Neurological Defect Spotlight: Anencephaly

One of the most severe developmental defects is called anencephaly, which literally means "without a brain." However, usually some brain tissue develops normally, but the forebrain and cerebrum is small or absent. This defect is caused by an error in the development of the nervous system and brain, and is thought to be somewhat related to the mother's intake of folate/folic acid (Vitamin B9). Babies born with anencephaly nearly almost always die either in the womb or shortly after birth, as their compromised nervous system is unable to sustain bodily functions (and certainly not consciousness). In addition, an anencephalic fetus often does not have a skull or scalp covering what neural tissue they have, leaving the brain exposed and susceptible to infection and damage.

How exactly does a fetus develop without a brain?

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Anencephaly is one of many types of "neural tube defects," and unfortunately one of the most common. As organisms develop during gestation, rudimentary neural tissue, which will further develop into the brain and nervous system, follows a very stereotypical series of events. These events are often conserved through many species and happen in very narrow windows of time. One event of particular importance is the closure of the neural tube.


In humans, neural tube development follows "primary neurulation" meaning that the cells of primitive neural plate form a cup and then fuse to form a tube, and then "secondary neurulation" where cells form a cord structure and migrate to make the tube hollow. For a short time, the neural tube is open at both ends (cranially and caudally; caudally referring to what will become the end of the spinal cord). These openings (neuropores) almost always close during the fourth week of gestation in humans, however sometimes they do not. Failure to close at the cranial end can result in anencephaly while failure to close at the caudal end can cause spina bifida.

The reason that distinct brain regions are affected in anencephalic fetuses has to do with the preliminary segmentation of the neural tube during its open/closing state. The neural tube is roughly segmented into 4 divisions, each which give rise to different CNS regions: the prosencephelon, the mesencephelon, the rhombencephelon, and the spinal cord. The prosencephelon is towards the cranial end of the neural tube, and is therefore most severely affected by a failure to close. The prosencephelon would have given rise to the forebrain and the diencephelon, which are compromised or missing in anencephalic fetuses.

The direct causes of neural tube defects are not crystal clear, but studies have shown that women who have folic acid deficiencies or are taking medication for epilepsy are more likely to have a child with this type of defect. However there also seems to be a genetic component which has not yet been pinpointed. Luckily aminocentresis and ultrasound can often indicate early on if a fetus displays this defect.

More info:
Check out a cool animation of neurulation and closure of the neural tube, here.
Pictures of anencephalic fetuses here (May be disturbing).

Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders.

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Brave of you to discuss this defect on your blog, Shel. Whenever I want to pull out a trump card in an abortion debate, usually I pull out two: anencephaly and ectopic pregnancy. If there are clear-cut cases where abortion is the probably the right thing to do, these are it. Edward's syndrome is another one that is right in there.

Just a Q, tho: who out there has seen the "Body Worlds" exhibit that's been touring science museums? I saw it in StPaul MN a few months ago, and the "fetus room" was quite remarkable. It included an anencephalic fetus.

If you have a chance, do not miss it.

By boojieboy (not verified) on 01 Jun 2007 #permalink

Well, I wasn't really putting it up there to delve into that debate, more just to discuss the defect in terms or neurological development. And, it is a common one, which mothers can do something about (take folic acid). Not that I disagree with you, though.

I did see Body Worlds in Chicago 2 years back and was blown away. Although I didn't see the fetus room as it was kinda a whirlwind tour....

Although Anencephaly is a serious neurological defect in humans, I wonder about the possible evolutionary relationship with Echinodermata.

From the California State University system:
"Echinoderms (except holothurians) generally lack respiratory systems, and many have only rudimentary circulatory systems; the water-vascular system takes over some of the functions of these systems. Nervous and sensory systems are generally poorly developed in echinoderms."

From Wiki:
"They have a simple radial nervous system that consists of a modified nerve net (interconnected neurons with no central organs); nerve rings with radiating nerves around the mouth extending into each arm; the branches of these nerves coordinate the movements of the animal. Echinoderms have no brain, although some do have ganglia."

Doug, interesting question. As I mentioned up top, the process of neurulation is highly conserved across species although creatures like sea urchin (which are radial vs bilateral) don't follow the exact same morphological placments. Also it happens much faster, ie over the course of minutes rather than days. Check out this figure which shows normal sea urchin neurulation: View image

Note the time frame. (figure from Kimberly et al. 1998 Dev Bio.)

The authors found that the process of neurulation can be disrupted if the arrangment and migration of specialized cells called bottle cells are changed (chemically). Following disruption, neurulation looked like this: View image

Depending on the severity, its embryonic lethal.

I may be misunderstanding your description of this, but...

Your description of primary and secondary neurulation seems to suggest that these two processes take place along the entire length of the neural tube, but as I understand it (from Larsen, in Human Embryology, 2001 and Gilbert, in Developmental Biology, 2006), the two processes produce separate regions of the neural tube, with secondary neurulation forming only the caudalmost portion, a blind "caudal eminence," that forms from a solid tube which hollows out and then joins end-to-end with the already-formed neural tube at the level of sacral vertebrae.

It seems awfully weird to this non-expert that development would proceed in such a convoluted manner, but that observation seems applicable to most developmental processes, part of what makes it all so fascinating. Thanks for your very interesting blog!

One of the things that regulates neural tube formation is nitric oxide. NOS activity is required for neural tube closure. NOS inhibitors will cause neural tube defects, as will NO donors (perhaps by inhibiting methionine synthase which is involved in folate metabolism). Folate rescues NO induced NTDs.

I think that some neuronal patterning is induced by gradients in NO and superoxide, the length scale of the neuronal patterning may depend on the size of that region during that period of fetal development.

One of the things that regulates neural proliferation is NO, also neuronal survival and differentiation, even in newborn rats. Zinc finger transcription factors are highly involved in neurodevelopment, and it is NO that regulates Zn transfer between metallothionein and Zn finger proteins.

There are Zn finger transcription factors important in both neural tube closure and hair cell differentiation, but you probably already know that.