Anencephaly

Absence of the cranial vault above the bony orbits. This is eventually associated with absence of the cerebral hemispheres with residual covering variable amounts of angiomatous stroma.

Exencephaly - anencepahly sequence.

ICD-10: Q00.0

Anencephaly is the single most common neural tube defect with a reported incidence of 3.76 per 10,000 births in Europe. At present, about 80% of these cases undergo selective termination, and the live birth rate is less than 10%.¹ There are geographic and race differences. The incidence is particularly high in portions of the United Kingdoms and low in Asia. As a consequence of prenatal diagnosis and selective termination the prevalence at birth has much decreased in England and continental Europe.² Females are usually more commonly affected than males, with a ratio as high as a 4:1 ratio. However, recent data would indicate that when all neural tube defects are considered together, there is probably an equal female:male incidence.³

Anencephaly is thought to result from incomplete closure of the cephalic end of the neural tube, which usually is completely fused by day 28. This will have secondary effects including 1) a partially developed generative forebrain; 2) incomplete calvarial development above the bony orbits; and 3) occasionally associated malformations including cleft palate, abnormal cervical vertebra, and abnormal development of the pituitary.⁴

In most situations the precise etiology for anencephaly is not determined. It is thought the etiology is multifactorial, resulting from a combination of genetic, nutritional, and environmental factors.⁵ The role of folic acid in the prevention of neural tube defects is well established.^{2, 6} and assumption of folic acid antagonists, such as some antiepileptic drugs, is associated with an increased incidence of these malformations.^{7, 8} While maternal obesity has been associated with an increased incidence of neural tube defects, it has not been specifically associated with an increased risk of anencephaly.⁹

Anencephaly is characterized by absence of the cerebral hemispheres and absence of the accompanying cranial vault. A layer of angiomatous stroma (area cerebrovasculosum) covers the defect. There is never skin overlying the lesion. The brainstem and variable portions of the midbrain (mesencephalon) are present. There is absence of the cranial bones above the orbits, while the base of the cranium which develops from cartilage is present. When diagnosed during the first trimester or early second trimester the cerebral hemispheres may sometimes be present.

Spina bifida urinary tract anomalies, cleft lip/palate, gastrointestinal abnormalities, and cardiac abnormalities (4%).¹⁰

Table 1 describes the risk or recurrence of neural tube defects.¹¹ The risk is significantly decreased with ingestion of folic acid supplements and/or multivitamins prior to and early in pregnancy.

The sonographic appearance of anencephaly depends upon gestational age. Diagnosis has been reported as early as 9 weeks’ gestation.¹² However, recognition is usually difficult prior to 11 weeks.¹³ At this time in gestation and up to 14-15 weeks the main finding is the presence of an irregular outline of the cephalic pole, with a distorted brain mass that is not surrounded by a bony calvarium and floats in the amniotic fluid. In a coronal view this results in a typical image (the Mickey Mouse face).

At migestation the most striking feature is absence of the calvarium above the bony orbits.¹⁵ The base of the skull is present and the orbits appear prominent. There may be tissue above the bony orbits which is the angiomatous stroma. This defect is usually easily recognized, and in Europe roughly 80% of cases undergo selective termination following prenatal diagnosis.¹ Polyhydramnios is found in almost 90% of cases, but appears usually only after 25 weeks.¹⁵

Differential diagnosis of anencephaly includes severe cerebral lesions such as extreme microcephaly, gross cephaloceles, acrania and amniotic band syndrome, and acardiac twins.

Extreme microcephaly can be potentially mistaken for anencephaly. However, a distinguishing feature is the presence of a bony calvarium. Large encephaloceles may be difficult to differentiate from anencephaly in early gestation, but this would be of little consequence as these lesions have a dismal prognosis, as anencephaly. Amniotic band syndrome may cause destruction of the brain and cranial vault. However, it is usually asymmetrical and bizarre in appearance and is virtually always associated with extracranial malformations such as amputation . The distinguishing feature of acrania is the presence of large amount of brain tissue, but like anencephaly there is absence of the cranial vault Distinguishing the two conditions in early gestation is virtually impossible. In the second and third trimester, acranic fetuses will have distorted cerebral hemispheres not surrounded by the calvarium. Some believe exencephaly is a continuum with anencephaly.¹⁶ The acardiac twin occurs within a monozygotic pregnancy as a consequence of reversed arterial perfusion.¹⁷ Oxygenated blood enters the acardiac twin from the umbilical arteries into the iliac arteries. Only the body torso and the lower limbs are well perfused and thus well developed. Distinguishing anencephaly from an acardiac twin is important because the latter condition poses at significant risk the unaffected co-twin. The differentiation however is usually easy, as the acardiac twin usually has no head and no facial structure, significant subcutaneous edema and retrograde perfusion in the umbilical cord and descending aorta.¹⁸

Anencephaly can be recognized as early as 11 weeks depending upon the expertise of the sonographer, and anyhow should always be identified by midgestation. The detection rate of anencephaly is 92% with alpha-fetoprotein and 100% with ultrasonography.¹⁹ In Europe about 80% of cases undergo selective termination after prenatal diagnosis.

Anencephaly is uniformly fatal. Newborns usually die within hours after birth, although reports of survival to a few months have been reported.

In singleton pregnancies, termination can be offered to the couples. A controversial issue is the management of twin pregnancies with one anencephalic fetus. It has been suggested that dichorionic twins are best managed with serial ultrasound examinations for early diagnosis of polyhydramnios, which can then be treated either by amniodrainage or selective feticide of the malformed fetus. In monochorionic twins it is uncertain whether the best management is expectant or by cord occlusion.²⁰

Folic acid assumption around the time of conception may reduce the risk of neural tube defects by two thirds.²¹ The U.S. Preventive Services Task Force (USPSTF) recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 microg) of folic acid. (Grade A recommendation). Patients at high risk for fetal neural tube defects should receive 4 mg daily.⁶ Universal folic acid fortification raises however medical and ethical controversies.²² Different policies to ensure folic acid administration to pregnant women exist in different European countries. The lack of a substantial decline in neural tube defect prevalence suggests however that this approach is not effective.² In USA and Canada floury nutrients are now supplemented with folic acid to ensure generalized fortification. This has indeed resulted in a reduction of approximately 30 % of neural tube defects in the USA.²²

1. European Surveillance of Congenital Anomalies. 2009; Available from: http://www.eurocat.ulster.ac.uk/.
2. Busby A, Abramsky L, Dolk H, Armstrong B. Preventing neural tube defects in Europe: population based study. BMJ. 2005;330(7491):574-5. Epub 2005/03/12.
3. Seller MJ. Sex, neural tube defects, and multisite closure of the human neural tube. Am J Med Genet. 1995;58(4):332-6. Epub 1995/09/25.
4. Jones KL. Smith’s Recognizable Patterns of Human Malformation, 4th ed. Philadelphia: WB Saunders; 1988.
5. Bassuk AG, Kibar Z. Genetic basis of neural tube defects. Semin Pediatr Neurol. 2009;16(3):101-10. Epub 2009/09/26.
6. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(9):626-31. Epub 2009/05/06.
7. Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother. 1998;32(7-8):802-17. Epub 1998/07/29.
8. Matok I, Gorodischer R, Koren G, Landau D, Wiznitzer A, Levy A. Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations. Br J Clin Pharmacol. 2009;68(6):956-62. Epub 2009/12/17.
9. Shaw GM, Velie EM, Schaffer D. Risk of neural tube defect-affected pregnancies among obese women. JAMA. 1996;275(14):1093-6. Epub 1996/04/10.
10. David TJ, Nixon A. Congenital malformations associated with anencephaly and iniencephaly. J Med Genet 1976;13:263-5.
11. Main DM, Mennuti MT. Neural tube defects: issues in prenatal diagnosis and counselling. Obstet Gynecol. 1986;67(1):1-16. Epub 1986/01/01.
12. Becker R, Mende B, Stiemer B, Entezami M. Sonographic markers of exencephaly at 9 + 3 weeks of gestation. Ultrasound Obstet Gynecol. 2000;16(6):582-4. Epub 2001/02/13.
13. Johnson SP, Sebire NJ, Snijders RJ, Tunkel S, Nicolaides KH. Ultrasound screening for anencephaly at 10-14 weeks of gestation. Ultrasound Obstet Gynecol. 1997;9(1):14-6. Epub 1997/01/01.
14. Chatzipapas IK, Whitlow BJ, Economides DL. The 'Mickey Mouse' sign and the diagnosis of anencephaly in early pregnancy. Ultrasound Obstet Gynecol. 1999;13(3):196-9. Epub 1999/04/16.
15. Goldstein RB, Filly RA. Prenatal diagnosis of anencephaly: spectrum of sonographic appearances and distinction from the amniotic band syndrome. AJR Am J Roentgenol. 1988;151(3):547-50. Epub 1988/09/01.
16. Timor-Tritsch IE, Greenebaum E, Monteagudo A, Baxi L. Exencephaly-anencephaly sequence: proof by ultrasound imaging and amniotic fluid cytology. J Matern Fetal Med. 1996;5(4):182-5. Epub 1996/07/01.
17. Benirschke K. The monozygotic twinning process, the twin-twin transfusion syndrome and acardiac twins. Placenta. 2009;30(11):923-8. Epub 2009/09/15.
18. Bornstein E, Monteagudo A, Dong R, Schwartz N, Timor-Tritsch IE. Detection of twin reversed arterial perfusion sequence at the time of first-trimester screening: the added value of 3-dimensional volume and color Doppler sonography. J Ultrasound Med. 2008;27(7):1105-9. Epub 2008/06/26.
19. Norem CT, Schoen EJ, Walton DL, Krieger RC, O'Keefe J, To TT, Ray GT. Routine ultrasonography compared with maternal serum alpha-fetoprotein for neural tube defect screening. Obstet Gynecol. 2005;106(4):747-52. Epub 2005/10/04.
20. Vandecruys H, Avgidou K, Surerus E, Flack N, Nicolaides KH. Dilemmas in the management of twins discordant for anencephaly diagnosed at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol. 2006;28(5):653-8. Epub 2006/07/25.
21. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338(8760):131-7. Epub 1991/07/20.
22. Smith AD. Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12. Am J Clin Nutr. 2007;85(1):3-5. Epub 2007/01/09.

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