Neural Tube Defects

Genetics: B.Sc Nursing II Year

1. NEURAL TUBE DEFECTS MRS BINCY VARGHESE ASSOCIATE PROFESSOR NURSING

2. INTRODUCTION Neural tube  defects (NTDs) are one of the most common congenital  central nervous system  ( CNS )  malformations . Develop between the 3 rd  and 4 th  week of  pregnancy  and are often caused by  folic acid deficiency . The deficiency results in improper closure of the  neural plate  in the embryo, mainly at the  caudal  or  cranial  ends . The most common type of birth defects and are thought to have multifactorial etiology . 

3. The diagnosis of NTDs is often established during  pregnancy  via  Ultrasound and detection of elevated  Alpha-fetoprotein  levels . Treatment involves prophylactic administration of  antibiotics  and swift surgical closure of the defect to avoid  CNS  infections. Supplementation with  folic acid  is an important preventative measure and should ideally be initiated 4 weeks prior to  conception .

4. DEFINITION Neural Tube Defects ( NTDs) are a heterogeneous group of malformations resulting from failure of neural tube closure between the third and fourth week of embryologic development.  Neural tube  defects are a group of congenital  malformations  of the Brain and  Spinal Cord . They are caused by improper closure of the  neural plate  in the embryo resulting in  malformations  of the  Central Nervous System  ( CNS ),  Spine and Cranium.

5. ETIOLOGY Neurulation is defined as the embryonic process that leads to the ultimate development of the neural tube, the precursor to the brain and spinal cord. There are two distinct phases of neurulation. In the primary phase (weeks 3–4) the brain and the neural tube form from the caudal region to the upper sacral level. Secondary neurulation (weeks 5–6) completes the distal sacral and coccygeal regions. The failure of neurulation at any stage leads to the formation of a neural tube defect. 

6. Multifactorial Genetic and Environmental Factors have been implicated in the pathogenesis of Neural Tube Defects (NTDs). The most common historical cause of NTDs globally is folate deficiency in the maternal diet.  Consanguineous marriages Chromosomal abnormalities (Trisomy 13: Patau syndrome, Trisomy18: Edward’s syndrome, Trisomy 21: Down’s syndrome) are also associated with NTDs. Associated maternal conditions : Diabetes mellitus, Obesity, Fever/Hyperthermia during first trimester

7. Single-gene (autosomal recessive) disorders Meckel syndrome : Rare , characterised by congenital anomaly; brain malformation, large polycystic kidneys, cleft lip/cleft palate, cardiac anomalies. Robert syndrome : Rare disorder characterised by growth delays, malformation of arms and legs, abnormalities of craniofacial region. Jarcho -Levin syndrome : Rare disorder characterised by defects of spine, ribs.

8. Teratogens Valproic acid: Antiepileptic drug Carbamazepine: Antiepileptic drug Aminopterin : Antineoplastic agent Thalidomide: Immunosuppressive agent Oral isotretinoin: Vitamin A derivative

9. CLASSIFICATION NTDs can be classified as “Open” or “Closed” types , based on embryological considerations and the presence or absence of exposed neural tissue . Open NTDs Involve multiple aspects of the CNS and are due to failure of primary neurulation , thus the neural tube fails to appropriately close along the dorsal midline. Neural tissue is completely exposed or covered by a membrane with associated cerebrospinal fluid (CSF) leakage .  

10. Open NTD’s represent roughly 80% of all NTD’s Open NTDs occur when the brain and/or spinal cord are exposed at birth through a defect in the skull or vertebrae with the most common being Spina bifida ( Meningocele, Myelomeningocele), Myelocele, Encephalocele and Anencephaly .

11. Closed NTDs Localized and confined to the Spine (the Brain is rarely affected) and result from a defect in secondary neurulation. Neural tissue is not exposed and the defect is fully covered by epithelium although the skin covering the defect may be dysplastic (i.e., tuft of hair, dimple, birthmark or other superficial abnormality).  Common examples of closed NTDs are  Lipomyelomeningocele ,  Lipomeningocele  and  Tethered cord .

12. Anatomical Classification of Neural Tube Defects Cranial defects Spinal defects

13. SPINA BIFIDA Spina bifida  is a  birth defect  in which there is incomplete closing of the  spine  and the  membranes  around the  spinal cord  during  early development in pregnancy . The term bifida is from the Latin  ” bifidus ”  or "left in 2 parts." Although the condition has also been referred to as Myelodysplasia . Spina bifida is a treatable spinal cord malformation that occurs in varying degrees of severity.  Spina bifida is a variable defect in which the vertebral arch of the spinal column is either incompletely formed or absent.

14. Classification Spina Bifida Cystica Spina bifida cystica can occur anywhere along the spinal axis but most commonly is found in the lumbar region . In this condition, the spine is bifid and a cyst forms.  Spina Bifida Cystica can then be broken down into Meningocele and Myelomeningocele . Meningocele In this form, a single developmental defect allows the  meninges  to herniate between the vertebrae . As the nervous system remains undamaged, individuals with Meningocele are unlikely to suffer long-term health problems .

15. MENINGOCOELE

16. Myelomeningocele Myelomeningocele (MMC) also known as “ Meningomyelocele” is the type of Spina Bifida that often results in the most severe complications and affects the Meninges and Nerves . In individuals with Myelomeningocele, the unfused portion of the spinal column allows the spinal cord to protrude through an opening.  Myelomeningocele occurs in the third week of embryonic development .

17. The meningeal membranes that cover the spinal cord also protrude through the opening, forming a sac enclosing the spinal elements such as Meninges, Cerebrospinal fluid, and parts of the spinal cord and nerve roots A child born with Myelomeningocele requires specialty care where Neonatal surgery and Closure can be performed. (Surgery involves freeing lateral muscles and skin for coverage and attempting to form a closure) .

18. MYELOMENINGOCELE

19. Spina Bifida Occulta Occulta  is  Latin  for "hidden". This is the mildest form of S pina bifida . Failure of one or more  vertebrae  to close completely; the  spinal cord , spinal  meninges , and overlying skin remain intact . Usually asymptomatic In occulta , the outer part of some of the vertebrae is not completely closed . The skin at the site of the  l esion  may be normal, or it may have some hair growing from it; there may be a dimple in the skin, or a  birthmark . Most people are diagnosed incidentally from spinal X-rays .

20. Clinical features of Spina Bifida In general, infants with Spina Bifida Cystica present with the following: Lethargy Poor feeding Irritability Stridor Ocular motor incoordination Development delay

21. Older children may present with the following: Cognitive or behavioral changes Decreased strength Changes in bowel or bladder function Lower cranial nerve dysfunction Back pain Worsening spinal or lower extremity orthopedic deformities

22. Diagnostic Evaluation Alpha-Fetoprotein The AFP level is elevated in 70-75% of cases in which the fetus has an open spina bifida. Fetal Ultrasonography Some Centres use Fetal Ultrasonography as the primary screening tool for neural tube defects, usually at approximately 18 weeks gestational age . The combination of maternal serum AFP screening with second-trimester ultrasonographic screening detects over 90% of neural tube defects from 20 weeks' gestation.

23. Gait Analysis Gait analysis has been introduced to evaluate patients functionally. It is also used to study muscle innervation, strength, and coordination patterns, which may interfere with ambulation or with a patient's ability to live independently. Gait analysis may serve as a useful preoperative diagnostic tool.

24. CT Scan and MRI Magnetic resonance imaging (MRI) of the spine and brain is helpful in neurologic assessment and provides a baseline for comparison in future investigations, especially in the context of progressive neurologic deterioration Radiography Radiographs of the vertebrae provide information for early evaluation 

25. Management Bracing The goal of bracing is to allow patients to function at the maximum level permitted by their neurologic lesion and intelligence. Bracing also ensures a normal developmental progression, its aim being to enable patients to ambulate and to participate in appropriate age-related activities.  In infants aged 9 months and younger, sitting balance and support may be provided with a standard car seat , elevated 45-60°. A car seat may be appropriate to maintain mobility with head and trunk control and to increase upper-extremity strength in children as old as 18 months.

26. A Standing F rame may be used for those aged 1-2 years to diminish the degree of osteoporosis and to limit the contracture of the hip, knee, and ankle. A Parapodium may be helpful for children aged 3-12 years , allowing them to gain greater experience in standing and in manipulating work with their upper extremities at a table or desk.  A Wheelchair can provide mobility and often is used with a molded ankle-foot orthosis .

27. STANDING FRAME PARAPODIUM

28. ANKLE ORTHOSIS KNEE ANKLE ORTHOSIS HIP KNEE ANKLE ORTHOSIS

29. Physical Therapy The Therapy programs should be designed to parallel the normal achievement of gross motor milestones . As the child develops, the Therapist monitors joint alignment, muscle imbalances, contractures, posture, and signs of progressive neurologic dysfunction. The P hysical therapist also provides caregivers with instruction in handling and positioning techniques and recommends orthotic positioning devices to prevent soft tissue contractures. For patients who are not likely to become ambulatory, place emphasis on developing proficiency in wheelchair skills. For patients who are predicted to ambulate, Pregait training should begin with use of a Parapodium .

30. Recreational Therapy Children with Myelomeningocele often experience restricted play and recreational opportunities because of limited mobility and physical limitations. Recreational therapy provides opportunities for participation in adapted sports and exercise programs , which can result in long-term interest in personal fitness and health. Myelomeningocele Closure Closure of the Myelomeningocele is performed immediately after birth if external cerebrospinal fluid (CSF) leakage is present. In the absence of CSF leakage, closure typically occurs within the first 24-48 hours. 

31. Shunting for Hydrocephalus Although in a few cases Hydrocephalus arrests spontaneously, 80-90% of children with Myelomeningocele ultimately require Shunting (Hollow tube placed in Brain/Spine to drain CSF or redirect it to another location of body where it can be reabsorbed. Ventriculoperitoneal shunting is the preferred modality (Procedure in which a device is used to drain CSF from Brain to peritoneal cavity). Alternatives include ventriculoatrial and ventriculopleural shunting.

32. Orthopaedic Procedures Musculoskeletal problems in Myelomeningocele can be congenital or acquired and often require Orthopedic intervention. Orthopedic surgeries are directed toward functional improvement as opposed to correction of radiologic findings. Spinal deformities are common in Myelomeningocele , and progressive Kyphosis or Scoliosis may lead to a decline in functional status and to an increased risk for the development of Decubitus Ulcers and cardiopulmonary compromise.

33. Spinal Orthotic Devices may serve as a temporizing measure . Because muscle imbalance causes progressive, resistant deformities, the patient with spina bifida must be evaluated frequently by members of his or her support team. In this way, they can assess muscle groups, emphasize the need for balance to prevent deformities

34. ENCEPHALOCELE/ MENINGOENCEPHALOCELE Encephalocele 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. In some cases, cerebrospinal fluid or meninges may also protrude through this gap. The portion of the brain that sticks outside the skull is usually covered by skin or a thin membrane so that the defect resembles a small sac.

35. Protruding tissue may be located on any part of the head, but most often affects the occipital area . Most Encephaloceles are large and significant birth defects that are diagnosed before birth. However, in extremely rare cases, some encephaloceles may be small and go unnoticed.

36. Etiology 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   like Trypan blue  (a stain used to color cells blue) and  A rsenic  may damage the developing  fetus  and cause E ncephaloceles .

37. Clinical Features D elays in reaching developmental milestones In tellectual disability L earning disabilities Gr owth delays S eizures

38. Vi sion impairment U ncoordinated voluntary movements (ataxia) H ydrocephalus , a condition in which excess cerebrospinal fluid in the skull causes pressure on the brain.  P rogressive weakness and loss of strength in the arms and legs due to increased muscle tone and stiffness (spastic paraplegia). 

39. Diagnostic Evaluation USG Fetal CT Scan/MRI Management Currently, the only effective treatment for Encephaloceles is reparative surgery, generally performed during  infancy .  Occasionally,  shunts  are placed to drain excess cerebrospinal fluid from the brain

40. ANENCEPHALY 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. 

41. Etiology: Genetic and environmental factors: The specific genes that are most important in NTDs have not yet been identified, although genes involved in folate metabolism are believed to be important. One such gene, Methylenetetrahydrofolate reductase (MTHFR), has been shown to be associated with the risk of NTDs. Valproic acid , an anticonvulsant have been shown to increase the chance of an NTD

42. Maternal type 1, or Insulin-dependent diabetes mellitus (IDDM), confers a significant increase in the risk for NTDs Maternal hyperthermia has been associated with an increased risk for NTD; therefore, pregnant women should avoid hot tubs and other environments that may induce transient hyperthermia. 

43. Clinical features baby born with anencephaly is usually blind, deaf, unaware of its surroundings and unable to feel pain.  Diagnostic evaluation USG Maternal AFP level

44. Prognosis There is no cure or standard treatment for Anencephaly and the prognosis for patients is death . Infants that are not  stillborn  will usually die within a few hours or days after birth from  cardiorespiratory arrest

45. ANENCEPHALY

46. CLOSED NTDs

47. Tethered cord syndrome Tethered cord syndrome (TCS) refers to a group of neurological disorders that relate to malformations of the spinal cord. Abnormal stretching of the  spinal cord  caused by adhesions or obstructions that tether the cord to the base of the  spinal canal Etiology: Tumour , Meningeal adhesions, Lipoma, Cysts Symptoms: Back pain, sensory motor deficits, skeletal deformities(scoliosis), bladder/bowel dysfunction, skin lesions in lower back Diagnosis: CT scan, MRI Management: Surgical removal and repair

48. LIPOMYELOMENINGOCOELE Lipomyelomeningocele is a condition in which an abnormal growth of fat ( lipo ) attaches to the spinal cord ( myelo ) and its membranes (meninges). Symptoms can include problems with bowel and bladder function, frequent urinary tract infections, back and leg pain, muscle weakness or sensory loss in the legs,  neuromuscular scoliosis , foot and leg orthopedic abnormalities, and difficulty walking. During surgery for L ipomyelomeningocele , the pediatric neurosurgeon will free the spinal cord from its attachment to the lipoma, remove as much of the lipoma as safely possible, and close the membranes over the spinal cord. The goals of the surgery are to prevent deterioration of neurological function in the future and to preserve or improve current function.

49. ROLE OF FOLIC ACID Maternal malnutrition is an important risk factor for development of NTD. Studies till date have shown decreased maternal folate levels in NTD affected pregnancies . Periconceptional folic acid supplementation has shown to decrease both the occurrence and recurrence of NTD , though the exact mechanism for this protective effect remains unknown . Folic acid is a B group vitamin , first isolated from spinach leaf in 1941 . Folic acid occurs naturally as folates , which are temperature and storage sensitive and cooking causes significant fall in their concentration. Sources rich in folates are liver, green leafy vegetables especially spinach and broccoli, nuts, egg, cereals, cheese, fruits, yeast, beans etc.

50. Folic acid is play an important role in cell division and development.  Folic acid is highly recommended for preventing both occurrence and recurrence of NTD. Strategies for improving maternal folate status : Dietary modifications : Dietary recommendations of consuming food high in folate content is beneficial . Vitamin supplementation : The second approach is daily folic acid supplementation to all women in the reproductive age group (18-44 years). 

51. Advise women trying to conceive to take a dose of 400 μ g folic acid daily, starting two months before the planned pregnancy . Advise women who have not been supplementing their diet and who suspect themselves to be pregnant to begin taking 400 μ g folic acid daily and to continue until they are 12 weeks pregnant . Counsel pregnant women who previously had a baby with NTD, For women with Diabetes or who are taking anticonvulsant about the risk of having a baby being affected . Advise them to take 5 mg Folic acid daily and to increase the consumption of Folate in diet.

52. THANK YOU