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Empty sella syndrome in nevoid basal cell carcinoma syndrome
Brain & Development 22 (2000) 272±274
www.elsevier.com/locate/braindev
Case report
Empty sella syndrome in nevoid basal cell carcinoma syndrome Jun-ichi Takanashi a,*, Katsunori Fujii a, Hideyuki Takano b, Katsuo Sugita c, Yoichi Kohno a a
Department of Pediatrics, Faculty of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan Department of Radiology, Faculty of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan c Department of Clinical Medicine, Faculty of Education, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba-shi, Chiba 263-8522, Japan b
Received 22 November 1999; received in revised form 29 February 2000; accepted 2 March 2000
Abstract We reported the magnetic resonance imaging of four young patients (13 to 19 years) with nevoid basal cell carcinoma syndrome (NBCCS), which showed empty sella, agenesis of the corpus callosum and empty sella, an interhemispheric lipoma with callosal dysgenesis, and an arachnoid cyst in the posterior fossa, respectively. Calci®cation of the diaphragma sellae, which is a protective barrier against the pulsating action of the cerebrospinal ¯uid, may cause the empty sella in NBCCS. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Nevoid basal cell carcinoma syndrome; Empty sella syndrome
1. Introduction Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder linked to chromosome 9q22.3±q31 and caused by mutations in PTC, the human homologue of the Drosophila patched gene [1], and comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, and spine and rib anomalies [2]. We herein report the brain magnetic resonance (MR) imaging of four patients with NBCCS, with special emphasis on the presence of empty sella syndrome. 1.1. Materials and methods There were four patients with a clinically established diagnosis of NBCCS, based on the criteria of Kimonis et al. [3]. Three were female patients (patients 1 and 2 were sisters), aged 13 to 19, and one male, aged 15. The clinical manifestations are summarized in Table 1. MRI was performed with a 1.5-T superconducting magnet. Axial and/or coronal T1 (440/10/2; [repetition time/echo time/excitation]) and T2 weighted images (3000/100, 30/2, 4000/100/2) were obtained in all four patients. For evaluation of midline structures, thin slice sagittal and coronal T1 weighted images were also obtained. The parameters were as follows: matrix size, 256 £ 256, ®eld of view, 25 cm; slice thickness, 6 mm; and slice gap, 1.5 mm for T1 and T2 weighted axial or coronal images, and 256 £ 256, 25 cm, 3 * Corresponding author. Tel.: 181-43-226-2144; fax: 181-43-226-2145. E-mail address: [email protected] (J.- Takanashi).
mm slices with 1 mm gaps for thin slice T1 weighted images. Calci®cation of the falx cerebri, the cerebellar tentorium and the diaphragma sellae was examined by means of X-ray ®lms and computed tomography (CT). A pediatric neurologist and a radiologist (JT and HT) reviewed the images in each patient, whose identity and disease severity were unknown. 2. Results The neuroradiological ®ndings in these four patients are summarized in Table 2. Plain X-ray ®lms and CT demonstrated calci®cation in the falx cerebri, cerebellar tentorium, and the diaphragma sellae in all four patients. MR imaging revealed an interhemispheric lipoma with callosal dysgenesis in patient 1, an empty sella in patient 2 (Fig. 1), an arachnoid cyst in the posterior fossa in patient 3, and agenesis of the corpus callosum and an empty sella in patient 4 (Fig. 2). Detection of the calci®cation of the cerebral falx and cerebellar tentorium was impossible on MR imaging. Coronal images demonstrated no markedly pneumatized lateral recess of the sphenoidal sinus interposing itself between the pituitary fossa and the cavernous sinus. No other parenchymal abnormality was recognized. 3. Discussion The neurologic manifestations of NBCCS include medul-
0387-7604/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S03 87-7604(00)0011 5-7
J.- Takanashi et al. / Brain & Development 22 (2000) 272±274 Table 1 Clinical manifestations a
Table 2 Neuroradiological ®ndings a
Patient
Age
Sex
Mentality
Seizures
Complication
1 2 3 4
19 17 15 13
Female Female Male Female
Normal Normal IQ 71 Subnormal
None None None None
Cardiac tumor Obesity Ulcerative colitis
a
273
Patient Calci®cation
MR ®ndings
Falx cerebri Cerebellar tentorium
Diaphragma sellae
1
Present
Present
Present
2 3
Present Present
Present Present
Present Present
4
Present
Present
Present
IQ, intelligence quotient.
loblastoma, meningioma, craniopharyngioma, mental retardation, agenesis of the corpus callosum, and lamellar calci®cation of the falx cerebri [2]. Calci®cation has also been described in the cerebellar tentorium, petroclinoid ligaments, dura, pia, chroid plexus, and basal ganglia, however, no symptoms associated with calci®cation have been reported. Empty sella syndrome (ESS) is a condition in which the sella turcica is partially or completely ®lled with cerebrospinal ¯uid. Primary ESS arises in the absence of previous pituitary surgery or irradiation, while secondary ESS arises from reduction of the intrasellar contents following pituitary surgery, radiation or infarction, allowing herniation of the subarachnoid space to ®ll the empty space. MR imaging demonstrated primary ESS in two of our four patients with NBCCS, which has never been reported previously. In general, a progressive increase in the incidence of the signs of primary ESS has been observed with aging, namely, in 9.6% of subjects under the age of 40 years and in 39.9% of those above 40 [4]. Primary ESS has been
a
Interhemispheric lipoma, dysplastic CC ES Arachnoid cyst in the posterior fossa Agenesis of CC, ES
ES, empty sella; CC, corpus callosum.
considered to be a rare ®nding in children and adolescents, however, the clinical picture is much less benign, with increases in familiar incidence, associated skeletal disorders, and endocrine abnormalities [5]. The factors possibly playing a role in primary ESS are an insuf®ciency or absence of diaphragma sellae, cerebrospinal ¯uid pressure, and pituitary involution related to aging [4]. In NBCCS, calci®cation of the diaphragma sellae (bridging of the sella turcica), which is a protective barrier against the pulsating action that the cerebrospinal ¯uid exerts on the sellar contents, is seen in at least 60±80% of cases, a ®nding noted in only about 4% of the normal population [2]. The incidence of calci®cation of the dural membrane in NBCCS increases with age, i.e. calci®cation of the falx cerebri was observed in 77±79% of cases over the age of 20 years, and in 37% under 20 [3]. It is considered
Fig. 1. Sagittal T1 (440/10/2) weighted image of patient 2 shows an empty sella.
274
J.- Takanashi et al. / Brain & Development 22 (2000) 272±274
Fig. 2. Sagittal T1 (440/10/2) weighted image of patient 4 shows agenesis of corpus callosum and an empty sella.
that calci®cation of the diaphragma sellae in NBCCS may reduce the protection against the cerebrospinal ¯uid pulsation, and thereafter cause primary ESS. Follow-up MR imaging should be performed for the other two patients without ESS at present to determine whether or not progressive calci®cation of the diaphragma sellae may cause ESS in the future. With regard to the abnormalities of the sella turcica in patients with NBCCS, the sella is small and often asymmetric due to hyperpneumatization of the sphenoidal bone [2,6]. The sinuses are hyperpneumatized in 60% of NBCCS patients due to the absence an intrasinusal septa. The present four cases did not demonstrate markedly pneumatized sphenoid sinus, however, Iwanaga et al. [6] recently reported a case of NBCCS in whom MRI showed a markedly pneumatized lateral recess of the sphenoid sinus interposing itself between the pituitary fossa and the cavernous sinus. In conclusion, two of our four patients with NBCCS exhibited empty sella on MR imaging, which suggested that calci®cation of the diaphragma sella may cause primary ESS.
Acknowledgements We wish to thank Okumura K, Nakano Y, Isobe T, and Morita F for their excellent technical support. References [1] Farndon PA, Del Mastro RG, Evans DG, Kilpatrich MW. Location of gene for Gorlin syndrome (naevoid basal cell carcinoma syndrome) on the long arm of chromosome 9. Lancet 1992;339:581±582. [2] Gorlin RJ. Nevoid basal-cell carcinoma syndrome. Medicine 1987;66:98±111. [3] Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299±308. [4] Foresti M, Guidali A, Susanna P. Primary empty sella. Incidence in 500 asymptomatic subjects examined with magnetic resonance. Radiologia Medica 1991;81:803±807. [5] Allen SS, Saxena KM. Empty sella syndrome in an adolescent. J Adolescent Health 1986;7:198±201. [6] Iwanaga S, Shimoura H, Shimizu M, Numaguchi Y. Gorlin syndrome: Unusual manifestations in the sella turcica and the sphenoidal sinus. Am J Neuroradiol 1998;19:956±958.
www.elsevier.com/locate/braindev
Case report
Empty sella syndrome in nevoid basal cell carcinoma syndrome Jun-ichi Takanashi a,*, Katsunori Fujii a, Hideyuki Takano b, Katsuo Sugita c, Yoichi Kohno a a
Department of Pediatrics, Faculty of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan Department of Radiology, Faculty of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan c Department of Clinical Medicine, Faculty of Education, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba-shi, Chiba 263-8522, Japan b
Received 22 November 1999; received in revised form 29 February 2000; accepted 2 March 2000
Abstract We reported the magnetic resonance imaging of four young patients (13 to 19 years) with nevoid basal cell carcinoma syndrome (NBCCS), which showed empty sella, agenesis of the corpus callosum and empty sella, an interhemispheric lipoma with callosal dysgenesis, and an arachnoid cyst in the posterior fossa, respectively. Calci®cation of the diaphragma sellae, which is a protective barrier against the pulsating action of the cerebrospinal ¯uid, may cause the empty sella in NBCCS. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Nevoid basal cell carcinoma syndrome; Empty sella syndrome
1. Introduction Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder linked to chromosome 9q22.3±q31 and caused by mutations in PTC, the human homologue of the Drosophila patched gene [1], and comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, and spine and rib anomalies [2]. We herein report the brain magnetic resonance (MR) imaging of four patients with NBCCS, with special emphasis on the presence of empty sella syndrome. 1.1. Materials and methods There were four patients with a clinically established diagnosis of NBCCS, based on the criteria of Kimonis et al. [3]. Three were female patients (patients 1 and 2 were sisters), aged 13 to 19, and one male, aged 15. The clinical manifestations are summarized in Table 1. MRI was performed with a 1.5-T superconducting magnet. Axial and/or coronal T1 (440/10/2; [repetition time/echo time/excitation]) and T2 weighted images (3000/100, 30/2, 4000/100/2) were obtained in all four patients. For evaluation of midline structures, thin slice sagittal and coronal T1 weighted images were also obtained. The parameters were as follows: matrix size, 256 £ 256, ®eld of view, 25 cm; slice thickness, 6 mm; and slice gap, 1.5 mm for T1 and T2 weighted axial or coronal images, and 256 £ 256, 25 cm, 3 * Corresponding author. Tel.: 181-43-226-2144; fax: 181-43-226-2145. E-mail address: [email protected] (J.- Takanashi).
mm slices with 1 mm gaps for thin slice T1 weighted images. Calci®cation of the falx cerebri, the cerebellar tentorium and the diaphragma sellae was examined by means of X-ray ®lms and computed tomography (CT). A pediatric neurologist and a radiologist (JT and HT) reviewed the images in each patient, whose identity and disease severity were unknown. 2. Results The neuroradiological ®ndings in these four patients are summarized in Table 2. Plain X-ray ®lms and CT demonstrated calci®cation in the falx cerebri, cerebellar tentorium, and the diaphragma sellae in all four patients. MR imaging revealed an interhemispheric lipoma with callosal dysgenesis in patient 1, an empty sella in patient 2 (Fig. 1), an arachnoid cyst in the posterior fossa in patient 3, and agenesis of the corpus callosum and an empty sella in patient 4 (Fig. 2). Detection of the calci®cation of the cerebral falx and cerebellar tentorium was impossible on MR imaging. Coronal images demonstrated no markedly pneumatized lateral recess of the sphenoidal sinus interposing itself between the pituitary fossa and the cavernous sinus. No other parenchymal abnormality was recognized. 3. Discussion The neurologic manifestations of NBCCS include medul-
0387-7604/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S03 87-7604(00)0011 5-7
J.- Takanashi et al. / Brain & Development 22 (2000) 272±274 Table 1 Clinical manifestations a
Table 2 Neuroradiological ®ndings a
Patient
Age
Sex
Mentality
Seizures
Complication
1 2 3 4
19 17 15 13
Female Female Male Female
Normal Normal IQ 71 Subnormal
None None None None
Cardiac tumor Obesity Ulcerative colitis
a
273
Patient Calci®cation
MR ®ndings
Falx cerebri Cerebellar tentorium
Diaphragma sellae
1
Present
Present
Present
2 3
Present Present
Present Present
Present Present
4
Present
Present
Present
IQ, intelligence quotient.
loblastoma, meningioma, craniopharyngioma, mental retardation, agenesis of the corpus callosum, and lamellar calci®cation of the falx cerebri [2]. Calci®cation has also been described in the cerebellar tentorium, petroclinoid ligaments, dura, pia, chroid plexus, and basal ganglia, however, no symptoms associated with calci®cation have been reported. Empty sella syndrome (ESS) is a condition in which the sella turcica is partially or completely ®lled with cerebrospinal ¯uid. Primary ESS arises in the absence of previous pituitary surgery or irradiation, while secondary ESS arises from reduction of the intrasellar contents following pituitary surgery, radiation or infarction, allowing herniation of the subarachnoid space to ®ll the empty space. MR imaging demonstrated primary ESS in two of our four patients with NBCCS, which has never been reported previously. In general, a progressive increase in the incidence of the signs of primary ESS has been observed with aging, namely, in 9.6% of subjects under the age of 40 years and in 39.9% of those above 40 [4]. Primary ESS has been
a
Interhemispheric lipoma, dysplastic CC ES Arachnoid cyst in the posterior fossa Agenesis of CC, ES
ES, empty sella; CC, corpus callosum.
considered to be a rare ®nding in children and adolescents, however, the clinical picture is much less benign, with increases in familiar incidence, associated skeletal disorders, and endocrine abnormalities [5]. The factors possibly playing a role in primary ESS are an insuf®ciency or absence of diaphragma sellae, cerebrospinal ¯uid pressure, and pituitary involution related to aging [4]. In NBCCS, calci®cation of the diaphragma sellae (bridging of the sella turcica), which is a protective barrier against the pulsating action that the cerebrospinal ¯uid exerts on the sellar contents, is seen in at least 60±80% of cases, a ®nding noted in only about 4% of the normal population [2]. The incidence of calci®cation of the dural membrane in NBCCS increases with age, i.e. calci®cation of the falx cerebri was observed in 77±79% of cases over the age of 20 years, and in 37% under 20 [3]. It is considered
Fig. 1. Sagittal T1 (440/10/2) weighted image of patient 2 shows an empty sella.
274
J.- Takanashi et al. / Brain & Development 22 (2000) 272±274
Fig. 2. Sagittal T1 (440/10/2) weighted image of patient 4 shows agenesis of corpus callosum and an empty sella.
that calci®cation of the diaphragma sellae in NBCCS may reduce the protection against the cerebrospinal ¯uid pulsation, and thereafter cause primary ESS. Follow-up MR imaging should be performed for the other two patients without ESS at present to determine whether or not progressive calci®cation of the diaphragma sellae may cause ESS in the future. With regard to the abnormalities of the sella turcica in patients with NBCCS, the sella is small and often asymmetric due to hyperpneumatization of the sphenoidal bone [2,6]. The sinuses are hyperpneumatized in 60% of NBCCS patients due to the absence an intrasinusal septa. The present four cases did not demonstrate markedly pneumatized sphenoid sinus, however, Iwanaga et al. [6] recently reported a case of NBCCS in whom MRI showed a markedly pneumatized lateral recess of the sphenoid sinus interposing itself between the pituitary fossa and the cavernous sinus. In conclusion, two of our four patients with NBCCS exhibited empty sella on MR imaging, which suggested that calci®cation of the diaphragma sella may cause primary ESS.
Acknowledgements We wish to thank Okumura K, Nakano Y, Isobe T, and Morita F for their excellent technical support. References [1] Farndon PA, Del Mastro RG, Evans DG, Kilpatrich MW. Location of gene for Gorlin syndrome (naevoid basal cell carcinoma syndrome) on the long arm of chromosome 9. Lancet 1992;339:581±582. [2] Gorlin RJ. Nevoid basal-cell carcinoma syndrome. Medicine 1987;66:98±111. [3] Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299±308. [4] Foresti M, Guidali A, Susanna P. Primary empty sella. Incidence in 500 asymptomatic subjects examined with magnetic resonance. Radiologia Medica 1991;81:803±807. [5] Allen SS, Saxena KM. Empty sella syndrome in an adolescent. J Adolescent Health 1986;7:198±201. [6] Iwanaga S, Shimoura H, Shimizu M, Numaguchi Y. Gorlin syndrome: Unusual manifestations in the sella turcica and the sphenoidal sinus. Am J Neuroradiol 1998;19:956±958.