The Cleft Palate–Craniofacial Journal 52(5) pp. 597–604 September 2015 Ó Copyright 2015 American Cleft Palate–Craniofacial Association
ORIGINAL ARTICLE Bridging the Gap: Sella Turcica in Unilateral Cleft Lip and Palate Patients Shobha Sundareswaran, B.D.S., M.D.S., C. A. Nipun, B.D.S., M.D.S. Objectives: The aims of this study were to analyze the prevalence of sella turcica bridging and to measure the size of the sella turcica on profile cephalograms in a homogenous group of surgically repaired unilateral cleft lip and palate (UCLP) patients. Setting: Tertiary care center. Design: Retrospective cross-sectional study. Patients: Preorthodontic lateral cephalometric radiographs of 64 UCLP individuals between the ages of 16 and 29 years along with an equal number of age- and sex-matched skeletal Class I controls. Main Outcome Measures: The extent of calcification of the interclinoid ligament was quantified (completely calcified, partially calcified, no calcification) and mean values compared. Length, depth, and diameter of the sella turcica were also measured. The results were statistically analyzed using paired t test and Wilcoxon signed ranks test. Results: Complete sella bridging of both type A (4.6%) and type B (21.7%) was significantly higher in UCLP patients. This has not been reported previously. Partial sella bridging was also higher in cleft patients as evaluated by two methods (42.18%, 39.06%). This study demonstrated a statistically significant decrease in all dimensions of sella turcica in UCLP patients. Conclusions: The UCLP patients apparently had higher predilection for sella turcica bridging. The dimensions of sella turcica were also seen to be significantly smaller than the control group. Defective proliferation and deviated pathways of neural crest cell migration as well as premature rupture of contact between neuroepithelium and oral ectoderm as postulated causes are discussed. KEY WORDS:
cleft lip and palate, neural crest cells, sella bridging, sella dimensions
surface of the body of the sphenoid bone, housing the pituitary gland with two anterior and two posterior clinoid processes projecting over it. In orthodontics, sella is considered to be an important structure, as the midpoint of sella turcica termed the Sella point (Bjork, 1947) is used ¨ extensively as a reference point in various cephalometric analyses. The anterior wall of sella turcica and the Walker point (the point at which the anterior wall of the pituitary fossa crosses the inferior surface of the anterior clinoid process) are very visible and used in the evaluation of craniofacial growth and orthodontic treatment results (Bjork and Skieller, 1983). The fact that bone apposition ¨ on the anterior part of the inner surface of the sella turcica ceases at an early age makes it a stable structure (Melsen, 1974). Resorption along the posterior wall and the floor of sella continues for a longer time, leading to a backward and downward displacement of the sella point during growth. Because these points are routine diagnostic tools, many pathological variations are likely to be discovered in lateral cephalograms during orthodontic therapy. The sella anatomy is variable in terms of shape, size, and morphology. Previous studies have focused on sella turcica of normal individuals (Bjork, 1955; Melsen, 1974; Bjork ¨ and Skieller, 1983; Axelsson et al., 2004a; Alkofide, 2007) as well as subjects with disorders such as Cri du chat (Kjær
Clefts of the lip and palate are considered to be the most common congenital anomalies of the craniofacial region. The fact that clefts are not localized defects but may be associated with widespread structural changes in other parts of the skull had been recognized very early (Wardill, 1928). A primary defect in one structure can lead to secondary defects in contiguous structures. Disturbances in the facial growth are said to occur due to a combination of intrinsic abnormalities as well as environmental factors, and the effect of this is said to extend to other areas in the cranium, leading to extensive studies on cranial base features in cleft lip and palate patients (Moss, 1956; Harris, 1993). However, the effect of these abnormalities on the sella turcica has not been fully investigated. Literally meaning ‘‘Turkish saddle,’’ the sella turcica is a saddle-shaped depression situated on the intracranial
Ms. Sundareswaran is Professor and Head and Mr. Nipun is Senior Resident, Department of Orthodontics, Government Dental College, Calicut, Kerala, India. Submitted October 2013; Revised February 2014, May 2014; Accepted September 2014. Address correspondence to: Ms. Shobha Sundareswaran, Department of Orthodontics, Government Dental College, Calicut, Kerala, India. E-mail [email protected]. DOI: 10.1597/13-258 597
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TABLE 1
Prevalence of Sella Bridging in Various Syndromes Syndrome/Anomaly
Authors
Prevalence of Sella Bridging (%)
Severe craniofacial deviations Solitary median maxillary central incisor Williams syndrome Dentofacial deformities Palatally displaced canines, agenesis of mandibular second premolars Skeletal Class III patients Axenfeld–Rieger syndrome with PITX2 mutation Skeletal Class III patients
Bektor et al. (2000) Kjaer et al. (2001) Axelsson et al. (2004b) Jones et al. (2005) Leonardi et al. (2006) Abdel-Kader (2007) Meyer-Marcotty et al. (2008) Meyer-Marcotty et al. (2010)
18.6 Not specified 13 16.70 17.60 10.71 Not specified 16.80
and Niebuhr, 1999), fragile X (Hjalgrim et al., 2000), holoprosencephaly (Kjær and Fischer Hansen, 1995; Kjær et al., 2002), solitary median maxillary central incisor ( Kjær et al., 2001), trisomy 18 (Kjær et al., 1998a), trisomy 21 ((Kjær et al., 1998b), spina bifida (Kjær et al., 1998c), Axenfeld–Rieger syndrome with PITX2 mutation (Meyer Marcotty et al., 2008), and Williams syndrome (Axelsson et al., 2004b). Despite cleft lip and palate being one of the most common congenital anomalies, the literature is scant with regard to their sella characteristics. One study based on radiographs of 40 newborns with cleft lip and palate revealed deviations in the sella morphology in approximately half of the sample, with the most severe deviations occurring in unilateral cleft lip and palate (UCLP) patients (Nielsen et al., 2005). In a recent overview of craniofacial patterning, Kjær (2010) described six main fields registered on the fetal craniofacial skeleton: theca, frontonasal, maxillary, palatine, mandibular, together with cerebellar and cervical. It is said that all craniofacial fields are developmentally interrelated with the sella turcica region. Hence, it can logically be hypothesized that malformations in the frontonasal, maxillary, and palatine fields will extend to the sella turcica as well. Fusion of the anterior and posterior clinoid processes is yet another reported anatomic abnormality of the sella turcica. In the literature, this bony formation is referred to as sella bridge (Lang, 1977), interclinoid osseous bridge (Inoue et al., 1990), or interclinoid taeina (Lang, 1995). This has been reported in various syndromes (Table 1). These bony interclinoid connections have important neuronal and vascular relations and are both clinically and surgically important. Knowledge of a detailed anatomy of the interclinoid ligament can increase the success of diagnostic evaluation and surgical approaches to the region (Ozdogmus et al., 2003). To date, there have been no studies on the prevalence of the sella turcica bridging in UCLP patients; hence, it is not known if they are more susceptible to these osseous interclinoid connections. Difference in the size of sella turcica has been reported in various syndromes (Table 2). Also, sella dimensions are apparently not the same in different populations. The dimensions of the sella in the Saudi sample were on average 1.07 to 2.97 mm larger than in the Norwegian sample of Axelsson (Alkofide, 2007). The Greek population is reported to have smaller dimensions of the sella turcica
(Andredaki et al., 2007). This obviously indicates racial differences and a need to assess normal dimensions in different populations to appreciate variations. The southern states of India, including Kerala, are populated by people of Dravidian ethnic origin. Dravidian ethnicity includes Tamil-, Telugu-, Kannada-, and Malayalamspeaking people (Jain et al., 2013). No literature exists regarding the sella dimensions of individuals belonging to this race. Hence, the aims of this study were to (1) analyze the prevalence of sella turcica bridging and (2) measure the sella dimensions in a group of UCLP patients and to compare them with Class I controls. The null hypothesis generated was that there may be no difference in the prevalence of sella bridging among UCLP patients as compared with the control group. MATERIALS
AND
METHODS
Approval for this retrospective study was obtained from the Institutional Research Board and Institutional Ethics Committee (IEC No. 14/2011/DCC, dated March 15, 2011). Sample size was determined using the formula n ¼ (Za þ Z"b)2SD2/d2, where Za ¼ 1.96, Z"b ¼ 0.84 (constant), SD ¼ standard deviation of key variable d ¼ X1 – X2, X1 ¼ mean of key variable in case, and X2 ¼ mean of key variable in control, based on the mean sella length value of individuals with Class I occlusion (Axelsson et al., 2004b). To detect a change of 0.5 mm from this mean value with 95% confidence and 80% power, we required a minimum sample size of 53 in each group. Accordingly, preorthodontic lateral cephalometric radiographs of 64 individuals (33 males and 31 females) with surgically repaired UCLP between the ages of 16 and 29 years were selected. A control group comprising of 64 skeletal Class I patients matched for age and sex were also selected. All cases and controls taken from the departmenTABLE 2
Sella Dimensional Variations in Various Syndromes
Decrease in the Size of the Sella Turcica
Increase in the Size of the Sella Turcica
Holoprosencephaly (Kjær and Fischer Hansen, 1995) Williams syndrome (Axelsson et al., 2004b)
Chondrodystrophy (Kjær, 2012) Turner syndrome (Kjær, 2012) Acromegaly (Kjær, 2012)s
Sundareswaran and Nipun, BRIDGING AND SIZE OF SELLA IN UCLP PATIENTS
FIGURE 1
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Patient selection process.
tal records belonged to the South Indian population of Dravidian race. Lateral cephalometric radiographs of patients taken with the Frankfurt horizontal plane parallel to the floor, lips in relaxed position, and teeth in maximum intercuspation were chosen. All of the radiographs had been taken by the trained radiographic technician of the institution using the same cephalostat in a standardized manner. The Planmeca 2002 CC Proline Cephalostat (Planmeca, Roselle, IL) was used. Radiographs of poor quality were not included.
To test the reliability, 20 randomly selected cephalograms were retraced after 2 weeks by the same investigator. The level of agreement was evaluated using Cronbach’s alpha. All of the scores exhibited very high agreement (Cronbach’s alpha values for sella bridging, 1; length of sella, 0.99; sella diameter, 0.89; depth of sella, 0.99). Cephalometric Landmarks and Parameters
Inclusion Criteria
The cephalometric landmarks and parameters were as follows (Fig. 2): Sp (dorsum sella), the most posterior
Records of UCLP patients were selected on the basis of the following inclusion criteria: (1) surgically repaired UCLP, (2) no associated syndromes, and (3) patients whose growth was largely completed. Inclusion criteria for the control group were (1) presence of skeletal Class I occlusion, (2) ANB angle between 08 and 48, and (3) Wits appraisal 61 mm. Radiographs of patients who did not give a clear reproduction of the sella turcica were excluded from this study. The patient selection process is given in Figure 1. Lateral cephalograms were hand traced onto 0.003inch matte acetate paper with a sharpened 2H lead drafting pencil by the same investigator under optimal illumination. Bilateral images were bisected and treated as midline structures. Linear measurements were recorded with a digital vernier caliper (6-inch, 0.01-mm accuracy; 500-196-20 Absolute Digimatic Digital Caliper, Mitutoyo, Kawasaki, Japan). Any disparities were addressed by retracing the structure.
FIGURE 2 Normal morphology of sella turcica with reference lines used to measure its size: TS (Tuberculum sella), Sp (Dorsum sella), Si (Floor of sella). Reference line: black line ¼ length of sella, dashed line ¼ depth of sella, dotted line ¼ diameter of sella.
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FIGURE 3 Types of sella turcica bridging. A: No sella bridging. B: Type A sella bridging. C: Type B sella bridging. D: Partial sella bridging.
point on the internal contour of the sella turcica; Ts (tuberculum sella), the anterior boundary of sella turcica; and Si (floor of sella), the lowermost point on the internal contour of the sella turcica. Sella Turcica Bridging According to Becktor et al. (2000), the sella turcica bridging (Fig. 3) is classified into two groups: sella turcica with no fusion (Fig. 3A) and sella turcica with a bridge, including type A, a ribbon-like fusion (Fig. 3B), and type B, extension of the anterior and/or posterior clinoid process, where these two meet either anteriorly, posteriorly, or in the middle, with a thinner fusion (Fig. 3C). When the calcified anterior and posterior clinoid processes fail to meet, it is referred to as partial sella bridging. This has been evaluated by Leonardi et al. (2006), according to whom, if the length of the sella turcica is less than or equal to three fourths of the diameter, it is classified as partially calcified (method A). However, as the length is measured from tuberculum sella (Ts) to dorsum sella (Sp), it does not take into consideration the variable extent of calcification of the clinoid processes. Hence, the current study adopted a second method, in which if the interclinoid distance (distance between anterior clinoid and posterior clinoid processes of sella turcica) is less than one third of the length of sella turcica, it is considered as partial sella bridging (method B; Fig. 3D).
Size of Sella To determine the linear dimensions of the sella turcica (Fig. 2), the methods of Silverman (1957) and Kisling (1966) were used. The tracing of the sella turcica was superimposed on graph paper marked in millimeters. The length of the sella turcica was measured as the distance from the tuberculum sella (Ts) to the tip of the dorsum sella (Sp). The depth of the sella turcica was measured as a perpendicular line from the length to the deepest point on the floor (Si). A line was drawn from the tuberculum sella (Ts) to the furthest point on the posterior inner wall of the sella turcica. This was considered as the anteroposterior diameter. Statistical Analysis All of the statistical analyses were performed using the SPSS statistical package (version 13) for Windows. Descriptive statistics, including means and standard deviations of the cephalometric parameters, were calculated for both groups. Paired-samples t test was used to assess differences in mean values between the cleft and control groups. The level of significance was set at P , .05. Wilcoxon signed ranks test was used to find the difference in sella bridging, as unequal observations were present between the two groups.
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TABLE 3
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Comparison of Sella Turcica Bridging Between Cleft and Control Groups Sella Turcica Bridging Partial Sella Bridging
No Bridging
Group
Type A
Type B
Method A (Leonardi’s Method)
Method B
Method A
Method B
UCLP group (64) Control group (64) Significance
4.68% (3) 0% (0) .000**
21.87% (14) 6.25% (4) .000**
42.18% (27) 23.43% (15) .029*
39.06% (25) 17.18% (11) .000**
31.27% (20) 70.32% (45) .000**
34.37% (22) 76.56% (49) .000**
* P , .05; ** P , .001.
RESULTS Sella Turcica Bridging Type A sella bridging was present in 4.68% of UCLP patients, whereas it was absent in the Class I control group (Table 3). Type B sella bridging was found in both groups, with a significantly higher prevalence in the UCLP patients (21.87%) as compared with the control group (6.25%). Partial sella bridging was also found to be higher in the UCLP group (42.18% in method A and 39.06% in method B). The prevalence of partial sella bridging in the control group was 23.43% in method A and 17.18% in method B. Sella Turcica Size Table 4 shows the linear dimensions of sella turcica in the cleft and control groups. The length, depth, and diameter of the control group was10.91 6 1.98 mm, 9.03 6 1.18 mm, and 13.17 6 1.89 mm, respectively. In the cleft group, all three linear dimensions, namely, length, depth, and diameter, showed a statistically highly significant (P , .001) reduction of 1.54 mm, 1.12 mm, and 1.21 mm, respectively, as compared with the controls. DISCUSSION Sella Bridging The osseous interclinoid ligament has been postulated as a developmental anomaly as early as 1940 by Hochstetter and also by Kier (1966). They had shown the existence of the foramen, which is formed by this ligament in the fetus and infant skull. Sellar bridges are laid down in cartilage at an early stage of development TABLE 4 Comparison of Linear Dimensions of Sella Turcica Between Cleft and Control Groups
Variable (mm)
UCLP Group Mean 6 SD
Control Group Mean 6 SD
Significance
Length Depth Diameter
9.37 6 1.54 7.91 6 1.26 11.96 6 1.64
10.91 6 1.98 9.03 6 1.18 13.17 6 1.89
.000* .000* .000*
* P , .001.
and ossify in early childhood (Lang, 1995). Ozdogmus et al. (2003) concluded that ossification of the interclinoid ligament is not age related. The ossifications that are observed in early life can be due to the complex embryology of the sphenoid bone, in which there are 18 to 19 ossification centers. Occurrence of sella bridging of both type A and type B was found to be significantly greater in the cleft group than among the controls in this study. In fact, type A sella bridging was absent in the control group. As an investigation into the occurrence of sella turcica bridging in UCLP cases does not seem to have been reported previously, it was not possible to compare the results with earlier findings. These results support the observations of Becktor et al. (2000), who had reported an increased sella bridging (18.6%) in a group of patients with severe craniofacial deviations. However, his sample did not specify inclusion of cleft patients. Another important finding in this study was the presence of partial calcification or partial bridging of the sella turcica in both groups. Two methods were used for this. When the method suggested by Leonardi (2006) was used to assess the partial sella bridging, a significantly higher incidence of 42.18% was observed in the cleft group as compared with 23.43% among the controls (method A). In the second method (method B), if the interclinoid distance was less than one third of the total sella length measured, it was considered to be partially calcified. According to this method, 39.06% of the cleft group showed partial sella bridging as compared with 17.18% in control group. The level of significance was found to be higher in method B. After conducting extensive research into fetal pathology, Kjær (2010) described several craniofacial fields, namely, the theca, frontonasal, maxillary, palatine, mandibular, and notochordal (cerebellar and cervical). These fields are stated to cover all areas on profile, frontal, and panoramic radiographs. The maxillary field includes the cranial part around the eyes, upper lip, hard palate, and sella turcica. The palatine field includes external tissues, posterior bony palate, soft palate, and alveolar bone around the molars. The sella turcica is formed at the most cranial extent of the notochord, and deviations in all cranial fields are said to be associated with deviations in sella turcica as well. This could
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account for the increased incidence of sella bridging in UCLP cases. Subjects without clefts such as skeletal Class III malocclusions have also been reported by many investigators to have a higher incidence of sella bridging (Abdel-Kader, 2007; Meyer-Marcotty et al., 2010). In a previous study, significant correlations between cranial base and maxillary parameters have been reported in skeletal Class III malocclusions with maxillary recession in terms of decreased cranial base angles and linear dimensions of anterior cranial base. Skeletal Class III cases with normal maxillae and prognathic mandibles did not exhibit a similar finding (Sundareswaran and Thirumoorty, 2012). This points to the fact that anomalies of the maxillary region could extend to the cranial base. This may account for the increased prevalence of sella bridging in such cases. Although the different skeletal combinations of the Class III samples used by previous investigators have not been specified, they may have included a significant number of cases with maxillary recession. The ligamentous or bony interclinoid connections have important neuronal and vascular relations and are both clinically and surgically important. Ossified interclinoid ligament could affect the surrounding neurovascular structures such as internal carotid artery and occulomotor nerve and cause clinical symptoms. These sella bridges might influence the blood flow of the internal carotid artery or cause dysfunction of the muscles of the eye, owing to possible compression of the occulomotor nerve (Skrzat et al., 2006). Presence of sella bridges presents difficulties in the surgery of aneurysms of the intracavernous portion of the internal carotid artery (Sekhar et al., 1987; Linskey et al., 1990; AlRodhan et al., 1993) and surgery for tuberculum sella meningiomas (Arai et al., 2000). Removing the anterior clinoid process is an important step in exposing the structures in the cavernous sinus and is highly complicated because of the neuronal and vascular relationships. The presence of the ossified interclinoid ligament makes this removal even more difficult (Inoue et al., 1990). Thus, knowledge of the detailed anatomy of the interclinoid ligament, its presence, and its prevalence can increase the success of diagnostic evaluation and surgical approaches to the region. Sella Turcica Dimension The mean sella dimensions of the Class I control group in this study comprising the Dravidian population of South India are similar to the Saudi (Alkofide, 2007) and Caucasian (Meyer-Marcotty et al., 2010) populations but larger than the Norwegian (Axelsson, 2004a), Iraqi (Najim and Al-Nakib, 2011), and Greek (Andredaki et al., 2007) populations.
All of the linear parameters (length, depth, and diameter) used to assess the dimensional features of sella turcica revealed a highly significant reduction in the cleft group as compared with controls (i.e., overall size of the sella turcica was smaller in the cleft group than in the control group). This agrees with the findings of Alkofide (2008). According to Sheng and Westphal (1999), the pituitary gland develops before the cartilaginous sella turcica has been formed. Kjær (2012) concluded that the development of the pituitary gland must be completed before the sella turcica can be formed and that the development of both of these are closely coordinated. Thus, lack of normal pituitary gland development may cause alterations in sella turcica growth, resulting in its smaller size. During development, the glandular or endocrine part of the pituitary gland is derived from the most anterior segment of midline surface ectoderm. As head development is initiated and the neuroepithelium expands to form the brain, the anterior neural ridge is displaced ventrally and eventually occupies the lower facial and oral area. It is thus the midline portion of the oral ectoderm that invaginates to become the pituitary anlage—Rathke’s pouch. This invagination does not form through an active process but rather appears to result from sustained contact between the neuroepithelium and oral ectoderm at the time when derivatives of the prechordal mesoderm and neural crest invade the space between the neuroepithelium and surface ectoderm and thus separate these tissue layers everywhere except in the midline at the pouch level. Rathke’s pouch is thus a simple epithelium that is a few cells thick extending at the back of the oral cavity toward the developing diencephalon, with which it maintains intimate contact. This contact is essential for proper pouch and pituitary development since its rupture either physically or through genetic manipulations leads to aborted pituitary development (Drouin, 2011). Neural crest cells, which arise from the final stages of formation of the embryonic neural tube, show specific migratory pathways away from the neural tube and into the facial and pharyngeal regions and have the remarkable capacity to differentiate into a wide variety of anatomical structures. Continued morphogenesis of the facial prominences as well as development of specific skeletal and muscular structures of each pharyngeal arch are critically dependent on continued viability and differentiation of these neural crest cells. Similarly, the anterior wall of the sella turcica also forms from neural crest cells. The migration of the neural crest cells is determined by factors intrinsic to the crest cells themselves and features of the external environment through which the crest cells migrate. Defective differentiation, proliferation, and migration of cranial neural crest cells have been linked to a variety of
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developmental defects called ‘‘neurocristopathies.’’ Deficiencies and excesses of retinoids, for example, can disrupt proliferation and migration of specific crest cells, resulting in craniofacial defects (e.g., clefts of the lip and palate; Burdi, 2006). Since the development of the face and pituitary gland occurs at the same period in intrauterine life, defective proliferation and deviated pathways of neural crest cell migration (either due to genetic or environmental influence) can cause altered development of the face and palate and may also cause premature rupture of the contact between neuroepithelium and oral ectoderm, resulting in the abnormal development of the pituitary gland. Since there exists a close interrelationship between the deviations observed in the pituitary gland and the characteristics observed in the sella turcica, the decreased dimensions of the sella turcica in UCLP subjects found in this study may be associated with abnormal or underdevelopment of the pituitary gland. This probably explains the findings of Jensen et al. (1983), whose study on physical development of cleft lip and palate patients had reported that children with clefts were smaller on average than children without clefts. Other investigators have also reported similar findings, indicating a correlation between cleft lip and palate and pituitary function (Zuppinger et al., 1971; Sultan et al., 1996). The shorter stature of the children with clefts, especially those involving the palate, as compared with their unaffected peers (Rudman et al., 1978; Bowers et al., 1987) has been attributed to pituitary insufficiency, which could vary from isolated growth hormone deficiency to complete congenital aplasia of the pituitary (Rimoin, 1976). Because of this association, a complete pituitary evaluation in short children with cleft lip and palate may be warranted (Rimoin, 1976; Kjær and Fischer Hansen, 2000). Limitations Only three-dimensional imaging such as computed tomography or digital volume tomography could generate more precise information about the sella area. However, because of the higher exposure to radiation, particularly with computed tomography, routine use of these imaging techniques in orthodontic patients is not indicated. Even though lateral cephalograms are not as accurate as three-dimensional techniques to detect sella turcica anomalies, they are, at present, the only routine diagnostic tools in orthodontics to evaluate the sella turcica region. Blinding of the maxillomandibular area could possibly eliminate measurement bias in the study. CONCLUSION This study was aimed at investigating the prevalence of sella bridging and dimensional characteristics of sella
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turcica in UCLP patients. The following conclusions can be drawn from the study: 1. Complete sella bridging of both type A (4.6%) and type B (21.7%) was significantly higher in UCLP patients. This has not been reported previously. Partial sella bridging was also higher among these cleft patients, as evidenced by the evaluation method of Leonardi (2006; 42.18 %) and another new method proposed in this investigation (39.06%). The null hypothesis is thus rejected. 2. All of the linear parameters used to assess the dimensional features of sella turcica, namely, length, depth, and diameter, showed a highly significant reduction of 1.54 mm, 1.12 mm, and 1.2 mm, respectively, in the UCLP group. The mean dimensions of sella turcica in the skeletal Class I controls of Dravidian ethnicity were almost similar to Saudi and Caucasian samples used in previous investigations. REFERENCES Abdel-Kader HM. Sella turcica bridges in orthodontic and orthognathic surgery patients: a retrospective cephalometric study. Aust Orthod J. 2007;23:30–35. Alkofide EA. Sella turcica morphology and dimensions in cleft subjects. Cleft Palate Craniofac J. 2008;45:647–653. Alkofide EA. The shape and size of the sella turcica in skeletal Class I, Class II, and Class III Saudi subjects. Eur J Orthod. 2007;29:457– 463. Al-Rodhan NR, Piepgras DG, Sundt TM Jr. Transitional cavernous aneurysms of the internal carotid artery. Neurosurgery. 1993;33:993–998. Andredaki M, Koumantanou A, Dorotheou D, Halazonetis D. A cephalometric morphometric study of the sella turcica. Eur J Orthod. 2007;29:449–456. Arai H, Sato K, Okuda O, Miyajima M, Hishii M, Nakanishi H, Ishii H. Transcranial transsphenoidal approach for tuberculum sellae meningiomas. Acta Neurochir. 2000;142:751–757. Axelsson S, Storhaug K, Kjær I. Post-natal size and morphology of the sella turcica: longitudinal cephalometric standards for Norwegians between 6 and 21 years of age. Eur J Orthod. 2004a;26:597– 604. Axelsson S, Storhaug K, Kjær I. Post-natal size and morphology of the sella turcica in Williams syndrome. Eur J Orthod. 2004b;26:613– 621. Becktor JP, Einersen S, Kjær I. A sella turcica bridge in subjects with severe craniofacial deviations. Eur J Orthod. 2000;22:69–74. Bjork ¨ A. The face in profile: an anthropological x-ray investigation on Swedish children and conscripts. Berlingska Boktryckeriet. 1947;40:180. Bjork A. Facial growth in man, studied with the aid of metallic ¨ implants. Acta Odontol Scand. 1955;13:9–34. Bjork A, Skieller V. Normal and abnormal growth of the mandible: a ¨ synthesis of longitudinal cephalometric implant studies over a period of 25 years. Eur J Orthod. 1983;5:1–46. Bowers EJ, Mayro RF, Whitaker LA, Pasquariello PS, Larossa D, Randall P. General body growth in children with clefts of the lip, palate, and craniofacial structure. Scand J Plast Reconstr Surg Hand Surg. 1987;21:7–14. Burdi A. Developmental biology and morphogenesis of the face, lip and palate. In: Berkowitz S, ed. Cleft Lip and Palate. New York: Springer Berlin Heidelberg; 2006:3–12.
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Drouin J. The Pituitary. 3rd ed. London: Elsevier; 2011. Harris EF. Size and form of the cranial base in isolated cleft lip and palate. Cleft Palate Craniofac J. 1993;30:170–174. Hjalgrim H, Fisher Hansen B, Brondum-Nielsen K, Nolting D, Kjaer I. Aspects of skeletal development in fragile X syndrome fetuses. Am J Med Genet. 2000;95:123–129. ¨ Hochstetter F. Uber die Taenia interclinoidea, die Commissura alicochlearis und die Cartilago supracochlearis des menschlichen Primordialkraniums. Gegenbaurs Morph Jb. 1940;84:220–243. Inoue T, Rhoton AL Jr, Theele D, Barry ME. Surgical approaches to the cavernous sinus: a microsurgical study. Neurosurgery. 1990:26:903–932. Jain N, Joseph R, Balan S, Arun R, Banerjee M. Association of interleukin-4 and interleukin-17F polymorphisms in periodontitis in Dravidian ethnicity. Indian J Hum Genet. 2013;19:58–64. Jensen BL, Dahl E, Kreiborg S. Longitudinal study of body height, radius length and skeletal maturity in Danish boys with cleft lip and palate. Eur J Oral Sci. 1983;91:473–481. Jones R, Faqir A, Millett D, Moos K, McHugh S. Bridging and dimensions of sella turcica in subjects treated by surgicalorthodontic means or orthodontics only. Angle Orthod. 2005;75:714–718. Kier EL. Embryology of the normal optic canal and its anomalies: an anatomic and roentgenographic study. Invest Radiol. 1966;1:346– 362. Kisling E. Cranial Morphology in Down’s Syndrome: A Comparative Roentgenencephalometric Study in Adult Males [dissertation]. Copenhagen: Munksgaard; 1966. Kjær I. Orthodontics and foetal pathology: a personal view on craniofacial patterning. Eur J Orthod. 2010;32:140–147. Kjær I. Sella turcica morphology and the pituitary gland—a new contribution to craniofacial diagnostics based on histology and neuroradiology [published online November 16, 2012]. Eur J Orthod. Kjær I, Becktor KB, Lisson J, Gormsen C, Russell BG. Face, palate, and craniofacial morphology in patients with a solitary median maxillary central incisor. Eur J Orthod. 2001;23:63–73. Kjær I, Fischer Hansen B. Human fetal pituitary gland in holoprosencephaly and anencephaly. J Craniofac Genet Dev Biol. 1995;15:222–229. Kjær I, Fischer Hansen B. The prenatal pituitary gland—hidden and forgotten. Pediatr Neurol. 2000;22:155–156. Kjær I, Keeling JW, Fischer Hansen B, Becktor KB. Midline skeletodental morphology in holoprosencephaly. Cleft Palate Craniofac J. 2002;39:357–363. Kjær I, Keeling JW, Reintoft I, Hjalgrim H, Nolting D, Hansen BF. Pituitary gland and sella turcica in human trisomy 18 fetuses. Am J Med Genet. 1998a;76:87–92. Kjær I, Keeling JW, Reintoft I, Nolting D, Fischer Hansen B. Pituitary gland and sella turcica in human trisomy 21 fetuses related to axial skeletal development. Am J Med Genet. 1998b;80:494–500. Kjær I, Niebuhr E. Studies of the cranial base in 23 patients with cridu-chat syndrome suggest a cranial developmental field involved in the condition. Am J Med Genet. 1999;82:6–14. Kjær I, Wagner A, Madsen P, Blichfeldt S, Rasmussen K, Russell B. The sella turcica in children with lumbosacral myelomeningocele. Eur J Orthod. 1998c;20:443–448. Lang J. Skull Base and Related Structures: Atlas of Clinical Anatomy. Stuttgart, Germany: Schattauer; 1995.
Lang J. Structure and postnatal organization of heretofore uninvestigated and infrequent ossifications of the sella turcica region. Cells Tissues Organs. 1977;99:121–139. Leonardi R, Barbato E, Vichi M, Caltabiano M. A sella turcica bridge in subjects with dental anomalies. Eur J Orthod. 2006;28:580–585. Linskey ME, Sekhar LN, Hirsch WL Jr, Yonas H, Horton JA. Aneurysms of the intracavernous carotid artery: natural history and indications for treatment. Neurosurgery. 1990;26:933–938. Melsen B. The cranial base: the postnatal development of the cranial base studied histologically on human autopsy material. Acta Odontol Scand. 1974;32:72–85. Meyer-Marcotty P, Reuther T, Stellzig-Eisenhauer A. Bridging of the sella turcica in skeletal Class III subjects. Eur J Orthod. 2010;32:148–153. Meyer-Marcotty P, Weisschuh N, Dressler P, Hartmann J, StellzigEisenhauer A. Morphology of the sella turcica in Axenfeld–Rieger syndrome with PITX2 mutation. J Oral Pathol Med. 2008;37:504– 510. Moss ML. Malformations of the skull base associated with cleft palate deformity. Plast Reconstr Surg. 1956;17:226–234. Najim AA, Al-Nakib L. A cephalometric study of sella turcica size and morphology among young Iraqi normal population in comparison to patients with maxillary malposed canine. Science Journal Published by the College of Dentistry–University of Baghdad. 2011:53. Nielsen BW, Mølsted K, Kjaer I. Maxillary and sella turcica morphology in newborns with cleft lip and palate. Cleft Palate Craniofac J. 2005;42:610–617. Ozdogmus O, Saka E, Tulay C, Gurdal E, Uzun I, Cavdar S. Ossification of interclinoid ligament and its clinical significance. Neuroanatomy. 2003;2:25–27. Rimoin DL. Hereditary forms of growth hormone deficiency and resistance. Birth Defects Orig Artic Ser. 1976;12:15–29. Rudman D, Davis GT, Priest JH, Patterson JH, Kutner MH, Heymsfield SB, Bethel RA. Prevalence of growth hormone deficiency in children with cleft lip or palate. J Pediatr. 1978;93:378–382. Sekhar LN, Burgess J, Akin O. Anatomical study of the cavernous sinus emphasizing operative approaches and related vascular and neural reconstruction. Neurosurgery. 1987;21:806–816. Sheng HZ, Westphal H. Early steps in pituitary organogenesis. Trends Genet. 1999;15:236–240. Silverman FN. Roentgen standards for size of the pituitary fossa from infancy through adolescence. Am J Roentgenol Radium Ther Nucl Med. 1957;78:451–460. Skrzat J, Szewczyk R, Walocha J. The ossified interclinoid ligament. Folia Morphol (Warsz). 2006;65:242–251. Sultan Z, Gnanaratnam J, Sharief N. Isolated aplasia of the anterior pituitary gland with unusual associations. Clin Dysmorphol. 1996;5:347–350. Sundareswaran, S, Thirumoorty SN. Anterior cranial base features in skeletal Class III patients with maxillary recession: a cephalometric study. Orthodontics (Chic). 2012;13:e105–e115. Wardill W. Cleft palate. Br J Surg. 1928;16:127–148. Zuppinger K, Sutter M, Zurbrugg R, Joss E, Oetliker O. Cleft lip and ¨ chorioideal coloboma associated with multiple hypothalamopituitary dysfunctions. J Clin Endocrinol Metab. 1971;33:934–939.
ORIGINAL ARTICLE Bridging the Gap: Sella Turcica in Unilateral Cleft Lip and Palate Patients Shobha Sundareswaran, B.D.S., M.D.S., C. A. Nipun, B.D.S., M.D.S. Objectives: The aims of this study were to analyze the prevalence of sella turcica bridging and to measure the size of the sella turcica on profile cephalograms in a homogenous group of surgically repaired unilateral cleft lip and palate (UCLP) patients. Setting: Tertiary care center. Design: Retrospective cross-sectional study. Patients: Preorthodontic lateral cephalometric radiographs of 64 UCLP individuals between the ages of 16 and 29 years along with an equal number of age- and sex-matched skeletal Class I controls. Main Outcome Measures: The extent of calcification of the interclinoid ligament was quantified (completely calcified, partially calcified, no calcification) and mean values compared. Length, depth, and diameter of the sella turcica were also measured. The results were statistically analyzed using paired t test and Wilcoxon signed ranks test. Results: Complete sella bridging of both type A (4.6%) and type B (21.7%) was significantly higher in UCLP patients. This has not been reported previously. Partial sella bridging was also higher in cleft patients as evaluated by two methods (42.18%, 39.06%). This study demonstrated a statistically significant decrease in all dimensions of sella turcica in UCLP patients. Conclusions: The UCLP patients apparently had higher predilection for sella turcica bridging. The dimensions of sella turcica were also seen to be significantly smaller than the control group. Defective proliferation and deviated pathways of neural crest cell migration as well as premature rupture of contact between neuroepithelium and oral ectoderm as postulated causes are discussed. KEY WORDS:
cleft lip and palate, neural crest cells, sella bridging, sella dimensions
surface of the body of the sphenoid bone, housing the pituitary gland with two anterior and two posterior clinoid processes projecting over it. In orthodontics, sella is considered to be an important structure, as the midpoint of sella turcica termed the Sella point (Bjork, 1947) is used ¨ extensively as a reference point in various cephalometric analyses. The anterior wall of sella turcica and the Walker point (the point at which the anterior wall of the pituitary fossa crosses the inferior surface of the anterior clinoid process) are very visible and used in the evaluation of craniofacial growth and orthodontic treatment results (Bjork and Skieller, 1983). The fact that bone apposition ¨ on the anterior part of the inner surface of the sella turcica ceases at an early age makes it a stable structure (Melsen, 1974). Resorption along the posterior wall and the floor of sella continues for a longer time, leading to a backward and downward displacement of the sella point during growth. Because these points are routine diagnostic tools, many pathological variations are likely to be discovered in lateral cephalograms during orthodontic therapy. The sella anatomy is variable in terms of shape, size, and morphology. Previous studies have focused on sella turcica of normal individuals (Bjork, 1955; Melsen, 1974; Bjork ¨ and Skieller, 1983; Axelsson et al., 2004a; Alkofide, 2007) as well as subjects with disorders such as Cri du chat (Kjær
Clefts of the lip and palate are considered to be the most common congenital anomalies of the craniofacial region. The fact that clefts are not localized defects but may be associated with widespread structural changes in other parts of the skull had been recognized very early (Wardill, 1928). A primary defect in one structure can lead to secondary defects in contiguous structures. Disturbances in the facial growth are said to occur due to a combination of intrinsic abnormalities as well as environmental factors, and the effect of this is said to extend to other areas in the cranium, leading to extensive studies on cranial base features in cleft lip and palate patients (Moss, 1956; Harris, 1993). However, the effect of these abnormalities on the sella turcica has not been fully investigated. Literally meaning ‘‘Turkish saddle,’’ the sella turcica is a saddle-shaped depression situated on the intracranial
Ms. Sundareswaran is Professor and Head and Mr. Nipun is Senior Resident, Department of Orthodontics, Government Dental College, Calicut, Kerala, India. Submitted October 2013; Revised February 2014, May 2014; Accepted September 2014. Address correspondence to: Ms. Shobha Sundareswaran, Department of Orthodontics, Government Dental College, Calicut, Kerala, India. E-mail [email protected]. DOI: 10.1597/13-258 597
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TABLE 1
Prevalence of Sella Bridging in Various Syndromes Syndrome/Anomaly
Authors
Prevalence of Sella Bridging (%)
Severe craniofacial deviations Solitary median maxillary central incisor Williams syndrome Dentofacial deformities Palatally displaced canines, agenesis of mandibular second premolars Skeletal Class III patients Axenfeld–Rieger syndrome with PITX2 mutation Skeletal Class III patients
Bektor et al. (2000) Kjaer et al. (2001) Axelsson et al. (2004b) Jones et al. (2005) Leonardi et al. (2006) Abdel-Kader (2007) Meyer-Marcotty et al. (2008) Meyer-Marcotty et al. (2010)
18.6 Not specified 13 16.70 17.60 10.71 Not specified 16.80
and Niebuhr, 1999), fragile X (Hjalgrim et al., 2000), holoprosencephaly (Kjær and Fischer Hansen, 1995; Kjær et al., 2002), solitary median maxillary central incisor ( Kjær et al., 2001), trisomy 18 (Kjær et al., 1998a), trisomy 21 ((Kjær et al., 1998b), spina bifida (Kjær et al., 1998c), Axenfeld–Rieger syndrome with PITX2 mutation (Meyer Marcotty et al., 2008), and Williams syndrome (Axelsson et al., 2004b). Despite cleft lip and palate being one of the most common congenital anomalies, the literature is scant with regard to their sella characteristics. One study based on radiographs of 40 newborns with cleft lip and palate revealed deviations in the sella morphology in approximately half of the sample, with the most severe deviations occurring in unilateral cleft lip and palate (UCLP) patients (Nielsen et al., 2005). In a recent overview of craniofacial patterning, Kjær (2010) described six main fields registered on the fetal craniofacial skeleton: theca, frontonasal, maxillary, palatine, mandibular, together with cerebellar and cervical. It is said that all craniofacial fields are developmentally interrelated with the sella turcica region. Hence, it can logically be hypothesized that malformations in the frontonasal, maxillary, and palatine fields will extend to the sella turcica as well. Fusion of the anterior and posterior clinoid processes is yet another reported anatomic abnormality of the sella turcica. In the literature, this bony formation is referred to as sella bridge (Lang, 1977), interclinoid osseous bridge (Inoue et al., 1990), or interclinoid taeina (Lang, 1995). This has been reported in various syndromes (Table 1). These bony interclinoid connections have important neuronal and vascular relations and are both clinically and surgically important. Knowledge of a detailed anatomy of the interclinoid ligament can increase the success of diagnostic evaluation and surgical approaches to the region (Ozdogmus et al., 2003). To date, there have been no studies on the prevalence of the sella turcica bridging in UCLP patients; hence, it is not known if they are more susceptible to these osseous interclinoid connections. Difference in the size of sella turcica has been reported in various syndromes (Table 2). Also, sella dimensions are apparently not the same in different populations. The dimensions of the sella in the Saudi sample were on average 1.07 to 2.97 mm larger than in the Norwegian sample of Axelsson (Alkofide, 2007). The Greek population is reported to have smaller dimensions of the sella turcica
(Andredaki et al., 2007). This obviously indicates racial differences and a need to assess normal dimensions in different populations to appreciate variations. The southern states of India, including Kerala, are populated by people of Dravidian ethnic origin. Dravidian ethnicity includes Tamil-, Telugu-, Kannada-, and Malayalamspeaking people (Jain et al., 2013). No literature exists regarding the sella dimensions of individuals belonging to this race. Hence, the aims of this study were to (1) analyze the prevalence of sella turcica bridging and (2) measure the sella dimensions in a group of UCLP patients and to compare them with Class I controls. The null hypothesis generated was that there may be no difference in the prevalence of sella bridging among UCLP patients as compared with the control group. MATERIALS
AND
METHODS
Approval for this retrospective study was obtained from the Institutional Research Board and Institutional Ethics Committee (IEC No. 14/2011/DCC, dated March 15, 2011). Sample size was determined using the formula n ¼ (Za þ Z"b)2SD2/d2, where Za ¼ 1.96, Z"b ¼ 0.84 (constant), SD ¼ standard deviation of key variable d ¼ X1 – X2, X1 ¼ mean of key variable in case, and X2 ¼ mean of key variable in control, based on the mean sella length value of individuals with Class I occlusion (Axelsson et al., 2004b). To detect a change of 0.5 mm from this mean value with 95% confidence and 80% power, we required a minimum sample size of 53 in each group. Accordingly, preorthodontic lateral cephalometric radiographs of 64 individuals (33 males and 31 females) with surgically repaired UCLP between the ages of 16 and 29 years were selected. A control group comprising of 64 skeletal Class I patients matched for age and sex were also selected. All cases and controls taken from the departmenTABLE 2
Sella Dimensional Variations in Various Syndromes
Decrease in the Size of the Sella Turcica
Increase in the Size of the Sella Turcica
Holoprosencephaly (Kjær and Fischer Hansen, 1995) Williams syndrome (Axelsson et al., 2004b)
Chondrodystrophy (Kjær, 2012) Turner syndrome (Kjær, 2012) Acromegaly (Kjær, 2012)s
Sundareswaran and Nipun, BRIDGING AND SIZE OF SELLA IN UCLP PATIENTS
FIGURE 1
599
Patient selection process.
tal records belonged to the South Indian population of Dravidian race. Lateral cephalometric radiographs of patients taken with the Frankfurt horizontal plane parallel to the floor, lips in relaxed position, and teeth in maximum intercuspation were chosen. All of the radiographs had been taken by the trained radiographic technician of the institution using the same cephalostat in a standardized manner. The Planmeca 2002 CC Proline Cephalostat (Planmeca, Roselle, IL) was used. Radiographs of poor quality were not included.
To test the reliability, 20 randomly selected cephalograms were retraced after 2 weeks by the same investigator. The level of agreement was evaluated using Cronbach’s alpha. All of the scores exhibited very high agreement (Cronbach’s alpha values for sella bridging, 1; length of sella, 0.99; sella diameter, 0.89; depth of sella, 0.99). Cephalometric Landmarks and Parameters
Inclusion Criteria
The cephalometric landmarks and parameters were as follows (Fig. 2): Sp (dorsum sella), the most posterior
Records of UCLP patients were selected on the basis of the following inclusion criteria: (1) surgically repaired UCLP, (2) no associated syndromes, and (3) patients whose growth was largely completed. Inclusion criteria for the control group were (1) presence of skeletal Class I occlusion, (2) ANB angle between 08 and 48, and (3) Wits appraisal 61 mm. Radiographs of patients who did not give a clear reproduction of the sella turcica were excluded from this study. The patient selection process is given in Figure 1. Lateral cephalograms were hand traced onto 0.003inch matte acetate paper with a sharpened 2H lead drafting pencil by the same investigator under optimal illumination. Bilateral images were bisected and treated as midline structures. Linear measurements were recorded with a digital vernier caliper (6-inch, 0.01-mm accuracy; 500-196-20 Absolute Digimatic Digital Caliper, Mitutoyo, Kawasaki, Japan). Any disparities were addressed by retracing the structure.
FIGURE 2 Normal morphology of sella turcica with reference lines used to measure its size: TS (Tuberculum sella), Sp (Dorsum sella), Si (Floor of sella). Reference line: black line ¼ length of sella, dashed line ¼ depth of sella, dotted line ¼ diameter of sella.
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FIGURE 3 Types of sella turcica bridging. A: No sella bridging. B: Type A sella bridging. C: Type B sella bridging. D: Partial sella bridging.
point on the internal contour of the sella turcica; Ts (tuberculum sella), the anterior boundary of sella turcica; and Si (floor of sella), the lowermost point on the internal contour of the sella turcica. Sella Turcica Bridging According to Becktor et al. (2000), the sella turcica bridging (Fig. 3) is classified into two groups: sella turcica with no fusion (Fig. 3A) and sella turcica with a bridge, including type A, a ribbon-like fusion (Fig. 3B), and type B, extension of the anterior and/or posterior clinoid process, where these two meet either anteriorly, posteriorly, or in the middle, with a thinner fusion (Fig. 3C). When the calcified anterior and posterior clinoid processes fail to meet, it is referred to as partial sella bridging. This has been evaluated by Leonardi et al. (2006), according to whom, if the length of the sella turcica is less than or equal to three fourths of the diameter, it is classified as partially calcified (method A). However, as the length is measured from tuberculum sella (Ts) to dorsum sella (Sp), it does not take into consideration the variable extent of calcification of the clinoid processes. Hence, the current study adopted a second method, in which if the interclinoid distance (distance between anterior clinoid and posterior clinoid processes of sella turcica) is less than one third of the length of sella turcica, it is considered as partial sella bridging (method B; Fig. 3D).
Size of Sella To determine the linear dimensions of the sella turcica (Fig. 2), the methods of Silverman (1957) and Kisling (1966) were used. The tracing of the sella turcica was superimposed on graph paper marked in millimeters. The length of the sella turcica was measured as the distance from the tuberculum sella (Ts) to the tip of the dorsum sella (Sp). The depth of the sella turcica was measured as a perpendicular line from the length to the deepest point on the floor (Si). A line was drawn from the tuberculum sella (Ts) to the furthest point on the posterior inner wall of the sella turcica. This was considered as the anteroposterior diameter. Statistical Analysis All of the statistical analyses were performed using the SPSS statistical package (version 13) for Windows. Descriptive statistics, including means and standard deviations of the cephalometric parameters, were calculated for both groups. Paired-samples t test was used to assess differences in mean values between the cleft and control groups. The level of significance was set at P , .05. Wilcoxon signed ranks test was used to find the difference in sella bridging, as unequal observations were present between the two groups.
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TABLE 3
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Comparison of Sella Turcica Bridging Between Cleft and Control Groups Sella Turcica Bridging Partial Sella Bridging
No Bridging
Group
Type A
Type B
Method A (Leonardi’s Method)
Method B
Method A
Method B
UCLP group (64) Control group (64) Significance
4.68% (3) 0% (0) .000**
21.87% (14) 6.25% (4) .000**
42.18% (27) 23.43% (15) .029*
39.06% (25) 17.18% (11) .000**
31.27% (20) 70.32% (45) .000**
34.37% (22) 76.56% (49) .000**
* P , .05; ** P , .001.
RESULTS Sella Turcica Bridging Type A sella bridging was present in 4.68% of UCLP patients, whereas it was absent in the Class I control group (Table 3). Type B sella bridging was found in both groups, with a significantly higher prevalence in the UCLP patients (21.87%) as compared with the control group (6.25%). Partial sella bridging was also found to be higher in the UCLP group (42.18% in method A and 39.06% in method B). The prevalence of partial sella bridging in the control group was 23.43% in method A and 17.18% in method B. Sella Turcica Size Table 4 shows the linear dimensions of sella turcica in the cleft and control groups. The length, depth, and diameter of the control group was10.91 6 1.98 mm, 9.03 6 1.18 mm, and 13.17 6 1.89 mm, respectively. In the cleft group, all three linear dimensions, namely, length, depth, and diameter, showed a statistically highly significant (P , .001) reduction of 1.54 mm, 1.12 mm, and 1.21 mm, respectively, as compared with the controls. DISCUSSION Sella Bridging The osseous interclinoid ligament has been postulated as a developmental anomaly as early as 1940 by Hochstetter and also by Kier (1966). They had shown the existence of the foramen, which is formed by this ligament in the fetus and infant skull. Sellar bridges are laid down in cartilage at an early stage of development TABLE 4 Comparison of Linear Dimensions of Sella Turcica Between Cleft and Control Groups
Variable (mm)
UCLP Group Mean 6 SD
Control Group Mean 6 SD
Significance
Length Depth Diameter
9.37 6 1.54 7.91 6 1.26 11.96 6 1.64
10.91 6 1.98 9.03 6 1.18 13.17 6 1.89
.000* .000* .000*
* P , .001.
and ossify in early childhood (Lang, 1995). Ozdogmus et al. (2003) concluded that ossification of the interclinoid ligament is not age related. The ossifications that are observed in early life can be due to the complex embryology of the sphenoid bone, in which there are 18 to 19 ossification centers. Occurrence of sella bridging of both type A and type B was found to be significantly greater in the cleft group than among the controls in this study. In fact, type A sella bridging was absent in the control group. As an investigation into the occurrence of sella turcica bridging in UCLP cases does not seem to have been reported previously, it was not possible to compare the results with earlier findings. These results support the observations of Becktor et al. (2000), who had reported an increased sella bridging (18.6%) in a group of patients with severe craniofacial deviations. However, his sample did not specify inclusion of cleft patients. Another important finding in this study was the presence of partial calcification or partial bridging of the sella turcica in both groups. Two methods were used for this. When the method suggested by Leonardi (2006) was used to assess the partial sella bridging, a significantly higher incidence of 42.18% was observed in the cleft group as compared with 23.43% among the controls (method A). In the second method (method B), if the interclinoid distance was less than one third of the total sella length measured, it was considered to be partially calcified. According to this method, 39.06% of the cleft group showed partial sella bridging as compared with 17.18% in control group. The level of significance was found to be higher in method B. After conducting extensive research into fetal pathology, Kjær (2010) described several craniofacial fields, namely, the theca, frontonasal, maxillary, palatine, mandibular, and notochordal (cerebellar and cervical). These fields are stated to cover all areas on profile, frontal, and panoramic radiographs. The maxillary field includes the cranial part around the eyes, upper lip, hard palate, and sella turcica. The palatine field includes external tissues, posterior bony palate, soft palate, and alveolar bone around the molars. The sella turcica is formed at the most cranial extent of the notochord, and deviations in all cranial fields are said to be associated with deviations in sella turcica as well. This could
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account for the increased incidence of sella bridging in UCLP cases. Subjects without clefts such as skeletal Class III malocclusions have also been reported by many investigators to have a higher incidence of sella bridging (Abdel-Kader, 2007; Meyer-Marcotty et al., 2010). In a previous study, significant correlations between cranial base and maxillary parameters have been reported in skeletal Class III malocclusions with maxillary recession in terms of decreased cranial base angles and linear dimensions of anterior cranial base. Skeletal Class III cases with normal maxillae and prognathic mandibles did not exhibit a similar finding (Sundareswaran and Thirumoorty, 2012). This points to the fact that anomalies of the maxillary region could extend to the cranial base. This may account for the increased prevalence of sella bridging in such cases. Although the different skeletal combinations of the Class III samples used by previous investigators have not been specified, they may have included a significant number of cases with maxillary recession. The ligamentous or bony interclinoid connections have important neuronal and vascular relations and are both clinically and surgically important. Ossified interclinoid ligament could affect the surrounding neurovascular structures such as internal carotid artery and occulomotor nerve and cause clinical symptoms. These sella bridges might influence the blood flow of the internal carotid artery or cause dysfunction of the muscles of the eye, owing to possible compression of the occulomotor nerve (Skrzat et al., 2006). Presence of sella bridges presents difficulties in the surgery of aneurysms of the intracavernous portion of the internal carotid artery (Sekhar et al., 1987; Linskey et al., 1990; AlRodhan et al., 1993) and surgery for tuberculum sella meningiomas (Arai et al., 2000). Removing the anterior clinoid process is an important step in exposing the structures in the cavernous sinus and is highly complicated because of the neuronal and vascular relationships. The presence of the ossified interclinoid ligament makes this removal even more difficult (Inoue et al., 1990). Thus, knowledge of the detailed anatomy of the interclinoid ligament, its presence, and its prevalence can increase the success of diagnostic evaluation and surgical approaches to the region. Sella Turcica Dimension The mean sella dimensions of the Class I control group in this study comprising the Dravidian population of South India are similar to the Saudi (Alkofide, 2007) and Caucasian (Meyer-Marcotty et al., 2010) populations but larger than the Norwegian (Axelsson, 2004a), Iraqi (Najim and Al-Nakib, 2011), and Greek (Andredaki et al., 2007) populations.
All of the linear parameters (length, depth, and diameter) used to assess the dimensional features of sella turcica revealed a highly significant reduction in the cleft group as compared with controls (i.e., overall size of the sella turcica was smaller in the cleft group than in the control group). This agrees with the findings of Alkofide (2008). According to Sheng and Westphal (1999), the pituitary gland develops before the cartilaginous sella turcica has been formed. Kjær (2012) concluded that the development of the pituitary gland must be completed before the sella turcica can be formed and that the development of both of these are closely coordinated. Thus, lack of normal pituitary gland development may cause alterations in sella turcica growth, resulting in its smaller size. During development, the glandular or endocrine part of the pituitary gland is derived from the most anterior segment of midline surface ectoderm. As head development is initiated and the neuroepithelium expands to form the brain, the anterior neural ridge is displaced ventrally and eventually occupies the lower facial and oral area. It is thus the midline portion of the oral ectoderm that invaginates to become the pituitary anlage—Rathke’s pouch. This invagination does not form through an active process but rather appears to result from sustained contact between the neuroepithelium and oral ectoderm at the time when derivatives of the prechordal mesoderm and neural crest invade the space between the neuroepithelium and surface ectoderm and thus separate these tissue layers everywhere except in the midline at the pouch level. Rathke’s pouch is thus a simple epithelium that is a few cells thick extending at the back of the oral cavity toward the developing diencephalon, with which it maintains intimate contact. This contact is essential for proper pouch and pituitary development since its rupture either physically or through genetic manipulations leads to aborted pituitary development (Drouin, 2011). Neural crest cells, which arise from the final stages of formation of the embryonic neural tube, show specific migratory pathways away from the neural tube and into the facial and pharyngeal regions and have the remarkable capacity to differentiate into a wide variety of anatomical structures. Continued morphogenesis of the facial prominences as well as development of specific skeletal and muscular structures of each pharyngeal arch are critically dependent on continued viability and differentiation of these neural crest cells. Similarly, the anterior wall of the sella turcica also forms from neural crest cells. The migration of the neural crest cells is determined by factors intrinsic to the crest cells themselves and features of the external environment through which the crest cells migrate. Defective differentiation, proliferation, and migration of cranial neural crest cells have been linked to a variety of
Sundareswaran and Nipun, BRIDGING AND SIZE OF SELLA IN UCLP PATIENTS
developmental defects called ‘‘neurocristopathies.’’ Deficiencies and excesses of retinoids, for example, can disrupt proliferation and migration of specific crest cells, resulting in craniofacial defects (e.g., clefts of the lip and palate; Burdi, 2006). Since the development of the face and pituitary gland occurs at the same period in intrauterine life, defective proliferation and deviated pathways of neural crest cell migration (either due to genetic or environmental influence) can cause altered development of the face and palate and may also cause premature rupture of the contact between neuroepithelium and oral ectoderm, resulting in the abnormal development of the pituitary gland. Since there exists a close interrelationship between the deviations observed in the pituitary gland and the characteristics observed in the sella turcica, the decreased dimensions of the sella turcica in UCLP subjects found in this study may be associated with abnormal or underdevelopment of the pituitary gland. This probably explains the findings of Jensen et al. (1983), whose study on physical development of cleft lip and palate patients had reported that children with clefts were smaller on average than children without clefts. Other investigators have also reported similar findings, indicating a correlation between cleft lip and palate and pituitary function (Zuppinger et al., 1971; Sultan et al., 1996). The shorter stature of the children with clefts, especially those involving the palate, as compared with their unaffected peers (Rudman et al., 1978; Bowers et al., 1987) has been attributed to pituitary insufficiency, which could vary from isolated growth hormone deficiency to complete congenital aplasia of the pituitary (Rimoin, 1976). Because of this association, a complete pituitary evaluation in short children with cleft lip and palate may be warranted (Rimoin, 1976; Kjær and Fischer Hansen, 2000). Limitations Only three-dimensional imaging such as computed tomography or digital volume tomography could generate more precise information about the sella area. However, because of the higher exposure to radiation, particularly with computed tomography, routine use of these imaging techniques in orthodontic patients is not indicated. Even though lateral cephalograms are not as accurate as three-dimensional techniques to detect sella turcica anomalies, they are, at present, the only routine diagnostic tools in orthodontics to evaluate the sella turcica region. Blinding of the maxillomandibular area could possibly eliminate measurement bias in the study. CONCLUSION This study was aimed at investigating the prevalence of sella bridging and dimensional characteristics of sella
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turcica in UCLP patients. The following conclusions can be drawn from the study: 1. Complete sella bridging of both type A (4.6%) and type B (21.7%) was significantly higher in UCLP patients. This has not been reported previously. Partial sella bridging was also higher among these cleft patients, as evidenced by the evaluation method of Leonardi (2006; 42.18 %) and another new method proposed in this investigation (39.06%). The null hypothesis is thus rejected. 2. All of the linear parameters used to assess the dimensional features of sella turcica, namely, length, depth, and diameter, showed a highly significant reduction of 1.54 mm, 1.12 mm, and 1.2 mm, respectively, in the UCLP group. The mean dimensions of sella turcica in the skeletal Class I controls of Dravidian ethnicity were almost similar to Saudi and Caucasian samples used in previous investigations. REFERENCES Abdel-Kader HM. Sella turcica bridges in orthodontic and orthognathic surgery patients: a retrospective cephalometric study. Aust Orthod J. 2007;23:30–35. Alkofide EA. Sella turcica morphology and dimensions in cleft subjects. Cleft Palate Craniofac J. 2008;45:647–653. Alkofide EA. The shape and size of the sella turcica in skeletal Class I, Class II, and Class III Saudi subjects. Eur J Orthod. 2007;29:457– 463. Al-Rodhan NR, Piepgras DG, Sundt TM Jr. Transitional cavernous aneurysms of the internal carotid artery. Neurosurgery. 1993;33:993–998. Andredaki M, Koumantanou A, Dorotheou D, Halazonetis D. A cephalometric morphometric study of the sella turcica. Eur J Orthod. 2007;29:449–456. Arai H, Sato K, Okuda O, Miyajima M, Hishii M, Nakanishi H, Ishii H. Transcranial transsphenoidal approach for tuberculum sellae meningiomas. Acta Neurochir. 2000;142:751–757. Axelsson S, Storhaug K, Kjær I. Post-natal size and morphology of the sella turcica: longitudinal cephalometric standards for Norwegians between 6 and 21 years of age. Eur J Orthod. 2004a;26:597– 604. Axelsson S, Storhaug K, Kjær I. Post-natal size and morphology of the sella turcica in Williams syndrome. Eur J Orthod. 2004b;26:613– 621. Becktor JP, Einersen S, Kjær I. A sella turcica bridge in subjects with severe craniofacial deviations. Eur J Orthod. 2000;22:69–74. Bjork ¨ A. The face in profile: an anthropological x-ray investigation on Swedish children and conscripts. Berlingska Boktryckeriet. 1947;40:180. Bjork A. Facial growth in man, studied with the aid of metallic ¨ implants. Acta Odontol Scand. 1955;13:9–34. Bjork A, Skieller V. Normal and abnormal growth of the mandible: a ¨ synthesis of longitudinal cephalometric implant studies over a period of 25 years. Eur J Orthod. 1983;5:1–46. Bowers EJ, Mayro RF, Whitaker LA, Pasquariello PS, Larossa D, Randall P. General body growth in children with clefts of the lip, palate, and craniofacial structure. Scand J Plast Reconstr Surg Hand Surg. 1987;21:7–14. Burdi A. Developmental biology and morphogenesis of the face, lip and palate. In: Berkowitz S, ed. Cleft Lip and Palate. New York: Springer Berlin Heidelberg; 2006:3–12.
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