Rathke Cleft Cyst with Entirely Ossified Cyst Wall and Partially Solid Cyst Content: A Case Report and Literature Review

Background: In Rathke cleft cysts (RCCs), inflammation by the cyst contents infrequently spreads to the surrounding structures. Calcification, which is regarded as a result of chronic inflammation of the cyst wall, can rarely be found in RCCs. Moreover, ossification is extremely rare. Case Description: A 60-year-old woman experienced headaches, fatigue, and weight loss owing to pan-hypopituitarism. Magnetic resonance imaging revealed a mass lesion in the sellar region, which was composed of two different parts, with hypointensity anteriorly and hyperintensity posteriorly on T1-weighted image, and the rim with significant hypointensity entirely on T2-weighted image. During the transsphenoidal surgery, the cyst wall was so rigid that it was difficult to cut and remove it. The cyst contained mucinous fluid with both old and new hemorrhages, and a yellowish, elastic hard, solid nodule. Postoperative histologic diagnosis was RCC with unusual lymphocyte infiltration, massive granulation, and mature bone formation. Six months later, the fluid in the cyst reaccumulated, and the patient complained of headaches. Removal of the entire cyst wall and the aspiration of the cyst content were performed to collapse the cyst cavity and, consequently, to prevent further recurrence. Postoperatively, panhypopituitarism was unchanged and the symptoms were treated with hormonal replacement. The cyst has not recurred for 2 years after the second surgery. Conclusions: Persistent, long-term inflammation induced by the RCC content, mucin-containing fluid, and several phases of hemorrhage presumably promoted the formation of mature bone on the cyst wall and of the elastically solid nodule within the cyst. © 2016 Elsevier Inc.Embargo Period 12 month

Significant Improvement in Chronic Persistent Headaches Caused by Small Rathke Cleft Cysts After Transsphenoidal Surgery

Purpose Rathke cleft cysts (RCC) usually are asymptomatic and can be observed via the use of conservative methods. Some patients with RCCs, however, have severe headaches even if they are small enough to be confined to the sella, and these small RCCs seldom have been discussed. This study presents an investigation into clinical characteristics of small RCCs associated with severe headaches, demonstrating efficacy and safety of endoscopic transsphenoidal surgery (ETSS) to relieve headaches. Methods In this study, 13 patients with small RCCs (maximum diameter <10 mm) who presented with headaches and were treated by ETSS at our institute from 2009 to 2014 were recruited. These RCCs were treated Headache Impact Test-6 (HIT-6) score was calculated both pre- and postoperatively to evaluate headache severity. Results All patients complained of severe headaches, which disturbed their daily life. Most headaches were nonpulsating and localized in the frontal area. Characteristically, 6 patients (46%) experienced severe headaches with sudden onset that continued chronically. HIT-6 score was 64 on average, meaning headaches affected daily life severely. After surgical decompression of the cyst, headache in all of the patients improved dramatically and HIT-6 score decreased significantly to 37, suggesting that headaches were diminished. No newly developed deficiencies of the anterior pituitary lobe function were detected. Postoperative occurrence of diabetes insipidus was found in 2 patients, both of which were transient. No recurring cysts were found. Conclusions Severe headaches can develop from small RCCs. In the present study, ETSS was performed on such patients effectively and safely to relieve their headaches. © 2017 Elsevier Inc.Embargo Period 12 month

Contribution of sellar dura integrity to symptom manifestation in pituitary adenomas with intratumoral hemorrhage

Purpose: Although hemorrhage within pituitary adenomas frequently exacerbates the symptoms, there are many grades of severity. Moreover, the contributing factors for symptom severity are still controversial. Methods: This retrospective study included 82 patients who underwent transsphenoidal surgery for pituitary adenomas with intratumoral hemorrhage. The grades of preoperative symptoms were classified into group A, asymptomatic or minor symptoms; group B, moderate symptoms sufficient for complain; and group C, severe symptoms disturbing daily life. Results: The hemorrhage volume within an adenoma was significantly higher in group C (92.6%) than in groups A (48.6%) and B (58.7%). Both headache and diplopia were dominant in group C, occurring in 72.2% and 27.8% of the patients, respectively. In group C, there was no significant difference in frequency between adenoma extensions into the sphenoid sinus (0%) and involvement of the cavernous sinus of Knosp grade 4 (0%), and extensions into the suprasellar region were not common (38.9%). The most distinctive feature was that “no extrasellar extension” was found only in group C (41.2%), and “multidirectional extension” was not detected in this group (0%). Multiple regression analysis revealed that the most powerful determining factors were the high frequencies of intratumoral hemorrhage and lack of extrasellar and multidirectional extensions. Conclusion: Rapid volume expansion of a hematoma and lack of extension or unidirectional extension might lead to significant compression of the sellar and surrounding structures. Of note, the integrity of the sellar dura might contribute to the acute onset of symptom manifestations caused by hemorrhage in pituitary adenomas. © 2017 Springer Science+Business Media, LLCEmbargo Period 12 month

Significant improvement of intractable headache after transsphenoidal surgery in patients with pituitary adenomas; preoperative neuroradiological evaluation and intraoperative intrasellar pressure measurement

Object: Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. Methods: We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11–20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. Results: All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34–59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16–30). Conclusion: In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas. © 2015 Springer Science+Business Media New YorkEmbargo Period 12 month

Preoperative Evaluation of the Interface Between Tuberculum Sellae Meningioma and the Optic Nerves on Fast Imaging with Steady-State Acquisition for Extended Endoscopic Endonasal Transsphenoidal Surgery

Introduction Endoscopic endonasal transsphenoidal surgery (EETS) is increasingly applied to treat tuberculum sellae meningiomas. However, if the tumor adheres firmly to the optic nerve, dissection of the interface between both structures should be prudent to preserve visual function. The purpose of this study was to investigate whether tumor adhesion to the optic nerve can be predicted preoperatively by fast imaging with steady-state acquisition (FIESTA). Methods Twenty-two patients with tuberculum sellae meningioma treated with EETS were retrospectively identified. Clinical characteristics, radiologic studies, intraoperative findings, and outcomes were reviewed from their clinical charts. Results Patients\u27 symptoms included visual function impairment in 18 patients and headaches in 4 patients. Symptoms were resolved in 19 patients after operation. Preoperative radiologic evaluation was performed in 44 sides (22 patients) of the interface between tumors and the optic nerves and showed absence of peritumoral hyperintensity on FIESTA in 7 sides in 7 patients. In 5 of the 7 sides, tumor dissection was complicated by firm adhesion to the optic nerves. Among these cases, visual functions were unchanged in 1 patient after complete removal of the adhesion but substantially improved in 3 patients after partial resection. In the remaining 37 sides with preoperative peritumoral hyperintensity, no adhesion was found between both structures intraoperatively. Conclusions Absence of peritumoral hyperintensity between tuberculum sellae meningioma and the optic nerve on FIESTA may indicate firm adhesion at the interface, severely complicating complete removal. Preoperative recognition of this adhesion is important for safe tumor removal and preservation of visual functions. © 2017 Elsevier Inc.Embargo Period 12 month

Midline dural filum of the sellar floor: Its relationship to the septum attachment to the sellar floor and the ossification in the sphenoid sinus

Objectives It is important to identify and maintain a midline orientation during endoscopic transsphenoidal surgery (ETSS) for sellar lesions to prevent critical injury to the internal carotid artery. Therefore, the preoperative neuroradiological assessment of the bony structures in the sphenoid sinus, including the septum attachment to the sellar floor and its surrounding structures, is essential. It has been reported that the midline filum of the sellar dura can function as a useful intraoperative orientation guide during ETSS. However, the relationship between the midline dural filum and the intrasinus bony structures, such as the sellar floor, the intrasinus septation and the ossification, remains unclear and the mechanisms underlying development of the midline dural filum have also not yet been explored. Methods This retrospective study included 160 patients undergoing ETSS to assess both the midline dural filum and the intrasinus bony structures, using video recording reviews. The intrasinus septum and the ossification in the sphenoid sinus were evaluated on the computed tomography images of the bone window. Results A midline dural filum was identified in 66 (41.3%) of 160 patients. Attachment of the septum to the sellar midline was found in 61 (39.4%) of 155 patients, after excluding 5 patients with the conchal type of sphenoid sinus, 55 (90.2%) of 61 patients with a septum on the midline and only 6 (6.4%) of the remaining 94 patients without a septum on the midline had a midline dural filum. The relationship between a midline dural filum and a septum on midline was statistically significant (p < 0.001), regardless of the number of intrasphenoidal septa. In terms of the types of sphenoid sinus, the midline dural filum was predominantly detected in patients where ossification extended over the midline filum. In patients with the sellar type of sphenoid sinus, 49 (36.0%) of 136 had a midline dural filum, meanwhile, 16 (84.2%) of 19 patients with the pre-sellar type (p = 0.039) and all 5 patients (100%) with the choncal type harbored a midline dural filum (p < 0.001). Conclusion This study clearly verified the importance of the midline dural filum in a large series and evaluated the obvious relationship between the midline dural filum and the bony structures on the sellar floor. Our results strongly suggest that, during developing of the midline dural filum, the sellar dura becomes tethered to the bony elements attached to the sellar surface, such as the septum on the midline and the ossification in both the pre-sellar and the conchal type of sphenoid sinus. © 2016 Elsevier B.V. All rights reserved.Embargo Period 12 month

Pediatric symptomatic Rathke cleft cyst compared with cystic craniopharyngioma

Introduction: Symptomatic Rathke cleft cysts (RCCs) are rarely detected in neuroradiological screening and are less commonly found in children than in adults. However, when RCCs are observed in children, it is important to carefully distinguish a RCC from a cystic craniopharyngioma (CP) even if surgically treated or conservatively followed up. Methods: We conducted a retrospective review of clinical data from 11 patients with symptomatic RCCs whose ages were under 18 years and compared the data with data from 15 age- and sex-matched patients with cystic CP who were treated at our institute. Results: The mean age of the patients with RCCs was 12.2 years (range, 6–18). There were six males and five females. As initial symptoms, nine patients presented with headache, while two each had impaired visual function, diabetes insipidus, and activity loss. The 14 patients with CP suffered from impaired visual function. Magnetic resonance imaging (MRI) mainly showed hyperintensity on T1-weighted images (WIs) and hypointensity on T2-WI in patients with RCC. However, patients with CP had characteristic hyperintensity on T2-WI. The average maximum diameter of the RCCs was 19.0 mm on average (range, 8–33 mm). The RCCs were thus significantly smaller than CPs (34.9 mm; range, 21–54 mm). The RCCs were usually oval or dumbbell-shaped and regular in appearance, while the larger CPs were lobular and irregular. A preoperative endocrinological evaluation revealed insufficiencies in four axes in five patients with RCC. Postoperative endocrinological status improved in three patients, remained unchanged in three, and worsened in one. The gonadotropin axis was damaged in a majority (nine) of the patients with CP preoperatively. Postoperative evaluation revealed deficits in five axes in 14 patients with CP, which is a significantly different trend than observed in patients with RCC. Eight patients underwent surgical procedures (transsphenoidal surgery (TSS) in four, craniotomy in four). Two of these patients experienced a recurrence of the cysts. One of these patients subsequently underwent two craniotomies followed by radiation and other underwent TSS. Among the three conservatively treated patients, two experienced a transient worsening of their symptoms along with cyst enlargement. However, none of the three conservatively treated patients required an operation. Conclusions: When RCCs become symptomatic in children, the most common symptom they lead to is headache. The cysts are commonly small, regular, and oval in shape. Hypointensity of cyst contents on MRI is a characteristic of RCCs, which distinguishes them from CPs. Surgical intervention can be effective and lead to the relief of symptoms without a high rate of complications. However, there seems to be a relatively high recurrence rate following surgery. Thus, if the patient’s symptoms remain minor, the surgical treatment option should be used only when prudent, as the patient’s symptoms may improve over time. © 2016 Springer-Verlag Berlin HeidelbergIn Press / Embargo Period 12 month

De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions. © The Author(s) 2017

De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30C>G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions