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Congenital Malformations of the Brain

Anencephaly is relatively common. It’s 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. This illustration is there in your handout on the right side, and what it is, is to schematically show that there are two types. One is called a meningocele where the meninges are herniating.

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.

Holoprosencephaly is a condition where you don’t 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 it’s a disorder of sulcation, another term. The brain does not form, gyri and sulci. There are heterotopias

Chiari malformations. Type I Chiari is one where there is herniation of the cerebellar tonsils. That’s a very classic type of description, many of you probably recall. Frequently Chiari’s are asymptomatic until later. Not everyone presents with major symptoms right away. Type II includes what’s 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.

So if anybody asks you, "What’s the most common neural tube problem, or the most common Chiari malformation?" it will be Chiari type II. So here we show you a picture that illustrates the major points. The blue structure here is the foramen magnum, here’s the foramen and this is the skull. Here we have the midbrain.

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.

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,.

Microcephaly. Microcephaly is a complex thing. Microcephaly can have a variety of etiologies, depending on when you discover it. What I mean by that is some people are born microcephalic because they may have a chromosomal syndrome, or Cornelia de Lange or fetal alcohol, or one of the STORCH, meaning syphilis, toxo, rubella, and all that type of syndromes. On the other hand, it can become an acquired process if you have perinatal asphyxia.

Macrocephaly is kids with big heads. Here we have again a big differential. It can be metabolic disease, like Sturge, Tay-Sachs, Hurler’s, some of those. Leukodystrophies like Alexander and Canavan are known to create progressively large head. You can see it sometimes in neurocutaneous syndromes, or bone disease. There is a syndrome called Sotos syndrome which is truly macrencephaly. There is no hydrocephalus. The brain looks normal.

Mobius syndrome. It’s basically a maldevelopment of cranial nerve nuclei. The most commonly affected one is facial nerve. And you may remember, what the major function of the facial nerve is, it’s muscles of facial expression. So those of you who are in Los Angeles know that there was a big story not too long ago.

Obstructive hydrocephalus can be due to a congenital problem, like aqueductal stenosis. We are referring to the aqueduct of Sylvius that connects the third ventricle to the fourth. It can also be acquired due to midline brain tumors that compress the aqueduct. It may be a congenital anomaly, such as Dandy-Walker syndrome.

Cranial synostosis. So here we first want to show you what the major sutures are. As you can see, here is the metopic suture, there is the coronal one going across, sagittal and the lambdoid.

Vascular malformations. Vein of Galen’s you should know. The important associations you make with vein of Galen’s is, first of all I told you it is not an aneurysm. It’s an AVM. You may get this question, not for neurology. You may get it for Neonatology. It’s very very big in the differential for high output heart failure.

Tuberous sclerosis occurs in about 1:30,000 births, dominant inheritance but many are spontaneous mutations. So if you see a baby with TS you should examine the skin of the patients family and inquire about seizure history in parents. It is certainly a dominant one but a large number of spontaneous mutations.

Sturge-Weber syndrome is sporadic. Sturge-Weber is actually not at all inherited in a predictable fashion. It’s sporadic but it’s very classic because of the vascular port-wine nevus in the V-1 or V-2 trigeminal distribution with contralateral hemiparesis and seizures. Where do the seizures come from? They come from the cerebral cortex.

Von Hippel-Lindau is a dominant disease, 1:40,000-50,000. Cerebellar hemangioblastomas, spinal cord angiomas. I saw one patient who had this disease and then this was treated.

Neurofibromatosis. The genetics is; it is again dominant with 50%, like tuberous sclerosis, 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. I didn’t put the names in your handout but nobody is going to bother you.

Clinical approach to the child with ataxia. A differential diagnosis, localization and so on. So the term comes from the Greek, atactos, which is out of order. So the true definition of ataxia is "It’s a disturbance of coordination and rhythm and volitional and postural movements." And the neuroanatomic substrates are the cerebellum, the midline structure of the vermis, and the hemispheres and its major inputs. One of the important things in neurology.

Friedreich ataxia, an important disease. Also called spinal cerebellar degeneration. And this is a multi-system disorder with first decade onset. It is autosomal recessive. What we have learned more recently is that, in people who are homozygous and have both alleles, there is a triplet repeat expansion.

Ataxia telangiectasia is another one that is an inexorably progressive disease. Again, it is autosomal recessive. The gene has been cloned. We know now that the defect here is in DNA repair and the onset of the disease is around 1-3 years. There are telangiectasias that are easiest to see in the conjunctiva and in the pinna.

Bassen-Kornzweig syndrome is another interesting disease that can cause ataxia -and this again is kind of related to something Marvin Ament told you speaking of vitamin deficiencies - it’s called Bassen-Kornzweig syndrome. Most of us just call it a-beta lipo-proteinemia, or more commonly, neuro-acanthocytosis.