Neural tube defects with high resolution sonography

Using high resolution sonography has allowed increased definition and detail study of the fetal brain from 12 to 14 weeks gestation for the Congenital anomalies that arise from Central nerves system (CNS).

Using color flow, Trans vaginal, 3 and 4d scan harmonic and compound scanning and high resolution transducers can be helpful to gain better diagnosis. With the use of maternal serum alpha-fetoprotein 9 MSAFP) screening combined with high resolution sonography, the potential exist to diagnosis most NTDs before the 20th week of pregnancy.

Key words: Ultrasound, NTD, fetal anomaly

Neural tube defects (NTD) a regroup of malformations resulting from failure of neural tube closure early in embryology stage. They could be mild or severe form of lethal conditions such as anencephaly to meningoceles that can be corrected by surgery. The frequency of NTDs in North America and Canada is 1 in 1000 live births.1, 3 Closed to 7000 live and stillborn infant are born with NTD each year in the USA & Canada. NTDs are more common congenital anomaly after congenital heart malformation in fetus. 2  

Most of these anomalies are equally divided between anencephaly and spinal bifida. 2 with slightly more female fetuses affected than male fetuses. 2, 4 Defect that open called NTDs exposed through the skin surface, or closed NTD skin covered. The open form of NTDs relates to the time of neural tube formation in the embryo; while closed NTDs develop later in the pregnancy.2 Almost 90% of NTDs is open malformation.2

The potential to diagnosis of the majority of NTDs in utero is by using biochemical markers and finding in the amniotic fluid or the use of sonography, many of these malformations can be detected before 20 weeks gestation. 5 

A fetus with open NTD shows an elevated amniotic fluid alpha-fetoprotein (AFAFP) level, This protein is produced by the fetal liver, kidneys, gastrointestinal tract, and yolk sac has direct access to the amniotic fluid by a fetal capillary system on the surface of the open NTDs. 2 BY the 13th to 15th week of gestation the AFAFP reaches peak levels. 2 Other malformation such as omphoaloceles, gastroschisis, and some form of esophageal defect can also elevate the AFAFP. 2

When a woman has an elevated AFAFP she is usually referred to do have an ultrasound scanning of the pregnancy and dating. If the fetus have normal ultrasound scan and the blood test is positive could be an error in dates, presence of twins, and placental hemorrhage, Alpha-phtoprotien and also appears in serum (MSAFP) around 16th to 18th weeks of gestation. 6

One in ten women with increased MSAFP will have open NTD. 2, 3 10% of NTDs are closed and will not show any increase in AFP. The most common risk factor is family history of NTD, diabetes, and teratogen exposure. The highest rate was reported in the British Isles in Ireland and Wales, with Anencephaly the most frequently occurring NTD, it occur in female more than male fetuses.2

There are different type of CNS and spinal defects malformation such as; anencephaly, hydranncephaly, hydrocephaly, encphalocele, chairi II malformation, Dandy walker malformation, holoprosencephaly, microcephaly, and spinal bifida (meningoceles and meningomyelocele).

Anencephaly (Acrania)

It is an absence of the cranial vault and cerebral hemispheres, portion of the mid-brain and brain may be present, it is the most common congenital finding involving the CNS, with 1 in 1000 birth indigence rate.1-3 It results from failure of the neural tube to close at the cephalic end around 2 to 3 weeks gestation, with recurrence rate of 4%.4 The uterus may appear to be large for gestational age, with 40 to 50% of the cases presenting with polyhydramnios, spinal bifida, meningomyelocele, cleft palate, and umbilical herniation also may be associated with this finding, these fetuses born a life but they die soon after birth. 2-7, with sonography the diagnosis can be made as early as 12 weeks of gestation.

Anencephaly shows orbits only ,without cranial vault

Chiari II Malformations

Lemon sign and / or banana sign are important sonographic markers of Chiari type 2 and spina bifida. In Chiari 2 malformation, down herniation of the cerebellum and structures like brain stem may cause non-communicative hydrocephalus by blocking the flow of cerebrospinal fluid. The Chiari II malformation (Arnold-Chiari malformation) is a complex congenital malformation of the brain, nearly always associated with, and the most common serious malformation of the posterior fossa.

lemon sign, and lateral ventricles dilatation .

This condition has skull, dural, brain, spinal, and spinal cord manifestations, including downward displacement of the medulla, fourth ventricle, and cerebellum into the cervical spinal canal, as well as elongation of the pons and fourth ventricle, probably due to a relatively small posterior fossa. 6-7 The differential diagnosis includes spinal astrocytoma, Chiari I malformation, chordoma, and encphalocele. Other conditions to be considered include fourth ventricle ependymoma, Lhermitte-Duclos disease, rhombencephalosynapsis, and tectocerebellar dysraphia with posterior encphalocele.

Type 2 and 3 Chairi malformation ,posterior ancephalocele.

Cerebellum shows Banana sign and CM is the citerna magna,and the Second image shows sacra l cystic area posterior spine .

The Dandy-Walker complex

It is a rare congenital intracranial malformation that comprises a spectrum of abnormalities of the posterior fossa which are classified as (a) Dandy-Walker malformation (cystic dilatation of the 4th ventricle, complete or partial a genesis of the cerebellar vermis and an enlarged posterior fossa) (b) Dandy-Walker variant (cystic posterior fossa mass with variable hypoplasia of the cerebellar vermis and no enlargement of the posterior fossa) and (c) Mega-cisterna magna (enlarged cisterna magna with normal cerebellar vermis and fourth ventricle).

Posterior fossa with Dandy walker syndrome , The images shows enlarged cisterna magna(CM), and normal cerebellum.

The prenatal sonographic diagnosis of the classic Dandy-Walker malformation is simple, however the definitive diagnosis of Dandy-Walker variant and Mega-cisterna magna is difficult before 18 weeks of gestation. This is because the sonographic appearance of normal cerebellum in the second trimester can resemble pathological anomalies as the posterior fossa structures are not established until then and the Sonologist must exercise caution before reaching a final diagnosis of Dandy-Walker variant or mega-cisterna magna. 8

Encphalocele

It is a defect in the cranial vault with a sac like structure at the surface of the ectoderm. Intracranial contents herniated through the defect and lie outside the skull. The meanings alone, or both meanings and brain tissue, may prolapsed out through the defect, 75% occur in the occipital region, with 13% occurring in the frontoethmoidal, and 12% in the parietal regions, generally present with polyhydramnios and microcephaly. 1 Mass that may be cystic or solid will be observed on ultrasound image with protruding from calvarium. Chiari II and Dandy walker malformation may also be associated. Those fetuses with brain tissue herniation have higher mortality rate of 40% and those who survive have 80% incidence of intellectual impairment, and other neurological problems. 1

Posterior skull cystic mass ( Encephalocele).

Hydrancephaly

Most common hypothesis is intrauterine cerebral infraction secondary to bilateral internal carotid artery occlusion, infectious disease, including toxoplasmosis, and cytomegalic viral infection. Absent of cerebral hemispheres except for portion of occipital lobe, The word hydranncephaly is a fusion of hydrocephalus, but the condition actually represents a distinct disorder and is primarily a disease of the fetus; encephaloclastic encephalomalacia can occur in cases of severe prenatal insult.  Hydranncephaly occurs in less than 1 in 10,000 births and is characterized by near-total or total absence of the cerebral cortex and basal ganglia. 8, 9

Mild form of Hydranencephaly,lateral ventricles dilatation.

The thalami, pons, cerebral peduncles, and cerebellum are usually present, as may be a small amount of tissue from the occipital, frontal, and temporal lobes.  There is no known sex or racial predilection. Knowledge about possible etiologies of hydranncephaly comes from various observations and experiments. Studies in sheep and monkeys have demonstrated that bilateral ligation of the carotid arteries results in destruction of the cerebral hemispheres, with relative preservation of the portions of the brain supplied by the posterior circulation, giving an appearance similar to that of hydranncephaly. 8, 9, and 10

Severe form of Hydranencephaly

Hydrocephalus

Hydrocephalus also called water in the brain is a condition where there is an abnormal build up of CSF (cerebrospinal fluid) in the cavities (ventricles) of the brain. The build-up is often caused by an obstruction that prevents proper fluid drainage .Hydrocephalus merely denotes an increase in the volume of CSF and thus of the cerebral ventricles (ventriculomegaly). Although hydrocephalus is typically referred to as either being "obstructive" or "communicating", this can lead to confusion as to the underlying cause of ventriculomegaly as the terms are referring to different aspects of the underlying pathophysiology. 11, 12

Severe Hydrocephalus

For example, acute subarachnoid hemorrhage confined to the basal cisterns can result in ventriculomegaly by obstructing the normal flow of CSF through the basal cisterns, and by filling the arachnoids granulations. Given that this is mechanistically an obstruction to CSF flow outside of the ventricular system should it be considered communicating or obstructive hydrocephalus? The correct answer is that is actually a communicating obstructive hydrocephalus. 11-14.

As such a more precise terminology is to divide hydrocephalus into:

Communicating and non-communicating: addressing "where" the obstruction is located. Obstructive and non-obstructive: on the grounds of whether or not there is obstruction of CSF pathways in the ventricles or the subarachnoid.

Non-communicating (i.e. CSF cannot exit the ventricular system, and thus there is by definition obstruction to CSF absorption) often merely referred to as Obstructive hydrocephalus. Upstream ventricles are dilated and exert mass effect upon adjacent brain (e.g. effacement of sulci)

Holoprosencephaly

Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres. Normally, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of human pregnancy. It is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. 

There are 4 types of holoprosencephaly, distinguished by severity.

From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). 15 In general, the severity of any facial defects corresponds to the severity of the brain defect.

Semi- lobar Holoprosencephaly.

The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes, chromosome abnormalities; or agents that can cause birth defects (teratogen). 15, 16 

Alobar Holoprosencephaly

Microcephaly

It is a condition where the head (circumference) is smaller than normal. Microcephaly may be caused by genetic abnormalities or by drugs, alcohol, certain viruses, and toxins that are exposed to the fetus during pregnancy and damage the developing brain tissue. Microcephaly is a condition where a baby’s head is much smaller than expected.

During pregnancy, a baby’s head grows because the baby’s brain grows. Microcephaly can occur because a baby’s brain has not developed properly during pregnancy or has stopped growing after birth, which results in a smaller head size. Microcephaly can be an isolated condition, meaning that it can occur with no other major birth defects, or it can occur in combination with other major birth defects. 17

Microcephaly caused by Zika virus infection

Severe microcephaly

Severe microcephaly is a more serious, extreme form of this condition where a baby’s head is much smaller than expected. Severe microcephaly can result because a baby’s brain has not developed properly during pregnancy, or the brain started to develop correctly and then was damaged at some point during pregnancy.

Microcephaly caused by dengue viral infection

Other Problems

Babies with microcephaly can have a range of other problems, depending on how severe their microcephaly is. Microcephaly has been linked with problems such as: Seizures, Developmental delay, such as problems with speech or other developmental milestones (like sitting, standing, and walking), Intellectual disability (decreased ability to learn and function in daily life)  Problems with movement and balance,  Feeding problems, such as difficulty swallowing,  Hearing loss, Vision problems.  

These problems can range from mild to severe, and are often lifelong problems. Because the baby’s brain is small and underdeveloped, babies with severe microcephaly can have more of these problems, or have more difficulty with them, than babies with milder microcephaly. Severe microcephaly also can be life-threatening. Because it is difficult to predict at birth what problems a baby will have from microcephaly, babies with microcephaly often need close follow-up through regular check-ups with a healthcare provider to monitor their growth and development(17). Microcephaly is not a common condition. Researchers estimate that about 1 in every 800-5,000 babies are born with microcephaly in the United States. 17

The causes of microcephaly in most babies are unknown. Some babies have microcephaly because of changes in their genes. Other causes of microcephaly, including severe microcephaly, can include the following exposures during pregnancy: Certain infections during pregnancy, such as rubella, toxoplasmosis, or cytomegalovirus,  Severe malnutrition, meaning a lack of nutrients or not getting enough food, Exposure to harmful substances, such as alcohol, certain drugs, or toxic chemicals,      Interruption of the blood supply to the baby’s brain during development.

Some babies with microcephaly have been reported among mothers who were infected with Zika virus while pregnant. CDC scientists announced that enough evidence has accumulated to conclude that Zika virus infection during pregnancy is a cause of microcephaly and other severe fetal brain defects. 17

CDC continues to study birth defects such as microcephaly and how to prevent them. If you are pregnant or thinking about becoming pregnant, talk with your doctor about ways to increase your chances of having a healthy baby. Zika Virus can cause Microcephaly and can be diagnosed during pregnancy or after the baby is born. 17

Microcephaly can be determined by measuring head circumference (HC) after birth. Although head circumference measurements may be influenced by molding and other factors related to delivery, the measurements should be taken on the first day of life because commonly-used birth head circumference reference charts by age and sex are based on measurements taken before 24 hours of age.

The most important factor is that the head circumference is carefully measured and documented. If measurement within the first 24 hours of life is not done, the head circumference should be measured as soon as possible after birth.

If the healthcare provider suspects the baby has microcephaly, he or she can request one or more tests to help confirm the diagnosis. For example, special tests like like magnetic resonance imaging can provide critical information on the structure of the baby’s brain that can help determine if the newborn baby had an infection during pregnancy. They also can help the healthcare provider look for other problems that might be present. 17

Spina bifida

It is a birth defect that occurs when the spine and spinal cord don't form properly. It's a type of neural tube defect. The neural tube is the structure in a developing embryo that eventually becomes the baby's brain, spinal cord and the tissues that enclose them.

Fetal ultrasound is the most accurate method to diagnose spina bifida in your baby before delivery. Ultrasound can be performed during the first trimester (11 to 14 weeks) and second trimester (18 to 22 weeks). 18, 19

Spina bifida can be accurately diagnosed during the second trimester ultrasound scan. Spina bifida is failure of the normal development of the neural tube. The etiology is often multi factorial with both genetic and environmental factors considered to play a role. Intake of adequate amounts of folic acid plays a protective role. Another method is based on the position, either anterior (ventral) or posterior (dorsal). The vast majority of cases are of dorsal spina bifida. 18-25

A spina bifida can also be sub typed as:Open: (80-90%) especially if detected antenatal. 20

Myeloschisis

Myelomeningocele (mostly open, associated with Chairi II malformation)

Closed: if covering skin present

Meningoceles (may be open), Lipomylomenngocele, Myelocystocel, Tethering cord, Diastematomyelia, and Syringomylia.

 Meningoceles

Are protrusions of the Meninges through a defect or weak point in the skull or spine, usually involving the soft tissues beneath the surface of the skin. 24, 25 In this least common type of spina bifida, the Meninges (membrane surrounding the spinal cord) protrude through the opening causing a lump or sac on the back. More severe than spina bifidaocculta, Meningoceles can nevertheless be repaired through surgery with little or no nerve damage resulting. The surgery is performed at any time during infancy. With meningoceles, the spinal cord has developed normally and is undamaged. The child has no neurological problems. 22-25

Myelomeningocele

Myelomeningocele is the most severe form of spina bifida, occurring nearly once for every 1,000 live births. For infants born with a myelomeningocele, the spinal cord does not form properly and a portion of the undeveloped cord protrudes through the back. A sac containing cerebrospinal fluid and blood vessels surrounds the protruding cord, which is usually not covered by skin so that the nerves and tissues are exposed. 22-25

Myelomeningocele

Between 70% and 90% of infants born with myelomeningocele also experience Hydrocephalus due to a defect at the base of the skull (Chiari malformation). Hydrocephalus is an excess buildup of spinal fluid on the brain that will cause brain damage, seizures or blindness if it is left untreated. To avoid this, plastic shunts must be surgically inserted beneath the skin to drain off excess fluid into the abdominal cavity. 22-24

Infants born with myelomeningocele often have paralysis or weakness below the level of the spinal lesion. This affects the lower limbs along with problems with bladder and bowel function. In extreme cases, the trunk and upper extremities are involved. 25

Ultrasound features of the Arnold-Chiari malformation in fetuses with open neural tube defects. The banana sign refers to the shape of the cerebellum owing to caudal displacement; the lemon sign refers to the lemon-shaped head resulting from scalloping of the frontal bones.

Typical frontal pinching of calvarium gives a lemon appearance of the skull and a banana shaped cerebellum is seen due to a shallow posterior fossa. These are signs we see with sonography exams of the posterior fossa anomalies, or Chiari malformation.

Conclusion

High resolution sonography has made it possible to better visualize the development fetus and diagnose fetal abnormalities before 20 weeks gestation .Screening for MSAFP and AFAFP levels has greatly assisted the diagnostic team in the detection of NTDs. Understanding of these pathological finding associated with NTD will make diagnosis and management easier to all that involves in the treatment and patient management.

The sonographic diagnosis of fetal neural tube defects (NTDs) has been enhanced by the recognition of associated brain and skull anomalies. Previous reports have found these anomalies to be accurate in predicting spina bifida after 16 weeks gestation. Therefore, we assumed that early second‐trimester sonography would be at least as accurate as that performed after 16 weeks' gestation.

Using transvaginal sonography (TVS), between the 12th and 17th week of gestation (menstrual age), high resolution sonography, and Serum test will improve the diagnosis of NTDs. ‘Banana’ sign, cerebellar absence, and hypoplasia were signs that can be detected using sonography and EV sonography can improve the imaging.

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21. Centers for Disease Control and Prevention. Whats is spina Bifida? Accessed 1/30/2020. https://www.cdc.gov/ncbddd/spinabifida/facts.html

22. Spina Bifida Association. Whats is spina Bifida? Accessed 1/30/2020. https://www.cdc.gov/ncbddd/spinabifida/facts.html

23. National Institution of Neurological Disorders and Stroke. Whats is spina Bifida? Accessed 1/30/2020. https://www.cdc.gov/ncbddd/spinabifida/facts.html

24. Genetics Home Reference, Whats is spina Bifida? Accessed 1/30/2020. https://www.cdc.gov/ncbddd/spinabifida/facts.html

Steve Ramsey, PhD.