Amyotrophic Lateral Sclerosis

Background: Anencephaly is a serious developmental defect of the central nervous system in which the brain and cranial vault are grossly malformed. The cerebrum and cerebellum are reduced or absent, but the hindbrain is present. Anencephaly is a part of the neural tube defect (NTD) spectrum. This defect results when the neural tube fails to close during the third to fourth weeks of development, leading to fetal loss, stillbirth, or neonatal death.

Pathophysiology: In the normal human embryo, the neural plate arises approximately 18 days after fertilization. During the fourth week of development, the neural plate invaginates along the embryonic midline to form the neural groove. The neural tube is formed as closure of the neural groove progresses from the middle toward the ends in both directions, with completion between day 24 for the cranial end and day 26 for the caudal end. Disruptions of the normal closure process give rise to NTDs. Anencephaly results from failure of neural tube closure at the cranial end of the developing embryo. Absence of the brain and calvaria may be partial or complete.

MTHFR) has been shown to be associated with the risk of NTDs; however, the overall effect is relatively weak. A variety of environmental factors appears to be influential in the closure of the neural tube. Most notably, folic acid and other naturally occurring folates have a strong preventive effect. Folate antimetabolites, maternal diabetes, maternal obesity, and hyperthermia in early development have been identified as stressors that increase the risk of NTDs, including anencephaly.

Frequency:

• <In the US: Average birth prevalence of anencephaly is approximately 1.2 per 10,000 births, with a gradient of increasing frequency from the West Coast to the East Coast. The frequency during pregnancy is considerably higher than the birth prevalence, with estimates as high as 1 case per 1000 pregnancies. Such pregnancies often end in early pregnancy loss, spontaneous abortion, fetal death, or pregnancy termination. Within the United States, South Carolina has historically reported the highest birth prevalence of NTDs, with a rate that has been approximately double that of the national average. The rate of NTDs in South Carolina has fallen dramatically over the past decade following the introduction of aggressive campaigning for periconceptional folic acid supplementation, fortification of wheat flour, and increased periconceptional vitamin supplementation. The reason for a higher occurrence of NTDs in South Carolina compared with other areas of the country is not known.

• Internationally: Considerable geographical variation in NTD rates exists, with noted hotspots in Guatemala, northern China, Mexico, and parts of the United Kingdom.

Race: Hispanic and non-Hispanic whites are affected more frequently than women of African descent.

Sex: Females are affected more frequently than males.

Age: Anencephaly is determined by the 28th day of conception and is therefore invariably present at the time of birth.

Treatment
Medical Care: Because anencephaly is a lethal condition, heroic measures to extend the life of the infant are contraindicated. The physician and medical care team should focus on providing a supportive environment in which the family can come to terms with the diagnosis and make preparations for their loss.

• Families not aware of the diagnosis of anencephaly prior to birth or for whom the diagnosis is still fresh probably will need extra emotional support and possibly grief counseling. Families who have had some time to adjust to the diagnosis prior to delivery and who have had an opportunity to begin the grieving process ahead of time may seem well prepared, but they also will need adequate time to grieve and come to closure. The presence of family, friends, or clergy may be helpful in many cases.

• Families often want to hold the baby after delivery, even if the baby is stillborn, and families wanting photographs of the baby with the family are not unusual. A cap or head covering of some sort is useful to minimize the visual impact of the malformation. Some families want to see the lesion, and this may help to dispel mental pictures, which are often worse than the actual malformations. In most cases, direct personal contact with the baby may help the parents to actualize the medical information they have been given and may help in the process of grief resolution.

• If parents have chosen a name for the baby, they may be comforted if the doctor refers to the baby by name.

• Feelings of guilt are normal responses of parents of a baby with serious birth defects. The involvement of genetic counselors, if available, may be particularly useful to parents in this situation because of their experience in dealing with a wide range of birth defects.

• With timely prenatal diagnosis of this lethal disorder, the option of pregnancy termination should be presented to the couple. For couples who elect to continue the pregnancy, the possibilities of preterm labor, oligohydramnios, failure to progress, and delayed onset of labor beyond term also should be discussed.

• Families commonly inquire about organ donation after the diagnosis of anencephaly. This cannot practically be arranged without crossing the lines of ethical care. Patients should be affirmed in their desires to see something meaningful come from the tragedy of having a pregnancy affected with anencephaly.

Consultations: Every couple with a child who has anencephaly should consult with a geneticist and/or a genetic counselor in order to obtain information regarding recurrence risks, prevention, screening, and diagnostic testing options for future pregnancies and to assess the family history. Ideally, a genetic counselor should be consulted prenatally and should remain involved, as needed, until the family comes to closure after the conclusion of the pregnancy.

Diet: Folic acid supplementation and/or a folate-enriched diet prior to and during future pregnancies are recommended. Obtaining enough folates from diet alone to effectively prevent recurrences in future pregnancies is extremely difficult.

Medication
Pharmaceutical interventions are not used in cases of anencephaly.