Pathophysiology and clinical manifestations of myelomeningocele (spina bifida)
- David G McLone, MD, PhD
David G McLone, MD, PhD
- Professor of Pediatric Neurosurgery
- Northwestern University's Feinberg School of Medicine
- Ann and Robert Lurie Children's Hospital of Chicago
- Robin M Bowman, MD
Robin M Bowman, MD
- Assistant Professor of Neurological Surgery
- Northwestern University's Feinberg School of Medicine
- Ann and Robert H Lurie Children's Hospital of Chicago
- Section Editors
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Leonard E Weisman, MD
Leonard E Weisman, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
Neural tube defects (NTDs), are the second most common congenital anomaly, and are the cause of chronic disability of between 70,000 and 100,000 individuals in the United States. Myelomeningocele (spina bifida) is the most common neural tube defect.
Myelomeningocele is characterized by a cleft in the vertebral column, with a corresponding defect in the skin so that the meninges and spinal cord are exposed. Because the neural tissue is exposed, it is also known as open spinal dysraphism, or spina bifida aperta. By contrast, occult spinal dysraphism is characterized by a cleft in the vertebral column, without a corresponding epithelial defect, and neural tissue is not exposed. There are many different forms of occult spinal dysraphism, ranging from asymptomatic vertebral anomalies to clinically significant defects in the spinal cord and related structures. Occult spinal dysraphism is discussed separately. (See "Closed spinal dysraphism: Pathogenesis and types".)
The embryology and pathophysiology of myelomeningocele will be reviewed here. The management of infants with myelomeningocele, prenatal aspects, and prevention of neural tube defects are discussed separately. (See "Overview of the management of myelomeningocele (spina bifida)" and "Prenatal screening and diagnosis of neural tube defects" and "Ultrasound diagnosis of neural tube defects" and "Folic acid supplementation in pregnancy".)
EMBRYOLOGY OF THE NEURAL TUBE
Primary neurulation — The central nervous system (CNS) initially appears as a plate of thickened ectoderm, called the neural plate, at the beginning of the third week of embryonic life . The lateral edges of the neural plate become elevated to form the neural folds . These folds subsequently become further elevated, approach each other, and fuse to form the neural tube (figure 1) . The fusion begins in the cervical region and proceeds in both the cephalad and caudal directions (figure 2).
The cranial neuropore closes on the 25th day after conception. Fusion is delayed at the caudal end of the embryo so that the caudal neuropore forms an open communication between the lumen of the neural tube (the neurocele) and the amniotic cavity. Closure of the caudal neuropore normally occurs approximately two days later. This process is called primary neurulation and forms all of the functional central nervous system, which extends to the mid sacral levels of the embryo .
- Müller F, O'Rahilly R. The primitive streak, the caudal eminence and related structures in staged human embryos. Cells Tissues Organs 2004; 177:2.
- Ybot-Gonzalez P, Copp AJ. Bending of the neural plate during mouse spinal neurulation is independent of actin microfilaments. Dev Dyn 1999; 215:273.
- Alvarez IS, Schoenwolf GC. Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate. J Exp Zool 1992; 261:340.
- Müller F, O'Rahilly R. The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12. Anat Embryol (Berl) 1987; 176:413.
- Desmond ME, Jacobson AG. Embryonic brain enlargement requires cerebrospinal fluid pressure. Dev Biol 1977; 57:188.
- McLone DG, Dias MS. The Chiari II malformation: cause and impact. Childs Nerv Syst 2003; 19:540.
- McLone DG, Knepper PA. The cause of Chiari II malformation: a unified theory. Pediatr Neurosci 1989; 15:1.
- Sutton LN, Adzick NS, Bilaniuk LT, et al. Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA 1999; 282:1826.
- Tulipan N, Hernanz-Schulman M, Lowe LH, Bruner JP. Intrauterine myelomeningocele repair reverses preexisting hindbrain herniation. Pediatr Neurosurg 1999; 31:137.
- Naidich TP, McLone DG, Fulling KH. The Chiari II malformation: Part IV. The hindbrain deformity. Neuroradiology 1983; 25:179.
- ACOG Committee on Practice Bulletins. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 44, July 2003. (Replaces Committee Opinion Number 252, March 2001). Obstet Gynecol 2003; 102:203.
- Frey L, Hauser WA. Epidemiology of neural tube defects. Epilepsia 2003; 44 Suppl 3:4.
- Canfield MA, Annegers JF, Brender JD, et al. Hispanic origin and neural tube defects in Houston/Harris County, Texas. II. Risk factors. Am J Epidemiol 1996; 143:12.
- Harmon JP, Hiett AK, Palmer CG, Golichowski AM. Prenatal ultrasound detection of isolated neural tube defects: is cytogenetic evaluation warranted? Obstet Gynecol 1995; 86:595.
- Centers for Disease Control and Prevention (CDC). Racial/ethnic differences in the birth prevalence of spina bifida - United States, 1995-2005. MMWR Morb Mortal Wkly Rep 2009; 57:1409.
- Cowchock S, Ainbender E, Prescott G, et al. The recurrence risk for neural tube defects in the United States: a collaborative study. Am J Med Genet 1980; 5:309.
- Papp C, Adám Z, Tóth-Pál E, et al. Risk of recurrence of craniospinal anomalies. J Matern Fetal Med 1997; 6:53.
- Shin M, Besser LM, Siffel C, et al. Prevalence of spina bifida among children and adolescents in 10 regions in the United States. Pediatrics 2010; 126:274.
- Moretti ME, Bar-Oz B, Fried S, Koren G. Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiology 2005; 16:216.
- Tulipan N, Bruner JP. Myelomeningocele repair in utero: a report of three cases. Pediatr Neurosurg 1998; 28:177.
- Adzick NS, Sutton LN, Crombleholme TM, Flake AW. Successful fetal surgery for spina bifida. Lancet 1998; 352:1675.
- Johnson MP, Sutton LN, Rintoul N, et al. Fetal myelomeningocele repair: short-term clinical outcomes. Am J Obstet Gynecol 2003; 189:482.
- Chen CP. Prenatal diagnosis, fetal surgery, recurrence risk and differential diagnosis of neural tube defects. Taiwan J Obstet Gynecol 2008; 47:283.
- Danzer E, Gerdes M, Bebbington MW, et al. Preschool neurodevelopmental outcome of children following fetal myelomeningocele closure. Am J Obstet Gynecol 2010; 202:450.e1.
- Sutton LN. Fetal surgery for neural tube defects. Best Pract Res Clin Obstet Gynaecol 2008; 22:175.
- Adzick NS, Thom EA, Spong CY, et al. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364:993.
- American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 550: maternal-fetal surgery for myelomeningocele. Obstet Gynecol 2013; 121:218.
- Cohen AR, Couto J, Cummings JJ, et al. Position statement on fetal myelomeningocele repair. Am J Obstet Gynecol 2014; 210:107.
- Nagler J, Levy JA, Bachur RG. Stridor in an infant with myelomeningocele. Pediatr Emerg Care 2007; 23:478.
- Holinger PC, Holinger LD, Reichert TJ, Holinger PH. Respiratory obstruction and apnea in infants with bilateral abductor vocal cord paralysis, meningomyelocele, hydrocephalus, and Arnold-Chiari malformation. J Pediatr 1978; 92:368.
- Tomita T, McLone DG. Acute respiratory arrest. A complication of malformation of the shunt in children with myelomeningocele and Arnold-Chiari malformation. Am J Dis Child 1983; 137:142.
- Rintoul NE, Sutton LN, Hubbard AM, et al. A new look at myelomeningoceles: functional level, vertebral level, shunting, and the implications for fetal intervention. Pediatrics 2002; 109:409.
- Dias MS, McLone DG. Hydrocephalus in the child with dysraphism. Neurosurg Clin N Am 1993; 4:715.
- Rekate, HL. Shunt revision: complications and their prevention. Pediatr Neurosurg 1991-1992; 17:155.
- EMBRYOLOGY OF THE NEURAL TUBE
- Primary neurulation
- - Occlusion
- - Chiari II malformation
- Secondary neurulation
- PRENATAL DIAGNOSIS
- Maternal AFP screening
- Ultrasound findings
- Fetal surgery
- The newborn
- Anatomy of the lesion
- NEUROLOGIC ABNORMALITIES
- Spinal cord
- INFORMATION FOR PATIENTS