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Incidentally-detected empty sellae
TH;/RAPHERS LLEGEOF RA
Radiography (1996) 2, 215-221
INCIDENTALLY-DETECTED
E M P T Y SELLAE
D. D. Gaton*, A. Loewensteint, O. Merimsky$§, M. Lazarl] and I. Reider-Groswasser¶ *The Department of Ophthalmology, Goldschlaeger Institute, Chaim-Sheba Medical Centre, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv, Departments of t Ophthalmology, ~Radiology (Section of Neuroradiology) and ¶Oncology, Tel-Aviv Sourasky Medical Centre and the Sackler School of Medicine, Tel-Aviv, Israel (Received 26 July 1995; accepted 25 May 1996)
Purpose. Empty sella syndrome (ESS) is being recognized increasingly because of the development of refined computed tomography (CT) techniques. ESS encompasses two distinct clinical entities. Primary benign and asymptomatic ESS occurs as an anatomic variation in the diaphragma sellae, a secondary syndrome occurs following surgery and/or irradiation or spontaneous regression of an intrasellar tumour and this may cause visual impairment post treatment. The aim of this study was to elucidate the possible association between age, ESS and any other pathological findings on brain CT studies, performed on 104 consecutive patients referred for various neurological and neurosurgical reasons.
Methods: In this study, empty sellae were found frequently, seen in 54% of the patients who were referred for a CT study of the brain for different clinical complaints of various unrelated aetiologies. ESS was found in equal frequency in men and women. We divided the patients into six groups according to their CT findings in the brain, i.e. normal appearance, cerebral atrophy, infarction or haemorrhage, space occupying lesion and others. The degree of central and cortical atrophy, the existence of carotid artery calcification and the sella turcica size were also evaluated. Results: We found no correlation between the size of sellae or the presence of empty sellae and patients age or with age-related CT features.
Conclusion: We suggest that an empty sella of normal size, with otherwise usual features, should be regarded as a normal anatomical variant. Key words:
empty sella; computed tomography scan; anatomical variant.
INTRODUCTION E m p t y sella s y n d r o m e (ESS) is due to an a c c u m u l a t i o n o f c e r e b r o s p i n a l fluid within the p i t u i t a r y fossa [1]. T h e t e r m ' e m p t y sella' was first coined b y Busch [2] in 1951 a n d was described as an i n t r a s e l l a r h e r n i a t i o n o f the c h i a s m a l cistern resulting f r o m a congenitally i n c o m p e t e n t d i a p h r a g m a sellae. A n e m p t y sella was p r e s e n t in 5.5% o f Busch's a u t o p s y series [2], in some cases the h y p o p h y s i s f o r m e d only a small p e r i p h e r a l r i m with the p i t u i t a r y g l a n d c o m p r e s s e d at the b o t t o m o f the sella turcica. T h e r e was a m a r k e d p r e p o n d e r a n c e o f females a m o n g these patients. O t h e r a u t o p s y studies indicate §Author to whom correspondence should be addressed at: Department of Oncology, Tel-Aviv Sourasky Medical Centre, 6 Weizman Street, Tel-Aviv 64239, Israel. 1078-8174/96/030215 + 07 $18.00
© 1996 The College of Radiographers 215
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an incidence of empty sellae in up to 23.5% of cases [3, 4]. ESS encompasses two distinct clinical entities. 'Idiopathic' or 'primary' ESS, in which sella remodelling occurs as a result of an anatomical variation in the diaphragma sellae, is a 'benign' condition associated with few, if any, clinical signs [5]. 'Secondary' ESS occurs following surgery, irradiation, or surgery and irradiation of an intrasellar tumour and may cause visual impairment post treatment [5, 6]. ESS is being recognized increasingly in vivo because of the common use of imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), which have replaced air contrast studies [6, 7]. CT parameters may help to distinguish between clinically significant and non-significant empty sella, and are necessary before deciding whether or not to proceed with expensive modalities such as MRI. In our study, the presence of ESS was evaluated in accordance with age, sex and other pathological findings on CT studies of the brain in consecutive patients referred for various neurological and neurosurgical reasons. The purpose of this study was to establish the relationship between frequent °empty sellae' observed coincidentally and other CT parameters of the sella turcica and of the brain. This relationship could assist in the distinction between clinically significant empty sellae necessitating further clinical and biochemically expensive evaluation and an insignificant incidental finding.
PATIENTS AND METHODS Patients
One hundred and four consecutive patients referred for brain CT scan studies performed at the Unit of Neuroradiology from January through June 1993, were included in the study. The indications for the CT studies included various unrelated neurological and neurosurgical pathologies. None of the patients in this series had undergone trauma, hypophysectomy, pituitary or cranial irradiation or had had any known endocrinopathy involving the pituitary. The age of the patients ranged from 4 months to 91 years (median 69 years; mean 56.6 years). C T studies All CT studies were performed on an Elscint 2400 Elite CT scanner, before and after the administration of intravenous contrast material (50 ml Urografin 60°/@ The sellae turcicae were well demonstrated on axial cuts which were performed parallel to the orbito-meatal lines in the supine position [8]. At the posterior fossa and sellar region the width of the adjacent cuts was 2.5 mm, whereas those for the rest of the brain were 10 mm each. Direct coronal cuts and coronal and sagittal computer reformations were performed. ESS was defined if present in the sella for at least two axial CT cuts. The 'emptiness' of the sella was indicated by the number of consecutive sections in which it was demonstrated. CT studies were assessed according to the following parameters: size of the ventricles, the sulci and the sellae turcicae. The size of the cerebral ventricles were evaluated by inspection and graded 1 to 3 [9]. The degree of atrophy (ATR) was estimated on a scale from 0-4 denoting the enlargement of the four ventricles and the subarachnoid space, in addition we measured the cerebroventricular indices CVI-1 and CVI-2 (bifrontal ratio = CVI-1, bicaudate ratio = CVI-2) as described by Hahn and Rim [10]. A CVI-1 index of 0.30 or less, and a CVI-2 index not greater than 0.15 were considered normal. The presence of carotid artery calcifications was noted. The linear
Empty Sellae
217
Table 1. CT diagnoses of patients and the presence of ESS or normal sellae Diagnosis
Empty sellae (n=56)
No empty sellae (n=48)
P value
13 20 9 4 8 2
11 9 12 8 5 3
N.S. 0.054 N.S. N.S. N.S. N.S.
Normal Cerebral atrophy Cerebral infarction Cerebral haemorrhage Space occupying lesion Others N.S., Not significantly different.
measurements that were performed included the width, length and height of the sellae. These were measured in m m between the anterior clinoid tips and from the planum sphenoidale to the dorsum sellae, following DiChiro and Nelson [11].
Statistics Descriptive statistics, Student's t-test, and Pearson's Z2 test, were used for statistical analysis. A P-value below 0.05 was considered as statistically significant.
RESULTS
Frequency ESS was established in 56 of 104 patients (54%), while in the other 48 (46%) CT studies showed no empty sellae (NES). The mean age in the ESS group was 61.3 years, compared to 53.0 years in the NES group. The difference was insignificant (P=0.11). There were 31 (55%) females and 25 (45%) males in the ESS group, and 31 (65%) females and 17 (35%) males in the NES group. The difference in sex distribution was insignificant (P=0.34).
Associated pathologies The patients were divided into five groups according to their radiological diagnosis of brain involvement: cerebral atrophy; cerebral infarction; cerebral haemorrhage; space occupying lesion and others such as hydrocephalus, orbital lesion or undefined orbital bone destruction were grouped together. A sixth group had normal radiological brain pictures (Table 1). None of the neuroradiological diagnoses were statistically significantly greater with ESS. Occurrence of ESS patients with cerebral atrophy was only slightly more frequent than occurrence of normal sellae (P=0.054). However, no correlation was found between the presence of ESS and CT parameters indicating atrophy (Table 2). The mean size of the sellae turcicae and that of the ventricles were similar in both groups (Table 3). Forty-four patients with ESS were found to have carotid artery calcification compared to 31 in the NES group. Carotid artery calcifications were not found to be typical of either group.
218
Gaton et at. Table 2. Patient distribution according to CT atrophy parameters Atrophy parameter
Sulci
No. of patients with: Degree
ESS
No ESS
P-value*
0
1
10
2 3 0
8 6 20 12 14 8 2
19 17 8 4 43 3 0 2 28 ll 6 3 18 11 11 8 1
N.S.
2 3 0 1 2 3 0
19 17 16 4 54 2 0 0 32
1
Fourth ventricle
Third ventricle
Lateral ventricles
1
2 3 4
N.S.
N.S.
N.S.
*The P-value was calculated for each degree of parameter and was always >0.05 (insignificantly different, N.S.). Table 3. Mean (standard deviation) values of ventricles and sellae turcicae Parameter CVI-1 (units CVI-2 (units) Sella: Width (mm) Length (mm)
ESS
No ESS
P-value
0.326 (0.076) 0.165 (0.053)
0.338 (0.073) 0.169 (0.05)
0.3 0.8
1.862 (0.528) 0.961 (0.267)
1.7354 (0.803) 0.9426 (0.6177)
0.6 0.8
Cerebro-ventricular indices: CVI-l, bifrontal ratio; CVI-2, bicaudate ratio.
E S S and age The patients were subgrouped by age. A n age o f 65 years was arbitrarily chosen as the cut-off point between groups. One subgroup consisted o f those older than 65 years, and the other g r o u p was 65 years or younger. The difference in age between the two groups was highly significant (P<0.0001). Parameters o f atrophy, i.e. A T R , CVI-2, sulci size, were significantly different in the two subgroups (Table 4). However, no correlation was noted between the width, height and length o f the sellae in each subgroup, or between the size o f the sulci and the size o f the lateral ventricles. The associated pathologies in patients over 65 years of age were mainly cerebral a t r o p h y followed by cerebral infarction. Those in the younger patients were mainly space occupying lesions, preceded by normal brain images (Table 5).
Empty Sellae
219
Table 4. The influence of patients' age on the atrophy parameters and the size of the sellae turcicae Parameter Mean age (S.D.) CVI-I (S.D.) CVI-2 (S.D.) ATR (S.D.) Sellae turcicae: Height (mm) (S.D.) Width (mm) (S.D.) Length (mm) (S.D.)
< 65 years (n = 45) 32.7 0.315 0.138 0.267
(20.9) (0.075) (0.036) (0.72)
1.667 (0.60) 1.714 (0.807) 0.885 (0.406)
> 65 years (n-- 59) 76.4 0.348 0.188 1.085
(6.0) (0.074) (0.052) (1.039)
1.644 (0.58) 1.885 (0.515) 1.008 (0.466)
P-value <0.0001 <0.05 <0.0001 <0.007 N.S. N.S. N.S.
The cerebro-ventricular indices CVI-I (bifrontal ratio) and CVI-2 (bicaudate ratio) were measured as described by Hahn and Rim [10]. A CVI-1 index of 0.30 or less, and a CVI-2 index not greater than 0.15 were considered normal. The degree of atrophy (ATR) was estimated on a scale from 0-4 denoting the enlargement of the four ventricles and the subarachnoid space. S.D., Standard deviation. Table 5. Distribution of ESS and associated brain CT diagnoses according to patient age CT diagnosis
Empty sellae Normal Cerebral atrophy Cerebral infarction Cerebral haemorrhage Space occupying lesion Miscellaneous
<65 years (n=45) (%)
>65 years (n= 59) (%)
P-value
53.3 40.0 6.7 15.6 11.1 17.8 8.9
54.2 10.2 44.1 23.7 11.9 8.5 1.7
N.S. <0.0001 <0.0001 N.S. N.S, 0.04 0.03
N.S., Not significantly different. ESS and CT parameters There was no correlation between the presence of ESS and sellar parameters (width and height of the sellae; Table 3), or between the size o f the CSF spaces in the brain and the presence of ESS (Table 4). There was no incidence o f large empty sellae in our patients.
DISCUSSION Our results show that empty sellae are a very c o m m o n incidental finding and unrelated to brain disorders. The advent of CT and the availability o f C T scanners have led to a rapid and non-invasive diagnosis of ESS. In our C T series the incidence of ESS was f o u n d to be 54% o f patients examined, in agreement with the findings o f Ishikawa et al. [12] and N a k a g a w a et al. [13]. Other authors f o u n d that the incidence of ESS was only 23-24% in r a n d o m a u t o p s y cases [3, 4]. Unlike the series summarized by J o r d a n et al. [14] in which ESS was reported to occur m o r e frequently in w o m e n (84%), we f o u n d an equal incidence in men and w o m e n in agreement with Brismar et al. [15]. However, Brismar et al. [15] using p n e u m o e n c e p h a l o g r a p h y (PEG) reported a significant increase
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Gaton et al.
in the incidence of ESS in association with communicating hydrocephalus and intracranial tumours. Our results differ from these findings. Our data show that the presence of an empty sella was not statistically associated with the presence of a space occupying lesion or hydrocephalus (Table 1). This difference could be due to the varying methods (PEG vs CT) and selection of patients. In our series, empty sellae were found frequently and were seen in 54% of patients referred for a CT brain scan for different clinical complaints of various unrelated aetiologies. ESS was found equally in men and women and was unrelated to age, using 65 years as the cut-off age. Brismar et al. [15] found increasing occurrence of ESS in patients over 40 years of age [15]. According to our results, the presence of CT-detected empty sellae are not strongly associated with common neuroradiological ageing parameters of the brain. Thus, the frequent presence of empty sellae in CT studies of the brain should be regarded as an anatomical variant, unless other evidence of sellar, pituitary pathology or optical disturbance is shown. The lack of correlation between the presence of empty sellae and size (Tables 3 and 4) supports the hypothesis that the presence of empty sellae is not related to a local process and is merely a developmental phenomenon. Several theories on the aetiology of primary ESS have been proposed. Many authors accept that this phenomenon is secondary to a deficient diaphragma sellae [1,4, 16, 17]. Various clinical features have been described in association with ESS. Obesity, hypertension, headache, visual field defects and two-tension glaucoma have been reported [14, 18-21]. Our results indicate that some degree of emptiness of the sellae can be found by routine CT examination of the sellar region. It seems that the presence of ESS should be distinguished from pituitary disease which requires further investigation. ESS is defined as a sella which, regardless of its size, contains cerebrospinal fluid (CSF). The detection of CSF density within a sella turcica is sufficient to establish the diagnosis of ESS [20, 22]. Low density within the sellae is an extremely common observation in CT studies of the brain. The distinction between the clinically significant empty sellae and the incidental non-significant finding is difficult, and the suggested parameters for this distinction have not yet been ascertained statistically. We suggest that where there is asymmetry of the sella turcica, particularly of the floor, clinoids or sphenoid plane, clinical and radiological investigation of the hypophysis should be performed. In the past, the size and 'emptiness' of the sella turcica was considered to be an indirect sign of pituitary pathology. As pituitary pathology can now be detected by neuroimaging even in normal or small pituitary glands the presence of ESS is not necessarily related. Without any associated finding, further investigation and searches for aetiology and pathogenesis are probably not warranted. References
1. Kaufman B. The "empty" sella turcia a manifestation of the intrasellar subarachnoid space. Radiology 1969; 90:931 41. 2. Busch W. Die Morphologie der Sella Turcica und ihre beziehungen zur Hypophyse. Virchow Arch Pathol Anat 1951; 320:437 58. 3. Bergland RM, Ray BS, Torack RM. Anatomical variation in the pituitary gland and adjacent structures in 225 human autopsy cases. J Neurosurg 1968; 28" 93 9. 4. Kaufman B, Chamberlin WB Jr. The ubiquitous "empty" sella turcica. Acta Radiol (Stockh) 1972; 13: 413-25. 5. Weiss SR, Rakind R. Non neoplastic intrasellar cysts, lnt Surg 1969; 51" 282 6.
Empty Sellae 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
221
Barjraktari X, Bergstorm M, Brismar K. Diagnosis ofintrasellar cisternal herniation (empty sella) by computer assisted tomography. J Comput Assist Tomogr 1977; 1" 105-16. Rozario R, Hammerschlag SB, Post KD. Diagnosis of empty sella with CT scan. Neuroradiology 1977; 13:85 8. Ambrose J. Computerized transverse axial scanning (tomograph). Clinical application. Br J Radiol 1973; 46: 1023-47. deLeon M J, Ferris SH, Blau I. Correlation between computerized tomographic changes and behavioural deficits in senile dementia. Lancet 1979; ii: 859-60. Hahn FJY, Rim K. Frontal ventricular dimensions on normal computed tomography. Am J Roentgenol 1976; 126: 593-6. DiChiro G, Nelson KB. The volume of the sella turcica. Am J Roentgenol Radium Ther Nucl Med 1962; 87: 989-1007. Ishikawa S, Furuse M, Saito T. Empty Sella in control subjects and patients with hypopituitarism. Endocrinol Jpn 1988; 35:665 74. Nakagawa Y, Matsomoto K, Fukami K. Exploration of the pituitary stalk and gland by high-resolution computed tomography: Comparative study of normal subjects and cases with microadenoma. Neuroradiology 1984; 26: 473-8. Jordan RM, Kendell JW, Kerver CW. The primary empty sella syndrome. Analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone. Am J Med 1977; 62" 569 80. Brismar K, Bajraktari X, Goulatia R. The empty sella syndrom~intracistemal herniation~n "normal" and in patients with communicating hydrocephalus and intracranial tumors. Neuroradiology 1978; 17" 35-43. Zats LM, Janon EA, Newton TH. The enlarged sella and the intrasellar cistern. Radiology 1969; 93: 1085-91. Obrador S. The empty sella and some related syndromes. J Neurosurg 1972; 36: 162-8. Berke JP, Buxton LF, Kokmen E. The 'empty sella'. Neurology 1975; 25: 1137-43. Bjerre P. The empty sella. A reappraisal of etiology and pathogenesis. Acta Neurol Scand 1990; 130" 3 25. Sage MR, Chan E, Reilly PL. The clinical and radiological features of the empty sella syndrome. Clin Radiol 1980; 31: 513-19. Yamabayashi S, Yamamoto T, Sasaki T. A case of 'low tension glaucoma' with primary empty sella. Br J Ophthalmol 1988; 72: 852-5. Naidich TP, Pinto RS, Kushner MJ. Evaluation of sellar and parasellar masses by computed tomography. Radiology 1976; 120:91 9.
Radiography (1996) 2, 215-221
INCIDENTALLY-DETECTED
E M P T Y SELLAE
D. D. Gaton*, A. Loewensteint, O. Merimsky$§, M. Lazarl] and I. Reider-Groswasser¶ *The Department of Ophthalmology, Goldschlaeger Institute, Chaim-Sheba Medical Centre, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv, Departments of t Ophthalmology, ~Radiology (Section of Neuroradiology) and ¶Oncology, Tel-Aviv Sourasky Medical Centre and the Sackler School of Medicine, Tel-Aviv, Israel (Received 26 July 1995; accepted 25 May 1996)
Purpose. Empty sella syndrome (ESS) is being recognized increasingly because of the development of refined computed tomography (CT) techniques. ESS encompasses two distinct clinical entities. Primary benign and asymptomatic ESS occurs as an anatomic variation in the diaphragma sellae, a secondary syndrome occurs following surgery and/or irradiation or spontaneous regression of an intrasellar tumour and this may cause visual impairment post treatment. The aim of this study was to elucidate the possible association between age, ESS and any other pathological findings on brain CT studies, performed on 104 consecutive patients referred for various neurological and neurosurgical reasons.
Methods: In this study, empty sellae were found frequently, seen in 54% of the patients who were referred for a CT study of the brain for different clinical complaints of various unrelated aetiologies. ESS was found in equal frequency in men and women. We divided the patients into six groups according to their CT findings in the brain, i.e. normal appearance, cerebral atrophy, infarction or haemorrhage, space occupying lesion and others. The degree of central and cortical atrophy, the existence of carotid artery calcification and the sella turcica size were also evaluated. Results: We found no correlation between the size of sellae or the presence of empty sellae and patients age or with age-related CT features.
Conclusion: We suggest that an empty sella of normal size, with otherwise usual features, should be regarded as a normal anatomical variant. Key words:
empty sella; computed tomography scan; anatomical variant.
INTRODUCTION E m p t y sella s y n d r o m e (ESS) is due to an a c c u m u l a t i o n o f c e r e b r o s p i n a l fluid within the p i t u i t a r y fossa [1]. T h e t e r m ' e m p t y sella' was first coined b y Busch [2] in 1951 a n d was described as an i n t r a s e l l a r h e r n i a t i o n o f the c h i a s m a l cistern resulting f r o m a congenitally i n c o m p e t e n t d i a p h r a g m a sellae. A n e m p t y sella was p r e s e n t in 5.5% o f Busch's a u t o p s y series [2], in some cases the h y p o p h y s i s f o r m e d only a small p e r i p h e r a l r i m with the p i t u i t a r y g l a n d c o m p r e s s e d at the b o t t o m o f the sella turcica. T h e r e was a m a r k e d p r e p o n d e r a n c e o f females a m o n g these patients. O t h e r a u t o p s y studies indicate §Author to whom correspondence should be addressed at: Department of Oncology, Tel-Aviv Sourasky Medical Centre, 6 Weizman Street, Tel-Aviv 64239, Israel. 1078-8174/96/030215 + 07 $18.00
© 1996 The College of Radiographers 215
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Gaton et al.
an incidence of empty sellae in up to 23.5% of cases [3, 4]. ESS encompasses two distinct clinical entities. 'Idiopathic' or 'primary' ESS, in which sella remodelling occurs as a result of an anatomical variation in the diaphragma sellae, is a 'benign' condition associated with few, if any, clinical signs [5]. 'Secondary' ESS occurs following surgery, irradiation, or surgery and irradiation of an intrasellar tumour and may cause visual impairment post treatment [5, 6]. ESS is being recognized increasingly in vivo because of the common use of imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), which have replaced air contrast studies [6, 7]. CT parameters may help to distinguish between clinically significant and non-significant empty sella, and are necessary before deciding whether or not to proceed with expensive modalities such as MRI. In our study, the presence of ESS was evaluated in accordance with age, sex and other pathological findings on CT studies of the brain in consecutive patients referred for various neurological and neurosurgical reasons. The purpose of this study was to establish the relationship between frequent °empty sellae' observed coincidentally and other CT parameters of the sella turcica and of the brain. This relationship could assist in the distinction between clinically significant empty sellae necessitating further clinical and biochemically expensive evaluation and an insignificant incidental finding.
PATIENTS AND METHODS Patients
One hundred and four consecutive patients referred for brain CT scan studies performed at the Unit of Neuroradiology from January through June 1993, were included in the study. The indications for the CT studies included various unrelated neurological and neurosurgical pathologies. None of the patients in this series had undergone trauma, hypophysectomy, pituitary or cranial irradiation or had had any known endocrinopathy involving the pituitary. The age of the patients ranged from 4 months to 91 years (median 69 years; mean 56.6 years). C T studies All CT studies were performed on an Elscint 2400 Elite CT scanner, before and after the administration of intravenous contrast material (50 ml Urografin 60°/@ The sellae turcicae were well demonstrated on axial cuts which were performed parallel to the orbito-meatal lines in the supine position [8]. At the posterior fossa and sellar region the width of the adjacent cuts was 2.5 mm, whereas those for the rest of the brain were 10 mm each. Direct coronal cuts and coronal and sagittal computer reformations were performed. ESS was defined if present in the sella for at least two axial CT cuts. The 'emptiness' of the sella was indicated by the number of consecutive sections in which it was demonstrated. CT studies were assessed according to the following parameters: size of the ventricles, the sulci and the sellae turcicae. The size of the cerebral ventricles were evaluated by inspection and graded 1 to 3 [9]. The degree of atrophy (ATR) was estimated on a scale from 0-4 denoting the enlargement of the four ventricles and the subarachnoid space, in addition we measured the cerebroventricular indices CVI-1 and CVI-2 (bifrontal ratio = CVI-1, bicaudate ratio = CVI-2) as described by Hahn and Rim [10]. A CVI-1 index of 0.30 or less, and a CVI-2 index not greater than 0.15 were considered normal. The presence of carotid artery calcifications was noted. The linear
Empty Sellae
217
Table 1. CT diagnoses of patients and the presence of ESS or normal sellae Diagnosis
Empty sellae (n=56)
No empty sellae (n=48)
P value
13 20 9 4 8 2
11 9 12 8 5 3
N.S. 0.054 N.S. N.S. N.S. N.S.
Normal Cerebral atrophy Cerebral infarction Cerebral haemorrhage Space occupying lesion Others N.S., Not significantly different.
measurements that were performed included the width, length and height of the sellae. These were measured in m m between the anterior clinoid tips and from the planum sphenoidale to the dorsum sellae, following DiChiro and Nelson [11].
Statistics Descriptive statistics, Student's t-test, and Pearson's Z2 test, were used for statistical analysis. A P-value below 0.05 was considered as statistically significant.
RESULTS
Frequency ESS was established in 56 of 104 patients (54%), while in the other 48 (46%) CT studies showed no empty sellae (NES). The mean age in the ESS group was 61.3 years, compared to 53.0 years in the NES group. The difference was insignificant (P=0.11). There were 31 (55%) females and 25 (45%) males in the ESS group, and 31 (65%) females and 17 (35%) males in the NES group. The difference in sex distribution was insignificant (P=0.34).
Associated pathologies The patients were divided into five groups according to their radiological diagnosis of brain involvement: cerebral atrophy; cerebral infarction; cerebral haemorrhage; space occupying lesion and others such as hydrocephalus, orbital lesion or undefined orbital bone destruction were grouped together. A sixth group had normal radiological brain pictures (Table 1). None of the neuroradiological diagnoses were statistically significantly greater with ESS. Occurrence of ESS patients with cerebral atrophy was only slightly more frequent than occurrence of normal sellae (P=0.054). However, no correlation was found between the presence of ESS and CT parameters indicating atrophy (Table 2). The mean size of the sellae turcicae and that of the ventricles were similar in both groups (Table 3). Forty-four patients with ESS were found to have carotid artery calcification compared to 31 in the NES group. Carotid artery calcifications were not found to be typical of either group.
218
Gaton et at. Table 2. Patient distribution according to CT atrophy parameters Atrophy parameter
Sulci
No. of patients with: Degree
ESS
No ESS
P-value*
0
1
10
2 3 0
8 6 20 12 14 8 2
19 17 8 4 43 3 0 2 28 ll 6 3 18 11 11 8 1
N.S.
2 3 0 1 2 3 0
19 17 16 4 54 2 0 0 32
1
Fourth ventricle
Third ventricle
Lateral ventricles
1
2 3 4
N.S.
N.S.
N.S.
*The P-value was calculated for each degree of parameter and was always >0.05 (insignificantly different, N.S.). Table 3. Mean (standard deviation) values of ventricles and sellae turcicae Parameter CVI-1 (units CVI-2 (units) Sella: Width (mm) Length (mm)
ESS
No ESS
P-value
0.326 (0.076) 0.165 (0.053)
0.338 (0.073) 0.169 (0.05)
0.3 0.8
1.862 (0.528) 0.961 (0.267)
1.7354 (0.803) 0.9426 (0.6177)
0.6 0.8
Cerebro-ventricular indices: CVI-l, bifrontal ratio; CVI-2, bicaudate ratio.
E S S and age The patients were subgrouped by age. A n age o f 65 years was arbitrarily chosen as the cut-off point between groups. One subgroup consisted o f those older than 65 years, and the other g r o u p was 65 years or younger. The difference in age between the two groups was highly significant (P<0.0001). Parameters o f atrophy, i.e. A T R , CVI-2, sulci size, were significantly different in the two subgroups (Table 4). However, no correlation was noted between the width, height and length o f the sellae in each subgroup, or between the size o f the sulci and the size o f the lateral ventricles. The associated pathologies in patients over 65 years of age were mainly cerebral a t r o p h y followed by cerebral infarction. Those in the younger patients were mainly space occupying lesions, preceded by normal brain images (Table 5).
Empty Sellae
219
Table 4. The influence of patients' age on the atrophy parameters and the size of the sellae turcicae Parameter Mean age (S.D.) CVI-I (S.D.) CVI-2 (S.D.) ATR (S.D.) Sellae turcicae: Height (mm) (S.D.) Width (mm) (S.D.) Length (mm) (S.D.)
< 65 years (n = 45) 32.7 0.315 0.138 0.267
(20.9) (0.075) (0.036) (0.72)
1.667 (0.60) 1.714 (0.807) 0.885 (0.406)
> 65 years (n-- 59) 76.4 0.348 0.188 1.085
(6.0) (0.074) (0.052) (1.039)
1.644 (0.58) 1.885 (0.515) 1.008 (0.466)
P-value <0.0001 <0.05 <0.0001 <0.007 N.S. N.S. N.S.
The cerebro-ventricular indices CVI-I (bifrontal ratio) and CVI-2 (bicaudate ratio) were measured as described by Hahn and Rim [10]. A CVI-1 index of 0.30 or less, and a CVI-2 index not greater than 0.15 were considered normal. The degree of atrophy (ATR) was estimated on a scale from 0-4 denoting the enlargement of the four ventricles and the subarachnoid space. S.D., Standard deviation. Table 5. Distribution of ESS and associated brain CT diagnoses according to patient age CT diagnosis
Empty sellae Normal Cerebral atrophy Cerebral infarction Cerebral haemorrhage Space occupying lesion Miscellaneous
<65 years (n=45) (%)
>65 years (n= 59) (%)
P-value
53.3 40.0 6.7 15.6 11.1 17.8 8.9
54.2 10.2 44.1 23.7 11.9 8.5 1.7
N.S. <0.0001 <0.0001 N.S. N.S, 0.04 0.03
N.S., Not significantly different. ESS and CT parameters There was no correlation between the presence of ESS and sellar parameters (width and height of the sellae; Table 3), or between the size o f the CSF spaces in the brain and the presence of ESS (Table 4). There was no incidence o f large empty sellae in our patients.
DISCUSSION Our results show that empty sellae are a very c o m m o n incidental finding and unrelated to brain disorders. The advent of CT and the availability o f C T scanners have led to a rapid and non-invasive diagnosis of ESS. In our C T series the incidence of ESS was f o u n d to be 54% o f patients examined, in agreement with the findings o f Ishikawa et al. [12] and N a k a g a w a et al. [13]. Other authors f o u n d that the incidence of ESS was only 23-24% in r a n d o m a u t o p s y cases [3, 4]. Unlike the series summarized by J o r d a n et al. [14] in which ESS was reported to occur m o r e frequently in w o m e n (84%), we f o u n d an equal incidence in men and w o m e n in agreement with Brismar et al. [15]. However, Brismar et al. [15] using p n e u m o e n c e p h a l o g r a p h y (PEG) reported a significant increase
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Gaton et al.
in the incidence of ESS in association with communicating hydrocephalus and intracranial tumours. Our results differ from these findings. Our data show that the presence of an empty sella was not statistically associated with the presence of a space occupying lesion or hydrocephalus (Table 1). This difference could be due to the varying methods (PEG vs CT) and selection of patients. In our series, empty sellae were found frequently and were seen in 54% of patients referred for a CT brain scan for different clinical complaints of various unrelated aetiologies. ESS was found equally in men and women and was unrelated to age, using 65 years as the cut-off age. Brismar et al. [15] found increasing occurrence of ESS in patients over 40 years of age [15]. According to our results, the presence of CT-detected empty sellae are not strongly associated with common neuroradiological ageing parameters of the brain. Thus, the frequent presence of empty sellae in CT studies of the brain should be regarded as an anatomical variant, unless other evidence of sellar, pituitary pathology or optical disturbance is shown. The lack of correlation between the presence of empty sellae and size (Tables 3 and 4) supports the hypothesis that the presence of empty sellae is not related to a local process and is merely a developmental phenomenon. Several theories on the aetiology of primary ESS have been proposed. Many authors accept that this phenomenon is secondary to a deficient diaphragma sellae [1,4, 16, 17]. Various clinical features have been described in association with ESS. Obesity, hypertension, headache, visual field defects and two-tension glaucoma have been reported [14, 18-21]. Our results indicate that some degree of emptiness of the sellae can be found by routine CT examination of the sellar region. It seems that the presence of ESS should be distinguished from pituitary disease which requires further investigation. ESS is defined as a sella which, regardless of its size, contains cerebrospinal fluid (CSF). The detection of CSF density within a sella turcica is sufficient to establish the diagnosis of ESS [20, 22]. Low density within the sellae is an extremely common observation in CT studies of the brain. The distinction between the clinically significant empty sellae and the incidental non-significant finding is difficult, and the suggested parameters for this distinction have not yet been ascertained statistically. We suggest that where there is asymmetry of the sella turcica, particularly of the floor, clinoids or sphenoid plane, clinical and radiological investigation of the hypophysis should be performed. In the past, the size and 'emptiness' of the sella turcica was considered to be an indirect sign of pituitary pathology. As pituitary pathology can now be detected by neuroimaging even in normal or small pituitary glands the presence of ESS is not necessarily related. Without any associated finding, further investigation and searches for aetiology and pathogenesis are probably not warranted. References
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