Malformations
NEURAL TUBE DEFECTS: DYSRAPHIC DISORDERS
The following classification is based on present understanding of the development of the neural tube and axial skeleton (Figs 3.1–3.3).
3.2 Primary and secondary neurulation.
Unlike the multisite mechanism of primary neural tube closure (i.e. primary neurulation) in the mouse, direct observation in man favors only two initiation sites. Closure begins at approximately 22 after ovulation at closure site 1 (the future cervical/hindbrain boundary), and separately soon after at site 2 (rostral tip of forebrain). Fusion spreads bidirectionally from site 1, and unidirectionally from site 2. About 26–28 after ovulation cranial closure is completed at the anterior neuropores, and cord closure at the posterior neuropore at the upper sacral level. Caudal to this level all non-epidermal tissues are formed from the tail bud of multipotential stem cells (shaded red) by a process of differentiation and canalization (i.e. secondary neurulation).
3.3 Development of the neural tube and axial skeleton.
(a) Induction of the neural plate from midline ectoderm occurs at around 16 after ovulation. (b,c) From 18–20 after ovulation, there is a gradual elevation of the lateral edges of plate to form the neural folds, and deepening of the longitudinal neural groove. Midline mesodermal tissue gives rise to both the centrally placed notochord and lateral somites. Neural crest arises at the boundary between the neural plate and ectoderm. (d) At about day 22, the neural folds start to close at the cervical/hindbrain boundary (see Fig. 3.2). (e) Fusion is completed to produce the neural tube. Soon after, the mesodermal somites migrate around the tube to produce the spinal vertebrae, skull vault, and occiput. The skull base and facial bones are derived from neural crest.
DEFECTS OF NEURAL TUBE CLOSURE
MACROSCOPIC APPEARANCES
Anencephaly is characterized by replacement of most of the intracranial contents by a ragged, cavitated, vascular mass, the area cerebrovasculosa (Fig. 3.4). Remaining neural tissue usually includes the gasserian ganglia, distal parts of the cranial nerves, a variable amount of the medulla, and rarely, a few cerebellar folia.
3.4 Anencephaly in an 18-week-old fetus.
The eyes are abnormally protuberant, the pinnae are low-set, and the neck is short. The calvarium is absent and the upper cervical vertebrae are not fused. The intracranial contents are a ragged vascular mass, the cerebrovasculosa. (a) Anterior view. (b) Posterior view.
The skull shows various abnormalities including:
an absent or hypoplastic skull vault
a thickened and flat skull base
ANENCEPHALY
Spinal involvement varies from failure of fusion of the upper cervical vertebrae to craniorachischisis (Fig. 3.5).
MICROSCOPIC APPEARANCES
Histologically, the area cerebrovasculosa consists of an angiomatous mass of small blood vessels (Fig. 3.6) mixed with disorganized neuroepithelial tissue, particularly glia, some neuroblasts or neurons, ependyma, and choroid plexus. Rarely, ependyma-lined cavities suggest forebrain ventricle.
MYELOMENINGOCELE
Myelomeningocele (Figs 3.7, 3.8) is the herniation of spinal cord and meningeal tissue through a vertebral defect.
3.7 Three examples of lumbosacral myelomeningocele in fetuses.
(a) An open disc of vascular and neural tissue, or myelocele. (b) A closed cystic lesion. (c,d) Spina bifida cystica in combination with exomphalos, the closed cord floating within a myelomeningocele sac, viewed from the side in (c), and viewed from behind, in (d).
3.8 Lumbosacral myelomeningocele in association with the Arnold–Chiari malformation.
A tangled mass of cord tissue, peripheral nerves, and fibrous tissue opens to the exterior and blends with surrounding skin.
MYELOMENINGOCELE
MACROSCOPIC APPEARANCES
MICROSCOPIC APPEARANCES
Histologically, the epidermis overlying a myelomeningocele is atrophic (Fig. 3.9), lacking rete pegs and skin appendages, and often ulcerates. Beneath the epidermis there are fibrotic connective tissue, many dilated thin-walled vessels, and islands of glial tissue, which are sometimes accompanied by nerve cells and ependymal tissue.
HERNIATION OF NEURAL TUBE THROUGH AXIAL MESODERMAL DEFECTS
Encephalocele is herniation of brain tissue through a skull defect (Figs 3.10–3.16) and is usually (75%) occipital. Rarer examples are parietal or fronto-ethmoidal.
3.10 Occipital encephalocele.
The encephalocele is a fluctuant mass covered by skin, which is peripherally hairy but centrally shiny and thin.
3.11 Anterior encephalocele.
This large swelling at the fronto-ethmoidal junction bulges out over the forehead and root of the nose and causes marked hypertelorism.
3.12 Nasal encephalocele.
Transection of a cystic polyp surgically excised from the nose revealed an ependyma-lined cavity containing a tuft of choroid plexus.
3.13 Occipital encephalocele.
Parts of both occipital horns and occipital poles fill the sac of this large surgical specimen. The cortex is markedly thinned and the lobes appear fused. Highly vascularized meninges are sandwiched between the cortical remnant and overlying skin. (a) Resection margin. (b) Section through the specimen.
3.14 Herniation due to a massive occipital encephalocele.
The herniation is usually asymmetric. This occipital sac contains much of the posterior part of the left hemisphere as well as cerebellum. (a) Viewed from the left side. (b) Viewed through the midline. (c) A coronal section at the thalamic level appears very confusing at first. The smaller left hemisphere remnant is out of register with the right side and there is marked distortion of central structures.
3.15 Histology of a surgically excised encephalocele.
(a) At low magnification, there is a recognizable cortical ribbon and ventricular cavity. The cortical ribbon has the undulating pattern of polymicrogyria, while heterotopic gray matter abuts the ventricular wall. (b) At higher magnification the surface shows an excessively folded polymicrogyric cortex and numerous nodular glioneuronal heterotopias within the overlying leptomeninges.
3.16 Surgically excised encephalocele.
Some encephaloceles contain only small islands of glial tissue, which can be readily demonstrated with hematoxylin–van Gieson.
MACROSCOPIC APPEARANCES
MECKEL SYNDROME
Occipital encephalocele may be associated with Meckel syndrome (also known as Meckel–Gruber syndrome) (Fig. 3.17). Other neuropathologic findings include midline and hindbrain anomalies. Protrusion of meninges alone is termed a cranial meningocele (Fig. 3.18).
OCCULT SPINA BIFIDA
MACROSCOPIC APPEARANCES
The cord may appear normal but often shows a distended central canal (hydromyelia) (Fig. 3.19), diastematomyelia (Fig. 3.20), or cord tethering (Fig. 3.21), all of which involve lower lumbar or sacral levels.
3.19 Hydromyelia.
(a) Horizontal sections of the cord showing marked dilation of the central canal at thoracic and lumbar levels. (b) Despite marked distension of the lumbar central canal the ependyma is virtually intact.
3.20 Diastematomyelia.
This is characterized by splitting of the cord into two hemicords separated by a median septum of fibrous meninges. This example is from a patient with Chiari type II malformation.
3.21 Tethered cord.
Lower limb motor and sensory deficits and neuropathic bladder are the principal presenting signs of the tethered cord syndrome. Operative findings include a low conus and thickening of the filum, often in association with a lipoma, as shown in this typical surgical specimen, which comprises remnants of ependymal canal (arrows) and lobules of mature adipose tissue.
Although a closed lesion, occult spina bifida is often indicated by overlying tufts of hairy skin or lipomatous skin tags (Fig. 3.22). It may be associated with sacral, anorectal, and urogenital defects.
CHIARI MALFORMATIONS
Chiari defined three anatomic types of cerebellar deformity associated with hydrocephalus.
CHIARI TYPE I MALFORMATION
Chiari type I malformation is the herniation of a peg of cerebellar tonsil through the foramen magnum in the absence of an intracranial space-occupying lesion or preceding hydrocephalus (Figs 3.23–3.25).
3.23 Chiari type I malformation, posterior view.
Both cerebellar tonsils are markedly but asymmetrically elongated into the spinal canal (towards the right).
3.24 Chiari type I malformation.
In a 10-month-old child presenting with polydactyly, hemihypertrophy, and hemimegalencephaly plus polymicrogyria, a bifid tongue of tonsillar tissue extends 2.5 cm below the inferior olives.
3.25 Chiari type I malformation associated with craniosynostosis due to craniometaphysial dysplasia.
(a) Superior view of the brain within the thickened skull. (b) MRI shows tonsillar herniation to the level of the second cervical vertebra. The brain, spinal cord, and roots are surrounded by a dark halo of massively thickened bone. (Courtesy of Dr K Chong, Great Ormond Street Hospital for Children, London, UK.)
CHIARI TYPE I MALFORMATION
CHIARI TYPE II (ARNOLD–CHIARI)
Chiari type II malformation combines herniation of the cerebellar vermis with malformation and downward displacement of the brain stem (Figs 3.26–3.29). The degree of cerebellar herniation varies from slight (in fetuses) to extensive, at which point the choroid plexus and tonsils may be included. The cerebellar tail is bound by fibrous adhesions to the dorsal surface of the medulla or occasionally is situated within the fourth ventricle. Folia in the herniated cerebellar tissue show neuronal loss, absence of myelinated fibers, and gliosis.
3.26 Chiari type II (Arnold–Chiari) malformation.
Midline section of the brain and cord within the skull and vertebral column, demonstrating the downward displacement of vermis and brain stem and beaking of the tectum. Chiari type II malformation is usually associated with a lumbosacral myelomeningocele and hydrocephalus, as illustrated here.
3.27 Chiari type II malformation.
Mid-sagittal sections of the hindbrain are most helpful when the diagnosis is not clear. (a) A tongue of vermis capped by choroid plexus extends down over the dorsal surface of the cervical cord. The lower brain stem is elongated and the tectum is beaked (arrow). (b) In this example, the ‘beaking’ of the tectum is more marked, and the lowest part of the medulla overrides the cord producing an S-shaped bend.
3.28 Horizontal microscopic sections of herniated tissue in Chiari type II malformation.
(a) Cerebellar vermis herniating over the medulla has markedly sclerotic folia. (b) A section through the region of the S-bend (see Fig. 3.27b) where low medulla overrides cervical cord.
3.29 Chiari type II malformation in three fetal brains.
Brain stem elongation and downward herniation over the upper cord are obvious, but there is only slight herniation of the vermis. (a) The brain of a 14-week-old fetus viewed from the side. (b) 18-week-old fetus. The herniation is seen in situ after removal of the atlanto-occipital membrane and upper vertebral arches, which is the most reliable method for arriving at a necropsy diagnosis. (c) 20-week-old fetus, the hindbrain viewed from the side. Note the lower medulla overrides the cervical cord.
CHIARI TYPE III MALFORMATION
Chiari type III malformation is the rare cerebello-encephalocele through an occipitocervical or high cervical bony defect (Fig. 3.30). Associated brain stem deformities and lumbar spina bifida are reminiscent of those associated with Chiari type II malformation.
3.30 Chiari type III malformation.
There is herniation of cerebellum into an occipitocervical encephalocele.
CHIARI TYPE II MALFORMATION
PATHOGENESIS OF CHIARI TYPE II MALFORMATION
Older theories attribute distortion of the cerebellum and brain stem to compression by hydrocephalic cerebral hemispheres or to traction from cord tethering, but these explanations cannot be sustained in the presence of an S-shaped brain stem deformity or the absence of spina bifida or hydrocephalus in a few cases.
DISORDERS OF FOREBRAIN INDUCTION
Various interrelated hemispheric anomalies result from failures in outgrowth and separation of the forebrain vesicles and in the development of the commissures (Fig. 3.31). The hemispheric anomalies are associated with craniofacial anomalies (see Fig. 3.38).
3.38 Craniofacial dysmorphology accompanying holoprosencephaly.
(a) The skull floor lacks an ethmoid plate and there is olfactory aplasia. In this case the optic nerves are hypoplastic (arrow). (b) Hypotelorism and cebocephaly with a single nostril. (c) Cleft lip and palate. (d) Cyclopia and proboscis in a case of trisomy 13. (e) External view of cyclopia and nasal pit in the case depicted in Fig. 3.36c–f. (f) Intracranial view of the single globe and minuscule anterior fossa in the case depicted in Fig. 3.36c–f.
HOLOPROSENCEPHALY
HOLOPROSENCEPHALY
ETIOLOGY OF HOLOPROSENCEPHALY
Holoprosencephaly is a heterogeneous group of conditions.
Mechanical or chemical methods have been used to induce it experimentally.
Holoprosencephaly is a feature of Smith–Lemli–Opitz syndrome.
ALOBAR HOLOPROSENCEPHALY
Alobar holoprosencephaly (Figs 3.32–3.37) is the severest form and is characterized by:
3.32 Alobar holoprosencephaly.
(a) Viewed from below, the small single fused holosphere is helmet shaped with minimal gyration, absent olfactory structures, and anomalous cerebral arteries, which run in shallow gutters. Although the hindbrain is relatively well preserved, overall there is marked microcephaly and the total brain weight is 150 g at 18 months. (b) Lifting the holosphere forwards allows a view from behind into the single ventricular cavity. Around its margin runs the hippocampus in a complete arch, while in the floor are fused basal ganglia and thalami. Just behind them is the quadrigeminal plate with the pineal and entrance to the aqueduct. Note the tattered remnant of the roof membrane at the lateral posterior edge of the holosphere. (c) A coronal section through the holosphere shows marked hydrocephaly, thin pallium, and fused thalami.
3.33 Alobar holoprosencephaly.
In all cases there is severe microcephaly, but the shape of the forebrain varies. (a) A globular holosphere viewed from below, and (b) viewed from behind, has only a small posterior membrane. (c) Coronal sections reveal the single forebrain and fused basal ganglia, but the ventricular cavity here is not dilated.
3.34 Alobar holoprosencephaly.
Viewed in situ within the skull the delicate cyst that covers the caudal part of the holosphere is well demonstrated.
3.35 Alobar holoprosencephaly in 17-week-old fetuses.
(a) An inferior view of a horseshoe holosphere with olfactory aplasia and aberrant vessels radiating across the orbital surface. (b) A similar case seen from behind and photographed in water so that the cystic roof membrane billows out.
3.36 Alobar holoprosencephaly.
There is extreme microcephaly in some fetal examples. (a) Tiny pancake-shaped forebrain viewed from below. (b) Tiny pancake-shaped forebrain viewed from behind. (c,d) An exceptionally hypoplastic brain for comparison with (a) and (b). (c) Viewed in situ within the skull. (d) Viewed as a fixed specimen: the minute prosencephalon is only a narrow rostral mass of tissue apparently lacking a ventricular cavity and caudal cyst, its connection to the basal ganglia and fused thalamus being only a thin ventrally situated bridge. (e,f)Microscopic coronal sections through the central part of the specimen reveal bilateral hippocampi and lateral ventricular horns (e) opening into a cystic space lined by ependyma. (f) Note the fused midline thalamus and dorsolateral striata.
3.37 Cortical dysplasias encountered in holoprosencephaly at microscopy.
(a) Status verrucosus. (b) A four-layer cortex with segregation of the superficial layers. (c) Thick cords of neurons running across the pallium. (d) Similar cords as in (c) associated with deeply placed acellular zones or glomeruli.
Craniofacial malformations are associated with alobar holoprosencephaly (Fig. 3.38). The face tends to predict the brain, particularly midfacial hypoplasia. The severest is cyclopia with fused orbits and eyes. Other anomalies include a proboscis (ethmocephaly), absent jaw (agnathia), fused ears (synotia, otocephaly), flat nose with a single nostril (cebocephaly), microphthalmia, hypotelorism, and occasionally hypertelorism.
SEMILOBAR HOLOPROSENCEPHALY
This lesion is intermediate between the alobar and lobar forms (Fig. 3.39). There are mild microcephaly, a partly formed shallow interhemispheric fissure, and some lobar structure with rudimentary temporal and occipital horns but continuity of the cortex across the midline. Olfactory structures are usually absent.
3.39 Semilobar holoprosencephaly.
(a) Superior view of brain within the skull showing anterior fusion and anomalous gyral pattern. (b) The fixed specimen viewed from below showing rudimentary temporal lobes. (c) In coronal sections there is a shallow interhemispheric fissure, but the cortical ribbon is continuous over the vertex and the orbital pallium is completely fused. (d) More posteriorly there is separation of the hemispheres.
LOBAR HOLOPROSENCEPHALY
Despite near-normal brain size, normal lobe formation, and separated hemispheres, the cerebral cortex is continuous across the midline, at the frontal pole, or in the orbital region, or above the callosum (cingulosynapsis) (Fig. 3.40).
3.40 Lobar holoprosencephaly.
(a) There is gyral fusion over the central part of the hemispheres. (b) In coronal sections the cingulate cortex runs continuously across the midline over the corpus callosum (cingulosynapsis). Slung beneath the callosum is a nodular gray heterotopia. (c) Further back the hemispheres remain incompletely separated. A continuous parietal cerebral wall and no sagittal fissure are evident superiorly. The occipital horns and temporal lobes are quite distinct. (d) Cingulosynapsis in fetal brain. The fused cingulate cortex is thin and looped, reminiscent of polymicrogyria. (e) Close-up view of the polymicrogyric fused cingulum.
OLFACTORY APLASIA
This is characterized by absent olfactory bulbs, tracts, trigone, and anterior perforated substance and is associated with anomalous cortical convolutions and an absent gyrus rectus (Fig. 3.41). Olfactory aplasia is usually an incidental postmortem finding or associated with holoprosencephaly, callosal agenesis, septo-optic dysplasia, or Kallmann or Meckel syndrome. It is usually bilateral. Unilateral absence is exceptional.
3.41 Olfactory aplasia.
(a) Bilateral absence of olfactory bulbs and tracts. There is an anomalous orbital convolutional pattern, lacking gyri recti. (b) An extremely rare example of right unilateral olfactory aplasia. Compare the abnormal gyral pattern on the right side of the brain with the normal left side, which includes the proximal part of the olfactory tract (arrow).
ATELENCEPHALY AND APROSENCEPHALY
These rare syndromes manifest as microcephaly (Fig. 3.42) and show features common to both anencephaly and holoprosencephaly.
3.42 Atelencephaly in a 9-month-old infant.
(a) Viewed from below. There is extreme microcephaly (total brain weight 95 g). The tiny uncleaved globular forebrain shows olfactory aplasia, but includes a myelinated optic chiasm. (b) When the forebrain is bisected coronally there are few distinguishing features, no visible ventricular cavity, and only a dorsal arch of myelinated fibers. (c,d) Histologic sections of the forebrain at low magnification suggest a symmetric organization, confirm the presence of myelinated fibers, and show a thin undulating cortex over the vertex, and a gliomesodermal thickening of the basal leptomeninges. (e) Histology also shows a midline raphe containing small calcospherites and tiny ependymal tubules. (f) A more laterally placed line of ependymal tubules is seen here, which may represent an abortive attempt to produce a ventricle. (g) The looped four-layer cortical ribbon is reminiscent of polymicrogyria.
AGENESIS OF THE CORPUS CALLOSUM
Agenesis of the corpus callosum may be:
Total or partial (e.g. missing only the splenium).
Isolated or combined with other malformations (e.g. holoprosencephaly).
MACROSCOPIC AND MICROSCOPIC APPEARANCES
AGENESIS OF THE CORPUS CALLOSUM
ETIOLOGY OF AGENESIS OF THE CORPUS CALLOSUM
If the callosum is deficient, the cingulate gyrus is also deficient. A radiating gyral pattern forms the medial surface of the cerebral hemisphere. The lateral ventricles have a membranous roof with upturned pointed corners, and a large longitudinal myelinated fiber bundle (of Probst) is present laterally. The membranous roof of the (usually distended) third ventricle bulges into the interhemispheric fissure, displacing the fornices laterally from where the widely separated leaves of the septum incline laterally towards the Probst bundles (Figs 3.43–3.45). The occipital horns are often markedly dilated. The anterior commissure is variably present, the posterior commissure is always present, and the psalterium is never present.
3.43 Agenesis of the corpus callosum in a 3-month-old child with maple syrup urine disease.
(a) Medial aspect of the hemisphere. The callosum and cingulum are absent, and an irregular arrangement of gyri surrounds the ventricle. (b) Frontal coronal sections show the absence of the corpus callosum and anterior commissure. The lateral angles of the lateral ventricles point upwards. There appears to be no septum pellucidum in the midline, but the leaves of the septum are swept laterally to cover the fornices and the bundles of Probst (arrow), which bulge into the medial walls of the frontal horns.
3.44 Agenesis of the corpus callosum.
(a) Medial aspect of the hemisphere showing replacement of the cingulate gyrus by radiating gyri. (b) In coronal sections, the myelinated Probst bundles of misdirected callosal fibers are prominent (arrow), and the frontal horn has a characteristic bat-wing appearance.
3.45 Agenesis of the corpus callosum in a 16-week-old fetus.
(a) The delicate membrane roofing the third ventricle balloons upward when placed in water. (b) The membrane has two layers: fibrovascular and ependymal.
Callosal anomalies are rarely associated with a midline mass (e.g. cyst, meningioma, hamartoma, lipoma) (Figs 3.46, 3.47). There is a high incidence of associated visceral and cerebral anomalies, especially hydrocephalus, and rhinencephalic and migration defects.
3.46 Partial agenesis of the corpus callosum associated with a lipoma.
(a) At the level of the anterior commissure the well-formed callosum is covered on its dorsal surface by a yellow lipoma. (b) At midthalamic level the callosum is discontinuous, the gap being filled by lipoma. Small longitudinal bundles of Probst can be seen (arrow). (Courtesy of Dr C Torre, Rome, and Professor F Scaravilli, Institute of Neurology, London.)
3.47 Callosal agenesis associated with a unilateral mass lesion.
(a) The left hemisphere is disorganized by massive gray heterotopias so no interhemispheric fibers have formed, while the relatively well-formed right hemisphere has a longitudinal Probst bundle. (b) In this 27-week-old fetus a large hamartoma disrupts the left hemisphere. (c) The otherwise normal right hemisphere has a Probst bundle (arrow). (Kindly referred by Dr Jeanne Bell, Edinburgh.)
SEPTO-OPTIC DYSPLASIA
Septo-optic dysplasia (Fig. 3.48) is the clinical triad of:
3.48 Septo-optic dysplasia.
(a) Olfactory aplasia and hypoplastic optic nerves. (b) Close-up of the thin gray optic nerves (arrow). (c) Coronal section showing absent septum pellucidum and thin callosum with a smooth ventricular surface.
CAVUM SEPTI PELLUCIDI AND CAVUM VERGAE
Cavum septi pellucidi (Fig. 3.49) and cavum vergae are rostral and caudal cavities, respectively, bounded above by the corpus callosum and laterally by the two leaves of the septum pellucidum and the fornices. They are normally present in fetal life and usually obliterated by term. A cavum septi pellucidi is seen in 20% of brains at necropsy with or without a cavum vergae. Glial tissue lines the cavity, which may contain macrophages.
MALFORMATIONS OF CORTICAL DEVELOPMENT
Our current classification of this huge and diverse group of disorders combines descriptive morphology with genetic analysis; a given phenotype may result from several genetic, chromosomal or non-genetic causes while different mutations in a given gene result in different phenotypes. Figure 3.50 presents a simplified summary of our rapidly expanding understanding of the developmental biology of primordial cerebral cortex. New concepts of molecular pathogenesis obtained from animal models and human genetic disorders will revolutionize and modify our approach to this complex field.
3.50 Development of the cerebral cortex.
(a) Coronal view of the embryonic forebrain. The cortical neuroepithelium (Ctx, green) gives rise to the excitatory pyramidal projection neurons which migrate radially. In contrast, inhibitory interneurons derive mainly from the medial ganglionic eminence (MGE, red) and lateral ganglionic eminence (LGE, orange). First, they migrate non-radially and, after entering the cortical plate, migrate radially. (b) The boxed area of cortex in (a) is expanded to illustrate sequential migration of projection neurons in the pallium. Progenitor cells proliferate (brown nuclei) in the ventricular zone (VZ) and subventricular zone (SVG) producing new neuroblasts which migrate through the intermediate zone (IZ) into the cortical plate (CP) utilizing the support of the long processes of the radial glial cells (RGC) which also have properties of neural stem cells. Neuronal identity and laminar fate are specified before migration, the earliest born neurons travel the least to settle in the deepest cortical layer, while later born cells migrate past existing cells settling in progressively more superficial layers. There is also evidence that interneurons derived from the ganglionic eminence follow a similar inside-out temporal sequence. (Modified from Hevner RF. Layer-specific markers as probes for neuron type identity in human neocortex and malformations of cortical development. J Neuropath Exp Neurol 2007; 66(2):101–109.)
AGYRIA AND PACHYGYRIA
A summary of normal gyral development is given in Figure 3.51. Agyria and pachygyria refer to an absence of gyri and sulci, or reduced numbers of broadened convolutions, respectively, associated both macroscopically and microscopically with a thickened cortical ribbon (Figs 3.52, 3.53 and see Fig. 3.57).
3.51 Development of the gyral patterns of the brain.
1, intrahemispheric fissure; 2, transverse cerebral fissure; 3, sylvian fissure; 4, callosal sulcus; 5, parieto-occipital fissure; 6, calcarine sulcus; 7, olfactory sulcus; 8, central sulcus; 9, precentral sulcus; 10, postcentral sulcus; 11, superior temporal sulcus; 12, lateral sulcus; 13, cingulate sulcus; 14, superior frontal sulcus; 15, supra-marginal gyrus; 16, angular gyrus; 17, superior occipital gyrus; 18, inferior occipital gyrus; 19, inferior temporal sulcus; 20, inferior frontal sulcus.
3.52 Agyria in a case of Miller–Dieker syndrome.
(a) Over the vertex the cortical surface is almost completely smooth. (b) Lateral view of the left hemisphere showing a lack of all sulci except the sylvian fissure. (c) Coronal section of the frontal lobe. The cortical surface is smooth and the ribbon greatly thickened, while the greatly reduced white matter contains a large heterotopia. (d) Coronal section of the occipital lobe showing agyria and periventricular gray matter heterotopia. (e) Section of the frontal lobe stained with Luxol fast blue/cresyl violet. The cortex is extremely thick. Heterotopic gray matter bulges into the ventricular lumen. (f) Horizontal section of one side of the medulla showing several islands of heterotopic olivary tissue stranded between the inferior cerebellar peduncle and the dysplastic inferior olivary nucleus (arrow). (g) Typical facies with microcephaly, bitemporal hollowing, high forehead, broad nasal bridge and upturned nares, thin upper lip, and micrognathia. Deletion of 17p resulted from a ring chromosome.
3.53 There is a continuous spectrum from agyria to pachygyria.
(a) Shallow cingulate and temporal gyri in a 4-year-old microcephalic boy presenting with infantile spasms. (b) Marked microcephaly (500 g brain at 8 months). Much of the vertex appears quite smooth. (c) In coronal sections of (b) there are cingulate and temporal gyri and a narrow Sylvian fissure, but the insula is poorly formed. Note the very thick cortex, attenuated white matter and corpus callosum, and periventricular heterotopic gray matter.
THE SMOOTH BRAIN
For almost completely smooth or unconvoluted brains – agyria or lissencephaly.
For reduced numbers of coarse or widened convolutions – macrogyria or pachygyria.
MACROSCOPIC APPEARANCES
The skull vault is small, misshapen, and thickened. Brain weight is usually low, and very occasionally heavy. A markedly thickened cortical ribbon is associated with reduced white matter (see Fig. 3.52). Pachygyria is occasionally combined with polymicrogyria. The claustrum and extreme capsule are absent. Lateral ventricles are dilated and often associated with periventricular nodular heterotopia.
MICROSCOPIC APPEARANCES
The most characteristic histological appearance is a four-layer cortex (Fig. 3.54):
3.54 A four-layer cortex in agyria or pachygyria (lissencephaly type I).
(a) A narrow band of faintly stained myelinated fibers indicates the third layer sandwiched between outer and inner gray laminae, the latter sending thick plumes into the thin underlying white matter, which also contains nodular heterotopias. (b) Close-up of the four-layer cortex showing the molecular layer, outer neuronal layer, paucicellular layer with myelin, and inner gray layer. (c) The deeply placed columns of the innermost layer and heterotopic nodules.
