The Craniofacial Skeleton in Anencephalic Human Fetuses II. CALVARIUM JAMES D. GAROL, HENRY W. FIELDS, JR., LOUIS METZNER AND VINCENT G. KOKICH Department ofOrthodontics, School ofDentistrv, Uniuersitv o f Washington. Seattle, Washington 981 95
ABSTRACT A detailed study of the calvarium of twelve anencephalic and four normal human fetuses 26 to 40 weeks gestational age using gross dissection, alizarin red S staining, silver nitrate radiography and histology revealed dramatic alterations in the presence, form, location and relationship of the individual bones. In the larger dorsal cranial defects the interparietal portions of the occipital bone were relocated anteriorly to approximate the frontal bone. The occipital components were rotated anterolaterally and inferiorly with lack of fusion of the chondrocranium posterior to the foramen magnum. The squamae of the frontal bone were collapsed horizontally and reduced in size to lie peripheral to the anterior cranial fossa forming most of the orbital roofs. In anencephaly the bones derived from the chondrocranium were not as severely affected morphologically as those derived from the neurocranium. The sutures were narrow and smooth instead of wide and serrated as in the normally developing calvarium. In general the degree of maldevelopment was proportional to the extent of the dorsal cranial defect in anencephaly. Anencephaly produces its greatest effect on the calvarium. Although the details of pathogenesis are unclear, much is known of the morphology in anencephaly. The purpose of this paper is to analyze the development of the neurocranium in human fetuses with regard to the alteration in the form and relationships of the bony components, and to compare specimens showing varying degrees of severity in anencephaly. The cranial floor and the facial skeleton are described in accompanying articles (Fields e t al., '78; Metzner e t al., '78). MATERIALS AND METHODS
Twelve human anencephalic specimens were chosen for study from a sample of 28 specimens 26 to 40 weeks gestational age on the basis of preservation, age, and extent of dorsal cranial defect. The specimens were classified and grouped as follows: meroacrania, a cranial defect not involving the foramen magnum; holoacrania, a cranial defect involving the foramen magnum; and holoacrania with rachischisis, a cranial defect involving the foramen magnum and extending into the vertebral column. Four normal fetuses of comparable gestational ages were chosen for comparison. TERATOLOGY(1978)17: 67-74.
The specimens were photographed, decapitated, dissected and sectioned sagittally one half impregnated with silver nitrate for radiographic analysis and the other half stained with alizarin red S for three-dimensional study. Tissue blocks were taken from selected areas for serial histologic sectioning. For a complete description of the sample and methodology see the initial article of the series (Fields et al., '78). RESULTS
Since the degree of maldevelopment of the calvarium was generally related to the extent of the dorsal cranial defect in anencephaly, i t is appropriate to present the observations under the following subheadings: meroacrania, holoacrania, and holoacrania with rachischisis. Meroacrania The size of the calvarial defect in the fetuses with meroacrania ranged from approximately one centimeter to several centimeters in diameter, the latter exposing the entire cranial floor. The opening in the calvarium was consistently bordered anteriorly by the fronReceived June 7, '71. Accepted Oct. 18, ' 7 1 .
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tal bone, laterally by the parietal or squamous temporal bones, and posteriorly by the parietal or occipital bones, depending on the size of the defect (fig. l b ) . As the size of the calvarial defect increased, t h e size, shape, and spatial orientation of the calvarial bones were more severely altered relative to the normal. In most specimens with meroacrania t h e frontal and parietal bones assumed a horizontal orientation and sloped posteroinferiorly and laterally (fig. 2b). The frontal bone extended posteriorly to cover the anterior cranial fossa, laterally to articulate with t h e greater wing of t h e sphenoid and anteriorly to articulate with t h e nasal bones, while t h e parietal bones covered t h e middle and posterior cranial fossae. The occipital and squamous temporal bones assumed a vertial orientation and t h e interparietal portion of the occipital curved anteriorly (fig. 2b). In the most severely affected specimen t h e parietal bones were absent. The frontal bones diverged laterally anterior to crista galli and extended posterolaterally until they approximated t h e squamous temporal bone. The occipital bone assumed a nearly horizontal orientation. All cranial sutures, including the metopic suture, were present, but their length and orientation were variably altered, depending on the extent of t h e calvarial defect. In addition, all sutures appeared to be narrower t h a n normal. Radiographically, t h e sutural margin of specimens with meroacrania was smooth, while the control sutures exhibited a serrated bony margin. The anterolateral and posterolateral fontanelles were reduced in size. Two dense layers of fibrous connective tissue were found between t h e frontal bone and the floor of the anterior cranial fossa (fig. 3). A third more delicate intermediate layer of fibrous tissue with numerqus neural cells and large vascular lumina lay between the dense layers. No normal cerebral structures were apparent within these layers under histologic examination.
Holoacrania In specimens with holoacrania the calvarial opening was extremely large and exposed the entire floor of t h e cranium. The defect was bounded anteriorly by t h e frontal bone, posteriorly by t h e first cervical vertebra and laterally by t h e nonfused halves of t h e occipital bone. The structures posterior to the foramen magnum diverged laterally (fig. lc). From a
superior view the cranium was generally triangular in shape with t h e apex pointing anteriorly. The anteroposterior and lateral dimensions of the skull were greatly reduced compared to the control. The normal cutaneous covering of the bones changed abruptly to a dark spongy mass of hemorrhagic, fibrovascular tissue superior to t h e cranial defect. Posteriorly t h e neck appeared both wider and shorter than in t h e control. The squamous skeletal components of the neurocranium were markedly reduced in size. The right and left parietal bones were absent in all but one specimen with holoacrania. The remaining bones were oriented in a horizontal plane from anterosuperior to posteroinferior a t the level of t h e cranial floor (fig. 2c). The occipital bone was divided sagittally posterior to the foramen magnum. Each half of the occipital bone was composed of three portions the exoccipital, t h e supraoccipital and the interparietal. The supraoccipital and interparietal components were fused in all specimens examined (fig. 4a). The exoccipital portion was reduced in size, was located further posterolaterally and sloped posteroinferiorly compared to t h e normal. The interparietal component tapered anteriorly and approximated the frontal bone just superior to the squamous portion of the temporal bone (figs. 5, 6). A condensed layer of fibrous connective tissue lay between these three structures (figs. 4b,c, 5b).
Holoacrania with rachischisis In these specimens t h e most severe alterations in calvarial size and morphology were found in the posterior portion of the cranium. The schisis was wider and t h e exoccipital portions of the occipital bone were rotated further laterally (fig. Id). I n addition, the supraoccipital and interparietal components were located more anteriorly compared to specimens without rachischisis. In general, the remaining calvarial bones in specimens with rachischisis sloped more laterally and posteriorly (fig. 2d). In one of the specimens remnants of the parietal bones were found between t h e interparietal portions of t h e occipital bone and t h e frontal bones. In t h e remaining specimens, the parietal bone was absent. The squamous portion of the temporal bone was smaller compared to the specimens without rachischisis. The size, shape, and spatial orientation of the frontal bone was unchanged by t h e presence of rachischisis.
69
CALVARIUM IN ANENCEPHALY
Abbreviations
CF. cranial floor CT, dense fibrous connective tissue E. Exoccipital portion of the occipital bone F, Frontal bone ICT, immature connective tissue
IL, intermediate layer IP, Interparietal portion of the occipital bone P. Patietal hone SO, Supraoccipital portion of the occipital bone T, Temporal bone
C
d
n
Fig. 1 Tracings made from basilar radiographs with additional information obtained from alizarin preparations of normal and anencephalic skulls. a Normal fetal skull. b Fetal skull with meroacrania. Note the cranial defect between the parietal bones, the presence of the frontoparietal suture, and the transverse constriction of the cranium between the temporal bones. c Fetal skull with holoacrania. Note the widely separated supraoccipital portions of the occipital bone which lie posterior to the exoccipital portions. The interparietal portions of the occipital bone are positioned anterolaterally and approximate the frontal bone. d Fetal skull with holoacrania and rachischisis. Note the more lateral position of the supraoccipital portion of the occipital bone relative to the exoccipital portion when compared to holoacrania k). The interparietal portion of the occipital bone approximates the frontal bone as in holoacrania.
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C
Fig. 2 Tracings made from lateral radiographs with additional information obtained from alizarin preparations of normal and anencephalic skulls. a Normal fetal skull. b Fetal skull with meroacrania showing collapsed neurocranium with a horizontally oriented frontal bone, reduced size of parietal and squamous temporal bones and vertically oriented supraoccipital portion of the occipital bone. c Fetal skull with holoacrania. Note the frontal, temporal, and interparietal and supraoccipital portions of the occipital bone are reduced in size. These bones have a posteroinferior inclination and the interparietal portion of the occipital bone approximates the frontal bone. The parietal bone is absent. d Fetal skull with holoacrania and rachischisis. Note the similar orientations of the bones and the absence of the parietal bone as in holoacrania.
The morphologic and spatial alterations of the vertebrae in specimens with rachischisis were similar to those seen in the components of the occipital bone. The arches of affected vertebrae were not fused dorsally and were rotated laterally. DISCUSSION
The discussion will be limited to the main features characterizing t h e calvarium in anencephaly. Of major concern here a r e changes in shape, location and relationship of
the frontal bone and components of the occipital bone. One of the most dramatic changes in the bones of the calvarium is the relocation of the interparietal portion of the occipital bone in holoacrania. This component appeared as a long tapering process located lateral to the cranial floor and extended anteriorly from the supraoccipital portion of the occipital bone to approximate the frontal bone. In previous descriptions it has been identified as the parietal bone by de Beer ('37) and Marin-Padilla ('65).
CALVARIUM IN ANENCEPHALY
Fig. 3 The anterior cranial fossa of a fetal skull with meroacrania (sagittal section). Note the intermediate layer of loose fibrous tissue with many cell nuclei between the dense fibrous connective tissue layers. This tissue is between the posteriorly collapsedfrontal bone (F) and the cranial floor (CF) x 10.
However, in all but one case in the present study, the parietal bone was absent in this group. In the exception it was small and located just medial to the squamous portion of the temporal bone and anterior to the interparietal portion of the occipital bone. Two developmental events may explain relocation of the interparietals: the incomplete formation of the membranous neurocranium or meninx, resulting in the lack of dorsal fusion of the interparietal components; and the subsequent collapse of the abnormally developing vault secondary to the degeneration of the brain. The interparietal component is then probably pulled laterally by the pe-
71
ripheral attachment of the meninx to the chondrocranium. Just as dramatic as the relocation of the interparietal portion of the occipital bone are the changes which occur with lack of fusion of the posterior chondrocranium in holoacrania. The occipital components which normally lie posterior to the foramen magnum are rotated anterolaterally and inferiorly in proportion to the extent of the neural defect. Marin-Padilla ('70) suggested that this lack of union of the posterior chondrocranium might be explained by incomplete migration of mesoderm dorsal to the neural tube. The rotation of the posterior chondrocranium may result from the remaining intact anterior fibrous connective tissue envelope and the influence of the capitus muscles due to their insertions on the nonfused supraoccipital components. The frontal bone is also severely affected by anencephaly. In holoacrania the squamae, still joined medially by the metopic suture, are collapsed horizontally and lie peripheral to the cranial floor superior to the orbits. Other investigators have not recognized the frontal squamae and have mistakenly identified them as orbital plates (de Beer, '37; Marin-Padilla, '65). The present findings indicate that the orbital plates are extremely rudimentary and that after degeneration of the brain most of the orbital roofs are comprised of the frontal squamae. The supraoccipital portions of the occipital bone derived from the chondrocranium more
Fig. 4 Selected serial coronal sections of the interparietal portion of the occipital bone in holoacrania. a Posterior section. Note the area of bony fusion between interparietal UP) and supraoccipital (SO) portions of the occipital bone. X 50. b Middle section. The cartilaginous temporal bone (T) and interparietal portion of the occipital bone (IP) are in close approximation and separated by dense fibrous connective tissue (CT). X 10. c Anterior section. Note the cartilaginous temporal bone (T)and interparietal portion of the occipital bone (IP) with the intervening dense fibrous connective tissue (CT). x 10.
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Fig. 5a Frontoparietal suture of a normal fetal specimen demonstrating the immature fibrous connective tissue (ICT) ligament. Note the horizontal orientation of the fibers across the sutural interval. x 15. b Approximation of the frontal bone (F)with the interparietal portion of the supraoccipital bone in an anencephalic specimen with holacrania. Note the oblique orientation of the dense fibrous connective tissue (CT) between these bones. This orientation is unrepresentative of a normal sutural articulation. X 50.
Fig. 6 Dry skull preparation showing the fusion of the supraoccipital (SO) and interparietal (IP) portions of the occipital bone posteriorly and the approximation of the interparietal portion of t h e occipital bone with the frontal bone (F) anteriorly. X 1.25.
closely resemble those in the control specimens while the membranous interparietal, frontal and parietal bones are markedly altered in form and location in anencephaly. The membranous neurocraniurn, unlike the chondrocranium, is too pliable to be self-supporting. Its position is dependent, therefore, on the underlying brain and on its attachment to the cranial base.
In addition to the dramatic changes seen in the form and location of the ossified structures, significant alterations were apparent in the structure of the fibrous sutures. The abnormal sutures were narrow and smooth instead of wide and serrated as in the normally growing calvarium. de Beer ('37)showed by contrasting cases of hydrocephaly and microcephaly that the rate of growth influences the distance between the developing membranous bones and the orientation of the growing bony spicules. The sutural changes in anencephaly are consistent with a lack of normal expansion of the neural contents. The morphology of the calvarium in anencephaly has been investigated in detail. The findings of the present study indicate that abnormal development of the brain has a direct effect on the membranous envelope of the neurocranium, the structures of the chondrocranium and adjacent vertebrae. These alterations result in secondary changes in the presence, form, and orientation of all calvarial bones. The degree of maldevelopment is proportional to the extent of the dorsal cranial defect in anencephaly. ACKNOWLEDGMENTS
Grateful acknowledgments are due to Doctor Benjamin C. Moffett for guidance and for assistance in the preparation of the manuscript; Doctors Ronald J. Lemire and J. Bruce Beckwith for making available a large
CALVARIUM IN ANENCEPHALY
sample of well documented specimens; and to M ~ ~~ . i ~~l~~~ ~ for i her ~ technical assistThis research was by Health Service Research Grant DE 02931 and the University of Washington Orthondontic Memorial Fund. LITERATURE CITED de Beer, G. R. 1937 The Development of the Vertebrate Skull. Clarendon Press, Oxford, pp. 484-486.
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Fields, H. W. Jr., L. Metzner, J. D. Garol and V. G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. I. Cranial floor. Teratology, 17: 57-66. Marin-Padilla, M. 1965 Study of the skull in human cranioschisis. Acts anat.. 62: 1-20. - 1970 Morphogenesis of anencephaly and related malformations. Curr. Top. Pathol., 51: 145-174. Metzner, L., J. D. Garol, H. W. Fields, Jr. and Vincent G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. 111. Facial skeleton. Teratology, 17; 75-82.
ABSTRACT A detailed study of the calvarium of twelve anencephalic and four normal human fetuses 26 to 40 weeks gestational age using gross dissection, alizarin red S staining, silver nitrate radiography and histology revealed dramatic alterations in the presence, form, location and relationship of the individual bones. In the larger dorsal cranial defects the interparietal portions of the occipital bone were relocated anteriorly to approximate the frontal bone. The occipital components were rotated anterolaterally and inferiorly with lack of fusion of the chondrocranium posterior to the foramen magnum. The squamae of the frontal bone were collapsed horizontally and reduced in size to lie peripheral to the anterior cranial fossa forming most of the orbital roofs. In anencephaly the bones derived from the chondrocranium were not as severely affected morphologically as those derived from the neurocranium. The sutures were narrow and smooth instead of wide and serrated as in the normally developing calvarium. In general the degree of maldevelopment was proportional to the extent of the dorsal cranial defect in anencephaly. Anencephaly produces its greatest effect on the calvarium. Although the details of pathogenesis are unclear, much is known of the morphology in anencephaly. The purpose of this paper is to analyze the development of the neurocranium in human fetuses with regard to the alteration in the form and relationships of the bony components, and to compare specimens showing varying degrees of severity in anencephaly. The cranial floor and the facial skeleton are described in accompanying articles (Fields e t al., '78; Metzner e t al., '78). MATERIALS AND METHODS
Twelve human anencephalic specimens were chosen for study from a sample of 28 specimens 26 to 40 weeks gestational age on the basis of preservation, age, and extent of dorsal cranial defect. The specimens were classified and grouped as follows: meroacrania, a cranial defect not involving the foramen magnum; holoacrania, a cranial defect involving the foramen magnum; and holoacrania with rachischisis, a cranial defect involving the foramen magnum and extending into the vertebral column. Four normal fetuses of comparable gestational ages were chosen for comparison. TERATOLOGY(1978)17: 67-74.
The specimens were photographed, decapitated, dissected and sectioned sagittally one half impregnated with silver nitrate for radiographic analysis and the other half stained with alizarin red S for three-dimensional study. Tissue blocks were taken from selected areas for serial histologic sectioning. For a complete description of the sample and methodology see the initial article of the series (Fields et al., '78). RESULTS
Since the degree of maldevelopment of the calvarium was generally related to the extent of the dorsal cranial defect in anencephaly, i t is appropriate to present the observations under the following subheadings: meroacrania, holoacrania, and holoacrania with rachischisis. Meroacrania The size of the calvarial defect in the fetuses with meroacrania ranged from approximately one centimeter to several centimeters in diameter, the latter exposing the entire cranial floor. The opening in the calvarium was consistently bordered anteriorly by the fronReceived June 7, '71. Accepted Oct. 18, ' 7 1 .
67
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J. GAROL, H. FIELDS, JR., L. METZNER AND V. KOKICH
tal bone, laterally by the parietal or squamous temporal bones, and posteriorly by the parietal or occipital bones, depending on the size of the defect (fig. l b ) . As the size of the calvarial defect increased, t h e size, shape, and spatial orientation of the calvarial bones were more severely altered relative to the normal. In most specimens with meroacrania t h e frontal and parietal bones assumed a horizontal orientation and sloped posteroinferiorly and laterally (fig. 2b). The frontal bone extended posteriorly to cover the anterior cranial fossa, laterally to articulate with t h e greater wing of t h e sphenoid and anteriorly to articulate with t h e nasal bones, while t h e parietal bones covered t h e middle and posterior cranial fossae. The occipital and squamous temporal bones assumed a vertial orientation and t h e interparietal portion of the occipital curved anteriorly (fig. 2b). In the most severely affected specimen t h e parietal bones were absent. The frontal bones diverged laterally anterior to crista galli and extended posterolaterally until they approximated t h e squamous temporal bone. The occipital bone assumed a nearly horizontal orientation. All cranial sutures, including the metopic suture, were present, but their length and orientation were variably altered, depending on the extent of t h e calvarial defect. In addition, all sutures appeared to be narrower t h a n normal. Radiographically, t h e sutural margin of specimens with meroacrania was smooth, while the control sutures exhibited a serrated bony margin. The anterolateral and posterolateral fontanelles were reduced in size. Two dense layers of fibrous connective tissue were found between t h e frontal bone and the floor of the anterior cranial fossa (fig. 3). A third more delicate intermediate layer of fibrous tissue with numerqus neural cells and large vascular lumina lay between the dense layers. No normal cerebral structures were apparent within these layers under histologic examination.
Holoacrania In specimens with holoacrania the calvarial opening was extremely large and exposed the entire floor of t h e cranium. The defect was bounded anteriorly by t h e frontal bone, posteriorly by t h e first cervical vertebra and laterally by t h e nonfused halves of t h e occipital bone. The structures posterior to the foramen magnum diverged laterally (fig. lc). From a
superior view the cranium was generally triangular in shape with t h e apex pointing anteriorly. The anteroposterior and lateral dimensions of the skull were greatly reduced compared to the control. The normal cutaneous covering of the bones changed abruptly to a dark spongy mass of hemorrhagic, fibrovascular tissue superior to t h e cranial defect. Posteriorly t h e neck appeared both wider and shorter than in t h e control. The squamous skeletal components of the neurocranium were markedly reduced in size. The right and left parietal bones were absent in all but one specimen with holoacrania. The remaining bones were oriented in a horizontal plane from anterosuperior to posteroinferior a t the level of t h e cranial floor (fig. 2c). The occipital bone was divided sagittally posterior to the foramen magnum. Each half of the occipital bone was composed of three portions the exoccipital, t h e supraoccipital and the interparietal. The supraoccipital and interparietal components were fused in all specimens examined (fig. 4a). The exoccipital portion was reduced in size, was located further posterolaterally and sloped posteroinferiorly compared to t h e normal. The interparietal component tapered anteriorly and approximated the frontal bone just superior to the squamous portion of the temporal bone (figs. 5, 6). A condensed layer of fibrous connective tissue lay between these three structures (figs. 4b,c, 5b).
Holoacrania with rachischisis In these specimens t h e most severe alterations in calvarial size and morphology were found in the posterior portion of the cranium. The schisis was wider and t h e exoccipital portions of the occipital bone were rotated further laterally (fig. Id). I n addition, the supraoccipital and interparietal components were located more anteriorly compared to specimens without rachischisis. In general, the remaining calvarial bones in specimens with rachischisis sloped more laterally and posteriorly (fig. 2d). In one of the specimens remnants of the parietal bones were found between t h e interparietal portions of t h e occipital bone and t h e frontal bones. In t h e remaining specimens, the parietal bone was absent. The squamous portion of the temporal bone was smaller compared to the specimens without rachischisis. The size, shape, and spatial orientation of the frontal bone was unchanged by t h e presence of rachischisis.
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Abbreviations
CF. cranial floor CT, dense fibrous connective tissue E. Exoccipital portion of the occipital bone F, Frontal bone ICT, immature connective tissue
IL, intermediate layer IP, Interparietal portion of the occipital bone P. Patietal hone SO, Supraoccipital portion of the occipital bone T, Temporal bone
C
d
n
Fig. 1 Tracings made from basilar radiographs with additional information obtained from alizarin preparations of normal and anencephalic skulls. a Normal fetal skull. b Fetal skull with meroacrania. Note the cranial defect between the parietal bones, the presence of the frontoparietal suture, and the transverse constriction of the cranium between the temporal bones. c Fetal skull with holoacrania. Note the widely separated supraoccipital portions of the occipital bone which lie posterior to the exoccipital portions. The interparietal portions of the occipital bone are positioned anterolaterally and approximate the frontal bone. d Fetal skull with holoacrania and rachischisis. Note the more lateral position of the supraoccipital portion of the occipital bone relative to the exoccipital portion when compared to holoacrania k). The interparietal portion of the occipital bone approximates the frontal bone as in holoacrania.
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C
Fig. 2 Tracings made from lateral radiographs with additional information obtained from alizarin preparations of normal and anencephalic skulls. a Normal fetal skull. b Fetal skull with meroacrania showing collapsed neurocranium with a horizontally oriented frontal bone, reduced size of parietal and squamous temporal bones and vertically oriented supraoccipital portion of the occipital bone. c Fetal skull with holoacrania. Note the frontal, temporal, and interparietal and supraoccipital portions of the occipital bone are reduced in size. These bones have a posteroinferior inclination and the interparietal portion of the occipital bone approximates the frontal bone. The parietal bone is absent. d Fetal skull with holoacrania and rachischisis. Note the similar orientations of the bones and the absence of the parietal bone as in holoacrania.
The morphologic and spatial alterations of the vertebrae in specimens with rachischisis were similar to those seen in the components of the occipital bone. The arches of affected vertebrae were not fused dorsally and were rotated laterally. DISCUSSION
The discussion will be limited to the main features characterizing t h e calvarium in anencephaly. Of major concern here a r e changes in shape, location and relationship of
the frontal bone and components of the occipital bone. One of the most dramatic changes in the bones of the calvarium is the relocation of the interparietal portion of the occipital bone in holoacrania. This component appeared as a long tapering process located lateral to the cranial floor and extended anteriorly from the supraoccipital portion of the occipital bone to approximate the frontal bone. In previous descriptions it has been identified as the parietal bone by de Beer ('37) and Marin-Padilla ('65).
CALVARIUM IN ANENCEPHALY
Fig. 3 The anterior cranial fossa of a fetal skull with meroacrania (sagittal section). Note the intermediate layer of loose fibrous tissue with many cell nuclei between the dense fibrous connective tissue layers. This tissue is between the posteriorly collapsedfrontal bone (F) and the cranial floor (CF) x 10.
However, in all but one case in the present study, the parietal bone was absent in this group. In the exception it was small and located just medial to the squamous portion of the temporal bone and anterior to the interparietal portion of the occipital bone. Two developmental events may explain relocation of the interparietals: the incomplete formation of the membranous neurocranium or meninx, resulting in the lack of dorsal fusion of the interparietal components; and the subsequent collapse of the abnormally developing vault secondary to the degeneration of the brain. The interparietal component is then probably pulled laterally by the pe-
71
ripheral attachment of the meninx to the chondrocranium. Just as dramatic as the relocation of the interparietal portion of the occipital bone are the changes which occur with lack of fusion of the posterior chondrocranium in holoacrania. The occipital components which normally lie posterior to the foramen magnum are rotated anterolaterally and inferiorly in proportion to the extent of the neural defect. Marin-Padilla ('70) suggested that this lack of union of the posterior chondrocranium might be explained by incomplete migration of mesoderm dorsal to the neural tube. The rotation of the posterior chondrocranium may result from the remaining intact anterior fibrous connective tissue envelope and the influence of the capitus muscles due to their insertions on the nonfused supraoccipital components. The frontal bone is also severely affected by anencephaly. In holoacrania the squamae, still joined medially by the metopic suture, are collapsed horizontally and lie peripheral to the cranial floor superior to the orbits. Other investigators have not recognized the frontal squamae and have mistakenly identified them as orbital plates (de Beer, '37; Marin-Padilla, '65). The present findings indicate that the orbital plates are extremely rudimentary and that after degeneration of the brain most of the orbital roofs are comprised of the frontal squamae. The supraoccipital portions of the occipital bone derived from the chondrocranium more
Fig. 4 Selected serial coronal sections of the interparietal portion of the occipital bone in holoacrania. a Posterior section. Note the area of bony fusion between interparietal UP) and supraoccipital (SO) portions of the occipital bone. X 50. b Middle section. The cartilaginous temporal bone (T) and interparietal portion of the occipital bone (IP) are in close approximation and separated by dense fibrous connective tissue (CT). X 10. c Anterior section. Note the cartilaginous temporal bone (T)and interparietal portion of the occipital bone (IP) with the intervening dense fibrous connective tissue (CT). x 10.
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Fig. 5a Frontoparietal suture of a normal fetal specimen demonstrating the immature fibrous connective tissue (ICT) ligament. Note the horizontal orientation of the fibers across the sutural interval. x 15. b Approximation of the frontal bone (F)with the interparietal portion of the supraoccipital bone in an anencephalic specimen with holacrania. Note the oblique orientation of the dense fibrous connective tissue (CT) between these bones. This orientation is unrepresentative of a normal sutural articulation. X 50.
Fig. 6 Dry skull preparation showing the fusion of the supraoccipital (SO) and interparietal (IP) portions of the occipital bone posteriorly and the approximation of the interparietal portion of t h e occipital bone with the frontal bone (F) anteriorly. X 1.25.
closely resemble those in the control specimens while the membranous interparietal, frontal and parietal bones are markedly altered in form and location in anencephaly. The membranous neurocraniurn, unlike the chondrocranium, is too pliable to be self-supporting. Its position is dependent, therefore, on the underlying brain and on its attachment to the cranial base.
In addition to the dramatic changes seen in the form and location of the ossified structures, significant alterations were apparent in the structure of the fibrous sutures. The abnormal sutures were narrow and smooth instead of wide and serrated as in the normally growing calvarium. de Beer ('37)showed by contrasting cases of hydrocephaly and microcephaly that the rate of growth influences the distance between the developing membranous bones and the orientation of the growing bony spicules. The sutural changes in anencephaly are consistent with a lack of normal expansion of the neural contents. The morphology of the calvarium in anencephaly has been investigated in detail. The findings of the present study indicate that abnormal development of the brain has a direct effect on the membranous envelope of the neurocranium, the structures of the chondrocranium and adjacent vertebrae. These alterations result in secondary changes in the presence, form, and orientation of all calvarial bones. The degree of maldevelopment is proportional to the extent of the dorsal cranial defect in anencephaly. ACKNOWLEDGMENTS
Grateful acknowledgments are due to Doctor Benjamin C. Moffett for guidance and for assistance in the preparation of the manuscript; Doctors Ronald J. Lemire and J. Bruce Beckwith for making available a large
CALVARIUM IN ANENCEPHALY
sample of well documented specimens; and to M ~ ~~ . i ~~l~~~ ~ for i her ~ technical assistThis research was by Health Service Research Grant DE 02931 and the University of Washington Orthondontic Memorial Fund. LITERATURE CITED de Beer, G. R. 1937 The Development of the Vertebrate Skull. Clarendon Press, Oxford, pp. 484-486.
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Fields, H. W. Jr., L. Metzner, J. D. Garol and V. G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. I. Cranial floor. Teratology, 17: 57-66. Marin-Padilla, M. 1965 Study of the skull in human cranioschisis. Acts anat.. 62: 1-20. - 1970 Morphogenesis of anencephaly and related malformations. Curr. Top. Pathol., 51: 145-174. Metzner, L., J. D. Garol, H. W. Fields, Jr. and Vincent G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. 111. Facial skeleton. Teratology, 17; 75-82.
