seizures, congenital pseudobulbar paresis, and developmental delay. The abnormal sylvian fissure may have cortical thickening on either side. Schizencephaly and anomalous venous drainage may also be present. There are rarer bilateral frontal and bilateral frontoparietal polymigrogyria variants as well.

Cerebellar polymicrogyria, lissencephaly, and clusters of intraparenchymal cerebellar cysts may occur in Fukuyama muscular dystrophy. When one sees disordered cerebellar folia and small cysts in the cerebellum in a Japanese patient, one should consider this diagnosis. The cysts may predominate in the semilunar lobule. Cerebral polymicrogyria or pachygyria, absent or delayed myelination, thickened meninges, vermian hypoplasia, fused folia, and hydrocephalus may coexist. The polymicrogyria tends to involve the frontal and parietotemporal lobe, whereas pachygyria involves the temporo-occipital lobes. The polymicrogyria, sometimes called cobblestone lissencephaly, can affect the frontoparietal regions with a smooth lissencephaly of the temporo-occipital zone. Other forms of congenital muscular dystrophy are also associated with polymicrogyria and cortical dysplasias.

Type 1 Focal Cortical Dysplasia (Without Balloon Cells)

Cortical dysplasia may be a source of seizures both for the patient and for the unwary neuroradiologist trying to find the entity. It is said that such developmental anomalies are present in 11% to 23% of specimens from surgical procedures performed for epilepsy. The findings may be very subtle, manifested as mild focal volume loss, thickening of cortex, abnormal sulcation, or blurring of cortical margins, without signal intensity variation from gray matter.

The CSF cleft overlying a cortical dimple is a specific sign of cortical dysgenesis. The cortex buckles inward away from the brain surface, leading to a dilated subarachnoid space overlying it. This is seen in more than 80% of patients with nonballoon cell focal cortical dysplasia, 100% of cases of polymicrogyria, and all cases of schizencephaly.

Other MR findings suggesting dysplasia rather than tumor include the presence of homogeneous hyperintense T2WI signal in the subcortical white matter that tapers as it extends to the lateral ventricle (Fig. 9-25). This signal may be due to hypomyelination or wallerian degeneration. Most clinical manifestations are motor, with spastic hemiplegia.

Figure 9-25 Cortical dysplasia. Notice the thickened cortex, dimpled surface with mildly expanded cerebrospinal fluid space, and abnormal subcortical signal in the white matter on T1-weighted (A), FLAIR (B) and T2-weighted image (C).

Microdysgenesis is a term used for a situation where there are too many cells in the cortex with clusters of ectopic neurons in the molecular layer, an excess of neurons in the white matter, and alterations in the cortical laminar architecture without balloon cells. It is a cause of generalized seizures. One etiology may be from hypoglycemia. On imaging, look for abnormal white matter signal with volume loss.

Balloon Cell Focal Cortical Dysplasia of Taylor

Disorders of abnormal neuronal proliferation include balloon cell focal cortical dysplasia of Taylor, in which the number of neurons are increased in number and maloriented. This entity manifests cortical thickening, hyperintense subcortical white matter on T2WI, indistinct gray-white borders, and radial bands from the ventricle to the cortex, usually affecting the frontal lobe. These bands may be of white or gray matter intensity. The appearance is similar to a cortical tuber. In focal gray transmantle dysplasia, gray matter extends from the subependymal zone to the cortex with associated pachygyria, heterotopia, polymicrogyria, and schizencephalic defects. A frontal lobe location favors a balloon cell dysplasia, whereas a temporal lobe (especially medial temporal lobe) location is more suggestive of a neoplasm. Clinical presentation is that of seizures and sensory motor deficits.

Rarely, one may see anomalous venous drainage from areas of cortical dysplasia. Other associations include dysembryoplastic neuroepithelial tumors, gangliogliomas, gangliocytomas, and mesial temporal sclerosis.

Megalencephaly

Megalencephaly is defined as enlargement of all or part of the cerebral hemisphere. Bilateral causes (Box 9-4) and unilateral causes (Box 9-5) may have some overlap and account for various head shapes. Often polymicrogyria (associated with increased hemispheric size) or agyria (associated with less severe hemispheric enlargement) is found on the affected side. MR demonstrates a distorted, thickened cortex with ipsilateral ventricular dilation (Fig. 9-26). This unique feature, that of ventricular dilation on the side of the enlarged hemisphere, separates congenital hemimegalencephaly from other infiltrative lesions. This disorder results from too many neurons and decreased apoptosis. Heterotopias and cortical thickening are characteristic. Myelination is delayed, but overall white matter volume is increased. Alternatively, megalencephaly may be an isolated finding. Patients have seizures, hemiplegia, developmental delay, and abnormal skull configurations.

Figure 9-26 Hemimegalencephaly. Axial T2-weighted image discloses enlargement of the left hemisphere with disorganized brain tissue and a neuronal migrational anomaly. Note the lack of sulcation and the abnormal white matter formation in this child. Big brain, big ventricle.

Interestingly, a patient with hemimegalencephaly of one hemisphere in infancy may actually show hemimicrocephaly of the hemisphere in later life due to retarded growth of the dysmorphic brain, causing the contralateral hemisphere to seem larger. Hemimegalencephaly may occur in a variety of syndromes, including neurofibromatosis type 1, Soto syndrome, proteus syndrome, epidermal nevus syndrome, tuberous sclerosis, and Klippel-Trenaunay-Weber syndrome.

Proteus syndrome, which has cutaneous manifestations similar to neurofibromatosis and encephalocraniocutaneous lipomatosis, may present with hemimegalencephaly, subependymal calcified nodules, and periventricular cysts. Irregularly shaped vertebrae may accompany the intracranial findings. Macrocephaly, macrodactyly, hemihypertrophy, cutaneous nevi, soft-tissue tumors, and lipomatosis may make for one unusual-looking patient.

Lipomas

It is now generally accepted that most intracranial lipomas represent congenital abnormalities rather than neoplasms. Lipomas occur because of persistence or maldevelopment of the meninx primitiva, the neural crest tissue that ultimately forms the neural tube. The most common sites of lipomas are the interhemispheric fissure (50%), quadrigeminal plate cistern, pineal region, hypothalamic region, and cerebellopontine angle cistern. These lesions do not grow and are symptomatic only because of other associated congenital anomalies or mass effect on neighboring structures. Many (up to 50%) are associated with agenesis of the corpus callosum. Treatment tends to be conservative because vessels often course through the lipoma, making surgical removal that much harder.

Lipomas have attenuation values on CT that are in the negative range, usually −30 to −100 HU, and are isodense to subcutaneous fat (see Fig. 9-19). High in intensity on T1WI, intermediate to low in intensity on conventional T2WI, and bright on fast spin-echo T2WI, the fat of the lipoma can be corroborated by the presence of a chemical shift artifact along the frequency-encoding direction. This causes one edge of the lesion to be highlighted as very bright on T2WI and the other edge along the frequency-encoded axis to be darkened. Alternatively, a fat-suppression pulse sequence can verify the fat by demonstrating signal diminution after it is applied. Calcification may be seen.

Aqueductal Stenosis

Aqueductal stenosis, causing lateral and third ventricular enlargement without fourth ventricular dilation, is usually seen in boys as part of an X-linked recessive hereditary disorder. This is thought to be due to an abnormality of proliferation and differentiation of the periaqueductal gray matter of the mesencephalon, leading to the stenosis. Acquired causes of aqueductal stenosis are numerous and include clots from subarachnoid hemorrhage and fibrosis after bleeds or infections. The congenital causes occur in the setting of enlarged head circumference in infant boys and may be due to webs, septa, or membranes. This entity is covered in greater depth in Chapter 8.