Pontoneocerebellar Hypoplasia

This multiple system malformation involves the cerebel-lar hemispheres and their pontine and medullary connections, resembling the pathology of olivoponto-cerebellar atrophy. The malformation is associated with a congenital disorder of glycosylation. Grossly, the cer-ebellar hemispheres are abnormally small, consisting of

figure 13.23

Cerebellar hypoplasia in a 5-year-old boy who was born during the fifth month of pregnancy following an accident involving the mother. A. The cerebellar hemispheres are represented by a few folia. B. The vermis is somewhat better developed. The pons is small. (Histologically, there was loss of Purkinje cells and transverse pontine fibers, and of inferior olivary neurons resembling a pontoneocerebellar hypoplasia.)

figure 13.23

Cerebellar hypoplasia in a 5-year-old boy who was born during the fifth month of pregnancy following an accident involving the mother. A. The cerebellar hemispheres are represented by a few folia. B. The vermis is somewhat better developed. The pons is small. (Histologically, there was loss of Purkinje cells and transverse pontine fibers, and of inferior olivary neurons resembling a pontoneocerebellar hypoplasia.)

figure 13.24

Aplasia of the granule cell layer in a 6-year-old boy. His development was abnormal from birth: He slept most of the time, was difficult to arouse and feed, and remained bedridden all his life. A. The cerebellum is abnormally small, has narrow folia separated by deep sulci. B. The cortex is devoid of granule cells, and some folia show Purkinje cells losses (cresyl violet).

merely a few thin folia. The pontine basis is small, and the medullary olives are flat.

Histologically, the cortex reveals a diminished number of Purkinje and granule cells; the dentate nuclei are severely disorganized; the pontine nuclei are hypo-plastic and the transverse pontine fibers are reduced in number; the hemispheric white matter and the middle and superior cerebellar peduncles are poorly myelinated; and the olivary neurons are hypoplastic.

Aplasia of the granular cell layer occurs sporadically, although a few familial cases have been reported (Fig. 13.24). Absence of the granule cells is associated figure 13.25

Cerebellar cortical dysplasia and het-erotopia. A. Abnormal convolutions show islands of granule cells and scattered Purkinje cells (cresyl violet). B. Cluster of Purkinje cells and granule cells in the hemispheric white matter (HE).

figure 13.25

Cerebellar cortical dysplasia and het-erotopia. A. Abnormal convolutions show islands of granule cells and scattered Purkinje cells (cresyl violet). B. Cluster of Purkinje cells and granule cells in the hemispheric white matter (HE).

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with anomalous Purkinje cells, which display a cactuslike dendritic arborization and axonal torpedoes.

Minor Histologic Anomalies

Cortical dysplasia consists of disorganized lamination, often with abnormal neurons (Fig. 13.25).

Heterotopias are nests of Purkinje cells and dentate neurons within the hemispheric white matter (see Fig. 13.25).

Dysplastic Gangliocytoma or Lhermitte-Duclos Disease

The pathology is characterized grossly by focal thickening of the folia and histologically by replacement of the Purkinje and granular cell layers with dysplastic ganglion cells. Abnormally myelinated fibers are present in the molecular layer.

Clinically, cerebellar symptoms and increased intra-cranial pressure (ICP) may develop at any age, but usually in the third and fourth decades. They gradually progress and often necessitat surgery. T2-weighted MR images reveal focal hyperintense thickening of the folia.

table 13.4.

Causes of Secondary Microencephaly and Megalencephaly

Microencephaly

Megalencephaly

Fetal/ Perinatal Injuries Hypoxic-ischemic Infectious Metabolic Traumatic Toxic

Malformations

Leukodystrophies Alexander's disease Canavan's disease Neuronal storage diseases Tay-Sachs disease Mucopolysaccharidosis Phakomatoses

Tuberous sclerosis Recklinghausen's disease

may be associated with syringomyelia and ependymoma of the fourth ventricle. Clinically, it presents with a combination of bulbar palsy, ataxia, and facial sensory deficits.

Other malformations are heterotopia and dysplasia of the inferior olivary nuclei and anomalous crossing of the pyramidal tracts.

DISORDERS OF BRAIN WEIGHT

MALFORMATIONS OF THE BRAINSTEM

Stenosis and atresia of the aqueduct of Sylvius are major causes of congenital hydrocephalus. In atresia, tiny channels of ependymal cells indicate the site of the aqueduct.

Syringobulbia is a slit-like cavity in the medulla extending from the floor of the fourth ventricle ven-trally, usually between the olives and the hypoglossal nerve roots, or between the olives and the pyramids. It

Microencephaly and Microcephaly

The brain volume can be diminished primarily or secondarily to a number of acquired or inherited metabolic disorders (Table 13.4). True or primary microencephaly implies a reduction of brain weight by two standard deviations from the normal for age and sex. It occurs sporadically or is inherited as an autosomal dominant, autosomal recessive, or X-linked trait. Microcephaly is also a feature of several chromosomal defects (trisomy 21, 18, 9, and 13). Clinical manifestation varies from normal intelligence to variable mental retardation.

figure 13.26

Brain weight disorders. A. Primary micrencephaly in a 70-year-old mentally retarded woman. The 510-g brain displays a greatly simplified convolu-tional pattern with broad convolutions. B. Primary megalencephaly in a 58-year-old mentally severely retarded man. The 1800-g brain displays a richness of haphazardly arranged convolutions.

figure 13.26

Brain weight disorders. A. Primary micrencephaly in a 70-year-old mentally retarded woman. The 510-g brain displays a greatly simplified convolu-tional pattern with broad convolutions. B. Primary megalencephaly in a 58-year-old mentally severely retarded man. The 1800-g brain displays a richness of haphazardly arranged convolutions.

Grossly, the adult microencephalic brain may weigh from 500 to 900 g and display a simple convolutional pattern of broad convolutions (Fig. 13.26). Histologically, minor cytoarchitectonic anomalies are present in the cortex and deep gray structures. The smallness of the head contrasts with the normal size of the face; the forehead recedes sharply, and the occiput is flat.

Megalencephaly and Macrocephaly

True or primary megalencephaly implies an increase of brain weight by two and a half standard deviations above the normal for age and sex. It occurs sporadically or is inherited as an autosomal dominant or recessive trait. Grossly, the bulky adult megalencephalic brain may weigh from 1,600 to 1,800 g or more (see Fig. 13.26). On section, the cortex is thick, and the volume of the white matter is increased. Histologically, hetero-topia and minor cytoarchitectonic anomalies are usually present. The head may be large at birth, or the size increases during early infancy.

MENINGEAL AND VASCULAR ANOMALIES

A congenital arachnoid cyst results from a separation of the arachnoid membrane. Common sites are the lateral aspects of the hemispheres, the interhemispheric fissure, the cerebellopontine angle, the posterior fossa, and around the spinal cord. Some cysts remain clinically silent; others enlarge to produce focal symptoms and increased ICP, necessitating surgery.

An arteriovenous fistula of the vein of Galen carries serious complications in neonates and infants. The vein of Galen is markedly dilated from draining the blood of the major basal cerebral arteries. Complications include cardiac failure, hydrocephalus, focal neurologic symptoms, seizures, and hemorrhages. Common vascular malformations are covered in Chapter 11.

PHAKOMATOSES: ECTOMESODERMAL DYSGENETIC SYNDROMES

Phakomatosis (Greek phakos, birth marks of skin and eyes) refers to a group of syndromes of multisystem malformations. The malformations derive from any of the three germinal layers of the embryonic disc: ectoderm, mesoderm, and entoderm. The nervous system, eyes, and skin are the primary sites of involvement. The visceral and endocrine organs, blood vessels, and skeleton are variably involved. Some malformations are apt to proliferate into neoplasms that may undergo malignant transformation.

Some syndromes occur sporadically, and some are inherited as an autosomal recessive or dominant transmission. The clinical presentation varies greatly from monosymptomatic abortive forms to full-blown syndromes. Symptoms may appear at various ages from infancy through adulthood. Some malformations are identifiable antenatally using ultrasonography and post-natally using MRI.

Tuberous Sclerosis Complex

The syndrome of tuberous sclerosis, or Bourneville-Pringle disease, occurs in 1 to 10,000 births. It presents with cerebral, cutaneous, and ocular malformations; visceral malformations occur with variable frequency. Familial cases are inherited as an autosomal dominant trait. Sporadic cases probably result from spontaneous

figure 13.27

Tuberous sclerosis in a 20-year-old mentally retarded epileptic man with numerous "warts" on his face. (A) Basal and (B) dorsal views of the brain show numerous tubers appearing as focal widening of the convolutions; a few have a central dimple. C. Small nodules are present in the ventricular walls.

figure 13.27

Tuberous sclerosis in a 20-year-old mentally retarded epileptic man with numerous "warts" on his face. (A) Basal and (B) dorsal views of the brain show numerous tubers appearing as focal widening of the convolutions; a few have a central dimple. C. Small nodules are present in the ventricular walls.

mutations. The defective genes TSC1 and TSC2 map to chromosomes 9 and 16, respectively.

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