The Craniofacial Skeleton in Anencephalic Human Fetuses I. CRANIAL FLOOR HENRY W. FIELDS, JR., LOUIS METZNER. JAMES D. GAROL AND VINCENT G. KOKICH Department oforthodontics, School ofDentistry, University of Washington, Seattle, Washington 98195
ABSTRACT
Twelve anencephalic and four normal fetuses 26 to 40 weeks gestational age were compared by anatomic, radiographic and histologic methods in order to gain information concerning morphogenesis. In the anencephalics, alterations located within the body of the sphenoid bone led to a reduced cranial floor angle and a more vertical clivus. The reduced lateral extension of the lesser and greater wings of the sphenoid constricted the anterior and middle cranial fossae respectively. The posterior cranial fossa tended to have an increased transverse dimension related to the supraoccipital and exoccipital bone orientation. The increased anterior and inferior position of the lateral end of the petrous temporal ridge was positively correlated with the degree of dorsal schisis in the anencephalics. Alterations in the size, form, or duration of the neural functional matrix are suggested as the cause of changes in the cranial floor.
Anencephaly is a common lethal defect with pronounced effects that can readily be described over its full range of severity. Thus, it serves a s a natural experiment for studying the normal and abnormal development of the skull. Earlier investigations fall into three categories: epidemiologic studies aimed a t etiology (Stevenson et al., '66; Naggan and MacMahon, '67); anatomic (Abd-El-Malek, '57; Keen, '63; Marin-Padilla, '65a,b) and embryologic (Dekaban, '63; Padget, '70) studies aimed a t morphology; and animal studies aimed a t pathogenesis (Giroud, '60; MarinPadilla and Ferm, '65; Langman and Welch, '66). The present study will compare craniofacial skeletal development in normal and anencephalic fetuses using a combination of anatomic, radiographic, and histologic techniques. The purpose of the study is to analyze the morphologic result of this developmental anomaly. Hopefully, these techniques will give additional information concerning craniofacial morphogenesis. This article describes the cranial floor. The articles which follow will deal with the calvarium (Garol e t al., '78) and the facial skeleton (Metzner e t al., '78). MATERIALS AND METHODS
Twelve anencephalic fetuses were chosen TERATOLOGY (1978) 17: 57-66.
for study from a sample of 28 specimens, 26 to 40 weeks gestational age, based on quality of preservation, age, and extent of the dorsal cranial defect (table 1). The gestational ages were determined according to foot length (Streeter, '20; Naiiagas, '25; Trolle, '48). The dorsal cranial defects were classified 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 (Lemire e t al., '77). Four fetuses of similar age with no malformations of the head and neck were chosen as controls. All fetuses were preserved in 10%formalin. After decapitation, each of the 12 specimens was examined grossly, photographed, and radiographed. Soft tissue was then dissected from the skeletal structures leaving the periosteum intact, and the heads were divided in a parasagittal plane to preserve the midline structures for histologic evaluation. In order to show the ossification centers and improve the quality of the radiographs, the larger portion containing the midline structures was impregnated with 0.5%aqueous silver nitrate (Hodges, '53) and radiographed (fig. 1). The Received June 7, '71. Accepted Oct. 18. '77.
57
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H. FIELDS, JR., L. METZNER, J. GAROL AND V. KOKICH
b
a
Fig. 1 Lateral radiographs of the parasagittally sectioned skulls of (a) a normal fetus (1658)and (b) a fetus with holoacrania (AN47) following silver nitrate impregnation. Note the well defined ossification centers and the increased detail yielded by this methodology.
midline structures were then removed from this larger section in a 5- to 7-mm thick sagittal slab and radiographed. Tissue blocks from any region containing anomalous structures were removed, decalcified, double embedded, and stained with hematoxylin and eosin, Mallory's aniline blue collagen stain, periodicacid Schiff s reagent, and Verhoeff s elastic stain after clearing of the silver nitrate (Molnar, '74, '75a,b,c, '76). Corresponding tissue blocks were obtained from the control specimens. The remainder of each specimen was stained with alizarin red S and examined as a cleared preparation. Tracings of t h e radiographs were made on acetate paper to illustrate bony contours and relationships. Dry skull preparation of two fetuses was made following dissection of t h e soft tissue. The skulls were air dried at 50°C for 48 hours. The dried periosteum held t h e bones in position for study. RESULTS
The observations will emphasize anatomic relationships in t h e three cranial fossae and t h e individual articular and skeletal compo-
nents which comprise the cranial floor. First t h e general configuration of the cranial floor will be described, followed by the articular relationships which account for these configurations. Then changes in the skeletal components will be reported. For each of these aspects a brief baseline description will be made of t h e normal specimens. Comparable observations will be presented for specimens with increasing severity of anencephaly ranging from meroacrania to holoacrania with rachischisis. The observations will proceed from the less variable anterior cranial structures to the more affected and variable posterior cranial structures. All specimens were in the gestational age range of 26- to 40 weeks. General configuration of the cranial floor In normal specimens viewed from above, the cranial floor had a n ovoid shape (fig. 2a). This gave a semicircular contour to the anterior and posterior cranial fossae with the intervening middle fossa having t h e greatest transverse dimension. The boundaries between the
59
CRANIAL FLOOR IN ANENCEPHALY
n
C Fig. 2 Schematic drawings of the cranial floor and configuration of the individual fossae in (a) a normal fetus (2537); (b) a fetus with meroacrania (AN10); and (c) a fetus with holoacrania (AN471 - superior view. Note the lateral constriction of the anterior cranial fossa (ACF) and middle cranial fossa (MCF) in the anencephalics. The increased lateral extension and anteroposterior constriction of the posterior cranial fossa (PCF) is also evident. In holoacrania the posterior cranial fossa exhibits schisis (arrows). TABLE 1
Sample of anencephalic and normal human fetuses used in this study Specimen number '
Anencephalic fetuses Meroacrania AN 50 AN 46 AN 10 AN 62 AN 30 Holoacrania AN 44 AN 47 AN 11 Holoacrania with rachischisis AN 1 AN 28 AN 13 AN 37 Normal fetuses H-2537 1658 H-2529 w-353 I
Foot length lmm)
Gestational age (weeks)
51 76 85 88 90
26.5' 1.5 37.0%2 40 40 40
58 60 61
29.5e 1 30.0' 2 31.02 2
60 60 75 86
30.02 2 30.0%2 36.5* 1.5 40
58 70 77 85
29.5%1 34.5e 2 37.5'2 40
Specimen numbers assigned and referred to by Lemire et al. ('771.
three fossae were sharply defined anatomically by bony contours and by the different cranial floor levels in each fossa. The boundary between t h e middle and posterior fossae was oriented 45" posterolaterally to the midline. The posterior fossa was the largest and deepest of the three with most of its area located lateral and posterior to the foramen magnum. In lateral view the cranial floor was most su-
perior in the anterior fossa and then gradually declined posteriorly to the foramen magnum (fig. 3a). Behind the foramen magnum the floor inclined superiorly, giving the posterior fossa its concave appearance. From a posterior view, the anterior cranial fossa was slightly concave; the midline structures were superior to the lateral structures in the middle cranial fossa; and the posterior fossa was deeply concave. The cranial floor in specimens with meroacrania changed from a n ovoid to a trapezoid shape with the narrow end located anteriorly (fig. 2b). This configuration was due to a decreased width in the anterior fossa and adjacent part of the middle fossa, as well as increased width in the posterior cranial fossa. The middle fossa was shallow anteriorly, and in front of its posterior boundary the floor was actually convex instead of concave. The boundary between the middle and posterior fossae was nearly perpendicular to the midline. The posterior fossa maintained the same width as the middle fossa instead of tapering posteriorly. In the lateral view, the floors of the anterior and middle fossae were on one level (fig. 3b). The depth of the posterior fossa was greatly increased by a n anterior wall which was sharply angulated inferiorly and by a vertical posterior wall. From the posterior view, the anterior fossa was flat and the midline structures were superior to the inferiorly sloping lateral part of the middle cranial fossa. The posterior fossa was concave due to the vertical lateral walls.
60
H. FIELDS, JR., L. METZNER, J . GAROL AND V. KOKICH Abbreviations B, Basiocciput E, Ethmoid EO, Exoccipital GW, Greater wing of the sphenoid
LW, Lesser wing of the sphenoid T, Petrous temporal S, Sphenoid SO, Supraoccipital V, Vomer
Fig. 3 Schematic drawings of the relationships of sagittal cranial floor structures in (a) a normal fetus (2537); (b) a fetus with meroacrania (ANlO); and (c) a fetus with holoacrania (AN47). All three drawings are oriented with t h e palatal plane horizontal. Note the concave (b) or irregular (c) pharyngeal surface of the sphenoid bone and the inferior angulation of the clivus (b and c) relative to the normal (a). The increased posterior height of the vomer and the enlarged nasopharynx (dashed line) are evident in the anencephalic fetuses. The supraoccipital is in a more vertical position in meroacrania (compare b to a ) , and not present in the midsagittal section in holoacrania (c).
In specimens with holoacrania and holoacrania with rachischisis, the cranial floor had a triangular configuration due to a narrowing of the anterior and middle fossae combined with a widening of the posterior fossa (fig. 2c). The border between the middle and posterior fossae was perpendicular to the midline. Behind the incomplete foramen magnum the posterior fossa was absent, but the lateral floor was present to a variable extent. As in the specimens with meroacrania, the anterior and middle fossae were on one level with the anterior wall of the posterior fossa sharply angulated inferiorly (fig. 3c). The posterior view showed a flat anterior fossa floor and superior midline structures in the middle fossa. From this perspective, the posterior fossa had no floor. Articular relationships In the normal specimens the floor of the an-
terior fossa was formed by the lateral extent of the orbital plate of the frontal bone. The posterior boundary of this fossa was delineated by the articulation of the lesser wing of the sphenoid with the orbital plate (fig. 4a). In the middle cranial fossa, the body of the sphenoid bone with its laterally extending wings formed most of the cranial floor. The posterior limits of this fossa was formed by the horizontal petrous ridge of the temporal bone traversing the cranial floor posterolaterally a t a 45" angle to the midline. The tympanic rings opened inferolaterally on the inferior surface of the petrous temporal bone. In the posterior cranial fossa the floor was formed partially by the exoccipital bones which lay lateral to the foramen magnum in a horizontal plane, and partially by the supraoccipital which was inclined superiorly from its articulation with the right and left exoccipital. The mean for the angle Nasion-Sella-Basion (which opens
61
CRANIAL FLOOR IN ANENCEPHALY
n
C Fig. 4 Schematic drawings of the bones of the cranial floor in (a) a normal fetus (2537);(b) a fetus with meroacrania (AN10); and (c) a fetus with holoacrania (AN47). Note the anteroposterior position of the lesser wings of the spenoid and the reduced transverse dimension of the greater wings of the sphenoid (band c ) relative to the normal (a). The more anterior position of the lateral end of the petrous portion of the temporal bone is also evident in anencephaly. In holoacrania the supraoccipital components are nonunited and widely divergent (c).
inferiorly) was 143.3't 4.7'. The 98% confidence interval lower limit was 132.3' and the upper limit was 153.7'. In the normal fetus the ethmoid was the most superior part of the cranial floor in a lateral view (fig. 3a). The cartilaginous interface between the sphenoid and ethmoid bones was oriented in a posterosuperior-anteroinferior plane. The anterior fossa in meroacrania was roofed and limited laterally by the underdeveloped squamous frontal bone (fig. 4b).The floor of the fossa was limited due to the diminished lateral extent of the orbital plate. The posterior border was indefinite because the lesser wing was rudimentary, extended parallel to the midline (instead of laterally) and had a limited articulation with the orbital plate only a t the midline. The greater wings were reduced in their anterior and lateral vertical development, which in turn reduced the width of the anterior portion of the middle cranial fossa. The petrous ridges of the temporal bones traversed the cranial floor a t a more obtuse angle in meroacrania than in the normal. This ridge ran horizontally from its medial end to the superior eminence of the semicircular canal. At this point, it inclined inferiorly toward its lateral end. As a result, the tympanic rings opened more inferiorly than normal. In addition this inclination gave a convex contour to the posterior portion of the middle cranial floor and reduced the depth of the fossa. In specimens with a nearly intact calvarium, the posterior cranial fossa was
much deeper than normal due to the more vertical position of the clivus, supraoccipital, and exoccipital components of the occipital bone. The exoccipital portion showed the same orientation as the normals. When more of the calvarium was lacking, the posterior fossa was flat with nearly normal anteroposterior dimensions. When viewed laterally, the anterior clinoid processes of the sphenoid bone formed the most superior part of the cranial floor (fig. 3b). The synchondrosis between the ethmoid and sphenoid was rotated almost 90' to an anterosuperior-posteroinferior orientation. The posterior part of the vomer, consisting of the ala and free border, was angled more superiorly from the palatal plane to its articulation with the sphenoid. An enlarged nasopharynx was also present. The angle Nasion-Sella-Basion was reduced to a mean of 112.6'2 16.9'. The 98%confidence interval had a lower limit of 99.3" and a n upper limit of 125.9'. As a result, the flexure of the cranial floor was increased, the pharyngeal surface of the sphenoid was concave, and the clivus was oriented vertically. Specimens with holoacrania and holoacrania with rachischisis showed a n anterior cranial fossa similar to specimens with meroacrania (fig. 4c). The middle cranial fossa had a more reduced transverse dimension anteriorly due to the more severely affected greater wings. The posterior boundary of the middle cranial fossa formed by the petrous ridge was
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H. FIELDS, JR., L. METZNER, J. GAROL AND V. KOKICH
perpendicular to the midline. As in meroacrania, the lateral ends of the ridges were oriented inferiorly, and the tympanic rings were located more inferiorly and closer to the midline. The width of the posterior fossa was variable depending on the orientation of the exoccipital and supraoccipital bones, but the clivus was consistently vertical. Whether the exoccipitals were in a normal anteroposterior position or divergent posterolaterally, they were inferolaterally oriented a t their posterior ends. The supraoccipital bones were posterior or posterolateral to the exoccipitals and always to their articulation with the exoccipitals. In a lateral view, the anterior cranial floor was inferior to the middle cranial floor (fig. 3c). The vomer was angulated superiorly to its articulation with the sphenoid. The articulation between the ethmoid and sphenoid was oriented perpendicular to the palatal plane. The increased flexure of the cranial floor again resulted in a concave pharyngeal surface of the sphenoid bone and a vertical clivus. The nasopharynx was also enlarged. Skeletal components The presphenoid and basisphenoid bones of the normal fetuses showed continuing endochondral ossification and some cartilaginous cores inside the bony trabeculae. In some specimens a vascular canal coursed from the pituitary fossa to the pharyngeal surface of the basisphenoid. The midsphenoidal synchondrosis was radiographically nonossified in three of the four normal specimens (fig. 3a). The fourth specimen, of intermediate age relative to the sample, showed a cartilaginous remnant of the synchondrosis present upon histologic examination. The basisphenoid and basiocciput exhibited smooth, rounded contours a t the pharyngeal end of the spheno-occipital synchondrosis (fig. 3a). In fetuses with meroacrania and holoacrania, the presphenoid, basisphenoid, and basiocciput were thicker than normal craniopharyngeally (figs. 3b,c) and contained fewer cartilaginous cores in the trabeculae. A vascular canal was also present in the basisphenoid, as in the normals. The midsphenoidal synchondrosis was radiographically obliterated in six of the eight anencephalic fetuses for which a midsagittal section was prepared. Histologically, one of these fetuses exhibited cartilaginous remnants of the synchondrosis; the
others were ossified. Two anencephalics showed synchondroses which were radiographically and histologically nonossified to the extent of the normals. In seven of eight anencephalic fetuses the pharyngeal end of the spheno-occipital synchondrosis was narrowed by bony projections into the cartilage from the adjacent ossification centers (figs. 3b,c). The bony projections in one of these specimens had already fused a t this location. Thus, the change in the anencephalic specimens most fundamental to this anomaly was the increased flexure of the cranial floor in the ossified body of the sphenoid and the resulting adaptation of the adjacent structures. These relationships will be considered in the DISCUSSION. DISCUSSION
Although vastly different theories regarding the pathogenesis of anencephaly have been proposed (von Recklinghausen, 1886; Gardner, '61; Vogel, '61; Marin-Padilla and Ferm, '65; Padget, '68) none adequately answer all questions concerning this defect. Recognizing this fact, the focus of the discussion will be on cranial floor morphogenesis and relationships. Several investigators (Ballantyne, '05; AbdEl-Malek, '57; Marin-Padilla, '65a) have reported a decrease in the cranial floor angle in anencephaly. Statistical analysis of the present sample supports this observation. In addition, these researchers felt that the cartilaginous spheno-occipital synchondrosis was the focal point a t which this alteration manifests itself. In the present study, however, superimposition of lateral radiographic tracings of the spheno-occipital complex indicates that the decrease in the cranial floor angle is due to alterations within the body of the sphenoid and not a t the synchondrosis. This observation is consistent with the concave pharyngeal surface of the sphenoid and Marin-Padilla's ('65b) finding that the sphenoid bone exhibited a high degree of morphologic alteration in the anencephalic. The central factor which influences the adaptive morphologic response in the sphenoid is unknown. In the present study, the cranial floor angle in anencephaly is similar to t h a t reported by Augier ('31) for the normally developing embryonic and early fetal cartilaginous cranial floor. According to Ford
CRANIAL FLOOR IN ANENCEPHALY
63
('56) a progressive flattening (increase) of the are accentuated. It appears, therefore, that cranial floor angle occurs during late fetal several different factors may influence the life, which he feels may be attributed to the cranial floor in a manner which varies only in forces transmitted to the chondrocranium magnitude. through its articulation with the enveloping The configuration of the posterior cranial bony calvarium in response to the rapidly ex- fossa in meroacrania is of interest. The supending neural mass. In anencephaly, how- praoccipital changes from a nearly horizontal ever, the brain and calvarium are largely ab- orientation in specimens with a very limited sent and unable to influence the developmen- amount of calvarium to a vertical position in tal orientation and angulation of the cranial those with a largely formed calvarium. This floor. We feel that the cranial floor angulation change reduces the anteroposterior dimension in anencephaly represents the early rudimen- of the fossa. The vertical position may be retary shape which exists in normal embryonic lated to the more complete calvarium and the and early fetal life prior to the adaptive mor- amount of neural tissue present which serve phologic alterations produced by the influ- as a greater functional matrix. ences of the neural functional matrix. Moss ('75) induced specific neural defects Since the vomer continues to have a normal and morphologic alterations in the adjacent articulation with the sphenoid, the superior basiocciput in rodents. Schowing ('61) also angulation of the ala and free border of the demonstrated neural and notochordal influvomer from the palatal plane may reflect a n ence on basioccipital differentiation and deaccomodation to the angulated cranial floor. velopment. In the present study the amount of Therefore, alterations in the cranial floor may neural tissue adjacent to the clivus was markbe transmitted via the vomer to the adjacent edly greater in meroacrania than holoacrania. facial skeleton (Metzner et al., '78) and the The length of the basiocciput, on the other nasopharynx. Marin-Padilla ('65b) has also hand, was remarkably consistent for all forms suggested that changes in the sphenoid are re- of anencephaly and the normals. This was surlated to other alterations in the anencephalic prising in light of the experimental evidence. skull. Since degeneration of the neural tissue may The anterior cranial fossa in anencephaly have occurred during the fetal period, comexhibits a consistently tapered form. The parison of the amount of neural tissue present functional matrices of the eye and the brain a t the time of examination has severe limitaare acting on the skeleton of this fossa to in- tions and is inconclusive. fluence its shape. Since the adjacent eye is There were several changes in ossification normally developed and intact, the changes in noted in the anencephalic fetuses. The adthe anterior cranial fossa may be the result of vanced state of ossification in the basiocciput, the altered neural functional matrix. basisphenoid, and presphenoid was one aspect The alterations in the orientation of the of these changes. Another aspect, the early temporal bone are directly related to the ex- ossification of the midsphenoidal synchondrotent of the cranial defect in anencephaly. As sis, has also been reported by Ballantyne ('051, the schisis becomes more pronounced, the lat- Abd-El-Malek ('571, and Marin-Padilla ('65b). eral end of the petrous ridge tends to rotate This synchondrosis normally is obliterated more anteriorly and inferiorly. As a result, the just before birth (Hoyte, '75). Finally, the tympanic rings lie closer to the midline. These basiocciput was partially fused with the findings are in agreement with those of Alt- sphenoid bone or a t least narrowed a t the man ('571, Marin-Padilla ('65a), and Wright et pharyngeal end of the spheno-occipital synal. ('76). In addition, those structures which chondrosis. Ballantyne ('05) and Abd-Elarticulate with the temporal bone, e.g., the Malek ('57) have also observed fusion of this mandibular condyle, are located more anteri- synchondrosis. According to de Beer ('37) the orly relative to the surrounding skeletal struc- normal fusion of these structures begins a t 18 tures (Metzner et al., '78). Since specimens months postnatally. More recent studies have with meroacrania have a complete foramen found first bony bridging to occur a t 12 to 18 magnum, the lack of an intact calvarium may years (Melsen, '72). Explanation of these alinitiate these temporal bone changes. With terations in ossification are beyond the scope the additional influence of an incomplete fora- of the present investigation. men magnum in holoacrania these alterations A canal within the basisphenoid containing
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H. FIELDS. J R . , L. METZNER, J. GAROL AND V. KOKICH
vascular and fibrous contents was observed in both the anencephalic and normal fetuses. Arey (’50)feels t h a t this entity is often mistaken for the “craniopharyngeal canal” which is obliterated by chondrification during t h e second month in utero. This vascular canal is found in 9% of newborns. The comprehensive methodology of t h e present study provided a n opportunity to investigate the general configurations of t h e anencephalic cranial floor as well a s the individual skeletal components responsible for these configuations. I t is felt t h a t t h e morphologic alterations of the anencephalic cranial floor are due to the altered size, form, or duration of the neural functional matrix, which in turn influences adaptive changes in the membranous bones of the neurocranium and t h e facial skeleton. 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 sample of well documented specimens; and to Mrs. Livia Molnar for her technical assistance. This research was supported by Public Health Service Research Grant DE 02931 and the University of Washington Orthodontic Memorial Fund. LITERATURE CITED Abd-El-Malek, S. 1957 The anencephalic skull and a vascular theory of causation. Egyptian Med. Assoc., 40: 216-224. Altmann, F. 1957 The ear in severe malformations of the head. A.M.A. Arch. Otolaryngol., 66: 7-25. Arey, L. B. 1950 The craniopharyngeal canal reviewed and reinterpreted. Anat. Rec., 106: 1-15, Augier, A. 1931 Traite d’Anatomie Humaine. Polrier and Charpy. Tome 1. Fasc. 1. fourth ed. Paris, Masson e t Cie, p. 627; Cited by E. H. R. Ford 1956 The growth of the foetal skull. J. Anat., 90: 63-72. Ballantyne, J. W. 1905 Manual of Antenatal Pathology and Hygiene: The Embryo. William Wood and Co., New York. pp. 332-351. de Beer, G. R. 1937 The Development of the Vertebrate Skull. Clarendon Press, Oxford, p. 364. Dekaban, A. S. 1963 Anencephaly in early human embryos. J. Neuropathol. Exp. Neurol., 22: 533-548. Ford, E. H. R. 1956 The growth of the foetal skull. J. Anat., 90: 63-72. Gardner, W. J. 1961 Rupture of the neural tube; the cause of myelomeningocele. Arch. Neurol., 4: 1-7. Garol, J. D., H. W. Fields, J r . L. Metzner and V. Koklch 1978 The craniofacial skeleton in anencephalic human fetuses. 11. Calvarium. Teratology, 17: 67-74. Giroud, A. 1960 Causes and morphogenesis of anen-
cephaly. In: Ciba Foundation Symposium on Congenital Ma1formations.G. E. W. Wolstenholme and M. O’Connor, eds. J. and A. Churchill, London, pp. 199-218. Hodges, P . C. 1953 Ossification in the fetal pig - a roentgenographic study. Anat. Rec., 116: 315.326. Hoyte, D. A. N. 1975 A critical analysis of the growth in length of the cranial base. In: Morphogenesis and Malformation of the Face and Brain. National Foundation March of Dimes Birth Defects: Original Article Series. D. Bergsma ed. XI (No. 7): pp. 255-282. Keen, J. A. 1962 Morphology of the skull in anencephalic monsters, South African J . Lab. and Clin. Med., 8: 1-9. Langman, J.,and G. W. Welch 1966 Effect of Vitamin A on the development of the central nervous system. J. Comp. Neur., 128: 1-16. Lemire, R. J., J. B. Beckwith and J. Warkany 1977 Anencephaly. Raven, New York, in press. Marin-Padilla, M. 1965a Study of the skull in human cranioschisis. Acta anat., 62: 1-20. 1965b Study of the sphenoid bone in cranioschisis and cranio-rhachischisis. Virchows Arch. path. Anat., 339: 245-253. Marin-Padilla, M., and V. H. Ferm 1965 Somite necrosis and develqpmental malformations induced by vitamin A in the golden hamster. J . Embryol. Exp. Morph., 13: 1-8. Melsen, B. 1972 Time and mode of closure of the sphenoccipital synchrondrosis determined in human autopsy material. Acta anat. (Basel), 83: 112-118. Metzner, L., J. D. Garol, H. W. Fields, Jr., and V. G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. 111. Facial skeleton. Teratology, 17: 75-82. Molnar, L. M. 1975a Decalcifying solution for hard and soft tissue. Histo-Logic, V: 71-72. 1974 Double embedding with nitrocellulose and paraffin. Stain Technol., 49: 311. 1975b Modification of Harris’ hemotoxylin for sections from tissue double embedded with nitrocellulose and paraffin. Histo-Logic, V: 59. 1975c Modification of Verhoeff s elastic stain for sections from tissue double embedded with nitrocellulose and paraffin. Histo-Logic, V: 64. 1976 Modification of Malloy’s aniline blue collagen stain. Histo-Logic, VZ: 78. Moss, M. L. 1975 The effect of rhombencephalon hypoplasia on posterior cranial base elongation in rodents. Arch. Oral Biol., 20: 489-492. Naggan, L., and B. MacMahon 1967 Ethnic differences in the prevalence of anencephaly and spina bifida in Boston, Massachusetts. New Engl. J. Med., 227: 1119-1123. Naxiagas, J. C. 1925 A comparison of the growth of the body dimensions of anencephalic human fetuses with normal fetal growth as determined by graphic analysis and empirical formulae. Am. J. Anat., 35: 455-494. Padget, D. H. 1968 Spina bifida and embryonic neuroschisis: a causal relationship. Johns Hopkins Med. J., 123: 233-252. 1970 Neuroschisis and human embryonic maldevelopment. J. Neuropathol. Exp. Neurol., 29: 192-216. Recklinghausen, F. von 1886 Untersuchungen uber die Spina bifida 11. Ueber die Art und die Entstehung der Spina bifida, ihre Beziehung zu Ruckenmarks- und Darmspalte. Virch. Arch. Path. Anat., 105: 296-330. Schowing, J. 1961 Influence inductrice de l’encephale e t de la chorde sur la morphogenese du squelette cranien chez l’embryon de poulet. J. Embryol. Exp. Morphol., 9: 326-334. Stevenson, A. C., H. A. Johnston, M. I. P. Stewart and D. R. Golding 1966 Malformation of structures developed from
CRANIAL FLOOR IN ANENCEPHALY the neural tube. Bull. of the World Health Org.,34 (Suppl. 9): 25-34. Streeter, G. L. 1920 Contributions to embryology, Carnegie Institute, Washington, D. C., XI (55): 143-170. Trolle, D. 1948 Age of foetus determined from its measures. Acta obstet. gynec. Scand., 27: 327-337.
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Vogel, F. S. 1961 The anatomic character of the vascular anomalies associated with anencephaly. Am. J. Pathol., 39: 163-174. Wright, J. L. W.. P. D. Phelps and I. Freedman 1976 Temporal bone studies in anencephaly ( I ) . J. Laryng. and Otol., 90: 919-927.
ABSTRACT
Twelve anencephalic and four normal fetuses 26 to 40 weeks gestational age were compared by anatomic, radiographic and histologic methods in order to gain information concerning morphogenesis. In the anencephalics, alterations located within the body of the sphenoid bone led to a reduced cranial floor angle and a more vertical clivus. The reduced lateral extension of the lesser and greater wings of the sphenoid constricted the anterior and middle cranial fossae respectively. The posterior cranial fossa tended to have an increased transverse dimension related to the supraoccipital and exoccipital bone orientation. The increased anterior and inferior position of the lateral end of the petrous temporal ridge was positively correlated with the degree of dorsal schisis in the anencephalics. Alterations in the size, form, or duration of the neural functional matrix are suggested as the cause of changes in the cranial floor.
Anencephaly is a common lethal defect with pronounced effects that can readily be described over its full range of severity. Thus, it serves a s a natural experiment for studying the normal and abnormal development of the skull. Earlier investigations fall into three categories: epidemiologic studies aimed a t etiology (Stevenson et al., '66; Naggan and MacMahon, '67); anatomic (Abd-El-Malek, '57; Keen, '63; Marin-Padilla, '65a,b) and embryologic (Dekaban, '63; Padget, '70) studies aimed a t morphology; and animal studies aimed a t pathogenesis (Giroud, '60; MarinPadilla and Ferm, '65; Langman and Welch, '66). The present study will compare craniofacial skeletal development in normal and anencephalic fetuses using a combination of anatomic, radiographic, and histologic techniques. The purpose of the study is to analyze the morphologic result of this developmental anomaly. Hopefully, these techniques will give additional information concerning craniofacial morphogenesis. This article describes the cranial floor. The articles which follow will deal with the calvarium (Garol e t al., '78) and the facial skeleton (Metzner e t al., '78). MATERIALS AND METHODS
Twelve anencephalic fetuses were chosen TERATOLOGY (1978) 17: 57-66.
for study from a sample of 28 specimens, 26 to 40 weeks gestational age, based on quality of preservation, age, and extent of the dorsal cranial defect (table 1). The gestational ages were determined according to foot length (Streeter, '20; Naiiagas, '25; Trolle, '48). The dorsal cranial defects were classified 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 (Lemire e t al., '77). Four fetuses of similar age with no malformations of the head and neck were chosen as controls. All fetuses were preserved in 10%formalin. After decapitation, each of the 12 specimens was examined grossly, photographed, and radiographed. Soft tissue was then dissected from the skeletal structures leaving the periosteum intact, and the heads were divided in a parasagittal plane to preserve the midline structures for histologic evaluation. In order to show the ossification centers and improve the quality of the radiographs, the larger portion containing the midline structures was impregnated with 0.5%aqueous silver nitrate (Hodges, '53) and radiographed (fig. 1). The Received June 7, '71. Accepted Oct. 18. '77.
57
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H. FIELDS, JR., L. METZNER, J. GAROL AND V. KOKICH
b
a
Fig. 1 Lateral radiographs of the parasagittally sectioned skulls of (a) a normal fetus (1658)and (b) a fetus with holoacrania (AN47) following silver nitrate impregnation. Note the well defined ossification centers and the increased detail yielded by this methodology.
midline structures were then removed from this larger section in a 5- to 7-mm thick sagittal slab and radiographed. Tissue blocks from any region containing anomalous structures were removed, decalcified, double embedded, and stained with hematoxylin and eosin, Mallory's aniline blue collagen stain, periodicacid Schiff s reagent, and Verhoeff s elastic stain after clearing of the silver nitrate (Molnar, '74, '75a,b,c, '76). Corresponding tissue blocks were obtained from the control specimens. The remainder of each specimen was stained with alizarin red S and examined as a cleared preparation. Tracings of t h e radiographs were made on acetate paper to illustrate bony contours and relationships. Dry skull preparation of two fetuses was made following dissection of t h e soft tissue. The skulls were air dried at 50°C for 48 hours. The dried periosteum held t h e bones in position for study. RESULTS
The observations will emphasize anatomic relationships in t h e three cranial fossae and t h e individual articular and skeletal compo-
nents which comprise the cranial floor. First t h e general configuration of the cranial floor will be described, followed by the articular relationships which account for these configurations. Then changes in the skeletal components will be reported. For each of these aspects a brief baseline description will be made of t h e normal specimens. Comparable observations will be presented for specimens with increasing severity of anencephaly ranging from meroacrania to holoacrania with rachischisis. The observations will proceed from the less variable anterior cranial structures to the more affected and variable posterior cranial structures. All specimens were in the gestational age range of 26- to 40 weeks. General configuration of the cranial floor In normal specimens viewed from above, the cranial floor had a n ovoid shape (fig. 2a). This gave a semicircular contour to the anterior and posterior cranial fossae with the intervening middle fossa having t h e greatest transverse dimension. The boundaries between the
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CRANIAL FLOOR IN ANENCEPHALY
n
C Fig. 2 Schematic drawings of the cranial floor and configuration of the individual fossae in (a) a normal fetus (2537); (b) a fetus with meroacrania (AN10); and (c) a fetus with holoacrania (AN471 - superior view. Note the lateral constriction of the anterior cranial fossa (ACF) and middle cranial fossa (MCF) in the anencephalics. The increased lateral extension and anteroposterior constriction of the posterior cranial fossa (PCF) is also evident. In holoacrania the posterior cranial fossa exhibits schisis (arrows). TABLE 1
Sample of anencephalic and normal human fetuses used in this study Specimen number '
Anencephalic fetuses Meroacrania AN 50 AN 46 AN 10 AN 62 AN 30 Holoacrania AN 44 AN 47 AN 11 Holoacrania with rachischisis AN 1 AN 28 AN 13 AN 37 Normal fetuses H-2537 1658 H-2529 w-353 I
Foot length lmm)
Gestational age (weeks)
51 76 85 88 90
26.5' 1.5 37.0%2 40 40 40
58 60 61
29.5e 1 30.0' 2 31.02 2
60 60 75 86
30.02 2 30.0%2 36.5* 1.5 40
58 70 77 85
29.5%1 34.5e 2 37.5'2 40
Specimen numbers assigned and referred to by Lemire et al. ('771.
three fossae were sharply defined anatomically by bony contours and by the different cranial floor levels in each fossa. The boundary between t h e middle and posterior fossae was oriented 45" posterolaterally to the midline. The posterior fossa was the largest and deepest of the three with most of its area located lateral and posterior to the foramen magnum. In lateral view the cranial floor was most su-
perior in the anterior fossa and then gradually declined posteriorly to the foramen magnum (fig. 3a). Behind the foramen magnum the floor inclined superiorly, giving the posterior fossa its concave appearance. From a posterior view, the anterior cranial fossa was slightly concave; the midline structures were superior to the lateral structures in the middle cranial fossa; and the posterior fossa was deeply concave. The cranial floor in specimens with meroacrania changed from a n ovoid to a trapezoid shape with the narrow end located anteriorly (fig. 2b). This configuration was due to a decreased width in the anterior fossa and adjacent part of the middle fossa, as well as increased width in the posterior cranial fossa. The middle fossa was shallow anteriorly, and in front of its posterior boundary the floor was actually convex instead of concave. The boundary between the middle and posterior fossae was nearly perpendicular to the midline. The posterior fossa maintained the same width as the middle fossa instead of tapering posteriorly. In the lateral view, the floors of the anterior and middle fossae were on one level (fig. 3b). The depth of the posterior fossa was greatly increased by a n anterior wall which was sharply angulated inferiorly and by a vertical posterior wall. From the posterior view, the anterior fossa was flat and the midline structures were superior to the inferiorly sloping lateral part of the middle cranial fossa. The posterior fossa was concave due to the vertical lateral walls.
60
H. FIELDS, JR., L. METZNER, J . GAROL AND V. KOKICH Abbreviations B, Basiocciput E, Ethmoid EO, Exoccipital GW, Greater wing of the sphenoid
LW, Lesser wing of the sphenoid T, Petrous temporal S, Sphenoid SO, Supraoccipital V, Vomer
Fig. 3 Schematic drawings of the relationships of sagittal cranial floor structures in (a) a normal fetus (2537); (b) a fetus with meroacrania (ANlO); and (c) a fetus with holoacrania (AN47). All three drawings are oriented with t h e palatal plane horizontal. Note the concave (b) or irregular (c) pharyngeal surface of the sphenoid bone and the inferior angulation of the clivus (b and c) relative to the normal (a). The increased posterior height of the vomer and the enlarged nasopharynx (dashed line) are evident in the anencephalic fetuses. The supraoccipital is in a more vertical position in meroacrania (compare b to a ) , and not present in the midsagittal section in holoacrania (c).
In specimens with holoacrania and holoacrania with rachischisis, the cranial floor had a triangular configuration due to a narrowing of the anterior and middle fossae combined with a widening of the posterior fossa (fig. 2c). The border between the middle and posterior fossae was perpendicular to the midline. Behind the incomplete foramen magnum the posterior fossa was absent, but the lateral floor was present to a variable extent. As in the specimens with meroacrania, the anterior and middle fossae were on one level with the anterior wall of the posterior fossa sharply angulated inferiorly (fig. 3c). The posterior view showed a flat anterior fossa floor and superior midline structures in the middle fossa. From this perspective, the posterior fossa had no floor. Articular relationships In the normal specimens the floor of the an-
terior fossa was formed by the lateral extent of the orbital plate of the frontal bone. The posterior boundary of this fossa was delineated by the articulation of the lesser wing of the sphenoid with the orbital plate (fig. 4a). In the middle cranial fossa, the body of the sphenoid bone with its laterally extending wings formed most of the cranial floor. The posterior limits of this fossa was formed by the horizontal petrous ridge of the temporal bone traversing the cranial floor posterolaterally a t a 45" angle to the midline. The tympanic rings opened inferolaterally on the inferior surface of the petrous temporal bone. In the posterior cranial fossa the floor was formed partially by the exoccipital bones which lay lateral to the foramen magnum in a horizontal plane, and partially by the supraoccipital which was inclined superiorly from its articulation with the right and left exoccipital. The mean for the angle Nasion-Sella-Basion (which opens
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CRANIAL FLOOR IN ANENCEPHALY
n
C Fig. 4 Schematic drawings of the bones of the cranial floor in (a) a normal fetus (2537);(b) a fetus with meroacrania (AN10); and (c) a fetus with holoacrania (AN47). Note the anteroposterior position of the lesser wings of the spenoid and the reduced transverse dimension of the greater wings of the sphenoid (band c ) relative to the normal (a). The more anterior position of the lateral end of the petrous portion of the temporal bone is also evident in anencephaly. In holoacrania the supraoccipital components are nonunited and widely divergent (c).
inferiorly) was 143.3't 4.7'. The 98% confidence interval lower limit was 132.3' and the upper limit was 153.7'. In the normal fetus the ethmoid was the most superior part of the cranial floor in a lateral view (fig. 3a). The cartilaginous interface between the sphenoid and ethmoid bones was oriented in a posterosuperior-anteroinferior plane. The anterior fossa in meroacrania was roofed and limited laterally by the underdeveloped squamous frontal bone (fig. 4b).The floor of the fossa was limited due to the diminished lateral extent of the orbital plate. The posterior border was indefinite because the lesser wing was rudimentary, extended parallel to the midline (instead of laterally) and had a limited articulation with the orbital plate only a t the midline. The greater wings were reduced in their anterior and lateral vertical development, which in turn reduced the width of the anterior portion of the middle cranial fossa. The petrous ridges of the temporal bones traversed the cranial floor a t a more obtuse angle in meroacrania than in the normal. This ridge ran horizontally from its medial end to the superior eminence of the semicircular canal. At this point, it inclined inferiorly toward its lateral end. As a result, the tympanic rings opened more inferiorly than normal. In addition this inclination gave a convex contour to the posterior portion of the middle cranial floor and reduced the depth of the fossa. In specimens with a nearly intact calvarium, the posterior cranial fossa was
much deeper than normal due to the more vertical position of the clivus, supraoccipital, and exoccipital components of the occipital bone. The exoccipital portion showed the same orientation as the normals. When more of the calvarium was lacking, the posterior fossa was flat with nearly normal anteroposterior dimensions. When viewed laterally, the anterior clinoid processes of the sphenoid bone formed the most superior part of the cranial floor (fig. 3b). The synchondrosis between the ethmoid and sphenoid was rotated almost 90' to an anterosuperior-posteroinferior orientation. The posterior part of the vomer, consisting of the ala and free border, was angled more superiorly from the palatal plane to its articulation with the sphenoid. An enlarged nasopharynx was also present. The angle Nasion-Sella-Basion was reduced to a mean of 112.6'2 16.9'. The 98%confidence interval had a lower limit of 99.3" and a n upper limit of 125.9'. As a result, the flexure of the cranial floor was increased, the pharyngeal surface of the sphenoid was concave, and the clivus was oriented vertically. Specimens with holoacrania and holoacrania with rachischisis showed a n anterior cranial fossa similar to specimens with meroacrania (fig. 4c). The middle cranial fossa had a more reduced transverse dimension anteriorly due to the more severely affected greater wings. The posterior boundary of the middle cranial fossa formed by the petrous ridge was
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H. FIELDS, JR., L. METZNER, J. GAROL AND V. KOKICH
perpendicular to the midline. As in meroacrania, the lateral ends of the ridges were oriented inferiorly, and the tympanic rings were located more inferiorly and closer to the midline. The width of the posterior fossa was variable depending on the orientation of the exoccipital and supraoccipital bones, but the clivus was consistently vertical. Whether the exoccipitals were in a normal anteroposterior position or divergent posterolaterally, they were inferolaterally oriented a t their posterior ends. The supraoccipital bones were posterior or posterolateral to the exoccipitals and always to their articulation with the exoccipitals. In a lateral view, the anterior cranial floor was inferior to the middle cranial floor (fig. 3c). The vomer was angulated superiorly to its articulation with the sphenoid. The articulation between the ethmoid and sphenoid was oriented perpendicular to the palatal plane. The increased flexure of the cranial floor again resulted in a concave pharyngeal surface of the sphenoid bone and a vertical clivus. The nasopharynx was also enlarged. Skeletal components The presphenoid and basisphenoid bones of the normal fetuses showed continuing endochondral ossification and some cartilaginous cores inside the bony trabeculae. In some specimens a vascular canal coursed from the pituitary fossa to the pharyngeal surface of the basisphenoid. The midsphenoidal synchondrosis was radiographically nonossified in three of the four normal specimens (fig. 3a). The fourth specimen, of intermediate age relative to the sample, showed a cartilaginous remnant of the synchondrosis present upon histologic examination. The basisphenoid and basiocciput exhibited smooth, rounded contours a t the pharyngeal end of the spheno-occipital synchondrosis (fig. 3a). In fetuses with meroacrania and holoacrania, the presphenoid, basisphenoid, and basiocciput were thicker than normal craniopharyngeally (figs. 3b,c) and contained fewer cartilaginous cores in the trabeculae. A vascular canal was also present in the basisphenoid, as in the normals. The midsphenoidal synchondrosis was radiographically obliterated in six of the eight anencephalic fetuses for which a midsagittal section was prepared. Histologically, one of these fetuses exhibited cartilaginous remnants of the synchondrosis; the
others were ossified. Two anencephalics showed synchondroses which were radiographically and histologically nonossified to the extent of the normals. In seven of eight anencephalic fetuses the pharyngeal end of the spheno-occipital synchondrosis was narrowed by bony projections into the cartilage from the adjacent ossification centers (figs. 3b,c). The bony projections in one of these specimens had already fused a t this location. Thus, the change in the anencephalic specimens most fundamental to this anomaly was the increased flexure of the cranial floor in the ossified body of the sphenoid and the resulting adaptation of the adjacent structures. These relationships will be considered in the DISCUSSION. DISCUSSION
Although vastly different theories regarding the pathogenesis of anencephaly have been proposed (von Recklinghausen, 1886; Gardner, '61; Vogel, '61; Marin-Padilla and Ferm, '65; Padget, '68) none adequately answer all questions concerning this defect. Recognizing this fact, the focus of the discussion will be on cranial floor morphogenesis and relationships. Several investigators (Ballantyne, '05; AbdEl-Malek, '57; Marin-Padilla, '65a) have reported a decrease in the cranial floor angle in anencephaly. Statistical analysis of the present sample supports this observation. In addition, these researchers felt that the cartilaginous spheno-occipital synchondrosis was the focal point a t which this alteration manifests itself. In the present study, however, superimposition of lateral radiographic tracings of the spheno-occipital complex indicates that the decrease in the cranial floor angle is due to alterations within the body of the sphenoid and not a t the synchondrosis. This observation is consistent with the concave pharyngeal surface of the sphenoid and Marin-Padilla's ('65b) finding that the sphenoid bone exhibited a high degree of morphologic alteration in the anencephalic. The central factor which influences the adaptive morphologic response in the sphenoid is unknown. In the present study, the cranial floor angle in anencephaly is similar to t h a t reported by Augier ('31) for the normally developing embryonic and early fetal cartilaginous cranial floor. According to Ford
CRANIAL FLOOR IN ANENCEPHALY
63
('56) a progressive flattening (increase) of the are accentuated. It appears, therefore, that cranial floor angle occurs during late fetal several different factors may influence the life, which he feels may be attributed to the cranial floor in a manner which varies only in forces transmitted to the chondrocranium magnitude. through its articulation with the enveloping The configuration of the posterior cranial bony calvarium in response to the rapidly ex- fossa in meroacrania is of interest. The supending neural mass. In anencephaly, how- praoccipital changes from a nearly horizontal ever, the brain and calvarium are largely ab- orientation in specimens with a very limited sent and unable to influence the developmen- amount of calvarium to a vertical position in tal orientation and angulation of the cranial those with a largely formed calvarium. This floor. We feel that the cranial floor angulation change reduces the anteroposterior dimension in anencephaly represents the early rudimen- of the fossa. The vertical position may be retary shape which exists in normal embryonic lated to the more complete calvarium and the and early fetal life prior to the adaptive mor- amount of neural tissue present which serve phologic alterations produced by the influ- as a greater functional matrix. ences of the neural functional matrix. Moss ('75) induced specific neural defects Since the vomer continues to have a normal and morphologic alterations in the adjacent articulation with the sphenoid, the superior basiocciput in rodents. Schowing ('61) also angulation of the ala and free border of the demonstrated neural and notochordal influvomer from the palatal plane may reflect a n ence on basioccipital differentiation and deaccomodation to the angulated cranial floor. velopment. In the present study the amount of Therefore, alterations in the cranial floor may neural tissue adjacent to the clivus was markbe transmitted via the vomer to the adjacent edly greater in meroacrania than holoacrania. facial skeleton (Metzner et al., '78) and the The length of the basiocciput, on the other nasopharynx. Marin-Padilla ('65b) has also hand, was remarkably consistent for all forms suggested that changes in the sphenoid are re- of anencephaly and the normals. This was surlated to other alterations in the anencephalic prising in light of the experimental evidence. skull. Since degeneration of the neural tissue may The anterior cranial fossa in anencephaly have occurred during the fetal period, comexhibits a consistently tapered form. The parison of the amount of neural tissue present functional matrices of the eye and the brain a t the time of examination has severe limitaare acting on the skeleton of this fossa to in- tions and is inconclusive. fluence its shape. Since the adjacent eye is There were several changes in ossification normally developed and intact, the changes in noted in the anencephalic fetuses. The adthe anterior cranial fossa may be the result of vanced state of ossification in the basiocciput, the altered neural functional matrix. basisphenoid, and presphenoid was one aspect The alterations in the orientation of the of these changes. Another aspect, the early temporal bone are directly related to the ex- ossification of the midsphenoidal synchondrotent of the cranial defect in anencephaly. As sis, has also been reported by Ballantyne ('051, the schisis becomes more pronounced, the lat- Abd-El-Malek ('571, and Marin-Padilla ('65b). eral end of the petrous ridge tends to rotate This synchondrosis normally is obliterated more anteriorly and inferiorly. As a result, the just before birth (Hoyte, '75). Finally, the tympanic rings lie closer to the midline. These basiocciput was partially fused with the findings are in agreement with those of Alt- sphenoid bone or a t least narrowed a t the man ('571, Marin-Padilla ('65a), and Wright et pharyngeal end of the spheno-occipital synal. ('76). In addition, those structures which chondrosis. Ballantyne ('05) and Abd-Elarticulate with the temporal bone, e.g., the Malek ('57) have also observed fusion of this mandibular condyle, are located more anteri- synchondrosis. According to de Beer ('37) the orly relative to the surrounding skeletal struc- normal fusion of these structures begins a t 18 tures (Metzner et al., '78). Since specimens months postnatally. More recent studies have with meroacrania have a complete foramen found first bony bridging to occur a t 12 to 18 magnum, the lack of an intact calvarium may years (Melsen, '72). Explanation of these alinitiate these temporal bone changes. With terations in ossification are beyond the scope the additional influence of an incomplete fora- of the present investigation. men magnum in holoacrania these alterations A canal within the basisphenoid containing
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H. FIELDS. J R . , L. METZNER, J. GAROL AND V. KOKICH
vascular and fibrous contents was observed in both the anencephalic and normal fetuses. Arey (’50)feels t h a t this entity is often mistaken for the “craniopharyngeal canal” which is obliterated by chondrification during t h e second month in utero. This vascular canal is found in 9% of newborns. The comprehensive methodology of t h e present study provided a n opportunity to investigate the general configurations of t h e anencephalic cranial floor as well a s the individual skeletal components responsible for these configuations. I t is felt t h a t t h e morphologic alterations of the anencephalic cranial floor are due to the altered size, form, or duration of the neural functional matrix, which in turn influences adaptive changes in the membranous bones of the neurocranium and t h e facial skeleton. 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 sample of well documented specimens; and to Mrs. Livia Molnar for her technical assistance. This research was supported by Public Health Service Research Grant DE 02931 and the University of Washington Orthodontic Memorial Fund. LITERATURE CITED Abd-El-Malek, S. 1957 The anencephalic skull and a vascular theory of causation. Egyptian Med. Assoc., 40: 216-224. Altmann, F. 1957 The ear in severe malformations of the head. A.M.A. Arch. Otolaryngol., 66: 7-25. Arey, L. B. 1950 The craniopharyngeal canal reviewed and reinterpreted. Anat. Rec., 106: 1-15, Augier, A. 1931 Traite d’Anatomie Humaine. Polrier and Charpy. Tome 1. Fasc. 1. fourth ed. Paris, Masson e t Cie, p. 627; Cited by E. H. R. Ford 1956 The growth of the foetal skull. J. Anat., 90: 63-72. Ballantyne, J. W. 1905 Manual of Antenatal Pathology and Hygiene: The Embryo. William Wood and Co., New York. pp. 332-351. de Beer, G. R. 1937 The Development of the Vertebrate Skull. Clarendon Press, Oxford, p. 364. Dekaban, A. S. 1963 Anencephaly in early human embryos. J. Neuropathol. Exp. Neurol., 22: 533-548. Ford, E. H. R. 1956 The growth of the foetal skull. J. Anat., 90: 63-72. Gardner, W. J. 1961 Rupture of the neural tube; the cause of myelomeningocele. Arch. Neurol., 4: 1-7. Garol, J. D., H. W. Fields, J r . L. Metzner and V. Koklch 1978 The craniofacial skeleton in anencephalic human fetuses. 11. Calvarium. Teratology, 17: 67-74. Giroud, A. 1960 Causes and morphogenesis of anen-
cephaly. In: Ciba Foundation Symposium on Congenital Ma1formations.G. E. W. Wolstenholme and M. O’Connor, eds. J. and A. Churchill, London, pp. 199-218. Hodges, P . C. 1953 Ossification in the fetal pig - a roentgenographic study. Anat. Rec., 116: 315.326. Hoyte, D. A. N. 1975 A critical analysis of the growth in length of the cranial base. In: Morphogenesis and Malformation of the Face and Brain. National Foundation March of Dimes Birth Defects: Original Article Series. D. Bergsma ed. XI (No. 7): pp. 255-282. Keen, J. A. 1962 Morphology of the skull in anencephalic monsters, South African J . Lab. and Clin. Med., 8: 1-9. Langman, J.,and G. W. Welch 1966 Effect of Vitamin A on the development of the central nervous system. J. Comp. Neur., 128: 1-16. Lemire, R. J., J. B. Beckwith and J. Warkany 1977 Anencephaly. Raven, New York, in press. Marin-Padilla, M. 1965a Study of the skull in human cranioschisis. Acta anat., 62: 1-20. 1965b Study of the sphenoid bone in cranioschisis and cranio-rhachischisis. Virchows Arch. path. Anat., 339: 245-253. Marin-Padilla, M., and V. H. Ferm 1965 Somite necrosis and develqpmental malformations induced by vitamin A in the golden hamster. J . Embryol. Exp. Morph., 13: 1-8. Melsen, B. 1972 Time and mode of closure of the sphenoccipital synchrondrosis determined in human autopsy material. Acta anat. (Basel), 83: 112-118. Metzner, L., J. D. Garol, H. W. Fields, Jr., and V. G. Kokich 1978 The craniofacial skeleton in anencephalic human fetuses. 111. Facial skeleton. Teratology, 17: 75-82. Molnar, L. M. 1975a Decalcifying solution for hard and soft tissue. Histo-Logic, V: 71-72. 1974 Double embedding with nitrocellulose and paraffin. Stain Technol., 49: 311. 1975b Modification of Harris’ hemotoxylin for sections from tissue double embedded with nitrocellulose and paraffin. Histo-Logic, V: 59. 1975c Modification of Verhoeff s elastic stain for sections from tissue double embedded with nitrocellulose and paraffin. Histo-Logic, V: 64. 1976 Modification of Malloy’s aniline blue collagen stain. Histo-Logic, VZ: 78. Moss, M. L. 1975 The effect of rhombencephalon hypoplasia on posterior cranial base elongation in rodents. Arch. Oral Biol., 20: 489-492. Naggan, L., and B. MacMahon 1967 Ethnic differences in the prevalence of anencephaly and spina bifida in Boston, Massachusetts. New Engl. J. Med., 227: 1119-1123. Naxiagas, J. C. 1925 A comparison of the growth of the body dimensions of anencephalic human fetuses with normal fetal growth as determined by graphic analysis and empirical formulae. Am. J. Anat., 35: 455-494. Padget, D. H. 1968 Spina bifida and embryonic neuroschisis: a causal relationship. Johns Hopkins Med. J., 123: 233-252. 1970 Neuroschisis and human embryonic maldevelopment. J. Neuropathol. Exp. Neurol., 29: 192-216. Recklinghausen, F. von 1886 Untersuchungen uber die Spina bifida 11. Ueber die Art und die Entstehung der Spina bifida, ihre Beziehung zu Ruckenmarks- und Darmspalte. Virch. Arch. Path. Anat., 105: 296-330. Schowing, J. 1961 Influence inductrice de l’encephale e t de la chorde sur la morphogenese du squelette cranien chez l’embryon de poulet. J. Embryol. Exp. Morphol., 9: 326-334. Stevenson, A. C., H. A. Johnston, M. I. P. Stewart and D. R. Golding 1966 Malformation of structures developed from
CRANIAL FLOOR IN ANENCEPHALY the neural tube. Bull. of the World Health Org.,34 (Suppl. 9): 25-34. Streeter, G. L. 1920 Contributions to embryology, Carnegie Institute, Washington, D. C., XI (55): 143-170. Trolle, D. 1948 Age of foetus determined from its measures. Acta obstet. gynec. Scand., 27: 327-337.
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Vogel, F. S. 1961 The anatomic character of the vascular anomalies associated with anencephaly. Am. J. Pathol., 39: 163-174. Wright, J. L. W.. P. D. Phelps and I. Freedman 1976 Temporal bone studies in anencephaly ( I ) . J. Laryng. and Otol., 90: 919-927.
