NÖRAL TÜP DEFEKTLERİ
DR. GÖKHAN YILDIRIM
En sık 2. konjenital anomali
İnsidansı 1/1000 doğum
Türkiye de insidansı ?
Folik asit kullanımı insidansı
azaltmıştır
Embriyoloji
Sınıflama
Kraniyal Defektler
Anensefali
Eksensefali
Ensefalosel
İniensefali
• Spinal defektler
Açık/kapalı
Meningosel/meningomiyelos el
304 N. D. E. GREENE AND A. J. COPP
Figure 1—Schematic diagram of neural tube closure and the affected events leading to NTDs (indicated by red arrows). Neural tube closure is initiated by closure 1 at the hindbrain/cervical boundary in mouse (a) and spreads caudally and rostrally from this site (black arrows). Closure 1 in human (b) may occur in the rhombencephalon, more rostrally than in mouse. Failure of closure 1 results in craniorachischisis. A second site of initial closure (closure 2) occurs at the forebrain/midbrain boundary in most mouse strains (a), although the position of the site of closure 2 may vary between strains. This site may be absent in humans (b). Closure also initiates at the rostral limit of the forebrain (closure 3) in mouse and an equivalent closure occurs in humans. Progress of neurulation from the initial sites of fusion results in shortening and closure of the anterior and hindbrain neuropores, indicated by arrows. Failure of initial closure sites or closure of neuropores results in anencephaly. Neurulation progresses caudally from the site of closure 1 until fusion is finally completed by closure of the posterior neuropore. Open spina bifida results from failure of posterior neuropore closure. Secondary neurulation proceeds from the level of the closed posterior neuropore. Modified from (Copp et al., 1994, 2003b)
In the human embryo, neural plate bending begins at about 17–18 days after fertilization. Initiation of neural tube closure occurs, as in mice, by a discontinuous pro- cess (Figure 1), and analogous events to closure 1 and 3 have been described (O’Rahilly and M¨uller, 1994, 2002).
The site of initial closure (equivalent to mouse closure 1) may occur at a slightly more rostral level in humans than in mouse, being located in the rhombencephalon as opposed to the rhombencephalon/cervical boundary (O’Rahilly and M¨uller, 2002). Closure at the extreme rostral end of the neural plate (closure 3) appears to occur in humans as in the mouse (O’Rahilly and M ¨uller, 2002). However, the existence of an event equivalent to closure 2 is more controversial, having been proposed in some studies (Van Allen et al., 1993; Golden and Chernoff, 1995; Seller, 1995b) but not others (O’Rahilly and M ¨uller, 2002). The presence of closure 2 has been inferred from observation of late stage anencephalic fetuses (Van Allen et al., 1993; Seller, 1995b), whereas direct analysis of early human embryos has suggested that a closure 2 event either occurs at a more caudal posi- tion than in mice, in the hindbrain (Nakatsu et al., 2000), or not at all (O’Rahilly and M ¨uller, 2002). Therefore, there may be variability in the position or occurrence of closure 2 in human neurulation. Closure in the cranial region is completed on day 25 and closure of the poste- rior neuropore, which completes primary neurulation, at 26–28 days postfertilization.
DIFFERING MECHANISMS OF CLOSURE IN THE CRANIAL AND SPINAL REGIONS
Although the principles of neurulation are conserved throughout primary neurulation, involving elevation and fusion of neural folds, the detailed mechanism appears
to differ markedly with axial level and developmental stage. Thus, in the cranial region of the mouse embryo bending of the neural folds during closure is quite different from that in the spinal region. As they initially elevate, about a midline hinge point, the neural folds assume a biconvex appearance in the midbrain with the tips of the folds facing away from the midline. The folds then switch orientation to assume a biconcave shape in which the tips approach each other in the midline, allowing fusion to occur (Morriss-Kay, 1981; Morriss- Kay et al., 1994).
Spinal neurulation contrasts with cranial closure in lacking a biconvex phase of neural fold elevation.
Instead, the spinal neural folds exhibit a stereotypical pattern of bending with hinge points at two locations:
the median hinge point (MHP) overlying the notochord, which creates the midline ‘neural groove’ with its V-shaped cross-section, and paired dorsolateral hinge points (DLHPs), which create longitudinal furrows that bring the neural fold tips toward each other in the dorsal midline. Different combinations of bending points are utilized as closure progresses down the spinal neuraxis (Figure 2). In the early stages of spinal neurulation, at E8.5, the neural plate bends solely at the MHP, whereas by early E9.5, as closure progresses to the thoracic level, bending occurs at DLHPs in addition to the MHP. At E10, when the low spinal neural tube is forming, MHP bending is lost and the neural plate bends solely at DLHPs (Shum and Copp, 1996).
FAILURE OF NEURULATION RESULTS IN NEURAL TUBE DEFECTS
Open NTDs (including open spina bifida and anen- cephaly in mammals) result from failure of the neural
Copyright Ó 2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 303–311.
DOI: 10.1002/pd
Etiyoloji ve Risk Faktörleri
Tekrarlama Riski
Biyokimyasal Tarama
Ultrasonografi
Transver/aksiyel kesit
Sagittal kesit Koronal kesit
İkinci trimester USG bulguları:
Kranyumun üst kısmı izlenmez
Heterojen kitle görünümü
Polihidroamnios
SONOEMBRYOLOGY OF CNS AND EARLY PRENATAL DIAGNOSIS 319
Figure 8— Section through heads of embryos with acrania/
exencephaly; the contours of the brain are irregular (arrows), the brain cavities are ‘empty’ (a) CRL 22 mm (b) CRL 28 mm
brain tissue can be seen, as we have reported in a case of craniorachischisis (Figure 9a) at 13 weeks of gesta- tion (Blaas and Eik-Nes, 1999b). As in acrania, cran- iorachischisis may also have ‘empty’ brain cavities. In addition, one will often find anomalous shape of the spine (Figure 9b).
Spinabifida
According to the embryological process of neurulation, neural tube defects have different modes of origin, sug- gesting different pathomechanisms (Copp et al., 1990).
Myelomeningocele (commonly called spina bifida) results from the failure of fusion in the spinal region of the neural tube. The defective development of the midbrain and hindbrain with elongation of the midbrain and a herniation of the cerebellum and medulla towards the foramen magnum is called Arnold–Chiari malfor- mation. The time of its origin is almost certainly in the embryonic period at the time of neural tube closure, especially the closure of the caudal neuropore (Gardner et al., 1975).
The typical features of spina bifida at midgestation are: the ‘lemon’ shape of the head, BPD somewhat
Figure 9— (a) Post abortem photography and ultrasound image of coronal section through the head of a 13-week-old foetus with cran- iorachischisis; the head was fluid-filled and covered by a membrane (arrows) that ruptured during the delivery (b) Craniorachischisis in a 22-mm CRL embryo; the brain cavities are ‘empty’, there is a sharp bend of the dysraphic spine (arrow) Y, yolk sac
smaller than expected, ‘hanging’ choroid plexuses in the dilated lateral ventricles, curved shape of the cerebellum (banana sign) and dysraphic defect of the spine.
The diagnosis of neural tube defect (NTD) has been made at early post-embryonic stages, in other words after 10 weeks: Blumenfeld and coworkers presented 10 cases with first-trimester and early second-trimester NTD detected by ultrasound (Blumenfeld et al., 1993).
In their earliest case, a sacral irregularity was suspected in a 10-week-old pregnancy (no biometric data pre- sented). Bernard and coworkers described a 10-week- 5-day-old foetus (CRL 31 mm) with a lumbo-sacral myelomeningocele (Bernard et al., 1997). In this foetus, the lemon shape and cerebellar signs of Arnold –Chiari malformation could not be detected at 12 weeks, prior to termination of the pregnancy.
Hern´adi and T¨or¨ocsik reported three cases of spina bifida at 12 to 14 weeks detected in a screening program in a population consisting of 3758 pregnancies at low risk for congenital anomalies, and 233 pregnancies at high risk (Hern´adi and T¨or¨ocsik, 1997). They did not report the diagnostic key for their diagnosis. The
‘lemon’ sign was found in three first-trimester cases of spina bifida at 12, 13 and 14 weeks (CRL 56, 62 and
CopyrightÓ2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 312 – 325.
DOI: 10.1002/pd
SONOEMBRYOLOGY OF CNS AND EARLY PRENATAL DIAGNOSIS 319
Figure 8—Section through heads of embryos with acrania/
exencephaly; the contours of the brain are irregular (arrows), the brain cavities are ‘empty’ (a) CRL 22 mm (b) CRL 28 mm
brain tissue can be seen, as we have reported in a case of craniorachischisis (Figure 9a) at 13 weeks of gesta- tion (Blaas and Eik-Nes, 1999b). As in acrania, cran- iorachischisis may also have ‘empty’ brain cavities. In addition, one will often find anomalous shape of the spine (Figure 9b).
Spina bifida
According to the embryological process of neurulation, neural tube defects have different modes of origin, sug- gesting different pathomechanisms (Copp et al., 1990).
Myelomeningocele (commonly called spina bifida) results from the failure of fusion in the spinal region of the neural tube. The defective development of the midbrain and hindbrain with elongation of the midbrain and a herniation of the cerebellum and medulla towards the foramen magnum is called Arnold–Chiari malfor- mation. The time of its origin is almost certainly in the embryonic period at the time of neural tube closure, especially the closure of the caudal neuropore (Gardner et al., 1975).
The typical features of spina bifida at midgestation are: the ‘lemon’ shape of the head, BPD somewhat
Figure 9—(a) Post abortem photography and ultrasound image of coronal section through the head of a 13-week-old foetus with cran- iorachischisis; the head was fluid-filled and covered by a membrane (arrows) that ruptured during the delivery (b) Craniorachischisis in a 22-mm CRL embryo; the brain cavities are ‘empty’, there is a sharp bend of the dysraphic spine (arrow) Y, yolk sac
smaller than expected, ‘hanging’ choroid plexuses in the dilated lateral ventricles, curved shape of the cerebellum (banana sign) and dysraphic defect of the spine.
The diagnosis of neural tube defect (NTD) has been made at early post-embryonic stages, in other words after 10 weeks: Blumenfeld and coworkers presented 10 cases with first-trimester and early second-trimester NTD detected by ultrasound (Blumenfeld et al., 1993).
In their earliest case, a sacral irregularity was suspected in a 10-week-old pregnancy (no biometric data pre- sented). Bernard and coworkers described a 10-week- 5-day-old foetus (CRL 31 mm) with a lumbo-sacral myelomeningocele (Bernard et al., 1997). In this foetus, the lemon shape and cerebellar signs of Arnold–Chiari malformation could not be detected at 12 weeks, prior to termination of the pregnancy.
Hern´adi and T¨or¨ocsik reported three cases of spina bifida at 12 to 14 weeks detected in a screening program in a population consisting of 3758 pregnancies at low risk for congenital anomalies, and 233 pregnancies at high risk (Hern´adi and T¨or¨ocsik, 1997). They did not report the diagnostic key for their diagnosis. The
‘lemon’ sign was found in three first-trimester cases of spina bifida at 12, 13 and 14 weeks (CRL 56, 62 and
CopyrightÓ2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 312–325.
DOI: 10.1002/pd
İntrakranyal içeriğin karanyal defektten protrüzyonu
Sonografik bulgular;
Kistik ve/veya solid kitle
Kalvaryumda defekt
Kist içinde kist
Ventrikülomegali
• Karyotip
404 M. CAMERON AND P. MORAN
Figure 2 — Occipital encephalocele
Figure 3 — Classical lemon shaped head with ventriculomegaly seen in a fetus with spinabifida
the frontal bones (Campbell et al. 1987; Nyberg et al., 1988).
Figure 4 — Banana cerebellum associated with spina bifida
The banana sign refers to the shape of the cerebellum, which is distorted as part of the Chiari type II malfor- mation. The cerebellum may also be absent as part of the Chiari type II malformation which is seen in 95%
of open NTD and does not resolve as the pregnancy advances.
Pooled data from 234 fetuses with spina bifida showed that 99% had at least one cranial finding at less than 24 weeks (Watson et al., 1991). Lemon and banana (or absent cerebellum) signs were both seen in 97% of fetuses, with ventriculomegaly seen in 75%, cisterna magna obliteration in 68% and small biparietal diameter in 61%. An Italian study recently reported on 49 fetuses with spina bifida and assessed six sonographic signs in prenatal diagnosis (D’Addario et al. 2008). They found a small cerebellum in 96% of cases, an effaced cisterna magna in 93% and a small posterior fossa in 96%. Less consistent cranial signs were ventriculomegaly (81%) and “lemon” sign (53%).
Subtle supratentorial signs are seen with the Chiari type II malformation. Fujisawa et al. (2006) described late pregnancy changes in the shape of the enlarged posterior horn of the lateral ventricle in the coronal view, and Callen and Filly described a lateral ventricle with a pointed shape in axial view although this was more common prior to 24 weeks and in ventricles of normal size (Callen and Filly 2008).
Ghi et al. (2006) reported that while all 53 cases of open spina bifida had alterations in cranial anatomy (including the “banana” and “lemon” signs), with closed spina bifida (7% of their population) cranial signs do not develop. They conclude that the “the differentiation between open and closed spina bifida is best shown by the sonographic demonstration of abnormal or normal cranial anatomy.”
To accurately identify the type and extent of the lesion sagittal, coronal and axial spinal views are all required (Figure 5). The bony defect is identified by splaying of the posterior lamina ossification centers in the coronal and axial plane (Figure 6). The bony defect may lie at or cranial to, the level at which there is protrusion of the meninges (meningocele) or meninges plus neural tissue (myelomeningocele).
All lesions arise from a dysraphism (defect of closure) and are classified as open or closed depending on
CopyrightÓ2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 402 – 411.
DOI: 10.1002/pd
404 M. CAMERON AND P. MORAN
Figure 2 — Occipital encephalocele
Figure 3 — Classical lemon shaped head with ventriculomegaly seen in a fetus with spinabifida
the frontal bones (Campbell et al. 1987; Nyberg et al., 1988).
Figure 4 — Banana cerebellum associated with spina bifida
The banana sign refers to the shape of the cerebellum, which is distorted as part of the Chiari type II malfor- mation. The cerebellum may also be absent as part of the Chiari type II malformation which is seen in 95%
of open NTD and does not resolve as the pregnancy advances.
Pooled data from 234 fetuses with spina bifida showed that 99% had at least one cranial finding at less than 24 weeks (Watson et al., 1991). Lemon and banana (or absent cerebellum) signs were both seen in 97% of fetuses, with ventriculomegaly seen in 75%, cisterna magna obliteration in 68% and small biparietal diameter in 61%. An Italian study recently reported on 49 fetuses with spina bifida and assessed six sonographic signs in prenatal diagnosis (D’Addario et al. 2008). They found a small cerebellum in 96% of cases, an effaced cisterna magna in 93% and a small posterior fossa in 96%. Less consistent cranial signs were ventriculomegaly (81%) and “lemon” sign (53%).
Subtle supratentorial signs are seen with the Chiari type II malformation. Fujisawa et al. (2006) described late pregnancy changes in the shape of the enlarged posterior horn of the lateral ventricle in the coronal view, and Callen and Filly described a lateral ventricle with a pointed shape in axial view although this was more common prior to 24 weeks and in ventricles of normal size (Callen and Filly 2008).
Ghi et al. (2006) reported that while all 53 cases of open spina bifida had alterations in cranial anatomy (including the “banana” and “lemon” signs), with closed spina bifida (7% of their population) cranial signs do not develop. They conclude that the “the differentiation between open and closed spina bifida is best shown by the sonographic demonstration of abnormal or normal cranial anatomy.”
To accurately identify the type and extent of the lesion sagittal, coronal and axial spinal views are all required (Figure 5). The bony defect is identified by splaying of the posterior lamina ossification centers in the coronal and axial plane (Figure 6). The bony defect may lie at or cranial to, the level at which there is protrusion of the meninges (meningocele) or meninges plus neural tissue (myelomeningocele).
All lesions arise from a dysraphism (defect of closure) and are classified as open or closed depending on
CopyrightÓ2009 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 402 – 411.
DOI: 10.1002/pd
