This section will very briefly cover malformations, specific cerebral vascular problems, hydrocephalus, kernicterus, and inherited metabolic disease of white and grey, the leukodystrophies and neuronal storage disorders.

Slide 90

Slide 91 & Slide 92 & Slide 93

Neonatal malformations comprise an extensive variety of defects in development. We will only discuss a few of these which illustrate problems at major developmental stages. Slides 90, 91, 92 and 93 depict anencepahaly, and meningomyelocele associated with the Arnold Chiari malformation. These malformations are related to a failure of closure of the neural plate to form neural tube. This represents failure of a complex of inductive interactions between developing mesodermal and neuroecodermal structures. In these situations structures covering the brain, like the bones of the posterior fossa, in the Arnold Chiari malformation, and skin and vertebra in meningomyelocele are malformed along with the neural defect.

Look at the extreme malformation of midline skull and face in slide 90, anencephaly. The brain is exposed due to failure of the skull to form over it. It is represented by a mass of vascular neuroglia tissue which is a combination of malformation and destruction secondary to exposure.

Now look at the complex malformation in slide 91. This child has a prominent meingomyelocele, a failure of closure of the covering structures of the cord associated with malformation of the cord. In addition, note the enlarged head. This infant has concomitant Arnold Chiari type 2 malformation. The big head is due to obstructive hydorcephalus. Note to that cortical gyri are malformed: too many, too small. In slide 93 you can visualize the typcial downward displacement of the cerebellar tonsils into the foramen magnum and medullary kinking which are essential components of this complex malformation. Associated with these CNS changes is a very small, flat posterior fossa cavity.

Slide 94

After neural tube closure, hemispheres form and sulcation takes place. This all requires normal cell proliferation, in the germinal mantle regions, programmed cell death (many too many are made), and successful neuronal migration, along radial glia, to final cortical positions. Lissencephaly represents a failure of normal sulcation. An example is seen in slide 94. Note the failure of parietal sulcation in this photograph at the level of the thalamus and hypothalamus.

Slide 95

Slide 95 illustrates coronal sections taken from an infant with arhinenceophaly who has failure of normal hemiphere formation. Note the single lateral ventricle and fusion of the deep nuclear structures the midline. This infant also had absent olfactory groves and bulbs.

Slide 96 & Slide 97

Slide 96 reveals aqueductal stenosis. This may occur secondary to failed normal formation, to intrauterine inflammation involving the aqueduct or as part of a complex malformation. The consequences in all cases will be obstructive hydorcephalus, shown in the next slide, 97.

In slide 97 note the dramatic loss of periventricular white matter which typlifies hydrocephalus. Ventricular shunting protects the brain from this tissue loss!

We will now briefly consider two forms of cerebral vascular disease particular to neonatal brain: germinal mantle hemorrhages and periventricular leukomalacia.

Slide 98a is good example of periventricular leukomalacia. This region, the periventricular white matter, of the developing brain is particularly prone to ischemic damage.

Slide 98a & 98

Slide 98 shows intraventricular hemorrhage in a premature infant consequent to germinal mantle hemorrhage(s) which extended from the germinal mantle into the lateral ventricle. As the germinal mantle is no longer present at term, these hemorrhages are seen only in premature infants. They may be:1. completely within the mantle, 2. extend into the ventricle, as in this example, 3. produce hydrocephalus, 4. extend into the adjacent brain.

Slide 98 is also good example of a complication of maternal sensitization to fetal RBC with extensive hemolysis of fetal blood and secondary elevations of unconjugated, lipid soluble, bilirubin beyond the binding ability of plasma albumin to retain it in the circulation. What I am getting at? Kernicterus. Note the yellow staining of deep nuclear structures. The movement of bilirubin into the brain is toxic to neurons.

Slide 101

Slide 101 shows a brain of a young boy who died with adrenal cortical insufficiency and leukodystrophy. He had sex-linked adrenoleukodystrophy, a peroxisomal abnormality involving the metabolism of very long chain fatty acids Other leukodystrophies involve lysosomal hydrolases. For example metachromatic leukodystrophy, Krabbe’s disease. In this group there is a progressive loss of myelin associated with variable inflammation. In adrenoleukodystrophy inflammation is quite impressive, in fact until this entity was defined many of these cases were thought to be early cases of multiple sclerosis. In Krabbe’s disease large clusters of macrphages filled with the storage product are the main responding cell type. You should review this group of disorders. Include the genetics, the type of hydrolytic defect, the metabolic pathway involved, and the storage material(s). Know which have systemic as well as CNS presentations.

Slide 102 & Slide 103

Now look at slides 102 and 103. These show neurons at stages of intraneuronal storage with resultant destruction of the involved neuron. This can be seen in lipid and mucopolysaccaride storage diseases. In this case the child had Tay Sachs disease. A gangliosidosis. Niemann- Pick Disease is another neuronal storage disease due to a deficiency of lysosomal metabolism. Review the genetics and biochemistry of these diseases.