Limited Dorsal Myeloschisis: Reconsideration of its Embryological Origin.

BACKGROUND: Limited dorsal myeloschisis (LDM) is postulated to be a result of incomplete dysjunction in primary neurulation. However, clinical experience of LDM located below the first-second sacral (S1-S2) vertebral level, which is formed from secondary neurulation (S2-coccyx), suggested that LDM may not be entirely explained as an error of primary neurulation. OBJECTIVE: To elucidate the location and characteristics of LDM to investigate the possible relation of its pathoembryogenesis to secondary neurulation. METHODS: Twenty-eight patients were surgically treated for LDM from 2010 to 2015. Since the level where the LDM stalk penetrates the interspinous ligament is most clearly defined on the preoperative MRI and operative field, this level was assessed to find out whether the lesions can occur in the region of secondary neurulation. RESULTS: Eleven patients (39%) with typical morphology of the stalk had interspinous defect levels lower than S1-S2. These patients were not different from 17 patients with classic LDMs at a level above or at S1-S2. This result shows that other than the low level of the interspinous level, 11 patients had lesions that could be defined as LDMs. CONCLUSION: By elucidating the location of LDM lesions (in particular, the interspinous level), we propose that LDM may be caused by errors of secondary neurulation. The hypothesis seems more plausible due to the supportive fact that the process of separation between the cutaneous and neural ectoderm is present during secondary neurulation. Hence, incomplete disjunction of the two ectoderms during secondary neurulation may result in LDM, similar to the pathomechanism proposed during primary neurulation.

Prenatal diagnosis of caudal regression with heterotaxy syndrome: "A mermaid with a broken heart".

Caudal regression syndrome (CRS) is a rare congenital malformation with varying degrees of early gestational developmental failure. It is characterized by agenesis of the sacrum and lumbar spine, with lower limb neurological deficit and accompanying deformities of the pelvis, lower extremities, genitourinary, and gastrointestinal systems. We report a case of CRS associated with rare complex congenital heart defect, that is, heterotaxy syndrome, diagnosed prenatally.

Normal development of costal element ossification centers of sacral vertebrae in the fetal spine: a postmortem magnetic resonance imaging study.

PURPOSE: This postmortem magnetic resonance imaging (MRI) study of the fetal spine aimed to describe the timing of appearance, shape, volume, and relative positions of the S1-S3 costal element ossification centers (CEOCs). METHODS: We obtained sagittal 3D dual-echo steady-state with water excitation T2 images of the entire spine in 71 fetuses (gestational ages (GAs), 17-42 weeks). Computed tomography and histological examinations were performed on two fetal specimens (GAs, 21 and 30 weeks) to validate the MR images. The presence/absence of each sacral CEOC was recorded according to the GA. CEOC volume was measured. We analyzed the CEOC position relative to the vertebral column and ilium. RESULTS: The S1, S2, and S3 CEOCs first appeared at 23, 22, and 29 weeks, respectively. The S1 and S2 CEOCs could be detected in all fetuses with GAs of ≥ 30 weeks and ≥ 35 weeks, respectively, while the S3 CEOCs were variably present until term. The percentages of detection of the S1 and S2 CEOCs were significantly greater than that of the S3 CEOCs at each GA. At S1 and S2, the CEOC volume increased exponentially with GA. The relative positions of the S1 and S2 CEOCs, but not the S3 CEOCs, significantly correlated with GA (P < 0.001). CONCLUSION: We have described the timeline of appearance as well as the volume and position of the S1-S3 CEOCs in the fetal spine on postmortem MRI according to GA.

The sacral autonomic outflow is sympathetic.

A kinship between cranial and pelvic visceral nerves of vertebrates has been accepted for a century. Accordingly, sacral preganglionic neurons are considered parasympathetic, as are their targets in the pelvic ganglia that prominently control rectal, bladder, and genital functions. Here, we uncover 15 phenotypic and ontogenetic features that distinguish pre- and postganglionic neurons of the cranial parasympathetic outflow from those of the thoracolumbar sympathetic outflow in mice. By every single one, the sacral outflow is indistinguishable from the thoracolumbar outflow. Thus, the parasympathetic nervous system receives input from cranial nerves exclusively and the sympathetic nervous system from spinal nerves, thoracic to sacral inclusively. This simplified, bipartite architecture offers a new framework to understand pelvic neurophysiology as well as development and evolution of the autonomic nervous system.

Reference ranges for vertebral body areas of the fetal lumbosacral spine on 3-dimensional sonography using volume contrast imaging with OmniView.

OBJECTIVES; The purpose of this study was to establish reference ranges for vertebral body areas of the fetal lumbosacral spine in the coronal plane on 3-dimensional sonography using volume contrast imaging with OmniView (GE Healthcare, Zipf, Austria). METHODS; An observational cross-sectional study was conducted on 576 healthy pregnant women at gestational ages of 20 weeks to 34 weeks 6 days. Volume contrast imaging with OmniView was used to measure the vertebral body areas (L1-L5, S1, and S2) by positioning a curved line along the fetal lumbosacral spine. To create reference ranges, first- and second-degree linear regression models adjusted using residual analysis and the coefficient of determination (R(2)) were created. To assess reproducibility, two examiners evaluated 40 random volumes using the intraclass correlation coefficient. RESULTS; The mean areas of the vertebral bodies were 102.72 (range, 25-254), 107.29 (range, 30-245), 105.10 (range, 31-231), 99.09 (range, 31-211), 87.74 (range, 11-178), 65.80 (range, 18-161), and 46.54 (range, 12-129) mm(2) for L1, L2, L3, L4, L5, S1, and S2, respectively. In the intraobserver and interobserver reproducibility assessments, intraclass correlation coefficients of greater than 0.80 were found for all fetal vertebral body areas. CONCLUSIONS; Reference values for fetal lumbosacral spine vertebral body areas were determined by 3-dimensional sonography using volume contrast imaging with OmniView, and they were shown to be reproducible.

Origin of presacral local recurrence after rectal cancer treatment.

BACKGROUND: The objective of this study was to obtain detailed anatomical information about the lateral lymph nodes, in order to determine whether they might play a role in presacral local recurrence of rectal cancer after total mesorectal excision without lateral lymph node dissection. METHODS: Ten serially sectioned human fetal pelvises were studied at high magnification and a three-dimensional reconstruction of the fetal pelvis was made. RESULTS: Examination of the histological sections and the three-dimensional reconstruction showed that lateral lymph node tissue comprises a major proportion of the pelvic tissue volume. There were no lymph nodes located in the presacral area. Connections between the mesorectal and extramesorectal lymph node system were found in all fetal pelvises, located below the peritoneal reflection on the anterolateral side of the fetal rectum. At this site middle rectal vessels passed to and from the mesorectum, and branches of the autonomic nervous system bridge to innervate the rectal wall. CONCLUSION: The findings of this study support the hypothesis that tumour recurrence might arise from lateral lymph nodes.

[Regularities of morphogenesis of the sacrourothelial joint in Anura].

The regularities in the formation of different types of Anura sacrourothelial joints have been determined. A review of factors that affect the form of this joint is presented. It has been established that the determinant role in the formation of a moveable or immoveable joint is played by the topography and time of the appearance of musces in the sacrourothelial area. The proposed mechanisms explain not only the diversity of structural norms depending on this feature, but also options of individual variability.

Lumbosacral lordosis in fetal spine: genetic or mechanic parameter.

Many believe that the fetus spine had only one curvature from cranial to caudal which is a global kyphosis and that the lumbosacral lordosis appears with the erect posture. They agree that the sacrum of Homo sapiens is not positioned posteriorly at birth and that it is during the first few years that the sacrum, in humans, moves dorsally in relation with the progressive acquisition of erect posture and the ontogeny of bipedal locomotion. Nevertheless, there is no biometric study assessing these parameters in vivo in utero during the fetal life. Cross-sectional biometric study of the lumbosacral junction of the spine in in utero fetuses was to document the presence of a lumbosacral lordosis in the fetal population in utero long before standing and walking and its change during growth. Forty-five MRIs (magnetic resonance imaging) of fetuses aged of 23-40 weeks of gestation were analyzed. The measurements were performed on computerized MRI DICOM images using a professional software to calculate the curvature and radius of the lumbosacral junction. The presence or absence of visual lumbosacral lordosis was noted for each case. Correlation tests were performed in order to disclose a correlation between the gestational age and the curvature calculated. A test was considered significant for P < 0.01. There were 14 males, 17 females and 14 undetermined. All the curves (100%) showed mathematically the presence of a lordosis in the lumbosacral region. The visual lumbosacral lordosis was present in 60% of cases. The measurement of the lumbosacral curvature varies between -0.133 and -0.033 mm(-1) and a mean of -0.054 mm(-1) with a corresponding radius ranging from -7 to -303 mm with a mean of -18.7 mm. The statistical analysis showed no correlation between the gestational age and the lumbosacral curvature (R (2) = 0.11). The hypothesis of increased lumbosacral lordosis with gestational age is rejected. It is difficult to accurately determine the role played separately by genetics and by erect posture. A visual lumbosacral lordosis was noted in 60% of cases with mean radius of -18.6691 mm. This lordosis was not correlated statistically to gestational age which means that it is not related to growth and might be genetically determined. Mechanical factors may play a major role in the determination of the shape of the growing pelvis. One can ask if the pelvis morphology is genetically determined or if it is mechanically determined under muscular and ligamentous stresses. This study shows that the sacrum of human fetuses is oriented posteriorly mathematically in 100% of cases, and in 60% of cases based on the morphologic appearance of the lumbosacral junction. So beside the effect of progressive acquisition of erect posture and bipedalism in determining the formation of lumbosacral angle, we believe that genetics play an important role in the formation of the lumbosacral angle.

Restricted patterns of Hoxd10 and Hoxd11 set segmental differences in motoneuron subtype complement in the lumbosacral spinal cord.

During normal vertebrate development, Hoxd10 and Hoxd11 are expressed by differentiating motoneurons in restricted patterns along the rostrocaudal axis of the lumbosacral (LS) spinal cord. To assess the roles of these genes in the attainment of motoneuron subtypes characteristic of LS subdomains, we examined subtype complement after overexpression of Hoxd10 or Hoxd11 in the embryonic chick LS cord and in a Hoxd10 loss-of-function mouse embryo. Data presented here provide evidence that Hoxd10 defines the position of the lateral motor column (LMC) as a whole and, in rostral LS segments, specifically promotes the development of motoneurons of the lateral subdivision of the lateral motor column (LMCl). In contrast, Hoxd11 appears to impart a caudal and medial LMC (LMCm) identity to some motoneurons and molecular profiles suggestive of a suppression of LMC development in others. We also provide evidence that Hoxd11 suppresses the expression of Hoxd10 and the retinoic acid synthetic enzyme, retinaldehyde dehydrogenase 2 (RALDH2). In a normal chick embryo, Hoxd10 and RALDH2 are expressed throughout the LS region at early stages of motoneuron differentiation but their levels decline in Hoxd11-expressing caudal LS segments that ultimately contain few LMCl motoneurons. We hypothesize that one of the roles played by Hoxd11 is to modulate Hoxd10 and local retinoic acid levels and thus, perhaps define the caudal boundaries of the LMC and its subtype complement.

Intramedullary dermoid in a low lying conus tethered by a fatty filum - embryological implications.

Intramedullary dermoids arising within the conus medullaris are rare. We report a rare association of an intramedullary dermoid cyst located in a low lying conus tethered by a thickened, fatty filum terminale and discuss the embryological implications of this association.

Phenotypes of neural-crest-derived cells in vagal and sacral pathways.

Enteric neurons arise from vagal and sacral level neural crest cells. To examine the phenotype of neural-crest-derived cells in vagal and sacral pathways, we used antisera to Sox10, p75, Phox2b, and Hu, and transgenic mice in which the expression of green fluorescent protein was under the control of the Ret promoter. Sox10 was expressed prior to the emigration of vagal cells, whereas p75 was expressed shortly after their emigration. Most crest-derived cells that emigrated adjacent to somites 1-4 migrated along a pathway that was later followed by the vagus nerve. A sub-population of these vagal cells coalesced to form vagal ganglia, whereas others continued their migration towards the heart and gut. Cells that coalesced into vagal ganglia showed a different phenotype from cells in the migratory streams proximal and distal to the ganglia. Only a sub-population of the vagal cells that first entered the foregut expressed Phox2b or Ret. Sacral neural crest cells gave rise to pelvic ganglia and some neurons in the hindgut. The pathways of sacral neural crest cells were examined by using DbetaH-nlacZ mice. Sacral cells appeared to enter the distal hindgut around embryonic day 14.5. Very few of the previously demonstrated, but rare, neurons that were present in the large intestine of Ret null mutants and that presumably arose from the sacral neural crest expressed nitric oxide synthase, unlike their counterparts in Ret heterozygous mice.

Development of the posterior neural tube in human embryos.

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.

Ossification timing of sacral vertebrae by ultrasound in the mid-second trimester of pregnancy.

OBJECTIVES: The aim of the study was to establish the ossification timing of sacral vertebrae by ultrasonography in the second trimester of pregnancy, for the diagnosis of caudal regression syndrome with isolated sacral agenesis. METHODS: The study was carried out on 77 normal single pregnancies, at gestational ages ranging from 15 to 21 weeks, using high-resolution transabdominal echography. The sacral region was visualized in a coronal plane, when the fetus was in anterodorsal position. The level of ossification of sacral vertebrae (S1 to S5) at each gestational age was recorded. Each sacral region was examined three times by the same observer and the nucleus was considered as present when it was visualized at least two times out of three. Blind assessment was performed three times by a second observer, who was not present at the previous examination, for interobserver and intraobserver error analysis. RESULTS: Interobserver and intraobserver error calculation demonstrated the reproducibility of the method. Concordance between the two observers as evaluated by Cohen Kappa index was 0.77 (C.I. 95%, 0.69-0.85).S1 ossification nuclei were visualized in all fetuses at 15 weeks and S2 nucleus was found in all fetuses within 17 weeks. S3 nucleus was detected in 45% of fetuses by the beginning of the 16th week. S4 was visualized in 55% of the cases at 18 weeks and progressively in a higher percentage of cases during the following weeks of gestation. CONCLUSION: The data obtained showed that the sequence of development of sacral region ossification was related to gestational age. This observation allows clinicians to accurately exclude isolated sacral agenesis at 16 to 17 weeks of gestation, when the S1-S2 ossification nuclei are visualized. This opportunity may be of particular value in the offspring of diabetic mothers.

Fetal bony pelvis in the bladder exstrophy complex: normal potential for growth?

OBJECTIVES: To provide the first look at the bony histologic features of fetuses with the exstrophy complex, specifically evaluating the endochondral ossification, stage of development, and microscopic potential for normal growth. METHODS: Three fetuses between 28 and 30 weeks of gestation, one with classic bladder exstrophy, one with cloacal exstrophy, and one control, were obtained from France. The bony pelves were dissected and preserved in formalin, and multiple representative sections were sliced from all pelvic areas: pubis, ischium, ilium, and sacrum. These slices were sequentially processed as slides, stained with hematoxylin-eosin, and evaluated microscopically for histologic changes, developmental stage, and degree of endochondral ossification. RESULTS: All slides from the three specimens showed cartilage analogue with endochondral ossification. Histologically the exstrophy specimens were identical to the control and appeared completely normal; bone development was occurring at an expected rate with the potential for continued normal growth. CONCLUSIONS: These new findings illustrate that fetal bone in the exstrophy complex displays normal microscopic growth patterns and unhindered endochondral ossification at 28 weeks of gestation, well beyond the embryologic period. With no evident microscopic bony defect, the gross bony anomalies in exstrophy should be surgically correctable, leading us to conclude that early reapproximation of the physiologic shape of the pelvis could lead to more normal gross bone growth, decreased shortage of bone, and a more appropriate distribution of the mechanical and developmental forces on a closed, normally functioning pelvic ring.

Sirenomelia sequence according to the distance between the first sacral vertebra and the ilia.

The development of the iliac bones and lower limbs are parallel processes depending on the normal ontogeny of the caudal blastema [O'Rahilly and Müller, 1989; Opitz, 1993; Opitz et al., 2000]. We hypothesized that the pathogenetic mechanisms leading to fused lower limbs would in parallel displace the ilia caudally and medially and that the degree of this displacement might correlate with the severity of the iliac and lower limb defects. Thus the purpose of the study was to test this hypothesis in a sample of 12 sirenomelic fetuses. The fetuses GA 16-39 weeks, spontaneously or therapeutically aborted, were radiographed in the frontal projection as part of a requested autopsy. From each radiograph, a line was drawn connecting the most cranial part or the two ilia. After that the distance was measured vertically between this line and the most cranial part of the first sacral vertebral body (iliac-sacral distance (ISD)). A second distance was measured horizontally between the most lateral part of the two iliae (bi-iliac distance (BD)). As a result, ISD correlates with the iliac/femur phenotype. Separate ilia and femora occur only in cases with normal ISD. Fused ilia or femora or both are seen only in fetuses with mildly increased ISD, whereas a single iliac bone and femur occur only in cases with greatly increased ISD. The increase of the ISD does not correlate with the severity of more distal limb involvement. There was a correlation between the ISD and the BD values; the higher the ISD, the shorter the BD. Based on these findings, we propose an extended classification of Sirenomelia to be tested by other researchers.

Sharing of the same embryogenic pathway in anorectal malformations and anterior sacral myelomeningocele formation.

The objective of this study was to determine whether anorectal malformations (ARMs) and anterior sacral myelomeningocele share the same embryogenic pathway in a mouse model. Etretinate (Ro 10-9359) was administrated to C57BL/6 mice on gestation day 9 (E9). Sections of embryos and fetuses from E9.5 to E18 were observed by HE staining. Immunohistochemical staining with anti-NeuN and anti-GFAP was also done to determine cell origins of a presacral mass. In etretinate-treated embryos, neuroepithelial cells proliferated in the presacral region on E9.5. On E12, a canal appeared between the ectopic proliferated neuroepithelium and hindgut. On E13, anorectum abnormally kept a canal with the ventral urogenital tract through a fistula. On E13.5, a huge mass formed in the presacral region. On E18, 76.9% (30/39) of fetuses had ARMs, 100% (39/39) had a presacral mass (71.8% were huge) and 100% (39/39) had a sacral defect. The types of ARMs were mainly rectourethral or rectocloacal fistula. The presacral mass was anterior sacral myelomeningocele. We thus established the first mouse model of the Currarino triad, congenital caudal anomalies, including ARM, sacral abnormality and presacral mass. These disorders share the same embryogenic pathway. The teratogenic target of etretinate is the tail bud. Abnormal differentiation of the tail bud mesenchyme leads to defects of the tailgut and caudal neural tube. The abnormal mass blocks normal descent of the dorsal cloaca through the most posterior part of the cloacal plate.

Anatomy of the sacrum.

One of the basic tenets of performing surgery is knowledge of the relevant anatomy. Surgeons incorporate this knowledge along with factors, such as biomechanics and physiology, to develop their operative approaches and procedures. In the diagnosis and management of sacral tumors, the need to be familiar with the anatomy of the sacrum is no less important than knowledge of the pathological entity involved. This article will provide an overview of the embryology and anatomy of the sacrum, along with concepts as applied to surgical intervention.