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Presented by William I. Rosenblum, MD
Material in this chapter provided by AJ Martinez, MD and MG Hadfield, MD


PRETEST: Answers will be found in the text of this chapter or click on link at end of questions

  1. Describe anencephale and encephalocele.
  2. Describe the Arnold Chiari malformation.
  3. What other defect is commonly [always] found with Arnold Chiari?
  4. Name a common developmental disease associated with a chromosomal defect--name the chromosome.
  5. adequate folate in diet of pregnant women protects against what?
  6. aqueductal stenosis is frequently found in_________ and may also be an independent anomaly leading to ______.
  7. Holes in the spinal cord may be called either ________ or _________.



Congenital malformations are anatomic abnormalities present at birth. They may be macroscopic or microscopic. About l5% of deaths in the neonatal period are due to congenital malformations and about 6% of one-year-old infants have congenital abnormalities. Malformations of the nervous system are expressions of arrested or perverted prenatal development. The pathogenesis of congenital malformation is not well understood. Two main hypotheses can be considered:

1. Induced in utero:

Abnormal metabolic or nutritional states during pregnancy, toxic agents, infectious agents (measles, rubella virus). Radiation effects (X-ray, atomic explosions) and faulty implantation of the fertilized ovum. Agents causing malformations are called teratogens.

2. Programmed by genetic defects:

Most malformations result from a complex interaction of genetic and environmental factors. Often these abnormalities take place in early fetal life (probably first trimester). Each organ has a critical period during which its development may be deranged. During the first two weeks of development, teratogenic agents may kill the embryo or cause chromosomal abnormalities which give rise to congenital malformations. During the 13-60 day period, teratogenic agents may cause major congenital malformations. From 9 weeks to term, little damage can be produced to the fetus by most of these agents. However, intrauterine infections (e.g., toxoplasmosis) may still be able to produce congenital defects even late in intrauterine life.



The image below is an example of anencephaly. In anencephaly (one per thousand births), there is no closure of the anterior portion of the neural groove. The vault of the skull is usually missing, and the cerebral hemispheres, the diencephalon and meningeal membranes are not developed and are usually represented by an exposed mass of undifferentiated vascular and dysplastic neural tissue. Acrania is always associated with this lethal condition (absence of cranial vault). This is a lateral view of an anencephalic fetus.


The image below is a posterior view of the anencephalic fetus. Note the failure of development of the skull. Instead there is an amorphous mass of soft, vascular connective tissue admixed with glial tissue. Sometimes no neural elements are identified within these structures. If the mesodermic growth around the developing nervous system is deficient, then the brain and cord lie, to a greater or lesser extent, open upon the surface.



The image below is a case of cranial encephalocele or meningoencephalocele, which is attached to the occipital area of the skull. Anterior and other presentations may occur less frequently. This condition occurs about once in 2000 births. In encephalocele, there is herniation of the brain into a sac lined by meninges and skin.



Hydrocephalus is an increase in the volume of the brain due to expansion of the ventricles. It may be due to an increase in production and/or a decrease in absorption of spinal fluid with a corresponding increase in intraventricular pressure. More commonly, it is the result of decreased absorption which is usually caused by a block in the CSF pathways, preventing CSF from reaching the arachnoid villi. In the infant whose cranial structures have not fused, the enlarged ventricles and increased intracranial pressure are manifested clinically by a progressively enlarging head. Sometimes adults develop increased intracranial pressure or hydrocephalus and are found to have aqueductal stenosis.

Congenital hydrocephalus has its basis frequently in occlusive malformations of the cerebral aqueduct of Sylvius. It may also be associated with other malformations leading to obstruction of CSF or with fetal infections (toxoplasmosis) leading to adhesive ependymitis or arachnoiditis which obstruct the free flow of CSF. There is a type of congenital communicating hydrocephalus in which no anatomic lesions are demonstrable, and presumably the increase in CSF is related to increased production or a functional lack of absorption.

The image above shows the hydrocephalic brain of a child. Note the markedly dilated ventricular system (both lateral ventricles and third ventricle) and the absence of septum pellucidum. The central white matter, cortex and basal ganglia have been compressed and somewhat deformed. At a later stage, the cerebral cortex may be atrophic and paper thin.



As mentioned above, this congenital defect is a frequent cause of hydrocephalus, and, in addition to being a congenital defect, it may be acquired later in life (e.g., as result of infectious diseases).

The image below illustrates aqueductal stenosis. The stenotic aqueduct (arrow) was the cause of hydrocephalus in this case. The aqueduct is present more caudally in the other two sections.


This image below also illustrates the aqueductal region. Instead of a single channel of normal dimensions, the aqueduct is replaced by multiple small channels or clefts, lined by ependyma. Many of these are blind sacs, and, in any case, the cross structural area available for CSF passage is inadequate. This morphologic pattern is one of several that can be found at the site of a stenotic aqueduct.



The Arnold-Chiari malformation is really a collection of defects, which may vary somewhat from case to case. Commonly, hydrocephalus is found. Aqueductal stenosis may also be present. In addition, many cases of Arnold-Chiari have a displacement of brainstem and cerebellar tonsilar tissue downward through the foramen magnum. 

The origin of this complex is still debated. A previously discredited theory suggested that the downwardly displaced tissues were actually pulled down because, in the same patients, there is a meningomyelocele which tethers the lower cord thus creating a downward pull on the entire neuraxis. This theory  was discredited when it was thought that the "pegs" of cerebellar tissue were not really displaced tonsils but rather were malpositioned cerebellar tissue. 

However some surgeons reported that surgical treatment of the meningomyelocele in utero caused reversal of the downwardly displaced brain tissue thus resurrecting the theory of downward pull. Other workers have concentrated on the relation between the aqueductal stenosis and the hydrocephalus in these cases. They have suggested that the stenosis leads to the hydrocephalus. Some suggest that the hydrocephalus then produces the downward force that leads to the downward displacements. 

This sequence of events has been observed in animals where a hydrocephalus was produced in utero. While many have believed that the aqueductal stenosis is the trigger for the hydrocephalus and the subsequent events, a careful analysis of human cases reported that the disease begins as a crowding of the bones at the base of the skull which leads to squeezing of the stem and its aqueduct.

The image below illustrates the position of the downwardly displaced portions of cerebellum. The lower medulla has a congenital "kink." The position of the foramen magnum, as it appeared in life, is marked on the image.

The image below illustrates the brain stem and cerebellum cut sagitally in a case of Arnold-Chiari malformation. The arrow points to the cerebellar tonsils or "pegs" of cerebellum which have been displaced caudally over the roof of the medulla.



As noted above Arnold-Chiari patients generally  have a meningomyeloceles. However meningomyelocele may develop alone from failure of the posterior neuropore to close. This failure has been associated with maternal deficiency of folic acid early in pregnancy. Great strides have been made in eliminating this problem by giving dietary supplements.

If the dura and leptomeninges, chiefly the arachnoid, protrude through the defect in bone, (i.e., through the bifid spine), a sac is created called a meningocele. A meningomyelocele or myelomeningocele occurs when neural elements such as the spinal cord, nerve roots and nerves protrude into the sac. Meningoceles and meningomyeloceles may occur anywhere along the spinal axis, but they are most common in the lumbar region. In the region of the skull, an analogous defect known as an encephalocele may be found. This was described in an earlier paragraph.

The image below illustrates a case of meningomyelocele. The spinal cord has been removed from the body, together with the attached abnormal, lower portion of the vertebral column. The latter displays the defect in the vertebral bodies through which is seen a sac containing cord and spinal roots.




Hydromyelia is a widening of the central canal of the spinal cord (image above). This figure illustrates four cross sections of spinal cord in a case of hydromyelia, and compares them with four cross-sections which do not display a cavity. The area around the cystic cavity disclosed degenerative changes of the nervous system. 

This condition is usually associated with hydrocephalus, myelomeningocele, and the Arnold-Chiari malformation. Many believe that most such cavities in the cord are acquired later in life and are due to cord destruction rather than widening of the central canal. The condition is then called syringomyelia and the cavity is a "syrinx." Syrinxes are also frequently accompanied by astrocytomas of the spinal cord. One theory of the syrinx formation in that setting is that it is a degenerative consequence of edema produced in the vicinity of the tumor.


Spina bifida refers to a defect of the vertebral column or lack of fusion of bony structures dorsal to the spinal cord. The vertebral arches may remain open at birth. In some instances called spina bifida occulta, the defect is not visible from the surface because only the bone is affected and the cord or meninges do not protrude into a sack. The skin over this defect essentially remains intact. It may occasionally display a tuft of hair, a dimple or sinus tract, and hyperpigmentation, or the defect may be discovered only by X-rays of the vertebral column.


Chromosomal abnormalities can cause alterations in the structure of the nervous system. Chromosomal abnormalities are present in about one of two hundred newborn infants. In the trisomy 18 syndrome, there is an extra or third chromosome 18, producing genetic imbalance.

The trisomy 21 condition is also known as Down's Syndrome. Chromosome 21 has numerous functions among which is control of production of the precursor protein for the beta A4 amyloid which is deposited in the brain in Alzheimers disease. If  this abnormal protein is a casuative factor in the production of the dementia of Alzheimers's disease then one might expect Downs patients to suffer a second disease due to overexpression of the protein caused by presence of the extra chromosome. And, indeed, Down's  patients develop the hallmarks of  Alzheimer's disease--neurofibrillary tangles and senile plaques with deposition of beta A4 amyloid-- and do so at relatively early age.

Down's patients often have a brain with a characteristic "boxy" shape and the abnormality shown in the figure below which illustrates the lateral surface of a Down's syndrome brain. It is characterized by the reduced size of the superior temporal gyrus.  




This common abnormality appears in diverse syndromes, including some familial settings in which case it has a basis in chromosomal aberrations. It is illustrated below in a brain divided in two in the sagittal plane and viewed from the medial surface of one of its halves.


Last Updated 15-May-2007