Anencephaly

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Anencephaly
Classification and external resources

A front view of an anencephalic fetus
ICD-10Q00.0
ICD-9740.0
OMIM206500
DiseasesDB705
MedlinePlus001580
eMedicineneuro/639
MeSHC10.500.680.196
 
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Anencephaly
Classification and external resources

A front view of an anencephalic fetus
ICD-10Q00.0
ICD-9740.0
OMIM206500
DiseasesDB705
MedlinePlus001580
eMedicineneuro/639
MeSHC10.500.680.196

Anencephaly is a cephalic disorder that results from a neural tube defect that occurs when the cephalic (head) end of the neural tube fails to close, usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp.[1] Strictly speaking, the translation of the Greek term to English is "no brain" (that is, totally lacking), but it is accepted that children with this disorder are born without a forebrain, the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for higher-level cognition. The remaining brain tissue is often exposed, i.e. not covered by bone or skin.[2] With very few exceptions,[3] most babies with this genetic disorder do not survive.

Contents

Signs and symptoms

An anencephalic newborn

The National Institute of Neurological Disorders and Stroke (NINDS) describes the presentation of this condition as follows: "A baby born with anencephaly is usually blind, deaf, unconscious, and unable to feel pain. Although some individuals with anencephaly may be born with a main brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness, reflex actions such as breathing and responses to sound or touch may occur."[2]

Causes

The cause of anencephaly is disputed. Generally, neural tube defects do not follow direct patterns of heredity, though there is some indirect evidence of inheritance,[4] and recent animal models indicate a possible association with deficiencies of the transcription factor TEAD2.[5] Studies show that a woman who has had one child with a neural tube defect such as anencephaly has about a 3% risk of having another child with a neural tube defect,[6] as opposed to the background rate of 0.1% occurrence in the population at large[7]

It is known that women taking certain medications for epilepsy and women with insulin-dependent diabetes have a higher risk of having a child with a neural tube defect.[8] Genetic counseling is usually offered to women at a higher risk of having a child with a neural tube defect to discuss available testing.

Recent studies have shown that the addition of folic acid to the diet of women of child-bearing age may significantly reduce, although not eliminate, the incidence of neural tube defects. Therefore, it is recommended that all women of child-bearing age consume 0.4 mg of folic acid daily,[2] especially those attempting to conceive or who may possibly conceive, as this can reduce the risk to 0.03%.[9] It is not advisable to wait until pregnancy has begun, since by the time a woman knows she is pregnant, the critical time for the formation of a neural tube defect has usually already passed. A physician may prescribe even higher dosages of folic acid(4 mg/day) for women who have had a previous pregnancy with a neural tube defect.[9]

Anencephaly and other physical and mental deformities have also been blamed on a high exposure to such toxins as lead, chromium, mercury, and nickel.[10]

Relation to genetic ciliopathy

Until recently, medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying set of medical symptoms that are clinically visible in the disorders. Anencephaly is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome, and some forms of retinal degeneration.[11]

Diagnosis

Ultrasound image of fetus with anencephaly

Anencephaly can often be diagnosed before birth through an ultrasound examination. The maternal serum alpha-fetoprotein (AFP screening)[12] and detailed fetal ultrasound[13] can be useful for screening for neural tube defects such as spina bifida or anencephaly.

Prognosis

There is no cure or standard treatment for anencephaly and the prognosis for patients is death. Most anencephalic fetuses do not survive birth, accounting for 55% of non-aborted cases. If the infant is not stillborn, then he or she will usually die within a few hours or days after birth from cardiorespiratory arrest.[2][14]

To date, there are only three recorded cases of anencephalic children surviving for longer periods of time: Stephanie Keene of Falls Church, Virginia, who lived for 2 years 174 days; Vitoria de Cristo, born in Portugal in January 2010 and surviving until July 17, 2012;[15] and Nicholas Coke[16] of Pueblo, Colorado, who as of July 2012, is still living at 3 and a half years old.

In almost all cases, anencephalic infants are not aggressively resuscitated because there is no chance of the infant ever achieving a conscious existence. Instead, the usual clinical practice is to offer hydration, nutrition, and comfort measures and to "let nature take its course". Artificial ventilation, surgery (to fix any co-existing congenital defects), and drug therapy (such as antibiotics) are usually regarded as futile efforts. Some clinicians and medical ethicists view even the provision of nutrition and hydration as medically futile.[citation needed]

Epidemiology

In the United States, anencephaly occurs in about 1 out of every 10,000 births.[17] Research has suggested that, overall, female babies are more likely to be affected by the disorder.[18]

Types of anencephaly

Meroanencephaly

Definition: Meronanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a median cranial defect, and a cranial protrusion called area cerebrovasculosa. Area cerebrovasculosa is a section of abnormal, spongy, vascular tissue admixed with glial tissue ranging from simply a membrane to a large mass of connective tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid plexuses.[19]

Holo anencephaly

The most common type of anencephaly, in which the brain is completely absent.[19]

Craniorachischisis

The most severe type of anencephaly where area cerebrovasculosa and area medullovasculosa fill both cranial defects and the spinal column. Craniorachischisis is characterized by anencephaly accompanied by bony defects in the spine and the exposure of neural tissue.[19][20]

Significant anencephaly research

Some genetic research has been conducted to determine the causes of anencephaly. It has been found that cartilage homeoprotein (CART1) is selectively expressed in chondrocytes (cartilage cells). The CART1 gene to chromosome 12q21.3–q22 has been mapped. Also, it has been found that mice homozygous for deficiency in the Cart1 gene manifested acrania and meroanencephaly, and prenatal treatment with folic acid will suppress acrania and meroanencephaly in the Cart1-deficient mutants.[21][22]

Ethical and legal implications of anencephaly

Varying ethical issues

Personhood

Modern philosophers[citation needed] define personhood as consciousness of the external world, in which a being sustains self-consciousness, self-determination, rational capacities, emotional expressions, willful direction, and communicative and social abilities. However, a conflicting issue is the idea of potentiality—someone who is in a coma can still have the capacity to function. In regards to those in a coma, such individuals are said to have latent capacity. Latent capacity describes a future or delayed ability to function. The crux of the ethical and legal implications of anencephaly lies with an anencephalic's status as a person.

One of the major issues concerning personhood is organ donation. Initial legal guidance came from the case of Baby Theresa in 1992, in which the boundaries of organ donation were tested for the first time.[23] Infant organs are scarce, and the high demand for pediatric organ transplants poses a major public health issue. In 1999, it was found that among children who die under the age of two, thirty to fifty percent do so while awaiting transplant.[23] In order for infant organs to be viable and used for transplant, they must be removed while the infant is still alive. However, this poses both legal and ethical issues. In the United States, some states have laws that forbid the removal of organs from a donor until after the donor has died. And from this, several questions have been posed. Are anencephalics, in fact, alive?

There are at least three different arguments in support of or against donation of anencephalic organs based on utilitarian, Kantian, and pro-life views. Utilitarians believe that the choice that benefits the most amount of people is the most ethical choice. In the case of organ donation, since anencephalics aren't sentient and can never experience either pain or pleasure, using their organs to maximize the happiness of society through saving the lives of other infants is the logical and ethical choice (rather than letting both infants die). The Kantian view follows that ethics should be based on duty and principle rather than end goals, and that moral imperatives are revealed by universalizing a moral decision. And since, if all anencephalic infants were to have their organs donated to other infants at birth, there would be no obviously societally detrimental effects while instead improving/saving the lives of that many more infants, we have the moral imperative to do so. Finally, the pro-life position is against organ donation in this case on the religious grounds that human life begins at conception. Thus anencephalics have the right to life, regardless of their non-sentience.

At the core of the dispute between pro-life and other views is the status of anencephalics as persons. Ultimately, the goal of those in support of organ donation is that it will decrease the shortage in infant organs. It has been estimated that 400-500 infant hearts and kidneys and 500-1,000 infant livers are needed in the United States each year.[24] Currently, laws in some states prevent organ transplantation from living persons, and federal laws forbid the use of any form of euthanasia. Because anencephalic neonates have partially functioning brain stems, they reserve some of the body’s autonomic functions, such as those of the heart, kidneys and intestines. For this reason, some believe that anencephalic neonates are functioning human beings despite the absence of all cognitive function.[25]

The pros of organ donations are that many children will be saved from death, and additionally, parents of many anencephalic children believe that some good comes from organ donation.[25] Furthermore, it saves the costs of caring for a terminally ill child; and instead of two babies dying, health care providers are able to save one.[26] The cons are that several laws prevent removing organs from a living being or make organ donation from anencephalics impossible, some organs from anencephalic children cannot be transported due to abnormalities and the fear that there is not a significant amount of anencephalic donors to reach the demand for certain organs, such as kidneys.[26]

Within the medical community, the main ethical issues with organ donation are a misdiagnosis of anencephaly, the slippery slope argument, that anencephalic neonates would rarely be a source of organs, and that it would undermine confidence in organ transplantation.[25] Slippery slope concerns are a major issue in personhood debates, across the board. In regards to anencephaly, those who oppose organ donation argue that it could open the door for involuntary organ donors such as an elderly person with severe dementia. Another point of contention is the number of children who would actually benefit. There are discrepancies in statistics; however, it is known that most anencephalic children are stillborn.[25]

Proposals have been made to bypass the legal and ethical issues surrounding organ donation. These include waiting for death to occur before harvesting organs, expanding the definition of death, creating a special legal category for anencephalic infants, and defining them as non-persons.[26]

Brain death

There are four different concepts used to determine brain death: failure of heart and lungs, whole brain death, and neocortical death. Some argue that anencephalics experience neocortical death, in which there is an irreversible loss of consciousness and self-awareness, two determinants of a person. Brain death is another source of support for organ donation.[27]

Neocortical death, similar to a persistent vegetative state (PVS), involves loss of cognitive functioning of the brain. A proposal by law professor, David Smith, in an attempt to prove that neocortical death should legally be treated the same as brain death, involved PET scans to determine the similarities. However this is not a well-received proposal considering the contradicting views on classifying brain death.[28]

To continue or end the pregnancy

Anencephaly can be diagnosed prenatally with a high degree of accuracy. Given that anencephaly is a fatal condition, parents receive the option of abortion either in the second or third trimester of pregnancy, depending on the abortion laws in the state.[24] In 2012, Brazil extended the right of abortion to mothers with anencephalic fetuses. This decision is, however, receiving much disapproval by several religious and human rights groups.[29]

"Drawing the line" rebuttal

The "drawing the line" rebuttal seeks to establish when a fetus becomes a person and if it is able to think by itself.[30]

Legal proceedings

The case of baby Theresa was the beginning of the ethical debate over anencephalic infant organ donation.[23] The story of baby Theresa remains a focus of basic moral philosophy. Baby Theresa was born with anencephaly in 1992. Her parents, knowing that their child was going to die, requested that her organs be given for transplantation. Although her physicians agreed, Florida law prohibited the infant's organs from being removed while she was still alive. By the time she died nine days after birth, her organs had deteriorated past the point of being viable.[31]

Baby K was an anenecephalic infant that was kept alive for two years and 174 days under intensive care by order of the Fourth Circuit Court of Appeals.

United States Uniform Acts

The Uniform Determination of Death Act (UDDA) is a model bill, adopted by many US states, stating that an individual who has sustained either 1) irreversible cessation of circulatory and respiratory functions or 2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. This bill was a result of much debate over the definition of death and is applicable to the debate over anencephaly. A related bill, the Uniform Anatomical Gift Act (UAGA), grants individuals and, after death, their family members the right to decide whether or not to donate organs. Because it is against the law for any person to pay money for an organ, the person in need of an organ transplant must rely on a volunteer.[24]

There have been two state bills that proposed to change current laws regarding death and organ donation. California Senate Bill 2019 proposed to amend the UDDA to define anencephalic infants as already dead, while New Jersey Assembly Bill 3367 proposed to allow anencephalic infants to be organ sources even if they are not dead.[32][33]

See also

References

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  2. ^ a b c d "Anencephaly Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". http://www.ninds.nih.gov/disorders/anencephaly/anencephaly.htm. 
  3. ^ koaa.com, Baby Without A Brain, Nicholas Coke, Update
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  7. ^ http://www.chg.duke.edu/diseases/ntd.html
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  9. ^ a b al.], [edited by] Stephen D. Ratcliffe ... [et (2008). Family medicine obstetrics (3rd ed. ed.). Philadephia: Mosby Elsevier. ISBN 0-323-04306-2. 
  10. ^ Goldsmith, Alexander (1996, quoted by Millen and Holtz, "Dying for Growth")
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  15. ^ "Beloved Vitoria Blog". http://www.belovedvitoria.blogspot.co.uk/2012/07/our-beloved-vitoria-is-now-with-christ.html. Retrieved 20 July 2012. 
  16. ^ "Boy without a brain". Archived from the original on 12 July 2012. http://www.koaa.com/videos/boy-without-a-brain/?fullsite. Retrieved 2012-07-16. 
  17. ^ "U.S. National Library of Medicine". http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002547/. 
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  19. ^ a b c Isada. "Meroanencephaly: Pathology and Prenatal Diagnosis.". U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/pubmed/8286034. 
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  23. ^ a b c Bard, Jennifer. "The Diagnosis Is Anencephaly And The Parents Ask About Organ Donation: Now What? A Guide For Hospital Counsel And Ethics Committees.". Western New England University School of Law,. http://digitalcommons.law.wne.edu/lawreview/vol21/iss1/3/. Retrieved 19 July 2012. 
  24. ^ a b c Meinke, Sue. "Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues". Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues. http://bioethics.georgetown.edu/publications/scopenotes/sn12.pdf. Retrieved 19 July 2012. 
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  32. ^ Meinke, Sue. [Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues "Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues"]. Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues. Anencephalic Infants as Potential Organ Sources: Ethical and Legal Issues. Retrieved 19 July 2012. 
  33. ^ "Uniform Declaration of Death Act (UDDA)". http://www.ascensionhealth.org/index.php?option=com_content. Retrieved 19 July 2012. 

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