Click here to view next page of this article

 

Neurofibromatosis

Neurofibromatosis is a genetically dominant disorder, with 50% being new mutations. There are two types. Neurofibromatosis I, which occurs in 1:3,000 - 5,000 births, and NF II on chromosome 22 is about ten times less common. Approximately. Both genes have been cloned. One is called neurofibromin and the other is called schwannoma.

The things they will want you to know are café-au-lait spots. They want you to know that six or more that are bigger than 5 mm in pre-pubertal, or greater than 15 mm in post-pubertal. Thatís an important diagnostic criteria. In other words, you may have already noted in the last several years that you are always seeing kids in your continuity clinic that have one or two café-au-lait spots. Thereís a lot of people like that, particularly among the darker skinned persuasion. Thatís not terribly important. Axillary freckling is considered fairly specific for this disease. Lisch nodules are considered fairly diagnostic, but they develop only later. Subcutaneous neurofibromas, intraspinal tumors, tumors of peripheral nerves, then if they say, "whatís the most common tumor in this thing where everything develops a tumor?" Correct answer is; optic glioma. And they can also have, of course, astrocytomas, meningiomas, medulloblastomas, ependymomas, and so on. Here is a picture showing Lisch nodules, some café-au-lait spots, as well as some schwannomas and neurofibromas. Every lesion is here in these two pictures.

Neurologic sequelae of NF-I is again seizures, cognitive disabilities, hypertension. Again, this is the reason neurologists always stress to you that when you do neurologic evaluation of an infant with seizures you have to look at the skin carefully. And then hypertension. Why do we get that? They have a lot of retroperitoneal fibrosis and therefore you get renovascular type.

Type II is simpler. They develop the classic association of neurofibromatosis type II. You should know this. Anytime they say "Bilateral acoustic neuroma" the answer is NF-II. Skin findings are not typically associated with this.

Anencephaly has an incidence of slightly less than 1:1,000 in the United States, and the recurrence rate is 3-5%. As you know probably, it can be monitored with alpha fetoprotein. Then there are encephaloceles. These are herniations of meninges with or without brain parenchyma, usually through a bony defect. Three out of four are occipital, and in the Orient there is an association with hypertelorism and short stature, and frontal encephaloceles.

One is called a meningocele where the meninges are herniating. The space would be of course CSF filled and in a meningo and encephalocele there is actually some extrusion or herniation of brain parenchyma, right down here. Neural tube closure defects will continue by briefly mentioning that there is a condition called diastematomyelia. As you know, anything with myelia pertains to spinal cord. And this is a failure of fusion with some persistence of mesodermal elements where the cord actually looks like a doublet. Itís a split cord. Then there is hydromyelia which is an enlarged central canal. Then there are syringomyelia and syringobulbia. Syrinx in Greek means tube. So these are somewhat like hydromyelia in the sense that it is a central cavity, however this can occur either in the spinal cord per se or more rosterally in the brain stem, in which case we call it syringobulbia. And it can be due to tumor. It may be due to tumor following resection, it can be from an infarction, and it can present with spasticity, depending on its size, and there can be very distinct sensory findings that I will demonstrate to you momentarily.

The sensory findings have to do with the anatomy. We told you in the morning, neurologists tend to be very interested in anatomic correlations. These are patients in whom you will get a very distinctive sensory examination. You will find that they have some deficiency in sensation to pain or temperature and yet seem to be capable of perception of vibratory sense and, in an old enough and mature enough child, you may be able to test them for graphesthesia and so on. And you may wonder, how can this be possible? They can barely feel the hot or cold tuning fork, and yet they know the vibration. It has to do with the fact that this is the dorsal root ganglion on this side where pain temperature fibers enter the segment and they cross.

Now we are going to disorders of cell division and migration. And here, before I go too far, let me just remind you of something from embryology. As the brain develops in early fetal stage, after the ventricular cavities are formed as you know there is a layer of cells there that are capable of cell division. These are the neuroblasts that divide in a highly orchestrated, controlled manner. When you think about the fact that we have billions of cells and each cell division doubles the number, one extra cycle.

Holoprosencephaly is a condition where you donít have cerebral hemispheres. This is because the telencephalic vesicles never formed. Basically you end up with one cavity and there may be arrhinencephaly and there is cleft lip, again a midline defect. And these patients have severe mental retardation and motor deficits, seizures. Lissencephaly is another migrational error. It is often called by different names. Most commonly it would be called agyria. What happens here is itís a disorder of sulcation, another term. The brain does not form, gyri and sulci.

Chiari malformations. Type I Chiari is one where there is herniation of the cerebellar tonsils. Thatís a very classic type of description, many of you probably recall. Frequently Chiariís are asymptomatic until later. Not everyone presents with major symptoms right away. Type II includes whatís said in type I, but there is an association of other anomalies. There is an elongation of caudal medulla, which is an important finding, and there is a kinking of the cervical medullary junction and type II always implies also a lumbosacral meningomyelocele.

Polymicrogyria is often due to some sort of acquired insult where the brain has a few too many neurons and there are too many gyri that are very very small. And it usually results in pretty severe seizure disorders. There is schizencephaly where there is a gray matter line cleft that may extend clear across the brain, from the pial lining to the ependymal lining. You may recall that the ependyma are the cells that line the ventricle. Agenesis of the corpus callosum is a fairly reasonably commonly encountered anomaly. It can be isolated, in which case you may not even know that a person has agenesis of the corpus callosum. The very first patient with agenesis I saw was already in his 60ís and presented with a small stroke. And when I did the CT scan it was an incidental finding. The person was a veteran, had been in World War II, and so on. On the other hand, it can be accompanied by other problems. It may be just a part of a bigger problem.

Porencephaly is not really often a malformation. This can often be simply the residue of a small stroke. It is just a CSF-filled space where there ought to be brain. Should be distinguished from hydranencephaly. Hydranencephaly is a congenital absence of the cerebral hemispheres and we are not fully sure how this comes about, but it is very striking when you look at an MRI or a CT scan. Because the cerebral mantel is completely missing. What you normally see is well-formed basal ganglia.