Presented to:Mary Anne M. Occo

Clinical Instructor

Presented By:Alimodian, Aiza A.

Camsain, Norizza R.De Guzman, Michelle S.

Igasan, Fahjir A.Jamasari, Adawiya S.

Lee, Vadimier A.Mendoza, Maricore A.Pedroso, She Marie B.

Sarmiento, Joanie Pazz P.Schuck, Sharida P.

Level IV Student

NEURAL TUBE DEFECTS

Neural tube defects (NTDs) are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In about the 3rd or 4th weeks of pregnancy, specialized cells on the dorsal side of the fetus begin to fuse and form the neural tube. When the neural tube does not close completely, an NTD develops.

The central nervous system starts to develop in week five of pregnancy. At that time, a thickening of cells called the neural plate forms, which folds in on itself

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to create what we know as the neural tube. One end of the neural tube will form the brain, and the remainder of the neural tube will form the spinal cord. In week six, openings in the neural tube close. If these openings do not close properly, abnormalities called neural tube defects can form. These defects are rare, but they account for most of the abnormalities of the brain and spinal cord.

A major birth defect caused by abnormal development of the neural tube, the structure present during embryonic life which gives rise to the central nervous system -- the brain and spinal cord. Neural tube defects (NTDs) are among the most common birth defects that cause infant mortality (death) and serious disability.

There are a number of different types of NTDs including anencephaly, spina bifida, and encephalocele. In anencephaly there is absence of the cranial vault (the skull) and absence of most or all of the cerebral hemispheres of the brain. Encephalocele is a hernia of part of the brain and the meninges (the membranes covering it) through a skull defect. spina bifida is an opening in the vertebral column encasing the spinal cord. Through this opening, the spinal cord and the meninges may herniate to create a meningomyelocele.

All pregnancies are at risk for an NTD. However, women with a history of a previous pregnancy resulting in a fetus with an NTD are at higher risk. So are women with a close relative (brother, sister, niece, or nephew) who has an NTD, women with type 1 diabetes mellitus, women with seizure disorders being treated with valproic acid or carbamazepine, and women or their partners who themselves have an NTD.

Landmark research has revealed that 50 percent or more of NTDs could be prevented if women consume a folic acid-containing supplement before and during the early weeks of pregnancy in addition to the folate in their diet. The US Public Health Service, Centers for Disease Control and Prevention (CDC), and American Academy of Pediatrics recommend that all women of childbearing age who are capable of becoming pregnant should consume 400 (0.4 mg) µg of folic acid daily. Because the risk for NTDs is not totally eliminated by folic acid use, routine prenatal screening for NTDs is still advisable

NORMAL FUNCTION

Spinal Cord

The spinal cord functions primarily in the transmission of neural signals between the brain and the rest of the body but also contains neural circuits that can independently control numerous reflexes and central pattern generators. The spinal cord has three major functions: A. Serve as a conduit for motor information, which travels down the spinal cord. B. Serve as a conduit for sensory information, which travels up the spinal cord. C. Serve as a center for coordinating certain reflexes.

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Brain

The brain monitors and regulates the body's actions and reactions. It continuously receives sensory information, and rapidly analyzes this data and then responds, controlling bodily actions and functions. The brainstem controls breathing, heart rate, and other autonomic processes that are independent of conscious brain functions. The neocortex is the center of higher-order thinking, learning, and memory. The cerebellum is responsible for the body's balance, posture, and the coordination of movement.

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Neural Tube

In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into a closed tube, the neural tube or neural canal (which strictly speaking is the center of the neural tube), the ectodermal wall of which forms the rudiment of the nervous system.

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Primary neurulation

Primary neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of BMP4 (bone morphogenic protein) and cells which receive BMP4 signal develop into epidermis. The inhibitory signals chordin, noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the spemann organiser. Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive FGF (fibroblast growth factor) in addition to the inhibitory signals form posterior neural plate cells.

Shape change

The cells of the neural plate are signaled to become high-columnar and can be identified through microscopy as different from the surrounding epiblastic ectoderm. The cells move laterally and away from the central axis and change into a truncated pyramid shape. This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move. The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape of the cell to change. This process is known as apical constriction

Folding

The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. As a result of the cellular shape changes, the neural plate forms the medial hinge point (MHP). The expanding epidermis puts pressure on the MHP and causes the neural plate to fold resulting in neural folds and the creation of the neural groove. The neural folds form dorsolateral hinge points (DLHP) and pressure on this hinge causes the neural folds to meet and fuse at the midline. The fusion requires the regulation of cell adhesion molecules. The neural plate switches from E-cadherin expression to N-cadherin and N-CAM expression to recognize each other as the same tissue and close the tube. This change in expression stops the binding of the neural tube to the epidermis. Neural plate folding is a complicated step.

The notochord plays an integral role in the development of the neural tube. Prior to neurulation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordal process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center section neural plate to later form the floor plate of the neural tube. The notochord plate separates and forms the solid notochord.The folding of the neural tube to form an actual tube does not occur all at once. Instead, it begins approximately at the level of the fourth somite at Carnegie stage 9 (around Embryonic day 20 in humans). The lateral edges of the neural plate touch in the midline and join together. This continues both cranially (toward the head) and caudally (toward the tail). The openings that are formed at the cranial and caudal regions are termed the cranial and caudal neuropores. In human embryos, the cranial neuropore closes approximately on day 25 and the caudal neuropore on day 27 (Carnegie stages 11 and 13 respectively). Failure of the cranial (anterior) and caudal (posterior) neuropore closure results in conditions

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called anecephaly and spina bifida, respectively. Additionally, failure of the neural tube to close throughout the length of the body results in a condition called cranioarchischisis.

Patterning

Transverse section of the neural tube showing the floor plate and roof plate.

After SHH from the notochord induces its formation, the floor plate of the incipient neural tube also secretes SHH. After closure, the neural tube forms a basal plate or floor plate and an alar plate or roof plate in response to the combined effects of Shh and factors including BMP4 secreted by the roof plate. The basal plate forms most of the ventral portion of the nervous system, including the motor portion of the spinal cord and brain stem; the alar plate forms the dorsal portions, devoted mostly to sensory processing.

The dorsal epidermis expresses BMP4 and BMP7. The roof plate of the neural tube responds to those signals to express more BMP4 and other TGF-b signals to form a dorsal/ventral gradient among the neural tube. The notochord expresses Sonic Hedgehog (Shh). The floor plate responds to Shh by producing its own Shh and forming a gradient. These gradients allows for the differential expression of transcription factors.

Complexities of the model

In actuality, the folding of the neural tube is still not entirely understood and is still being studied. The simplistic model of the closure occurring in one step cranially and caudally does not explain the high frequency of neural tube defects. Proposed theories include closure of the neural tube occurs in regions, rather than entirely linearly.

Secondary neurulation

In secondary neurulation, the neural ectoderm and some cells from the endoderm form the medullary cord. The medullary cord condenses, separates and then forms cavities. These cavities then merge to form a single tube. Secondary Neurulation occurs in the posterior section of most animals but it is better expressed in birds. Tubes from both primary and secondary neurulation eventually connect.

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ETIOLOGICAL FACTORS

Chromosomal abnormalities

Neural tube defects are cause by multiple genes and environmental factors which are not completely understood. Although more than 200 genes are known to cause NTDs in mice, the cause of NTDs in human is still poorly understood. The failure to identify a single gene factor suggests that the major causes of human NTDs are from the summation of genetic, environmental and nutritional factors. Research has shown that women with folic acid deficiencies also have a higher chance of having a child with a neural tube defect, but this is only one factor. Taking folic acid does not completely negate the risk of neural tube problems, but it does significantly reduce the risk. Folic acid deficiency leads to hyper-homocysteinemia,which in turn results in neural tube defects.

Some birth defects are caused by chromosomal abnormalities. Chromosomes are structures that are found in the nucleus of every human cell and that contain genes, the units of heredity. Genes are responsible for the physical traits and genetic makeup of an individual. A human fetus inherits 23 chromosomes from its mother and 23 chromosomes from its father, making a total of 46 chromosomes in 23 pairs.

The most common chromosomal abnormalities seen in humans involve an extra chromosome or a missing chromosome. Down syndrome (named for nineteenth-century English physician J. L. H. Down) is a birth disorder caused by the presence of an extra chromosome, so that a fetus with this condition has 47 chromosomes instead of 46. Down syndrome babies have distinctive facial features and other physical abnormalities, are mentally impaired, and often have heart defects. The likelihood of a baby being born with Down syndrome increases with the mother's age.

Physical birth defects

Physical birth defects may result from a combination of genetic and environmental factors that affect the normal development of the fetus. Common

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physical defects present at birth include clubfoot, in which one or both feet are deformed, and cleft lip and cleft palate, in which a split is present in the lip and roof of the mouth. Spina bifida is a malformation of the spine caused by incomplete closure of the vertebral column (backbone) during development.

Environmental factors

Environmental factors such as the mother's use of tobacco, alcohol, or drugs can affect fetal development and contribute to or cause birth defects. In addition, if the mother is exposed to or infected by an active virus, she may pass it to her child while it is in the womb or during delivery, resulting in complications such as mental retardation in the newborn.

Heavy use of alcohol during pregnancy can result in fetal alcohol syndrome. Babies with this condition typically have low birth weights, physical deformities of the face and head, and varying degrees of mental retardation. They may also have behavioral problems and learning difficulties later in life.

Folic Acid Deficiency

Folic acid and vitamin B12 are very important in reducing the occurrences of NTDs. Folate is required for production and maintenance of new cells., for DNA synthesis and RNA synthesis. Folate is needed to carry one carbon groups for methylation and nucleic acid synthesis. Vitamin B12 is also an important receptor in the folic acid biopathway such that studies have shown deficiency in vitamin B12

contributes to risk of NTDs as well.

Other Causes

Other potential causes can include folate antimetabolites (such as methotrexate), maternal diabetes, maternal obesity, mycotoxins in contaminated corn meal, arsenic, and hyperthermia in early development. Studies have shown that both maternal cigarette smoking and maternal exposure to secondhand smoke increased the risk for neural tube defects in offspring. A mechanism by which maternal exposure to cigarette smoke could increase NTD risk in offspring is suggested by several studies which show an association between cigarette smoking and homocysteine levels. The study suggests that cigarette smoke including secondhand exposure is not only hazardous to the mother but may also interfere with neural tube closure in the developing embryo.

Pathophysiology

Two distinct processes appear to be involved in the formation of the neural tube: primary neurulation and secondary neurulation (ie, canalization). The neural plate and the notochord are formed during early embryonic development. The neural groove develops by the third gestational week. Subsequently, the neural folds form bilaterally.

Primary neurulation

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The neural folds elevate, approximate each other, and start closing, thus forming the neural tube.

The point of initial closure occurs at the caudal rhombencephalon or cranial spinal cord.

The cutaneous ectoderm fuses first, followed by the neuroectoderm. The cranial neuropore closes during the fourth gestational week. The last

area to close is the commissural plate. The caudal neuropore closes between T11 and S2. Parallel to this process, the cutaneous ectoderm separates from the

neuroectoderm to form the overlying skin, while the lateral mesoderm migrates between the 2 ectodermal layers to form the posterior vertebral arches.

Secondary neurulation (canalization) This comprises further neural development occurring caudal to the caudal

neuropore after the termination of primary neurulation. This process includes formation of the filum terminale and conus medullaris

from a poorly differentiated cell mass of the medial eminence. Because of differential growth between the vertebral column and the spinal

cord, the conus becomes more rostral during later development.

Open NTDs have been suggested to result from defective primary neurulation while defective secondary neurulation gives rise to closed NTDs. However, this issue is not settled. Another possible explanation is that open NTDs (spina bifida in particular) result from defects in either primary or secondary neurulation, depending on their site being cranial or caudal to the posterior neuropore (ie, upper and lower spina bifida, respectively).

Types of Neural Tube Defects

There are two types of NTDs: open, which are more common, and closed.

Open NTDs :Open NTDs occur when the brain and/or spinal cord are exposed at birth

through a defect in the skull or vertebrae (back bones).

anencephaly encephaloceles hydranencephaly iniencephaly spina bifida

Closed NTDs :Closed NTDs occur when the spinal defect is covered by skin.

lipomyelomeningocele lipomeningocele

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tethered cord

Open NTDs :

Anencephaly

Anencephaly (without brain) is a neural tube defect that occurs when the head end of the neural tube fails to close, usually during the 23rd and 26th days of pregnancy, resulting in an absence of a major portion of the scalp, brain and skull. Infants born with this condition are born without the main part of the forebrain-the largest part of the cerebrum. Infants born with this condition are usually blind, deaf and unconscious. The lack of a functioning cerebrum will ensure that the infant will never gain consciousness. Infants are either stillborn or usually die within a few hours or days after birth.

Children with this disorder are born without a forebrain, the largest part of the brain consisting mainly of the cerebral hemispheres (which include the neocortex, which is responsible for higher-level cognition, thinking).

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, and recent animal models indicating a possible association with deficiencies of the transcription factor TEAD2. 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.

It is known that women taking certain medication for epilepsy and women with insulin-dependent diabetes have a higher chance of having a child with a neural tube defect. 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, especially those attempting to conceive or who may possibly conceive, as this can reduce the risk to 0.03%. 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.

Anencephaly and other physical and mental deformities have also been blamed on a high exposure to such toxins as lead, chromium, mercury, and nickel. Exposure to depleted uranium is also a possible cause of anencephaly, as well as a host of other fetal deformities. The risk of infants being born with this disease is higher in areas where there are high levels of man-made isotopes and depleted uranium radiation.

Signs and symptomsA 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

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possibility of ever gaining consciousness. Reflex actions such as breathing and responses to sound or touch occur.

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Encephaloceles

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Encephaloceles are a neural tube defect that characterize by sac-like protrusion of the brain through the opening in the skull. The defect is caused by the incomplete closure of the cranium during development.

Encephaloceles - in those affected, part of the brain and its membranes bulge out through openings in the skull. Patients may have microcephaly (small head) and hydrocephalus. Prognosis depends on severity.

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Encephalocele, sometimes known by the Latin name cranium bifidum, is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal development. Encephaloceles cause a groove down the middle of the skull, or between the forehead and nose, or on the back side of the skull. The severity of encephalocele varies, depending on its location.

Classifications

Encephaloceles are generally classified as nasofrontal, nasoethmoidal, or naso-orbital, however, there can be some overlap in the type of encephalocele. If the bulging portion contains only cerebrospinal fluid and the overlaying membrane, it may be called a meningocele. If brain tissue is present, it may be referred to as an encephalomeningocele.

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Occurrence

Encephaloceles occur rarely, at a rate of one per 5,000 live births worldwide. Encephaloceles of the back of the head are more common in Europe and North America, while encephaloceles on the front of the head more frequently occur in Southeast Asia, Africa, Malaysia, and Russia. Ethnic, genetic, and environmental factors, as well as parental age, can all affect the likelihood of encephaloceles. The condition can occur in families with a family history of spina bifida.

Causes

Although the exact cause is unknown, encephaloceles are caused by failure of the neural tube to close completely during fetal development. Research has indicated that teratogens (substances known to cause birth defects), trypan blue (a stain used to color dead tissues or cells blue), and arsenic may damage the developing fetus and cause encephaloceles.

Symptoms

Encephaloceles are often accompanied by craniofacial abnormalities or other brain malformations. Symptoms may include neurologic problems, hydrocephalus (cerebrospinal fluid accumulated in the brain), spastic quadriplegia (paralysis of the limbs), microcephaly (an abnormally small head), ataxia (uncoordinated muscle movement), developmental delay, vision problems, mental and growth retardation, and seizures.

Hydranencephaly

Hydranencephaly is a condition in which the cerebral hemispheres are missing and instead filled with sacs filled with cerebrospinal fluid.

Hydranencephaly is a type of cephalic disorder. This is a rare condition in which the cerebral hemispheres are absent and replaced by sacs filled with cerebrospinal fluid.

This should not be confused with hydrocephalus, which is an accumulation of cerebrospinal fluid in the ventricles.

In "hemihydranencephaly", only half of the brain is filled with fluid

Presentation

Usually the cerebellum and brainstem are formed normally, although in some cases the cerebellum may also be absent. An infant with hydranencephaly may appear normal at birth or may have some distortion of the skull and upper facial features due to fluid pressure inside the skull. The infant's head size and spontaneous reflexes such as sucking, swallowing, crying, and moving the arms and legs may all seem normal, depending on the severity of the condition. However, after a few weeks the infant usually becomes irritable and has increased muscle tone (hypertonia). After several months of life, seizures and hydrocephalus may develop. Other symptoms may include visual impairment, lack of growth, deafness, blindness, spastic quadriparesis (paralysis), and intellectual deficits.

Some infants may have additional abnormalities at birth including seizures, myoclonus (involuntary sudden, rapid jerks), and respiratory problems.

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Causes

Hydranencephaly is an extreme form of porencephaly, which is characterized by a cyst or cavity in the cerebral hemispheres, and may be caused by vascular insult or injuries, infections, or traumatic disorders after the 12th week of pregnancy.

Diagnosis

Diagnosis may be delayed for several months because the infant's early behavior appears to be relatively normal. Transillumination, an examination in which light is passed through body tissues, usually confirms the diagnosis.

Preliminary diagnosis may be made in utero via standard ultrasound, and can be confirmed with a level II or higher ultrasound.

Prognosis

There is no standard treatment for hydranencephaly. Treatment is symptomatic and supportive. Hydrocephalus may be treated with a shunt.

The prognosis for children with Hydranencephaly is generally quite poor. Death usually occurs in the first year of life.

In a survey completed by 88 families of children with Hydranencephaly from 2006-2007, 69% of the children who had died, did so after their first birthday.[citation

needed] The oldest of the children who had died was in their 20s. 62% of the children represented in the survey were over the age of 1 at the time it was filled out. The first year is the hardest for children with Hydranencephaly but survival is possible.

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Iniencephaly

Iniencephaly is a type of cephalic disorder. It is a rare neural tube defect that combines extreme retroflexion (backward bending) of the head with severe defects of the spine and the patient does not usually have a neck. The diagnosis can usually be made on antenatal ultrasound scanning but if not will undoubtedly be made immediately after birth because the head is bent backwards and the face looks upwards. Usually the neck is absent. The skin of the face connects directly to the chest and the scalp connect to the upper back. The infant usually will not survive more than a few hours.

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This is iniencephaly. The key features are: (1) imperfect formation of the base of the skull, (2) rachischisis, and (3) exaggerated lordosis of the vertebral column.

Iniencephaly it is defect involving the occiput and inion combined with rachischisis of the cervical and thoracic spine and retroflexion of the head. The first syllable of "iniencephaly" is derived from the word inion, which in turn is derived from the Greek word for 'nape of the neck'. The inion is the most prominent posterioinferior projection of the occipital bone of the skull. The inion appears to fuse with the spine resulting in no discernible neck.

Presentation

The affected infant tends to be short, with a disproportionately large head. Diagnosis can be made immediately after birth because the head is so severely retroflexed that the face looks upward. The skin of the face is connected directly to the skin of the chest and the scalp is directly connected to the skin of the back. Generally, the neck is absent.

Most individuals with iniencephaly have other associated anomalies such as anencephaly, encephalocele (a disorder in which part of the cranial contents protrudes from the skull), hydrocephalus, cyclopia, absence of the mandible (lower jaw bone), cleft lip and palate, cardiovascular disorders, diaphragmatic hernia, and gastrointestinal malformation. The disorder is more common among females.

Prognosis

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The prognosis for those with iniencephaly is extremely poor. Newborns with iniencephaly seldom live more than a few hours. The distortion of the fetal body may also pose a danger to the mother's life.

Spina Bifida

Spina bifida (Latin: "split spine") is a developmental birth defect involving the neural tube: incomplete closure of the embryonic neural tube results in an incompletely formed spinal cord. In addition, the vertebrae overlying the open portion of the spinal cord may not fully form and remain unfused and open. This allows the abnormal portion of the spinal cord to stick out through the opening in the bones. There may or may not be a fluid filled sac surrounding the open spinal cord. Other neural tube defects include anencephaly, a condition in which the portion of the neural tube which will become the cerebrum does not close, and encephalocele, which results when other parts of the brain remain unfused.

Spina bifida malformations fall into four categories: spina bifida occulta, spina bifida cystica (myelomeningocele), meningocele and lipomeningocele. The most common location of the malformations is the lumbar and sacral areas . Myelomeningocele is the most significant form and it is this that leads to disability in most affected individuals. The terms spina bifida and myelomeningocele are usually used interchangeably.

Spina bifida can be surgically closed after birth, but this does not restore normal function to the affected part of the spinal cord. Intrauterine surgery for spina bifida has also been performed and the safety and efficacy of this procedure is currently being investigated. The incidence of spina bifida can be decreased by up to 75% when daily folic acid supplements

According to the Spina Bifida Association, approximately 70 to 90 percent of those affected by myelomeningocele will develop hydrocephalus. This complication occurs when the flow of cerebrospinal fluid is obstructed and accumulates in the brain. The child’s head becomes larger and the fluid applies pressure on the brain. Left untreated, this condition can cause mental retardation and learning disabilities and can in some cases be fatal. Hydrocephalus is usually treated by putting in a shunt that allows excess cerebrospinal fluid to drain into the abdomen.

Spina Bifida Cystica

This includes meningocele and myelomeningocele. Meningocele is less severe and is characterized by herniation of the meninges, but not the spinal cord, through the opening in the spinal canal. Myeolomeningocele involves herniation of the meninges as well as the spinal cord through the opening.

In spina bifida cystica, a cyst protrudes through the defect in the vertebral arch. These conditions can be diagnosed in utero on the basis of elevated levels of alpha-fetoprotein, after amniocentesis, and by ultrasound imaging. Spina bifida cystica may result in hydrocephalus and neurological deficits.

Meningocele

With this type of spina bifida, cerebrospinal fluid and meninges have ballooned out of the spinal opening to form a bulge or sac, but the spinal cord is usually in its normal location. This bulge may or may not be covered with a layer of

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skin. This bulge will be noticeable on the back of the baby. Symptoms of those with this type are variable.

Meningocele, the meninges protrude from the spinal opening, and the malformation may or may not be covered by a layer of skin. Some patients with meningocele may have few or no symptoms while others may experience symptoms similar to closed neural tube defects.

In the third type, meningocele, the meninges protrude from the spinal opening, and the malformation may or may not be covered by a layer of skin. Some patients with meningocele may have few or no symptoms while others may experience symptoms similar to closed neural tube defects. Meningocele - the sac contains tissues that cover the spinal cord (meninges) and cerebrospinal fluid. Nerve damage is minimal, so there's often little disability.

Myelomeningocele

Myelomeningocele is the most severe and occurs when the spinal cord is exposed through the opening in the spine, resulting in partial or complete paralysis of the parts of the body below the spinal opening the sac contains tissue, cerebrospinal fluid, nerves and part of the spinal cord. Spinal cord damage or incomplete development always occurs, resulting in paralysis and sensation loss below the damaged region. The paralysis may be so severe that the affected individual is unable to walk and may have urinary and bowel dysfunction.

There's often an accompanying condition called hydrocephalus (increased pressure in the fluid in the brain, which causes some very young children's heads to swell with the pressure), which can gradually damage brain function especially if untreated. Other problems include incontinence and urinary tract infections.

Myelomeningocele is more common and more serious than meningocele.

Spina Bifida Occulta

In this type of neural tube defect, the meninges do not herniate through the opening in the spinal canal.

Occulta is the mildest and most common form in which one or more vertebrae are malformed. The name "occulta," which means "hidden," indicates that the malformation, or opening in the spine, is covered by a layer of skin. This form of spina bifida rarely causes disability or symptoms.

Spina bifida occulta is often called hidden spina bifida. A small gap may exist in one or more of the vertebrae, but the spinal cord and tissues are normal. Many people with this condition do not have any symptoms and may never know that it exists unless it is identified during testing that is done for another reason.

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Closed Neural Tube Defects

Closed neural tube defects are frequently grouped with spina bifida occulta. They consist of a wide variety of spinal defects with malformed bone, tissue, and/or fat deposits at the location of the defect. Often there is a visible sign on the outside of the baby’s skin. This may be a tuft of hair, a dimple, a birthmark, lump, or skin opening. Many patients with this condition will have few symptoms, but some may have nerve damage that affects normal bowel or urinary function and/or can cause lower body weakness and pain.

Closed neural tube defects make up the second type of spina bifida. This form consists of a diverse group of spinal defects in which the spinal cord is marked by a malformation of fat, bone, or membranes. In some patients there are few or no symptoms; in others the malformation causes incomplete paralysis with urinary and bowel dysfunction.

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Symptoms of Spina bifida:

In spina bifida occulta, which affects up to one in ten people, there may be visible signs of a dimple or small hair growth on the back. Often people don’t even know that they have it and it is noticed on an xray that is taken for another reason. This is a mild form and rarely causes disability.In spina bifida cystica there is a sac or cyst (like a blister) on the back, covered by a thin layer of skin. The sac contains tissues that cover the spinal cord, cerebrospinal fluid and sometimes even the nerves and tissues of the spinal cord itself.

Complications of spina bifida:

Complications of spina bifida can range from minor physical problems to severe physical and mental disabilities. It is important to note, however, that most people with spina bifida are of normal intelligence. Severity is determined by the size and location of the malformation, whether or not skin covers it, whether or not spinal nerves protrude from it, and which spinal nerves are involved. Generally all nerves located below the malformation are affected. Therefore, the higher the malformation occurs on the back, the greater the amount of nerve damage and loss of muscle function and sensation.

In addition to loss of sensation and paralysis, another neurological complication associated with spina bifida is Chiari II malformation—a rare condition (but common in children with myelomeningocele) in which the brainstem and the cerebellum, or rear portion of the brain, protrude downward into the spinal canal or neck area. This condition can lead to compression of the spinal cord and cause a variety of symptoms including difficulties with feeding, swallowing, and breathing; choking; and arm stiffness.

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Chiari II malformation may also result in a blockage of cerebrospinal fluid, causing a condition called hydrocephalus, which is an abnormal buildup of cerebrospinal fluid in the brain. Cerebrospinal fluid is a clear liquid that surrounds the brain and spinal cord. The buildup of fluid puts damaging pressure on the brain. Hydrocephalus is commonly treated by surgically implanting a shunt—a hollow tube—in the brain to drain the excess fluid into the abdomen.

Some newborns with myelomeningocele may develop meningitis, an infection in the meninges. Meningitis may cause brain injury and can be life-threatening.

Children with both myelomeningocele and hydrocephalus may have learning disabilities, including difficulty paying attention, problems with language and reading comprehension, and trouble learning math.

Additional problems such as latex allergies, skin problems, gastrointestinal conditions, and depression may occur as children with spina bifida get older.

Causes and Risk Factors of Spina Bifida:

The most important risk factor for spina bifida is poor nutrition, especially a diet deficient in folic acid.

There appears to be factors other than nutrition in the development of spinal bifida. Genetics also seems to play a role. People of Northern European and Hungarian ancestry have the highest rates of the disease, and the condition tends to run in families, though not consistently. In fact, 90 to 95 percent of children with spina bifida are born to women who have no other children or anyone in the family with the defect.

Pathophysiology

Spina bifida is caused by the failure of the neural tube to close during the first month of embryonic development (often before the mother knows she is pregnant).

Normally the closure of the neural tube occurs around 28 days after fertilization.[14] However, if something interferes and the tube fails to close properly, a neural tube defect will occur. Medications such as some anticonvulsants, diabetes, having a relative with spina bifida, obesity, and an increased body temperature from fever or external sources such as hot tubs and electric blankets can increase the chances a woman will conceive a baby with a spina bifida. However, most women who give birth to babies with spina bifida have none of these risk factors, and so in spite of much research, it is still unknown what causes the majority of cases.

The varying prevalence of spina bifida in different human populations and extensive evidence from mouse strains with spina bifida suggests a genetic basis for the condition. As with other human diseases such as cancer, hypertension and atherosclerosis (coronary artery disease), spina bifida likely results from the interaction of multiple genes and environmental factors.

Research has shown that lack of folic acid (folate) is a contributing factor in the pathogenesis of neural tube defects, including spina bifida. Supplementation of the mother's diet with folate can reduce the incidence of neural tube defects by about 70 percent, and can also decrease the severity of these defects when they

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occur. It is unknown how or why folic acid has this effect.

Spina bifida does not follow direct patterns of heredity like muscular dystrophy or haemophilia. Studies show that a woman who has had one child with a neural tube defect such as spina bifida, has about a three percent risk of having another child with a neural tube defect. This risk can be reduced to about one percent if the woman takes high doses (4 mg/day) of folic acid before and during pregnancy. For the general population, low-dose folic acid supplements are advised (0.4 mg/day).

Closed NTDs :

Lipomyelomeningocele

A lipomyelomeningocele (pronounced lipo-my-elo-men-IN-go-seal) is a rare birth defect. It affects a child’s backbone (spine).

A lipomyelomeningocele is a fatty mass that is located under the skin on the child’s back. It is usually located in the middle of the back. The mass goes inward to the spinal canal. A lipomyelomeningocele is covered in skin. You can usually see it on the outside of the child's body. It looks like a large lump.

The two biggest problems that develop with lipomyelomeningocele in children are:• The spinal cord gets stuck (fixed) to the fatty mass.• The fatty mass puts pressure on the spinal cord.

Lipomyelomeningocele in Children

Lipomyelomeningoceles are present when a baby is born (congenital). It is a

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rare defect. Lipomyelomeningoceles only happens in one to two of every 10,000 babies born. The problem is slightly more common in girls.

Babies develop lipomyelomeningoceles early in their mother’s pregnancy — during the fourth to sixth week. The problem has no known cause. Unlike a myelomeningocele, the genes a baby inherits don't play a role in the development of a lipomyelomeningocele. It is not caused by mothers getting too little folic acid during pregnancy.

Symptoms of Lipomyelomeningocele

All babies with a lipomyelomeningocele have a spinal cord that is stuck (tethered) into the fatty mass. This pulls the spinal cord downward. Tethered spinal cord can cause symptoms, including:

• Back and leg pain• Weak and numb legs• Changes in bladder and bowel control

Lipomyelomeningocele Diagnosis

Usually, doctors can see a lipomyelomeningocele when a baby is born. They may see a lump or some other type of mark on your baby's back, such as a fat pad, birthmark, dimple or tuft of hair.Your child's doctor will ask for an MRI (magnetic resonance imaging). A process that creates high-quality pictures of the inside of the body. An MRI uses a large magnet to create these pictures. of the spine to get a better view of your baby's spinal cord and any abnormalities associated with it.

All babies with a lipomyelomeningocele need surgery to fix the problem. About two in 10 children who have had a lipomyelomeningocele repair develop a tethered cord as they grow and need further surgeries.

If the fatty mass is not removed and the spinal cord remains tethered, your child will develop neurological damage over time. Slowly, the child loses sensory and movement abilities, also called motor function. They may lose the ability to walk. Bladder and bowel function may get worse or be lost. These changes may be permanent.

Lipomyelomeningocele Treatment Options

Most often, babies treated at Seattle Children's have lipomyelomeningocele repair when they are 4 to 8 months old.

Your child's neurosurgeon begins with an operation called a laminectomy. Neurosurgeons remove parts of some bones in the spine (vertebrae). This lets the neurosurgeon get to the spinal cord or spinal nerve roots that need repair.

Next neurosurgeons remove some of the fatty mass and free up the spinal cord. Finally, they close the hole where the fatty mass enters your baby’s spinal canal.

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Tethered spinal cord syndrome

Tethered spinal cord syndrome or occult spinal dysraphism sequence is a rare neurological disorder (occurring in 0.05 to 0.25 of 1000 births) caused by tissue attachments that limit the movement of the spinal cord within the spinal column. These attachments cause an abnormal stretching of the spinal cord. This stretching interferes with the function of the nerves in the spinal cord and can cause problems with sensation, movement, and control of body functions.

In addition to the 'typical' tethering, there is a more common variation referred to as Occult Tight Filum Terminale Syndrome. In this variation, the filum terminale (which joins the spinal cord to the backbone) thickens or hardens and causes downward pressure on the spinal cord. This can actually cause scoliosis as well as most of the other symptoms of the more typical tethered cord. This syndrome was first noticed and documented in the late 1800s.

Signs and symptoms

In children, symptoms may include lesions, hairy patches, dimples, or fatty tumours on the lower back; foot and spinal deformities; weakness in the legs; low back pain; scoliosis; and incontinence. Tethered spinal cord syndrome may go undiagnosed until adulthood, when sensory and motor problems and loss of bowel and bladder control emerge. This delayed presentation of symptoms is related to the degree of strain placed on the spinal cord over time. Tethered spinal cord syndrome appears to be the result of improper growth of the neural tube during fetal development, and is closely linked to spina bifida. Tethering may also develop after spinal cord injury and scar tissue can block the flow of fluids around the spinal cord. Fluid pressure may cause cysts to form in the spinal cord, a condition called syringomyelia. This can lead to additional loss of movement or feeling, or the onset of pain or autonomic symptoms.

In adults, onset of symptoms typically include severe pain (in the lower back and radiating into the legs, groin, and perineum), bilateral muscle weakness, and bladder and/or bowel incontinence. Neurological symptoms can include a mixed picture of upper and lower motor neuron findings, such as amyotrophy, hyperreflexia, and pathologic plantar response, occurring in the same limb. Profound sensory changes, such as loss of pain, temperature, and proprioceptive sensations, are common. Last, progressive symptoms of a neuropathic bladder are noted on over 70% of adult patients, versus only 20% to 30% of children. These symptoms include urinary frequency and urgency, feeling of incomplete voiding, poor voluntary control, and urge and stress incontinence. Chronic recurrent infections are common and occasionally lead to nephrolithiasis (kidney stones), renal failure, or renal transplantation. Female patients also give a history of ineffective labor and postpartum rectal prolapse, presumably due to an atonic pelvic floor.

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Assessment Parameters

Tests The goals with testing for NTDs are to detect and diagnose the disorders in the fetus, and/or in the newborn, and to evaluate severity and complications. Very mild cases of NTDs may never be detected or may be detected later in life when testing is performed for other reasons.

Laboratory Tests

Laboratory tests may include:

Triple screen or Quad screen - this group of tests is performed on the mother during her 2nd trimester and includes an AFP (alpha-fetoprotein) test. Increased levels of AFP have been associated with an increased risk of an open NTD.

AFP and acetylcholinesterase in amniotic fluid. If the serum AFP is elevated, AFP and acetylcholinesterase can be measured in amniotic fluid, as confirmatory tests. A fetal karyotype test may also be done on the fluid to rule out chromosomal abnormalities. These tests are followed by or performed with a fetal ultrasound.

Neural tube defects can be detected in utero by determination of alpha-fetoprotein (AFP) and acetylcholinesterase in the amniotic fluid and maternal blood. Alpha- fetoprotein, a circulating fetal protein produced by the liver, peaks at 12-14 weeks of gestation and subsequently declines. AFP leaks from the fetus into the amniotic fluid through exposed capillaries of the NTD. This results in persistently high levels of AFP in the amniotic fluid and in the maternal blood. Elevated AFP is also seen in other lesions where fetal capillaries are exposed to the amniotic fluid such as omphalocele and sacrococcygeal teratoma. Acetylcholinesterase leaks directly from exposed neural tissue into the amniotic fluid.

Amniocentesis: Diagnostic technique in which a needle is inserted into the abdomen of a pregnant woman to remove amniotic fluid from the uterus for examination of fetal cells.

Chorionic villus sampling: Diagnostic technique in which a needle is inserted through the abdomen or a thin plastic tube is inserted through the cervix of a pregnant woman to obtain a sample of villi (from the membrane surrounding the fetus) for examination of cells.

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Maternal Serum Alpha Fetoprotein (MSAFP), a screening test that is performed on a pregnant woman's blood at approximately 16-18 weeks of pregnancy

Non-Laboratory Tests

Tests include: Fetal ultrasound – to help diagnose NTDs prior to birth. X-ray, MRI (magnetic resonance imaging), and/or CT scan (computed

tomography) – of spine and vertebrae after birth to look for defects and deformities.

X-ray or CT scans of the head to detect excess fluid when hydrocephalus is suspected.

Ultrasound: A diagnostic technique that uses sound waves to produce an image of the fetus within the uterus.

Regular clinical examinations – to detect and address complications as they arise.

Apgar Score - is the evaluation of a newborn baby's physical condition based on skin color, heart rate, response to stimulation, muscle tone, and respiratory effort. Each criteria is rated from zero to two with a total score of 10 indicating the best possible physical condition. The evaluation determines whether immediate emergency measures are needed. (A low score can indicate possible brain damage.) Because the score is closely related to an infant's life expectancy, it is used as a guideline to advise parents of their baby's chances of survival.

Medical Management

The goals with treatment are to prevent as many cases of NTDs as possible. For those affected, the goals are to minimize symptoms and complications and to lead as normal and active a life as possible. Treatments must be tailored to the individual, and new options are constantly emerging. Patients and their parents should work with their doctors to determine what treatments are right for them.

Adequate folate/folic acid is the primary prevention tool. Recent evidence suggests that folic acid supplementation could reduce the incidence of NTDs by up to 70%, but the protection it provides must be in place at the time of conception. It is recommended that all women of childbearing age get at least 400 micrograms of folic acid/folate a day. Since folic acid is a water-soluble vitamin, it must be constantly replenished. Folic acid can be found in dark green vegetables and some fruit. Most grain products in the U.S. are good sources because they have been fortified with added folic acid. Women who have spina bifida, or who already have a child with spina bifida, or who are otherwise considered at an increased risk of having a baby with an NTD may be given a prescription for about 10 times the recommended dose for several months before becoming pregnant. This higher dose is not recommended, however, for the general population.

Treatment for Anencephaly

Treatments of NTDs depends on the severity of the complication. No treatment is available for anencephaly because the infants usually do not survive more than few hours. Aggressive surgical management has improved survival and functions of infants with spina bifida and meningoceles and mild

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myelomeningoceles. The success of surgery often depends on the amount of brain tissue involved in the encephalocele. The goal of treatment for NTDs is to allow the individual to achieve the highest level of function and independence.

In almost all cases, anencephalic infants are not aggressively resuscitated since 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. Clinicians and medical ethicists may view the provision of nutrition and hydration as medically futile.

Treament for Encephaloceles

Occasionally, surgery has been successful in babies with encephalocele. However, almost all babies with NTDs who survive the newborn period have spina bifida, and its treatment depends on its severity. Spina bifida occulta (in which the spinal cord doesn't protrude out of the spine) often causes no symptoms at all, and usually requires no treatment. When the spinal cord does protrude through a defect in the bony spine, the treatment requires a coordinated approach involving both a primary caregiver such as a pediatrician or family physician, and a team of health professionals such as neurosurgeons, orthopedic surgeons, physical therapists, social workers, and urologists. Generally, surgery is required soon after birth--often within the first 24 to 48 hours--to protect the exposed spinal cord, help preserve whatever nerve function the baby has, and to help prevent infection of the exposed nerves and other tissues.

Currently, the only effective treatment for encephaloceles is reparative surgery, generally performed during infancy. The extent to which it can be corrected depends on the location and size of the encephaloceles; however large protrusions can be removed without causing major disability. Surgery repositions the bulging area back into the skull, removes the protrusions, and corrects the deformities, typically relieving pressure that can delay normal brain development. Occasionally, shunts are placed to drain excess cerebrospinal fluid from the brain.

The goals of treatment include:

closure of open skin defects to prevent infection and desiccation of brain tissue

removal of nonfunctional extracranial cerebral tissue with water-tight closure of the dura

total craniofacial reconstruction with particular emphasis on avoiding the long-nose deformity (nasal elongation that results from depression of the cribiform plate and nasal placode). Without proper management, the long-nose deformity can be more obvious after repair.

Proper levels of folic acid have been shown to help prevent such defects when taken before pregnancy, and early in pregnancy. It is recommended that women who may become pregnant take 400 micrograms of folic acid daily.

Treatment for Spina Bifida Cystica

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There is no known cure for nerve damage due to spina bifida. To prevent further damage of the nervous tissue and to prevent infection, pediatric neurosurgeons operate to close the opening on the back. During the operation for spina bifida cystica, the spinal cord and its nerve roots are put back inside the spine and covered with meninges. In addition, a shunt may be surgically installed to provide a continuous drain for the cerebrospinal fluid produced in the brain, as happens with hydrocephalus. Shunts most commonly drain into the abdomen. However, if spina bifida is detected during pregnancy, then open fetal surgery can be performed.

Treatment for Hydranencephaly

There is no standard treatment for hydranencephaly. Treatment is symptomatic and supportive. Hydrocephalus may be treated with a shunt.

The prognosis for children with Hydranencephaly is generally quite poor. Death usually occurs in the first year of life.

In a survey completed by 88 families of children with Hydranencephaly from 2006-2007, 69% of the children who had died, did so after their first birthday. The oldest of the children who had died was in their 20s. 62% of the children represented in the survey were over the age of 1 at the time it was filled out. The first year is the hardest for children with Hydranencephaly but survival is possible.

Treatment for LipomyelomeningoceleBecause neurological deficits are generally irreversible, early surgery is

recommended. In children, early surgery is recommended to prevent further neurological deterioration, including but not limited to chronic urinary incontinence. In adults, surgery to free (detether) the spinal cord can reduce the size and further development of cysts in the cord and may restore some function or alleviate other symptoms. Tethered cord syndrome is causally linked to Chiari Malformation and any affirmative diagnosis of TCS must be followed by screening for Chiari's several degrees. TCS may also be related to Ehlers-Danlos syndrome which should also be screened for upon a positive TCS diagnosis.

Tethered cord syndrome presents varied and almost uncontrollable neurophenomenae in pediatric cases.

Other treatment is symptomatic and supportive. NSAIDs, opiates, synthetic opiates, Cox II inhibitors, off-label applications of tricyclic anti-depressants combined with anti-seizure compounds have yet to prove they are of value in treatment of this affliction's pain manifestations. There is anecdotal evidence that TENS units may benefit some patients.

Treatment may be needed in adults who, while previously asymptomatic, begin to experience lower back degeneration, scoliosis, neck and upper back problems and incontinence and bladder control issues. This syndrome was first noticed in the late 1800s and while information has been available for years, little widespread blind research has been done. More research has been called for and many studies have been done by doctors with great results. There is a low morbidity rate and no known complications have been documented other than those from any type of typical back surgery. The association of this condition with others has been noticed and also needs further research to understand the relations. Spinal compression and the resulting relief is a known issue with this disorder. Like with the early-onset form, this disease form is linked to the Arnold-Chiari malformation, in which the brain is pulled or lowers into the top of the spine.

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PrognosisThe natural course of the disorder is progressive as children age, but the

aforementioned treatments can help prevent or sometimes relieve symptoms. With treatment, individuals with tethered spinal cord syndrome have a normal life expectancy. However, most neurological and motor impairments are irreversible.

Treatment for Spina Bifida.

There is no known cure for nerve damage due to spina bifida. To prevent further damage of the nervous tissue and to prevent infection, pediatric neurosurgeons operate to close the opening on the back. During the operation for spina bifida cystica, the spinal cord and its nerve roots are put back inside the spine and covered with meninges. In addition, a shunt may be surgically installed to provide a continuous drain for the cerebrospinal fluid produced in the brain, as happens with hydrocephalus. Shunts most commonly drain into the .

However, if spina bifida is detected during pregnancy, then open fetal surgery can be performedMost individuals with myelomeningocele will need periodic evaluations by specialists including orthopedists to check on their bones and muscles, neurosurgeons to evaluate the brain and spinal cord and urologists for the kidneys and bladder. Such care is best begun immediately after birth. Most affected individuals will require braces, crutches, walkers or wheelchairs to maximize their mobility. As a general rule, the higher the level of the spina bifida defect the more severe the paralysis, but paralysis does not always occur. Thus, those with low levels may need only short leg braces while those with higher levels do best with a wheelchair, and some may be able to walk unaided. Many will need to manage their urinary system with a program of catheterization. Most will also require some sort of bowel management program, though some may be virtually unaffected.

Treament for Myelomeningocele

Management of Myelomeningocele Study (MOMS) is a phase III clinical trial to evaluate the safety and efficacy of fetal surgery to close a myelomeningocele. This involves surgically opening the pregnant mother's abdomen and uterus to operate on the fetus. This route of access to the fetus is called "open fetal surgery". Fetal skin grafts are used to cover the exposed spinal cord, to protect it from further damage caused by prolonged exposure to amniotic fluid. The fetal surgery may decrease some of the damaging effects of the spina bifida, but at some risk to both the fetus and the pregnant woman.

In contrast to the open fetal operative approach tested in the MOMS, a minimally invasive approach has been developed by the German Center for Fetal Surgery & Minimally Invasive Therapy at the University of Bonn, Germany. This minimally invasive approach uses three small tubes (trocars) with an external diameter of 5 mm that are directly placed via small needle punctures through the maternal abdominal wall into the uterine cavity. Via this route, the unborn can be postured and its spina bifida defect be closed using small instruments. In contrast to open fetal surgery for spina bifida, the fetoscopic approach results in less trauma to the mother as large incisions of her abdomen and uterus is not require

Nursing Intervention:

* Assess the sac and measure the lesion * Assess neurological system

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* Assess and monitor for increasing ICP * Measure head circumferences * Protect the sac, cover with a sterile, moist (normal saline), nonadherent dressing and change the dressing every 2-4 hours * Place patient in prone position and head to one side * Use antiseptic technique * Assess and monitor the sac for redness, clear or purulent drainage, abrasions, irritation, and signs of infection * Assess for hip and joint deformities * Administer medication: antibiotics, anticholinergics, and laxatives as prescribed

Conclusion

We therefore conclude that neural tube defect is a congenital and a type of disease that has a unique characteristics when it regards to its disease process, deformities and its structures in the medical world. It is kind an awkward and nigh in the sense that the disease process called neural tube defects has a complicated states of disease process because even strict monitoring the patient as well as the occurence of the disease is somehow inevitabe and has a multiple varieties of complications and alterations of its disease process.

Recommendation

We initially recommend that pregnant women should have enough proper and balance nutrition especially drinking liqiufied meds or supplements which are high in folic acid. Such recommendations are based, because on the research process folic acid helps in developing the nervous system of the fetus and, therefore has a great contributing factor in fetal development. Based on such cases it is not only folic acid deficiency is the primary cause of Neural Tube Defect. Healthy and balance nutrition is the basic protocol and strict monitoring in the pregnant women is a must, and must always be, the most basic necessity during at the time of pregnancy.

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"http://en.wikipedia.org/wiki/Neural_tube_defect"Categories: Obstetrics | Congenital disorders | Developmental biology

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